miladalsh/processed_scinews_dataset · Datasets at Hugging Face

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Cooperation is essential for all domains of life. Yet, ironically, it is intrinsically vulnerable to exploitation by cheats. Hence, an explanatory necessity spurs many evolutionary biologists to search for mechanisms that could support cooperation. In general, cooperation can emerge and be maintained when cooperators are sufficiently interacting with themselves. This communication provides a kind of assortment and reciprocity. The most crucial and common mechanisms to achieve that task are kin selection, spatial structure, and enforcement (punishment). Here, we used agent-based simulation models to investigate these pivotal mechanisms against conditional defector strategies. We concluded that the latter could easily violate the former and take over the population. This surprising outcome may urge us to rethink the evolution of cooperation, as it illustrates that maintaining cooperation may be more difficult than previously thought. Moreover, empirical applications may support these theoretical findings, such as invading the cooperator population of pathogens by genetically engineered conditional defectors, which could be a potential therapy for many incurable diseases. Introduction A long-standing puzzle in evolution theory is how cooperative behavior can evolve and persist within the selfish natural world. Once cooperation exists, it is always prone to exploitation by defective free riders who adopt selfish strategies for reaping the highest possible profit without paying the share. Thus, they invest most of their energy in reproduction. Therefore, cheaters could outcompete the cooperators and take over the population. Haldane pointed out that there was no general principle to solve this problem 1 . Since then, many partial mechanisms have been suggested, such as kin selection, group selection, reciprocity, policing, spatial structure, sanction, reward, and punishment 2 , 3 , 4 . Darwin himself suggested some core concepts of these mechanisms. This paper introduced conditional defector strategies that violate the kin selection, punishment, and spatial structure mechanisms. What are conditional defector strategies? From a conceptual viewpoint, a conditional defector strategy may be any cheating strategy that could somehow cooperate. In other words, it is a cheater who pays additional costs or wastes a portion of the profit to survive. Therefore, it is not necessarily defective in all behaviors or at all times. However, it may cooperate in some behaviors now and then. Consequently, they are not pure defectors. Some forms of conditional defector strategies Cooperate for the spread Dispersal is beneficial because it decreases Kin competition, sustains resources, and outsets colonization. Without dispersal, the fate of all populations is extinction 5 . Hence, an intermediate dispersal rate of cooperators is essential for cooperation maintenance 6 , 7 . Furthermore, migration can induce an explosive outbreak of cooperation, even in a world of selfish individuals with various sources of randomness, starting with defectors only 8 . Recently 9 showed for the first time that strategy-neutral migration triggered strategy oscillation in a two-strategy game even without the bridging of any transition strategies (states), thus defining a novel oscillating behavior fundamentally different from the conventional cyclic dominance previously found in a game of at least three or more strategies. Reference 10 studied the impact of varying migration preferences in promoting cooperation. They revealed the role of orientation-driven migration, where individuals prefer to move closer to their neighboring cooperators or favor escape away from their neighboring defectors. Nevertheless, dispersal is a costly behavior that increases the mortality of dispersers or decreases their fecundity 11 , 12 . Therefore, some studies have focused on the joint evolution of dispersal and cooperation 13 . Alternatively, there is a correlation between cooperation, dispersal rate, and dispersal cost 14 . Their findings asserted that the low dispersal cost selects against cooperation. Thus, if cheaters reduce their dispersal costs, they may turn the game against cooperators. Usually, cheats are not good migrators because dispersal itself is a cooperative behavior. The migrators leave their suitable habitats to other unknown environments and face dangerous predators to colonize a new patch. Therefore, such behavior is costly for migrators. Nevertheless, its benefits are also gained by non-migrators because it decreases kin competition. Thus, dispersal is considered a cooperative behavior that naturally does not expect to be abundant in cheats. Hence, cheaters go extinct rapidly with the depletion of local patches they dominated without global prevalence like cooperators; this might be the fundamental problem of cheaters. However, the probable solution is adopting a conditional defection strategy wherein free riders would cooperate only for the spread. The actors of this selfish strategy would have a high dispersal rate with the lowest possible cost because they share migration costs. Thus, the exploitation rate of public goods and interactions among defectors and cooperators will increase. In other words, the conditional defectors can exclusively cooperate in all collective behaviors related to migration (coalition dispersal) but defect otherwise. Therefore, these selfish successful migrators can convert the structured meta-population into a well-mixed game and violate the spatial structure mechanism. In fact 15 , is considered empirical evidence to assume that individuals reduce their dispersal costs by sharing it. Thereby, they can achieve successful migrations. Additionally, in metastatic cancer, migrating in groups (coalition dispersal) raises the efficacy to 50-fold more than individual dispersal 16 , 17 . Pay for the escape Conditional defectors can pay some of their wealth or waste some profits to escape punishment by producing substances to mislead punishers. Or possession of the significant tag that marks cooperators. Similarly, by reducing their payoff to be more similar and familiar to cooperators. If cheaters reduced the benefits, it might be hard to have been noticed by a quorum-sensing system or other defense mechanisms. It is considered a kind of imitation or tag-based decision that prevents cooperators from detecting and punishing defectors. Those cheaters pay a cost to escape sanctions or reduce the accuracy of the monitoring/punishment system. Therefore, they can merge with cooperator populations accordingly, violating punishment and kin-selection mechanisms. Methods We used two agent-based simulation models to investigate the concepts of \"cooperate for the spread\" and \"pay for the escape,\" both were net logo models created by Dr. Susan Hanisch. Afterward, we modified the first model to", "role": "user" }, { "content": "In the war between good and evil, I was there seeking to design powerful selfish strategies for investigating the defense mechanisms of cooperators. Surprisingly, the results serve a different domain of science. It gave me the hope to develop novel therapies using selfish strains as traitors betray their original species in favor of us. They commit treason inside cancer and microbial pathogen populations that usually resist traditional drugs, and destroy these harmful populations and drive them to go extinct. In a nutshell, I recruited villains to do something good. Unlikely beginning From an unlikely beginning, I took on the task of finding new treatments. The story began when I attempted to better understand how massive cooperative behavior evolved in populations of the living world under natural conditions in which selfishness was the only way to survive. Since Darwin's time, the problem of cooperation has preoccupied evolutionary biologists. How can cooperative behavior evolve and persist within the selfish natural world? This is \"the most important unanswered question in evolutionary biology,\" according to Lord Robert May. Why does cooperation matter? Cooperation is fundamental not only for social insects, as you may think, but also for humans, bacteria, viruses, cancer cells, and every living organism. However, it is inherently prone to exploitation by cheats or defective free riders, who reap the highest profit without paying their share. Therefore, they invest more in proliferation than cooperators. Consequently, their numbers rise and take over the population. However, the realm of living organisms is still here despite the infinite attacks of cheats. Evolutionary biologists explain this phenomenon by suggesting mechanisms that promote cooperation against cheats as kin selection, punishment, multilevel selection, and spatial structure. Computational models I created agent-based simulation models to examine the substantial promoting mechanisms—the ones that have already been mentioned above—against some specific selfish strategies I designed and coined \"conditional defector strategies.\" The conditional defector strategies were frequently dominant in the computational experiments, as they could outcompete the cooperating majority, which in turn declares the failure of the most crucial promoting mechanisms of cooperation. \"Therefore, it can be said that maintaining cooperation may be far harder than previously thought,\" the study says. The conditional defector (red) significantly dominated the other cooperative and selfish strategies. Credit: Figure 2. Scientific Reports (2022). DOI: 10.1038/s41598-022-18797-2 Conditional defector therapy Although the new insights revive a long-standing puzzle in evolution theory, they also pave the way for a new therapy for incurable diseases. The study said, \"Conditional defectors can be used as suicidal agents to drive the population of pathogens into self-destruction.\" From an evolutionary point of view, we can consider tumors or microbes as cooperating populations. They are clusters of cells wherein each cell incurs costly actions to produce essential substances in favor of all. They resist cheats by the mentioned defense mechanisms. However, conditional defectors can violate these mechanisms and outcompete natural cooperating strains. Ultimately, the entire population would die, as the selfish agents could not last after the extinction of cooperators due to the lack of the necessary collective actions, which is a phenomenon known as the tragedy of the commons. Creating the tragedy of the commons within pathogen populations means healing many uncontrolled incurable diseases. What are conditional defector strategies? The conditional defector strategy may be any cheating strategy that could occasionally cooperate, such as cooperating in some behaviors and cheating in others, or incurring additional costs to reap a group advantage even though still selfish in other behaviors. For instance: 1. Cooperate for spread The fundamental problem of ordinary cheaters is that they cannot arrange successful migrations. Therefore, their patches rapidly go to extinction. However, the conditional defection strategy can avoid this problem, as they cooperate only for the spread. They only share migration costs to decrease the portion of each participant. Hence, the conditional defectors have a high dispersal rate with the lowest possible price. Consequently, they could escape the local extinction threat. (Fig. 1.) 2. Pay for the escape \"Conditional defectors can pay some of their wealth or waste some profits to escape punishment,\" the study says. For example, some individuals produce substances to mislead punishers, or possess a significant tag that marks cooperators to escape punishment. Therefore, conditional defectors can safely merge within the cooperator's populations without consequences. (Fig. 2.) The idea of using cheaters to attack pathogens as a cooperator population is not new; many papers have suggested similar ideas previously. However, cooperators' defense mechanisms are always a major obstacle. Now, conditional defector strategies can surpass these obstacles to provide promising therapeutic applications. This story is part of Science X Dialog, where researchers can report findings from their published research articles. Visit this page for information about ScienceX Dialog and how to participate. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Cooperation is essential for all domains of life. Yet, ironically, it is intrinsically vulnerable to exploitation by cheats. Hence, an explanatory necessity spurs many evolutionary biologists to search for mechanisms that could support cooperation. In general, cooperation can emerge and be maintained when cooperators are sufficiently interacting with themselves. This communication provides a kind of assortment and reciprocity. The most crucial and common mechanisms to achieve that task are kin selection, spatial structure, and enforcement (punishment). Here, we used agent-based simulation models to investigate these pivotal mechanisms against conditional defector strategies. We concluded that the latter could easily violate the former and take over the population. This surprising outcome may urge us to rethink the evolution of cooperation, as it illustrates that maintaining cooperation may be more difficult than previously thought. Moreover, empirical applications may support these theoretical findings, such as invading the cooperator population of pathogens by genetically engineered conditional defectors, which could be a potential therapy for many incurable diseases. Introduction A long-standing puzzle in evolution theory is how cooperative behavior can evolve and persist within the selfish natural world. Once cooperation exists, it is always prone to exploitation by defective free riders who adopt selfish strategies for reaping the highest possible profit without paying the share. Thus, they invest most of their energy in reproduction. Therefore, cheaters could outcompete the cooperators and take over the population. Haldane pointed out that there was no general principle to solve this problem 1 . Since then, many partial mechanisms have been suggested, such as kin selection, group selection, reciprocity, policing, spatial structure, sanction, reward, and punishment 2 , 3 , 4 . Darwin himself suggested some core concepts of these mechanisms. This paper introduced conditional defector strategies that violate the kin selection, punishment, and spatial structure mechanisms. What are conditional defector strategies? From a conceptual viewpoint, a conditional defector strategy may be any cheating strategy that could somehow cooperate. In other words, it is a cheater who pays additional costs or wastes a portion of the profit to survive. Therefore, it is not necessarily defective in all behaviors or at all times. However, it may cooperate in some behaviors now and then. Consequently, they are not pure defectors. Some forms of conditional defector strategies Cooperate for the spread Dispersal is beneficial because it decreases Kin competition, sustains resources, and outsets colonization. Without dispersal, the fate of all populations is extinction 5 . Hence, an intermediate dispersal rate of cooperators is essential for cooperation maintenance 6 , 7 . Furthermore, migration can induce an explosive outbreak of cooperation, even in a world of selfish individuals with various sources of randomness, starting with defectors only 8 . Recently 9 showed for the first time that strategy-neutral migration triggered strategy oscillation in a two-strategy game even without the bridging of any transition strategies (states), thus defining a novel oscillating behavior fundamentally different from the conventional cyclic dominance previously found in a game of at least three or more strategies. Reference 10 studied the impact of varying migration preferences in promoting cooperation. They revealed the role of orientation-driven migration, where individuals prefer to move closer to their neighboring cooperators or favor escape away from their neighboring defectors. Nevertheless, dispersal is a costly behavior that increases the mortality of dispersers or decreases their fecundity 11 , 12 . Therefore, some studies have focused on the joint evolution of dispersal and cooperation 13 . Alternatively, there is a correlation between cooperation, dispersal rate, and dispersal cost 14 . Their findings asserted that the low dispersal cost selects against cooperation. Thus, if cheaters reduce their dispersal costs, they may turn the game against cooperators. Usually, cheats are not good migrators because dispersal itself is a cooperative behavior. The migrators leave their suitable habitats to other unknown environments and face dangerous predators to colonize a new patch. Therefore, such behavior is costly for migrators. Nevertheless, its benefits are also gained by non-migrators because it decreases kin competition. Thus, dispersal is considered a cooperative behavior that naturally does not expect to be abundant in cheats. Hence, cheaters go extinct rapidly with the depletion of local patches they dominated without global prevalence like cooperators; this might be the fundamental problem of cheaters. However, the probable solution is adopting a conditional defection strategy wherein free riders would cooperate only for the spread. The actors of this selfish strategy would have a high dispersal rate with the lowest possible cost because they share migration costs. Thus, the exploitation rate of public goods and interactions among defectors and cooperators will increase. In other words, the conditional defectors can exclusively cooperate in all collective behaviors related to migration (coalition dispersal) but defect otherwise. Therefore, these selfish successful migrators can convert the structured meta-population into a well-mixed game and violate the spatial structure mechanism. In fact 15 , is considered empirical evidence to assume that individuals reduce their dispersal costs by sharing it. Thereby, they can achieve successful migrations. Additionally, in metastatic cancer, migrating in groups (coalition dispersal) raises the efficacy to 50-fold more than individual dispersal 16 , 17 . Pay for the escape Conditional defectors can pay some of their wealth or waste some profits to escape punishment by producing substances to mislead punishers. Or possession of the significant tag that marks cooperators. Similarly, by reducing their payoff to be more similar and familiar to cooperators. If cheaters reduced the benefits, it might be hard to have been noticed by a quorum-sensing system or other defense mechanisms. It is considered a kind of imitation or tag-based decision that prevents cooperators from detecting and punishing defectors. Those cheaters pay a cost to escape sanctions or reduce the accuracy of the monitoring/punishment system. Therefore, they can merge with cooperator populations accordingly, violating punishment and kin-selection mechanisms. Methods We used two agent-based simulation models to investigate the concepts of "cooperate for the spread" and "pay for the escape," both were net logo models created by Dr. Susan Hanisch. Afterward, we modified the first model to<|im_end|> <|im_start|>assistant In the war between good and evil, I was there seeking to design powerful selfish strategies for investigating the defense mechanisms of cooperators. Surprisingly, the results serve a different domain of science. It gave me the hope to develop novel therapies using selfish strains as traitors betray their original species in favor of us. They commit treason inside cancer and microbial pathogen populations that usually resist traditional drugs, and destroy these harmful populations and drive them to go extinct. In a nutshell, I recruited villains to do something good. Unlikely beginning From an unlikely beginning, I took on the task of finding new treatments. The story began when I attempted to better understand how massive cooperative behavior evolved in populations of the living world under natural conditions in which selfishness was the only way to survive. Since Darwin's time, the problem of cooperation has preoccupied evolutionary biologists. How can cooperative behavior evolve and persist within the selfish natural world? This is "the most important unanswered question in evolutionary biology," according to Lord Robert May. Why does cooperation matter? Cooperation is fundamental not only for social insects, as you may think, but also for humans, bacteria, viruses, cancer cells, and every living organism. However, it is inherently prone to exploitation by cheats or defective free riders, who reap the highest profit without paying their share. Therefore, they invest more in proliferation than cooperators. Consequently, their numbers rise and take over the population. However, the realm of living organisms is still here despite the infinite attacks of cheats. Evolutionary biologists explain this phenomenon by suggesting mechanisms that promote cooperation against cheats as kin selection, punishment, multilevel selection, and spatial structure. Computational models I created agent-based simulation models to examine the substantial promoting mechanisms—the ones that have already been mentioned above—against some specific selfish strategies I designed and coined "conditional defector strategies." The conditional defector strategies were frequently dominant in the computational experiments, as they could outcompete the cooperating majority, which in turn declares the failure of the most crucial promoting mechanisms of cooperation. "Therefore, it can be said that maintaining cooperation may be far harder than previously thought," the study says. The conditional defector (red) significantly dominated the other cooperative and selfish strategies. Credit: Figure 2. Scientific Reports (2022). DOI: 10.1038/s41598-022-18797-2 Conditional defector therapy Although the new insights revive a long-standing puzzle in evolution theory, they also pave the way for a new therapy for incurable diseases. The study said, "Conditional defectors can be used as suicidal agents to drive the population of pathogens into self-destruction." From an evolutionary point of view, we can consider tumors or microbes as cooperating populations. They are clusters of cells wherein each cell incurs costly actions to produce essential substances in favor of all. They resist cheats by the mentioned defense mechanisms. However, conditional defectors can violate these mechanisms and outcompete natural cooperating strains. Ultimately, the entire population would die, as the selfish agents could not last after the extinction of cooperators due to the lack of the necessary collective actions, which is a phenomenon known as the tragedy of the commons. Creating the tragedy of the commons within pathogen populations means healing many uncontrolled incurable diseases. What are conditional defector strategies? The conditional defector strategy may be any cheating strategy that could occasionally cooperate, such as cooperating in some behaviors and cheating in others, or incurring additional costs to reap a group advantage even though still selfish in other behaviors. For instance: 1. Cooperate for spread The fundamental problem of ordinary cheaters is that they cannot arrange successful migrations. Therefore, their patches rapidly go to extinction. However, the conditional defection strategy can avoid this problem, as they cooperate only for the spread. They only share migration costs to decrease the portion of each participant. Hence, the conditional defectors have a high dispersal rate with the lowest possible price. Consequently, they could escape the local extinction threat. (Fig. 1.) 2. Pay for the escape "Conditional defectors can pay some of their wealth or waste some profits to escape punishment," the study says. For example, some individuals produce substances to mislead punishers, or possess a significant tag that marks cooperators to escape punishment. Therefore, conditional defectors can safely merge within the cooperator's populations without consequences. (Fig. 2.) The idea of using cheaters to attack pathogens as a cooperator population is not new; many papers have suggested similar ideas previously. However, cooperators' defense mechanisms are always a major obstacle. Now, conditional defector strategies can surpass these obstacles to provide promising therapeutic applications. This story is part of Science X Dialog, where researchers can report findings from their published research articles. Visit this page for information about ScienceX Dialog and how to participate. <|im_end|>

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4420, 359, 16409, 1887, 13, 15636, 11, 814, 649, 11117, 449, 1080, 8043, 22673, 28178, 11, 45462, 25060, 323, 24890, 76805, 24717, 13, 19331, 1226, 1511, 1403, 8479, 6108, 19576, 4211, 311, 19874, 279, 19476, 315, 330, 1030, 86299, 369, 279, 9041, 1, 323, 330, 14214, 369, 279, 12731, 1359, 2225, 1051, 4272, 12708, 4211, 3549, 555, 2999, 13, 31033, 21296, 16438, 13, 4740, 1637, 11, 584, 11041, 279, 1176, 1646, 311, 128257, 198, 128256, 78191, 198, 644, 279, 4208, 1990, 1695, 323, 14289, 11, 358, 574, 1070, 11125, 311, 2955, 8147, 45743, 15174, 369, 24834, 279, 9232, 24717, 315, 22415, 3046, 13, 8242, 49264, 11, 279, 3135, 8854, 264, 2204, 8106, 315, 8198, 13, 1102, 6688, 757, 279, 3987, 311, 2274, 11775, 52312, 1701, 45743, 42400, 439, 18027, 1105, 34568, 872, 4113, 9606, 304, 4799, 315, 603, 13, 2435, 5379, 79359, 4871, 9572, 323, 75418, 1853, 11968, 22673, 430, 6118, 22884, 8776, 11217, 11, 323, 7066, 1521, 28856, 22673, 323, 6678, 1124, 311, 733, 69918, 13, 763, 264, 94013, 11, 358, 45425, 61810, 311, 656, 2555, 1695, 13, 1252, 14617, 7314, 5659, 459, 17821, 7314, 11, 358, 3952, 389, 279, 3465, 315, 9455, 502, 22972, 13, 578, 3446, 6137, 994, 358, 17644, 311, 2731, 3619, 1268, 11191, 48566, 7865, 28995, 304, 22673, 315, 279, 5496, 1917, 1234, 5933, 4787, 304, 902, 45743, 2136, 574, 279, 1193, 1648, 311, 18167, 13, 8876, 45480, 596, 892, 11, 279, 3575, 315, 23915, 706, 864, 41456, 41993, 6160, 22012, 13, 2650, 649, 48566, 7865, 38680, 323, 23135, 2949, 279, 45743, 5933, 1917, 30, 1115, 374, 330, 1820, 1455, 3062, 76547, 3488, 304, 41993, 34458, 1359, 4184, 311, 10425, 8563, 3297, 13, 8595, 1587, 23915, 5030, 30, 73808, 374, 16188, 539, 1193, 369, 3674, 41911, 11, 439, 499, 1253, 1781, 11, 719, 1101, 369, 12966, 11, 24032, 11, 42068, 11, 9572, 7917, 11, 323, 1475, 5496, 47120, 13, 4452, 11, 433, 374, 49188, 38097, 311, 40761, 555, 76488, 477, 64903, 1949, 30803, 11, 889, 58003, 279, 8592, 11626, 2085, 12798, 872, 4430, 13, 15636, 11, 814, 2793, 810, 304, 53840, 1109, 22415, 3046, 13, 53123, 11, 872, 5219, 10205, 323, 1935, 927, 279, 7187, 13, 4452, 11, 279, 22651, 315, 5496, 44304, 374, 2103, 1618, 8994, 279, 24746, 8951, 315, 76488, 13, 38321, 661, 6160, 22012, 10552, 420, 25885, 555, 23377, 24717, 430, 12192, 23915, 2403, 76488, 439, 24890, 6727, 11, 25060, 11, 2814, 458, 899, 6727, 11, 323, 29079, 6070, 13, 93028, 4211, 358, 3549, 8479, 6108, 19576, 4211, 311, 21635, 279, 12190, 22923, 24717, 22416, 6305, 430, 617, 2736, 1027, 9932, 3485, 2345, 69849, 1063, 3230, 45743, 15174, 358, 6319, 323, 78718, 330, 46468, 711, 1279, 15174, 1210, 578, 35787, 711, 1279, 15174, 1051, 14134, 25462, 304, 279, 55580, 21896, 11, 439, 814, 1436, 704, 5807, 7870, 279, 82589, 8857, 11, 902, 304, 2543, 50888, 279, 8060, 315, 279, 1455, 16996, 22923, 24717, 315, 23915, 13, 330, 55915, 11, 433, 649, 387, 1071, 430, 20958, 23915, 1253, 387, 3117, 16127, 1109, 8767, 3463, 1359, 279, 4007, 2795, 13, 578, 35787, 711, 1279, 320, 1171, 8, 12207, 30801, 279, 1023, 48566, 323, 45743, 15174, 13, 16666, 25, 19575, 220, 17, 13, 38130, 29140, 320, 2366, 17, 570, 59670, 25, 220, 605, 13, 6889, 23, 2754, 18136, 3264, 12, 18642, 12, 9674, 3534, 12, 17, 93073, 711, 1279, 15419, 10541, 279, 502, 26793, 59816, 264, 1317, 56703, 25649, 304, 15740, 10334, 11, 814, 1101, 94123, 279, 1648, 369, 264, 502, 15419, 369, 62622, 481, 19338, 13, 578, 4007, 1071, 11, 330, 80333, 711, 10829, 649, 387, 1511, 439, 66153, 13307, 311, 6678, 279, 7187, 315, 78284, 1139, 659, 6953, 3099, 1210, 5659, 459, 41993, 1486, 315, 1684, 11, 584, 649, 2980, 56071, 477, 80727, 439, 82589, 22673, 13, 2435, 527, 28066, 315, 7917, 42418, 1855, 2849, 3709, 1759, 34348, 6299, 311, 8356, 7718, 33155, 304, 4799, 315, 682, 13, 2435, 22884, 76488, 555, 279, 9932, 9232, 24717, 13, 4452, 11, 35787, 711, 10829, 649, 41587, 1521, 24717, 323, 704, 5807, 7870, 5933, 82589, 42400, 13, 55106, 11, 279, 4553, 7187, 1053, 2815, 11, 439, 279, 45743, 13307, 1436, 539, 1566, 1306, 279, 52609, 315, 22415, 3046, 4245, 311, 279, 6996, 315, 279, 5995, 22498, 6299, 11, 902, 374, 264, 25885, 3967, 439, 279, 31926, 315, 279, 66062, 13, 32406, 279, 31926, 315, 279, 66062, 2949, 1853, 11968, 22673, 3445, 21730, 1690, 653, 59707, 62622, 481, 19338, 13, 3639, 527, 35787, 711, 1279, 15174, 30, 578, 35787, 711, 1279, 8446, 1253, 387, 904, 42823, 8446, 430, 1436, 23781, 47903, 11, 1778, 439, 82589, 304, 1063, 28198, 323, 42823, 304, 3885, 11, 477, 304, 46839, 5217, 7194, 311, 58003, 264, 1912, 9610, 1524, 3582, 2103, 45743, 304, 1023, 28198, 13, 1789, 2937, 25, 220, 16, 13, 24421, 349, 369, 9041, 578, 16188, 3575, 315, 19664, 3091, 11796, 374, 430, 814, 4250, 31993, 6992, 17500, 13, 15636, 11, 872, 29760, 19019, 733, 311, 52609, 13, 4452, 11, 279, 35787, 11211, 407, 8446, 649, 5766, 420, 3575, 11, 439, 814, 47903, 1193, 369, 279, 9041, 13, 2435, 1193, 4430, 12172, 7194, 311, 18979, 279, 13651, 315, 1855, 25923, 13, 32140, 11, 279, 35787, 711, 10829, 617, 264, 1579, 79835, 278, 4478, 449, 279, 15821, 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369, 2038, 922, 10170, 55, 13698, 323, 1268, 311, 16136, 13, 220, 128257, 198 ]

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Background Conventional corn dry-grind ethanol production process requires exogenous alpha and glucoamylases enzymes to breakdown starch into glucose, which is fermented to ethanol by yeast. This study evaluates the potential use of new genetically engineered corn and yeast, which can eliminate or minimize the use of these external enzymes, improve the economics and process efficiencies, and simplify the process. An approach of in situ ethanol removal during fermentation was also investigated for its potential to improve the efficiency of high-solid fermentation, which can significantly reduce the downstream ethanol and co-product recovery cost. Results The fermentation of amylase corn (producing endogenous α-amylase) using conventional yeast and no addition of exogenous α-amylase resulted in ethanol concentration of 4.1 % higher compared to control treatment (conventional corn using exogenous α-amylase). Conventional corn processed with exogenous α-amylase and superior yeast (producing glucoamylase or GA) with no exogenous glucoamylase addition resulted in ethanol concentration similar to control treatment (conventional yeast with exogenous glucoamylase addition). Combination of amylase corn and superior yeast required only 25 % of recommended glucoamylase dose to complete fermentation and achieve ethanol concentration and yield similar to control treatment (conventional corn with exogenous α-amylase, conventional yeast with exogenous glucoamylase). Use of superior yeast with 50 % GA addition resulted in similar increases in yield for conventional or amylase corn of approximately 7 % compared to that of control treatment. Combination of amylase corn, superior yeast, and in situ ethanol removal resulted in a process that allowed complete fermentation of 40 % slurry solids with only 50 % of exogenous GA enzyme requirements and 64.6 % higher ethanol yield compared to that of conventional process. Conclusions Use of amylase corn and superior yeast in the dry-grind processing industry can reduce the total external enzyme usage by more than 80 %, and combining their use with in situ removal of ethanol during fermentation allows efficient high-solid fermentation. Background Due to increasing population and industrialization, global energy demand has increased steadily over the last few decades, and currently, about 80 % of this energy is derived from non-renewable fossil fuel supplies [ 1 ]. Transportation sector is one of the major consumers of the fossil fuels in the United States [ 2 ]. The concerns of depleting fossil fuel and the negative environmental impacts from their use necessitate the need to identify and develop renewable and sustainable energy sources. Bioethanol is considered as the most promising renewable transportation fuel, which can be produced in significant quantities from fermentation of sugars obtained from starch, sugary or cellulosic materials. United States is the biggest bioethanol producer in world with about 14.3 billion gallon (54.1 billion liters; 58 % of world production) production in year 2014 [ 3 ]. Most of the ethanol in the United States is produced from corn using dry-grind or wet milling process. Dry-grind is the most common used method for corn ethanol production [ 4 ]. In year 2014, about 5.4 billion bushels (25.4 kg in one bushel) of corn (37.8 % of total production) was processed in dry-grind industry [ 5 ]. Figure 1 illustrates the major steps used during laboratory scale conventional dry-grind process. The ground corn and water slurry is liquefied using α-amylase enzymes at high temperatures to convert starch into dextrins. The dextrins are further converted to glucose using glucoamylase (GA) enzymes during saccharification process, which is fermented to ethanol by yeast. Currently, these alpha and glucoamylases enzymes are added externally in liquid form during the liquefaction and saccharification process respectively. Saccharification and fermentation are performed in single step in the same reactor by process known as simultaneous saccharification and fermentation (SSF). Ethanol is recovered from the fermentation broth using distillation process. Remaining non-carbohydrate fractions in corn (germ, fiber, and protein) are recovered as a co-product called distillers dried grains with soluble (DDGS) at the end of the process. Fig. 1 Schematic of laboratory scale dry-grind corn process for ethanol production. Figure illustrates the steps followed during lab scale dry-grind processing for ethanol production from corn Full size image Over the last few decades, several advances have been made to improve the ethanol yields and profitability of the dry-grind process, including modifications in the production process [ 6 ], recovery of high-value co-products [ 5 , 7 ], use of advanced enzymes [ 8 , 9 ], and use of high-yield corn varieties [ 10 ]. A new corn developed by transgenic technology, known as amylase corn, produces an endogenous α-amylase in endosperm that is activated at high temperature and moisture [ 10 , 11 ]. Due to high expression levels of enzymes, only a small amount of the corn is required to be mixed with the conventional dent corn. Use of the amylase corn mix during the dry-grind process can eliminate the need of external addition of exogenous α-amylase. Similarly, a new engineered yeast, referred as “superior yeast” in this manuscript, is an advanced strain of Saccharomyces cerevisiae which expresses endogenous glucoamylases and provides novel metabolic pathways for high ethanol yields by reducing glycerol production. Use of this yeast can eliminate or alleviate the addition of expensive glucoamylase enzymes during SSF process, potentially improving the process efficiency, and reducing the overall ethanol production cost. Increasing the solid loadings during dry-grind process can be another approach to reduce the overall cost of ethanol production process. Using high-solid slurries in dry-grind process can decrease the overall energy use and process cost by reducing load on downstream processing of ethanol and co-product recovery and lowering the volumes of the processing equipment. However, the solid loadings during the ethanol process are restricted to 30–32 % w/w due to high viscosities, and yeast stress by high glucose and ethanol concentrations [ 12 – 14 ]. High-solid loadings can lead to higher final ethanol concentrations; however, low ethanol yields (liters/metric ton or gallons/bushel) are observed because of strong ethanol inhibition [ 15 ]. Simultaneous stripping off ethanol under vacuum during SSF process is one of the potential approaches to reduce the ethanol inhibition", "role": "user" }, { "content": "New research at the Integrated Bioprocessing Research Laboratory (IBRL) on the University of Illinois Urbana-Champaign campus could significantly change ethanol production by lowering operating costs and simplifying the dry grind process. \"There are currently more than 200 dry grind plants that are processing corn to produce ethanol,\" says Vijay Singh, director of IBRL and a professor in agricultural and biological engineering. \"The dry grind process requires two different enzymes to convert corn starch to glucose, which is further fermented to ethanol by yeast.\" Singh says that process has been simplified by combined use and optimization of three new technologies. \"A new corn developed by transgenic technology, known as amylase corn, produces one of these enzymes in the grain itself, and a newly engineered 'superior yeast' provides the second enzyme, as well as fermenting the glucose. \"There is a high expression level of the first enzyme, α-amylase, in the new corn, so only a small amount [15 percent was tested in these studies] of this corn is required to be mixed with conventional dent corn,\" Singh notes. \"The superior yeast provides the second enzyme, glucoamylase, and also provides an alternate metabolic pathway to reduce by-product formation during fermentation. Combined use of this corn and superior yeast can reduce the total enzyme addition by more than 80 percent.\" Another approach to improve the dry grind process is to use high solids in the plant. However, according to Singh, high solid concentrations leads to high ethanol build-up in the tank. \"High ethanol affects the yeast viability and inhibits its fermentation performance, so we have added a third technology to the process. We remove the ethanol as it is being produced, using a vacuum flashing process that is patented technology from the University of Illinois. Only a couple of vacuum cycles of 1 to 1.5 hours can bring the ethanol concentration below the inhibitory levels without affecting yeast health and allow complete fermentation of corn solids up to 40 percent,\" says Singh. Deepak Kumar, a postdoctoral research associate in agricultural and biological engineering, says because the dry grind process uses a significant amount of water, using more solid material in the slurry - 40 percent as opposed to 30-35 percent - means less water going into the process. \"When ethanol is produced, it is in a very dilute solution. You have a small amount of ethanol and a large amount of water,\" says Kumar. \"We cut down the water use by pushing high solids. When we reduce the amount of water, we also reduce the amount of energy required to remove the water.\" Singh believes this new research has the potential to improve the economics and process efficiencies and simplify the dry grind process. \"By developing highly optimized technologies, we will benefit the entire dry grind industry,\" he concludes. Singh and Kumar received the 2016 Bioenergy Society of Singapore (BESS) Achievement Award for their work, in particular their paper \"Dry-grind Processing using Amylase Corn and Superior Yeast to Reduce the Exogenous Enzyme Requirements in Bioethanol Production.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Background Conventional corn dry-grind ethanol production process requires exogenous alpha and glucoamylases enzymes to breakdown starch into glucose, which is fermented to ethanol by yeast. This study evaluates the potential use of new genetically engineered corn and yeast, which can eliminate or minimize the use of these external enzymes, improve the economics and process efficiencies, and simplify the process. An approach of in situ ethanol removal during fermentation was also investigated for its potential to improve the efficiency of high-solid fermentation, which can significantly reduce the downstream ethanol and co-product recovery cost. Results The fermentation of amylase corn (producing endogenous α-amylase) using conventional yeast and no addition of exogenous α-amylase resulted in ethanol concentration of 4.1 % higher compared to control treatment (conventional corn using exogenous α-amylase). Conventional corn processed with exogenous α-amylase and superior yeast (producing glucoamylase or GA) with no exogenous glucoamylase addition resulted in ethanol concentration similar to control treatment (conventional yeast with exogenous glucoamylase addition). Combination of amylase corn and superior yeast required only 25 % of recommended glucoamylase dose to complete fermentation and achieve ethanol concentration and yield similar to control treatment (conventional corn with exogenous α-amylase, conventional yeast with exogenous glucoamylase). Use of superior yeast with 50 % GA addition resulted in similar increases in yield for conventional or amylase corn of approximately 7 % compared to that of control treatment. Combination of amylase corn, superior yeast, and in situ ethanol removal resulted in a process that allowed complete fermentation of 40 % slurry solids with only 50 % of exogenous GA enzyme requirements and 64.6 % higher ethanol yield compared to that of conventional process. Conclusions Use of amylase corn and superior yeast in the dry-grind processing industry can reduce the total external enzyme usage by more than 80 %, and combining their use with in situ removal of ethanol during fermentation allows efficient high-solid fermentation. Background Due to increasing population and industrialization, global energy demand has increased steadily over the last few decades, and currently, about 80 % of this energy is derived from non-renewable fossil fuel supplies [ 1 ]. Transportation sector is one of the major consumers of the fossil fuels in the United States [ 2 ]. The concerns of depleting fossil fuel and the negative environmental impacts from their use necessitate the need to identify and develop renewable and sustainable energy sources. Bioethanol is considered as the most promising renewable transportation fuel, which can be produced in significant quantities from fermentation of sugars obtained from starch, sugary or cellulosic materials. United States is the biggest bioethanol producer in world with about 14.3 billion gallon (54.1 billion liters; 58 % of world production) production in year 2014 [ 3 ]. Most of the ethanol in the United States is produced from corn using dry-grind or wet milling process. Dry-grind is the most common used method for corn ethanol production [ 4 ]. In year 2014, about 5.4 billion bushels (25.4 kg in one bushel) of corn (37.8 % of total production) was processed in dry-grind industry [ 5 ]. Figure 1 illustrates the major steps used during laboratory scale conventional dry-grind process. The ground corn and water slurry is liquefied using α-amylase enzymes at high temperatures to convert starch into dextrins. The dextrins are further converted to glucose using glucoamylase (GA) enzymes during saccharification process, which is fermented to ethanol by yeast. Currently, these alpha and glucoamylases enzymes are added externally in liquid form during the liquefaction and saccharification process respectively. Saccharification and fermentation are performed in single step in the same reactor by process known as simultaneous saccharification and fermentation (SSF). Ethanol is recovered from the fermentation broth using distillation process. Remaining non-carbohydrate fractions in corn (germ, fiber, and protein) are recovered as a co-product called distillers dried grains with soluble (DDGS) at the end of the process. Fig. 1 Schematic of laboratory scale dry-grind corn process for ethanol production. Figure illustrates the steps followed during lab scale dry-grind processing for ethanol production from corn Full size image Over the last few decades, several advances have been made to improve the ethanol yields and profitability of the dry-grind process, including modifications in the production process [ 6 ], recovery of high-value co-products [ 5 , 7 ], use of advanced enzymes [ 8 , 9 ], and use of high-yield corn varieties [ 10 ]. A new corn developed by transgenic technology, known as amylase corn, produces an endogenous α-amylase in endosperm that is activated at high temperature and moisture [ 10 , 11 ]. Due to high expression levels of enzymes, only a small amount of the corn is required to be mixed with the conventional dent corn. Use of the amylase corn mix during the dry-grind process can eliminate the need of external addition of exogenous α-amylase. Similarly, a new engineered yeast, referred as “superior yeast” in this manuscript, is an advanced strain of Saccharomyces cerevisiae which expresses endogenous glucoamylases and provides novel metabolic pathways for high ethanol yields by reducing glycerol production. Use of this yeast can eliminate or alleviate the addition of expensive glucoamylase enzymes during SSF process, potentially improving the process efficiency, and reducing the overall ethanol production cost. Increasing the solid loadings during dry-grind process can be another approach to reduce the overall cost of ethanol production process. Using high-solid slurries in dry-grind process can decrease the overall energy use and process cost by reducing load on downstream processing of ethanol and co-product recovery and lowering the volumes of the processing equipment. However, the solid loadings during the ethanol process are restricted to 30–32 % w/w due to high viscosities, and yeast stress by high glucose and ethanol concentrations [ 12 – 14 ]. High-solid loadings can lead to higher final ethanol concentrations; however, low ethanol yields (liters/metric ton or gallons/bushel) are observed because of strong ethanol inhibition [ 15 ]. Simultaneous stripping off ethanol under vacuum during SSF process is one of the potential approaches to reduce the ethanol inhibition<|im_end|> <|im_start|>assistant New research at the Integrated Bioprocessing Research Laboratory (IBRL) on the University of Illinois Urbana-Champaign campus could significantly change ethanol production by lowering operating costs and simplifying the dry grind process. "There are currently more than 200 dry grind plants that are processing corn to produce ethanol," says Vijay Singh, director of IBRL and a professor in agricultural and biological engineering. "The dry grind process requires two different enzymes to convert corn starch to glucose, which is further fermented to ethanol by yeast." Singh says that process has been simplified by combined use and optimization of three new technologies. "A new corn developed by transgenic technology, known as amylase corn, produces one of these enzymes in the grain itself, and a newly engineered 'superior yeast' provides the second enzyme, as well as fermenting the glucose. "There is a high expression level of the first enzyme, α-amylase, in the new corn, so only a small amount [15 percent was tested in these studies] of this corn is required to be mixed with conventional dent corn," Singh notes. "The superior yeast provides the second enzyme, glucoamylase, and also provides an alternate metabolic pathway to reduce by-product formation during fermentation. Combined use of this corn and superior yeast can reduce the total enzyme addition by more than 80 percent." Another approach to improve the dry grind process is to use high solids in the plant. However, according to Singh, high solid concentrations leads to high ethanol build-up in the tank. "High ethanol affects the yeast viability and inhibits its fermentation performance, so we have added a third technology to the process. We remove the ethanol as it is being produced, using a vacuum flashing process that is patented technology from the University of Illinois. Only a couple of vacuum cycles of 1 to 1.5 hours can bring the ethanol concentration below the inhibitory levels without affecting yeast health and allow complete fermentation of corn solids up to 40 percent," says Singh. Deepak Kumar, a postdoctoral research associate in agricultural and biological engineering, says because the dry grind process uses a significant amount of water, using more solid material in the slurry - 40 percent as opposed to 30-35 percent - means less water going into the process. "When ethanol is produced, it is in a very dilute solution. You have a small amount of ethanol and a large amount of water," says Kumar. "We cut down the water use by pushing high solids. When we reduce the amount of water, we also reduce the amount of energy required to remove the water." Singh believes this new research has the potential to improve the economics and process efficiencies and simplify the dry grind process. "By developing highly optimized technologies, we will benefit the entire dry grind industry," he concludes. Singh and Kumar received the 2016 Bioenergy Society of Singapore (BESS) Achievement Award for their work, in particular their paper "Dry-grind Processing using Amylase Corn and Superior Yeast to Reduce the Exogenous Enzyme Requirements in Bioethanol Production." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The exact anatomical location for an iron particle-based magnetic sense remains enigmatic in vertebrates. For mammals, findings from a cornea anaesthesia experiment in mole rats suggest that it carries the primary sensors for magnetoreception. Yet, this has never been tested in a free-ranging mammal. Here, we investigated whether intact corneal sensation is crucial for navigation in migrating Nathusius’ bats, Pipistrellus nathusii , translocated from their migratory corridor. We found that bats treated with corneal anaesthesia in both eyes flew in random directions after translocation and release, contrasting bats with a single eye treated, and the control group, which both oriented in the seasonally appropriate direction. Using a Y-maze test, we confirmed that light detection remained unaffected by topical anaesthesia. Therefore our results suggest the cornea as a possible site of magnetoreception in bats, although other conceivable effects of the anaesthetic are also explored. Furthermore, we demonstrate that the corneal based sense is of bilateral nature but can function in a single eye if necessary. Introduction While the capacity for magnetoreception among mammals is evident from a number of behavioural experiments 1 , 2 , 3 , 4 , 5 , 6 , 7 , the anatomical location of the involved receptors remains as enigmatic as in any other animal to date 8 , 9 . Interestingly enough, when tested in darkness, mammals 10 , 11 , 12 , 13 , fish 14 , 15 and sea turtles 16 were able to orient by a magnetic polarity compass. The underlying magnetic sense is hypothesized to involve intra-cellular iron oxide, i.e., magnetite nanoparticles (Fe 3 O 4 ), which would be sensitive to the horizontal polarity of a magnetic field, enabling these animals to distinguish between magnetic north and south, independent of light. Intra-cellular iron oxide could also be responsible for magnetic signal transmission through control of ion channels depending on the alignment of animals in relation to the magnetic field 8 , 15 , 17 , 18 . Wegner and colleagues postulated that the cornea may be the location of the primary magnetoreceptors in mammals 19 . Specifically, they showed that in mole rats, Fukomys anselli , bilateral anaesthesia of the cornea resulted in randomly oriented nest-building, contrary to the usually magnetic polarity-dependent nesting behaviour 10 , 19 . According to the innervation of the cornea, the ophthalmic branch of the trigeminal nerve would transmit the magnetic signal to the midbrain where magnetic stimuli could be processed 11 , 13 , 20 , 21 , 22 . Yet, to date, the hypothesis of a corneal magnetic sense has never been challenged nor expanded from laboratory conditions to freely moving animals by performing a true navigation task in the field, e.g., during seasonal migration. Non-migratory bats are known to possess a polarity-sensitive magnetic compass, which they use for homing tasks 5 , 12 , 23 . Furthermore, results from a classic ‘Kalmijn-Blakemore’ pulse re-magnetization experiment in big brown bats ( Eptesicus fuscus ) are consistent with the hypothesis that magneto-sensory cells located somewhere in a bat’s body carry single-domain magnetite 24 . In contrast, the compass cues and sensory structures the migratory bats use for long-range in-flight navigation still remain undetermined. Only recently, it was demonstrated that bats calibrate their compass system to the solar azimuth at sunset and could take up a seasonally appropriate migratory heading after moderate displacement from their migration corridor 25 , 26 . To study the role of the cornea in navigation of vertebrates that are adapted to long-range navigation, we performed translocation experiments with 80 adult Nathusius’ bats ( Pipistrellus nathusii ) caught at the Baltic Sea during the late summer migration season. A geographical displacement of the bats was necessary to study their individual orientation behaviour at an unfamiliar site after astronomical twilight and when remote from the high density of conspecifics along the migration corridor, as well as the landmark cues emanating from the shore over short range. Half of the bats received either unilateral or bilateral topical corneal anaesthesia prior to release, while the other half were treated with a saline solution to create a sham control condition. Importantly, we also conducted tests of photoreception in another 76 bats using a Y-maze choice experiment to validate retinal function; specifically, the capacity of bats to still discriminate between light and dark in their environment, despite corneal anaesthesia, was tested. We hypothesized that migratory bats depend on corneal magnetoreception for navigation. If the cornea plays a role in magnetic orientation, we predicted that translocated bats treated with a topical anaesthetic on both eyes would vanish in random directions after release. However, bats with a single eye treated would be able to navigate because the other eye’s cornea would still be functional, i.e., to transmit sensory stimuli through the ophthalmic branch of the trigeminal nerve, and to enable the released bats to fly in a correct migratory direction similar to bats of the sham treated group. Results Detection of a light source is unimpaired after topical corneal anaesthesia In previous Y-maze experiments with one dark and one lit exit, the bats chose the lit exit instead of the dark one 27 . In contrast, blindfolded bats totally deprived of light perception chose the exits randomly 28 . We performed similar tests, yet without blindfolding, to evaluate our bats’ principal ability of light detection after administering topical corneal anaesthesia by oxybuprocaine eye drops. When we tested the unilateral and bilateral treatment groups that received the topical corneal anaesthetic, and the two sham control groups that received eye drops of saline solution bilaterally, our tests did not indicate a differential effect between these applications on the bats’ phototactic behaviour, i.e., animals of both the treatment groups and the sham control groups preferred the lit exit of the Y-maze (sham control 1: n = 22, 77% (proportion of bats choosing the lit exit in %), χ 2 = 6.55, W = 0.55, P = 0.011; single eye treated: n = 16, 81.3%, χ 2 = 6.25, W =", "role": "user" }, { "content": "Mammals see with their eyes, hear with their ears and smell with their nose. But which sense or organ allows them to orient themselves on their migrations, which sometimes go far beyond their local foraging areas and therefore require an extended ability to navigate? Scientific experiments led by the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW), published together with Prof. Richard A. Holland (Bangor University, UK) and Dr. Gunārs Petersons (Latvia University of Life Sciences and Technologies) now show that the cornea of the eyes is the location of this important sense in migrating bats. If the cornea is anesthetized, the otherwise reliable sense of orientation is disturbed while light detection remains unimpaired. The experiment suggests the localisation of a magnetic sense in mammals. The paper is published in the scientific journal Communications Biology. A research team led by Dr. Oliver Lindecke and PD Dr. Christian Voigt from Leibniz-IZW has demonstrated for the first time that environmental signals that are important for navigating over long distances are picked up via the cornea. They conducted experiments with Nathusius' bats (Pipistrellus nathusii) during the late summer migration period. In bats of one test group, the scientists locally anesthetized the cornea with a drop of oxybuprocaine. This surface anesthetic is widely used in ophthalmology to temporarily desensitize the patient's cornea when the eyes are overly irritated. Effects on orientation, however, had not been previously recorded. In another test group of bats, the research team anesthetized the cornea of only one eye. The individuals in the control group were not anesthetized, but instead received an isotonic saline solution as eye drops. All animals in this scientific experiment were captured within a migration corridor at the coastline of the Baltic Sea and released singly in the open field 11 kilometers inland from the capture site immediately after treatment. The scientists first used bat detectors to make sure that there were no other bats above the field at the time of release that the test animals could have followed. The person observing the direction of movement of released bats was unaware of how bats were treated experimentally. \"The control group and the group with unilateral corneal anesthesia oriented themselves clearly in the expected southerly directions, whereas the bats with bilateral anesthetized corneas flew off in random directions,\" explains Dr. Oliver Lindecke, first author of the paper. \"This evident difference in behavior suggests that corneal anesthesia disrupted a sense of direction, yet orientation apparently still works well with one eye.\" As corneal treatment wears off after a short time, the bats were able to resume their journeys south after the experiment. \"We observed here for the first time in an experiment how a migrating mammal was literally blown off course—a milestone in behavioral and sensory biology that allows us to study the biological navigation system in a more targeted way.\" In order to rule out the possibility that the anaesthetisation of the cornea also affects the sense of sight and that the scientists would thus come to the wrong conclusions, they carried out a complementary test. Once again dividing the bats into experimental and control groups, the researchers tested whether the response of bats to light changed after anesthesia of the corneas on one or both sides. \"We know from previous research that bats prefer an illuminated exit when leaving a simple Y-shaped labyrinth,\" explains PD Dr. Christian Voigt, head of the Leibniz-IZW Department of Evolutionary Ecology. \"In our experiment, the animals with one-sided or two-sided anesthesia also showed this preference; we therefore can rule out that the ability to see light was altered after corneal treatment. The ability to see light would, of course, also influence long-distance navigation.\" Many vertebrates such as bats, dolphins, whales, fish and turtles, for example, are able to safely navigate in darkness, whether it is under the open night sky, when it is cloudy at night or in caves and tunnels as well as in the depths of the oceans. For many decades, scientists have been searching for the sense or a sensory organ that enables animals to perform orientation and navigation tasks that seemed difficult to imagine for people. A magnetic sense, so far only demonstrated in a few mammals but poorly understood, is an obvious candidate. Experiments suggest that iron oxide particles within cells may act as microscopic compass needles, as is the case in some species of bacteria. Recent laboratory experiments on Ansell's mole rats, relatives of the well-known naked mole rats that spend their lives in elaborate underground tunnel systems, suggest that the magnetic sense is located in the eye. This magnetic sense of orientation has not been verified in migratory mammals nor has it been possible to identify the specific organ or tissue which could provide the morphological basis for the required sensory receptors. The experiments by the team around Lindecke and Voigt now provide the first reliable data for the localisation of a sense of orientation in free-ranging, migratory mammals. Exactly what the sense in the cornea of the bats looks like, how it works and whether it is the long-sought magnetic sense must be shown in future scientific investigations. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The exact anatomical location for an iron particle-based magnetic sense remains enigmatic in vertebrates. For mammals, findings from a cornea anaesthesia experiment in mole rats suggest that it carries the primary sensors for magnetoreception. Yet, this has never been tested in a free-ranging mammal. Here, we investigated whether intact corneal sensation is crucial for navigation in migrating Nathusius’ bats, Pipistrellus nathusii , translocated from their migratory corridor. We found that bats treated with corneal anaesthesia in both eyes flew in random directions after translocation and release, contrasting bats with a single eye treated, and the control group, which both oriented in the seasonally appropriate direction. Using a Y-maze test, we confirmed that light detection remained unaffected by topical anaesthesia. Therefore our results suggest the cornea as a possible site of magnetoreception in bats, although other conceivable effects of the anaesthetic are also explored. Furthermore, we demonstrate that the corneal based sense is of bilateral nature but can function in a single eye if necessary. Introduction While the capacity for magnetoreception among mammals is evident from a number of behavioural experiments 1 , 2 , 3 , 4 , 5 , 6 , 7 , the anatomical location of the involved receptors remains as enigmatic as in any other animal to date 8 , 9 . Interestingly enough, when tested in darkness, mammals 10 , 11 , 12 , 13 , fish 14 , 15 and sea turtles 16 were able to orient by a magnetic polarity compass. The underlying magnetic sense is hypothesized to involve intra-cellular iron oxide, i.e., magnetite nanoparticles (Fe 3 O 4 ), which would be sensitive to the horizontal polarity of a magnetic field, enabling these animals to distinguish between magnetic north and south, independent of light. Intra-cellular iron oxide could also be responsible for magnetic signal transmission through control of ion channels depending on the alignment of animals in relation to the magnetic field 8 , 15 , 17 , 18 . Wegner and colleagues postulated that the cornea may be the location of the primary magnetoreceptors in mammals 19 . Specifically, they showed that in mole rats, Fukomys anselli , bilateral anaesthesia of the cornea resulted in randomly oriented nest-building, contrary to the usually magnetic polarity-dependent nesting behaviour 10 , 19 . According to the innervation of the cornea, the ophthalmic branch of the trigeminal nerve would transmit the magnetic signal to the midbrain where magnetic stimuli could be processed 11 , 13 , 20 , 21 , 22 . Yet, to date, the hypothesis of a corneal magnetic sense has never been challenged nor expanded from laboratory conditions to freely moving animals by performing a true navigation task in the field, e.g., during seasonal migration. Non-migratory bats are known to possess a polarity-sensitive magnetic compass, which they use for homing tasks 5 , 12 , 23 . Furthermore, results from a classic ‘Kalmijn-Blakemore’ pulse re-magnetization experiment in big brown bats ( Eptesicus fuscus ) are consistent with the hypothesis that magneto-sensory cells located somewhere in a bat’s body carry single-domain magnetite 24 . In contrast, the compass cues and sensory structures the migratory bats use for long-range in-flight navigation still remain undetermined. Only recently, it was demonstrated that bats calibrate their compass system to the solar azimuth at sunset and could take up a seasonally appropriate migratory heading after moderate displacement from their migration corridor 25 , 26 . To study the role of the cornea in navigation of vertebrates that are adapted to long-range navigation, we performed translocation experiments with 80 adult Nathusius’ bats ( Pipistrellus nathusii ) caught at the Baltic Sea during the late summer migration season. A geographical displacement of the bats was necessary to study their individual orientation behaviour at an unfamiliar site after astronomical twilight and when remote from the high density of conspecifics along the migration corridor, as well as the landmark cues emanating from the shore over short range. Half of the bats received either unilateral or bilateral topical corneal anaesthesia prior to release, while the other half were treated with a saline solution to create a sham control condition. Importantly, we also conducted tests of photoreception in another 76 bats using a Y-maze choice experiment to validate retinal function; specifically, the capacity of bats to still discriminate between light and dark in their environment, despite corneal anaesthesia, was tested. We hypothesized that migratory bats depend on corneal magnetoreception for navigation. If the cornea plays a role in magnetic orientation, we predicted that translocated bats treated with a topical anaesthetic on both eyes would vanish in random directions after release. However, bats with a single eye treated would be able to navigate because the other eye’s cornea would still be functional, i.e., to transmit sensory stimuli through the ophthalmic branch of the trigeminal nerve, and to enable the released bats to fly in a correct migratory direction similar to bats of the sham treated group. Results Detection of a light source is unimpaired after topical corneal anaesthesia In previous Y-maze experiments with one dark and one lit exit, the bats chose the lit exit instead of the dark one 27 . In contrast, blindfolded bats totally deprived of light perception chose the exits randomly 28 . We performed similar tests, yet without blindfolding, to evaluate our bats’ principal ability of light detection after administering topical corneal anaesthesia by oxybuprocaine eye drops. When we tested the unilateral and bilateral treatment groups that received the topical corneal anaesthetic, and the two sham control groups that received eye drops of saline solution bilaterally, our tests did not indicate a differential effect between these applications on the bats’ phototactic behaviour, i.e., animals of both the treatment groups and the sham control groups preferred the lit exit of the Y-maze (sham control 1: n = 22, 77% (proportion of bats choosing the lit exit in %), χ 2 = 6.55, W = 0.55, P = 0.011; single eye treated: n = 16, 81.3%, χ 2 = 6.25, W =<|im_end|> <|im_start|>assistant Mammals see with their eyes, hear with their ears and smell with their nose. But which sense or organ allows them to orient themselves on their migrations, which sometimes go far beyond their local foraging areas and therefore require an extended ability to navigate? Scientific experiments led by the Leibniz Institute for Zoo and Wildlife Research (Leibniz-IZW), published together with Prof. Richard A. Holland (Bangor University, UK) and Dr. Gunārs Petersons (Latvia University of Life Sciences and Technologies) now show that the cornea of the eyes is the location of this important sense in migrating bats. If the cornea is anesthetized, the otherwise reliable sense of orientation is disturbed while light detection remains unimpaired. The experiment suggests the localisation of a magnetic sense in mammals. The paper is published in the scientific journal Communications Biology. A research team led by Dr. Oliver Lindecke and PD Dr. Christian Voigt from Leibniz-IZW has demonstrated for the first time that environmental signals that are important for navigating over long distances are picked up via the cornea. They conducted experiments with Nathusius' bats (Pipistrellus nathusii) during the late summer migration period. In bats of one test group, the scientists locally anesthetized the cornea with a drop of oxybuprocaine. This surface anesthetic is widely used in ophthalmology to temporarily desensitize the patient's cornea when the eyes are overly irritated. Effects on orientation, however, had not been previously recorded. In another test group of bats, the research team anesthetized the cornea of only one eye. The individuals in the control group were not anesthetized, but instead received an isotonic saline solution as eye drops. All animals in this scientific experiment were captured within a migration corridor at the coastline of the Baltic Sea and released singly in the open field 11 kilometers inland from the capture site immediately after treatment. The scientists first used bat detectors to make sure that there were no other bats above the field at the time of release that the test animals could have followed. The person observing the direction of movement of released bats was unaware of how bats were treated experimentally. "The control group and the group with unilateral corneal anesthesia oriented themselves clearly in the expected southerly directions, whereas the bats with bilateral anesthetized corneas flew off in random directions," explains Dr. Oliver Lindecke, first author of the paper. "This evident difference in behavior suggests that corneal anesthesia disrupted a sense of direction, yet orientation apparently still works well with one eye." As corneal treatment wears off after a short time, the bats were able to resume their journeys south after the experiment. "We observed here for the first time in an experiment how a migrating mammal was literally blown off course—a milestone in behavioral and sensory biology that allows us to study the biological navigation system in a more targeted way." In order to rule out the possibility that the anaesthetisation of the cornea also affects the sense of sight and that the scientists would thus come to the wrong conclusions, they carried out a complementary test. Once again dividing the bats into experimental and control groups, the researchers tested whether the response of bats to light changed after anesthesia of the corneas on one or both sides. "We know from previous research that bats prefer an illuminated exit when leaving a simple Y-shaped labyrinth," explains PD Dr. Christian Voigt, head of the Leibniz-IZW Department of Evolutionary Ecology. "In our experiment, the animals with one-sided or two-sided anesthesia also showed this preference; we therefore can rule out that the ability to see light was altered after corneal treatment. The ability to see light would, of course, also influence long-distance navigation." Many vertebrates such as bats, dolphins, whales, fish and turtles, for example, are able to safely navigate in darkness, whether it is under the open night sky, when it is cloudy at night or in caves and tunnels as well as in the depths of the oceans. For many decades, scientists have been searching for the sense or a sensory organ that enables animals to perform orientation and navigation tasks that seemed difficult to imagine for people. A magnetic sense, so far only demonstrated in a few mammals but poorly understood, is an obvious candidate. Experiments suggest that iron oxide particles within cells may act as microscopic compass needles, as is the case in some species of bacteria. Recent laboratory experiments on Ansell's mole rats, relatives of the well-known naked mole rats that spend their lives in elaborate underground tunnel systems, suggest that the magnetic sense is located in the eye. This magnetic sense of orientation has not been verified in migratory mammals nor has it been possible to identify the specific organ or tissue which could provide the morphological basis for the required sensory receptors. The experiments by the team around Lindecke and Voigt now provide the first reliable data for the localisation of a sense of orientation in free-ranging, migratory mammals. Exactly what the sense in the cornea of the bats looks like, how it works and whether it is the long-sought magnetic sense must be shown in future scientific investigations. <|im_end|>

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2,436

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract There is growing evidence for the efficacy of music, specifically Mozart’s Sonata for Two Pianos in D Major (K448), at reducing ictal and interictal epileptiform activity. Nonetheless, little is known about the mechanism underlying this beneficial “Mozart K448 effect” for persons with epilepsy. Here, we measured the influence that K448 had on intracranial interictal epileptiform discharges (IEDs) in sixteen subjects undergoing intracranial monitoring for refractory focal epilepsy. We found reduced IEDs during the original version of K448 after at least 30-s of exposure. Nonsignificant IED rate reductions were witnessed in all brain regions apart from the bilateral frontal cortices, where we observed increased frontal theta power during transitions from prolonged musical segments. All other presented musical stimuli were associated with nonsignificant IED alterations. These results suggest that the “Mozart K448 effect” is dependent on the duration of exposure and may preferentially modulate activity in frontal emotional networks, providing insight into the mechanism underlying this response. Our findings encourage the continued evaluation of Mozart’s K448 as a noninvasive, non-pharmacological intervention for refractory epilepsy. Introduction Epilepsy impacts approximately 1% of the global population, and of these people, 1/3 suffer from medication-resistant or refractory epilepsy 1 . Besides seizures and their associated comorbidities, persons with epilepsy experience interictal epileptiform discharges (IEDs). IEDs arise from the brief, synchronous firing of neural populations that are typically involved with epileptic networks 2 . These IEDs are known epileptic biomarkers that are associated with seizure frequency and impaired cognition 3 , 4 , 5 , 6 . Thus, IED-related interventions may provide insight into novel therapies for epilepsy and its related comorbidities. An IED-related intervention with accumulating evidence is the use of music as a noninvasive, non-pharmacologic form of neuromodulation 7 , 8 . Specifically, Mozart’s Sonata for Two Pianos in D Major (K448) has been shown to reduce ictal and interictal epileptiform activity in several scalp-EEG and fMRI studies 9 , 10 , 11 , 12 . While effect sizes varied, a meta-analysis demonstrated that approximately 84% of subjects had significant IED reductions during Mozart’s K448 13 . This reputed “Mozart K448 effect” was first described in 1993 by Rauscher et al. 14 when they demonstrated enhancement on a spatial task during exposure to K448. Later, Hughes et al. (1998) 15 were the first to witness the “Mozart K448 effect” in persons with epilepsy by showing that K448 was associated with reduced epileptiform activity. Following Hughes et al.’s discovery, there has been continued support for the “Mozart K448 effect” in epilepsy research—generally demonstrating that exposure to K448 was associated with some therapeutic reduction in seizures and IEDs 7 , 9 , 12 , 16 , 17 . Apart from one other composition—Mozart’s Piano Sonata in C Major (K545)—the therapeutic properties of K448 could not be replicated with other musical stimuli 18 . Stimuli previously tested were other Mozart compositions 16 , Beethoven’s Fur Elise 19 , and a string version of K448 10 . This led to several theories about the mechanisms underlying Mozart’s therapeutic effects for epilepsy; however, the specific properties driving the “Mozart K448 effect” remain unknown. Consequently, there is a general reluctance to fully accept this effect due to the unknown mechanism of K448 and to heterogeneous past findings that are likely linked with the use of different study protocols and inferior imaging modalities. The latter limitation is noteworthy, as scalp-EEG is much less sensitive for quantifying epilepsy-related outcomes, especially interictal events 20 , 21 . Our previous work demonstrated that 40 Hz auditory stimulation could reduce IEDs in subjects with refractory epilepsy and high baseline IED rates 22 . Historically, the relevance of gamma sensory stimulation emerged from findings of reduced gamma oscillations in humans with Alzheimer’s disease (AD) 23 . This was followed by observations of improved disease states (e.g., AD 24 , 25 , 26 and stroke 27 ) after exposure to exogenous gamma stimulation. Lin et al. (2010) 10 even demonstrated that musical stimuli with more fundamental tones (i.e., higher gamma power) reduced the number of epileptiform discharges. A major pitfall to this noninvasive intervention is that while the 40 Hz tone could effectively reduce IEDs in refractory epilepsy, it was not especially pleasant to listen to for a prolonged time. In this study, we evaluate the use of Mozart’s K448 to see (1) if we can validate previous scalp-EEG findings with intracranial Stereo-EEG in adults with refractory epilepsy, (2) if there is a temporal dependence for eliciting the “Mozart K448 effect”, and (3) if the “Mozart K448 effect” is associated with preferential brain networks. We also examined if preferred music and music with enhanced gamma frequencies (i.e., either gamma-matched to K448 or gamma-boosted) could elicit a therapeutic response; this was motivated by our past findings and the theory that increased fundamental frequencies may be beneficial for epilepsy 10 , 22 . We hypothesized that eliciting the “Mozart K448 effect” would be dependent on a longer stimulus duration and prolonged internal musical segments. This is based on the theory that emotional responses result from positive reward prediction errors 28 . Further, we expected this effect would extend to regions outside of the primary auditory pathways, owing to past observations of music and its involvement with higher order systems (e.g., emotion and mirror neurons) 29 . This research may guide future work in uncovering how Mozart’s K448 elicits therapeutic responses, which may facilitate the development of novel, noninvasive music therapies for refractory epilepsy. Results Detecting interictal activity in subjects with refractory epilepsy An automated template-matching interictal epileptiform discharge detector was utilized to calculate subject-specific IED rates (Fig. 1 ). We recruited 16 neurosurgical subjects undergoing clinical monitoring for refractory epilepsy to participate in sessions of a music task (Fig. 2 a,b). To determine if the duration of exposure was an important factor for eliciting the “Mozart K448 effect”, stimuli were presented for either 15-s (“Group 15”) or 90-s (“Group 90”). Subjects in Group 15 had a mean age of 43.75 (SD 16.46), an average normalized baseline IED rate of", "role": "user" }, { "content": "Listening to Mozart's Sonata for Two Pianos in D Major (K448) for at least 30 seconds may be associated with less frequent spikes of epilepsy-associated electrical activity in the brain in people with medication-resistant epilepsy. The findings, which also suggest that positive emotional responses to K448 may contribute to its therapeutic effects, are published in Scientific Reports. Previous research has shown that listening to K448 is associated with less frequent spikes of epilepsy-associated electrical activity in the brain in people with epilepsy. However, the impact of music duration on this association and the reasons for it have been unclear. Robert Quon and colleagues used electroencephalogram (EEG) to measure electrical activity in the brains of 16 adults with medication-resistant epilepsy as they listened to a series of either 15 or 90 second music clips, including K448. The authors found that listening to between 30 and 90 seconds of K448, but not the other music clips, was associated with a 66.5% average reduction in the number of epilepsy-associated electrical activity spikes throughout the brain. These reductions were found to be greatest in the brain's left and right frontal cortices, parts of the brain involved in regulating emotional responses. The researchers also observed that when participants listened to the ending of long, repetitive sections within K448, a type of electrical activity known as theta activity increased in their frontal cortices. Previous research has suggested that theta activity may be associated with positive emotional responses to music. The authors hypothesize that listening to K448 for as little as 30 seconds may activate networks within the brain that are associated with positive emotional responses to music and are regulated by the frontal cortex. The activation of these networks may contribute to reductions in epilepsy-associated electrical activity spikes among those with medication-resistant epilepsy, they suggest. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract There is growing evidence for the efficacy of music, specifically Mozart’s Sonata for Two Pianos in D Major (K448), at reducing ictal and interictal epileptiform activity. Nonetheless, little is known about the mechanism underlying this beneficial “Mozart K448 effect” for persons with epilepsy. Here, we measured the influence that K448 had on intracranial interictal epileptiform discharges (IEDs) in sixteen subjects undergoing intracranial monitoring for refractory focal epilepsy. We found reduced IEDs during the original version of K448 after at least 30-s of exposure. Nonsignificant IED rate reductions were witnessed in all brain regions apart from the bilateral frontal cortices, where we observed increased frontal theta power during transitions from prolonged musical segments. All other presented musical stimuli were associated with nonsignificant IED alterations. These results suggest that the “Mozart K448 effect” is dependent on the duration of exposure and may preferentially modulate activity in frontal emotional networks, providing insight into the mechanism underlying this response. Our findings encourage the continued evaluation of Mozart’s K448 as a noninvasive, non-pharmacological intervention for refractory epilepsy. Introduction Epilepsy impacts approximately 1% of the global population, and of these people, 1/3 suffer from medication-resistant or refractory epilepsy 1 . Besides seizures and their associated comorbidities, persons with epilepsy experience interictal epileptiform discharges (IEDs). IEDs arise from the brief, synchronous firing of neural populations that are typically involved with epileptic networks 2 . These IEDs are known epileptic biomarkers that are associated with seizure frequency and impaired cognition 3 , 4 , 5 , 6 . Thus, IED-related interventions may provide insight into novel therapies for epilepsy and its related comorbidities. An IED-related intervention with accumulating evidence is the use of music as a noninvasive, non-pharmacologic form of neuromodulation 7 , 8 . Specifically, Mozart’s Sonata for Two Pianos in D Major (K448) has been shown to reduce ictal and interictal epileptiform activity in several scalp-EEG and fMRI studies 9 , 10 , 11 , 12 . While effect sizes varied, a meta-analysis demonstrated that approximately 84% of subjects had significant IED reductions during Mozart’s K448 13 . This reputed “Mozart K448 effect” was first described in 1993 by Rauscher et al. 14 when they demonstrated enhancement on a spatial task during exposure to K448. Later, Hughes et al. (1998) 15 were the first to witness the “Mozart K448 effect” in persons with epilepsy by showing that K448 was associated with reduced epileptiform activity. Following Hughes et al.’s discovery, there has been continued support for the “Mozart K448 effect” in epilepsy research—generally demonstrating that exposure to K448 was associated with some therapeutic reduction in seizures and IEDs 7 , 9 , 12 , 16 , 17 . Apart from one other composition—Mozart’s Piano Sonata in C Major (K545)—the therapeutic properties of K448 could not be replicated with other musical stimuli 18 . Stimuli previously tested were other Mozart compositions 16 , Beethoven’s Fur Elise 19 , and a string version of K448 10 . This led to several theories about the mechanisms underlying Mozart’s therapeutic effects for epilepsy; however, the specific properties driving the “Mozart K448 effect” remain unknown. Consequently, there is a general reluctance to fully accept this effect due to the unknown mechanism of K448 and to heterogeneous past findings that are likely linked with the use of different study protocols and inferior imaging modalities. The latter limitation is noteworthy, as scalp-EEG is much less sensitive for quantifying epilepsy-related outcomes, especially interictal events 20 , 21 . Our previous work demonstrated that 40 Hz auditory stimulation could reduce IEDs in subjects with refractory epilepsy and high baseline IED rates 22 . Historically, the relevance of gamma sensory stimulation emerged from findings of reduced gamma oscillations in humans with Alzheimer’s disease (AD) 23 . This was followed by observations of improved disease states (e.g., AD 24 , 25 , 26 and stroke 27 ) after exposure to exogenous gamma stimulation. Lin et al. (2010) 10 even demonstrated that musical stimuli with more fundamental tones (i.e., higher gamma power) reduced the number of epileptiform discharges. A major pitfall to this noninvasive intervention is that while the 40 Hz tone could effectively reduce IEDs in refractory epilepsy, it was not especially pleasant to listen to for a prolonged time. In this study, we evaluate the use of Mozart’s K448 to see (1) if we can validate previous scalp-EEG findings with intracranial Stereo-EEG in adults with refractory epilepsy, (2) if there is a temporal dependence for eliciting the “Mozart K448 effect”, and (3) if the “Mozart K448 effect” is associated with preferential brain networks. We also examined if preferred music and music with enhanced gamma frequencies (i.e., either gamma-matched to K448 or gamma-boosted) could elicit a therapeutic response; this was motivated by our past findings and the theory that increased fundamental frequencies may be beneficial for epilepsy 10 , 22 . We hypothesized that eliciting the “Mozart K448 effect” would be dependent on a longer stimulus duration and prolonged internal musical segments. This is based on the theory that emotional responses result from positive reward prediction errors 28 . Further, we expected this effect would extend to regions outside of the primary auditory pathways, owing to past observations of music and its involvement with higher order systems (e.g., emotion and mirror neurons) 29 . This research may guide future work in uncovering how Mozart’s K448 elicits therapeutic responses, which may facilitate the development of novel, noninvasive music therapies for refractory epilepsy. Results Detecting interictal activity in subjects with refractory epilepsy An automated template-matching interictal epileptiform discharge detector was utilized to calculate subject-specific IED rates (Fig. 1 ). We recruited 16 neurosurgical subjects undergoing clinical monitoring for refractory epilepsy to participate in sessions of a music task (Fig. 2 a,b). To determine if the duration of exposure was an important factor for eliciting the “Mozart K448 effect”, stimuli were presented for either 15-s (“Group 15”) or 90-s (“Group 90”). Subjects in Group 15 had a mean age of 43.75 (SD 16.46), an average normalized baseline IED rate of<|im_end|> <|im_start|>assistant Listening to Mozart's Sonata for Two Pianos in D Major (K448) for at least 30 seconds may be associated with less frequent spikes of epilepsy-associated electrical activity in the brain in people with medication-resistant epilepsy. The findings, which also suggest that positive emotional responses to K448 may contribute to its therapeutic effects, are published in Scientific Reports. Previous research has shown that listening to K448 is associated with less frequent spikes of epilepsy-associated electrical activity in the brain in people with epilepsy. However, the impact of music duration on this association and the reasons for it have been unclear. Robert Quon and colleagues used electroencephalogram (EEG) to measure electrical activity in the brains of 16 adults with medication-resistant epilepsy as they listened to a series of either 15 or 90 second music clips, including K448. The authors found that listening to between 30 and 90 seconds of K448, but not the other music clips, was associated with a 66.5% average reduction in the number of epilepsy-associated electrical activity spikes throughout the brain. These reductions were found to be greatest in the brain's left and right frontal cortices, parts of the brain involved in regulating emotional responses. The researchers also observed that when participants listened to the ending of long, repetitive sections within K448, a type of electrical activity known as theta activity increased in their frontal cortices. Previous research has suggested that theta activity may be associated with positive emotional responses to music. The authors hypothesize that listening to K448 for as little as 30 seconds may activate networks within the brain that are associated with positive emotional responses to music and are regulated by the frontal cortex. The activation of these networks may contribute to reductions in epilepsy-associated electrical activity spikes among those with medication-resistant epilepsy, they suggest. <|im_end|>

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1,821

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstracts Collections Free Sample Issue Print on Demand Information For Authors Open Access and Subscription Publishing Submission Subscribers Proprietary Rights Notice for AJEV Online Permissions and Reproductions About Us Feedback Alerts Help Login ASEV MEMBER LOGIN User menu Log in Search Search for this keyword Advanced search Log in Follow ajev on Twitter Follow ajev on Linkedin Search for this keyword Advanced Search Home Content Current Volume AJEV and Catalyst Archive Best Papers ASEV National Conference Technical Abstracts Collections Free Sample Issue Print on Demand Information For Authors Open Access and Subscription Publishing Submission Subscribers Permissions and Reproductions About Us Feedback Alerts Help Login ASEV MEMBER LOGIN Review Mechanization of Pruning, Canopy Management, and Harvest in Winegrape Vineyards S. Kaan Kurtural , Matthew W. Fidelibus Am J Enol Vitic. June 2021 5: 29-44; published ahead of print June 07, 2021 ; DOI: 10.5344/catalyst.2021.20011 S. Kaan Kurtural 1 Department of Viticulture and Enology, University of California Davis, 1 Shields Avenue, Davis, CA 95616. Find this author on Google Scholar Find this author on PubMed Find this author on ADS search Find this author on Agricola Search for this author on this site For correspondence: skkurtural@ucdavis.edu Matthew W. Fidelibus 1 Department of Viticulture and Enology, University of California Davis, 1 Shields Avenue, Davis, CA 95616. Find this author on Google Scholar Find this author on PubMed Find this author on ADS search Find this author on Agricola Search for this author on this site /.panel-row-wrapper Article Figures & Data Supplemental Info & Metrics PDF Summary Aim: In winegrape production, pruning, canopy management, and harvest are essential practices that are increasingly being done by machines. How well these practices are executed can substantially affect fruit yield and quality. Mechanization offers timeliness, uniformity, and cost benefits, but most methods available to date are nonselective and optimal execution requires careful attention to vineyard design, management, and machine settings. This review provides information to help growers make the best use of machines for these tasks. Key Themes: Vineyard design considerations Winter pruning Canopy management Harvesting Impact and Significance: The need to manage large vineyards in a contracting labor market is achievable with mechanization. This review summarizes the best practices in consideration of vineyard design, as well as operation of machines for optimal productivity for the winegrape grower. This review also provides information to help growers effectively incorporate the machines in their vineyards for consistent and economical production of winegrapes including pruning, shoot-thinning, fruit-zone leaf removal, crop load management, and mechanical harvest. canopy management crop removal fruit-zone leaf removal mechanization pruning shoot-thinning viticultural practice Overview Many winegrape cultural practices, including pruning, canopy management, and harvest, are laborious and time sensitive. However, California and many other winegrape production regions are facing rising wage costs and labor shortages. 1 , 2 Ongoing labor shortages were heightened in 2020 because of the novel coronavirus pandemic. 3 Thus, there is an increasing need to farm with fewer people, in a more cost-effective and timely manner. 4 The most laborious vineyard tasks are dormant pruning, canopy management, and harvesting, 5 and mechanization for these methods has received considerable attention from academics, equipment manufacturers, and growers. 6 As growers adapted to mechanical harvest 7 and pruning, they searched for other methods to mechanize other cultural operations such as shoot 6 and fruit-zone leaf removal, 8 , 9 , 10 berry thinning, 11 and shoot positioning. 12 Machinery was developed and commercialized by researchers at the University of Arkansas 13 , 14 and commercialized by partners for these practices. Adoption of such machinery is increasing with economic necessity and as growers develop the knowledge and experience necessary to use these tools effectively. Current vineyard mechanization equipment reduces the need for seasonal manual labor for certain tasks, but does not eliminate it. 15 The degree to which manual labor can be reduced depends on the growing region (coastal versus inland), grapevine cultivar (upright versus downright growth habit), and the number of cultural practices (harvest only or pruning and other practices) the grower is able to mechanize. Furthermore, because vineyard mechanization relies heavily on information-based decision-making, growers need fewer, but more highly skilled, personnel for optimal vineyard management. This review will provide information to help growers effectively incorporate machines in their vineyards for consistent and economical production of winegrapes. Key Themes Vineyard design considerations Preparation for vineyard mechanization ideally starts before grapevines are planted. Some key elements to consider, as in traditionally farmed vineyards, are soil uniformity within blocks, 16 blocking by cultivar or irrigation need, 17 drainage, slope, and consistency of grade. Ideally, mechanization will optimize investment per unit land area and production consistency. This is best achieved by optimizing uniformity within blocks for soil properties such as fertility and soil water drainage, which are helpful in this regard. 18 Sites with inconsistent grade with irregular knolls should be avoided because of safety concerns and variability. Variable grades within a vineyard will often increase vine-to-vine 19 variability because of changes in soil properties. 4 , 19 , 20 Vineyard management in mechanized vineyards is further simplified when vineyard blocks are planted to the same rootstock and cultivar. Well-drained soils are important in mechanized vineyards because equipment access and deployment are hindered in waterlogged vineyards after heavy precipitation. Most equipment will operate safely on slopes up to 7%. 5 , 21 Factors that need consideration when designing a vineyard for mechanization are available equipment, adequate inter- and in-row spacing, headland size, trellising, irrigation, and cultivar selection. Growers must pay attention to certain details to maximize success in future years when designing a vineyard for mechanization. Desired properties are listed in Table 1 . View this table: View inline View popup Download powerpoint Table 1 Checklist of desired vineyard properties for successful vineyard mechanization. Long, straight rows that are adequately spaced are essential. Long rows increase operating efficiency, while straight rows minimize vine injury and damage to line posts ( Figure 1 ). Adequate interrow spacing is desired to allow for lateral adjustment of equipment during operations.", "role": "user" }, { "content": "Wine grape growers in California and elsewhere face increasing labor costs and severe labor shortages, making it difficult to manage and harvest a vineyard while maintaining profitability. Growers are increasingly turning to machines for pruning, canopy management and harvesting, but how well these practices are executed can substantially affect yield and quality. A new review by researchers at the University of California, Davis, published in the journal Catalyst, provides guidelines for growers to make the best use of machines. \"Wine grape laborers have been virtually nonexistent. People don't want to work in vineyards anymore because it's remote, tough work,\" said Kaan Kurtural, professor of viticulture and enology and extension specialist at UC Davis. \"There is now machinery available to do everything without touching a vineyard.\" Kurtural has designed a \"touchless\" experimental vineyard at the UC Davis Oakville Station to help growers understand how machines can help them cope with the labor shortage. While machines reduce the need for seasonal manual labor, they do not eliminate it. The degree of labor reduction depends on growing region, grapevine type and the number of practices growers mechanize. The review provides guidance on using machines for winter pruning, canopy management and harvesting as well as how to design a grape vineyard for machines before planting. Videos showing the operation of different types of machinery and practices can also be found in the review. Economic savings, quality grapes About 90% of the wine grapes crushed in the U.S. are mechanically harvested. Previous studies have found about a 50% savings in labor costs from using machines to harvest instead of hand harvesting. Credit: Catalyst \"Using more mechanization in a vineyard beyond just harvesting can also reduce labor costs without affecting grape quality.\" Kurtural said. Mechanical pruning, for example, can save between 60% to 80% of labor operation costs per acre compared to manual pruning alone. One experiment in the San Joaquin Valley, where more than 50% of California's wine grapes are grown, also showed using mechanical canopy management machines to manage merlot grapes resulted in twice the amount of color. The more color, or higher anthocyanin concentrations, the better the quality. It can significantly improve returns from vineyards in California's heartland. Kurtural said there are machines available to manage canopies, including machines for leaf removal, shoot thinning and trunk suckering. Kurtural noted that the machines are American made, developed by researchers at the University of Arkansas and commercialized by manufacturers in Fresno and Woodland, California. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstracts Collections Free Sample Issue Print on Demand Information For Authors Open Access and Subscription Publishing Submission Subscribers Proprietary Rights Notice for AJEV Online Permissions and Reproductions About Us Feedback Alerts Help Login ASEV MEMBER LOGIN User menu Log in Search Search for this keyword Advanced search Log in Follow ajev on Twitter Follow ajev on Linkedin Search for this keyword Advanced Search Home Content Current Volume AJEV and Catalyst Archive Best Papers ASEV National Conference Technical Abstracts Collections Free Sample Issue Print on Demand Information For Authors Open Access and Subscription Publishing Submission Subscribers Permissions and Reproductions About Us Feedback Alerts Help Login ASEV MEMBER LOGIN Review Mechanization of Pruning, Canopy Management, and Harvest in Winegrape Vineyards S. Kaan Kurtural , Matthew W. Fidelibus Am J Enol Vitic. June 2021 5: 29-44; published ahead of print June 07, 2021 ; DOI: 10.5344/catalyst.2021.20011 S. Kaan Kurtural 1 Department of Viticulture and Enology, University of California Davis, 1 Shields Avenue, Davis, CA 95616. Find this author on Google Scholar Find this author on PubMed Find this author on ADS search Find this author on Agricola Search for this author on this site For correspondence: skkurtural@ucdavis.edu Matthew W. Fidelibus 1 Department of Viticulture and Enology, University of California Davis, 1 Shields Avenue, Davis, CA 95616. Find this author on Google Scholar Find this author on PubMed Find this author on ADS search Find this author on Agricola Search for this author on this site /.panel-row-wrapper Article Figures & Data Supplemental Info & Metrics PDF Summary Aim: In winegrape production, pruning, canopy management, and harvest are essential practices that are increasingly being done by machines. How well these practices are executed can substantially affect fruit yield and quality. Mechanization offers timeliness, uniformity, and cost benefits, but most methods available to date are nonselective and optimal execution requires careful attention to vineyard design, management, and machine settings. This review provides information to help growers make the best use of machines for these tasks. Key Themes: Vineyard design considerations Winter pruning Canopy management Harvesting Impact and Significance: The need to manage large vineyards in a contracting labor market is achievable with mechanization. This review summarizes the best practices in consideration of vineyard design, as well as operation of machines for optimal productivity for the winegrape grower. This review also provides information to help growers effectively incorporate the machines in their vineyards for consistent and economical production of winegrapes including pruning, shoot-thinning, fruit-zone leaf removal, crop load management, and mechanical harvest. canopy management crop removal fruit-zone leaf removal mechanization pruning shoot-thinning viticultural practice Overview Many winegrape cultural practices, including pruning, canopy management, and harvest, are laborious and time sensitive. However, California and many other winegrape production regions are facing rising wage costs and labor shortages. 1 , 2 Ongoing labor shortages were heightened in 2020 because of the novel coronavirus pandemic. 3 Thus, there is an increasing need to farm with fewer people, in a more cost-effective and timely manner. 4 The most laborious vineyard tasks are dormant pruning, canopy management, and harvesting, 5 and mechanization for these methods has received considerable attention from academics, equipment manufacturers, and growers. 6 As growers adapted to mechanical harvest 7 and pruning, they searched for other methods to mechanize other cultural operations such as shoot 6 and fruit-zone leaf removal, 8 , 9 , 10 berry thinning, 11 and shoot positioning. 12 Machinery was developed and commercialized by researchers at the University of Arkansas 13 , 14 and commercialized by partners for these practices. Adoption of such machinery is increasing with economic necessity and as growers develop the knowledge and experience necessary to use these tools effectively. Current vineyard mechanization equipment reduces the need for seasonal manual labor for certain tasks, but does not eliminate it. 15 The degree to which manual labor can be reduced depends on the growing region (coastal versus inland), grapevine cultivar (upright versus downright growth habit), and the number of cultural practices (harvest only or pruning and other practices) the grower is able to mechanize. Furthermore, because vineyard mechanization relies heavily on information-based decision-making, growers need fewer, but more highly skilled, personnel for optimal vineyard management. This review will provide information to help growers effectively incorporate machines in their vineyards for consistent and economical production of winegrapes. Key Themes Vineyard design considerations Preparation for vineyard mechanization ideally starts before grapevines are planted. Some key elements to consider, as in traditionally farmed vineyards, are soil uniformity within blocks, 16 blocking by cultivar or irrigation need, 17 drainage, slope, and consistency of grade. Ideally, mechanization will optimize investment per unit land area and production consistency. This is best achieved by optimizing uniformity within blocks for soil properties such as fertility and soil water drainage, which are helpful in this regard. 18 Sites with inconsistent grade with irregular knolls should be avoided because of safety concerns and variability. Variable grades within a vineyard will often increase vine-to-vine 19 variability because of changes in soil properties. 4 , 19 , 20 Vineyard management in mechanized vineyards is further simplified when vineyard blocks are planted to the same rootstock and cultivar. Well-drained soils are important in mechanized vineyards because equipment access and deployment are hindered in waterlogged vineyards after heavy precipitation. Most equipment will operate safely on slopes up to 7%. 5 , 21 Factors that need consideration when designing a vineyard for mechanization are available equipment, adequate inter- and in-row spacing, headland size, trellising, irrigation, and cultivar selection. Growers must pay attention to certain details to maximize success in future years when designing a vineyard for mechanization. Desired properties are listed in Table 1 . View this table: View inline View popup Download powerpoint Table 1 Checklist of desired vineyard properties for successful vineyard mechanization. Long, straight rows that are adequately spaced are essential. Long rows increase operating efficiency, while straight rows minimize vine injury and damage to line posts ( Figure 1 ). Adequate interrow spacing is desired to allow for lateral adjustment of equipment during operations.<|im_end|> <|im_start|>assistant Wine grape growers in California and elsewhere face increasing labor costs and severe labor shortages, making it difficult to manage and harvest a vineyard while maintaining profitability. Growers are increasingly turning to machines for pruning, canopy management and harvesting, but how well these practices are executed can substantially affect yield and quality. A new review by researchers at the University of California, Davis, published in the journal Catalyst, provides guidelines for growers to make the best use of machines. "Wine grape laborers have been virtually nonexistent. People don't want to work in vineyards anymore because it's remote, tough work," said Kaan Kurtural, professor of viticulture and enology and extension specialist at UC Davis. "There is now machinery available to do everything without touching a vineyard." Kurtural has designed a "touchless" experimental vineyard at the UC Davis Oakville Station to help growers understand how machines can help them cope with the labor shortage. While machines reduce the need for seasonal manual labor, they do not eliminate it. The degree of labor reduction depends on growing region, grapevine type and the number of practices growers mechanize. The review provides guidance on using machines for winter pruning, canopy management and harvesting as well as how to design a grape vineyard for machines before planting. Videos showing the operation of different types of machinery and practices can also be found in the review. Economic savings, quality grapes About 90% of the wine grapes crushed in the U.S. are mechanically harvested. Previous studies have found about a 50% savings in labor costs from using machines to harvest instead of hand harvesting. Credit: Catalyst "Using more mechanization in a vineyard beyond just harvesting can also reduce labor costs without affecting grape quality." Kurtural said. Mechanical pruning, for example, can save between 60% to 80% of labor operation costs per acre compared to manual pruning alone. One experiment in the San Joaquin Valley, where more than 50% of California's wine grapes are grown, also showed using mechanical canopy management machines to manage merlot grapes resulted in twice the amount of color. The more color, or higher anthocyanin concentrations, the better the quality. It can significantly improve returns from vineyards in California's heartland. Kurtural said there are machines available to manage canopies, including machines for leaf removal, shoot thinning and trunk suckering. Kurtural noted that the machines are American made, developed by researchers at the University of Arkansas and commercialized by manufacturers in Fresno and Woodland, California. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Star formation in half of massive galaxies was quenched by the time the Universe was 3 billion years old 1 . Very low amounts of molecular gas seem to be responsible for this, at least in some cases 2 , 3 , 4 , 5 , 6 , 7 , although morphological gas stabilization, shock heating or activity associated with accretion onto a central supermassive black hole are invoked in other cases 8 , 9 , 10 , 11 . Recent studies of quenching by gas depletion have been based on upper limits that are insufficiently sensitive to determine this robustly 2 , 3 , 4 , 5 , 6 , 7 , or stacked emission with its problems of averaging 8 , 9 . Here we report 1.3 mm observations of dust emission from 6 strongly lensed galaxies where star formation has been quenched, with magnifications of up to a factor of 30. Four of the six galaxies are undetected in dust emission, with an estimated upper limit on the dust mass of 0.0001 times the stellar mass, and by proxy (assuming a Milky Way molecular gas-to-dust ratio) 0.01 times the stellar mass in molecular gas. This is two orders of magnitude less molecular gas per unit stellar mass than seen in star forming galaxies at similar redshifts 12 , 13 , 14 . It remains difficult to extrapolate from these small samples, but these observations establish that gas depletion is responsible for a cessation of star formation in some fraction of high-redshift galaxies. Main The 1.3 mm observations of dust emission were made with the Atacama Large Millimeter/submillimeter Array (ALMA), and the sample comprises six galaxies selected from the REsolving QUIEscent Magnified (REQUIEM) galaxy survey: MRG-M1341 (ref. 15 ), MRG-M0138 (ref. 16 ), MRG-M2129 (ref. 17 ), MRG-M0150 (ref. 16 ), MRG-M0454 (ref. 18 ) and MRG-M1423 (ref. 18 ) (Fig. 1 ). The targets are all strongly lensed, with magnification factors ranging from a factor of 2.7 (MRG-M1423) to 30 (MRG-M1341). Five out of the six galaxies are classified as quiescent owing to unusually low star-formation rates that reach down to 0.1 M ☉ yr −1 , as measured from fitting the optical to infrared spectral energy distributions ( Methods ). Although the most distant target, MRG-M1423, has a more typical star-formation rate of about 140 M ☉ yr −1 over the previous 100 Myr, consistent with normal star-forming galaxies at z = 3, its spectrum reveals classic post-starburst signatures that support a picture in which it has quenched rapidly within the last 100 Myr (ref. 18 ). These targets are qualitatively different to existing millimetre continuum/carbon monoxide (CO) spectroscopic observations tracing cold interstellar medium phases in quenched galaxies in that these galaxies have star-formation rates that are an order of magnitude lower for their stellar mass 2 , 4 , 5 , 6 , 8 , 11 , higher redshifts 3 , 7 , 9 , 10 , and uniquely deep flux limits facilitated by strong lensing magnification. Fig. 1: Images of six massive lensed galaxies for which star formation has been quenched. The panels are rank-ordered from z = 1.6 to z = 3.2 ( a – f ), showing a composite HST colour image ( i F814W , J F125W , H F160W generally, substituting J F110W for e ) and contours of ALMA/Band 6 dust continuum observations, with levels defined by signal to noise ratio (SNR). Each image is centred on the target galaxy, whose redshift is listed in the top-left corner. The dashed ellipse indicates the ALMA beam size, with the 1 σ noise level noted at the bottom of each panel in units of mJy per beam. Full size image For the redshift range of our sample, our 1.3 mm wavelength observations correspond to 300–500 μm rest frame on the Rayleigh–Jeans tail of the dust emission, which serves as a robust proxy for the cold molecular gas mass 19 . We clearly detect two of the sources in the dust continuum: MRG-M0138 at 0.27 ± 0.03 mJy and MRG-M2129 at 9.74 ± 0.16 mJy. Such direct detections of cold dust in individual quiescent galaxies outside the local universe, implying per cent-level molecular gas fractions, are scant owing to the extreme sensitivity requirements. In contrast with the extended stellar light profiles, and despite the enhanced resolution from strong lensing magnification, both sources remain unresolved with no evidence for missing extended flux ( Methods ). This suggests that they have high dust and molecular gas surface densities, as the dust continuum is centrally concentrated and significantly less extended than the stellar light (Fig. 1 ). Such a result has also been found in star-forming galaxies at similar redshifts 20 . The sensitive ALMA dust continuum imaging of the remaining four sources all yield strong upper limits, with the 3 σ detection limits ranging from 30−150 μJy before lensing corrections. We estimate the dust mass, M dust , by adopting a modified blackbody fit and making standard assumptions about dust temperature and emissivity ( Methods ). We show the redshift evolution of the dust fraction, f dust = M dust / M ★ , for our sample of lensed quenched galaxies in Fig. 2 . By adopting a ratio of the molecular gas mass to dust mass of 100 ( Methods ), we estimate M H2 directly from M dust and also show the inferred molecular gas fraction, f H2 = M H2 / M ★ (right axis). Even if we adopt an extremely conservative molecular gas to dust mass ratio that is a factor of ten higher, f H2 is still well below that of normal star-forming galaxies at this epoch 14 . Both of our unambiguously detected galaxies have low molecular gas fractions of 4.6 ± 0.5% and 0.6 ± 0.1%, respectively, with systematic uncertainties in dust temperature and molecular gas mass to dust mass ratio of a factor of 1.7. Strong upper limits from CO emission for these two targets", "role": "user" }, { "content": "Early massive galaxies—those that formed in the 3 billion years following the Big Bang—should have contained large amounts of cold hydrogen gas, the fuel required to make stars. But scientists observing the early universe with the Atacama Large Millimeter/submillimeter Array (ALMA) and the Hubble Space Telescope have spotted something strange: a half-dozen early massive galaxies that ran out of fuel. The results of the research are published today in Nature. Known as \"quenched\" galaxies—or galaxies that have shut down star formation—the six high-redshift galaxies that were selected for observation from the REQUIEM survey are inconsistent with what astronomers expect of the early universe. \"The most massive galaxies in the universe lived fast and furious, creating their stars in a remarkably short amount of time. Gas, the fuel of star formation, should be plentiful at these early times in the universe,\" said Kate Whitaker, lead author on the study, and assistant professor of astronomy at the University of Massachusetts, Amherst. \"We originally believed that these quenched galaxies hit the brakes just a few billion years after the Big Bang. In our new research, we've concluded that early galaxies didn't actually put the brakes on, but rather, they were running on empty.\" To better understand how the galaxies formed and died, the team observed them using Hubble, which revealed details about the stars residing in the galaxies. Concurrent observations with ALMA revealed the galaxies' continuum emission—a tracer of dust—at millimeter wavelengths, allowing the team to infer the amount of gas in the galaxies. The use of the two telescopes is by careful design, as the purpose of REQUIEM is to use strong gravitational lensing as a natural telescope to observe dormant galaxies with higher spatial resolution. This, in turn, gives scientists a clear view of galaxies' internal goings-on, a task often impossible with those running on empty. This composite image of galaxy cluster MACSJ 0138 shows data from the Atacama Large Millimeter/submillimeter Array (ALMA) and NASA’s Hubble Space Telescope, as observed by REsolving QUIEscent Magnified galaxies at high redshift, or the REQUIEM survey. The early massive galaxies studied by REQUIEM were found to be lacking in cold hydrogen gas, the fuel required to form stars. Credit: ALMA (ESO/NAOJ/NRAO)/S. Dagnello (NRAO), STScI, K. Whitaker et al \"If a galaxy isn't making many new stars it gets very faint very fast so it is difficult or impossible to observe them in detail with any individual telescope. REQUIEM solves this by studying galaxies that are gravitationally lensed, meaning their light gets stretched and magnified as it bends and warps around other galaxies much closer to the Milky Way,\" said Justin Spilker, a co-author on the new study, and a NASA Hubble postdoctoral fellow at the University of Texas at Austin. \"In this way, gravitational lensing, combined with the resolving power and sensitivity of Hubble and ALMA, acts as a natural telescope and makes these dying galaxies appear bigger and brighter than they are in reality, allowing us to see what's going on and what isn't.\" The new observations showed that the cessation of star formation in the six target galaxies was not caused by a sudden inefficiency in the conversion of cold gas to stars. Instead, it was the result of the depletion or removal of the gas reservoirs in the galaxies. \"We don't yet understand why this happens, but possible explanations could be that either the primary gas supply fueling the galaxy is cut off, or perhaps a supermassive black hole is injecting energy that keeps the gas in the galaxy hot,\" said Christina Williams, an astronomer at the University of Arizona and co-author on the research. \"Essentially, this means that the galaxies are unable to refill the fuel tank, and thus, unable to restart the engine on star production.\" The study also represents a number of important firsts in the measurement of early massive galaxies, synthesizing information that will guide future studies of the early universe for years to come. \"These are the first measurements of the cold dust continuum of distant dormant galaxies, and in fact, the first measurements of this kind outside the local universe,\" said Whitaker, adding that the new study has allowed scientists to see how much gas individual dead galaxies have. \"We were able to probe the fuel of star formation in these early massive galaxies deep enough to take the first measurements of the gas tank reading, giving us a critically missing viewpoint of the cold gas properties of these galaxies.\" Although the team now knows that these galaxies are running on empty and that something is keeping them from refilling the tank and from forming new stars, the study represents just the first in a series of inquiries into what made early massive galaxies go, or not. \"We still have so much to learn about why the most massive galaxies formed so early in the universe and why they shut down their star formation when so much cold gas was readily available to them,\" said Whitaker. \"The mere fact that these massive beasts of the cosmos formed 100 billion stars within about a billion years and then suddenly shut down their star formation is a mystery we would all love to solve, and REQUIEM has provided the first clue.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Star formation in half of massive galaxies was quenched by the time the Universe was 3 billion years old 1 . Very low amounts of molecular gas seem to be responsible for this, at least in some cases 2 , 3 , 4 , 5 , 6 , 7 , although morphological gas stabilization, shock heating or activity associated with accretion onto a central supermassive black hole are invoked in other cases 8 , 9 , 10 , 11 . Recent studies of quenching by gas depletion have been based on upper limits that are insufficiently sensitive to determine this robustly 2 , 3 , 4 , 5 , 6 , 7 , or stacked emission with its problems of averaging 8 , 9 . Here we report 1.3 mm observations of dust emission from 6 strongly lensed galaxies where star formation has been quenched, with magnifications of up to a factor of 30. Four of the six galaxies are undetected in dust emission, with an estimated upper limit on the dust mass of 0.0001 times the stellar mass, and by proxy (assuming a Milky Way molecular gas-to-dust ratio) 0.01 times the stellar mass in molecular gas. This is two orders of magnitude less molecular gas per unit stellar mass than seen in star forming galaxies at similar redshifts 12 , 13 , 14 . It remains difficult to extrapolate from these small samples, but these observations establish that gas depletion is responsible for a cessation of star formation in some fraction of high-redshift galaxies. Main The 1.3 mm observations of dust emission were made with the Atacama Large Millimeter/submillimeter Array (ALMA), and the sample comprises six galaxies selected from the REsolving QUIEscent Magnified (REQUIEM) galaxy survey: MRG-M1341 (ref. 15 ), MRG-M0138 (ref. 16 ), MRG-M2129 (ref. 17 ), MRG-M0150 (ref. 16 ), MRG-M0454 (ref. 18 ) and MRG-M1423 (ref. 18 ) (Fig. 1 ). The targets are all strongly lensed, with magnification factors ranging from a factor of 2.7 (MRG-M1423) to 30 (MRG-M1341). Five out of the six galaxies are classified as quiescent owing to unusually low star-formation rates that reach down to 0.1 M ☉ yr −1 , as measured from fitting the optical to infrared spectral energy distributions ( Methods ). Although the most distant target, MRG-M1423, has a more typical star-formation rate of about 140 M ☉ yr −1 over the previous 100 Myr, consistent with normal star-forming galaxies at z = 3, its spectrum reveals classic post-starburst signatures that support a picture in which it has quenched rapidly within the last 100 Myr (ref. 18 ). These targets are qualitatively different to existing millimetre continuum/carbon monoxide (CO) spectroscopic observations tracing cold interstellar medium phases in quenched galaxies in that these galaxies have star-formation rates that are an order of magnitude lower for their stellar mass 2 , 4 , 5 , 6 , 8 , 11 , higher redshifts 3 , 7 , 9 , 10 , and uniquely deep flux limits facilitated by strong lensing magnification. Fig. 1: Images of six massive lensed galaxies for which star formation has been quenched. The panels are rank-ordered from z = 1.6 to z = 3.2 ( a – f ), showing a composite HST colour image ( i F814W , J F125W , H F160W generally, substituting J F110W for e ) and contours of ALMA/Band 6 dust continuum observations, with levels defined by signal to noise ratio (SNR). Each image is centred on the target galaxy, whose redshift is listed in the top-left corner. The dashed ellipse indicates the ALMA beam size, with the 1 σ noise level noted at the bottom of each panel in units of mJy per beam. Full size image For the redshift range of our sample, our 1.3 mm wavelength observations correspond to 300–500 μm rest frame on the Rayleigh–Jeans tail of the dust emission, which serves as a robust proxy for the cold molecular gas mass 19 . We clearly detect two of the sources in the dust continuum: MRG-M0138 at 0.27 ± 0.03 mJy and MRG-M2129 at 9.74 ± 0.16 mJy. Such direct detections of cold dust in individual quiescent galaxies outside the local universe, implying per cent-level molecular gas fractions, are scant owing to the extreme sensitivity requirements. In contrast with the extended stellar light profiles, and despite the enhanced resolution from strong lensing magnification, both sources remain unresolved with no evidence for missing extended flux ( Methods ). This suggests that they have high dust and molecular gas surface densities, as the dust continuum is centrally concentrated and significantly less extended than the stellar light (Fig. 1 ). Such a result has also been found in star-forming galaxies at similar redshifts 20 . The sensitive ALMA dust continuum imaging of the remaining four sources all yield strong upper limits, with the 3 σ detection limits ranging from 30−150 μJy before lensing corrections. We estimate the dust mass, M dust , by adopting a modified blackbody fit and making standard assumptions about dust temperature and emissivity ( Methods ). We show the redshift evolution of the dust fraction, f dust = M dust / M ★ , for our sample of lensed quenched galaxies in Fig. 2 . By adopting a ratio of the molecular gas mass to dust mass of 100 ( Methods ), we estimate M H2 directly from M dust and also show the inferred molecular gas fraction, f H2 = M H2 / M ★ (right axis). Even if we adopt an extremely conservative molecular gas to dust mass ratio that is a factor of ten higher, f H2 is still well below that of normal star-forming galaxies at this epoch 14 . Both of our unambiguously detected galaxies have low molecular gas fractions of 4.6 ± 0.5% and 0.6 ± 0.1%, respectively, with systematic uncertainties in dust temperature and molecular gas mass to dust mass ratio of a factor of 1.7. Strong upper limits from CO emission for these two targets<|im_end|> <|im_start|>assistant Early massive galaxies—those that formed in the 3 billion years following the Big Bang—should have contained large amounts of cold hydrogen gas, the fuel required to make stars. But scientists observing the early universe with the Atacama Large Millimeter/submillimeter Array (ALMA) and the Hubble Space Telescope have spotted something strange: a half-dozen early massive galaxies that ran out of fuel. The results of the research are published today in Nature. Known as "quenched" galaxies—or galaxies that have shut down star formation—the six high-redshift galaxies that were selected for observation from the REQUIEM survey are inconsistent with what astronomers expect of the early universe. "The most massive galaxies in the universe lived fast and furious, creating their stars in a remarkably short amount of time. Gas, the fuel of star formation, should be plentiful at these early times in the universe," said Kate Whitaker, lead author on the study, and assistant professor of astronomy at the University of Massachusetts, Amherst. "We originally believed that these quenched galaxies hit the brakes just a few billion years after the Big Bang. In our new research, we've concluded that early galaxies didn't actually put the brakes on, but rather, they were running on empty." To better understand how the galaxies formed and died, the team observed them using Hubble, which revealed details about the stars residing in the galaxies. Concurrent observations with ALMA revealed the galaxies' continuum emission—a tracer of dust—at millimeter wavelengths, allowing the team to infer the amount of gas in the galaxies. The use of the two telescopes is by careful design, as the purpose of REQUIEM is to use strong gravitational lensing as a natural telescope to observe dormant galaxies with higher spatial resolution. This, in turn, gives scientists a clear view of galaxies' internal goings-on, a task often impossible with those running on empty. This composite image of galaxy cluster MACSJ 0138 shows data from the Atacama Large Millimeter/submillimeter Array (ALMA) and NASA’s Hubble Space Telescope, as observed by REsolving QUIEscent Magnified galaxies at high redshift, or the REQUIEM survey. The early massive galaxies studied by REQUIEM were found to be lacking in cold hydrogen gas, the fuel required to form stars. Credit: ALMA (ESO/NAOJ/NRAO)/S. Dagnello (NRAO), STScI, K. Whitaker et al "If a galaxy isn't making many new stars it gets very faint very fast so it is difficult or impossible to observe them in detail with any individual telescope. REQUIEM solves this by studying galaxies that are gravitationally lensed, meaning their light gets stretched and magnified as it bends and warps around other galaxies much closer to the Milky Way," said Justin Spilker, a co-author on the new study, and a NASA Hubble postdoctoral fellow at the University of Texas at Austin. "In this way, gravitational lensing, combined with the resolving power and sensitivity of Hubble and ALMA, acts as a natural telescope and makes these dying galaxies appear bigger and brighter than they are in reality, allowing us to see what's going on and what isn't." The new observations showed that the cessation of star formation in the six target galaxies was not caused by a sudden inefficiency in the conversion of cold gas to stars. Instead, it was the result of the depletion or removal of the gas reservoirs in the galaxies. "We don't yet understand why this happens, but possible explanations could be that either the primary gas supply fueling the galaxy is cut off, or perhaps a supermassive black hole is injecting energy that keeps the gas in the galaxy hot," said Christina Williams, an astronomer at the University of Arizona and co-author on the research. "Essentially, this means that the galaxies are unable to refill the fuel tank, and thus, unable to restart the engine on star production." The study also represents a number of important firsts in the measurement of early massive galaxies, synthesizing information that will guide future studies of the early universe for years to come. "These are the first measurements of the cold dust continuum of distant dormant galaxies, and in fact, the first measurements of this kind outside the local universe," said Whitaker, adding that the new study has allowed scientists to see how much gas individual dead galaxies have. "We were able to probe the fuel of star formation in these early massive galaxies deep enough to take the first measurements of the gas tank reading, giving us a critically missing viewpoint of the cold gas properties of these galaxies." Although the team now knows that these galaxies are running on empty and that something is keeping them from refilling the tank and from forming new stars, the study represents just the first in a series of inquiries into what made early massive galaxies go, or not. "We still have so much to learn about why the most massive galaxies formed so early in the universe and why they shut down their star formation when so much cold gas was readily available to them," said Whitaker. "The mere fact that these massive beasts of the cosmos formed 100 billion stars within about a billion years and then suddenly shut down their star formation is a mystery we would all love to solve, and REQUIEM has provided the first clue." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Fructose consumption is linked to the rising incidence of obesity and cancer, which are two of the leading causes of morbidity and mortality globally 1 , 2 . Dietary fructose metabolism begins at the epithelium of the small intestine, where fructose is transported by glucose transporter type 5 (GLUT5; encoded by SLC2A5 ) and phosphorylated by ketohexokinase to form fructose 1-phosphate, which accumulates to high levels in the cell 3 , 4 . Although this pathway has been implicated in obesity and tumour promotion, the exact mechanism that drives these pathologies in the intestine remains unclear. Here we show that dietary fructose improves the survival of intestinal cells and increases intestinal villus length in several mouse models. The increase in villus length expands the surface area of the gut and increases nutrient absorption and adiposity in mice that are fed a high-fat diet. In hypoxic intestinal cells, fructose 1-phosphate inhibits the M2 isoform of pyruvate kinase to promote cell survival 5 , 6 , 7 . Genetic ablation of ketohexokinase or stimulation of pyruvate kinase prevents villus elongation and abolishes the nutrient absorption and tumour growth that are induced by feeding mice with high-fructose corn syrup. The ability of fructose to promote cell survival through an allosteric metabolite thus provides additional insights into the excess adiposity generated by a Western diet, and a compelling explanation for the promotion of tumour growth by high-fructose corn syrup. Main Humans in the Western world consume more fructose now than ever before in recorded history. Agricultural and industrial advances have improved the access to sweeteners like sucrose and high-fructose corn syrup (HFCS), which have tripled the total consumption of fructose and contributed to a burgeoning epidemic of obesity and related diseases 8 , 9 . The global rise in obesity is directly linked to an increase in obesity-related cancers such as colorectal cancer (CRC), the incidence and mortality of which are rising among young adults 10 , 11 . Several observations suggest that there is a causal relationship between fructose consumption and CRC. For example, fructose consumption is associated with the incidence and progression of gastrointestinal cancer 2 , 12 , 13 , 14 , and drives tumour growth and metastasis in mouse models of CRC 15 , 16 . As tumour growth is driven by hyperplasia and tumour cells frequently retain metabolic pathways from their tissue of origin, we hypothesized that fructose would promote hyperplasia of the normal intestinal epithelium just as it promotes growth in intestinal tumours. To assess this, we fed mice HFCS for four weeks and quantified the mean intestinal villus length using a high-throughput, unbiased image-segmentation-based approach (Extended Data Fig. 1a–f ). Mice of both sexes and a variety of ages and genetic backgrounds that were treated with HFCS showed a 25–40% increase in intestinal villus length in the duodenum and proximal jejunum compared to H 2 O-treated control mice (Fig. 1a , Extended Data Fig. 1h ). The increase in villus length correlated with increased weight gain and fat accumulation as well as lipid absorption (Extended Data Fig. 2a–l ). Fig. 1: Dietary fructose increases intestinal villus length and lipid absorption. a , Haematoxylin and eosin (H&E)-stained duodenum from mice that were fed normal chow with ad libitum H 2 O or 25% HFCS for four weeks. Scale bars, 3 mm (top); 200 μm (bottom). b , Relative change in the body mass of mice that were fed a control diet, a high-fat diet (45% kcal fat) (HF) or a high-fat, high-sucrose diet (HFHS) ( n = 5 mice per group). c , Mass of white adipose tissue from the gonadal depot after five weeks on each diet ( n = 5 mice per group; two depots per mouse). d , Relative duodenal villus length after five weeks on each diet ( n = 5 mice per group). e , Serum triglyceride levels in fasted mice after an oral gavage with olive oil ( n = 3 mice per group). f , BrdU immunohistochemistry (IHC) of duodenal sections from H 2 O or HFCS-treated mice 72 h after intraperitoneal BrdU injection. Scale bars, 200 μm. g , Duodenal villus length distal to the BrdU front ( n = 3 mice per group; 40 villi per mouse). h , i , IHC for CC3 ( h ) and pimodinazole ( i ) in duodenal sections from H 2 O-treated mice. Scale bars, 200 μm. b – e , One-way ANOVA followed by Holm–Sidak post-hoc test for multiple comparisons; g , two-sided Student’s t -test. NS, not significant; * P < 0.05, ** P < 0.01, **** P < 0.0001; exact P values are provided in the Source Data for all figures. All data are mean ± s.e.m. Source data Full size image We hypothesized that this increase in absorption would exacerbate weight gain in mice placed on a high-fat diet (HFD) that contained fructose. Over four weeks, mice were treated with a control diet that contained no fructose, a standard HFD (45% of calories from fat) that contained dextrose but no fructose, or an isocaloric HFD in which the dextrose was replaced by sucrose (Supplementary Table 1 ). Mice on the sucrose-fortified HFD gained significantly more weight and fat mass than those on the standard HFD, despite consuming and expending the same amount of energy (Fig. 1b, c , Extended Data Fig. 2m–v ). In agreement with the data from mice that consumed a normal chow (low-fat) diet, mice that were fed fructose in the form of sucrose had a similar small intestinal length but longer villi (Fig. 1d , Extended Data Fig. 2r ), exhibited increased levels of serum triglycerides after an oral lipid bolus (Fig. 1e ) and lost less energy in the faeces compared to isocaloric, sucrose-free control mice (Extended Data Fig. 2w–z ). These data suggest that dietary fructose increases intestinal villus length and nutrient absorption. Intestinal villus length is determined by a balance between the rates of proliferation and death of epithelial cells.", "role": "user" }, { "content": "Eating fructose appears to alter cells in the digestive tract in a way that enables it to take in more nutrients, according to a preclinical study from investigators at Weill Cornell Medicine and NewYork-Presbyterian. These changes could help to explain the well-known link between rising fructose consumption around the world and increased rates of obesity and certain cancers. The research, published August 18 in Nature, focused on the effect of a high-fructose diet on villi, the thin, hairlike structures that line the inside of the small intestine. Villi expand the surface area of the gut and help the body to absorb nutrients, including dietary fats, from food as it passes through the digestive tract. The study found that mice that were fed diets that included fructose had villi that were 25 percent to 40 percent longer than those of mice that were not fed fructose. Additionally, the increase in villus length was associated with increased nutrient absorption, weight gain and fat accumulation in the animals. \"Fructose is structurally different from other sugars like glucose, and it gets metabolized differently,\" said senior author Dr. Marcus DaSilva Goncalves, the Ralph L. Nachman Research Scholar, an assistant professor of medicine in the Division of Endocrinology, Diabetes and Metabolism and an endocrinologist at NewYork-Presbyterian/Weill Cornell Medical Center. \"Our research has found that fructose's primary metabolite promotes the elongation of villi and supports intestinal tumor growth.\" The investigators didn't plan to study villi. Previous research from the team, published in 2019, found that dietary fructose could increase tumor size in mouse models of colorectal cancer, and that blocking fructose metabolism could prevent that from happening. Reasoning that fructose might also promote hyperplasia, or accelerated growth, of the small intestine, the researchers examined tissues from mice treated with fructose or a control diet under the microscope. The observation that the mice on the high-fructose diet had increased villi length, which was made by first author Samuel Taylor, a Tri-Institutional M.D.-Ph.D. Program student in Dr. Goncalves' lab, was a complete surprise. And once he made the discovery, he and Dr. Goncalves set out to learn more. After observing that the villi were longer, the team wanted to determine whether those villi were functioning differently. So they put mice into three groups: a normal low-fat diet, a high-fat diet, and a high-fat diet with added fructose. Not only did the mice in the third group develop longer villi, but they became more obese than the mice receiving the high-fat diet without fructose. The researchers took a closer look at the changes in metabolism and found that a specific metabolite of fructose, called fructose-1-phosphate, was accumulating at high levels. This metabolite interacted with a glucose-metabolizing enzyme called pyruvate kinase, to alter cell metabolism and promote villus survival and elongation. When pyruvate kinase or the enzyme that makes fructose-1-phospate were removed, fructose had no effect on villus length. Previous animal studies have suggested that this metabolite of fructose also aids in tumor growth. According to Taylor, the observations in mice make sense from an evolutionary perspective. \"In mammals, especially hibernating mammals in temperate climates, you have fructose being very available in the fall months when the fruit is ripe,\" he said. \"Eating a lot of fructose may help these animals to absorb and convert more nutrients to fat, which they need to get through the winter.\" Dr. Goncalves added that humans did not evolve to eat what they eat now. \"Fructose is nearly ubiquitous in modern diets, whether it comes from high-fructose corn syrup, table sugar, or from natural foods like fruit,\" he said. \"Fructose itself is not harmful. It's a problem of overconsumption. Our bodies were not designed to eat as much of it as we do.\" Future research will aim to confirm that the findings in mice translate to humans. \"There are already drugs in clinical trials for other purposes that target the enzyme responsible for producing fructose-1-phosphate,\" said Dr. Goncalves, who is also a member of the Sandra and Edward Meyer Cancer Center. \"We're hoping to find a way to repurpose them to shrink the villi, reduce fat absorption, and possibly slow tumor growth.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Fructose consumption is linked to the rising incidence of obesity and cancer, which are two of the leading causes of morbidity and mortality globally 1 , 2 . Dietary fructose metabolism begins at the epithelium of the small intestine, where fructose is transported by glucose transporter type 5 (GLUT5; encoded by SLC2A5 ) and phosphorylated by ketohexokinase to form fructose 1-phosphate, which accumulates to high levels in the cell 3 , 4 . Although this pathway has been implicated in obesity and tumour promotion, the exact mechanism that drives these pathologies in the intestine remains unclear. Here we show that dietary fructose improves the survival of intestinal cells and increases intestinal villus length in several mouse models. The increase in villus length expands the surface area of the gut and increases nutrient absorption and adiposity in mice that are fed a high-fat diet. In hypoxic intestinal cells, fructose 1-phosphate inhibits the M2 isoform of pyruvate kinase to promote cell survival 5 , 6 , 7 . Genetic ablation of ketohexokinase or stimulation of pyruvate kinase prevents villus elongation and abolishes the nutrient absorption and tumour growth that are induced by feeding mice with high-fructose corn syrup. The ability of fructose to promote cell survival through an allosteric metabolite thus provides additional insights into the excess adiposity generated by a Western diet, and a compelling explanation for the promotion of tumour growth by high-fructose corn syrup. Main Humans in the Western world consume more fructose now than ever before in recorded history. Agricultural and industrial advances have improved the access to sweeteners like sucrose and high-fructose corn syrup (HFCS), which have tripled the total consumption of fructose and contributed to a burgeoning epidemic of obesity and related diseases 8 , 9 . The global rise in obesity is directly linked to an increase in obesity-related cancers such as colorectal cancer (CRC), the incidence and mortality of which are rising among young adults 10 , 11 . Several observations suggest that there is a causal relationship between fructose consumption and CRC. For example, fructose consumption is associated with the incidence and progression of gastrointestinal cancer 2 , 12 , 13 , 14 , and drives tumour growth and metastasis in mouse models of CRC 15 , 16 . As tumour growth is driven by hyperplasia and tumour cells frequently retain metabolic pathways from their tissue of origin, we hypothesized that fructose would promote hyperplasia of the normal intestinal epithelium just as it promotes growth in intestinal tumours. To assess this, we fed mice HFCS for four weeks and quantified the mean intestinal villus length using a high-throughput, unbiased image-segmentation-based approach (Extended Data Fig. 1a–f ). Mice of both sexes and a variety of ages and genetic backgrounds that were treated with HFCS showed a 25–40% increase in intestinal villus length in the duodenum and proximal jejunum compared to H 2 O-treated control mice (Fig. 1a , Extended Data Fig. 1h ). The increase in villus length correlated with increased weight gain and fat accumulation as well as lipid absorption (Extended Data Fig. 2a–l ). Fig. 1: Dietary fructose increases intestinal villus length and lipid absorption. a , Haematoxylin and eosin (H&E)-stained duodenum from mice that were fed normal chow with ad libitum H 2 O or 25% HFCS for four weeks. Scale bars, 3 mm (top); 200 μm (bottom). b , Relative change in the body mass of mice that were fed a control diet, a high-fat diet (45% kcal fat) (HF) or a high-fat, high-sucrose diet (HFHS) ( n = 5 mice per group). c , Mass of white adipose tissue from the gonadal depot after five weeks on each diet ( n = 5 mice per group; two depots per mouse). d , Relative duodenal villus length after five weeks on each diet ( n = 5 mice per group). e , Serum triglyceride levels in fasted mice after an oral gavage with olive oil ( n = 3 mice per group). f , BrdU immunohistochemistry (IHC) of duodenal sections from H 2 O or HFCS-treated mice 72 h after intraperitoneal BrdU injection. Scale bars, 200 μm. g , Duodenal villus length distal to the BrdU front ( n = 3 mice per group; 40 villi per mouse). h , i , IHC for CC3 ( h ) and pimodinazole ( i ) in duodenal sections from H 2 O-treated mice. Scale bars, 200 μm. b – e , One-way ANOVA followed by Holm–Sidak post-hoc test for multiple comparisons; g , two-sided Student’s t -test. NS, not significant; * P < 0.05, ** P < 0.01, **** P < 0.0001; exact P values are provided in the Source Data for all figures. All data are mean ± s.e.m. Source data Full size image We hypothesized that this increase in absorption would exacerbate weight gain in mice placed on a high-fat diet (HFD) that contained fructose. Over four weeks, mice were treated with a control diet that contained no fructose, a standard HFD (45% of calories from fat) that contained dextrose but no fructose, or an isocaloric HFD in which the dextrose was replaced by sucrose (Supplementary Table 1 ). Mice on the sucrose-fortified HFD gained significantly more weight and fat mass than those on the standard HFD, despite consuming and expending the same amount of energy (Fig. 1b, c , Extended Data Fig. 2m–v ). In agreement with the data from mice that consumed a normal chow (low-fat) diet, mice that were fed fructose in the form of sucrose had a similar small intestinal length but longer villi (Fig. 1d , Extended Data Fig. 2r ), exhibited increased levels of serum triglycerides after an oral lipid bolus (Fig. 1e ) and lost less energy in the faeces compared to isocaloric, sucrose-free control mice (Extended Data Fig. 2w–z ). These data suggest that dietary fructose increases intestinal villus length and nutrient absorption. Intestinal villus length is determined by a balance between the rates of proliferation and death of epithelial cells.<|im_end|> <|im_start|>assistant Eating fructose appears to alter cells in the digestive tract in a way that enables it to take in more nutrients, according to a preclinical study from investigators at Weill Cornell Medicine and NewYork-Presbyterian. These changes could help to explain the well-known link between rising fructose consumption around the world and increased rates of obesity and certain cancers. The research, published August 18 in Nature, focused on the effect of a high-fructose diet on villi, the thin, hairlike structures that line the inside of the small intestine. Villi expand the surface area of the gut and help the body to absorb nutrients, including dietary fats, from food as it passes through the digestive tract. The study found that mice that were fed diets that included fructose had villi that were 25 percent to 40 percent longer than those of mice that were not fed fructose. Additionally, the increase in villus length was associated with increased nutrient absorption, weight gain and fat accumulation in the animals. "Fructose is structurally different from other sugars like glucose, and it gets metabolized differently," said senior author Dr. Marcus DaSilva Goncalves, the Ralph L. Nachman Research Scholar, an assistant professor of medicine in the Division of Endocrinology, Diabetes and Metabolism and an endocrinologist at NewYork-Presbyterian/Weill Cornell Medical Center. "Our research has found that fructose's primary metabolite promotes the elongation of villi and supports intestinal tumor growth." The investigators didn't plan to study villi. Previous research from the team, published in 2019, found that dietary fructose could increase tumor size in mouse models of colorectal cancer, and that blocking fructose metabolism could prevent that from happening. Reasoning that fructose might also promote hyperplasia, or accelerated growth, of the small intestine, the researchers examined tissues from mice treated with fructose or a control diet under the microscope. The observation that the mice on the high-fructose diet had increased villi length, which was made by first author Samuel Taylor, a Tri-Institutional M.D.-Ph.D. Program student in Dr. Goncalves' lab, was a complete surprise. And once he made the discovery, he and Dr. Goncalves set out to learn more. After observing that the villi were longer, the team wanted to determine whether those villi were functioning differently. So they put mice into three groups: a normal low-fat diet, a high-fat diet, and a high-fat diet with added fructose. Not only did the mice in the third group develop longer villi, but they became more obese than the mice receiving the high-fat diet without fructose. The researchers took a closer look at the changes in metabolism and found that a specific metabolite of fructose, called fructose-1-phosphate, was accumulating at high levels. This metabolite interacted with a glucose-metabolizing enzyme called pyruvate kinase, to alter cell metabolism and promote villus survival and elongation. When pyruvate kinase or the enzyme that makes fructose-1-phospate were removed, fructose had no effect on villus length. Previous animal studies have suggested that this metabolite of fructose also aids in tumor growth. According to Taylor, the observations in mice make sense from an evolutionary perspective. "In mammals, especially hibernating mammals in temperate climates, you have fructose being very available in the fall months when the fruit is ripe," he said. "Eating a lot of fructose may help these animals to absorb and convert more nutrients to fat, which they need to get through the winter." Dr. Goncalves added that humans did not evolve to eat what they eat now. "Fructose is nearly ubiquitous in modern diets, whether it comes from high-fructose corn syrup, table sugar, or from natural foods like fruit," he said. "Fructose itself is not harmful. It's a problem of overconsumption. Our bodies were not designed to eat as much of it as we do." Future research will aim to confirm that the findings in mice translate to humans. "There are already drugs in clinical trials for other purposes that target the enzyme responsible for producing fructose-1-phosphate," said Dr. Goncalves, who is also a member of the Sandra and Edward Meyer Cancer Center. "We're hoping to find a way to repurpose them to shrink the villi, reduce fat absorption, and possibly slow tumor growth." <|im_end|>

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4211, 315, 30495, 220, 868, 1174, 220, 845, 662, 1666, 15756, 414, 6650, 374, 16625, 555, 17508, 501, 36259, 323, 15756, 414, 7917, 14134, 14389, 41861, 44014, 505, 872, 20438, 315, 6371, 11, 584, 22601, 83979, 430, 1448, 87873, 1053, 12192, 17508, 501, 36259, 315, 279, 4725, 63900, 64779, 301, 2411, 1120, 439, 433, 39990, 6650, 304, 63900, 15756, 2530, 13, 2057, 8720, 420, 11, 584, 23114, 24548, 51658, 6546, 369, 3116, 5672, 323, 10484, 1908, 279, 3152, 63900, 9077, 355, 3160, 1701, 264, 1579, 43847, 631, 11, 74315, 2217, 7962, 9247, 367, 6108, 5603, 320, 54290, 2956, 23966, 13, 220, 16, 64, 4235, 69, 7609, 386, 560, 315, 2225, 76032, 323, 264, 8205, 315, 17051, 323, 19465, 36576, 430, 1051, 12020, 449, 51658, 6546, 8710, 264, 220, 914, 4235, 1272, 4, 5376, 304, 63900, 9077, 355, 3160, 304, 279, 3930, 347, 9195, 323, 22267, 2931, 4864, 58781, 372, 7863, 311, 473, 220, 17, 507, 88186, 2585, 24548, 320, 30035, 13, 220, 16, 64, 1174, 41665, 2956, 23966, 13, 220, 16, 71, 7609, 578, 5376, 304, 9077, 355, 3160, 49393, 449, 7319, 4785, 8895, 323, 8834, 46835, 439, 1664, 439, 68700, 44225, 320, 54290, 2956, 23966, 13, 220, 17, 64, 4235, 75, 7609, 23966, 13, 220, 16, 25, 83808, 1448, 87873, 12992, 63900, 9077, 355, 3160, 323, 68700, 44225, 13, 264, 1174, 14433, 336, 4428, 4223, 3817, 323, 62894, 258, 320, 39, 69248, 7435, 267, 2692, 3930, 347, 9195, 505, 24548, 430, 1051, 23114, 4725, 523, 363, 449, 1008, 3127, 275, 372, 473, 220, 17, 507, 477, 220, 914, 4, 51658, 6546, 369, 3116, 5672, 13, 25635, 16283, 11, 220, 18, 9653, 320, 3565, 1237, 220, 1049, 33983, 76, 320, 15205, 570, 293, 1174, 40502, 2349, 304, 279, 2547, 3148, 315, 24548, 430, 1051, 23114, 264, 2585, 10173, 11, 264, 1579, 64354, 10173, 320, 1774, 4, 96103, 8834, 8, 320, 50816, 8, 477, 264, 1579, 64354, 11, 1579, 1355, 1791, 25888, 10173, 320, 50816, 12228, 8, 320, 308, 284, 220, 20, 24548, 824, 1912, 570, 272, 1174, 9346, 315, 4251, 30366, 974, 20438, 505, 279, 64592, 51588, 45719, 1306, 4330, 5672, 389, 1855, 10173, 320, 308, 284, 220, 20, 24548, 824, 1912, 26, 1403, 2219, 2469, 824, 8814, 570, 294, 1174, 40502, 3930, 55836, 278, 9077, 355, 3160, 1306, 4330, 5672, 389, 1855, 10173, 320, 308, 284, 220, 20, 24548, 824, 1912, 570, 384, 1174, 94591, 54033, 68590, 579, 5990, 304, 5043, 291, 24548, 1306, 459, 21308, 342, 68256, 449, 33213, 5707, 320, 308, 284, 220, 18, 24548, 824, 1912, 570, 282, 1174, 3320, 67, 52, 33119, 2319, 26407, 52755, 320, 40, 23263, 8, 315, 3930, 55836, 278, 14491, 505, 473, 220, 17, 507, 477, 51658, 6546, 88186, 24548, 220, 5332, 305, 1306, 10805, 3271, 85166, 278, 3320, 67, 52, 26127, 13, 25635, 16283, 11, 220, 1049, 33983, 76, 13, 342, 1174, 16062, 55836, 278, 9077, 355, 3160, 1612, 278, 311, 279, 3320, 67, 52, 4156, 320, 308, 284, 220, 18, 24548, 824, 1912, 26, 220, 1272, 9077, 72, 824, 8814, 570, 305, 1174, 602, 1174, 358, 23263, 369, 13844, 18, 320, 305, 883, 323, 281, 318, 347, 258, 77001, 320, 602, 883, 304, 3930, 55836, 278, 14491, 505, 473, 220, 17, 507, 88186, 24548, 13, 25635, 16283, 11, 220, 1049, 33983, 76, 13, 293, 1389, 384, 1174, 3861, 27896, 2147, 46, 13114, 8272, 555, 16071, 76, 4235, 50, 61489, 1772, 2902, 511, 1296, 369, 5361, 36595, 26, 342, 1174, 1403, 50858, 11988, 753, 259, 482, 1985, 13, 3119, 11, 539, 5199, 26, 353, 393, 366, 220, 15, 13, 2304, 11, 3146, 393, 366, 220, 15, 13, 1721, 11, 31804, 393, 366, 220, 15, 13, 931, 16, 26, 4839, 393, 2819, 527, 3984, 304, 279, 8922, 2956, 369, 682, 12678, 13, 2052, 828, 527, 3152, 20903, 274, 1770, 749, 13, 8922, 828, 8797, 1404, 2217, 1226, 22601, 83979, 430, 420, 5376, 304, 44225, 1053, 52875, 349, 4785, 8895, 304, 24548, 9277, 389, 264, 1579, 64354, 10173, 320, 39, 14938, 8, 430, 13282, 1448, 87873, 13, 6193, 3116, 5672, 11, 24548, 1051, 12020, 449, 264, 2585, 10173, 430, 13282, 912, 1448, 87873, 11, 264, 5410, 473, 14938, 320, 1774, 4, 315, 25247, 505, 8834, 8, 430, 13282, 294, 428, 25888, 719, 912, 1448, 87873, 11, 477, 459, 374, 3768, 27456, 473, 14938, 304, 902, 279, 294, 428, 25888, 574, 12860, 555, 11405, 25888, 320, 10254, 67082, 6771, 220, 16, 7609, 386, 560, 389, 279, 11405, 25888, 2269, 371, 1908, 473, 14938, 18661, 12207, 810, 4785, 323, 8834, 3148, 1109, 1884, 389, 279, 5410, 473, 14938, 11, 8994, 35208, 323, 1367, 2518, 279, 1890, 3392, 315, 4907, 320, 30035, 13, 220, 16, 65, 11, 272, 1174, 41665, 2956, 23966, 13, 220, 17, 76, 4235, 85, 7609, 763, 9306, 449, 279, 828, 505, 24548, 430, 27073, 264, 4725, 523, 363, 320, 10516, 64354, 8, 10173, 11, 24548, 430, 1051, 23114, 1448, 87873, 304, 279, 1376, 315, 11405, 25888, 1047, 264, 4528, 2678, 63900, 3160, 719, 5129, 9077, 72, 320, 30035, 13, 220, 16, 67, 1174, 41665, 2956, 23966, 13, 220, 17, 81, 7026, 51713, 7319, 5990, 315, 41529, 54033, 68590, 3422, 1306, 459, 21308, 68700, 21434, 355, 320, 30035, 13, 220, 16, 68, 883, 323, 5675, 2753, 4907, 304, 279, 2267, 762, 288, 7863, 311, 374, 3768, 27456, 11, 11405, 25888, 12862, 2585, 24548, 320, 54290, 2956, 23966, 13, 220, 17, 86, 4235, 89, 7609, 4314, 828, 4284, 430, 34625, 1448, 87873, 12992, 63900, 9077, 355, 3160, 323, 50123, 44225, 13, 1357, 65050, 9077, 355, 3160, 374, 11075, 555, 264, 8335, 1990, 279, 7969, 315, 53840, 323, 4648, 315, 64779, 59544, 7917, 13, 128257, 198, 128256, 78191, 198, 36, 1113, 1448, 87873, 8111, 311, 11857, 7917, 304, 279, 60071, 42929, 304, 264, 1648, 430, 20682, 433, 311, 1935, 304, 810, 37493, 11, 4184, 311, 264, 864, 91899, 4007, 505, 26453, 520, 1226, 484, 56819, 19152, 323, 1561, 100077, 9483, 417, 80436, 13, 4314, 4442, 1436, 1520, 311, 10552, 279, 1664, 22015, 2723, 1990, 16448, 1448, 87873, 15652, 2212, 279, 1917, 323, 7319, 7969, 315, 33048, 323, 3738, 51423, 13, 578, 3495, 11, 4756, 6287, 220, 972, 304, 22037, 11, 10968, 389, 279, 2515, 315, 264, 1579, 51478, 87873, 10173, 389, 9077, 72, 11, 279, 15792, 11, 7013, 4908, 14726, 430, 1584, 279, 4871, 315, 279, 2678, 92234, 13, 16959, 72, 9407, 279, 7479, 3158, 315, 279, 18340, 323, 1520, 279, 2547, 311, 35406, 37493, 11, 2737, 34625, 50127, 11, 505, 3691, 439, 433, 16609, 1555, 279, 60071, 42929, 13, 578, 4007, 1766, 430, 24548, 430, 1051, 23114, 41943, 430, 5343, 1448, 87873, 1047, 9077, 72, 430, 1051, 220, 914, 3346, 311, 220, 1272, 3346, 5129, 1109, 1884, 315, 24548, 430, 1051, 539, 23114, 1448, 87873, 13, 23212, 11, 279, 5376, 304, 9077, 355, 3160, 574, 5938, 449, 7319, 50123, 44225, 11, 4785, 8895, 323, 8834, 46835, 304, 279, 10099, 13, 330, 23376, 87873, 374, 2080, 43024, 2204, 505, 1023, 70913, 1093, 34323, 11, 323, 433, 5334, 28168, 1534, 22009, 1359, 1071, 10195, 3229, 2999, 13, 36783, 14569, 28671, 6723, 80806, 5531, 2396, 11, 279, 40904, 445, 13, 29375, 1543, 8483, 25542, 11, 459, 18328, 14561, 315, 16088, 304, 279, 14829, 315, 4060, 91153, 2508, 11, 53689, 323, 6344, 53904, 2191, 323, 459, 842, 91153, 16549, 520, 1561, 100077, 9483, 417, 80436, 14, 1687, 484, 56819, 13235, 5955, 13, 330, 8140, 3495, 706, 1766, 430, 1448, 87873, 596, 6156, 28168, 635, 39990, 279, 74595, 367, 315, 9077, 72, 323, 11815, 63900, 36254, 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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Growth of long bones and vertebrae is maintained postnatally by a long-lasting pool of progenitor cells. Little is known about the molecular mechanisms that regulate the output and maintenance of the cells that give rise to mature cartilage. Here we demonstrate that postnatal chondrocyte-specific deletion of a transcription factor Stat3 results in severely reduced proliferation coupled with increased hypertrophy, growth plate fusion, stunting and signs of progressive dysfunction of the articular cartilage. This effect is dimorphic, with females more strongly affected than males. Chondrocyte-specific deletion of the IL-6 family cytokine receptor gp130, which activates Stat3, phenocopied Stat3-deletion; deletion of Lifr, one of many co-receptors that signals through gp130, resulted in a milder phenotype. These data define a molecular circuit that regulates chondrogenic cell maintenance and output and reveals a pivotal positive function of IL-6 family cytokines in the skeletal system with direct implications for skeletal development and regeneration. Introduction The continual growth of long bones and vertebrae is fueled by chondrogenic stem and progenitor cells in the growth plate 1 . Beginning in embryogenesis and continuing through adolescence, these chondroprogenitors provide a steady stream of progeny that undergo endochondral ossification and contribute to bone growth 2 . Chondrocytes enter a phase of rapid division as they leave the resting zone of the growth plate, forming characteristic columns of mitotic cells that begin to secrete increased levels of extracellular matrix (ECM) proteins such as collagen II and aggrecan 3 . Once their distance from the niche within the resting zone increases to its maximum extent, they become hypertrophic, deposit lower amounts of ECM, and begin secreting collagen X and alkaline phosphatase, which is essential for calcification of the ECM 4 . Once surrounded by calcified matrix, these chondrocytes either undergo apoptosis or transdifferentiate into osteoprogenitors 5 ; osteoprogenitors derived from the growth plate, or invading from the periosteum, differentiate into osteoblasts and secrete bone matrix. Endochondral ossification takes place during fracture repair, with similar coordinated cellular dynamics 6 . In humans, growth plates become inactive at the end of puberty, resulting in replacement with bone; this occurs earlier in the long bones than in the spine 7 . Females undergo growth plate fusion an average of 2 years earlier than males, suggesting sexually dimorphic regulation of chondroprogenitors 8 . In mice, growth plates in the long bones and spine persist throughout the lifespan of the animal, providing an opportunity to study how specific molecular pathways impact the dynamics of chondroprogenitors. Recently, Newton et al. defined a population of chondrogenic cells localized to the growth plate that generate clonal progeny and support long bone growth 9 . Their data supported previous work showing that Hedgehog (Hh) signaling is required for growth plate maintenance; if this pathway is inhibited, growth plates fuse and differentiate into trabecular bone 10 . These results highlight the need for controlled, sustained proliferation of chondroprogenitors to maintain active growth plates. Data from our group has shown that the transcription factor STAT3 regulates human chondrocyte proliferation at both fetal and adult stages 11 , 12 . Chondrocytes enriched for active STAT3 are more proliferative and are also enriched for SOX9 protein, the master regulator of chondrogenesis, while evidencing negligible levels of the osteogenic transcription factor RUNX2 12 . Inhibition of either Il6ST (gp130), the obligate co-receptor for all IL-6 family cytokines, or LIFR which heterodimerizes with gp130 to facilitate LIF signaling, greatly reduced chondrocyte proliferation and STAT3 activation, respectively 11 . Inhibition of STAT3 activity in human fetal chondrocytes greatly reduced proliferation while increasing apoptosis, suggesting an important role for this molecule and the signaling mediated by gp130 in developmental chondrogenesis 11 . This is supported by data from zebrafish, in which stat3 null fish evidence fully penetrant scoliosis, reduced proliferation and increased apoptosis 13 . Moreover, deletion of Stat3 in mesodermal and early skeletal tissues using T -Cre and Prrx1 -Cre, respectively, caused dwarfism, skeletal abnormalities and kyphosis; the authors did not assess proliferation, but did observe significantly reduced SOX9 levels in Stat3 −/− chondrocytes 14 . They went on to show that stimulation with the IL-6 family cytokine oncostatin M (OSM), which can signal through a LIFR/gp130 complex and/or a OSMR/gp130 complex 15 , could increase both STAT3 activation and SOX9 levels in vitro. Few of these animals survived past P7, precluding the analysis of chondroprogenitors at later stages of growth plate function. Together, these studies identify an important role for STAT3 in regulating developing chondrocyte proliferation and apoptosis. However, the function of STAT3 in postnatal developing chondrocytes, the upstream regulators of this transcription factor and the potential role of STAT3 in the sexual dimorphism of growth plate closure remain to be elucidated. Here we show that postnatal deletion of Stat3 in chondrocytes using Acan -Cre ERT2 results in decreased proliferation, increased hypertrophy and apoptosis, stunting and growth plate fusions in the long bones and the spine. Female mice are more strongly impacted than males. We also demonstrate that chondrocyte-specific deletion of Stat3 results in progressive dysfunction of articular cartilage, although this compartment appears to be less affected than the growth plate. Deletion of gp130, the obligate co-receptor for all IL-6 cytokines in postnatal chondrocytes mostly phenocopies deletion of Stat3 , while deletion of Lifr results in a milder phenotype. Conversely, Stat3 overexpression in postnatal chondrocytes resulted in hyperproliferation and skeletal abnormalities and rescued the thin growth plates observed in gp130 deletion mutants. Finally, we show that estradiol increases STAT3 levels and activity in vitro and inhibition of estrogen signaling in female mice reduces Stat3 levels and activation, suggesting a potential mechanism behind the dimorphic effects seen following Stat3 deletion in mice. Collectively, these data define Stat3 as a regulator of postnatal chondrocyte cell proliferation, differentiation and survival and implicates IL-6 family cytokine signaling as a positive regulator of chondrogenic cell proliferation and maintenance. Results Stat3 promotes proliferation and survival in postnatal growth plate chondrocytes During development, chondrocytes form a highly proliferative blastema to supply rapidly growing limbs 16 . We have recently published a survey", "role": "user" }, { "content": "The IL-6 family of proteins has a bad reputation: it can promote inflammation, arthritis, autoimmune disease and even cancer. However, a new USC-led study published in Communications Biology reveals the importance of IL-6 and associated genes for maintaining and regenerating cartilage in both the joints and in the growth plates that enable skeletal growth in children. \"We show, for the first time, that the IL-6 family, previously almost exclusively associated in the musculoskeletal field with arthritis, bone and muscle loss, and other chronic inflammatory diseases, is required for the maintenance of skeletal stem and progenitor cells, and for the healthy growth and function of the joints and spine,\" said the study's corresponding author Denis Evseenko, who is the J. Harold and Edna LaBriola Chair in Genetic Orthopedic Research, and an associate professor of orthopedic surgery, and stem cell biology and regenerative medicine at USC. \"Our study establishes a link between inflammation and regeneration, and may explain why stem and progenitors are exhausted in chronic inflammation.\" In the study, first author Nancy Q. Liu from USC and her colleagues took a close look at a key gene activated by IL-6: STAT3. In both lab-grown human cells and in mice, the scientists demonstrated that STAT3 is critical for the proliferation, survival, maturation and regeneration of cartilage-forming cells in the joints and growth plates. When the gene ceased to function, cartilage-forming cells became increasingly dysfunctional over time, resulting in smaller body size, prematurely fused growth plates, underdeveloped skeletons and mildly degenerated joint cartilage. Mice experienced the same issues when they lacked a protein called glycoprotein 130 (gp130), which all IL-6 proteins use to activate Stat3. Deactivating another gene Lifr, which encodes a protein that works with gp130 to recognize one of the IL-6 proteins called Lif, produced similar but milder skeletal and cartilage changes. In mice lacking gp130, the scientists could restore normal growth plates by over-activating Stat3—although this also caused an overgrowth of cartilage that led to other skeletal abnormalities. Interestingly, the researchers noted significant sex-related differences: when Stat3 ceased to function, females experienced more severe cartilage and skeletal changes than males. To understand why, the researchers altered estrogen levels in mice, as well as in lab-grown pig cartilage cells. In both cases, estrogen increased the amount and activity of Stat3, suggesting that females might rely more heavily on this gene. The study has clinical implications for the use of existing drugs that inhibit STAT3 to curb inflammation in autoimmune diseases: these drugs may also interfere with growth and regeneration. Conversely, the Evseenko Lab has leveraged their understanding of the nuances of STAT3 and associated genes and proteins to develop a highly targeted drug with the potential to regenerate joint cartilage without triggering inflammation. This drug will soon be tested in human clinical trials. \"Our findings really shift the paradigm and challenge the existing dogmas in the field about how IL-6, STAT3, and associated genes and proteins influence not only inflammation, but also regeneration,\" said Evseenko. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Growth of long bones and vertebrae is maintained postnatally by a long-lasting pool of progenitor cells. Little is known about the molecular mechanisms that regulate the output and maintenance of the cells that give rise to mature cartilage. Here we demonstrate that postnatal chondrocyte-specific deletion of a transcription factor Stat3 results in severely reduced proliferation coupled with increased hypertrophy, growth plate fusion, stunting and signs of progressive dysfunction of the articular cartilage. This effect is dimorphic, with females more strongly affected than males. Chondrocyte-specific deletion of the IL-6 family cytokine receptor gp130, which activates Stat3, phenocopied Stat3-deletion; deletion of Lifr, one of many co-receptors that signals through gp130, resulted in a milder phenotype. These data define a molecular circuit that regulates chondrogenic cell maintenance and output and reveals a pivotal positive function of IL-6 family cytokines in the skeletal system with direct implications for skeletal development and regeneration. Introduction The continual growth of long bones and vertebrae is fueled by chondrogenic stem and progenitor cells in the growth plate 1 . Beginning in embryogenesis and continuing through adolescence, these chondroprogenitors provide a steady stream of progeny that undergo endochondral ossification and contribute to bone growth 2 . Chondrocytes enter a phase of rapid division as they leave the resting zone of the growth plate, forming characteristic columns of mitotic cells that begin to secrete increased levels of extracellular matrix (ECM) proteins such as collagen II and aggrecan 3 . Once their distance from the niche within the resting zone increases to its maximum extent, they become hypertrophic, deposit lower amounts of ECM, and begin secreting collagen X and alkaline phosphatase, which is essential for calcification of the ECM 4 . Once surrounded by calcified matrix, these chondrocytes either undergo apoptosis or transdifferentiate into osteoprogenitors 5 ; osteoprogenitors derived from the growth plate, or invading from the periosteum, differentiate into osteoblasts and secrete bone matrix. Endochondral ossification takes place during fracture repair, with similar coordinated cellular dynamics 6 . In humans, growth plates become inactive at the end of puberty, resulting in replacement with bone; this occurs earlier in the long bones than in the spine 7 . Females undergo growth plate fusion an average of 2 years earlier than males, suggesting sexually dimorphic regulation of chondroprogenitors 8 . In mice, growth plates in the long bones and spine persist throughout the lifespan of the animal, providing an opportunity to study how specific molecular pathways impact the dynamics of chondroprogenitors. Recently, Newton et al. defined a population of chondrogenic cells localized to the growth plate that generate clonal progeny and support long bone growth 9 . Their data supported previous work showing that Hedgehog (Hh) signaling is required for growth plate maintenance; if this pathway is inhibited, growth plates fuse and differentiate into trabecular bone 10 . These results highlight the need for controlled, sustained proliferation of chondroprogenitors to maintain active growth plates. Data from our group has shown that the transcription factor STAT3 regulates human chondrocyte proliferation at both fetal and adult stages 11 , 12 . Chondrocytes enriched for active STAT3 are more proliferative and are also enriched for SOX9 protein, the master regulator of chondrogenesis, while evidencing negligible levels of the osteogenic transcription factor RUNX2 12 . Inhibition of either Il6ST (gp130), the obligate co-receptor for all IL-6 family cytokines, or LIFR which heterodimerizes with gp130 to facilitate LIF signaling, greatly reduced chondrocyte proliferation and STAT3 activation, respectively 11 . Inhibition of STAT3 activity in human fetal chondrocytes greatly reduced proliferation while increasing apoptosis, suggesting an important role for this molecule and the signaling mediated by gp130 in developmental chondrogenesis 11 . This is supported by data from zebrafish, in which stat3 null fish evidence fully penetrant scoliosis, reduced proliferation and increased apoptosis 13 . Moreover, deletion of Stat3 in mesodermal and early skeletal tissues using T -Cre and Prrx1 -Cre, respectively, caused dwarfism, skeletal abnormalities and kyphosis; the authors did not assess proliferation, but did observe significantly reduced SOX9 levels in Stat3 −/− chondrocytes 14 . They went on to show that stimulation with the IL-6 family cytokine oncostatin M (OSM), which can signal through a LIFR/gp130 complex and/or a OSMR/gp130 complex 15 , could increase both STAT3 activation and SOX9 levels in vitro. Few of these animals survived past P7, precluding the analysis of chondroprogenitors at later stages of growth plate function. Together, these studies identify an important role for STAT3 in regulating developing chondrocyte proliferation and apoptosis. However, the function of STAT3 in postnatal developing chondrocytes, the upstream regulators of this transcription factor and the potential role of STAT3 in the sexual dimorphism of growth plate closure remain to be elucidated. Here we show that postnatal deletion of Stat3 in chondrocytes using Acan -Cre ERT2 results in decreased proliferation, increased hypertrophy and apoptosis, stunting and growth plate fusions in the long bones and the spine. Female mice are more strongly impacted than males. We also demonstrate that chondrocyte-specific deletion of Stat3 results in progressive dysfunction of articular cartilage, although this compartment appears to be less affected than the growth plate. Deletion of gp130, the obligate co-receptor for all IL-6 cytokines in postnatal chondrocytes mostly phenocopies deletion of Stat3 , while deletion of Lifr results in a milder phenotype. Conversely, Stat3 overexpression in postnatal chondrocytes resulted in hyperproliferation and skeletal abnormalities and rescued the thin growth plates observed in gp130 deletion mutants. Finally, we show that estradiol increases STAT3 levels and activity in vitro and inhibition of estrogen signaling in female mice reduces Stat3 levels and activation, suggesting a potential mechanism behind the dimorphic effects seen following Stat3 deletion in mice. Collectively, these data define Stat3 as a regulator of postnatal chondrocyte cell proliferation, differentiation and survival and implicates IL-6 family cytokine signaling as a positive regulator of chondrogenic cell proliferation and maintenance. Results Stat3 promotes proliferation and survival in postnatal growth plate chondrocytes During development, chondrocytes form a highly proliferative blastema to supply rapidly growing limbs 16 . We have recently published a survey<|im_end|> <|im_start|>assistant The IL-6 family of proteins has a bad reputation: it can promote inflammation, arthritis, autoimmune disease and even cancer. However, a new USC-led study published in Communications Biology reveals the importance of IL-6 and associated genes for maintaining and regenerating cartilage in both the joints and in the growth plates that enable skeletal growth in children. "We show, for the first time, that the IL-6 family, previously almost exclusively associated in the musculoskeletal field with arthritis, bone and muscle loss, and other chronic inflammatory diseases, is required for the maintenance of skeletal stem and progenitor cells, and for the healthy growth and function of the joints and spine," said the study's corresponding author Denis Evseenko, who is the J. Harold and Edna LaBriola Chair in Genetic Orthopedic Research, and an associate professor of orthopedic surgery, and stem cell biology and regenerative medicine at USC. "Our study establishes a link between inflammation and regeneration, and may explain why stem and progenitors are exhausted in chronic inflammation." In the study, first author Nancy Q. Liu from USC and her colleagues took a close look at a key gene activated by IL-6: STAT3. In both lab-grown human cells and in mice, the scientists demonstrated that STAT3 is critical for the proliferation, survival, maturation and regeneration of cartilage-forming cells in the joints and growth plates. When the gene ceased to function, cartilage-forming cells became increasingly dysfunctional over time, resulting in smaller body size, prematurely fused growth plates, underdeveloped skeletons and mildly degenerated joint cartilage. Mice experienced the same issues when they lacked a protein called glycoprotein 130 (gp130), which all IL-6 proteins use to activate Stat3. Deactivating another gene Lifr, which encodes a protein that works with gp130 to recognize one of the IL-6 proteins called Lif, produced similar but milder skeletal and cartilage changes. In mice lacking gp130, the scientists could restore normal growth plates by over-activating Stat3—although this also caused an overgrowth of cartilage that led to other skeletal abnormalities. Interestingly, the researchers noted significant sex-related differences: when Stat3 ceased to function, females experienced more severe cartilage and skeletal changes than males. To understand why, the researchers altered estrogen levels in mice, as well as in lab-grown pig cartilage cells. In both cases, estrogen increased the amount and activity of Stat3, suggesting that females might rely more heavily on this gene. The study has clinical implications for the use of existing drugs that inhibit STAT3 to curb inflammation in autoimmune diseases: these drugs may also interfere with growth and regeneration. Conversely, the Evseenko Lab has leveraged their understanding of the nuances of STAT3 and associated genes and proteins to develop a highly targeted drug with the potential to regenerate joint cartilage without triggering inflammation. This drug will soon be tested in human clinical trials. "Our findings really shift the paradigm and challenge the existing dogmas in the field about how IL-6, STAT3, and associated genes and proteins influence not only inflammation, but also regeneration," said Evseenko. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Alzheimer’s disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD. Introduction Alzheimer’s disease (AD), the leading cause of dementia named for Dr. Alois Alzheimer, is characterized by pathologic hallmarks amyloid plaques and neurofibrillary tangles, and accompanied by other prominent pathological changes such as progressive atrophy of the brain, neuropil threads, dystrophic neurites, granulovacuolar degeneration, Hirano bodies, and cerebrovascular amyloid 1 . Amyloid plaques are spherical extracellular lesions composed of amyloid-β (Aβ) peptides, whereas neurofibrillary tangles are intracellular lesions made up of hyperphosphorylated form of the microtubule-associated protein tau. Although many risk factors such as aging, lifestyle, and environmental factors are usually considered for the pathogenesis, AD is increasingly proposed to be a genetically dichotomous disease in the early-onset familial form showing classical Mendelian inheritance with little influence from the environment (EOAD), or in the late-onset sporadic form inherited in a non-Mendelian fashion (LOAD) 2 . Less than 10% of AD cases are EOAD with only a small fraction caused by autosomal dominantly inherited genetic changes in amyloid precursor protein (APP), presenilin 1 (PS1) or presenilin 2 (PS2), all of which are responsible for the overproduction of Aβ and the earlier formation of amyloid plaques 3 . Though more than 90% of AD cases are LOAD referred to as sporadic AD without family history, they have the similar clinical and pathologic phenotypes as EOAD and are heritable 4 . In the past decade, intensive efforts have been made to identify over 25 genes associated with AD 5 . In support of the dominant amyloid cascade hypothesis suggesting Aβ deposition in the brain as the primary cause, a number of AD-associated genes are enriched in the APP processing pathway, and involved in Aβ overproduction and amyloid plaque deposition though their encoded proteins are usually not directly associated with amyloid plaques. Quantitative structural magnetic resonance imaging (MRI) has been extensively used for assessment of AD-related structural differences in selective brain regions 6 . Genome-wide association studies (GWAS) using MRI measures have identified several AD risk variants 7 , 8 . Likewise, the MRI changes in statistically-defined regions of interest (ROI) were found closely associated with reported AD risk variants 9 , 10 . Genetic loci harboring variants can be associated with multiple, sometimes seemingly distinct, traits 11 , 12 . The test for such associations, i.e., cross-phenotype association test, has been increasingly employed to investigate the genetic overlap between multiple traits and diseases. Our previous study has developed a cross-phenotype association analysis (CPASSOC) that can integrate association evidence from GWAS summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, and has been successfully used to identify four loci associated with hypertension-related traits missed by a single-trait analysis 13 . In this study, we performed CPASSOC analysis of MRI measures and genetic datasets, and identified a possible link between FAM222A and AD-related regional brain atrophy. To understand its pathological role in AD, we investigated the protein encoded by FAM222A in patients with AD or transgenic mice for AD, and found its characteristic accumulation within the center of amyloid deposits. Further mechanistic study revealed that this protein could physically interact with Aβ and regulate Aβ aggregation and amyloid formation. Our results therefore identify a protein that likely plays an important role in amyloidosis, a finding providing perspective for AD pathogenesis. Results Susceptibility of regional brain atrophy to FAM222A in AD To identify brain atrophy-related imaging quantitative trait loci, we employed a genome-wide whole brain approach to analyze the imaging genetic dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (Supplementary Fig. 1a ). After GWAS and the estimation of shared genetic contributions among 145 ROIs spanning the entire brain by linkage disequilibrium (LD) regression method 14 (Supplementary Fig. 1b, c ), we attempted to extract disease-related ROIs and detect genetic variants associated with them. With hierarchical clustering analysis on a genetic correlation network (Supplementary Fig. 1d–k ), 16 modules of ROIs with high within-module genetic correlation were generated (Supplementary Fig. 1l, m ). We further combined GWAS summary statistics of ROIs in each module using CPASSOC we developed 13 . Previously reported AD top markers, APOE single nucleotide polymorphism (SNP) rs429358 15 , TOMM40 SNP rs2075650 15 , APOC1 SNP rs12721051 16 , and rs117028417 on FAM222A were found in one module (Fig. 1 , Supplementary Figs. 2 , 3 and Supplementary Table 1 ), which consists of five ROIs including left hippocampus, right hippocampus, basal forebrain, entorhinal area, and planum polare, brain areas we know are affected by AD 17 , 18 , 19 and well predict AD (Supplementary Fig. 4 ). SNP rs117028417 had a minor allele A (frequency = 0.044) with positive effects for all 5 ROIs in the ADNI cohort ( P = 1.95 × 10 −8 for CPASSOC analysis; Supplementary Table 2 ), and was further validated to be associated with the mean volume of hippocampus, one of the earliest affected brain regions in AD, in the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium cohort comprising MRI images of 30,717 individuals from 50 cohorts 20 with the same effect direction ( β = 38.1, P = 8.29 × 10 −3 ; Supplementary Table 2 ). Fig. 1: CPASSOC analysis of the ADNI cohort. Manhattan plot of CPASSOC analysis combining", "role": "user" }, { "content": "Researchers at the Case Western University School of Medicine say they have identified a previously unknown gene and associated protein which could potentially be suppressed to slow the advance of Alzheimer's disease. \"Based on the data we have, this protein can be an unrecognized new risk factor for Alzheimer's disease (AD),\" said Xinglong Wang, an associate professor of pathology at the School of Medicine. \"We also see this as a potential novel therapeutic target for this devastating disease.\" Wang said proving the latter assertion, which has not yet been tested in humans, would require additional research to corroborate the function of the protein they have dubbed \"aggregatin.\" Eventually, that would someday mean clinical trials with Alzheimer's patients, he said. \"This protein characteristically accumulates, or aggregates, within the center of plaque in AD patients, like the yolk of an egg—which is part of the reason we named it \"aggregatin,\" Wang said. A research team led by Wang and Xiaofeng Zhu, a professor of Population and Quantitative Health Sciences at the School of Medicine, has filed for a patent through the university's Office of Research and Technology Management for \"novel Alzheimer's disease treatments and diagnosis based on this and related study,\" Wang said. \"We're very excited about this because our study is likely the first systematic work combining the identification from a genome-wide association study of high dimensional brain-imaging data and experimental validation so perfectly in Alzheimer's disease,\" Zhu said. Their research was published this month by the scientific journal Nature Communications and supported by grants from the National Institutes of Health (NIH) and the Alzheimer's Association. Genomic and brain imaging data was obtained from the Alzheimer's Disease Neuroimaging Initiative, which is supported by the NIH. Alzheimer's Disease affects millions More than 5.7 million Americans have Alzheimer's disease, which is the primary cause of dementia and sixth-leading cause of death in the United States. That population is predicted to reach 14 million by the year 2050, according to the Alzheimer's Association. The relationship between Alzheimer's (and subsequent brain atrophy) and amyloid plaques—the hard accumulations of beta amyloid proteins that clump together between the nerve cells (neurons) in the brains of Alzheimer's patients—has been well-established among researchers. Less understood is precisely how that amyloid-beta actually leads to plaque formation—and where this new work appears to have broken new ground, Wang said. Further, while there has been much research into what genes might influence whether or not someone gets Alzheimer's, there is less understanding of genes that might be linked to the progression of the disease, meaning the formation of plaque and subsequent atrophy in the brain. The role of 'aggregatin' protein In the new work, the researchers began by correlating roughly a million genetic markers (called single-nucleotide polymorphisms, or SNPs) with brain images. They were able to identify a specific SNP in the FAM222, a gene linked to different patterns of regional brain atrophy. Further experiments then suggested that the protein encoded by gene FAM222A is not only associated with AD patient-related beta-amyloid plaques and regional brain atrophy, but that \"aggregatin\" attaches to amyloid beta peptide—the major component of plaque and facilitates the plaque formation. So when researchers injected mouse models with the \"aggregatin\" protein (made from the FAM222A gene), plaque (amyloid deposits) formation accelerated in the brain, resulting in more neuroinflammation and cognitive dysfunction. This happened, they report, because the protein was found to bind directly the amyloid beta peptide, thus facilitating the aggregation and placque formation, Wang said. Conversely, when they suppressed the protein, the plaques were reduced and neuroinflammation and cognitive impairment alleviated. Their findings indicate that reducing levels of this protein and inhibition of its interaction with amyloid beta peptide could potentially be therapeutic—not necessarily to prevent Alzheimer's but to slow its progression. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Alzheimer’s disease (AD) is characterized by amyloid plaques and progressive cerebral atrophy. Here, we report FAM222A as a putative brain atrophy susceptibility gene. Our cross-phenotype association analysis of imaging genetics indicates a potential link between FAM222A and AD-related regional brain atrophy. The protein encoded by FAM222A is predominantly expressed in the CNS and is increased in brains of patients with AD and in an AD mouse model. It accumulates within amyloid deposits, physically interacts with amyloid-β (Aβ) via its N-terminal Aβ binding domain, and facilitates Aβ aggregation. Intracerebroventricular infusion or forced expression of this protein exacerbates neuroinflammation and cognitive dysfunction in an AD mouse model whereas ablation of this protein suppresses the formation of amyloid deposits, neuroinflammation and cognitive deficits in the AD mouse model. Our data support the pathological relevance of protein encoded by FAM222A in AD. Introduction Alzheimer’s disease (AD), the leading cause of dementia named for Dr. Alois Alzheimer, is characterized by pathologic hallmarks amyloid plaques and neurofibrillary tangles, and accompanied by other prominent pathological changes such as progressive atrophy of the brain, neuropil threads, dystrophic neurites, granulovacuolar degeneration, Hirano bodies, and cerebrovascular amyloid 1 . Amyloid plaques are spherical extracellular lesions composed of amyloid-β (Aβ) peptides, whereas neurofibrillary tangles are intracellular lesions made up of hyperphosphorylated form of the microtubule-associated protein tau. Although many risk factors such as aging, lifestyle, and environmental factors are usually considered for the pathogenesis, AD is increasingly proposed to be a genetically dichotomous disease in the early-onset familial form showing classical Mendelian inheritance with little influence from the environment (EOAD), or in the late-onset sporadic form inherited in a non-Mendelian fashion (LOAD) 2 . Less than 10% of AD cases are EOAD with only a small fraction caused by autosomal dominantly inherited genetic changes in amyloid precursor protein (APP), presenilin 1 (PS1) or presenilin 2 (PS2), all of which are responsible for the overproduction of Aβ and the earlier formation of amyloid plaques 3 . Though more than 90% of AD cases are LOAD referred to as sporadic AD without family history, they have the similar clinical and pathologic phenotypes as EOAD and are heritable 4 . In the past decade, intensive efforts have been made to identify over 25 genes associated with AD 5 . In support of the dominant amyloid cascade hypothesis suggesting Aβ deposition in the brain as the primary cause, a number of AD-associated genes are enriched in the APP processing pathway, and involved in Aβ overproduction and amyloid plaque deposition though their encoded proteins are usually not directly associated with amyloid plaques. Quantitative structural magnetic resonance imaging (MRI) has been extensively used for assessment of AD-related structural differences in selective brain regions 6 . Genome-wide association studies (GWAS) using MRI measures have identified several AD risk variants 7 , 8 . Likewise, the MRI changes in statistically-defined regions of interest (ROI) were found closely associated with reported AD risk variants 9 , 10 . Genetic loci harboring variants can be associated with multiple, sometimes seemingly distinct, traits 11 , 12 . The test for such associations, i.e., cross-phenotype association test, has been increasingly employed to investigate the genetic overlap between multiple traits and diseases. Our previous study has developed a cross-phenotype association analysis (CPASSOC) that can integrate association evidence from GWAS summary statistics of multiple traits, either correlated, independent, continuous, or binary traits, and has been successfully used to identify four loci associated with hypertension-related traits missed by a single-trait analysis 13 . In this study, we performed CPASSOC analysis of MRI measures and genetic datasets, and identified a possible link between FAM222A and AD-related regional brain atrophy. To understand its pathological role in AD, we investigated the protein encoded by FAM222A in patients with AD or transgenic mice for AD, and found its characteristic accumulation within the center of amyloid deposits. Further mechanistic study revealed that this protein could physically interact with Aβ and regulate Aβ aggregation and amyloid formation. Our results therefore identify a protein that likely plays an important role in amyloidosis, a finding providing perspective for AD pathogenesis. Results Susceptibility of regional brain atrophy to FAM222A in AD To identify brain atrophy-related imaging quantitative trait loci, we employed a genome-wide whole brain approach to analyze the imaging genetic dataset from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (Supplementary Fig. 1a ). After GWAS and the estimation of shared genetic contributions among 145 ROIs spanning the entire brain by linkage disequilibrium (LD) regression method 14 (Supplementary Fig. 1b, c ), we attempted to extract disease-related ROIs and detect genetic variants associated with them. With hierarchical clustering analysis on a genetic correlation network (Supplementary Fig. 1d–k ), 16 modules of ROIs with high within-module genetic correlation were generated (Supplementary Fig. 1l, m ). We further combined GWAS summary statistics of ROIs in each module using CPASSOC we developed 13 . Previously reported AD top markers, APOE single nucleotide polymorphism (SNP) rs429358 15 , TOMM40 SNP rs2075650 15 , APOC1 SNP rs12721051 16 , and rs117028417 on FAM222A were found in one module (Fig. 1 , Supplementary Figs. 2 , 3 and Supplementary Table 1 ), which consists of five ROIs including left hippocampus, right hippocampus, basal forebrain, entorhinal area, and planum polare, brain areas we know are affected by AD 17 , 18 , 19 and well predict AD (Supplementary Fig. 4 ). SNP rs117028417 had a minor allele A (frequency = 0.044) with positive effects for all 5 ROIs in the ADNI cohort ( P = 1.95 × 10 −8 for CPASSOC analysis; Supplementary Table 2 ), and was further validated to be associated with the mean volume of hippocampus, one of the earliest affected brain regions in AD, in the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium cohort comprising MRI images of 30,717 individuals from 50 cohorts 20 with the same effect direction ( β = 38.1, P = 8.29 × 10 −3 ; Supplementary Table 2 ). Fig. 1: CPASSOC analysis of the ADNI cohort. Manhattan plot of CPASSOC analysis combining<|im_end|> <|im_start|>assistant Researchers at the Case Western University School of Medicine say they have identified a previously unknown gene and associated protein which could potentially be suppressed to slow the advance of Alzheimer's disease. "Based on the data we have, this protein can be an unrecognized new risk factor for Alzheimer's disease (AD)," said Xinglong Wang, an associate professor of pathology at the School of Medicine. "We also see this as a potential novel therapeutic target for this devastating disease." Wang said proving the latter assertion, which has not yet been tested in humans, would require additional research to corroborate the function of the protein they have dubbed "aggregatin." Eventually, that would someday mean clinical trials with Alzheimer's patients, he said. "This protein characteristically accumulates, or aggregates, within the center of plaque in AD patients, like the yolk of an egg—which is part of the reason we named it "aggregatin," Wang said. A research team led by Wang and Xiaofeng Zhu, a professor of Population and Quantitative Health Sciences at the School of Medicine, has filed for a patent through the university's Office of Research and Technology Management for "novel Alzheimer's disease treatments and diagnosis based on this and related study," Wang said. "We're very excited about this because our study is likely the first systematic work combining the identification from a genome-wide association study of high dimensional brain-imaging data and experimental validation so perfectly in Alzheimer's disease," Zhu said. Their research was published this month by the scientific journal Nature Communications and supported by grants from the National Institutes of Health (NIH) and the Alzheimer's Association. Genomic and brain imaging data was obtained from the Alzheimer's Disease Neuroimaging Initiative, which is supported by the NIH. Alzheimer's Disease affects millions More than 5.7 million Americans have Alzheimer's disease, which is the primary cause of dementia and sixth-leading cause of death in the United States. That population is predicted to reach 14 million by the year 2050, according to the Alzheimer's Association. The relationship between Alzheimer's (and subsequent brain atrophy) and amyloid plaques—the hard accumulations of beta amyloid proteins that clump together between the nerve cells (neurons) in the brains of Alzheimer's patients—has been well-established among researchers. Less understood is precisely how that amyloid-beta actually leads to plaque formation—and where this new work appears to have broken new ground, Wang said. Further, while there has been much research into what genes might influence whether or not someone gets Alzheimer's, there is less understanding of genes that might be linked to the progression of the disease, meaning the formation of plaque and subsequent atrophy in the brain. The role of 'aggregatin' protein In the new work, the researchers began by correlating roughly a million genetic markers (called single-nucleotide polymorphisms, or SNPs) with brain images. They were able to identify a specific SNP in the FAM222, a gene linked to different patterns of regional brain atrophy. Further experiments then suggested that the protein encoded by gene FAM222A is not only associated with AD patient-related beta-amyloid plaques and regional brain atrophy, but that "aggregatin" attaches to amyloid beta peptide—the major component of plaque and facilitates the plaque formation. So when researchers injected mouse models with the "aggregatin" protein (made from the FAM222A gene), plaque (amyloid deposits) formation accelerated in the brain, resulting in more neuroinflammation and cognitive dysfunction. This happened, they report, because the protein was found to bind directly the amyloid beta peptide, thus facilitating the aggregation and placque formation, Wang said. Conversely, when they suppressed the protein, the plaques were reduced and neuroinflammation and cognitive impairment alleviated. Their findings indicate that reducing levels of this protein and inhibition of its interaction with amyloid beta peptide could potentially be therapeutic—not necessarily to prevent Alzheimer's but to slow its progression. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Since the spring 2018, a large part of Europe has been in the midst of a record-setting drought. Using long-term observations, we demonstrate that the occurrence of the 2018–2019 (consecutive) summer drought is unprecedented in the last 250 years, and its combined impact on the growing season vegetation activities is stronger compared to the 2003 European drought. Using a suite of climate model simulation outputs, we underpin the role of anthropogenic warming on exacerbating the future risk of such a consecutive drought event. Under the highest Representative Concentration Pathway, (RCP 8.5), we notice a seven-fold increase in the occurrence of the consecutive droughts, with additional 40 ( \$\\pm \\, 5\$ ) million ha of cultivated areas being affected by such droughts, during the second half of the twenty-first century. The occurrence is significantly reduced under low and medium scenarios (RCP 2.6 and RCP 4.5), suggesting that an effective mitigation strategy could aid in reducing the risk of future consecutive droughts. Introduction Human-induced climate change is evident and it poses a great concern to society, primarily due to its potential to intensify extreme events around the globe 1 , 2 . In the past 2 decades, Europe experienced an increased frequency of droughts 3 , 4 with estimated loss of about EUR 100 billion 5 . One such devastating event was the drought in summer 2003, which was an exceptionally warm and dry year across most of central and western Europe. Historical reconstructions since 1500 C.E. suggest that it was one of the hottest summers 6 , and the event was estimated to result in a 30% reduction in gross primary production compared to previous years between 1998–2002 3 . Although, the 2003 drought event was rare and exceptional, even in a multi-centennial time window, its likelihood is expected to increase in the near future 7 , mainly due to the anthropogenic warming 8 , 9 , 10 , 11 . In the summer of 2018, temperature anomaly broke the record again in several locations across Europe, but with distinct spatial patterns. While in summer 2003 the increase in temperature was more concentrated in central and southern Europe (Fig. 1 a), summer 2018 was characterised by an anomalous increase in central and north-eastern Europe (Fig. 1 b). Unlike the 2003 event—where the temperature anomaly (Supplementary Fig. S1 ) and the ecosystem carbon and energy fluxes recovered early after the summer 12 , the extreme event of 2018 persisted to the subsequent year 2019 (Fig. 1 c). For all these years, the impact was strongest in the Central European region, where the increase in temperature was accompanied by concurrent significant reduction of summer precipitation (Fig. 1 d–f), which led to extreme drought conditions. Figure 1 Anomalies of climate and vegetation health index (VHI) during 2003, 2018 and 2019. ( a , b , c ) Mean summer (June–August) temperature anomalies ( \$^\\circ \\hbox {C}\$ ) for 2003, 2018 and 2019 based on the 1980–2010 climatology, and ( d , e , f ) their corresponding precipitation anomalies (%). ( g , h , i ) Vegetation condition in terms of VHI during 2003, 2018 and 2019, respectively. ( j ) Yearly development of the summer time, percentage area with poor vegetation health (i.e., VHI \$\\le 30\$ ) estimated over the Central European region (depicted by a black rectangular region in the panel g ) during the period 2000–2019. The thick black line shows the year-wise weekly mean of VHI during summer months, and the pink bar represents the corresponding 95% confidence limit based on the sampling distribution of the mean. The years 2003, 2015, 2018 and 2019 experienced the deprivation in the vegetation health, where the poor vegetation health extends over more than 20% of the central European region. The gray shaded region highlights the years 2018 and 2019, during which the poor vegetation health persists over more than 20% of the central European area, consecutively in 2 years. (k) Yearly summer-time precipitation and temperature anomalies estimated over the central Europe region during the 254 years. Three exceptional years of 2003, 2018 and 2019 are shown by the red dots, where the mean summer temperature anomalies over the Central Europe reached the record extreme conditions of more than \$2\\,^\\circ \\hbox {C}\$ ; and precipitation anomalies show deficit of more than 20%. The maps in the figure are generated using Python version 3.7.3 ( ). Full size image The intensity and spatial extent of droughts significantly affects the plant and agricultural productivity 13 , 14 , underlying the severity of the drought impact in Central European region, where the focus on agriculture is strong 3 , 7 , 15 , 16 , 17 . With the use of remote sensing data-sets 18 , we find that the concurrent increased temperature with deficit precipitation impaired the condition for vegetation activities (Fig. 1 g) in the summer of 2003. We show this in terms of vegetation health index (VHI), which represents the vegetation stress due to the droughts (see methods for detailed description). Similar observations have been made during the summer 2018 as well (Fig. 1 h), when several countries suffered agro-economic shocks 19 . Further, the deprivation of vegetation health persisted and it is noticed even during the summer 2019 (Fig. 1 i). In the case of the exceptional 2003 and 2015 events 4 , 20 , the vegetation health recovered and returned to its normal condition during the following years. On the contrary, the impact of the 2018 drought on vegetation activities propagated to 2019 and the recovery is still underway, as shown in the time series of VHI (Fig. 1 j). Additionally, we note that the vegetation health being categorised in poor condition for at-least 20% of the Central European area in both 2018 and 2019 is unprecedented from the observations in the previous years of twenty-first century. Thus, it is with the utmost urgency that we need to recognise the importance of these persevering consecutive year events, and to develop", "role": "user" }, { "content": "Punishing two-year droughts like the record-breaking one that gripped Central Europe from 2018 to 2019 could become much more frequent if the region fails to curb greenhouse gas emissions, researchers said Thursday, affecting huge swathes of its cultivated land. The five hottest years in recorded history have occurred in the last five years. This extreme heat was exacerbated in 2018 and 2019 by two consecutive summers of drought that affected more than half of Central Europe, according to a new study published in the Nature journal Scientific Reports. Researchers in Germany and the Czech Republic used data going back to 1766 to conclude the drought was the largest-scale and most severe dry spell ever recorded. \"The observational record suggests that the ongoing 2018–2019 European drought event is unprecedented in the last 250 years, with substanprolongedtial implications for vegetation health,\" the study said. Researchers then sought to estimate whether prolonged droughts would become more frequent in the future by using global climate change models. Under a scenario where greenhouse gas emissions continue their inexorable rise, the researchers predicted that the number of extreme two-year droughts will increase sevenfold in Europe in the second half of this century. \"This projection also suggested that drought-affected cropland areas across Central Europe will nearly double,\" said co-author Rohini Kumar, of the UFZ-Helmholtz Centre for Environmental Research, in Leipzig. This would result in a total of 40 million hectares of cultivated land affected—equivalent to 60 percent of all crop areas in the region. When researchers modelled for moderate emissions, the predicted number of two-year droughts halved compared to the worst case scenario, while the area expected to be hit by the drought also reduced. Kumar said this suggests a reduction in emissions could lower the risk of these damaging dry periods. The five hottest years in recorded history have occurred in the last five years Threat to agriculture The researcher said a two-year dry period presents a far greater threat to vegetation than the single-summer droughts of previous years because the land cannot recover as quickly. He said around a fifth of the Central European region had recorded poor vegetation health in the last two years. \"Thus, it is with the utmost urgency that we need to recognise the importance of these persevering consecutive year events, and to develop a holistic framework to model the risk,\" he added. The study defined Central Europe as including parts of Germany, France, Poland, Switzerland, Italy, Austria, as well as Czech Republic, Belgium, Slovenia, Hungary, Slovakia. Over 34 percent of the total land area in the region is extensively used for agricultural purposes, it said. The 2015 Paris climate deal commits nations to capping temperature rises to \"well-below\" 2C (3.6 degrees Fahrenheit) above pre-industrial levels and to strive for a 1.5C limit if at all possible. With just 1C of warming so far, Earth is already buffeted by record-breaking droughts, wildfires and super storms made more potent by rising sea levels. To keep in line with the 1.5C target, the United Nations says global emissions must fall by 7.6 percent every year this decade. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Since the spring 2018, a large part of Europe has been in the midst of a record-setting drought. Using long-term observations, we demonstrate that the occurrence of the 2018–2019 (consecutive) summer drought is unprecedented in the last 250 years, and its combined impact on the growing season vegetation activities is stronger compared to the 2003 European drought. Using a suite of climate model simulation outputs, we underpin the role of anthropogenic warming on exacerbating the future risk of such a consecutive drought event. Under the highest Representative Concentration Pathway, (RCP 8.5), we notice a seven-fold increase in the occurrence of the consecutive droughts, with additional 40 ( $\pm \, 5$ ) million ha of cultivated areas being affected by such droughts, during the second half of the twenty-first century. The occurrence is significantly reduced under low and medium scenarios (RCP 2.6 and RCP 4.5), suggesting that an effective mitigation strategy could aid in reducing the risk of future consecutive droughts. Introduction Human-induced climate change is evident and it poses a great concern to society, primarily due to its potential to intensify extreme events around the globe 1 , 2 . In the past 2 decades, Europe experienced an increased frequency of droughts 3 , 4 with estimated loss of about EUR 100 billion 5 . One such devastating event was the drought in summer 2003, which was an exceptionally warm and dry year across most of central and western Europe. Historical reconstructions since 1500 C.E. suggest that it was one of the hottest summers 6 , and the event was estimated to result in a 30% reduction in gross primary production compared to previous years between 1998–2002 3 . Although, the 2003 drought event was rare and exceptional, even in a multi-centennial time window, its likelihood is expected to increase in the near future 7 , mainly due to the anthropogenic warming 8 , 9 , 10 , 11 . In the summer of 2018, temperature anomaly broke the record again in several locations across Europe, but with distinct spatial patterns. While in summer 2003 the increase in temperature was more concentrated in central and southern Europe (Fig. 1 a), summer 2018 was characterised by an anomalous increase in central and north-eastern Europe (Fig. 1 b). Unlike the 2003 event—where the temperature anomaly (Supplementary Fig. S1 ) and the ecosystem carbon and energy fluxes recovered early after the summer 12 , the extreme event of 2018 persisted to the subsequent year 2019 (Fig. 1 c). For all these years, the impact was strongest in the Central European region, where the increase in temperature was accompanied by concurrent significant reduction of summer precipitation (Fig. 1 d–f), which led to extreme drought conditions. Figure 1 Anomalies of climate and vegetation health index (VHI) during 2003, 2018 and 2019. ( a , b , c ) Mean summer (June–August) temperature anomalies ( $^\circ \hbox {C}$ ) for 2003, 2018 and 2019 based on the 1980–2010 climatology, and ( d , e , f ) their corresponding precipitation anomalies (%). ( g , h , i ) Vegetation condition in terms of VHI during 2003, 2018 and 2019, respectively. ( j ) Yearly development of the summer time, percentage area with poor vegetation health (i.e., VHI $\le 30$ ) estimated over the Central European region (depicted by a black rectangular region in the panel g ) during the period 2000–2019. The thick black line shows the year-wise weekly mean of VHI during summer months, and the pink bar represents the corresponding 95% confidence limit based on the sampling distribution of the mean. The years 2003, 2015, 2018 and 2019 experienced the deprivation in the vegetation health, where the poor vegetation health extends over more than 20% of the central European region. The gray shaded region highlights the years 2018 and 2019, during which the poor vegetation health persists over more than 20% of the central European area, consecutively in 2 years. (k) Yearly summer-time precipitation and temperature anomalies estimated over the central Europe region during the 254 years. Three exceptional years of 2003, 2018 and 2019 are shown by the red dots, where the mean summer temperature anomalies over the Central Europe reached the record extreme conditions of more than $2\,^\circ \hbox {C}$ ; and precipitation anomalies show deficit of more than 20%. The maps in the figure are generated using Python version 3.7.3 ( ). Full size image The intensity and spatial extent of droughts significantly affects the plant and agricultural productivity 13 , 14 , underlying the severity of the drought impact in Central European region, where the focus on agriculture is strong 3 , 7 , 15 , 16 , 17 . With the use of remote sensing data-sets 18 , we find that the concurrent increased temperature with deficit precipitation impaired the condition for vegetation activities (Fig. 1 g) in the summer of 2003. We show this in terms of vegetation health index (VHI), which represents the vegetation stress due to the droughts (see methods for detailed description). Similar observations have been made during the summer 2018 as well (Fig. 1 h), when several countries suffered agro-economic shocks 19 . Further, the deprivation of vegetation health persisted and it is noticed even during the summer 2019 (Fig. 1 i). In the case of the exceptional 2003 and 2015 events 4 , 20 , the vegetation health recovered and returned to its normal condition during the following years. On the contrary, the impact of the 2018 drought on vegetation activities propagated to 2019 and the recovery is still underway, as shown in the time series of VHI (Fig. 1 j). Additionally, we note that the vegetation health being categorised in poor condition for at-least 20% of the Central European area in both 2018 and 2019 is unprecedented from the observations in the previous years of twenty-first century. Thus, it is with the utmost urgency that we need to recognise the importance of these persevering consecutive year events, and to develop<|im_end|> <|im_start|>assistant Punishing two-year droughts like the record-breaking one that gripped Central Europe from 2018 to 2019 could become much more frequent if the region fails to curb greenhouse gas emissions, researchers said Thursday, affecting huge swathes of its cultivated land. The five hottest years in recorded history have occurred in the last five years. This extreme heat was exacerbated in 2018 and 2019 by two consecutive summers of drought that affected more than half of Central Europe, according to a new study published in the Nature journal Scientific Reports. Researchers in Germany and the Czech Republic used data going back to 1766 to conclude the drought was the largest-scale and most severe dry spell ever recorded. "The observational record suggests that the ongoing 2018–2019 European drought event is unprecedented in the last 250 years, with substanprolongedtial implications for vegetation health," the study said. Researchers then sought to estimate whether prolonged droughts would become more frequent in the future by using global climate change models. Under a scenario where greenhouse gas emissions continue their inexorable rise, the researchers predicted that the number of extreme two-year droughts will increase sevenfold in Europe in the second half of this century. "This projection also suggested that drought-affected cropland areas across Central Europe will nearly double," said co-author Rohini Kumar, of the UFZ-Helmholtz Centre for Environmental Research, in Leipzig. This would result in a total of 40 million hectares of cultivated land affected—equivalent to 60 percent of all crop areas in the region. When researchers modelled for moderate emissions, the predicted number of two-year droughts halved compared to the worst case scenario, while the area expected to be hit by the drought also reduced. Kumar said this suggests a reduction in emissions could lower the risk of these damaging dry periods. The five hottest years in recorded history have occurred in the last five years Threat to agriculture The researcher said a two-year dry period presents a far greater threat to vegetation than the single-summer droughts of previous years because the land cannot recover as quickly. He said around a fifth of the Central European region had recorded poor vegetation health in the last two years. "Thus, it is with the utmost urgency that we need to recognise the importance of these persevering consecutive year events, and to develop a holistic framework to model the risk," he added. The study defined Central Europe as including parts of Germany, France, Poland, Switzerland, Italy, Austria, as well as Czech Republic, Belgium, Slovenia, Hungary, Slovakia. Over 34 percent of the total land area in the region is extensively used for agricultural purposes, it said. The 2015 Paris climate deal commits nations to capping temperature rises to "well-below" 2C (3.6 degrees Fahrenheit) above pre-industrial levels and to strive for a 1.5C limit if at all possible. With just 1C of warming so far, Earth is already buffeted by record-breaking droughts, wildfires and super storms made more potent by rising sea levels. To keep in line with the 1.5C target, the United Nations says global emissions must fall by 7.6 percent every year this decade. <|im_end|>

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2,054

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The rise of ancient genomics has revolutionised our understanding of human prehistory but this work depends on the availability of suitable samples. Here we present a complete ancient human genome and oral microbiome sequenced from a 5700 year-old piece of chewed birch pitch from Denmark. We sequence the human genome to an average depth of 2.3× and find that the individual who chewed the pitch was female and that she was genetically more closely related to western hunter-gatherers from mainland Europe than hunter-gatherers from central Scandinavia. We also find that she likely had dark skin, dark brown hair and blue eyes. In addition, we identify DNA fragments from several bacterial and viral taxa, including Epstein-Barr virus, as well as animal and plant DNA, which may have derived from a recent meal. The results highlight the potential of chewed birch pitch as a source of ancient DNA. Introduction Birch pitch is a black-brown substance obtained by heating birch bark and has been used as an adhesive and hafting agent as far back as the Middle Pleistocene 1 , 2 . Small lumps of this organic material are commonly found on archaeological sites in Scandinavia and beyond, and while their use is still debated, they often show tooth imprints, indicating that they were chewed 3 . Freshly produced birch pitch hardens on cooling and it has been suggested that chewing was a means to make it pliable again before using it, e.g. for hafting composite stone tools. Medicinal uses have also been suggested, since one of the main constituents of birch pitch, betulin, has antiseptic properties 4 . This is supported by a large body of ethnographic evidence, which suggests that birch pitch was used as a natural antiseptic for preventing and treating dental ailments and other medical conditions 3 . The oldest examples of chewed pitch found in Europe date back to the Mesolithic period and chemical analysis by Gas Chromatography-Mass Spectrometry (GC-MS) has shown that many of them were made from birch ( Betula pendula ) 3 . Recent work by Kashuba et al 5 . has shown that pieces of chewed birch pitch contain ancient human DNA, which can be used to link the material culture and genetics of ancient populations. In the current study, we analyse a further piece of chewed birch pitch, which was discovered at a Late Mesolithic/Early Neolithic site in southern Denmark (Fig. 1a ; Supplementary Note 1 ) and demonstrate that it does not only contain ancient human DNA, but also microbial DNA that reflects the oral microbiome of the person who chewed the pitch, as well as plant and animal DNA which may have derived from a recent meal. The DNA is so exceptionally well preserved that we were able to recover a complete ancient human genome from the sample (sequenced to an average depth of coverage of 2.3×), which is particularly significant since, so far, no human remains have been recovered from the site 6 . The results highlight the potential of chewed birch pitch as a source of ancient human and non-human DNA, which can be used to shed light on the population history, health status, and even subsistence strategies of ancient populations. Fig. 1 A chewed piece of birch pitch from southern Denmark. ( a ) Photograph of the Syltholm birch pitch and its find location at the site of Syltholm on the island of Lolland, Denmark (map created using data from Astrup 78 ). ( b ) Calibrated date for the Syltholm birch pitch (5,858–5,661 cal. BP; 5,007 ± 7). ( c ) GC-MS chromatogram of the Syltholm pitch showing the presence of a series of dicarboxylic acids (Cxx diacid) and saturated fatty acids (Cxx:0) and methyl 16-Hydroxyhexadecanoate (C 16 OH) together with the triterpenes betulin and lupeol, which are characteristic of birch pitch 3 . Full size image Results Radiocarbon dating and chemical analysis Radiocarbon dating of the specimen yielded a direct date of 5,858–5,661 cal. BP (GrM-13305; 5,007 ± 11) (Fig. 1b ; Supplementary Note 2 ), which places it at the onset of the Neolithic period in Denmark. Chemical analysis by Fourier-Transform Infrared (FTIR) spectroscopy produced a spectrum very similar to modern birch pitch (Supplementary Fig. 4 ) and GC-MS revealed the presence of the triterpenes betulin and lupeol, which are characteristic of birch pitch (Fig. 1c ; Supplementary Note 3 ) 3 . The GC-MS spectrum also shows a range of dicarboxylic acids and saturated fatty acids, which are all considered intrinsic to birch pitch and thus support its identification 7 . DNA sequencing We generated approximately 390 million DNA reads for the sample, nearly a third of which could be uniquely mapped to the human reference genome (hg19) (Supplementary Table 2 ). The human reads displayed all the features characteristic of ancient DNA, including (i) short average fragment lengths, (ii) an increased occurrence of purines before strand breaks, and (iii) an increased frequency of apparent cytosine (C) to thymine (T) substitutions at 5′-ends of DNA fragments (Supplementary Fig. 6 ) and the amount of modern human contamination was estimated to be around 1–3% (Supplementary Table 3 ). In addition to the human reads, we generated around 7.3 Gb of sequence data (68.8%) from the ancient pitch that did not align to the human reference genome. DNA preservation and genome reconstruction With over 30%, the human endogenous DNA content in the sample was extremely high and comparable to that found in well-preserved teeth and petrous bones 8 . We used the human reads to reconstruct a complete ancient human genome, sequenced to an effective depth-of-coverage of 2.3×, as well as a high-coverage mitochondrial genome (91×), which was assigned to haplogroup K1e (see Methods). To further investigate the preservation of the human DNA in the sample we calculated a molecular decay rate ( k , per site per year) and find that it is comparable to that of other ancient human genomes from temperate regions (Supplementary Table 3 ). Sex determination and phenotypic traits Based", "role": "user" }, { "content": "Danish scientists have managed to extract a complete human DNA sample from a piece of birch pitch more than 5,000 years old, used as a kind of chewing gum, a study revealed Tuesday. The Stone-Age sample yielded enough information to determine the source's sex, what she had last eaten and the germs in her mouth. It also told them she probably had dark hair, dark skin and blue eyes. And genetically, she was more closely related to hunter-gatherers from the mainland Europe than to those living in central Scandinavia at the time, they concluded. \"It is the first time that an entire ancient human genome has been extracted from anything other than human bones,\" Hannes Schroeder of the University of Copenhagen, told AFP. Schroeder is co-author of the study, which was published in the review Nature Communications. They found the sample during an archaeological dig at Syltholm, in southern Denmark, said Tehis Jensen, one of the other authors. \"Syltholm is completely unique,\" he said. \"Almost everything is sealed in mud, which means that the preservation of organic remains is absolutely phenomenal.\" Artistic reconstruction of Lola. Credit: Tom Björklund The researchers also recovered traces of plant and animal DNA—hazelnut and duck—confirming what archaeologists already know about the people who lived there at the time. But they were not sure why their subject chose to chew the bark: whether to turn it into a kind of glue, to clean her teeth, to stave off hunger—or simply as chewing gum. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The rise of ancient genomics has revolutionised our understanding of human prehistory but this work depends on the availability of suitable samples. Here we present a complete ancient human genome and oral microbiome sequenced from a 5700 year-old piece of chewed birch pitch from Denmark. We sequence the human genome to an average depth of 2.3× and find that the individual who chewed the pitch was female and that she was genetically more closely related to western hunter-gatherers from mainland Europe than hunter-gatherers from central Scandinavia. We also find that she likely had dark skin, dark brown hair and blue eyes. In addition, we identify DNA fragments from several bacterial and viral taxa, including Epstein-Barr virus, as well as animal and plant DNA, which may have derived from a recent meal. The results highlight the potential of chewed birch pitch as a source of ancient DNA. Introduction Birch pitch is a black-brown substance obtained by heating birch bark and has been used as an adhesive and hafting agent as far back as the Middle Pleistocene 1 , 2 . Small lumps of this organic material are commonly found on archaeological sites in Scandinavia and beyond, and while their use is still debated, they often show tooth imprints, indicating that they were chewed 3 . Freshly produced birch pitch hardens on cooling and it has been suggested that chewing was a means to make it pliable again before using it, e.g. for hafting composite stone tools. Medicinal uses have also been suggested, since one of the main constituents of birch pitch, betulin, has antiseptic properties 4 . This is supported by a large body of ethnographic evidence, which suggests that birch pitch was used as a natural antiseptic for preventing and treating dental ailments and other medical conditions 3 . The oldest examples of chewed pitch found in Europe date back to the Mesolithic period and chemical analysis by Gas Chromatography-Mass Spectrometry (GC-MS) has shown that many of them were made from birch ( Betula pendula ) 3 . Recent work by Kashuba et al 5 . has shown that pieces of chewed birch pitch contain ancient human DNA, which can be used to link the material culture and genetics of ancient populations. In the current study, we analyse a further piece of chewed birch pitch, which was discovered at a Late Mesolithic/Early Neolithic site in southern Denmark (Fig. 1a ; Supplementary Note 1 ) and demonstrate that it does not only contain ancient human DNA, but also microbial DNA that reflects the oral microbiome of the person who chewed the pitch, as well as plant and animal DNA which may have derived from a recent meal. The DNA is so exceptionally well preserved that we were able to recover a complete ancient human genome from the sample (sequenced to an average depth of coverage of 2.3×), which is particularly significant since, so far, no human remains have been recovered from the site 6 . The results highlight the potential of chewed birch pitch as a source of ancient human and non-human DNA, which can be used to shed light on the population history, health status, and even subsistence strategies of ancient populations. Fig. 1 A chewed piece of birch pitch from southern Denmark. ( a ) Photograph of the Syltholm birch pitch and its find location at the site of Syltholm on the island of Lolland, Denmark (map created using data from Astrup 78 ). ( b ) Calibrated date for the Syltholm birch pitch (5,858–5,661 cal. BP; 5,007 ± 7). ( c ) GC-MS chromatogram of the Syltholm pitch showing the presence of a series of dicarboxylic acids (Cxx diacid) and saturated fatty acids (Cxx:0) and methyl 16-Hydroxyhexadecanoate (C 16 OH) together with the triterpenes betulin and lupeol, which are characteristic of birch pitch 3 . Full size image Results Radiocarbon dating and chemical analysis Radiocarbon dating of the specimen yielded a direct date of 5,858–5,661 cal. BP (GrM-13305; 5,007 ± 11) (Fig. 1b ; Supplementary Note 2 ), which places it at the onset of the Neolithic period in Denmark. Chemical analysis by Fourier-Transform Infrared (FTIR) spectroscopy produced a spectrum very similar to modern birch pitch (Supplementary Fig. 4 ) and GC-MS revealed the presence of the triterpenes betulin and lupeol, which are characteristic of birch pitch (Fig. 1c ; Supplementary Note 3 ) 3 . The GC-MS spectrum also shows a range of dicarboxylic acids and saturated fatty acids, which are all considered intrinsic to birch pitch and thus support its identification 7 . DNA sequencing We generated approximately 390 million DNA reads for the sample, nearly a third of which could be uniquely mapped to the human reference genome (hg19) (Supplementary Table 2 ). The human reads displayed all the features characteristic of ancient DNA, including (i) short average fragment lengths, (ii) an increased occurrence of purines before strand breaks, and (iii) an increased frequency of apparent cytosine (C) to thymine (T) substitutions at 5′-ends of DNA fragments (Supplementary Fig. 6 ) and the amount of modern human contamination was estimated to be around 1–3% (Supplementary Table 3 ). In addition to the human reads, we generated around 7.3 Gb of sequence data (68.8%) from the ancient pitch that did not align to the human reference genome. DNA preservation and genome reconstruction With over 30%, the human endogenous DNA content in the sample was extremely high and comparable to that found in well-preserved teeth and petrous bones 8 . We used the human reads to reconstruct a complete ancient human genome, sequenced to an effective depth-of-coverage of 2.3×, as well as a high-coverage mitochondrial genome (91×), which was assigned to haplogroup K1e (see Methods). To further investigate the preservation of the human DNA in the sample we calculated a molecular decay rate ( k , per site per year) and find that it is comparable to that of other ancient human genomes from temperate regions (Supplementary Table 3 ). Sex determination and phenotypic traits Based<|im_end|> <|im_start|>assistant Danish scientists have managed to extract a complete human DNA sample from a piece of birch pitch more than 5,000 years old, used as a kind of chewing gum, a study revealed Tuesday. The Stone-Age sample yielded enough information to determine the source's sex, what she had last eaten and the germs in her mouth. It also told them she probably had dark hair, dark skin and blue eyes. And genetically, she was more closely related to hunter-gatherers from the mainland Europe than to those living in central Scandinavia at the time, they concluded. "It is the first time that an entire ancient human genome has been extracted from anything other than human bones," Hannes Schroeder of the University of Copenhagen, told AFP. Schroeder is co-author of the study, which was published in the review Nature Communications. They found the sample during an archaeological dig at Syltholm, in southern Denmark, said Tehis Jensen, one of the other authors. "Syltholm is completely unique," he said. "Almost everything is sealed in mud, which means that the preservation of organic remains is absolutely phenomenal." Artistic reconstruction of Lola. Credit: Tom Björklund The researchers also recovered traces of plant and animal DNA—hazelnut and duck—confirming what archaeologists already know about the people who lived there at the time. But they were not sure why their subject chose to chew the bark: whether to turn it into a kind of glue, to clean her teeth, to stave off hunger—or simply as chewing gum. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Background and hypothesis Recently, the world has experienced a rapidly escalating outbreak of infectious syphilis primarily affecting men who have sex with men (MSM); many are taking highly active antiretroviral therapy (HAART) for HIV-1 infection. The prevailing hypothesis is that HAART availability and effectiveness have led to the perception among both individuals who are HIV-1 infected and those who are uninfected that HIV-1 transmission has become much less likely, and the effects of HIV-1 infection less deadly. This is expected to result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 STDs, including gonorrhoea, chlamydia and syphilis. However, syphilis incidence has increased more rapidly than other STDs. We hypothesise that HAART downregulates the innate and acquired immune responses to Treponema pallidum and that this biological explanation plays an important role in the syphilis epidemic. Methods We performed a literature search and developed a mathematical model of HIV-1 and T. pallidum confection in a population with two risk groups with assortative mixing to explore the consequence on syphilis prevalence of HAART-induced changes in behaviour versus HAART-induced biological effects. Conclusions and implications Since rising syphilis incidence appears to have outpaced gonorrhoea and chlamydia, predominantly affecting HIV-1 positive MSM, behavioural factors alone may be insufficient to explain the unique, sharp increase in syphilis incidence. HAART agents have the potential to alter the innate and acquired immune responses in ways that may enhance susceptibility to T. pallidum . This raises the possibility that therapeutic and preventative HAART may inadvertently increase the incidence of syphilis, a situation that would have significant and global public health implications. We propose that additional studies investigating the interplay between HAART and enhanced T. pallidum susceptibility are needed. If our hypothesis is correct, HAART should be combined with enhanced patient management including frequent monitoring for pathogens such as T. pallidum . SYPHILIS HIV ANTERETROVIRAL THERAPY MATHEMATICAL MODEL INFECTION This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: googletag.cmd.push(function() { googletag.display(\"dfp-ad-mpu\"); }); Statistics from Altmetric.com See more details Picked up by 23 news outlets Blogged by 2 Tweeted by 36 On 2 Facebook pages 107 readers on Mendeley Linked Articles Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. ?xml version=\"1.0\" encoding=\"UTF-8\" ? Request permissions SYPHILIS HIV ANTERETROVIRAL THERAPY MATHEMATICAL MODEL INFECTION sextrans-2016-052870 Share Play Video Play Mute Current Time 0:00 / Duration Time 4:40 Loaded : 0% 0:00 Progress : 0% 0:00 Progress : 0% Stream Type LIVE Remaining Time -4:40 Playback Rate 1 Chapters Chapters descriptions off , selected Descriptions subtitles off , selected Subtitles captions settings , opens captions settings dialog captions off , selected Captions en (Main) , selected Audio Track Fullscreen This is a modal window. Caption Settings Dialog Beginning of dialog window. Escape will cancel and close the window. 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Video abstract Introduction STDs, HIV-1 and men who have sex with men In British Columbia (BC), Canada, from 2005 to 2014, infectious syphilis case reports (primary, secondary and early latent) rose 90.6% (288–549), chlamydia 39.9% (9540–13 348) and gonorrhoea 63.8% (1100–1802), corresponding to rate changes per 100 000 population of +72.4%, +33.9% and +47.6%, respectively. 1 Female syphilis cases decreased while male cases jumped from 202 to 524, accounting for 95% of all 2014 cases. Men who have sex with men (MSM) accounted for 60.4% (122) of cases in 2005, rising to 88.9% (466) in 2014. There was a fourfold increase in MSM syphilis from 2010 to 2014 (115–466 cases), including 112 reinfections (24%) in 2014. The HIV-1 coinfection rate in MSM during this period was 50%–75%. From 2005 to 2014, the male infectious syphilis rate increased 235% (9.7–22.8) compared with a much smaller increase for chlamydia (56.9%; 141.7–222.4) and gonorrhoea (42.1%; 39.7–56.4) in men. Comparatively larger increases in syphilis cases were also observed in the USA from 2005 to 2014. Primary and secondary syphilis cases rose 128.1% (8724–19 999), chlamydia 47.7% (976 445–1 441 789) and gonorrhoea 3.1% (339 593–350 062), corresponding to rate changes of +117.2%, +38.5% and −3.4%, respectively. 2 Males contributed an increasing proportion of syphilis cases, accounting for 91% in 2014. From 2007 to 2014, among the 27 US states that collected sex partner data for ≥70% of males, MSM cases increased steadily to 82.9%. In Los Angeles County between January and May, 2010, 76% of 537 early syphilis cases were MSM and ≥58% of these were HIV-1 positive. 3 HIV-1 infection in US MSM has also been statistically associated with repeat syphilis infection. 4 In the UK from 1998 to 2013, new syphilis cases in MSM rose from 23 (26.0% of all cases) to 2546 (71.3% of all cases). From 2009 to 2013 in England, the odds of being diagnosed with syphilis increased from 2.71 (95% CI 2.41 to 3.05, p<0.001) to 4.05 (95% CI 3.70 to 4.45, p<0.001) in", "role": "user" }, { "content": "The antiretroviral drugs used to treat HIV infection might inadvertently be boosting gay/bisexual men's susceptibility to the bacteria responsible for syphilis, Treponema pallidum, conclude researchers in the journal Sexually Transmitted Infections. This might explain why new and repeat cases in these groups have risen so sharply compared with other sexually transmitted infections over the past decade, they suggest. The availability of highly active antiretroviral therapy (HAART) for the treatment of HIV infection has meant that HIV is no longer the automatic death sentence that it once was. The absence of the fear factor is thought to have prompted higher rates of sexually transmitted infections as a result of risky, unprotected sex. But it's not clear why rates of syphilis among gay/bisexual men should be so much higher than those of chlamydia or gonorrhoea, especially as HAART boosts immune system activity, and so would be expected to lower susceptibility to infections, say the Canadian and South African researchers. They therefore reviewed the available evidence on the impact of HAART on behavioural and immune system change to come up with a numerical analysis to explore which might affect the prevalence of the infection the most. They used two risk 'models' to test the likelihood of syphilis infection: one (lower risk) which compared HAART with no treatment in an HIV positive partner; and the other (higher risk) which compared existing infection with no infection in a partner who was either HIV negative or positive. Behaviour change was taken to mean that HAART would result in more sexual partners; and immune system changes were taken to mean that HAART would boost susceptibility to Treponema pallidum. The calculations showed that either factor could produce outbreaks of syphilis that would be substantially higher than expected, but that both factors combined produced a peak in the number of infections that was greater than that associated with either factor alone—and equivalent to the sorts of figures seen in the current outbreak. This suggests that there's an interplay between behavioural change and immune system changes, say the researchers, who offer a possible explanation for a biological effect on the immune system. The body's clearance of T pallidum relies on an increase in the number of an immune system cell called a T cell and a cascade of chemicals that stimulate an inflammatory response. HAART dampens down these activities. Clearance of chlamydia and gonorrhoea is less reliant on these processes, say the researchers. The researchers also refer to other relevant associations, such as the increased risk of certain types of cancer that have been linked to HAART. \"Overall, these findings suggest a possible link between HAART and an increased risk for selected diseases of infectious and non-infectious origin, a potential unforeseen consequence that warrants further study,\" they write. In a linked editorial, Drs Susan Tuddenham, Maunank Shah, and Khalil Ghanem from Johns Hopkins University School of Medicine, Baltimore, caution that the rise in syphilis cases may simply reflect inadequate screening for chlamydia and gonorrhoea. They also point to previous outbreaks of syphilis in straight men and women in the 1980s and 1990s before the advent of HAART. Similarly, they suggest that the calculations used by the researchers don't take account of the complexities of sexual relationships, such as relationship length or the number of concurrent partners, or decreased use of condoms in long term relationships, all of which might influence infection risk. But despite these caveats, they describe the researchers' hypothesis as \"intriguing,\" and one that \"warrants careful consideration.\" They continue: \"We are living in an era where [antiretroviral therapy] is being used to effectively treat and prevent HIV infection. To some extent this seems to have tempered the urgency to control other [sexually transmitted infections]. As history has shown many times over, that would be a costly mistake.\" And they conclude: \"Over the past 15 years, syphilis rates among [men who have sex with men] have been rising unabated. We are not aware of any recent intervention that has led to a sustained decline in [these rates] in this population. \"If further investigations support a role for [antiretroviral therapy] in increasing susceptibility to syphilis, this will provide one more reason why screening, diagnosis and treatment of [sexually transmitted infections] in [men who have sex with men] must be prioritised.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Background and hypothesis Recently, the world has experienced a rapidly escalating outbreak of infectious syphilis primarily affecting men who have sex with men (MSM); many are taking highly active antiretroviral therapy (HAART) for HIV-1 infection. The prevailing hypothesis is that HAART availability and effectiveness have led to the perception among both individuals who are HIV-1 infected and those who are uninfected that HIV-1 transmission has become much less likely, and the effects of HIV-1 infection less deadly. This is expected to result in increased sexual risk-taking, especially unprotected anal intercourse, leading to more non-HIV-1 STDs, including gonorrhoea, chlamydia and syphilis. However, syphilis incidence has increased more rapidly than other STDs. We hypothesise that HAART downregulates the innate and acquired immune responses to Treponema pallidum and that this biological explanation plays an important role in the syphilis epidemic. Methods We performed a literature search and developed a mathematical model of HIV-1 and T. pallidum confection in a population with two risk groups with assortative mixing to explore the consequence on syphilis prevalence of HAART-induced changes in behaviour versus HAART-induced biological effects. Conclusions and implications Since rising syphilis incidence appears to have outpaced gonorrhoea and chlamydia, predominantly affecting HIV-1 positive MSM, behavioural factors alone may be insufficient to explain the unique, sharp increase in syphilis incidence. HAART agents have the potential to alter the innate and acquired immune responses in ways that may enhance susceptibility to T. pallidum . This raises the possibility that therapeutic and preventative HAART may inadvertently increase the incidence of syphilis, a situation that would have significant and global public health implications. We propose that additional studies investigating the interplay between HAART and enhanced T. pallidum susceptibility are needed. If our hypothesis is correct, HAART should be combined with enhanced patient management including frequent monitoring for pathogens such as T. pallidum . SYPHILIS HIV ANTERETROVIRAL THERAPY MATHEMATICAL MODEL INFECTION This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: googletag.cmd.push(function() { googletag.display("dfp-ad-mpu"); }); Statistics from Altmetric.com See more details Picked up by 23 news outlets Blogged by 2 Tweeted by 36 On 2 Facebook pages 107 readers on Mendeley Linked Articles Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. ?xml version="1.0" encoding="UTF-8" ? Request permissions SYPHILIS HIV ANTERETROVIRAL THERAPY MATHEMATICAL MODEL INFECTION sextrans-2016-052870 Share Play Video Play Mute Current Time 0:00 / Duration Time 4:40 Loaded : 0% 0:00 Progress : 0% 0:00 Progress : 0% Stream Type LIVE Remaining Time -4:40 Playback Rate 1 Chapters Chapters descriptions off , selected Descriptions subtitles off , selected Subtitles captions settings , opens captions settings dialog captions off , selected Captions en (Main) , selected Audio Track Fullscreen This is a modal window. Caption Settings Dialog Beginning of dialog window. Escape will cancel and close the window. Text Color White Black Red Green Blue Yellow Magenta Cyan Transparency Opaque Semi-Transparent Background Color Black White Red Green Blue Yellow Magenta Cyan Transparency Opaque Semi-Transparent Transparent Window Color Black White Red Green Blue Yellow Magenta Cyan Transparency Transparent Semi-Transparent Opaque Font Size 50% 75% 100% 125% 150% 175% 200% 300% 400% Text Edge Style None Raised Depressed Uniform Dropshadow Font Family Proportional Sans-Serif Monospace Sans-Serif Proportional Serif Monospace Serif Casual Script Small Caps Defaults Done Close Modal Dialog This is a modal window. This modal can be closed by pressing the Escape key or activating the close button. Close Modal Dialog This is a modal window. This modal can be closed by pressing the Escape key or activating the close button. Video abstract Introduction STDs, HIV-1 and men who have sex with men In British Columbia (BC), Canada, from 2005 to 2014, infectious syphilis case reports (primary, secondary and early latent) rose 90.6% (288–549), chlamydia 39.9% (9540–13 348) and gonorrhoea 63.8% (1100–1802), corresponding to rate changes per 100 000 population of +72.4%, +33.9% and +47.6%, respectively. 1 Female syphilis cases decreased while male cases jumped from 202 to 524, accounting for 95% of all 2014 cases. Men who have sex with men (MSM) accounted for 60.4% (122) of cases in 2005, rising to 88.9% (466) in 2014. There was a fourfold increase in MSM syphilis from 2010 to 2014 (115–466 cases), including 112 reinfections (24%) in 2014. The HIV-1 coinfection rate in MSM during this period was 50%–75%. From 2005 to 2014, the male infectious syphilis rate increased 235% (9.7–22.8) compared with a much smaller increase for chlamydia (56.9%; 141.7–222.4) and gonorrhoea (42.1%; 39.7–56.4) in men. Comparatively larger increases in syphilis cases were also observed in the USA from 2005 to 2014. Primary and secondary syphilis cases rose 128.1% (8724–19 999), chlamydia 47.7% (976 445–1 441 789) and gonorrhoea 3.1% (339 593–350 062), corresponding to rate changes of +117.2%, +38.5% and −3.4%, respectively. 2 Males contributed an increasing proportion of syphilis cases, accounting for 91% in 2014. From 2007 to 2014, among the 27 US states that collected sex partner data for ≥70% of males, MSM cases increased steadily to 82.9%. In Los Angeles County between January and May, 2010, 76% of 537 early syphilis cases were MSM and ≥58% of these were HIV-1 positive. 3 HIV-1 infection in US MSM has also been statistically associated with repeat syphilis infection. 4 In the UK from 1998 to 2013, new syphilis cases in MSM rose from 23 (26.0% of all cases) to 2546 (71.3% of all cases). From 2009 to 2013 in England, the odds of being diagnosed with syphilis increased from 2.71 (95% CI 2.41 to 3.05, p<0.001) to 4.05 (95% CI 3.70 to 4.45, p<0.001) in<|im_end|> <|im_start|>assistant The antiretroviral drugs used to treat HIV infection might inadvertently be boosting gay/bisexual men's susceptibility to the bacteria responsible for syphilis, Treponema pallidum, conclude researchers in the journal Sexually Transmitted Infections. This might explain why new and repeat cases in these groups have risen so sharply compared with other sexually transmitted infections over the past decade, they suggest. The availability of highly active antiretroviral therapy (HAART) for the treatment of HIV infection has meant that HIV is no longer the automatic death sentence that it once was. The absence of the fear factor is thought to have prompted higher rates of sexually transmitted infections as a result of risky, unprotected sex. But it's not clear why rates of syphilis among gay/bisexual men should be so much higher than those of chlamydia or gonorrhoea, especially as HAART boosts immune system activity, and so would be expected to lower susceptibility to infections, say the Canadian and South African researchers. They therefore reviewed the available evidence on the impact of HAART on behavioural and immune system change to come up with a numerical analysis to explore which might affect the prevalence of the infection the most. They used two risk 'models' to test the likelihood of syphilis infection: one (lower risk) which compared HAART with no treatment in an HIV positive partner; and the other (higher risk) which compared existing infection with no infection in a partner who was either HIV negative or positive. Behaviour change was taken to mean that HAART would result in more sexual partners; and immune system changes were taken to mean that HAART would boost susceptibility to Treponema pallidum. The calculations showed that either factor could produce outbreaks of syphilis that would be substantially higher than expected, but that both factors combined produced a peak in the number of infections that was greater than that associated with either factor alone—and equivalent to the sorts of figures seen in the current outbreak. This suggests that there's an interplay between behavioural change and immune system changes, say the researchers, who offer a possible explanation for a biological effect on the immune system. The body's clearance of T pallidum relies on an increase in the number of an immune system cell called a T cell and a cascade of chemicals that stimulate an inflammatory response. HAART dampens down these activities. Clearance of chlamydia and gonorrhoea is less reliant on these processes, say the researchers. The researchers also refer to other relevant associations, such as the increased risk of certain types of cancer that have been linked to HAART. "Overall, these findings suggest a possible link between HAART and an increased risk for selected diseases of infectious and non-infectious origin, a potential unforeseen consequence that warrants further study," they write. In a linked editorial, Drs Susan Tuddenham, Maunank Shah, and Khalil Ghanem from Johns Hopkins University School of Medicine, Baltimore, caution that the rise in syphilis cases may simply reflect inadequate screening for chlamydia and gonorrhoea. They also point to previous outbreaks of syphilis in straight men and women in the 1980s and 1990s before the advent of HAART. Similarly, they suggest that the calculations used by the researchers don't take account of the complexities of sexual relationships, such as relationship length or the number of concurrent partners, or decreased use of condoms in long term relationships, all of which might influence infection risk. But despite these caveats, they describe the researchers' hypothesis as "intriguing," and one that "warrants careful consideration." They continue: "We are living in an era where [antiretroviral therapy] is being used to effectively treat and prevent HIV infection. To some extent this seems to have tempered the urgency to control other [sexually transmitted infections]. As history has shown many times over, that would be a costly mistake." And they conclude: "Over the past 15 years, syphilis rates among [men who have sex with men] have been rising unabated. We are not aware of any recent intervention that has led to a sustained decline in [these rates] in this population. "If further investigations support a role for [antiretroviral therapy] in increasing susceptibility to syphilis, this will provide one more reason why screening, diagnosis and treatment of [sexually transmitted infections] in [men who have sex with men] must be prioritised." <|im_end|>

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2,588

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The origins of life on Earth required the establishment of self-replicating chemical systems capable of maintaining and evolving biological information. In an RNA world, single self-replicating RNAs would have faced the extreme challenge of possessing a mutation rate low enough both to sustain their own information and to compete successfully against molecular parasites with limited evolvability. Thus theoretical analyses suggest that networks of interacting molecules were more likely to develop and sustain life-like behaviour. Here we show that mixtures of RNA fragments that self-assemble into self-replicating ribozymes spontaneously form cooperative catalytic cycles and networks. We find that a specific three-membered network has highly cooperative growth dynamics. When such cooperative networks are competed directly against selfish autocatalytic cycles, the former grow faster, indicating an intrinsic ability of RNA populations to evolve greater complexity through cooperation. We can observe the evolvability of networks through in vitro selection. Our experiments highlight the advantages of cooperative behaviour even at the molecular stages of nascent life. Main The ‘RNA world’ is a plausible stage in the development of life because RNA simultaneously possesses evolvability and catalytic function 1 . An RNA organism that could evolve in such a fashion is likely to have been one of the Earth’s first life forms. A search is underway 2 , 3 for an RNA autoreplicase that relies on its individual genotype to compete for survival and reproduction by Darwinian-type evolution in a fitness landscape. Yet the transition from a prebiotic chemistry to this stage of life is not understood. Several authors have proposed that the most primitive life thrived less on discrete genotypes and instead on collections of molecular types more subject to systems chemistry than to straightforward selection dynamics 4 , 5 , 6 , 7 , 8 , 9 . In particular, it was suggested that webs of functionally linked, genetically related replicators were required in the earliest phases of life’s appearance to prevent informational decay (the so-called error catastrophe) 4 , 10 , 11 , 12 . An empirical demonstration of RNA replicator networks could illuminate critical features of this early stage of life. Ribozymes are good candidates for this because they can evolve outside of an organismal context, construct other RNAs, exhibit self-sustained reproduction, and explore sequence space in efficient ways 13 , 14 , 15 . However, their ability to form catalytic networks capable of expanding as predicted from theory has not yet been shown, despite the observation that collections of nucleic acids have the potential to manifest complexity 6 , 16 . Simulations show that molecular networks should arise, evolve and provide a population with resistance against parasitic sequences 8 . These results are robust within structured environments such as cells or on grids, but are less so in a solution phase. Recent experimental work in vitro has been very successful at demonstrating simple ecologies 17 , 18 , 19 , reciprocity between two species 6 , 16 , 20 , and sustained exponential growth via cross catalysis 15 . Empirical efforts to date have been limited by an inability to expand past reciprocal interactions between two species to prebiotically relevant systems that have the capacity to increase their complexity by expanding to three, and then more, members 18 , 21 . Specifically, the use of systems in which the recognition domain in the catalyst and the target domain in the substrate are co-located in each replicator has prevented networks of more than two members from forming. If this molecular feature could be circumvented, larger networks could be realized within RNA populations in the test tube and help demonstrate a potential escape from the error catastrophe problem that tends to plague selfish systems. The Azoarcus ribozyme system The ∼ 200-nucleotide (nt) Azoarcus group I intron ribozyme 22 can be broken into fragments that can covalently self-assemble by catalysing recombination reactions in an autocatalytic fashion 23 , 24 ( Supplementary Fig. 1 ). By allowing variation in the sequence recognition mechanism by which this assembly occurs, which is provided by the 3-nt internal guide sequence (IGS) at the 5′ end of the ribozyme, many such autonomously self-assembling ribozymes become possible. We sought to determine if these ribozymes could display cooperative behaviour if their IGS sequences target the assembly of other ribozymes, but not themselves. To create a cooperative network, we fragmented the Azoarcus ribozyme into two pieces in three different ways with the intent of observing how they could spontaneously reassemble via intermolecular cooperation ( Fig. 1a, b ). We manipulated the IGS (canonically GUG) and its target triplet to generate both matched and mismatched partners. We mixed various IGS and target pairs in two-piece constructs to test the ability of mismatched pairs to promote self-assembly ( Supplementary Fig. 2 ). From these data, we chose three mismatched pairs that exhibit relatively little autocatalysis: GUG/CGU, GAG/CAU, and GCG/CUU. These crippled pairs are denoted I 1 , I 2 and I 3 , respectively, meaning that they are informational subsystems, albeit weakly autocatalytic. Figure 1: Cooperative covalent assembly of recombinase ribozymes. a , Design of recombinase ribozymes capable of spontaneous cooperative covalent assembly from fragments. The Azoarcus ribozyme 25 can be broken at three loop regions to obtain four oligomers capable of self-assembling into a full-length molecule 26 , 27 . The grey box in W (magenta) is the internal guide sequence (IGS), whereas those at the 3′ ends of the W , X (lime) and Y (blue) fragments are recombination targets (tags) recognized by the IGS, which guides the catalysis of a covalent closure (•) of the loops. b , A cooperative system comprised of three subsystems, each created from partitioning the molecule into two pieces at different junctions: I 1 ( W + h • X • Y • Z ), I 2 ( W • X + h • Y • Z ) and I 3 ( W • X • Y + h • Z ). Numbers over arrows estimate the cooperative advantage for each step (see text). c", "role": "user" }, { "content": "(Phys.org)—A team of chemistry and applied sciences researchers from several universities in the United States has shown that RNA fragments torn apart in the lab work together to reassemble themselves. This finding, the team claims in their paper published in the journal Nature suggests that early life may have started with cooperative efforts between RNA molecules eventually leading to cooperative replication. The team based its work on mathematical theories proposed by Manfred Eigen, a chemist who suggested that because early RNA wouldn't be able to successfully evolve from short stranded molecules, they must have had help. That help, he said, may have come in the form of cooperative efforts between molecules. In earlier work team lead Niles Lehman had found that if long RNA molecules known as ribozymes were cut into fragments and then placed together in a Petri dish, they would over time reassemble themselves into their original configuration. In this new research, Lehman et al altered three ribozyme samples so that they were identical save for one letter that allowed for distinguishing among them. Each was cut into two pieces and placed in a Petri dish. The team found that if the ribozymes were placed together in a Petri dish, they reassembled themselves faster than if they were put in the dish alone. This occurred, they report, because one of the ribozymes helped another reassemble, who then helped a third reassemble who in turn helped the first reassemble, which formed a closed loop network. To see if the same result might be possible in a more chaotic environment, the researchers placed 48 cut ribozymenes in a test tube with millions of other RNA molecules and found that the original 48 found a way to locate their other parts and each other and helped one another reassemble; again much faster than any of them would have alone. The team suggests that a similar type of cooperation among short RNA molecules in Earth's primordial soup may have allowed them to replicate in a way that avoided the problem of building up mistakes when making copies that mathematical models have suggested would have led to evolutionary death. That would have allowed them to evolve into longer more complex RNA molecules and eventually into all the other molecules that exist today. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The origins of life on Earth required the establishment of self-replicating chemical systems capable of maintaining and evolving biological information. In an RNA world, single self-replicating RNAs would have faced the extreme challenge of possessing a mutation rate low enough both to sustain their own information and to compete successfully against molecular parasites with limited evolvability. Thus theoretical analyses suggest that networks of interacting molecules were more likely to develop and sustain life-like behaviour. Here we show that mixtures of RNA fragments that self-assemble into self-replicating ribozymes spontaneously form cooperative catalytic cycles and networks. We find that a specific three-membered network has highly cooperative growth dynamics. When such cooperative networks are competed directly against selfish autocatalytic cycles, the former grow faster, indicating an intrinsic ability of RNA populations to evolve greater complexity through cooperation. We can observe the evolvability of networks through in vitro selection. Our experiments highlight the advantages of cooperative behaviour even at the molecular stages of nascent life. Main The ‘RNA world’ is a plausible stage in the development of life because RNA simultaneously possesses evolvability and catalytic function 1 . An RNA organism that could evolve in such a fashion is likely to have been one of the Earth’s first life forms. A search is underway 2 , 3 for an RNA autoreplicase that relies on its individual genotype to compete for survival and reproduction by Darwinian-type evolution in a fitness landscape. Yet the transition from a prebiotic chemistry to this stage of life is not understood. Several authors have proposed that the most primitive life thrived less on discrete genotypes and instead on collections of molecular types more subject to systems chemistry than to straightforward selection dynamics 4 , 5 , 6 , 7 , 8 , 9 . In particular, it was suggested that webs of functionally linked, genetically related replicators were required in the earliest phases of life’s appearance to prevent informational decay (the so-called error catastrophe) 4 , 10 , 11 , 12 . An empirical demonstration of RNA replicator networks could illuminate critical features of this early stage of life. Ribozymes are good candidates for this because they can evolve outside of an organismal context, construct other RNAs, exhibit self-sustained reproduction, and explore sequence space in efficient ways 13 , 14 , 15 . However, their ability to form catalytic networks capable of expanding as predicted from theory has not yet been shown, despite the observation that collections of nucleic acids have the potential to manifest complexity 6 , 16 . Simulations show that molecular networks should arise, evolve and provide a population with resistance against parasitic sequences 8 . These results are robust within structured environments such as cells or on grids, but are less so in a solution phase. Recent experimental work in vitro has been very successful at demonstrating simple ecologies 17 , 18 , 19 , reciprocity between two species 6 , 16 , 20 , and sustained exponential growth via cross catalysis 15 . Empirical efforts to date have been limited by an inability to expand past reciprocal interactions between two species to prebiotically relevant systems that have the capacity to increase their complexity by expanding to three, and then more, members 18 , 21 . Specifically, the use of systems in which the recognition domain in the catalyst and the target domain in the substrate are co-located in each replicator has prevented networks of more than two members from forming. If this molecular feature could be circumvented, larger networks could be realized within RNA populations in the test tube and help demonstrate a potential escape from the error catastrophe problem that tends to plague selfish systems. The Azoarcus ribozyme system The ∼ 200-nucleotide (nt) Azoarcus group I intron ribozyme 22 can be broken into fragments that can covalently self-assemble by catalysing recombination reactions in an autocatalytic fashion 23 , 24 ( Supplementary Fig. 1 ). By allowing variation in the sequence recognition mechanism by which this assembly occurs, which is provided by the 3-nt internal guide sequence (IGS) at the 5′ end of the ribozyme, many such autonomously self-assembling ribozymes become possible. We sought to determine if these ribozymes could display cooperative behaviour if their IGS sequences target the assembly of other ribozymes, but not themselves. To create a cooperative network, we fragmented the Azoarcus ribozyme into two pieces in three different ways with the intent of observing how they could spontaneously reassemble via intermolecular cooperation ( Fig. 1a, b ). We manipulated the IGS (canonically GUG) and its target triplet to generate both matched and mismatched partners. We mixed various IGS and target pairs in two-piece constructs to test the ability of mismatched pairs to promote self-assembly ( Supplementary Fig. 2 ). From these data, we chose three mismatched pairs that exhibit relatively little autocatalysis: GUG/CGU, GAG/CAU, and GCG/CUU. These crippled pairs are denoted I 1 , I 2 and I 3 , respectively, meaning that they are informational subsystems, albeit weakly autocatalytic. Figure 1: Cooperative covalent assembly of recombinase ribozymes. a , Design of recombinase ribozymes capable of spontaneous cooperative covalent assembly from fragments. The Azoarcus ribozyme 25 can be broken at three loop regions to obtain four oligomers capable of self-assembling into a full-length molecule 26 , 27 . The grey box in W (magenta) is the internal guide sequence (IGS), whereas those at the 3′ ends of the W , X (lime) and Y (blue) fragments are recombination targets (tags) recognized by the IGS, which guides the catalysis of a covalent closure (•) of the loops. b , A cooperative system comprised of three subsystems, each created from partitioning the molecule into two pieces at different junctions: I 1 ( W + h • X • Y • Z ), I 2 ( W • X + h • Y • Z ) and I 3 ( W • X • Y + h • Z ). Numbers over arrows estimate the cooperative advantage for each step (see text). c<|im_end|> <|im_start|>assistant (Phys.org)—A team of chemistry and applied sciences researchers from several universities in the United States has shown that RNA fragments torn apart in the lab work together to reassemble themselves. This finding, the team claims in their paper published in the journal Nature suggests that early life may have started with cooperative efforts between RNA molecules eventually leading to cooperative replication. The team based its work on mathematical theories proposed by Manfred Eigen, a chemist who suggested that because early RNA wouldn't be able to successfully evolve from short stranded molecules, they must have had help. That help, he said, may have come in the form of cooperative efforts between molecules. In earlier work team lead Niles Lehman had found that if long RNA molecules known as ribozymes were cut into fragments and then placed together in a Petri dish, they would over time reassemble themselves into their original configuration. In this new research, Lehman et al altered three ribozyme samples so that they were identical save for one letter that allowed for distinguishing among them. Each was cut into two pieces and placed in a Petri dish. The team found that if the ribozymes were placed together in a Petri dish, they reassembled themselves faster than if they were put in the dish alone. This occurred, they report, because one of the ribozymes helped another reassemble, who then helped a third reassemble who in turn helped the first reassemble, which formed a closed loop network. To see if the same result might be possible in a more chaotic environment, the researchers placed 48 cut ribozymenes in a test tube with millions of other RNA molecules and found that the original 48 found a way to locate their other parts and each other and helped one another reassemble; again much faster than any of them would have alone. The team suggests that a similar type of cooperation among short RNA molecules in Earth's primordial soup may have allowed them to replicate in a way that avoided the problem of building up mistakes when making copies that mathematical models have suggested would have led to evolutionary death. That would have allowed them to evolve into longer more complex RNA molecules and eventually into all the other molecules that exist today. <|im_end|>

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1243, 810, 11, 3697, 220, 972, 1174, 220, 1691, 662, 45863, 11, 279, 1005, 315, 6067, 304, 902, 279, 18324, 8106, 304, 279, 51483, 323, 279, 2218, 8106, 304, 279, 54057, 527, 1080, 12, 40563, 304, 1855, 29641, 859, 706, 32098, 14488, 315, 810, 1109, 1403, 3697, 505, 30164, 13, 1442, 420, 31206, 4668, 1436, 387, 10408, 74228, 11, 8294, 14488, 1436, 387, 15393, 2949, 41214, 22673, 304, 279, 1296, 14019, 323, 1520, 20461, 264, 4754, 12731, 505, 279, 1493, 65396, 3575, 430, 28335, 311, 55537, 45743, 6067, 13, 578, 362, 13028, 8362, 355, 20735, 9700, 31218, 1887, 578, 12264, 120, 220, 1049, 5392, 22935, 69044, 320, 406, 8, 362, 13028, 8362, 355, 1912, 358, 10805, 263, 20735, 9700, 31218, 220, 1313, 649, 387, 11102, 1139, 35603, 430, 649, 1080, 838, 4501, 659, 33534, 16167, 555, 34454, 1065, 287, 312, 76128, 25481, 304, 459, 57253, 4306, 70504, 11401, 220, 1419, 1174, 220, 1187, 320, 99371, 23966, 13, 220, 16, 7609, 3296, 10923, 23851, 304, 279, 8668, 18324, 17383, 555, 902, 420, 14956, 13980, 11, 902, 374, 3984, 555, 279, 220, 18, 12, 406, 5419, 8641, 8668, 320, 1953, 50, 8, 520, 279, 220, 20, 39615, 842, 315, 279, 20735, 9700, 31218, 11, 1690, 1778, 95103, 7162, 659, 33534, 43064, 20735, 9700, 79809, 3719, 3284, 13, 1226, 16495, 311, 8417, 422, 1521, 20735, 9700, 79809, 1436, 3113, 48566, 17432, 422, 872, 358, 16929, 24630, 2218, 279, 14956, 315, 1023, 20735, 9700, 79809, 11, 719, 539, 5694, 13, 2057, 1893, 264, 48566, 4009, 11, 584, 87195, 279, 362, 13028, 8362, 355, 20735, 9700, 31218, 1139, 1403, 9863, 304, 2380, 2204, 5627, 449, 279, 7537, 315, 46071, 1268, 814, 1436, 88558, 312, 70208, 4669, 958, 76, 43943, 23915, 320, 23966, 13, 220, 16, 64, 11, 293, 7609, 1226, 55315, 279, 358, 16929, 320, 4919, 263, 2740, 480, 3014, 8, 323, 1202, 2218, 99809, 311, 7068, 2225, 18545, 323, 36401, 291, 8717, 13, 1226, 9709, 5370, 358, 16929, 323, 2218, 13840, 304, 1403, 56964, 57327, 311, 1296, 279, 5845, 315, 36401, 291, 13840, 311, 12192, 659, 12, 15343, 320, 99371, 23966, 13, 220, 17, 7609, 5659, 1521, 828, 11, 584, 14896, 2380, 36401, 291, 13840, 430, 31324, 12309, 2697, 57253, 4306, 4548, 25, 480, 3014, 14, 8974, 52, 11, 480, 1929, 14, 5158, 52, 11, 323, 480, 8974, 11547, 87664, 13, 4314, 99052, 13840, 527, 3453, 9437, 358, 220, 16, 1174, 358, 220, 17, 323, 358, 220, 18, 1174, 15947, 11, 7438, 430, 814, 527, 47735, 53885, 82, 11, 43169, 7621, 398, 57253, 4306, 70504, 13, 19575, 220, 16, 25, 86805, 1080, 838, 306, 14956, 315, 38301, 7006, 521, 20735, 9700, 79809, 13, 264, 1174, 7127, 315, 38301, 7006, 521, 20735, 9700, 79809, 13171, 315, 54557, 48566, 1080, 838, 306, 14956, 505, 35603, 13, 578, 362, 13028, 8362, 355, 20735, 9700, 31218, 220, 914, 649, 387, 11102, 520, 2380, 6471, 13918, 311, 6994, 3116, 55984, 69638, 13171, 315, 659, 33534, 43064, 1139, 264, 2539, 30425, 43030, 220, 1627, 1174, 220, 1544, 662, 578, 20366, 3830, 304, 468, 320, 76, 48162, 8, 374, 279, 5419, 8641, 8668, 320, 1953, 50, 705, 20444, 1884, 520, 279, 220, 18, 39615, 10548, 315, 279, 468, 1174, 1630, 320, 40043, 8, 323, 816, 320, 12481, 8, 35603, 527, 312, 76128, 11811, 320, 14412, 8, 15324, 555, 279, 358, 16929, 11, 902, 28292, 279, 34454, 4548, 315, 264, 1080, 838, 306, 22722, 320, 6806, 8, 315, 279, 30853, 13, 293, 1174, 362, 48566, 1887, 40056, 315, 2380, 53885, 82, 11, 1855, 3549, 505, 17071, 287, 279, 43030, 1139, 1403, 9863, 520, 2204, 49341, 82, 25, 358, 220, 16, 320, 468, 489, 305, 7436, 1630, 7436, 816, 7436, 1901, 7026, 358, 220, 17, 320, 468, 7436, 1630, 489, 305, 7436, 816, 7436, 1901, 883, 323, 358, 220, 18, 320, 468, 7436, 1630, 7436, 816, 489, 305, 7436, 1901, 7609, 35813, 927, 38057, 16430, 279, 48566, 9610, 369, 1855, 3094, 320, 4151, 1495, 570, 272, 128257, 198, 128256, 78191, 198, 7, 67171, 2726, 68850, 32, 2128, 315, 30903, 323, 9435, 36788, 12074, 505, 3892, 23978, 304, 279, 3723, 4273, 706, 6982, 430, 41214, 35603, 21830, 10980, 304, 279, 10278, 990, 3871, 311, 312, 70208, 5694, 13, 1115, 9455, 11, 279, 2128, 8349, 304, 872, 5684, 4756, 304, 279, 8486, 22037, 13533, 430, 4216, 2324, 1253, 617, 3940, 449, 48566, 9045, 1990, 41214, 35715, 9778, 6522, 311, 48566, 48891, 13, 578, 2128, 3196, 1202, 990, 389, 37072, 26018, 11223, 555, 2418, 29093, 25059, 11, 264, 8590, 380, 889, 12090, 430, 1606, 4216, 41214, 8434, 956, 387, 3025, 311, 7946, 38680, 505, 2875, 63205, 35715, 11, 814, 2011, 617, 1047, 1520, 13, 3011, 1520, 11, 568, 1071, 11, 1253, 617, 2586, 304, 279, 1376, 315, 48566, 9045, 1990, 35715, 13, 763, 6931, 990, 2128, 3063, 452, 3742, 63658, 1543, 1047, 1766, 430, 422, 1317, 41214, 35715, 3967, 439, 20735, 9700, 79809, 1051, 4018, 1139, 35603, 323, 1243, 9277, 3871, 304, 264, 11586, 462, 12269, 11, 814, 1053, 927, 892, 312, 70208, 5694, 1139, 872, 4113, 6683, 13, 763, 420, 502, 3495, 11, 63658, 1543, 1880, 453, 29852, 2380, 20735, 9700, 31218, 10688, 779, 430, 814, 1051, 20086, 3665, 369, 832, 6661, 430, 5535, 369, 86055, 4315, 1124, 13, 9062, 574, 4018, 1139, 1403, 9863, 323, 9277, 304, 264, 11586, 462, 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1648, 430, 31890, 279, 3575, 315, 4857, 709, 21294, 994, 3339, 11236, 430, 37072, 4211, 617, 12090, 1053, 617, 6197, 311, 41993, 4648, 13, 3011, 1053, 617, 5535, 1124, 311, 38680, 1139, 5129, 810, 6485, 41214, 35715, 323, 9778, 1139, 682, 279, 1023, 35715, 430, 3073, 3432, 13, 220, 128257, 198 ]

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Fragile X syndrome (FXS) is the leading monogenic cause of autism spectrum disorders (ASD). Trinucleotide repeat expansions in FMR1 abolish FMRP expression, leading to hyperactivation of ERK and mTOR signaling upstream of mRNA translation. Here we show that metformin, the most widely used drug for type 2 diabetes, rescues core phenotypes in Fmr1 −/y mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9. Thus, metformin is a potential FXS therapeutic. Main Dysregulated mRNA translation is linked to core pathologies diagnosed in FXS, such as social and behavioral problems, developmental delays and learning disabilities 1 , 2 . In the brains of individuals with FXS and knockout mice ( Fmr1 −/y ; X-linked Fmr1 deletion in male mice), loss of the fragile X mental retardation protein (FMRP) results in hyperactivation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1) and the extracellular-signal-regulated kinase (ERK) signaling pathways 1 , 2 . Consistent with increased ERK activity, eukaryotic initiation factor 4E (eIF4E) phosphorylation is elevated in the brains of individuals with FXS and Fmr1 −/y mice, thereby promoting translation of the mRNA encoding matrix metalloproteinase 9 (MMP-9), which is also elevated in the brains of both individuals with FXS and Fmr1 −/y mice 1 , 2 , 3 , 4 , 5 . In accordance with these findings, knockout of Mmp9 rescues the majority of known cellular and behavioral phenotypes in Fmr1 −/y mice. MMP-9 degrades components of the extracellular matrix, including proteins that are important for synaptic function and maturation, which have been implicated in FXS and ASD. Recent observations indicate that metformin, a first-line therapy for type 2 diabetes, imparts numerous health benefits beyond its original therapeutic use, such as decreased cancer risk and improved cancer prognosis 6 . Metformin inhibits mitochondrial respiratory chain complex 1, leading to a decrease in the cellular energy state and, thus, activation of the energy sensor AMP-activated protein kinase (AMPK) 6 . Several AMPK-independent activities of metformin have also been reported 7 , 8 . As metformin suppresses translation by inhibiting the mTORC1 and ERK pathways, we reasoned that metformin could have beneficial therapeutic effects in Fmr1 −/y mice 9 . Adult (aged 8–12 weeks) wild-type (WT) and Fmr1 −/y mice were injected intraperitoneally (i.p.) with metformin (200 mg per kg bodyweight per day, a dose previously used in preclinical studies 8 ) or vehicle for 10 d ( Fig. 1a ). Metformin, as previously reported 10 , crossed the blood–brain barrier (BBB), with lower concentrations found in the brain than in plasma after acute and chronic injection ( Supplementary Figs. 1 and 2 ). Twenty-four hours after the last injection of metformin, mice were subjected to a social novelty test. Vehicle-treated Fmr1 −/y mice were impaired in their preference for social novelty, showing no preference for interaction with the novel stimulus (stranger 2) over the original social stimulus (stranger 1; Fig. 1b,c ). Metformin treatment restored the impaired preference of Fmr1 −/y mice for the novel stranger mouse, thus rescuing the social deficit. Next, we examined the effect of metformin on repetitive behavior, a core characteristic of individuals with FXS that is recapitulated in Fmr1 −/y mice as increased self-grooming 1 , 11 . Metformin reversed the increased grooming in Fmr1 −/y mice ( Fig. 1d ) and decreased the number of grooming bouts ( Fig. 1e ) measured 24 h after the last injection. Prolonged exposure to metformin was required to rescue behavioral deficits, as metformin treatment of Fmr1 −/y mice for 1 or 5 d failed to correct the core FXS phenotypes ( Supplementary Figs. 3 and 4 ). We tested several other behavioral phenotypes, including audiogenic seizures, hyperactivity and cognitive function, in Fmr1 −/y mice after metformin treatment and observed no cognitive impairment. Ten-day treatment with metformin reduced the incidence of seizures but did not have an effect on hyperactivity ( Supplementary Figs. 5 and 6 ). Figure 1: Chronic metformin treatment corrects the social deficit, repetitive behavior, aberrant dendritic spine morphology and exaggerated LTD in Fmr1 −/y mice. ( a ) Metformin (met) or vehicle (veh) was injected i.p. over 10 d (200 mg per kg bodyweight per day), followed by analysis of social behavior, grooming, dendritic spine morphology and LTD. ( b , c ) Preference for social novelty was assessed in the three-chamber social interaction test by measuring the time spent with the novel social stimulus (stranger 2, S2) or the previously encountered mouse (stranger 1, S1) ( b ) and the time spent in each chamber ( c ). Vehicle-treated WT mice ( n = 10), vehicle-treated Fmr1 −/y mice ( n = 10), metformin-treated WT mice ( n = 9), metformin-treated Fmr1 −/y mice ( n = 12). ( d , e ) Self-grooming test examining the total time spent grooming ( d ) and the total number of grooming bouts ( e ). Vehicle-treated WT mice ( n = 10), vehicle-treated Fmr1 −/y mice ( n = 10), metformin-treated WT mice ( n = 8), metformin-treated Fmr1 −/y mice ( n = 12). ( f ) Golgi–Cox staining of CA1 dendritic spines in metformin- and vehicle-injected WT and Fmr1 −/y mice. Scale bar, 2 μm; representative images shown ( n = 4 mice in each group). ( g , h ) Quantification of spine density, measured as the number of spines per 10-μm dendrite length ( g ), and spine subtype analysis (S/M, spiny or mushroom; F, filopodial), presented as the fraction of the total spines for each subtype ( h ) ( n = 4 mice in each group). ( i , j ) mGluR-dependent LTD was measured in CA1 in response to ( S )-3,5-dihydroxyphenylglycine (DHPG; 50 μM for 10 min) in slices prepared from vehicle-treated WT ( n = 4) and Fmr1 −/y ( n = 9) mice ( i ) and metformin-treated WT ( n = 5) and Fmr1 −/y ( n = 6) mice ( j ). ( k ) Field excitatory postsynaptic potential (fEPSP)", "role": "user" }, { "content": "A widely used diabetes medication could help people with a common inherited form of autism, research shows. Scientists found that a drug called metformin improves sociability and reduces symptomatic behaviours in adult mice with a form of Fragile X syndrome. Researchers say that metformin could be repurposed as a therapy for Fragile X syndrome within a few years - if clinical trials prove successful. Fragile X syndrome is caused by inherited defects in a gene called FMR1, which leads to excess protein production in the brain. This results in the breakdown of connections between brain cells, leading to changes in behaviour. The team led by the University of Edinburgh and McGill University in Canada looked at the effects of metformin on mice that lack the FMR1 gene. These mice usually have symptoms consistent with Fragile X syndrome - they exhibit repetitive behaviours such as increased grooming and do not socialise with other mice. After mice had treatment with metformin for ten days, protein production in the brain returned to typical levels, brain connections were repaired and they displayed normal behaviour patterns, the researchers found. The therapy also reduced the occurrence of seizures, which are reported to affect between 10 and 20 per cent of people with Fragile X. Fragile X Syndrome affects around 1 in 4,000 boys and 1 in 6,000 girls. It is the most common known cause of inherited intellectual disability. Affected children have developmental delays that impair speech and language, problems with social interactions and are often co-diagnosed with autism, anxiety and seizures. Metformin is already approved by the UK's Medicines and Healthcare products Regulatory Agency and the US Food and Drug Administration as a therapy for type 2 diabetes. Dr. Christos Gkogkas, Chancellor's Fellow at the University of Edinburgh's Patrick Wild Centre, said: \"Metformin has been extensively used as a therapy for type 2 diabetes for more than 30 years, and its safety and tolerability are well documented. Our study suggests the drug could be a novel therapeutic for Fragile X syndrome, a common type of autism. We next plan to investigate whether metformin offers any benefits for other types of autism.\" Dr. Nahum Sonenberg, James McGill Professor at McGill University's Biochemistry Department, commented: \"This is some of the most exciting research work in my career, as it offers great promise in treating a pernicious genetic disease for which there is no cure.\" Dr. Andrew Stanfield, Co-director of the Patrick Wild Centre for Research into Autism, Fragile X Syndrome and Intellectual Disabilities, said: \"'These findings are particularly important as metformin is a commonly used drug for other conditions so we already know a lot about its safety profile. If clinical trials in people with Fragile X syndrome are successful then it could be in use much more quickly than would be the case for a brand new medication.\" The study is published in the journal Nature Medicine. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Fragile X syndrome (FXS) is the leading monogenic cause of autism spectrum disorders (ASD). Trinucleotide repeat expansions in FMR1 abolish FMRP expression, leading to hyperactivation of ERK and mTOR signaling upstream of mRNA translation. Here we show that metformin, the most widely used drug for type 2 diabetes, rescues core phenotypes in Fmr1 −/y mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9. Thus, metformin is a potential FXS therapeutic. Main Dysregulated mRNA translation is linked to core pathologies diagnosed in FXS, such as social and behavioral problems, developmental delays and learning disabilities 1 , 2 . In the brains of individuals with FXS and knockout mice ( Fmr1 −/y ; X-linked Fmr1 deletion in male mice), loss of the fragile X mental retardation protein (FMRP) results in hyperactivation of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1) and the extracellular-signal-regulated kinase (ERK) signaling pathways 1 , 2 . Consistent with increased ERK activity, eukaryotic initiation factor 4E (eIF4E) phosphorylation is elevated in the brains of individuals with FXS and Fmr1 −/y mice, thereby promoting translation of the mRNA encoding matrix metalloproteinase 9 (MMP-9), which is also elevated in the brains of both individuals with FXS and Fmr1 −/y mice 1 , 2 , 3 , 4 , 5 . In accordance with these findings, knockout of Mmp9 rescues the majority of known cellular and behavioral phenotypes in Fmr1 −/y mice. MMP-9 degrades components of the extracellular matrix, including proteins that are important for synaptic function and maturation, which have been implicated in FXS and ASD. Recent observations indicate that metformin, a first-line therapy for type 2 diabetes, imparts numerous health benefits beyond its original therapeutic use, such as decreased cancer risk and improved cancer prognosis 6 . Metformin inhibits mitochondrial respiratory chain complex 1, leading to a decrease in the cellular energy state and, thus, activation of the energy sensor AMP-activated protein kinase (AMPK) 6 . Several AMPK-independent activities of metformin have also been reported 7 , 8 . As metformin suppresses translation by inhibiting the mTORC1 and ERK pathways, we reasoned that metformin could have beneficial therapeutic effects in Fmr1 −/y mice 9 . Adult (aged 8–12 weeks) wild-type (WT) and Fmr1 −/y mice were injected intraperitoneally (i.p.) with metformin (200 mg per kg bodyweight per day, a dose previously used in preclinical studies 8 ) or vehicle for 10 d ( Fig. 1a ). Metformin, as previously reported 10 , crossed the blood–brain barrier (BBB), with lower concentrations found in the brain than in plasma after acute and chronic injection ( Supplementary Figs. 1 and 2 ). Twenty-four hours after the last injection of metformin, mice were subjected to a social novelty test. Vehicle-treated Fmr1 −/y mice were impaired in their preference for social novelty, showing no preference for interaction with the novel stimulus (stranger 2) over the original social stimulus (stranger 1; Fig. 1b,c ). Metformin treatment restored the impaired preference of Fmr1 −/y mice for the novel stranger mouse, thus rescuing the social deficit. Next, we examined the effect of metformin on repetitive behavior, a core characteristic of individuals with FXS that is recapitulated in Fmr1 −/y mice as increased self-grooming 1 , 11 . Metformin reversed the increased grooming in Fmr1 −/y mice ( Fig. 1d ) and decreased the number of grooming bouts ( Fig. 1e ) measured 24 h after the last injection. Prolonged exposure to metformin was required to rescue behavioral deficits, as metformin treatment of Fmr1 −/y mice for 1 or 5 d failed to correct the core FXS phenotypes ( Supplementary Figs. 3 and 4 ). We tested several other behavioral phenotypes, including audiogenic seizures, hyperactivity and cognitive function, in Fmr1 −/y mice after metformin treatment and observed no cognitive impairment. Ten-day treatment with metformin reduced the incidence of seizures but did not have an effect on hyperactivity ( Supplementary Figs. 5 and 6 ). Figure 1: Chronic metformin treatment corrects the social deficit, repetitive behavior, aberrant dendritic spine morphology and exaggerated LTD in Fmr1 −/y mice. ( a ) Metformin (met) or vehicle (veh) was injected i.p. over 10 d (200 mg per kg bodyweight per day), followed by analysis of social behavior, grooming, dendritic spine morphology and LTD. ( b , c ) Preference for social novelty was assessed in the three-chamber social interaction test by measuring the time spent with the novel social stimulus (stranger 2, S2) or the previously encountered mouse (stranger 1, S1) ( b ) and the time spent in each chamber ( c ). Vehicle-treated WT mice ( n = 10), vehicle-treated Fmr1 −/y mice ( n = 10), metformin-treated WT mice ( n = 9), metformin-treated Fmr1 −/y mice ( n = 12). ( d , e ) Self-grooming test examining the total time spent grooming ( d ) and the total number of grooming bouts ( e ). Vehicle-treated WT mice ( n = 10), vehicle-treated Fmr1 −/y mice ( n = 10), metformin-treated WT mice ( n = 8), metformin-treated Fmr1 −/y mice ( n = 12). ( f ) Golgi–Cox staining of CA1 dendritic spines in metformin- and vehicle-injected WT and Fmr1 −/y mice. Scale bar, 2 μm; representative images shown ( n = 4 mice in each group). ( g , h ) Quantification of spine density, measured as the number of spines per 10-μm dendrite length ( g ), and spine subtype analysis (S/M, spiny or mushroom; F, filopodial), presented as the fraction of the total spines for each subtype ( h ) ( n = 4 mice in each group). ( i , j ) mGluR-dependent LTD was measured in CA1 in response to ( S )-3,5-dihydroxyphenylglycine (DHPG; 50 μM for 10 min) in slices prepared from vehicle-treated WT ( n = 4) and Fmr1 −/y ( n = 9) mice ( i ) and metformin-treated WT ( n = 5) and Fmr1 −/y ( n = 6) mice ( j ). ( k ) Field excitatory postsynaptic potential (fEPSP)<|im_end|> <|im_start|>assistant A widely used diabetes medication could help people with a common inherited form of autism, research shows. Scientists found that a drug called metformin improves sociability and reduces symptomatic behaviours in adult mice with a form of Fragile X syndrome. Researchers say that metformin could be repurposed as a therapy for Fragile X syndrome within a few years - if clinical trials prove successful. Fragile X syndrome is caused by inherited defects in a gene called FMR1, which leads to excess protein production in the brain. This results in the breakdown of connections between brain cells, leading to changes in behaviour. The team led by the University of Edinburgh and McGill University in Canada looked at the effects of metformin on mice that lack the FMR1 gene. These mice usually have symptoms consistent with Fragile X syndrome - they exhibit repetitive behaviours such as increased grooming and do not socialise with other mice. After mice had treatment with metformin for ten days, protein production in the brain returned to typical levels, brain connections were repaired and they displayed normal behaviour patterns, the researchers found. The therapy also reduced the occurrence of seizures, which are reported to affect between 10 and 20 per cent of people with Fragile X. Fragile X Syndrome affects around 1 in 4,000 boys and 1 in 6,000 girls. It is the most common known cause of inherited intellectual disability. Affected children have developmental delays that impair speech and language, problems with social interactions and are often co-diagnosed with autism, anxiety and seizures. Metformin is already approved by the UK's Medicines and Healthcare products Regulatory Agency and the US Food and Drug Administration as a therapy for type 2 diabetes. Dr. Christos Gkogkas, Chancellor's Fellow at the University of Edinburgh's Patrick Wild Centre, said: "Metformin has been extensively used as a therapy for type 2 diabetes for more than 30 years, and its safety and tolerability are well documented. Our study suggests the drug could be a novel therapeutic for Fragile X syndrome, a common type of autism. We next plan to investigate whether metformin offers any benefits for other types of autism." Dr. Nahum Sonenberg, James McGill Professor at McGill University's Biochemistry Department, commented: "This is some of the most exciting research work in my career, as it offers great promise in treating a pernicious genetic disease for which there is no cure." Dr. Andrew Stanfield, Co-director of the Patrick Wild Centre for Research into Autism, Fragile X Syndrome and Intellectual Disabilities, said: "'These findings are particularly important as metformin is a commonly used drug for other conditions so we already know a lot about its safety profile. If clinical trials in people with Fragile X syndrome are successful then it could be in use much more quickly than would be the case for a brand new medication." The study is published in the journal Nature Medicine. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract More than two hundred individuals developed Creutzfeldt–Jakob disease (CJD) worldwide as a result of treatment, typically in childhood, with human cadaveric pituitary-derived growth hormone contaminated with prions 1 , 2 . Although such treatment ceased in 1985, iatrogenic CJD (iCJD) continues to emerge because of the prolonged incubation periods seen in human prion infections. Unexpectedly, in an autopsy study of eight individuals with iCJD, aged 36–51 years, in four we found moderate to severe grey matter and vascular amyloid-β (Aβ) pathology. The Aβ deposition in the grey matter was typical of that seen in Alzheimer’s disease and Aβ in the blood vessel walls was characteristic of cerebral amyloid angiopathy 3 and did not co-localize with prion protein deposition. None of these patients had pathogenic mutations, APOE ε4 or other high-risk alleles 4 associated with early-onset Alzheimer’s disease. Examination of a series of 116 patients with other prion diseases from a prospective observational cohort study 5 showed minimal or no Aβ pathology in cases of similar age range, or a decade older, without APOE ε4 risk alleles. We also analysed pituitary glands from individuals with Aβ pathology and found marked Aβ deposition in multiple cases. Experimental seeding of Aβ pathology has been previously demonstrated in primates and transgenic mice by central nervous system or peripheral inoculation with Alzheimer’s disease brain homogenate 6 , 7 , 8 , 9 , 10 , 11 . The marked deposition of parenchymal and vascular Aβ in these relatively young patients with iCJD, in contrast with other prion disease patients and population controls, is consistent with iatrogenic transmission of Aβ pathology in addition to CJD and suggests that healthy exposed individuals may also be at risk of iatrogenic Alzheimer’s disease and cerebral amyloid angiopathy. These findings should also prompt investigation of whether other known iatrogenic routes of prion transmission may also be relevant to Aβ and other proteopathic seeds associated with neurodegenerative and other human diseases. Main Human transmission of prion disease has occurred as a result of a range of medical and surgical procedures worldwide as well as by endocannibalism in Papua New Guinea, with incubation periods that can exceed five decades 12 , 13 . A well-recognized iatrogenic route of transmission was by treatment of persons of short stature with preparations of human growth hormone, extracted from large pools of cadaver-sourced pituitary glands, some of which were inadvertently prion-contaminated. Such treatments commenced in 1958 and ceased in 1985 following the reports of the occurrence of CJD amongst recipients. A review of all 1,848 patients who were treated with cadaveric-derived human growth hormone (c-hGH) in the United Kingdom from 1959 through 1985 found that 38 had developed CJD by the year 2000 with a peak incubation period of 20 years 1 . Multiple preparations using different extraction methods were used over this period and patients received batches from several preparations. One preparation (Wilhelmi) was common to all patients who developed iCJD and size-exclusion chromatography, used in non-Wilhelmi preparation methods, may have reduced prion contamination 1 . As of 2012, a total of 450 cases of iatrogenic CJD have been recognized worldwide after treatment with c-hGH or gonadotropin (226 cases), transplantation of dura mater (228) or cornea (2), and neurosurgery (4) or electroencephalography recording using invasive medical devices (2) 2 . In France, 119/1,880 (6.3%) recipients developed iCJD, in the UK 65/1,800 (3.6%) and in the USA 29/7,700 (0.4%) 2 , 14 . Since 2008, most UK patients with prion disease have been recruited into the National Prion Monitoring Cohort study 5 , including 22 of 24 recent patients with iatrogenic CJD (iCJD) related to treatment with c-hGH over this period, all of whom necessarily have very long incubation periods. Of this group of patients with iCJD, eight patients (referenced no.s 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , Supplementary Information ) aged 36–51 years, with an incubation period from first treatment to onset of 27.9–38.9 years (mean 33 years) and from last treatment to onset of 18.8–30.8 years (mean 25.5 years), underwent autopsy with extensive brain tissue sampling at our hospital. In all eight brain samples we confirmed prion disease with abnormal prion protein labelling of the neuropil, perineuronal network and in most cases microplaques as described previously 15 , 16 , 17 . However, four (no.s 4, 5, 6, 8) of the eight patients with iCJD also showed substantial amyloid-β (Aβ) deposition in the central nervous system parenchyma by histology ( Fig. 1 ) and immunoblotting ( Fig. 2 ). A further two brain samples (no.s 1, 3) had focal Aβ pathology in one of the brain regions; one showed Aβ entrapment in PrP plaques and only one was entirely negative for Aβ. Furthermore, there was widespread cortical and leptomeningeal cerebral Aβ angiopathy (CAA) 3 in three patients (no.s 4, 6, 8) and focal CAA in one patient (no. 5) ( Fig. 1 ). Such pathology is extremely rare in this age range, 10/290 in the equivalent 36–50 year age strata without CJD 18 , P = 0.0002, Fisher’s test. None of our patients with iCJD had pathogenic mutations in the prion protein gene ( PRNP ). We used a custom next generation sequencing panel 4 to exclude mutation in any of 16 other genes associated with early-onset Alzheimer’s disease, CAA, or other neurodegenerative disorders, and none carried APOE ε4 or TREM2 R47H alleles ( Supplementary Table 2 ). Although such observations are unprecedented in our wide experience of human prion diseases, we nevertheless considered whether prion disease itself might predispose to, or accelerate, Aβ pathology, for example by cross-seeding of protein aggregation or overload of clearance mechanisms for misfolded proteins. We therefore compared the Aβ pathology in the iCJD cohort with that of a cohort of 116 patients with other prion diseases who had undergone autopsy: sporadic CJD (sCJD) ( n = 85, age 42–83), variant CJD ( n = 2, age 25 and 36) and inherited prion diseases (IPD) ( n = 29,", "role": "user" }, { "content": "People injected with hormones extracted from cadaver brains in a long-abandoned procedure may have received \"seeds\" of Alzheimer's disease, said a study Wednesday, urging research into possible risks for \"accidental\" medical transmission. Published in the journal Nature, the research claims to provide evidence for the hypothesis that the protein fragments which assemble into Alzheimer's-causing plaques, can be passed between humans via diseased tissue transfer. But this did not mean that Alzheimer's was contagious, the study authors and independent commentators stressed. \"This relates to a very special situation where people have been injected with essentially extracts of human tissue,\" said co-author John Collinge of University College London (UCL). \"I don't think there needs to be any alarm that we're saying in any way that you can catch Alzheimer's Disease.\" Further research, however, would be \"prudent,\" he said during a telephone press briefing. \"We should think about whether there might be accidental routes in which these diseases might be transmitted by medical or surgical procedures.\" While conducting research into an unrelated disease, Collinge and a team examined the brains of eight people who had received injections in childhood of a hormone to treat dwarfism. The hormone had been extracted from pituitary glands harvested from thousands of human cadavers. This practice was halted in 1985 when doctors realised it could transmit a variant of Creutzfeldt-Jakob disease (CJD)—the human version of \"mad cow\" disease. Eight subjects in the study in fact died from this ailment. Too young Collinge and colleagues, \"very much to our surprise,\" found that seven of the eight had brain deposits of Alzheimer's-linked amyloid beta (Abeta) fragments—with four of them having high concentrations. Strikingly the patients were 36-51 years old, whereas such deposits are normally seen in elderly people. \"We think the most likely explanation is that the growth hormone preparations with which these people were treated as children, in addition to being contaminated with CJD prions (a different protein type), was probably also contaminated with Abeta seeds.\" Previous laboratory studies showed that Abeta in Alzheimer's-ridden brain tissue, when transferred to mice or monkeys, could infect the host animal brain—even when it had been injected into their abdomens. \"So there are mechanisms to transport these protein seeds to the brain,\" said Collinge. \"We don't know what they are, but clearly it can happen. So that's consistent with these seeds spreading from an intramuscular injection in the children to their brains.\" Amyloid beta seeds, the team wrote, \"are known, like prions, to adhere to metal surfaces and to resist... conventional hospital sterilisation.\" Experts who were not part of the study underlined there was no evidence of any modern-day medical treatment, including dental surgery or blood transfusions, raising the Alzheimer's risk. Cautious, not concerned For the time being, \"this paper should make us cautious but not overly concerned,\" said Simon Lovestone of the University of Oxford. John Hardy, of UCL, added it seemed \"relatively sure\" that Abeta can be transferred by injection. \"Does it have implications for... blood transfusions: probably not, but this definitely deserves systematic epidemiological investigation,\" he said via the Science Media Centre (SMC) in London. \"Does it suggest Alzheimer's disease is infectious through contact? Almost certainly not.\" The study authors said the eight fatalities in the study did not have the full-blown features of Alzheimer's—they were missing the \"tangles\" caused by a different protein called Tau. It was impossible to know whether they would have gone on to develop the disease. \"I wouldn't want to cause alarm on this. I don't think anyone should delay or reconsider having surgery on the basis of these data at all,\" said Collinge. \"We've got no evidence that this is a risk to humans, but I think it would be prudent to do some research in this area going forward.\" Some 30,000 people, mostly children with growth deficiency, received the hormone injections, of whom over 200 developed CJD. The disease has a very long incubation period, and new diagnoses continue to be made. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract More than two hundred individuals developed Creutzfeldt–Jakob disease (CJD) worldwide as a result of treatment, typically in childhood, with human cadaveric pituitary-derived growth hormone contaminated with prions 1 , 2 . Although such treatment ceased in 1985, iatrogenic CJD (iCJD) continues to emerge because of the prolonged incubation periods seen in human prion infections. Unexpectedly, in an autopsy study of eight individuals with iCJD, aged 36–51 years, in four we found moderate to severe grey matter and vascular amyloid-β (Aβ) pathology. The Aβ deposition in the grey matter was typical of that seen in Alzheimer’s disease and Aβ in the blood vessel walls was characteristic of cerebral amyloid angiopathy 3 and did not co-localize with prion protein deposition. None of these patients had pathogenic mutations, APOE ε4 or other high-risk alleles 4 associated with early-onset Alzheimer’s disease. Examination of a series of 116 patients with other prion diseases from a prospective observational cohort study 5 showed minimal or no Aβ pathology in cases of similar age range, or a decade older, without APOE ε4 risk alleles. We also analysed pituitary glands from individuals with Aβ pathology and found marked Aβ deposition in multiple cases. Experimental seeding of Aβ pathology has been previously demonstrated in primates and transgenic mice by central nervous system or peripheral inoculation with Alzheimer’s disease brain homogenate 6 , 7 , 8 , 9 , 10 , 11 . The marked deposition of parenchymal and vascular Aβ in these relatively young patients with iCJD, in contrast with other prion disease patients and population controls, is consistent with iatrogenic transmission of Aβ pathology in addition to CJD and suggests that healthy exposed individuals may also be at risk of iatrogenic Alzheimer’s disease and cerebral amyloid angiopathy. These findings should also prompt investigation of whether other known iatrogenic routes of prion transmission may also be relevant to Aβ and other proteopathic seeds associated with neurodegenerative and other human diseases. Main Human transmission of prion disease has occurred as a result of a range of medical and surgical procedures worldwide as well as by endocannibalism in Papua New Guinea, with incubation periods that can exceed five decades 12 , 13 . A well-recognized iatrogenic route of transmission was by treatment of persons of short stature with preparations of human growth hormone, extracted from large pools of cadaver-sourced pituitary glands, some of which were inadvertently prion-contaminated. Such treatments commenced in 1958 and ceased in 1985 following the reports of the occurrence of CJD amongst recipients. A review of all 1,848 patients who were treated with cadaveric-derived human growth hormone (c-hGH) in the United Kingdom from 1959 through 1985 found that 38 had developed CJD by the year 2000 with a peak incubation period of 20 years 1 . Multiple preparations using different extraction methods were used over this period and patients received batches from several preparations. One preparation (Wilhelmi) was common to all patients who developed iCJD and size-exclusion chromatography, used in non-Wilhelmi preparation methods, may have reduced prion contamination 1 . As of 2012, a total of 450 cases of iatrogenic CJD have been recognized worldwide after treatment with c-hGH or gonadotropin (226 cases), transplantation of dura mater (228) or cornea (2), and neurosurgery (4) or electroencephalography recording using invasive medical devices (2) 2 . In France, 119/1,880 (6.3%) recipients developed iCJD, in the UK 65/1,800 (3.6%) and in the USA 29/7,700 (0.4%) 2 , 14 . Since 2008, most UK patients with prion disease have been recruited into the National Prion Monitoring Cohort study 5 , including 22 of 24 recent patients with iatrogenic CJD (iCJD) related to treatment with c-hGH over this period, all of whom necessarily have very long incubation periods. Of this group of patients with iCJD, eight patients (referenced no.s 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , Supplementary Information ) aged 36–51 years, with an incubation period from first treatment to onset of 27.9–38.9 years (mean 33 years) and from last treatment to onset of 18.8–30.8 years (mean 25.5 years), underwent autopsy with extensive brain tissue sampling at our hospital. In all eight brain samples we confirmed prion disease with abnormal prion protein labelling of the neuropil, perineuronal network and in most cases microplaques as described previously 15 , 16 , 17 . However, four (no.s 4, 5, 6, 8) of the eight patients with iCJD also showed substantial amyloid-β (Aβ) deposition in the central nervous system parenchyma by histology ( Fig. 1 ) and immunoblotting ( Fig. 2 ). A further two brain samples (no.s 1, 3) had focal Aβ pathology in one of the brain regions; one showed Aβ entrapment in PrP plaques and only one was entirely negative for Aβ. Furthermore, there was widespread cortical and leptomeningeal cerebral Aβ angiopathy (CAA) 3 in three patients (no.s 4, 6, 8) and focal CAA in one patient (no. 5) ( Fig. 1 ). Such pathology is extremely rare in this age range, 10/290 in the equivalent 36–50 year age strata without CJD 18 , P = 0.0002, Fisher’s test. None of our patients with iCJD had pathogenic mutations in the prion protein gene ( PRNP ). We used a custom next generation sequencing panel 4 to exclude mutation in any of 16 other genes associated with early-onset Alzheimer’s disease, CAA, or other neurodegenerative disorders, and none carried APOE ε4 or TREM2 R47H alleles ( Supplementary Table 2 ). Although such observations are unprecedented in our wide experience of human prion diseases, we nevertheless considered whether prion disease itself might predispose to, or accelerate, Aβ pathology, for example by cross-seeding of protein aggregation or overload of clearance mechanisms for misfolded proteins. We therefore compared the Aβ pathology in the iCJD cohort with that of a cohort of 116 patients with other prion diseases who had undergone autopsy: sporadic CJD (sCJD) ( n = 85, age 42–83), variant CJD ( n = 2, age 25 and 36) and inherited prion diseases (IPD) ( n = 29,<|im_end|> <|im_start|>assistant People injected with hormones extracted from cadaver brains in a long-abandoned procedure may have received "seeds" of Alzheimer's disease, said a study Wednesday, urging research into possible risks for "accidental" medical transmission. Published in the journal Nature, the research claims to provide evidence for the hypothesis that the protein fragments which assemble into Alzheimer's-causing plaques, can be passed between humans via diseased tissue transfer. But this did not mean that Alzheimer's was contagious, the study authors and independent commentators stressed. "This relates to a very special situation where people have been injected with essentially extracts of human tissue," said co-author John Collinge of University College London (UCL). "I don't think there needs to be any alarm that we're saying in any way that you can catch Alzheimer's Disease." Further research, however, would be "prudent," he said during a telephone press briefing. "We should think about whether there might be accidental routes in which these diseases might be transmitted by medical or surgical procedures." While conducting research into an unrelated disease, Collinge and a team examined the brains of eight people who had received injections in childhood of a hormone to treat dwarfism. The hormone had been extracted from pituitary glands harvested from thousands of human cadavers. This practice was halted in 1985 when doctors realised it could transmit a variant of Creutzfeldt-Jakob disease (CJD)—the human version of "mad cow" disease. Eight subjects in the study in fact died from this ailment. Too young Collinge and colleagues, "very much to our surprise," found that seven of the eight had brain deposits of Alzheimer's-linked amyloid beta (Abeta) fragments—with four of them having high concentrations. Strikingly the patients were 36-51 years old, whereas such deposits are normally seen in elderly people. "We think the most likely explanation is that the growth hormone preparations with which these people were treated as children, in addition to being contaminated with CJD prions (a different protein type), was probably also contaminated with Abeta seeds." Previous laboratory studies showed that Abeta in Alzheimer's-ridden brain tissue, when transferred to mice or monkeys, could infect the host animal brain—even when it had been injected into their abdomens. "So there are mechanisms to transport these protein seeds to the brain," said Collinge. "We don't know what they are, but clearly it can happen. So that's consistent with these seeds spreading from an intramuscular injection in the children to their brains." Amyloid beta seeds, the team wrote, "are known, like prions, to adhere to metal surfaces and to resist... conventional hospital sterilisation." Experts who were not part of the study underlined there was no evidence of any modern-day medical treatment, including dental surgery or blood transfusions, raising the Alzheimer's risk. Cautious, not concerned For the time being, "this paper should make us cautious but not overly concerned," said Simon Lovestone of the University of Oxford. John Hardy, of UCL, added it seemed "relatively sure" that Abeta can be transferred by injection. "Does it have implications for... blood transfusions: probably not, but this definitely deserves systematic epidemiological investigation," he said via the Science Media Centre (SMC) in London. "Does it suggest Alzheimer's disease is infectious through contact? Almost certainly not." The study authors said the eight fatalities in the study did not have the full-blown features of Alzheimer's—they were missing the "tangles" caused by a different protein called Tau. It was impossible to know whether they would have gone on to develop the disease. "I wouldn't want to cause alarm on this. I don't think anyone should delay or reconsider having surgery on the basis of these data at all," said Collinge. "We've got no evidence that this is a risk to humans, but I think it would be prudent to do some research in this area going forward." Some 30,000 people, mostly children with growth deficiency, received the hormone injections, of whom over 200 developed CJD. The disease has a very long incubation period, and new diagnoses continue to be made. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Topological complex transient electromagnetic fields give access to nontrivial light-matter interactions and provide additional degrees of freedom for information transfer. An important example of such electromagnetic excitations are space-time non-separable single-cycle pulses of toroidal topology, the exact solutions of Maxwell’s equations described by Hellwarth and Nouchi in 1996 and recently observed experimentally. Here we introduce an extended family of electromagnetic excitation, the supertoroidal electromagnetic pulses, in which the Hellwarth-Nouchi pulse is just the simplest member. The supertoroidal pulses exhibit skyrmionic structure of the electromagnetic fields, multiple singularities in the Poynting vector maps and fractal-like distributions of energy backflow. They are of interest for transient light-matter interactions, ultrafast optics, spectroscopy, and toroidal electrodynamics. Introduction Topology of complex electromagnetic fields is attracting growing interest of the photonics and electromagnetics communities 1 , 2 , 3 , 4 , 5 , while topologically structured light fields find applications in super-resolution microscopy 6 , metrology 7 , 8 , and beyond 9 , 10 . For example, the vortex beam with twisted phase, akin to a Mobius strips in phase domain, can carry orbital angular momentum with tunable topological charges enabling advanced applications of optical tweezers, machining, and communications 9 , 10 , 11 , 12 . The complex electromagnetic topological strips, knots, and caustic structures were also proposed as novel information carriers 13 , 14 , 15 , 16 . Recently, skyrmions, as topologically protected quasiparticles in high-energy physics and magnetic materials 17 , were also studied in optical electromagnetic fields. Optical skyrmionic fields were first demonstrated in the evanescent field of a plasmonic surface 18 , 19 , followed by the spin field of confined free-space waves 20 , 21 , Stokes vectors of paraxial vector beams 22 , 23 , 24 , 25 , polarizations in momentum-space 26 , and pseudospins in photonic crystals 27 . The sophisticated vector topology of optical skyrmions holds potential for applications in ultrafast nanometric metrology 28 , deeply subwavelength microscopy 20 , and topological Hall devices 27 . While a large body of work on topological properties of structured continuous light beams may be found in literatures, works on the topology of the time-dependent electromagnetic excitations and pulses only start to appear. For instance, the “Flying Doughnut” pulses, or toroidal light pulses (TLPs) first described in 1996 by Hellwarth and Nouchi 29 , with unique spatiotemporal topology predicted recently 30 , have only very recently observed experimentally 31 . Fueled by a combination of advances in ultrafast lasers and metamaterials in our ability to control the spatiotemporal structure of light 32 , 33 together with the introduction of experimental and theoretical pulse characterization methods 34 , 35 , 36 , 37 , TLPs are attracting growing attention. Indeed, TLPs exhibit their complex topological structure with vector singularities and interact with matter through coupling to toroidal and anapole localized modes 38 , 39 , 40 , 41 . However, while higher order, supertoroidal modes in matter have been introduced in the form of the fractal iterations of solenoidal currents 42 , 43 , 44 , 45 , 46 , 47 , generalizations of free-space propagating toroidal pulses have not been considered to date. In this paper, we report that the Hellwarth and Nouchi pulses, are, in fact, the simplest example of an extended family of pulses that we will call supertoroidal light pulses (STLPs). We will show that supertoroidal light pulses introduced here exhibit complex topological structures that can be controlled by a single numerical parameter. The STLP display skyrmion-like arrangements of the transient electromagnetic fields organized in a fractal-like, self-affine manner, while the Poynting vector of the pulses feature singularities linked to the multiple energy backflow zones. Results Supertoroidal electromagnetic pulses Following Ziolkowski, localized finite-energy pulses can be obtained as superpositions of “electromagnetic directed-energy pulse trains” 48 . A special case of the localized finite-energy pulses was investigated by Hellwarth and Nouchi 29 , who found the closed-form expression describing a single-cycle finite energy electromagnetic excitation with toroidal topology obtained from a scalar generating function f ( r , t ) that satisfies the wave equation \$({\\nabla }^{2}-\\frac{1}{{c}^{2}}\\frac{{\\partial }^{2}}{\\partial {t}^{2}})f\\left({{{{{\\bf{r}}}}}},t\\right)=0\$ , where r = ( r , θ , z ) are cylindrical coordinates, t is time, \$c=1/\\sqrt{{\\varepsilon }_{0}{\\mu }_{0}}\$ is the speed of light, and the ε 0 and μ 0 are the permittivity and permeability of medium. Then, the exact solution of f ( r , t ) can be given by the modified power spectrum method 29 , 48 , as \$f({{{{{\\bf{r}}}}}},t)={f}_{0}/\\left[({q}_{1}+i\\tau ){(s+{q}_{2})}^{\\alpha }\\right]\$ , where f 0 is a normalizing constant, s = r 2 /( q 1 + i τ ) − i σ , τ = z − c t , σ = z + c t , q 1 and q 2 are parameters with dimensions of length and act as effective wavelength and Rayleigh range under the paraxial limit, while α is a real dimensionless parameter that must satisfy α ≥ 1 to ensure finite energy solutions. In particular, the parameter α is related to the energy confinement of the pulse with α < 1 resulting in pulses of infinite energy, such as planar waves and cylindrical waves, while α ≥ 1 leads to finite-energy pulses. Next, transverse electric (TE) and transverse magnetic (TM) solutions are readily obtained by using Hertz potentials. The electromagnetic fields for the TE solution can be derived by the potential \${{{{{\\bf{A}}}}}}({{{{{\\bf{r}}}}}},t)={\\mu }_{0}{{{{{\\boldsymbol{\\nabla }}}}}}\\times \\widehat{{{{{{\\bf{z}}}}}}}f({{{{{\\bf{r}}}}}},t)\$ as \${{{{{\\bf{E}}}}}}({{{{{\\bf{r}}}}}},t)=-{\\mu }_{0}\\frac{\\partial }{\\partial t}{{{{{\\boldsymbol{\\nabla }}}}}}\\times {{{{{\\bf{A}}}}}}\$ and H ( r , t ) = ∇ × ( ∇ × A ) 29 , 48 . Finally assuming α = 1, the electromagnetic fields of the TLP are described by 29 : $${E}_{\\theta }=-4i{f}_{0}\\sqrt{\\frac{{\\mu }_{0}}{{\\varepsilon }_{0}}}\\frac{r({q}_{1}+{q}_{2}-2ict)}{{\\left[{r}^{2}+\\left({q}_{1}+i\\tau \\right)\\left({q}_{2}-i\\sigma \\right)\\right]}^{3}}$$ (1) $${H}_{r}=4i{f}_{0}\\frac{r({q}_{2}-{q}_{1}-2iz)}{{\\left[{r}^{2}+\\left({q}_{1}+i\\tau \\right)\\left({q}_{2}-i\\sigma \\right)\\right]}^{3}}$$ (2) $${H}_{z}=-4{f}_{0}\\frac{{r}^{2}-\\left({q}_{1}+i\\tau \\right)\\left({q}_{2}-i\\sigma \\right)}{{\\left[{r}^{2}+\\left({q}_{1}+i\\tau \\right)\\left({q}_{2}-i\\sigma \\right)\\right]}^{3}}$$ (3) where E θ represents the azimuthally directed component of electric field, and H r and H z are the radially and longitudinally directed components of magnetic field, respectively. Note that the TE mode field does not possess other", "role": "user" }, { "content": "Topology in optics and photonics has been a hot topic since 1890 where singularities in electromagnetic fields have been considered. The recent award of the Nobel prize for topology developments in condensed matter physics has led to renewed surge in topology in optics with most recent developments in implementing condensed matter particle-like topological structures in photonics. Recently, topological photonics, especially the topological electromagnetic pulses, hold promise for nontrivial wave-matter interactions and provide additional degrees of freedom for information and energy transfer. However, to date the topology of ultrafast transient electromagnetic pulses had been largely unexplored. In their paper Nat. Commun., physicists in the UK and Singapore report a new family of electromagnetic pulses, the exact solutions of Maxwell's equation with toroidal topology, in which topological complexity can be continuously controlled, namely supertoroidal topology. The electromagnetic fields in such supertoroidal pulses have skyrmionic structures as they propagate in free space with the speed of light. Skyrmions, sophisticated topological particles originally proposed as a unified model of the nucleon by Tony Skyrme in 1962, behave like nanoscale magnetic vortices with spectacular textures. They have been widely studied in many condensed matter systems, including chiral magnets and liquid crystals, as nontrivial excitations showing great importance for information storing and transferring. If skyrmions can fly, open up infinite possibilities for the next generation of informatics revolution. \"This is the first know examples of propagating skyrmions,\" says Prof. Nikolay Zheludev, the project supervisor, \"the fundamental topological constructs previously observed as spin formations in solids and localized electromagnetic excitations in the nearfield of metamaterial patterns.\" The supertoroidal pulse is as a generalization of the so-called \"Flying Doughnut,\" a toroidal single-cycle pulse with space-time non-separable structure with links to vector singularities and non-radiating anapole excitations. The supertoroidal pulse has increasingly complex fractal-like toroidal topological structures, exhibiting electromagnetic field configurations with matryoshka-like singular shells, skyrmionic structures of various skyrmion numbers, and multiple singularities in the Poynting vector field accompanied by multi-layer energy backflow effects. And the topological complexity can be controlled by increasing a supertoroidal order of the pulse increases. These results put forward supertoroidal pulses as a playground for the study of topological field configurations and their dynamics. The topological features of the supertoroidal pulses presented here provide additional degrees of freedom that could find applications in a number of fields, such as information encoding/decoding schemes involving structured light, optical trapping, manufacturing by light, and particle acceleration. \"We believe this is the first time that the skyrmionic structure is proposed in ultrafast structured pulses, and the multiple skyrmionic structure with various textures exist in the instantaneous electromagnetic field of a supertoroidal pulse. Such photonics skyrmionic structures harness intriguing sharp spatial features, promising the potential applications in high-precision metrology and superresolution imaging,\" says Dr. Yijie Shen, the lead author of the paper. This work opens many intriguing opportunities for the study of light-matter interaction, ultrafast optics, and topological optics with supertoroidal light pulses (e.g. coupling to electromagnetic anapoles and localized skyrmions) and their applications in superresolution metrology and imaging, information and energy transfer. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Topological complex transient electromagnetic fields give access to nontrivial light-matter interactions and provide additional degrees of freedom for information transfer. An important example of such electromagnetic excitations are space-time non-separable single-cycle pulses of toroidal topology, the exact solutions of Maxwell’s equations described by Hellwarth and Nouchi in 1996 and recently observed experimentally. Here we introduce an extended family of electromagnetic excitation, the supertoroidal electromagnetic pulses, in which the Hellwarth-Nouchi pulse is just the simplest member. The supertoroidal pulses exhibit skyrmionic structure of the electromagnetic fields, multiple singularities in the Poynting vector maps and fractal-like distributions of energy backflow. They are of interest for transient light-matter interactions, ultrafast optics, spectroscopy, and toroidal electrodynamics. Introduction Topology of complex electromagnetic fields is attracting growing interest of the photonics and electromagnetics communities 1 , 2 , 3 , 4 , 5 , while topologically structured light fields find applications in super-resolution microscopy 6 , metrology 7 , 8 , and beyond 9 , 10 . For example, the vortex beam with twisted phase, akin to a Mobius strips in phase domain, can carry orbital angular momentum with tunable topological charges enabling advanced applications of optical tweezers, machining, and communications 9 , 10 , 11 , 12 . The complex electromagnetic topological strips, knots, and caustic structures were also proposed as novel information carriers 13 , 14 , 15 , 16 . Recently, skyrmions, as topologically protected quasiparticles in high-energy physics and magnetic materials 17 , were also studied in optical electromagnetic fields. Optical skyrmionic fields were first demonstrated in the evanescent field of a plasmonic surface 18 , 19 , followed by the spin field of confined free-space waves 20 , 21 , Stokes vectors of paraxial vector beams 22 , 23 , 24 , 25 , polarizations in momentum-space 26 , and pseudospins in photonic crystals 27 . The sophisticated vector topology of optical skyrmions holds potential for applications in ultrafast nanometric metrology 28 , deeply subwavelength microscopy 20 , and topological Hall devices 27 . While a large body of work on topological properties of structured continuous light beams may be found in literatures, works on the topology of the time-dependent electromagnetic excitations and pulses only start to appear. For instance, the “Flying Doughnut” pulses, or toroidal light pulses (TLPs) first described in 1996 by Hellwarth and Nouchi 29 , with unique spatiotemporal topology predicted recently 30 , have only very recently observed experimentally 31 . Fueled by a combination of advances in ultrafast lasers and metamaterials in our ability to control the spatiotemporal structure of light 32 , 33 together with the introduction of experimental and theoretical pulse characterization methods 34 , 35 , 36 , 37 , TLPs are attracting growing attention. Indeed, TLPs exhibit their complex topological structure with vector singularities and interact with matter through coupling to toroidal and anapole localized modes 38 , 39 , 40 , 41 . However, while higher order, supertoroidal modes in matter have been introduced in the form of the fractal iterations of solenoidal currents 42 , 43 , 44 , 45 , 46 , 47 , generalizations of free-space propagating toroidal pulses have not been considered to date. In this paper, we report that the Hellwarth and Nouchi pulses, are, in fact, the simplest example of an extended family of pulses that we will call supertoroidal light pulses (STLPs). We will show that supertoroidal light pulses introduced here exhibit complex topological structures that can be controlled by a single numerical parameter. The STLP display skyrmion-like arrangements of the transient electromagnetic fields organized in a fractal-like, self-affine manner, while the Poynting vector of the pulses feature singularities linked to the multiple energy backflow zones. Results Supertoroidal electromagnetic pulses Following Ziolkowski, localized finite-energy pulses can be obtained as superpositions of “electromagnetic directed-energy pulse trains” 48 . A special case of the localized finite-energy pulses was investigated by Hellwarth and Nouchi 29 , who found the closed-form expression describing a single-cycle finite energy electromagnetic excitation with toroidal topology obtained from a scalar generating function f ( r , t ) that satisfies the wave equation $({\nabla }^{2}-\frac{1}{{c}^{2}}\frac{{\partial }^{2}}{\partial {t}^{2}})f\left({{{{{\bf{r}}}}}},t\right)=0$ , where r = ( r , θ , z ) are cylindrical coordinates, t is time, $c=1/\sqrt{{\varepsilon }_{0}{\mu }_{0}}$ is the speed of light, and the ε 0 and μ 0 are the permittivity and permeability of medium. Then, the exact solution of f ( r , t ) can be given by the modified power spectrum method 29 , 48 , as $f({{{{{\bf{r}}}}}},t)={f}_{0}/\left[({q}_{1}+i\tau ){(s+{q}_{2})}^{\alpha }\right]$ , where f 0 is a normalizing constant, s = r 2 /( q 1 + i τ ) − i σ , τ = z − c t , σ = z + c t , q 1 and q 2 are parameters with dimensions of length and act as effective wavelength and Rayleigh range under the paraxial limit, while α is a real dimensionless parameter that must satisfy α ≥ 1 to ensure finite energy solutions. In particular, the parameter α is related to the energy confinement of the pulse with α < 1 resulting in pulses of infinite energy, such as planar waves and cylindrical waves, while α ≥ 1 leads to finite-energy pulses. Next, transverse electric (TE) and transverse magnetic (TM) solutions are readily obtained by using Hertz potentials. The electromagnetic fields for the TE solution can be derived by the potential ${{{{{\bf{A}}}}}}({{{{{\bf{r}}}}}},t)={\mu }_{0}{{{{{\boldsymbol{\nabla }}}}}}\times \widehat{{{{{{\bf{z}}}}}}}f({{{{{\bf{r}}}}}},t)$ as ${{{{{\bf{E}}}}}}({{{{{\bf{r}}}}}},t)=-{\mu }_{0}\frac{\partial }{\partial t}{{{{{\boldsymbol{\nabla }}}}}}\times {{{{{\bf{A}}}}}}$ and H ( r , t ) = ∇ × ( ∇ × A ) 29 , 48 . Finally assuming α = 1, the electromagnetic fields of the TLP are described by 29 : $${E}_{\theta }=-4i{f}_{0}\sqrt{\frac{{\mu }_{0}}{{\varepsilon }_{0}}}\frac{r({q}_{1}+{q}_{2}-2ict)}{{\left[{r}^{2}+\left({q}_{1}+i\tau \right)\left({q}_{2}-i\sigma \right)\right]}^{3}}$$ (1) $${H}_{r}=4i{f}_{0}\frac{r({q}_{2}-{q}_{1}-2iz)}{{\left[{r}^{2}+\left({q}_{1}+i\tau \right)\left({q}_{2}-i\sigma \right)\right]}^{3}}$$ (2) $${H}_{z}=-4{f}_{0}\frac{{r}^{2}-\left({q}_{1}+i\tau \right)\left({q}_{2}-i\sigma \right)}{{\left[{r}^{2}+\left({q}_{1}+i\tau \right)\left({q}_{2}-i\sigma \right)\right]}^{3}}$$ (3) where E θ represents the azimuthally directed component of electric field, and H r and H z are the radially and longitudinally directed components of magnetic field, respectively. Note that the TE mode field does not possess other<|im_end|> <|im_start|>assistant Topology in optics and photonics has been a hot topic since 1890 where singularities in electromagnetic fields have been considered. The recent award of the Nobel prize for topology developments in condensed matter physics has led to renewed surge in topology in optics with most recent developments in implementing condensed matter particle-like topological structures in photonics. Recently, topological photonics, especially the topological electromagnetic pulses, hold promise for nontrivial wave-matter interactions and provide additional degrees of freedom for information and energy transfer. However, to date the topology of ultrafast transient electromagnetic pulses had been largely unexplored. In their paper Nat. Commun., physicists in the UK and Singapore report a new family of electromagnetic pulses, the exact solutions of Maxwell's equation with toroidal topology, in which topological complexity can be continuously controlled, namely supertoroidal topology. The electromagnetic fields in such supertoroidal pulses have skyrmionic structures as they propagate in free space with the speed of light. Skyrmions, sophisticated topological particles originally proposed as a unified model of the nucleon by Tony Skyrme in 1962, behave like nanoscale magnetic vortices with spectacular textures. They have been widely studied in many condensed matter systems, including chiral magnets and liquid crystals, as nontrivial excitations showing great importance for information storing and transferring. If skyrmions can fly, open up infinite possibilities for the next generation of informatics revolution. "This is the first know examples of propagating skyrmions," says Prof. Nikolay Zheludev, the project supervisor, "the fundamental topological constructs previously observed as spin formations in solids and localized electromagnetic excitations in the nearfield of metamaterial patterns." The supertoroidal pulse is as a generalization of the so-called "Flying Doughnut," a toroidal single-cycle pulse with space-time non-separable structure with links to vector singularities and non-radiating anapole excitations. The supertoroidal pulse has increasingly complex fractal-like toroidal topological structures, exhibiting electromagnetic field configurations with matryoshka-like singular shells, skyrmionic structures of various skyrmion numbers, and multiple singularities in the Poynting vector field accompanied by multi-layer energy backflow effects. And the topological complexity can be controlled by increasing a supertoroidal order of the pulse increases. These results put forward supertoroidal pulses as a playground for the study of topological field configurations and their dynamics. The topological features of the supertoroidal pulses presented here provide additional degrees of freedom that could find applications in a number of fields, such as information encoding/decoding schemes involving structured light, optical trapping, manufacturing by light, and particle acceleration. "We believe this is the first time that the skyrmionic structure is proposed in ultrafast structured pulses, and the multiple skyrmionic structure with various textures exist in the instantaneous electromagnetic field of a supertoroidal pulse. Such photonics skyrmionic structures harness intriguing sharp spatial features, promising the potential applications in high-precision metrology and superresolution imaging," says Dr. Yijie Shen, the lead author of the paper. This work opens many intriguing opportunities for the study of light-matter interaction, ultrafast optics, and topological optics with supertoroidal light pulses (e.g. coupling to electromagnetic anapoles and localized skyrmions) and their applications in superresolution metrology and imaging, information and energy transfer. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Two-dimensional (2D) boron (that is, borophene) was recently synthesized following theoretical predictions 1 , 2 , 3 , 4 , 5 . Its metallic nature and high in-plane anisotropy combine many of the desirable attributes of graphene 6 and monolayer black phosphorus 7 . As a synthetic 2D material, its structural properties cannot be deduced from bulk boron, which implies that the intrinsic defects of borophene remain unexplored. Here we investigate borophene line defects at the atomic scale with ultrahigh vacuum (UHV) scanning tunnelling microscopy/spectroscopy (STM/STS) and density functional theory (DFT). Under suitable growth conditions, borophene phases that correspond to the v 1/6 and v 1/5 models are found to intermix and accommodate line defects in each other with structures that match the constituent units of the other phase. These line defects energetically favour spatially periodic self-assembly that gives rise to new borophene phases, which ultimately blurs the distinction between borophene crystals and defects. This phenomenon is unique to borophene as a result of its high in-plane anisotropy and energetically and structurally similar polymorphs. Low-temperature measurements further reveal subtle electronic features that are consistent with a charge density wave (CDW), which are modulated by line defects. This atomic-level understanding is likely to inform ongoing efforts to devise and realize applications based on borophene. Main Direct synthetic pathways in the atomically thin limit enable 2D materials that are not layered in the bulk 8 . For example, atomically thin phases of boron, collectively referred to as borophene 1 , 2 , have been realized experimentally. Theoretical calculations predict multiple possible borophene polymorphs that possess similar formation energies, but different arrangements of hollow hexagons (HHs) in an otherwise triangular lattice 3 , 4 , 5 . Indeed, experimental studies have revealed multiple borophene phases whose relative occurrence depends on the growth conditions 1 , 2 . The growth substrate plays a major role in stabilizing borophene and determining its structural properties, such as substrate-induced undulations 9 and the shift of the structural ground state when grown on substrates compared with vacuum 3 . Practically, borophene stability is an important factor towards realistic applications, which include the transfer of borophene onto other substrates. Theoretically, both dynamic stability 10 and instability 11 of free-standing borophene, as indicated by the absence and presence of imaginary portions of the phonon spectrum, respectively, have been reported. Compared with semiconducting bulk boron, borophene is an anisotropic metal 1 , 2 , 9 , 12 with unique surface chemistry that strongly influences molecular self-assembly 13 . Moreover, experimental evidence for massless Dirac fermions 14 and theoretically predicted superconductivity 15 expand its desirable characteristics, which makes borophene a highly promising platform for novel material physics with potential utility in next-generation electronic technologies. Although most theoretical predictions have assumed perfect crystalline structures, defects are inevitable in as-grown borophene, which necessitates atomic-scale studies of defects. Although extensive research has explored point and line defects in graphene 16 , 17 and transition metal dichalcogenide monolayers 18 , 19 , 20 , borophene defects remain essentially unexplored. Here we perform an atomically resolved study of borophene under growth conditions that concurrently yield multiple borophene phases and thus relatively high concentrations of line defects. Figure 1a shows an STM image of submonolayer borophene after the deposition of boron on Ag(111) in UHV. The bright dots correspond to small boron particles that are typically present as minority species after borophene growth 1 , 2 , 13 . Due to the convolution of the topographic and electronic structure in STM imaging, the borophene islands appear as depressions under these imaging conditions, consistent with previous reports 1 , 2 , 13 . Atomically thin island structures have also been observed for the submonolayer coverage of metals deposited on surfaces 21 and nitridized metal surfaces 22 . However, those islands are either alloys with the substrate or covalently bonded to the substrates, which is distinct from the weaker non-covalent interaction between borophene and the silver substrate. The borophene islands of the same region are more clearly distinguished in the STS (d I /d V ) map (Fig. 1b ) as brighter domains. At substrate growth temperatures between 440 and 470 °C, two distinct borophene phases are consistently observed, and correspond to the v 1/6 and v 1/5 structures with HH concentrations of v = 1/6 and 1/5, respectively ( v = n / N , where n is the number of HHs in an otherwise triangular lattice with N lattice sites) 1 , 2 , 13 . The temperature dependence of borophene growth over a wider temperature window is given in Supplementary Fig. 1 , which shows a gradual transition from the v 1/6 to the v 1/5 phases of borophene as the growth temperature is increased from 350 to 500 °C. DFT calculations show similar chemical potentials and thus similar thermal stabilities of these two phases ( v 1/6 , −6.359 eV atom –1 ; v 1/5 , −6.357 eV atom –1 (Supplementary Fig. 2 )), in agreement with previous studies 3 , 4 . Fig. 1: Growth of pristine borophene on Ag(111) thin films. a , b , Large-scale STM topography ( a ) and STS map ( b ) of the density of states (DOS) of borophene grown on Ag(111). c , d , Atomic-resolution STM images of v 1/6 ( c ) and v 1/5 ( d ) borophene sheets with inter row spacings of 0.54 ± 0.03 nm and 0.45 ± 0.02 nm, respectively. e , Six STS spectra taken on different positions of the v 1/6 and v 1/5 borophene sheets show a metallic behaviour. f , g , In situ XPS spectra of the B 1 s ( f ) and O 1 s ( g ) core levels indicate pristine borophene growth. STM bias voltages ( V s ) = –1 V in a and b , –0.35 V in c and –1.2 V in d . a.u., arbitrary units. Full size image Atomic-scale STM images of the two phases", "role": "user" }, { "content": "Borophene, the atomically flat form of boron with unique properties, is even more interesting when different forms of the material mix and mingle, according to scientists at Rice and Northwestern universities. Scientists at the institutions made and analyzed borophene with different lattice arrangements and discovered how amenable the varied structures are to combining into new crystal-like forms. These, they indicated, have properties electronics manufacturers may wish to explore. The research led by Rice materials theorist Boris Yakobson and Northwestern materials scientist Mark Hersam appears in Nature Materials. Borophene differs from graphene and other 2-D materials in an important way: It doesn't appear in nature. When graphene was discovered, it was famously yanked from a piece of graphite with Scotch tape. But semiconducting bulk boron doesn't have layers, so all borophene is synthetic. Also unlike graphene, in which atoms connect to form chicken wire-like hexagons, borophene forms as linked triangles. Periodically, atoms go missing from the grid and leave hexagonal vacancies. The labs investigated forms of borophene with \"hollow hexagon\" concentrations of one per every five triangles and one per every six in the lattice. Scanning tunneling electron microscope images of line defects in 1-to-6 and 1-to-5 borophene, indicated by blue and red arrowheads, respectively, show how the defects align in a way that preserves the synthetic material's metallic nature. Scientists at Rice and Northwestern universities made the first detailed analysis of ordered defect structures in borophene. Credit: Hersam Research Group/Northwestern University These are the most common phases the Northwestern lab observed when it created borophene on a silver substrate through atomic boron deposition in an ultrahigh vacuum, according to the researchers, but \"perfect\" borophene arrays weren't the target of the study. The lab found that at temperatures between 440 and 470 degrees Celsius (824-878 degrees Fahrenheit), both 1-to-5 and 1-to-6 phases grew simultaneously on the silver substrate, which acts as a template that guides the deposition of atoms into aligned phases. The labs' interest was heightened by what happened where these domains met. Unlike what they had observed in graphene, the atoms easily accommodated each other at the boundaries and adopted the structures of their neighbors. These boundary adjustments gave rise to more exotic—but still metallic—forms of borophene, with ratios such as 4-to-21 and 7-to-36 appearing among the parallel phases. \"In graphene, these boundaries would be disordered structures, but in borophene the line defects, in effect, are a perfect structure for each other,\" said Rice graduate student Luqing Wang, who led a theoretical analysis of atom-level energies to explain the observations. \"The intermixing between the phases is very different from what we see in other 2-D materials.\" \"While we did expect some intermixing between the 1-to-5 and 1-to-6 phases, the seamless alignment and ordering into periodic structures was surprising,\" Hersam said. \"In the two-dimensional limit, boron has proven to be an exceptionally rich and interesting materials system.\" A scanning electron microscope image (top) shows two periodic assemblies of borophene, a synthetic, two-dimensional array of boron atoms, that join at a line defect. Computational models in the middle and bottom images correspond to the regions, with 1-to-6 borophene in red and 1-to-5 in blue. Researchers at Rice and Northwestern universities determined that phases of borophene line up in such a way that the material's conductive, metallic nature is maintained. Credit: Luqing Wang/Rice University Wang's density functional theory calculations revealed the metallic nature of the line defects; this implied that unlike insulating defects in otherwise metallic graphene, they have minimal impact on the material's electronic properties at room temperature. At low temperature, the material shows evidence of a charge density wave, a highly ordered flow of electrons. Theoretical calculations also suggested subtle differences in stiffness, thermal conductivity and electrochemical properties among borophene phases, which also suggested the material can be tuned for applications. \"The unique polymorphisms of borophene are on full display in this study,\" Yakobson said. \"This suggests intriguing interplay in the material's electronic structure through charge density waves, which may lead to tantalizing switchable electronics.\" \"As an atomically thin material, borophene has properties that should be a function of the substrate, neighboring materials and surface chemistry,\" Hersam said. \"We hope to gain further control over its properties through chemical functionalization and/or integration with other materials into heterostructures.\" Yakobson and Hersam also co-authored a recent Nature Nanotechnology perspective about \"the lightest 2-D metal.\" In that piece, the authors suggested borophene may be ideal for flexible and transparent electronic interconnects, electrodes and displays. It could also be suitable for superconducting quantum interference devices and, when stacked, for hydrogen storage and battery applications. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Two-dimensional (2D) boron (that is, borophene) was recently synthesized following theoretical predictions 1 , 2 , 3 , 4 , 5 . Its metallic nature and high in-plane anisotropy combine many of the desirable attributes of graphene 6 and monolayer black phosphorus 7 . As a synthetic 2D material, its structural properties cannot be deduced from bulk boron, which implies that the intrinsic defects of borophene remain unexplored. Here we investigate borophene line defects at the atomic scale with ultrahigh vacuum (UHV) scanning tunnelling microscopy/spectroscopy (STM/STS) and density functional theory (DFT). Under suitable growth conditions, borophene phases that correspond to the v 1/6 and v 1/5 models are found to intermix and accommodate line defects in each other with structures that match the constituent units of the other phase. These line defects energetically favour spatially periodic self-assembly that gives rise to new borophene phases, which ultimately blurs the distinction between borophene crystals and defects. This phenomenon is unique to borophene as a result of its high in-plane anisotropy and energetically and structurally similar polymorphs. Low-temperature measurements further reveal subtle electronic features that are consistent with a charge density wave (CDW), which are modulated by line defects. This atomic-level understanding is likely to inform ongoing efforts to devise and realize applications based on borophene. Main Direct synthetic pathways in the atomically thin limit enable 2D materials that are not layered in the bulk 8 . For example, atomically thin phases of boron, collectively referred to as borophene 1 , 2 , have been realized experimentally. Theoretical calculations predict multiple possible borophene polymorphs that possess similar formation energies, but different arrangements of hollow hexagons (HHs) in an otherwise triangular lattice 3 , 4 , 5 . Indeed, experimental studies have revealed multiple borophene phases whose relative occurrence depends on the growth conditions 1 , 2 . The growth substrate plays a major role in stabilizing borophene and determining its structural properties, such as substrate-induced undulations 9 and the shift of the structural ground state when grown on substrates compared with vacuum 3 . Practically, borophene stability is an important factor towards realistic applications, which include the transfer of borophene onto other substrates. Theoretically, both dynamic stability 10 and instability 11 of free-standing borophene, as indicated by the absence and presence of imaginary portions of the phonon spectrum, respectively, have been reported. Compared with semiconducting bulk boron, borophene is an anisotropic metal 1 , 2 , 9 , 12 with unique surface chemistry that strongly influences molecular self-assembly 13 . Moreover, experimental evidence for massless Dirac fermions 14 and theoretically predicted superconductivity 15 expand its desirable characteristics, which makes borophene a highly promising platform for novel material physics with potential utility in next-generation electronic technologies. Although most theoretical predictions have assumed perfect crystalline structures, defects are inevitable in as-grown borophene, which necessitates atomic-scale studies of defects. Although extensive research has explored point and line defects in graphene 16 , 17 and transition metal dichalcogenide monolayers 18 , 19 , 20 , borophene defects remain essentially unexplored. Here we perform an atomically resolved study of borophene under growth conditions that concurrently yield multiple borophene phases and thus relatively high concentrations of line defects. Figure 1a shows an STM image of submonolayer borophene after the deposition of boron on Ag(111) in UHV. The bright dots correspond to small boron particles that are typically present as minority species after borophene growth 1 , 2 , 13 . Due to the convolution of the topographic and electronic structure in STM imaging, the borophene islands appear as depressions under these imaging conditions, consistent with previous reports 1 , 2 , 13 . Atomically thin island structures have also been observed for the submonolayer coverage of metals deposited on surfaces 21 and nitridized metal surfaces 22 . However, those islands are either alloys with the substrate or covalently bonded to the substrates, which is distinct from the weaker non-covalent interaction between borophene and the silver substrate. The borophene islands of the same region are more clearly distinguished in the STS (d I /d V ) map (Fig. 1b ) as brighter domains. At substrate growth temperatures between 440 and 470 °C, two distinct borophene phases are consistently observed, and correspond to the v 1/6 and v 1/5 structures with HH concentrations of v = 1/6 and 1/5, respectively ( v = n / N , where n is the number of HHs in an otherwise triangular lattice with N lattice sites) 1 , 2 , 13 . The temperature dependence of borophene growth over a wider temperature window is given in Supplementary Fig. 1 , which shows a gradual transition from the v 1/6 to the v 1/5 phases of borophene as the growth temperature is increased from 350 to 500 °C. DFT calculations show similar chemical potentials and thus similar thermal stabilities of these two phases ( v 1/6 , −6.359 eV atom –1 ; v 1/5 , −6.357 eV atom –1 (Supplementary Fig. 2 )), in agreement with previous studies 3 , 4 . Fig. 1: Growth of pristine borophene on Ag(111) thin films. a , b , Large-scale STM topography ( a ) and STS map ( b ) of the density of states (DOS) of borophene grown on Ag(111). c , d , Atomic-resolution STM images of v 1/6 ( c ) and v 1/5 ( d ) borophene sheets with inter row spacings of 0.54 ± 0.03 nm and 0.45 ± 0.02 nm, respectively. e , Six STS spectra taken on different positions of the v 1/6 and v 1/5 borophene sheets show a metallic behaviour. f , g , In situ XPS spectra of the B 1 s ( f ) and O 1 s ( g ) core levels indicate pristine borophene growth. STM bias voltages ( V s ) = –1 V in a and b , –0.35 V in c and –1.2 V in d . a.u., arbitrary units. Full size image Atomic-scale STM images of the two phases<|im_end|> <|im_start|>assistant Borophene, the atomically flat form of boron with unique properties, is even more interesting when different forms of the material mix and mingle, according to scientists at Rice and Northwestern universities. Scientists at the institutions made and analyzed borophene with different lattice arrangements and discovered how amenable the varied structures are to combining into new crystal-like forms. These, they indicated, have properties electronics manufacturers may wish to explore. The research led by Rice materials theorist Boris Yakobson and Northwestern materials scientist Mark Hersam appears in Nature Materials. Borophene differs from graphene and other 2-D materials in an important way: It doesn't appear in nature. When graphene was discovered, it was famously yanked from a piece of graphite with Scotch tape. But semiconducting bulk boron doesn't have layers, so all borophene is synthetic. Also unlike graphene, in which atoms connect to form chicken wire-like hexagons, borophene forms as linked triangles. Periodically, atoms go missing from the grid and leave hexagonal vacancies. The labs investigated forms of borophene with "hollow hexagon" concentrations of one per every five triangles and one per every six in the lattice. Scanning tunneling electron microscope images of line defects in 1-to-6 and 1-to-5 borophene, indicated by blue and red arrowheads, respectively, show how the defects align in a way that preserves the synthetic material's metallic nature. Scientists at Rice and Northwestern universities made the first detailed analysis of ordered defect structures in borophene. Credit: Hersam Research Group/Northwestern University These are the most common phases the Northwestern lab observed when it created borophene on a silver substrate through atomic boron deposition in an ultrahigh vacuum, according to the researchers, but "perfect" borophene arrays weren't the target of the study. The lab found that at temperatures between 440 and 470 degrees Celsius (824-878 degrees Fahrenheit), both 1-to-5 and 1-to-6 phases grew simultaneously on the silver substrate, which acts as a template that guides the deposition of atoms into aligned phases. The labs' interest was heightened by what happened where these domains met. Unlike what they had observed in graphene, the atoms easily accommodated each other at the boundaries and adopted the structures of their neighbors. These boundary adjustments gave rise to more exotic—but still metallic—forms of borophene, with ratios such as 4-to-21 and 7-to-36 appearing among the parallel phases. "In graphene, these boundaries would be disordered structures, but in borophene the line defects, in effect, are a perfect structure for each other," said Rice graduate student Luqing Wang, who led a theoretical analysis of atom-level energies to explain the observations. "The intermixing between the phases is very different from what we see in other 2-D materials." "While we did expect some intermixing between the 1-to-5 and 1-to-6 phases, the seamless alignment and ordering into periodic structures was surprising," Hersam said. "In the two-dimensional limit, boron has proven to be an exceptionally rich and interesting materials system." A scanning electron microscope image (top) shows two periodic assemblies of borophene, a synthetic, two-dimensional array of boron atoms, that join at a line defect. Computational models in the middle and bottom images correspond to the regions, with 1-to-6 borophene in red and 1-to-5 in blue. Researchers at Rice and Northwestern universities determined that phases of borophene line up in such a way that the material's conductive, metallic nature is maintained. Credit: Luqing Wang/Rice University Wang's density functional theory calculations revealed the metallic nature of the line defects; this implied that unlike insulating defects in otherwise metallic graphene, they have minimal impact on the material's electronic properties at room temperature. At low temperature, the material shows evidence of a charge density wave, a highly ordered flow of electrons. Theoretical calculations also suggested subtle differences in stiffness, thermal conductivity and electrochemical properties among borophene phases, which also suggested the material can be tuned for applications. "The unique polymorphisms of borophene are on full display in this study," Yakobson said. "This suggests intriguing interplay in the material's electronic structure through charge density waves, which may lead to tantalizing switchable electronics." "As an atomically thin material, borophene has properties that should be a function of the substrate, neighboring materials and surface chemistry," Hersam said. "We hope to gain further control over its properties through chemical functionalization and/or integration with other materials into heterostructures." Yakobson and Hersam also co-authored a recent Nature Nanotechnology perspective about "the lightest 2-D metal." In that piece, the authors suggested borophene may be ideal for flexible and transparent electronic interconnects, electrodes and displays. It could also be suitable for superconducting quantum interference devices and, when stacked, for hydrogen storage and battery applications. <|im_end|>

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4701, 7, 5037, 8, 15792, 12631, 13, 264, 1174, 293, 1174, 20902, 13230, 48273, 1948, 5814, 320, 264, 883, 323, 4015, 50, 2472, 320, 293, 883, 315, 279, 17915, 315, 5415, 320, 35, 3204, 8, 315, 32732, 5237, 1994, 15042, 389, 4701, 7, 5037, 570, 272, 1174, 294, 1174, 31416, 64036, 48273, 5448, 315, 348, 220, 16, 14, 21, 320, 272, 883, 323, 348, 220, 16, 14, 20, 320, 294, 883, 32732, 5237, 1994, 25112, 449, 958, 2872, 100108, 826, 315, 220, 15, 13, 4370, 20903, 220, 15, 13, 2839, 26807, 323, 220, 15, 13, 1774, 20903, 220, 15, 13, 2437, 26807, 11, 15947, 13, 384, 1174, 19198, 4015, 50, 63697, 4529, 389, 2204, 10093, 315, 279, 348, 220, 16, 14, 21, 323, 348, 220, 16, 14, 20, 32732, 5237, 1994, 25112, 1501, 264, 46258, 17432, 13, 282, 1174, 342, 1174, 763, 10109, 1630, 5119, 63697, 315, 279, 426, 220, 16, 274, 320, 282, 883, 323, 507, 220, 16, 274, 320, 342, 883, 6332, 5990, 13519, 66085, 32732, 5237, 1994, 6650, 13, 48273, 15837, 16798, 1154, 320, 650, 274, 883, 284, 1389, 16, 650, 304, 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13, 3277, 66192, 574, 11352, 11, 433, 574, 51287, 379, 41872, 505, 264, 6710, 315, 95273, 449, 93050, 17401, 13, 2030, 5347, 1965, 1076, 287, 20155, 32732, 263, 3250, 956, 617, 13931, 11, 779, 682, 32732, 5237, 1994, 374, 28367, 13, 7429, 20426, 66192, 11, 304, 902, 33299, 4667, 311, 1376, 16553, 9244, 12970, 12651, 351, 2439, 11, 32732, 5237, 1994, 7739, 439, 10815, 43546, 13, 26572, 2740, 11, 33299, 733, 7554, 505, 279, 5950, 323, 5387, 12651, 24346, 67751, 13, 578, 51048, 27313, 7739, 315, 32732, 5237, 1994, 449, 330, 71, 1573, 12651, 6241, 1, 32466, 315, 832, 824, 1475, 4330, 43546, 323, 832, 824, 1475, 4848, 304, 279, 55372, 13, 2522, 6073, 26711, 287, 17130, 73757, 5448, 315, 1584, 42655, 304, 220, 16, 4791, 12, 21, 323, 220, 16, 4791, 12, 20, 32732, 5237, 1994, 11, 16717, 555, 6437, 323, 2579, 18404, 36910, 11, 15947, 11, 1501, 1268, 279, 42655, 5398, 304, 264, 1648, 430, 75998, 279, 28367, 3769, 596, 46258, 7138, 13, 57116, 520, 30616, 323, 67363, 23978, 1903, 279, 1176, 11944, 6492, 315, 11713, 23011, 14726, 304, 32732, 5237, 1994, 13, 16666, 25, 65466, 309, 8483, 5856, 20906, 2419, 31382, 3907, 4314, 527, 279, 1455, 4279, 35530, 279, 67363, 10278, 13468, 994, 433, 3549, 32732, 5237, 1994, 389, 264, 15310, 54057, 1555, 25524, 32732, 263, 65374, 304, 459, 37232, 1494, 1108, 29302, 11, 4184, 311, 279, 12074, 11, 719, 330, 64185, 1, 32732, 5237, 1994, 18893, 15058, 956, 279, 2218, 315, 279, 4007, 13, 578, 10278, 1766, 430, 520, 20472, 1990, 220, 14868, 323, 220, 17711, 12628, 62447, 320, 25016, 12, 25890, 12628, 69823, 705, 2225, 220, 16, 4791, 12, 20, 323, 220, 16, 4791, 12, 21, 35530, 14264, 25291, 389, 279, 15310, 54057, 11, 902, 14385, 439, 264, 3896, 430, 28292, 279, 65374, 315, 33299, 1139, 27210, 35530, 13, 578, 51048, 6, 2802, 574, 60487, 555, 1148, 7077, 1405, 1521, 31576, 2322, 13, 27140, 1148, 814, 1047, 13468, 304, 66192, 11, 279, 33299, 6847, 14252, 660, 1855, 1023, 520, 279, 23546, 323, 18306, 279, 14726, 315, 872, 19228, 13, 4314, 19254, 34074, 6688, 10205, 311, 810, 39418, 38542, 2103, 46258, 2345, 10008, 315, 32732, 5237, 1994, 11, 449, 42338, 1778, 439, 220, 19, 4791, 12, 1691, 323, 220, 22, 4791, 12, 1927, 26449, 4315, 279, 15638, 35530, 13, 330, 644, 66192, 11, 1521, 23546, 1053, 387, 834, 10767, 14726, 11, 719, 304, 32732, 5237, 1994, 279, 1584, 42655, 11, 304, 2515, 11, 527, 264, 4832, 6070, 369, 1855, 1023, 1359, 1071, 30616, 19560, 5575, 18866, 90684, 29346, 11, 889, 6197, 264, 32887, 6492, 315, 19670, 11852, 49969, 311, 10552, 279, 24654, 13, 330, 791, 958, 36171, 287, 1990, 279, 35530, 374, 1633, 2204, 505, 1148, 584, 1518, 304, 1023, 220, 17, 9607, 7384, 1210, 330, 8142, 584, 1550, 1755, 1063, 958, 36171, 287, 1990, 279, 220, 16, 4791, 12, 20, 323, 220, 16, 4791, 12, 21, 35530, 11, 279, 47970, 17632, 323, 22106, 1139, 39445, 14726, 574, 15206, 1359, 65466, 309, 1071, 13, 330, 644, 279, 1403, 33520, 4017, 11, 32732, 263, 706, 17033, 311, 387, 459, 48298, 9257, 323, 7185, 7384, 1887, 1210, 362, 36201, 17130, 73757, 2217, 320, 3565, 8, 5039, 1403, 39445, 62407, 315, 32732, 5237, 1994, 11, 264, 28367, 11, 1403, 33520, 1358, 315, 32732, 263, 33299, 11, 430, 5249, 520, 264, 1584, 23011, 13, 93028, 4211, 304, 279, 6278, 323, 5740, 5448, 8024, 311, 279, 13918, 11, 449, 220, 16, 4791, 12, 21, 32732, 5237, 1994, 304, 2579, 323, 220, 16, 4791, 12, 20, 304, 6437, 13, 59250, 520, 30616, 323, 67363, 23978, 11075, 430, 35530, 315, 32732, 5237, 1994, 1584, 709, 304, 1778, 264, 1648, 430, 279, 3769, 596, 6929, 535, 11, 46258, 7138, 374, 18908, 13, 16666, 25, 18866, 90684, 29346, 19945, 560, 3907, 29346, 596, 17915, 16003, 10334, 29217, 10675, 279, 46258, 7138, 315, 279, 1584, 42655, 26, 420, 6259, 430, 20426, 1672, 15853, 42655, 304, 6062, 46258, 66192, 11, 814, 617, 17832, 5536, 389, 279, 3769, 596, 14683, 6012, 520, 3130, 9499, 13, 2468, 3428, 9499, 11, 279, 3769, 5039, 6029, 315, 264, 6900, 17915, 12330, 11, 264, 7701, 11713, 6530, 315, 57678, 13, 578, 91867, 29217, 1101, 12090, 27545, 12062, 304, 70334, 11, 29487, 98971, 323, 25396, 32056, 6012, 4315, 32732, 5237, 1994, 35530, 11, 902, 1101, 12090, 279, 3769, 649, 387, 33519, 369, 8522, 13, 330, 791, 5016, 46033, 16751, 13978, 315, 32732, 5237, 1994, 527, 389, 2539, 3113, 304, 420, 4007, 1359, 71968, 677, 942, 1071, 13, 330, 2028, 13533, 41765, 958, 1387, 304, 279, 3769, 596, 14683, 6070, 1555, 6900, 17915, 17301, 11, 902, 1253, 3063, 311, 95685, 4954, 3480, 481, 31591, 1210, 330, 2170, 459, 19670, 2740, 15792, 3769, 11, 32732, 5237, 1994, 706, 6012, 430, 1288, 387, 264, 734, 315, 279, 54057, 11, 42617, 7384, 323, 7479, 30903, 1359, 65466, 309, 1071, 13, 330, 1687, 3987, 311, 8895, 4726, 2585, 927, 1202, 6012, 1555, 11742, 16003, 2065, 323, 5255, 18052, 449, 1023, 7384, 1139, 30548, 78, 47194, 1210, 71968, 677, 942, 323, 65466, 309, 1101, 1080, 96471, 264, 3293, 22037, 33242, 52536, 13356, 922, 330, 1820, 3177, 478, 220, 17, 9607, 9501, 1210, 763, 430, 6710, 11, 279, 12283, 12090, 32732, 5237, 1994, 1253, 387, 10728, 369, 19303, 323, 18300, 14683, 958, 6595, 82, 11, 80390, 323, 19207, 13, 1102, 1436, 1101, 387, 14791, 369, 2307, 77752, 287, 31228, 32317, 7766, 323, 11, 994, 42415, 11, 369, 35784, 5942, 323, 11863, 8522, 13, 220, 128257, 198 ]

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Inflammasomes are important sentinels of innate immune defence, sensing pathogens and inducing cell death in infected cells 1 . There are several inflammasome sensors that each detect and respond to a specific pathogen- or damage-associated molecular pattern (PAMP or DAMP, respectively) 1 . During infection, live pathogens can induce the release of multiple PAMPs and DAMPs, which can simultaneously engage multiple inflammasome sensors 2 , 3 , 4 , 5 . Here we found that AIM2 regulates the innate immune sensors pyrin and ZBP1 to drive inflammatory signalling and a form of inflammatory cell death known as PANoptosis, and provide host protection during infections with herpes simplex virus 1 and Francisella novicida . We also observed that AIM2, pyrin and ZBP1 were members of a large multi-protein complex along with ASC, caspase-1, caspase-8, RIPK3, RIPK1 and FADD, that drove inflammatory cell death (PANoptosis). Collectively, our findings define a previously unknown regulatory and molecular interaction between AIM2, pyrin and ZBP1 that drives assembly of an AIM2-mediated multi-protein complex that we term the AIM2 PANoptosome and comprising multiple inflammasome sensors and cell death regulators. These results advance the understanding of the functions of these molecules in innate immunity and inflammatory cell death, suggesting new therapeutic targets for AIM2-, ZBP1- and pyrin-mediated diseases. Main Inflammasomes are critical components of the innate immune response 1 . Following exposure to PAMPs and DAMPs, inflammasome sensors form a multi-protein complex that activates caspase-1, leading to cleavage of its downstream substrates, inflammatory signalling and inflammatory cell death. Individual inflammasome sensors detect and respond to specific PAMPs and DAMPs, but emerging evidence suggests that multiple inflammasome sensors can be activated in response to disease, particularly live pathogen infection, owing to the presence of multiple PAMPs and DAMPs 2 , 3 , 4 , 5 . The AIM2 inflammasome is known to sense double-stranded DNA (dsDNA) and has essential roles in development, infectious diseases, inflammatory diseases and cancer 6 , 7 , 8 , 9 , 10 , 11 . However, several critical functions of AIM2 beyond its canonically described role in inflammasome formation and pyroptosis have been observed that cannot be explained by our current understanding of the AIM2 inflammasome 2 . Herpes simplex virus 1 (HSV1), a dsDNA virus that causes lifelong incurable, recurrent pathologies, and Francisella , a Gram-negative bacterium that can cause rapid lethality upon infection, are two diverse pathogens that are known to activate the AIM2 inflammasome and cell death 6 , 10 , 11 , 12 , 13 . To investigate whether cells exposed to numerous PAMPs and DAMPs during these viral and bacterial infections can simultaneously engage multiple inflammasome sensors, we infected wild-type bone marrow-derived macrophages (BMDMs) and BMDMs singly deficient in several major inflammasome sensors with HSV1 or F. novicida . Infection with HSV1 or F. novicida induced AIM2-dependent and NLRP3- and NLRC4-independent cleavage of caspase-1, release of the inflammasome-dependent cytokines interleukin (IL)-1β and IL-18, and cell death (Fig. 1a–o , Extended Data Fig. 1a–i ). However, inflammasome activation and cell death were also partially reduced in Mefv –/– BMDMs during HSV1 and F. novicida infections (Fig. 1p–t , Extended Data Fig. 1j–l ), suggesting that these infections activate pyrin to drive AIM2-mediated inflammatory signalling and cell death. Fig. 1: HSV1 induces AIM2-, pyrin- and ZBP1-mediated caspase-1 activation, cytokine release and cell death. a , Immunoblot analysis of pro-caspase-1 (P45) and cleaved caspase-1 (CASP1) (P20) in HSV1-infected or poly(dA:dT)-transfected wild-type (WT) or Aim2 −/− BMDMs. b , c , IL-1β ( b ) and IL-18 ( c ) release following HSV1 infection. d , Cell death in BMDMs after HSV1 infection for 16 h, measured by SYTOX Green uptake assay. Red indicates dead cells. e , Quantification of the cell death in d . f – j , Immunoblot analysis of CASP1 ( f ), release of IL-1β ( g ) and IL-18 ( h ), cell death images at 16 h after infection ( i ) and quantification of cell death ( j ) from WT or Nlrp3 −/− BMDMs after HSV1 infection or lipopolysaccharide (LPS) plus nigericin (Ni) treatment. k – o , Immunoblot analysis of CASP1 ( k ), release of IL-1β ( l ) and IL-18 ( m ), cell death images at 16 h after infection ( n ) and quantification of cell death ( o ) from WT or Nlrc4 −/− BMDMs after HSV1 or Salmonella Typhimurium infection. p – t , Immunoblot analysis of CASP1 ( p ), release of IL-1β ( q ) and IL-18 ( r ), cell death images at 16 h after infection ( s ) and quantification of cell death ( t ) from WT or Mefv −/− BMDMs after HSV1 infection or C. difficile toxin AB + supernatant treatment. u – y , Immunoblot analysis of CASP1 ( u ), release of IL-1β ( v ) and IL-18 ( w ), cell death images at 16 h after infection ( x ), and quantification of cell death ( y ) from WT or Zbp1 −/− BMDMs after HSV1 or influenza A virus (IAV) infection. a , f , k , p , u , Data are representative of at least three independent experiments. b , c , g , h , l , m , q , r , v , w , Data are mean ± s.e.m. NS, not significant; **** P < 0.0001 (two-tailed t -test; n = 6 from 3 biologically independent samples). d , i , n , s , x , Images are representative of at least three independent experiments. Scale bars, 50 μm. e , j , o , t , y , Data are mean ± s.e.m. NS, not significant; **** P < 0.0001 (two-tailed t -test; n = 8 from 4 biologically independent samples). Exact P values are presented in Supplementary Table 1 . For gel source data, see Supplementary Figure 1 . Source data Full size image Because we observed residual AIM2-mediated caspase cleavage in Mefv –/– BMDMs", "role": "user" }, { "content": "St. Jude Children's Research Hospital immunologists have identified how immune sensors in infected cells organize and launch a multi-faceted innate immune response to infections with live viruses and bacteria. The discovery appears today in Nature. The findings offer a new paradigm for understanding the functional and regulatory role that inflammasome sensors and cell death complexes play in infections. The work also highlights new therapeutic targets for treatment of diseases such as cancer and inflammatory autoimmune disorders that are associated with abnormal inflammasome sensor activation. Inflammasomes are protein complexes that form in infected cells or cells that sense damage. The complexes include sensors that recognize different viruses, bacteria and other pathogens or danger signals. Inflammasomes drive inflammatory signaling. Those signals activate inflammatory cell death pathways and eliminate the infection but can also contribute to pathological inflammation. Previous research has focused on inflammasomes working alone. \"This new work builds on our quest to identify inflammasome regulation,\" said corresponding author Thirumala-Devi Kanneganti, Ph.D., of the St. Jude Department of Immunology. \"Our study highlights how inflammasomes and multiple cell death components can and do work together in a mega-protein complex called the PANoptosome to activate the innate immune response and unleash PANoptosis.\" The Kanneganti laboratory showed that regulatory and molecular interactions among three inflammasome sensors, in concert with cell death proteins, drive formation of a mega-cell death complex called a PANoptosome. Rather than regulating one type of inflammatory programmed cell death, PANoptosomes control three—pyroptosis, apoptosis and necroptosis, referred to as PANoptosis. Investigators also determined that the AIM2 inflammasome sensor served as a master regulator of PANoptosome assembly in response to infections with herpes simplex virus 1 and the Francisella novicida bacterium. AIM2 also proved essential for helping mice survive the infections. \"The findings address a central question in the fields of innate immunity, cell death and inflammasome biology,\" Kanneganti said. From inflammasomes to PANoptosomes The findings build on previous research from Kanneganti's laboratory, which is a pioneer in the field. Kanneganti identified one of the first inflammasome sensors and helped to establish inflammasome research. Researchers in the field have focused on how individual inflammasome sensors detect invading pathogens or other threats. Inflammasomes were historically thought to respond by activating one inflammatory cell death pathway. The Kanneganti laboratory has a longstanding interest in understanding regulation of inflammasomes and have identified redundancies among cell death pathways. In 2016, the researchers reported for the first time that influenza infections activated molecules in all three cell death pathways. The scientists called the process PANoptosis. Investigators also determined that a single innate immune sensor called ZBP1 regulated PANoptosis in flu-infected cells. This study laid the foundation for the development of the PANoptosis research area. PANoptosomes today Now, Kanneganti's group has identified AIM2 as the master regulator of a new PANoptosome. First author SangJoon Lee, Ph.D., a postdoctoral fellow in the Kanneganti laboratory, used immunoprecipitation, microscopy and other techniques to show that AIM2, other inflammasome sensors Pyrin and ZBP1, and cell death molecules were part of this AIM2-PANoptosome. The PANoptosome drove inflammatory cell death. \"This was critical evidence that the inflammasome sensors and molecules from multiple cell death pathways are in the same complex and highlighted the PANoptosome's role in protecting the host during live pathogenic infections,\" Lee said. Live pathogens broadcast their presence more widely to the immune system, which helps to explain why the infections trigger PANoptosome assembly and a more robust immune response. Pathogens can also carry proteins that prevent activation of specific cell death pathways. PANoptosis provides an immune system workaround to protect the host. \"Our working hypothesis is that while the sensors involved may vary, most infections will induce formation of these unique innate immune complexes called PANoptosomes to unleash inflammatory cell death, PANoptosis,\" Kanneganti said. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Inflammasomes are important sentinels of innate immune defence, sensing pathogens and inducing cell death in infected cells 1 . There are several inflammasome sensors that each detect and respond to a specific pathogen- or damage-associated molecular pattern (PAMP or DAMP, respectively) 1 . During infection, live pathogens can induce the release of multiple PAMPs and DAMPs, which can simultaneously engage multiple inflammasome sensors 2 , 3 , 4 , 5 . Here we found that AIM2 regulates the innate immune sensors pyrin and ZBP1 to drive inflammatory signalling and a form of inflammatory cell death known as PANoptosis, and provide host protection during infections with herpes simplex virus 1 and Francisella novicida . We also observed that AIM2, pyrin and ZBP1 were members of a large multi-protein complex along with ASC, caspase-1, caspase-8, RIPK3, RIPK1 and FADD, that drove inflammatory cell death (PANoptosis). Collectively, our findings define a previously unknown regulatory and molecular interaction between AIM2, pyrin and ZBP1 that drives assembly of an AIM2-mediated multi-protein complex that we term the AIM2 PANoptosome and comprising multiple inflammasome sensors and cell death regulators. These results advance the understanding of the functions of these molecules in innate immunity and inflammatory cell death, suggesting new therapeutic targets for AIM2-, ZBP1- and pyrin-mediated diseases. Main Inflammasomes are critical components of the innate immune response 1 . Following exposure to PAMPs and DAMPs, inflammasome sensors form a multi-protein complex that activates caspase-1, leading to cleavage of its downstream substrates, inflammatory signalling and inflammatory cell death. Individual inflammasome sensors detect and respond to specific PAMPs and DAMPs, but emerging evidence suggests that multiple inflammasome sensors can be activated in response to disease, particularly live pathogen infection, owing to the presence of multiple PAMPs and DAMPs 2 , 3 , 4 , 5 . The AIM2 inflammasome is known to sense double-stranded DNA (dsDNA) and has essential roles in development, infectious diseases, inflammatory diseases and cancer 6 , 7 , 8 , 9 , 10 , 11 . However, several critical functions of AIM2 beyond its canonically described role in inflammasome formation and pyroptosis have been observed that cannot be explained by our current understanding of the AIM2 inflammasome 2 . Herpes simplex virus 1 (HSV1), a dsDNA virus that causes lifelong incurable, recurrent pathologies, and Francisella , a Gram-negative bacterium that can cause rapid lethality upon infection, are two diverse pathogens that are known to activate the AIM2 inflammasome and cell death 6 , 10 , 11 , 12 , 13 . To investigate whether cells exposed to numerous PAMPs and DAMPs during these viral and bacterial infections can simultaneously engage multiple inflammasome sensors, we infected wild-type bone marrow-derived macrophages (BMDMs) and BMDMs singly deficient in several major inflammasome sensors with HSV1 or F. novicida . Infection with HSV1 or F. novicida induced AIM2-dependent and NLRP3- and NLRC4-independent cleavage of caspase-1, release of the inflammasome-dependent cytokines interleukin (IL)-1β and IL-18, and cell death (Fig. 1a–o , Extended Data Fig. 1a–i ). However, inflammasome activation and cell death were also partially reduced in Mefv –/– BMDMs during HSV1 and F. novicida infections (Fig. 1p–t , Extended Data Fig. 1j–l ), suggesting that these infections activate pyrin to drive AIM2-mediated inflammatory signalling and cell death. Fig. 1: HSV1 induces AIM2-, pyrin- and ZBP1-mediated caspase-1 activation, cytokine release and cell death. a , Immunoblot analysis of pro-caspase-1 (P45) and cleaved caspase-1 (CASP1) (P20) in HSV1-infected or poly(dA:dT)-transfected wild-type (WT) or Aim2 −/− BMDMs. b , c , IL-1β ( b ) and IL-18 ( c ) release following HSV1 infection. d , Cell death in BMDMs after HSV1 infection for 16 h, measured by SYTOX Green uptake assay. Red indicates dead cells. e , Quantification of the cell death in d . f – j , Immunoblot analysis of CASP1 ( f ), release of IL-1β ( g ) and IL-18 ( h ), cell death images at 16 h after infection ( i ) and quantification of cell death ( j ) from WT or Nlrp3 −/− BMDMs after HSV1 infection or lipopolysaccharide (LPS) plus nigericin (Ni) treatment. k – o , Immunoblot analysis of CASP1 ( k ), release of IL-1β ( l ) and IL-18 ( m ), cell death images at 16 h after infection ( n ) and quantification of cell death ( o ) from WT or Nlrc4 −/− BMDMs after HSV1 or Salmonella Typhimurium infection. p – t , Immunoblot analysis of CASP1 ( p ), release of IL-1β ( q ) and IL-18 ( r ), cell death images at 16 h after infection ( s ) and quantification of cell death ( t ) from WT or Mefv −/− BMDMs after HSV1 infection or C. difficile toxin AB + supernatant treatment. u – y , Immunoblot analysis of CASP1 ( u ), release of IL-1β ( v ) and IL-18 ( w ), cell death images at 16 h after infection ( x ), and quantification of cell death ( y ) from WT or Zbp1 −/− BMDMs after HSV1 or influenza A virus (IAV) infection. a , f , k , p , u , Data are representative of at least three independent experiments. b , c , g , h , l , m , q , r , v , w , Data are mean ± s.e.m. NS, not significant; **** P < 0.0001 (two-tailed t -test; n = 6 from 3 biologically independent samples). d , i , n , s , x , Images are representative of at least three independent experiments. Scale bars, 50 μm. e , j , o , t , y , Data are mean ± s.e.m. NS, not significant; **** P < 0.0001 (two-tailed t -test; n = 8 from 4 biologically independent samples). Exact P values are presented in Supplementary Table 1 . For gel source data, see Supplementary Figure 1 . Source data Full size image Because we observed residual AIM2-mediated caspase cleavage in Mefv –/– BMDMs<|im_end|> <|im_start|>assistant St. Jude Children's Research Hospital immunologists have identified how immune sensors in infected cells organize and launch a multi-faceted innate immune response to infections with live viruses and bacteria. The discovery appears today in Nature. The findings offer a new paradigm for understanding the functional and regulatory role that inflammasome sensors and cell death complexes play in infections. The work also highlights new therapeutic targets for treatment of diseases such as cancer and inflammatory autoimmune disorders that are associated with abnormal inflammasome sensor activation. Inflammasomes are protein complexes that form in infected cells or cells that sense damage. The complexes include sensors that recognize different viruses, bacteria and other pathogens or danger signals. Inflammasomes drive inflammatory signaling. Those signals activate inflammatory cell death pathways and eliminate the infection but can also contribute to pathological inflammation. Previous research has focused on inflammasomes working alone. "This new work builds on our quest to identify inflammasome regulation," said corresponding author Thirumala-Devi Kanneganti, Ph.D., of the St. Jude Department of Immunology. "Our study highlights how inflammasomes and multiple cell death components can and do work together in a mega-protein complex called the PANoptosome to activate the innate immune response and unleash PANoptosis." The Kanneganti laboratory showed that regulatory and molecular interactions among three inflammasome sensors, in concert with cell death proteins, drive formation of a mega-cell death complex called a PANoptosome. Rather than regulating one type of inflammatory programmed cell death, PANoptosomes control three—pyroptosis, apoptosis and necroptosis, referred to as PANoptosis. Investigators also determined that the AIM2 inflammasome sensor served as a master regulator of PANoptosome assembly in response to infections with herpes simplex virus 1 and the Francisella novicida bacterium. AIM2 also proved essential for helping mice survive the infections. "The findings address a central question in the fields of innate immunity, cell death and inflammasome biology," Kanneganti said. From inflammasomes to PANoptosomes The findings build on previous research from Kanneganti's laboratory, which is a pioneer in the field. Kanneganti identified one of the first inflammasome sensors and helped to establish inflammasome research. Researchers in the field have focused on how individual inflammasome sensors detect invading pathogens or other threats. Inflammasomes were historically thought to respond by activating one inflammatory cell death pathway. The Kanneganti laboratory has a longstanding interest in understanding regulation of inflammasomes and have identified redundancies among cell death pathways. In 2016, the researchers reported for the first time that influenza infections activated molecules in all three cell death pathways. The scientists called the process PANoptosis. Investigators also determined that a single innate immune sensor called ZBP1 regulated PANoptosis in flu-infected cells. This study laid the foundation for the development of the PANoptosis research area. PANoptosomes today Now, Kanneganti's group has identified AIM2 as the master regulator of a new PANoptosome. First author SangJoon Lee, Ph.D., a postdoctoral fellow in the Kanneganti laboratory, used immunoprecipitation, microscopy and other techniques to show that AIM2, other inflammasome sensors Pyrin and ZBP1, and cell death molecules were part of this AIM2-PANoptosome. The PANoptosome drove inflammatory cell death. "This was critical evidence that the inflammasome sensors and molecules from multiple cell death pathways are in the same complex and highlighted the PANoptosome's role in protecting the host during live pathogenic infections," Lee said. Live pathogens broadcast their presence more widely to the immune system, which helps to explain why the infections trigger PANoptosome assembly and a more robust immune response. Pathogens can also carry proteins that prevent activation of specific cell death pathways. PANoptosis provides an immune system workaround to protect the host. "Our working hypothesis is that while the sensors involved may vary, most infections will induce formation of these unique innate immune complexes called PANoptosomes to unleash inflammatory cell death, PANoptosis," Kanneganti said. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Decisions that favor one’s own interest versus the interest of another individual depend on context and the relationships between individuals. The neurobiology underlying selfish choices or choices that benefit others is not understood. We developed a two-choice social decision-making task in which mice can decide whether to share a reward with their conspecifics. Preference for altruistic choices was modulated by familiarity, sex, social contact, hunger, hierarchical status and emotional state matching. Fiber photometry recordings and chemogenetic manipulations demonstrated that basolateral amygdala (BLA) neurons are involved in the establishment of prosocial decisions. In particular, BLA neurons projecting to the prelimbic (PL) region of the prefrontal cortex mediated the development of a preference for altruistic choices, whereas PL projections to the BLA modulated self-interest motives for decision-making. This provides a neurobiological model of altruistic and selfish choices with relevance to pathologies associated with dysfunctions in social decision-making. Main Many decisions are made in the context of social interactions. These decisions require the integration of different cognitive processes and behaviors, which allow an individual to understand and interact with others 1 . The psychological conflict between self-interest and the interest of others (especially when this involves a personal cost) is a key element of social decisions 2 . From an evolutionary perspective, altruism likely evolved to promote survival through actions associated with kin selection, parental care and reciprocity 3 , 4 , 5 . Increasing evidence suggests that nonhuman animals, including rodents, engage in prosocial behaviors that resemble altruism; rats help conspecifics that are in need 6 , have been harmed 7 or are seeking food 8 and reciprocate previously received help 9 , and mice display consolatory 10 and collaborative 11 behaviors. Current research paradigms can detect animals’ cooperative propensity to help or to prevent pain in others 4 , 12 . However, the social factors and neurobiological determinants of whether an animal engages in altruism or self-interest are unclear. Mammals live in social groups with dominant and subordinate members, which determine a hierarchy that can affect multiple behaviors 13 and represent an important variable in social relationships and prosocial behaviors 14 . Moreover, socially close individuals share more easily subjective affective states of another through emotional contagion 14 . How social interaction and relationships might change decisions affecting selves and others among members of a group has been overlooked. In nonhuman primates, activity in a prefrontal–amygdala network contributes to social decision-making (SDM) 15 . Further, the same structures are involved in social interactions 16 and social transmission in rodents 17 . In particular, the basolateral amygdala (BLA) has a central position in the neurobiological circuit for our abilities of choosing among options that differ in rewards and costs 18 . Yet, our understanding of its role in decisions involving altruism is still limited. Here we devised a SDM task for mice, modeled on the human game-theoretical paradigm known as the ‘dictator game’ (ref. 19 ), in which a ‘dictator’ (that is, the actor) decides whether to share food with a ‘recipient’ (that is, the observer), who is a passive player. We found that the majority of male mice, but not females, displayed a preference for sharing food with familiar, but not unfamiliar, conspecifics. Substantial individual differences in altruistic choices originated from the hierarchy status of each individual. Chemogenetic silencing of either the BLA or its projections to the prefrontal cortex (PFC) abolished the development of altruistic choices, whereas PFC inputs to the BLA modulated self-interest motives for decision-making. Results Mice choose altruistic actions over selfish decisions To develop a SDM for mice, we expanded a standard operant cage with an adjacent compartment, separated by a metal mesh. This compartment hosted a ‘recipient’ that would receive food rewards depending on the ‘dictator’s’ choice (hereafter referred to as the ‘actor’). The recipient was a passive player with a chance to receive a food reward from a magazine depending on the actor’s choice. The actor was presented with a two-choice decision-making paradigm in which nose poking resulted in either food rewards for themselves only (selfish choice) or for both themselves and the recipient (altruistic choice; Fig. 1a ). We compared this condition against a control group of actor mice without recipients. The structure of the task was identical between these two conditions (‘with recipient’ and ‘no recipient’). Thus, any differences in the response could be attributed to the influence of the recipient. Fig. 1: Mice prefer altruistic over selfish decisions. a , Experimental design of the SDM. b , Decision preference score in mice tested in the SDM with a recipient (orange) or no recipient (gray) (two-way repeated-measures (RM) ANOVA, group (with recipient, no recipient) × time (days 1–5): F (4, 116) = 2.771, P = 0.0305; the decision preference scores were found to fit a normal distribution across 5 days of testing (D’Agostino and Pearson normality test, ‘with recipient’: min K 2 = 3.122, P = 0.225, n = 16; ‘no recipient’: min K 2 = 0.944, P = 0.623, n = 15). Inset, altruistic responses on left ( n = 9) and right ( n = 7) nose pokes on day 1 (two-tailed unpaired t -test: t = 3.37, degrees of freedom (d.f.) = 14, P = 0.0046) and day 5 ( t = 0.79, d.f. = 14, P = 0.4419). c , Number of nose pokes with a recipient ( n = 16) and no recipient ( n = 15; two-way RM ANOVA, group (with recipient, no recipient) × response (nose poke 1, nose poke 2): F (1, 58) = 6.877, P = 0.0111). d , Change of preference in an additional session with a recipient (R→R, n = 10) or with a toy (R→T, n = 10) (two-tailed unpaired t -test: t = 2.24, d.f. = 18, P = 0.0374). e , Left, the total number of mice grouped by preference and sex. Right, altruistic and selfish preferences in males and females. f , Data distribution of decision preference score in altruistic and selfish mice. g , Cumulative frequency", "role": "user" }, { "content": "Humans and animals can exhibit a wide variety of behaviors when interacting with their peers. These include both prosocial behaviors, voluntary actions aimed at supporting or helping others, and selfish or opportunistic behaviors, which prioritize one's own needs or desires. Several past neuroscience studies have investigated the neural processes involved in social connection, particularly in terms of the brain regions and neurotransmitters associated with bonding or intimacy. However, so far very little is known about the brain mechanisms underlying selfish or altruistic actions. Researchers at the Italian Institute of Technology (IIT) and University of Milan have recently carried out a study aimed at filling this gap in the literature, by examining the activation and firing of neurons in the mice brain as the animals engaged in prosocial or selfish behaviors. Their paper, published in Nature Neuroscience, identifies a series of prosocial or selfish behavior-specific reciprocal connections between neurons in the prefrontal cortex and amygdala, two brain regions associated with complex behavioral planning and emotional regulation, respectively. \"Over the past years, I felt a loss of the common sense of collectiveness, even before the pandemic, that contributed to self-centered concern and a disregard of others,\" Diego Scheggia, one of the researchers who carried out the study, told MedicalXpress. \"Of course, recent physical distancing and quarantine policies further disrupted our daily social interactions and resulted in increased social isolation. The goal of my recent study was to understand the social factors and neurobiological determinants of altruism and self-interest.\" To examine the neural mechanisms underpinning altruistic and selfish behaviors, Scheggia and his colleagues first designed a new experimental task that would encourage these different types of behaviors in animals. This social decision-making task offered animals two simple choices: sharing a reward with their peers or not. The researchers then used this task to perform an experiment on several adult mice. \"The task we used was modeled on the human game-theoretical paradigm known as the 'dictator game' in which a 'dictator' decides whether to share a reward with a conspecific,\" Scheggia explained. \"In this task, we measured the neural activity of the basolateral nucleus of the amygdala that show substantial differences between prosocial and selfish subjects.\" Magnification of the basolateral amygdala. In red the neurons activated during the behavioral task \"dictator game.\" Credit: Scheggia et al. Essentially, Scheggia and his colleagues found that the mice's decision to share their food reward with other mice depended on several factors. These factors included the mice's level of familiarity with their peers, their sex, previous social contacts, levels of hunger, hierarchical status and their emotional attunement. Subsequently, the researchers used chemogenetics, techniques that entail the use of synthetic drugs to manipulate specific brain pathways, to silence the activity of some neurons. This allowed them to determine whether silencing specific neurons automatically resulted in more prosocial or selfish behaviors. \"We observed that silencing the neurons in the prefrontal cortex that are connected to the basolateral amygdala modulated choices guided by self-interest,\" Scheggia said. The results gathered by this team of researchers highlight the role of neurons in the basolateral amygdala (BLA) in promoting prosocial decisions. Specifically, they suggest that BLA neurons projecting on the prelimbic (PL) part of the prefrontal cortex mediate the development of a preference for altruistic choices in mice. In contrast, the preference for selfish behaviors appeared to be mediated by the projection of neurons in the PL prefrontal cortex to the BLA brain region. In the future, the findings of this study could pave the way for interesting new discoveries about the impact of interactions between neurons in the amygdala and prefrontal cortex on the nature of animal behaviors. The work by Scheggia and his colleagues also outlines a possible neurobiological model of altruistic and selfish choices, which could help to better understand the issues with social decision-making associated with some psychiatric disorders. \"As a result of the pandemic, more selfish and antisocial behavior have risen, thus threatening to multiply psychiatric diagnoses in the next few years,\" Scheggia added. \"Unraveling the nature of brain mechanisms underlying social decision-making could represent a crucial step to suggest novel treatments for social dysfunctions and antisocial behavior that occur in several psychiatric conditions and neurodegenerative disorders. Building on the findings of our recent study, we are now exploring the role of previous experience and emotional memories on prosocial and selfish choices.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Decisions that favor one’s own interest versus the interest of another individual depend on context and the relationships between individuals. The neurobiology underlying selfish choices or choices that benefit others is not understood. We developed a two-choice social decision-making task in which mice can decide whether to share a reward with their conspecifics. Preference for altruistic choices was modulated by familiarity, sex, social contact, hunger, hierarchical status and emotional state matching. Fiber photometry recordings and chemogenetic manipulations demonstrated that basolateral amygdala (BLA) neurons are involved in the establishment of prosocial decisions. In particular, BLA neurons projecting to the prelimbic (PL) region of the prefrontal cortex mediated the development of a preference for altruistic choices, whereas PL projections to the BLA modulated self-interest motives for decision-making. This provides a neurobiological model of altruistic and selfish choices with relevance to pathologies associated with dysfunctions in social decision-making. Main Many decisions are made in the context of social interactions. These decisions require the integration of different cognitive processes and behaviors, which allow an individual to understand and interact with others 1 . The psychological conflict between self-interest and the interest of others (especially when this involves a personal cost) is a key element of social decisions 2 . From an evolutionary perspective, altruism likely evolved to promote survival through actions associated with kin selection, parental care and reciprocity 3 , 4 , 5 . Increasing evidence suggests that nonhuman animals, including rodents, engage in prosocial behaviors that resemble altruism; rats help conspecifics that are in need 6 , have been harmed 7 or are seeking food 8 and reciprocate previously received help 9 , and mice display consolatory 10 and collaborative 11 behaviors. Current research paradigms can detect animals’ cooperative propensity to help or to prevent pain in others 4 , 12 . However, the social factors and neurobiological determinants of whether an animal engages in altruism or self-interest are unclear. Mammals live in social groups with dominant and subordinate members, which determine a hierarchy that can affect multiple behaviors 13 and represent an important variable in social relationships and prosocial behaviors 14 . Moreover, socially close individuals share more easily subjective affective states of another through emotional contagion 14 . How social interaction and relationships might change decisions affecting selves and others among members of a group has been overlooked. In nonhuman primates, activity in a prefrontal–amygdala network contributes to social decision-making (SDM) 15 . Further, the same structures are involved in social interactions 16 and social transmission in rodents 17 . In particular, the basolateral amygdala (BLA) has a central position in the neurobiological circuit for our abilities of choosing among options that differ in rewards and costs 18 . Yet, our understanding of its role in decisions involving altruism is still limited. Here we devised a SDM task for mice, modeled on the human game-theoretical paradigm known as the ‘dictator game’ (ref. 19 ), in which a ‘dictator’ (that is, the actor) decides whether to share food with a ‘recipient’ (that is, the observer), who is a passive player. We found that the majority of male mice, but not females, displayed a preference for sharing food with familiar, but not unfamiliar, conspecifics. Substantial individual differences in altruistic choices originated from the hierarchy status of each individual. Chemogenetic silencing of either the BLA or its projections to the prefrontal cortex (PFC) abolished the development of altruistic choices, whereas PFC inputs to the BLA modulated self-interest motives for decision-making. Results Mice choose altruistic actions over selfish decisions To develop a SDM for mice, we expanded a standard operant cage with an adjacent compartment, separated by a metal mesh. This compartment hosted a ‘recipient’ that would receive food rewards depending on the ‘dictator’s’ choice (hereafter referred to as the ‘actor’). The recipient was a passive player with a chance to receive a food reward from a magazine depending on the actor’s choice. The actor was presented with a two-choice decision-making paradigm in which nose poking resulted in either food rewards for themselves only (selfish choice) or for both themselves and the recipient (altruistic choice; Fig. 1a ). We compared this condition against a control group of actor mice without recipients. The structure of the task was identical between these two conditions (‘with recipient’ and ‘no recipient’). Thus, any differences in the response could be attributed to the influence of the recipient. Fig. 1: Mice prefer altruistic over selfish decisions. a , Experimental design of the SDM. b , Decision preference score in mice tested in the SDM with a recipient (orange) or no recipient (gray) (two-way repeated-measures (RM) ANOVA, group (with recipient, no recipient) × time (days 1–5): F (4, 116) = 2.771, P = 0.0305; the decision preference scores were found to fit a normal distribution across 5 days of testing (D’Agostino and Pearson normality test, ‘with recipient’: min K 2 = 3.122, P = 0.225, n = 16; ‘no recipient’: min K 2 = 0.944, P = 0.623, n = 15). Inset, altruistic responses on left ( n = 9) and right ( n = 7) nose pokes on day 1 (two-tailed unpaired t -test: t = 3.37, degrees of freedom (d.f.) = 14, P = 0.0046) and day 5 ( t = 0.79, d.f. = 14, P = 0.4419). c , Number of nose pokes with a recipient ( n = 16) and no recipient ( n = 15; two-way RM ANOVA, group (with recipient, no recipient) × response (nose poke 1, nose poke 2): F (1, 58) = 6.877, P = 0.0111). d , Change of preference in an additional session with a recipient (R→R, n = 10) or with a toy (R→T, n = 10) (two-tailed unpaired t -test: t = 2.24, d.f. = 18, P = 0.0374). e , Left, the total number of mice grouped by preference and sex. Right, altruistic and selfish preferences in males and females. f , Data distribution of decision preference score in altruistic and selfish mice. g , Cumulative frequency<|im_end|> <|im_start|>assistant Humans and animals can exhibit a wide variety of behaviors when interacting with their peers. These include both prosocial behaviors, voluntary actions aimed at supporting or helping others, and selfish or opportunistic behaviors, which prioritize one's own needs or desires. Several past neuroscience studies have investigated the neural processes involved in social connection, particularly in terms of the brain regions and neurotransmitters associated with bonding or intimacy. However, so far very little is known about the brain mechanisms underlying selfish or altruistic actions. Researchers at the Italian Institute of Technology (IIT) and University of Milan have recently carried out a study aimed at filling this gap in the literature, by examining the activation and firing of neurons in the mice brain as the animals engaged in prosocial or selfish behaviors. Their paper, published in Nature Neuroscience, identifies a series of prosocial or selfish behavior-specific reciprocal connections between neurons in the prefrontal cortex and amygdala, two brain regions associated with complex behavioral planning and emotional regulation, respectively. "Over the past years, I felt a loss of the common sense of collectiveness, even before the pandemic, that contributed to self-centered concern and a disregard of others," Diego Scheggia, one of the researchers who carried out the study, told MedicalXpress. "Of course, recent physical distancing and quarantine policies further disrupted our daily social interactions and resulted in increased social isolation. The goal of my recent study was to understand the social factors and neurobiological determinants of altruism and self-interest." To examine the neural mechanisms underpinning altruistic and selfish behaviors, Scheggia and his colleagues first designed a new experimental task that would encourage these different types of behaviors in animals. This social decision-making task offered animals two simple choices: sharing a reward with their peers or not. The researchers then used this task to perform an experiment on several adult mice. "The task we used was modeled on the human game-theoretical paradigm known as the 'dictator game' in which a 'dictator' decides whether to share a reward with a conspecific," Scheggia explained. "In this task, we measured the neural activity of the basolateral nucleus of the amygdala that show substantial differences between prosocial and selfish subjects." Magnification of the basolateral amygdala. In red the neurons activated during the behavioral task "dictator game." Credit: Scheggia et al. Essentially, Scheggia and his colleagues found that the mice's decision to share their food reward with other mice depended on several factors. These factors included the mice's level of familiarity with their peers, their sex, previous social contacts, levels of hunger, hierarchical status and their emotional attunement. Subsequently, the researchers used chemogenetics, techniques that entail the use of synthetic drugs to manipulate specific brain pathways, to silence the activity of some neurons. This allowed them to determine whether silencing specific neurons automatically resulted in more prosocial or selfish behaviors. "We observed that silencing the neurons in the prefrontal cortex that are connected to the basolateral amygdala modulated choices guided by self-interest," Scheggia said. The results gathered by this team of researchers highlight the role of neurons in the basolateral amygdala (BLA) in promoting prosocial decisions. Specifically, they suggest that BLA neurons projecting on the prelimbic (PL) part of the prefrontal cortex mediate the development of a preference for altruistic choices in mice. In contrast, the preference for selfish behaviors appeared to be mediated by the projection of neurons in the PL prefrontal cortex to the BLA brain region. In the future, the findings of this study could pave the way for interesting new discoveries about the impact of interactions between neurons in the amygdala and prefrontal cortex on the nature of animal behaviors. The work by Scheggia and his colleagues also outlines a possible neurobiological model of altruistic and selfish choices, which could help to better understand the issues with social decision-making associated with some psychiatric disorders. "As a result of the pandemic, more selfish and antisocial behavior have risen, thus threatening to multiply psychiatric diagnoses in the next few years," Scheggia added. "Unraveling the nature of brain mechanisms underlying social decision-making could represent a crucial step to suggest novel treatments for social dysfunctions and antisocial behavior that occur in several psychiatric conditions and neurodegenerative disorders. Building on the findings of our recent study, we are now exploring the role of previous experience and emotional memories on prosocial and selfish choices." <|im_end|>

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11, 4756, 304, 22037, 85879, 11, 36611, 264, 4101, 315, 8882, 2772, 477, 45743, 7865, 19440, 87298, 13537, 1990, 34313, 304, 279, 864, 7096, 278, 49370, 323, 64383, 29684, 6181, 11, 1403, 8271, 13918, 5938, 449, 6485, 36695, 9293, 323, 14604, 19812, 11, 15947, 13, 330, 1959, 279, 3347, 1667, 11, 358, 6612, 264, 4814, 315, 279, 4279, 5647, 315, 6667, 13071, 11, 1524, 1603, 279, 28522, 11, 430, 20162, 311, 659, 50482, 4747, 323, 264, 58817, 315, 3885, 1359, 18842, 5124, 29468, 689, 11, 832, 315, 279, 12074, 889, 11953, 704, 279, 4007, 11, 3309, 13235, 55, 1911, 13, 330, 2173, 3388, 11, 3293, 7106, 73669, 323, 71489, 10396, 4726, 69627, 1057, 7446, 3674, 22639, 323, 19543, 304, 7319, 3674, 31398, 13, 578, 5915, 315, 856, 3293, 4007, 574, 311, 3619, 279, 3674, 9547, 323, 18247, 8385, 5848, 6449, 1821, 315, 93592, 2191, 323, 659, 65873, 1210, 2057, 21635, 279, 30828, 24717, 1234, 13576, 1251, 93592, 4633, 323, 45743, 28198, 11, 5124, 29468, 689, 323, 813, 18105, 1176, 6319, 264, 502, 22772, 3465, 430, 1053, 15253, 1521, 2204, 4595, 315, 28198, 304, 10099, 13, 1115, 3674, 5597, 28846, 3465, 9076, 10099, 1403, 4382, 11709, 25, 11821, 264, 11565, 449, 872, 26081, 477, 539, 13, 578, 12074, 1243, 1511, 420, 3465, 311, 2804, 459, 9526, 389, 3892, 6822, 24548, 13, 330, 791, 3465, 584, 1511, 574, 62653, 389, 279, 3823, 1847, 10826, 91867, 49340, 3967, 439, 279, 364, 8644, 859, 1847, 6, 304, 902, 264, 364, 8644, 859, 6, 28727, 3508, 311, 4430, 264, 11565, 449, 264, 1615, 15934, 1359, 5124, 29468, 689, 11497, 13, 330, 644, 420, 3465, 11, 584, 17303, 279, 30828, 5820, 315, 279, 3122, 337, 19715, 62607, 315, 279, 64383, 29684, 6181, 430, 1501, 12190, 12062, 1990, 8882, 2772, 323, 45743, 15223, 1210, 20918, 2461, 315, 279, 3122, 337, 19715, 64383, 29684, 6181, 13, 763, 2579, 279, 34313, 22756, 2391, 279, 36695, 3465, 330, 8644, 859, 1847, 1210, 16666, 25, 5124, 29468, 689, 1880, 453, 13, 71854, 11, 5124, 29468, 689, 323, 813, 18105, 1766, 430, 279, 24548, 596, 5597, 311, 4430, 872, 3691, 11565, 449, 1023, 24548, 79101, 389, 3892, 9547, 13, 4314, 9547, 5343, 279, 24548, 596, 2237, 315, 71540, 449, 872, 26081, 11, 872, 1877, 11, 3766, 3674, 19015, 11, 5990, 315, 34906, 11, 70994, 2704, 323, 872, 14604, 1651, 359, 1133, 13, 3804, 39742, 11, 279, 12074, 1511, 8590, 11968, 25265, 11, 12823, 430, 87092, 279, 1005, 315, 28367, 11217, 311, 37735, 3230, 8271, 44014, 11, 311, 21847, 279, 5820, 315, 1063, 34313, 13, 1115, 5535, 1124, 311, 8417, 3508, 5554, 11627, 3230, 34313, 9651, 19543, 304, 810, 8882, 2772, 477, 45743, 28198, 13, 330, 1687, 13468, 430, 5554, 11627, 279, 34313, 304, 279, 864, 7096, 278, 49370, 430, 527, 8599, 311, 279, 3122, 337, 19715, 64383, 29684, 6181, 1491, 7913, 11709, 33687, 555, 659, 65873, 1359, 5124, 29468, 689, 1071, 13, 578, 3135, 20802, 555, 420, 2128, 315, 12074, 11415, 279, 3560, 315, 34313, 304, 279, 3122, 337, 19715, 64383, 29684, 6181, 320, 9574, 32, 8, 304, 22923, 8882, 2772, 11429, 13, 45863, 11, 814, 4284, 430, 15195, 32, 34313, 82382, 389, 279, 30713, 94598, 320, 2989, 8, 961, 315, 279, 864, 7096, 278, 49370, 1812, 6629, 279, 4500, 315, 264, 22698, 369, 93592, 4633, 11709, 304, 24548, 13, 763, 13168, 11, 279, 22698, 369, 45743, 28198, 9922, 311, 387, 78926, 555, 279, 22343, 315, 34313, 304, 279, 10528, 864, 7096, 278, 49370, 311, 279, 15195, 32, 8271, 5654, 13, 763, 279, 3938, 11, 279, 14955, 315, 420, 4007, 1436, 94123, 279, 1648, 369, 7185, 502, 54098, 922, 279, 5536, 315, 22639, 1990, 34313, 304, 279, 64383, 29684, 6181, 323, 864, 7096, 278, 49370, 389, 279, 7138, 315, 10065, 28198, 13, 578, 990, 555, 5124, 29468, 689, 323, 813, 18105, 1101, 50729, 264, 3284, 18247, 8385, 5848, 1646, 315, 93592, 4633, 323, 45743, 11709, 11, 902, 1436, 1520, 311, 2731, 3619, 279, 4819, 449, 3674, 5597, 28846, 5938, 449, 1063, 47657, 24673, 13, 330, 2170, 264, 1121, 315, 279, 28522, 11, 810, 45743, 323, 65617, 2772, 7865, 617, 41482, 11, 8617, 27903, 311, 31370, 47657, 85488, 304, 279, 1828, 2478, 1667, 1359, 5124, 29468, 689, 3779, 13, 330, 1844, 114348, 287, 279, 7138, 315, 8271, 24717, 16940, 3674, 5597, 28846, 1436, 4097, 264, 16996, 3094, 311, 4284, 11775, 22972, 369, 3674, 22709, 22124, 323, 65617, 2772, 7865, 430, 12446, 304, 3892, 47657, 4787, 323, 18247, 451, 7642, 1413, 24673, 13, 17283, 389, 279, 14955, 315, 1057, 3293, 4007, 11, 584, 527, 1457, 24919, 279, 3560, 315, 3766, 3217, 323, 14604, 19459, 389, 8882, 2772, 323, 45743, 11709, 1210, 220, 128257, 198 ]

2,378

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Over two centuries of economic growth have put undeniable pressure on the ecological systems that underpin human well-being. While it is agreed that these pressures are increasing, views divide on how they may be alleviated. Some suggest technological advances will automatically keep us from transgressing key environmental thresholds; others that policy reform can reconcile economic and ecological goals; while a third school argues that only a fundamental shift in societal values can keep human demands within the Earth’s ecological limits. Here we use novel integrated analysis of the energy–water–food nexus, rural land use (including biodiversity), material flows and climate change to explore whether mounting ecological pressures in Australia can be reversed, while the population grows and living standards improve. We show that, in the right circumstances, economic and environmental outcomes can be decoupled. Although economic growth is strong across all scenarios, environmental performance varies widely: pressures are projected to more than double, stabilize or fall markedly by 2050. However, we find no evidence that decoupling will occur automatically. Nor do we find that a shift in societal values is required. Rather, extensions of current policies that mobilize technology and incentivize reduced pressure account for the majority of differences in environmental performance. Our results show that Australia can make great progress towards sustainable prosperity, if it chooses to do so. Main Our analysis uses a new integrated multi-model framework developed for the Australian National Outlook 1 . Australia is globally relevant: a major exporter of energy, mineral and agricultural products, with high per capita income, greenhouse gas emissions, water extractions, and habitat loss. The framework assesses energy–water–food interactions (and links to ecosystem services) in the context of climate change 2 , and uses more than 20 scenarios to explore a diverse range of factors shaping future Australian economic and environmental outcomes 1 , 2 . Interacting national trends and policies include energy and resource efficiency, agricultural productivity, consumption and working hours, and new land-sector markets for energy feed-stocks and ecosystem services (carbon sequestration and biodiversity conservation). These are modelled against four levels of national and global greenhouse gas emissions reduction effort (from no abatement to very strong abatement), and associated global climate trajectories (see Extended Data Fig. 9 ). As well as assessing the range of scenario outcomes, we identify the relative contributions of different types of choices. ‘Collective choices’ are defined as decisions that can only be implemented by groups of actors, and then constrain or empower ‘individual choices’ (particularly through changing rules and institutions). For example, individual choices about whether to drive or catch a train to work are strongly shaped by prior collective choices about transport infrastructure. The framework accounts for detailed interactions across sectors and spatial scales. The focal scale is national (the continent of Australia), accounting for key processes at higher (global) and lower (sub-national) spatial scales. This cross-domain integrated approach is needed because partial assessments may not account for constraints or adverse impacts that would undermine an otherwise ‘sustainable’ trajectory 3 , 4 , 5 , 6 , 7 , 8 . The projections and indicators are fully consistent with the international System of National Accounts 9 . We provide more details in the Supplementary Methods (section ‘Overview of modelling framework and scenarios’) and results for more than 60 national and global indicators in the Supplementary Data . Novel aspects of the analysis include assessing the potential for markets for ecosystem services to supply carbon sequestration and habitat restoration (and implications for agricultural output 7 and extinction risk) 10 , 11 ; assessing future water stress rather than simple volume of water extracted 2 , 12 ; exploring material extractions and environmental footprints 13 ; and integrating these elements with established models for analysing energy, greenhouse gas emissions and economic performance 2 , 14 , 15 , 16 , 17 . We are not aware of any other future-looking modelling that integrates this range of issues and indicators ( Supplementary Methods , ‘Overview of modelling framework and scenarios’). Economic and physical decoupling is possible We find that substantial economic and physical decoupling is possible 18 . Economically, Australia can achieve strong economic growth to 2050, indicated by rising gross domestic product (GDP) and gross national income (GNI) per capita, in scenarios where environmental pressures fall or are stable. Physically, we find the services derived from natural resources (energy ( Extended Data Fig. 2 ), water ( Extended Data Fig. 3 ), food ( Extended Data Fig. 4 )) can increase, while associated environmental pressures ease (greenhouse emissions ( Extended Data Fig. 6 ), water stress ( Extended Data Fig. 3 ), native habitat loss ( Extended Data Fig. 5 )). Importantly, these projected decouplings do not involve a reduction in the value of Australia’s heavy industry ( Extended Data Fig. 1g ), or outsourcing its environmental footprint to other nations 13 , 19 . Instead energy- and material-intensive sectors are projected to increase their share of economic activity, even in scenarios with the strongest global abatement efforts 1 , 2 . In all scenarios, Australia’s economy and living standards are projected to grow strongly (see Extended Data Fig. 1 ). As shown in Fig. 1 , the value of economic activity (GDP) is projected to rise tenfold over the 80 years to 2050, driven by a 2.9-fold increase in population ( Extended Data Fig. 8 ) and a 3.2–3.6-fold increase in GDP per capita (all values are in real 2010 Australian dollars, adjusted for inflation). National income (GNI) grows at a similar rate as GDP, with GNI per capita increasing by 58–82% from 2010 to 2050. Around two-thirds of the range of outcomes is explained by choices about working hours and consumption rather than environmental constraints. Average incomes rise by up to 66% if average working hours decline another 11% over the next four decades, in line with recent trends, and rise by 75% or more if there is no decline in working hours. The remaining income differential is accounted for by different assumptions", "role": "user" }, { "content": "A sustainable Australia is possible – but we have to choose it. That's the finding of a paper published today in Nature. The paper is the result of a larger project to deliver the first Australian National Outlook report, more than two years in the making, which CSIRO is also releasing today. As part of this analysis we looked at whether achieving sustainability will require a shift in our values, such as rejecting consumerism. We also looked at the contributions of choices made by individuals (such as consuming less water or energy) and of choices made collectively by society (such as policies to reduce greenhouse gas emissions). We found that collective policy choices are crucial, and that Australia could make great progress to sustainability without any changes in social values. Competing views Few topics generate more heat, and less light, than debates over economic growth and sustainability. At one end of the spectrum, \"technological optimists\" suggest that the marvellous invisible hand will take care of everything, with market-driven improvements in technology automatically protecting essential natural resources while also improving living standards. Unfortunately, there is no real evidence to back this, particularly in protecting unpriced natural resources such as ocean fisheries, or the services provided by a stable climate. Instead the evidence suggests we are already crossing important planetary boundaries. Other the other end of the spectrum, people argue that achieving sustainability will require a rejection of economic growth, or a shift in values away from consumerism and towards a more ecologically attuned lifestyles. We refer to this group as advocating \"communitarian limits\". A third \"institutional reform\" approach argues that policy reform can reconcile economic and ecological goals – and is attacked from one side as anti-business alarmism, and from the other as indulging in pro-growth greenwash. Income up, environmental pressures down My colleagues and I have spent much of the past two years developing a new framework to explore how Australia can decouple economic growth from multiple environmental pressures – including greenhouse emissions, water stress, and the loss of native habitat. We use nine linked models to assess interactions between energy, water and food (and links to ecosystem services) in the context of climate change. The project provides projections for more than 20 scenarios, exploring different potential trends for consumption and working hours; energy and resource efficiency; agricultural productivity; new land-sector markets for energy feedstocks and ecosystem services; national and global abatement efforts, climate, and global economic growth. While our major focus is on Australia, at the national scale, we also model what might happen globally, and at more detailed state and local scales within Australia. We find economic growth and environmental impacts can be decoupled − in the right circumstances. National income per person increases by 12-15% per decade from now to 2050, while the value of economic activity almost triples. In stark contrast to income, which rises across all scenarios, environmental performance varies widely. Key environmental indicators such as greenhouse gas emissions, water stress, and native habitat and biodiversity are projected to more than double, stabilise, or fall across different scenarios to 2050. As shown in the chart below, we find that energy rises in all scenarios, but that greenhouse emissions can fall at the same time – with the right choices and technologies. Water use can also rise without increasing extractions from already stressed catchments. Food output (here indicated by protein) can increase, while native habitat is restored. Many of the 20 scenarios explored would represent substantial progress towards sustainable prosperity. Indeed, we find that Australia could begin to repair past damage: restoring significant areas of native habitat and achieving negative emissions (net sequestration) of greenhouse gasses. Growth of what? We use the normal definition of economic growth as measured by increase in Gross Domestic Product (GDP) – the value of goods and services produced in an economy – consistent with the national accounts framework. Some authors use a different definition, most notably Herman Daly a leading advocate for a steady state economy. Daly defines growth as an increase in physical economic scale, such as resource extraction, and goes on to argue that indefinite (material) economic growth is not possible. While this may be true, for his definition, it can be confusing for people that do not realise he is not referring to GDP growth. Indeed, Daly recently acknowledged that economic (GDP) growth is possible with finite resources and steady material throughput. These definitions matter: we project growth (GDP - measured in real dollars, adjusted for inflation) increases by more than 160% in scenarios where domestic material extractions and throughput (measured in tonnes) decreases by around 40%. Choosing a sustainable future But here is the real crunch: we find these substantial steps toward sustainability could build on policy approaches that are already in place in Australia or other countries. This implies Australia could make enormous progress towards a more sustainable future without a major change in what we value. We can be confident that a values shift is not required to achieve these outcomes – at least before 2050 – because none of the scenarios we modelled assume change in values or a new social or environmental ethic. Instead, we show that people will make choices to change their behaviour to make the best of particular policy settings. These choices shape production and consumption. For instance, we consider increasing Australia's climate effort in line with other countries would be consistent with Australian public opinion and assessments of Australia's national interest in limiting the rise in average global temperature to 2°C. So we do not interpret this as implying a change in values. But we find collective choices are crucial. For example, individual choices about whether to drive or catch a train to work are strongly shaped by prior collective choices about transport infrastructure. Collective choices are often, but not always implemented through changes in government policy, legislation, and programs. We find collective choices explain around 50-90% of differences in environmental performance and resource use across the scenarios we model. Consistent with the institutional reform approach, we find top-down collective choices are particularly important in shaping \"public good\" outcomes – accounting for at least 83% of the difference between scenarios for greenhouse gas emissions. Bottom-up individual choices play a greater role when private and public benefits are aligned. For instance individual choices account for up to half of the difference between scenarios for energy use (33–47%) and non-agricultural water consumption (16–53%). While individual choices are important, we find decisions we make as a society are likely to shape Australia's future sustainability more than the decisions we make as businesses and households. Sustainable prosperity is possible, but not predestined. Australia is free to choose. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Over two centuries of economic growth have put undeniable pressure on the ecological systems that underpin human well-being. While it is agreed that these pressures are increasing, views divide on how they may be alleviated. Some suggest technological advances will automatically keep us from transgressing key environmental thresholds; others that policy reform can reconcile economic and ecological goals; while a third school argues that only a fundamental shift in societal values can keep human demands within the Earth’s ecological limits. Here we use novel integrated analysis of the energy–water–food nexus, rural land use (including biodiversity), material flows and climate change to explore whether mounting ecological pressures in Australia can be reversed, while the population grows and living standards improve. We show that, in the right circumstances, economic and environmental outcomes can be decoupled. Although economic growth is strong across all scenarios, environmental performance varies widely: pressures are projected to more than double, stabilize or fall markedly by 2050. However, we find no evidence that decoupling will occur automatically. Nor do we find that a shift in societal values is required. Rather, extensions of current policies that mobilize technology and incentivize reduced pressure account for the majority of differences in environmental performance. Our results show that Australia can make great progress towards sustainable prosperity, if it chooses to do so. Main Our analysis uses a new integrated multi-model framework developed for the Australian National Outlook 1 . Australia is globally relevant: a major exporter of energy, mineral and agricultural products, with high per capita income, greenhouse gas emissions, water extractions, and habitat loss. The framework assesses energy–water–food interactions (and links to ecosystem services) in the context of climate change 2 , and uses more than 20 scenarios to explore a diverse range of factors shaping future Australian economic and environmental outcomes 1 , 2 . Interacting national trends and policies include energy and resource efficiency, agricultural productivity, consumption and working hours, and new land-sector markets for energy feed-stocks and ecosystem services (carbon sequestration and biodiversity conservation). These are modelled against four levels of national and global greenhouse gas emissions reduction effort (from no abatement to very strong abatement), and associated global climate trajectories (see Extended Data Fig. 9 ). As well as assessing the range of scenario outcomes, we identify the relative contributions of different types of choices. ‘Collective choices’ are defined as decisions that can only be implemented by groups of actors, and then constrain or empower ‘individual choices’ (particularly through changing rules and institutions). For example, individual choices about whether to drive or catch a train to work are strongly shaped by prior collective choices about transport infrastructure. The framework accounts for detailed interactions across sectors and spatial scales. The focal scale is national (the continent of Australia), accounting for key processes at higher (global) and lower (sub-national) spatial scales. This cross-domain integrated approach is needed because partial assessments may not account for constraints or adverse impacts that would undermine an otherwise ‘sustainable’ trajectory 3 , 4 , 5 , 6 , 7 , 8 . The projections and indicators are fully consistent with the international System of National Accounts 9 . We provide more details in the Supplementary Methods (section ‘Overview of modelling framework and scenarios’) and results for more than 60 national and global indicators in the Supplementary Data . Novel aspects of the analysis include assessing the potential for markets for ecosystem services to supply carbon sequestration and habitat restoration (and implications for agricultural output 7 and extinction risk) 10 , 11 ; assessing future water stress rather than simple volume of water extracted 2 , 12 ; exploring material extractions and environmental footprints 13 ; and integrating these elements with established models for analysing energy, greenhouse gas emissions and economic performance 2 , 14 , 15 , 16 , 17 . We are not aware of any other future-looking modelling that integrates this range of issues and indicators ( Supplementary Methods , ‘Overview of modelling framework and scenarios’). Economic and physical decoupling is possible We find that substantial economic and physical decoupling is possible 18 . Economically, Australia can achieve strong economic growth to 2050, indicated by rising gross domestic product (GDP) and gross national income (GNI) per capita, in scenarios where environmental pressures fall or are stable. Physically, we find the services derived from natural resources (energy ( Extended Data Fig. 2 ), water ( Extended Data Fig. 3 ), food ( Extended Data Fig. 4 )) can increase, while associated environmental pressures ease (greenhouse emissions ( Extended Data Fig. 6 ), water stress ( Extended Data Fig. 3 ), native habitat loss ( Extended Data Fig. 5 )). Importantly, these projected decouplings do not involve a reduction in the value of Australia’s heavy industry ( Extended Data Fig. 1g ), or outsourcing its environmental footprint to other nations 13 , 19 . Instead energy- and material-intensive sectors are projected to increase their share of economic activity, even in scenarios with the strongest global abatement efforts 1 , 2 . In all scenarios, Australia’s economy and living standards are projected to grow strongly (see Extended Data Fig. 1 ). As shown in Fig. 1 , the value of economic activity (GDP) is projected to rise tenfold over the 80 years to 2050, driven by a 2.9-fold increase in population ( Extended Data Fig. 8 ) and a 3.2–3.6-fold increase in GDP per capita (all values are in real 2010 Australian dollars, adjusted for inflation). National income (GNI) grows at a similar rate as GDP, with GNI per capita increasing by 58–82% from 2010 to 2050. Around two-thirds of the range of outcomes is explained by choices about working hours and consumption rather than environmental constraints. Average incomes rise by up to 66% if average working hours decline another 11% over the next four decades, in line with recent trends, and rise by 75% or more if there is no decline in working hours. The remaining income differential is accounted for by different assumptions<|im_end|> <|im_start|>assistant A sustainable Australia is possible – but we have to choose it. That's the finding of a paper published today in Nature. The paper is the result of a larger project to deliver the first Australian National Outlook report, more than two years in the making, which CSIRO is also releasing today. As part of this analysis we looked at whether achieving sustainability will require a shift in our values, such as rejecting consumerism. We also looked at the contributions of choices made by individuals (such as consuming less water or energy) and of choices made collectively by society (such as policies to reduce greenhouse gas emissions). We found that collective policy choices are crucial, and that Australia could make great progress to sustainability without any changes in social values. Competing views Few topics generate more heat, and less light, than debates over economic growth and sustainability. At one end of the spectrum, "technological optimists" suggest that the marvellous invisible hand will take care of everything, with market-driven improvements in technology automatically protecting essential natural resources while also improving living standards. Unfortunately, there is no real evidence to back this, particularly in protecting unpriced natural resources such as ocean fisheries, or the services provided by a stable climate. Instead the evidence suggests we are already crossing important planetary boundaries. Other the other end of the spectrum, people argue that achieving sustainability will require a rejection of economic growth, or a shift in values away from consumerism and towards a more ecologically attuned lifestyles. We refer to this group as advocating "communitarian limits". A third "institutional reform" approach argues that policy reform can reconcile economic and ecological goals – and is attacked from one side as anti-business alarmism, and from the other as indulging in pro-growth greenwash. Income up, environmental pressures down My colleagues and I have spent much of the past two years developing a new framework to explore how Australia can decouple economic growth from multiple environmental pressures – including greenhouse emissions, water stress, and the loss of native habitat. We use nine linked models to assess interactions between energy, water and food (and links to ecosystem services) in the context of climate change. The project provides projections for more than 20 scenarios, exploring different potential trends for consumption and working hours; energy and resource efficiency; agricultural productivity; new land-sector markets for energy feedstocks and ecosystem services; national and global abatement efforts, climate, and global economic growth. While our major focus is on Australia, at the national scale, we also model what might happen globally, and at more detailed state and local scales within Australia. We find economic growth and environmental impacts can be decoupled − in the right circumstances. National income per person increases by 12-15% per decade from now to 2050, while the value of economic activity almost triples. In stark contrast to income, which rises across all scenarios, environmental performance varies widely. Key environmental indicators such as greenhouse gas emissions, water stress, and native habitat and biodiversity are projected to more than double, stabilise, or fall across different scenarios to 2050. As shown in the chart below, we find that energy rises in all scenarios, but that greenhouse emissions can fall at the same time – with the right choices and technologies. Water use can also rise without increasing extractions from already stressed catchments. Food output (here indicated by protein) can increase, while native habitat is restored. Many of the 20 scenarios explored would represent substantial progress towards sustainable prosperity. Indeed, we find that Australia could begin to repair past damage: restoring significant areas of native habitat and achieving negative emissions (net sequestration) of greenhouse gasses. Growth of what? We use the normal definition of economic growth as measured by increase in Gross Domestic Product (GDP) – the value of goods and services produced in an economy – consistent with the national accounts framework. Some authors use a different definition, most notably Herman Daly a leading advocate for a steady state economy. Daly defines growth as an increase in physical economic scale, such as resource extraction, and goes on to argue that indefinite (material) economic growth is not possible. While this may be true, for his definition, it can be confusing for people that do not realise he is not referring to GDP growth. Indeed, Daly recently acknowledged that economic (GDP) growth is possible with finite resources and steady material throughput. These definitions matter: we project growth (GDP - measured in real dollars, adjusted for inflation) increases by more than 160% in scenarios where domestic material extractions and throughput (measured in tonnes) decreases by around 40%. Choosing a sustainable future But here is the real crunch: we find these substantial steps toward sustainability could build on policy approaches that are already in place in Australia or other countries. This implies Australia could make enormous progress towards a more sustainable future without a major change in what we value. We can be confident that a values shift is not required to achieve these outcomes – at least before 2050 – because none of the scenarios we modelled assume change in values or a new social or environmental ethic. Instead, we show that people will make choices to change their behaviour to make the best of particular policy settings. These choices shape production and consumption. For instance, we consider increasing Australia's climate effort in line with other countries would be consistent with Australian public opinion and assessments of Australia's national interest in limiting the rise in average global temperature to 2°C. So we do not interpret this as implying a change in values. But we find collective choices are crucial. For example, individual choices about whether to drive or catch a train to work are strongly shaped by prior collective choices about transport infrastructure. Collective choices are often, but not always implemented through changes in government policy, legislation, and programs. We find collective choices explain around 50-90% of differences in environmental performance and resource use across the scenarios we model. Consistent with the institutional reform approach, we find top-down collective choices are particularly important in shaping "public good" outcomes – accounting for at least 83% of the difference between scenarios for greenhouse gas emissions. Bottom-up individual choices play a greater role when private and public benefits are aligned. For instance individual choices account for up to half of the difference between scenarios for energy use (33–47%) and non-agricultural water consumption (16–53%). While individual choices are important, we find decisions we make as a society are likely to shape Australia's future sustainability more than the decisions we make as businesses and households. Sustainable prosperity is possible, but not predestined. Australia is free to choose. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract In most human societies, there are taboos and laws banning mating between first- and second-degree relatives, but actual prevalence and effects on health and fitness are poorly quantified. Here, we leverage a large observational study of ~450,000 participants of European ancestry from the UK Biobank (UKB) to quantify extreme inbreeding (EI) and its consequences. We use genotyped SNPs to detect large runs of homozygosity (ROH) and call EI when >10% of an individual’s genome comprise ROHs. We estimate a prevalence of EI of ~0.03%, i.e., ~1/3652. EI cases have phenotypic means between 0.3 and 0.7 standard deviation below the population mean for 7 traits, including stature and cognitive ability, consistent with inbreeding depression estimated from individuals with low levels of inbreeding. Our study provides DNA-based quantification of the prevalence of EI in a European ancestry sample from the UK and measures its effects on health and fitness traits. Introduction Mating between close relatives, that is inbreeding, is reported in many species to yield deleterious outcomes, such as reduced fertility 1 , 2 , 3 , 4 , stature 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 and lifespan 2 . In humans, consanguineous mating leads to higher childhood mortality 3 , 11 , 12 and to adverse effects on traits such as lung function 4 , 10 , 13 and cognitive ability 4 , 8 , 10 , 13 . Because of its detrimental consequences, also referred to as inbreeding depression, a number of species have developed inbreeding avoidance mechanisms to limit its effects 14 . In humans, inbreeding avoidance mechanisms, include cultural and religious taboos on incest, and laws explicitly forbidding certain types of mating. For instance, the Sexual Offences Act (2003) in the UK specifically forbids mating between first-degree (parent–offspring or fullsibs (FS), i.e., coefficient of relationship of 0.5) and second-degree (halfsibs (HS), grandparent–grandchild, avuncular or double-first cousins, i.e., coefficient of relationship of 0.25) relatives; and also forbids mating between step and relatives when one of the family members is below 18 years old. Cultural, legal, religious and health-related constraints strongly weigh on the ability to observe, and therefore study the causes and consequences of inbreeding between first- and second-degree relatives, hereafter referred to as extreme inbreeding (EI). A number of previous studies have attempted to quantify the prevalence and incidence of EI 15 , 16 , 17 , 18 , 19 , 20 . However, as underlined by van den Berghe 21 , the estimates which they produced are questionable given the “disinclination of family members to report incest when it occurs, and the countervailing bias of many scholars and crusaders to magnify the problem on which they build their career”. Add to these limitations, the relatively small size of these studies (often <1000 participants) and the discrepancies between them with respect to the definition of EI, as some of these studies included mating between step-relatives 21 . Here, we leverage a large observational study of ~450,000 participants, the UK Biobank (UKB), to quantify EI and its consequences in contemporary European descents from the UK population. We compare our estimates with the prevalence of police-recorded cases of incest offences reported in the Crime Survey for England and Wales (CSEW) between April 2002 and March 2017. We also characterise the distribution of runs of homozygosity (ROHs) in EI cases and assess its consistency with theoretical predictions. Finally, we characterise the phenotypic consequences of EI on a number of health-related traits measured in UKB participants. Results Prevalence of EI in European descents from the UKB We previously identified 22 456,426 individuals of European ancestry among the 487,409 UKB participants who have been genotyped. Ancestry was called in our previous study using projected principal components analysis based on known ancestry and whole-genome sequence data from 2504 participants of the 1000 Genomes Project 23 (Methods). Given that 12 participants had retracted consent, we only analysed 456,414 UKB participants in the present study. We used 301,412 quality-controlled genotyped single-nucleotide polymorphisms (SNPs) to call ROHs using the PLINK software (Methods). As in previous studies 4 , 8 , 10 , ROHs were defined as homozygous >1.5 Mb long genomic segments (Methods). We then estimated for each study participant the percentage of their autosome comprising ROHs as a measure of inbreeding. Such inbreeding measure, hereafter denoted F ROH , is a well-established predictor of pedigree inbreeding 24 , 25 . Following guidelines from the American College of Medical Genetics and Genomics (ACMG) 26 , 27 , EI was called for individuals with F ROH > 0.1. The use of both F ROH as a measure of inbreeding and of this threshold are recommended by the ACMG for detecting suspected consanguinity between parents. We thus identified 125 unrelated participants (65 males and 60 females) whose genomes are consistent with their parents being first- or second-degree relatives. That represents a prevalence of EI ~0.03%, i.e., ~1/3652 (95% confidence interval—CI 95% : [1/4428–1/3106]). As a sensitivity analysis, and consistent with theory predicting much longer ROHs under EI, we re-estimated the prevalence of EI considering only ROHs > 2 Mb or >5 Mb long. Using these alternative definitions of ROH, also recommended in the ACMG guidelines, we detected 115 (prevalence of ~1/3969; CI 95% : [1/4857–1/3355]) and 98 (prevalence of ~1/4658; CI 95% : [1/5807–1/3887]) cases of EI, respectively. We also estimated the prevalence of EI using allele-frequency based inbreeding measures or using ROHs detected on both autosome and X-chromosomes of female participants. (Supplementary Table 1 ). Given that the latter estimates of the prevalence of EI are not statistically distinct (paired t test: p > 0.05) from our first estimate based on ROHs > 1.5 Mb, we will hereafter only consider ROHs > 1.5 Mb. We then compared our estimate of the prevalence of EI with the prevalence of incest offences reported in the CSEW between April 2002 and March 2017. That survey reports a total of 11,196 cases of police-recorded incest offences over this time period (URLs). Relative", "role": "user" }, { "content": "A team of researchers has found a way to gauge the rate of extreme inbreeding (EI) in the U.K. and its possible health repercussions. In their paper published in the journal Nature Communications, the group describes their study of data from the U.K. Biobank and what they found. The researchers began their study by noting that not a lot of research has been done surrounding EI, which they define as reproduction between people that are closely related, such as siblings or aunts or uncles. They note that EI is considered taboo in most societies, and is very often outlawed. This has led to limited information on the topic. To learn more about EI in the U.K., the researchers turned to the U.K. Biobank, which contains information from approximately 450,000 voluntary participants, all of whom have European ancestry. In sifting through the data in the Biobank, the researchers looked at genetic information, specifically, for large runs of homozygosity—an indicator of close family ties between parents. They report that they found 125 cases of individuals who they believed were the product of inbreeding—a rate of one in 3,652. That number differs significantly from police incest reports, which show a rate of one in 5,247. The researchers then looked at the health histories of those individuals and compared them with people in society at large. They report that they found that such individuals were at a slightly higher risk of a variety of health effects. They were on average slightly shorter, were less smart, and were less able to reproduce. They also were more likely to have lung function problems and were more likely to contract diseases than the average person. The researchers acknowledge that their dataset might have been somewhat limited—people who volunteer to be tested and have their data added to the Biobank tend to be wealthy, healthy and more highly educated. That could have skewed the results. If so, the researchers suggest it likely skews low, because those with more health problems due to inbreeding would not volunteer to as participants. They conclude by claiming that their study backs up claims of the ill health effects of inbreeding. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract In most human societies, there are taboos and laws banning mating between first- and second-degree relatives, but actual prevalence and effects on health and fitness are poorly quantified. Here, we leverage a large observational study of ~450,000 participants of European ancestry from the UK Biobank (UKB) to quantify extreme inbreeding (EI) and its consequences. We use genotyped SNPs to detect large runs of homozygosity (ROH) and call EI when >10% of an individual’s genome comprise ROHs. We estimate a prevalence of EI of ~0.03%, i.e., ~1/3652. EI cases have phenotypic means between 0.3 and 0.7 standard deviation below the population mean for 7 traits, including stature and cognitive ability, consistent with inbreeding depression estimated from individuals with low levels of inbreeding. Our study provides DNA-based quantification of the prevalence of EI in a European ancestry sample from the UK and measures its effects on health and fitness traits. Introduction Mating between close relatives, that is inbreeding, is reported in many species to yield deleterious outcomes, such as reduced fertility 1 , 2 , 3 , 4 , stature 2 , 4 , 5 , 6 , 7 , 8 , 9 , 10 and lifespan 2 . In humans, consanguineous mating leads to higher childhood mortality 3 , 11 , 12 and to adverse effects on traits such as lung function 4 , 10 , 13 and cognitive ability 4 , 8 , 10 , 13 . Because of its detrimental consequences, also referred to as inbreeding depression, a number of species have developed inbreeding avoidance mechanisms to limit its effects 14 . In humans, inbreeding avoidance mechanisms, include cultural and religious taboos on incest, and laws explicitly forbidding certain types of mating. For instance, the Sexual Offences Act (2003) in the UK specifically forbids mating between first-degree (parent–offspring or fullsibs (FS), i.e., coefficient of relationship of 0.5) and second-degree (halfsibs (HS), grandparent–grandchild, avuncular or double-first cousins, i.e., coefficient of relationship of 0.25) relatives; and also forbids mating between step and relatives when one of the family members is below 18 years old. Cultural, legal, religious and health-related constraints strongly weigh on the ability to observe, and therefore study the causes and consequences of inbreeding between first- and second-degree relatives, hereafter referred to as extreme inbreeding (EI). A number of previous studies have attempted to quantify the prevalence and incidence of EI 15 , 16 , 17 , 18 , 19 , 20 . However, as underlined by van den Berghe 21 , the estimates which they produced are questionable given the “disinclination of family members to report incest when it occurs, and the countervailing bias of many scholars and crusaders to magnify the problem on which they build their career”. Add to these limitations, the relatively small size of these studies (often <1000 participants) and the discrepancies between them with respect to the definition of EI, as some of these studies included mating between step-relatives 21 . Here, we leverage a large observational study of ~450,000 participants, the UK Biobank (UKB), to quantify EI and its consequences in contemporary European descents from the UK population. We compare our estimates with the prevalence of police-recorded cases of incest offences reported in the Crime Survey for England and Wales (CSEW) between April 2002 and March 2017. We also characterise the distribution of runs of homozygosity (ROHs) in EI cases and assess its consistency with theoretical predictions. Finally, we characterise the phenotypic consequences of EI on a number of health-related traits measured in UKB participants. Results Prevalence of EI in European descents from the UKB We previously identified 22 456,426 individuals of European ancestry among the 487,409 UKB participants who have been genotyped. Ancestry was called in our previous study using projected principal components analysis based on known ancestry and whole-genome sequence data from 2504 participants of the 1000 Genomes Project 23 (Methods). Given that 12 participants had retracted consent, we only analysed 456,414 UKB participants in the present study. We used 301,412 quality-controlled genotyped single-nucleotide polymorphisms (SNPs) to call ROHs using the PLINK software (Methods). As in previous studies 4 , 8 , 10 , ROHs were defined as homozygous >1.5 Mb long genomic segments (Methods). We then estimated for each study participant the percentage of their autosome comprising ROHs as a measure of inbreeding. Such inbreeding measure, hereafter denoted F ROH , is a well-established predictor of pedigree inbreeding 24 , 25 . Following guidelines from the American College of Medical Genetics and Genomics (ACMG) 26 , 27 , EI was called for individuals with F ROH > 0.1. The use of both F ROH as a measure of inbreeding and of this threshold are recommended by the ACMG for detecting suspected consanguinity between parents. We thus identified 125 unrelated participants (65 males and 60 females) whose genomes are consistent with their parents being first- or second-degree relatives. That represents a prevalence of EI ~0.03%, i.e., ~1/3652 (95% confidence interval—CI 95% : [1/4428–1/3106]). As a sensitivity analysis, and consistent with theory predicting much longer ROHs under EI, we re-estimated the prevalence of EI considering only ROHs > 2 Mb or >5 Mb long. Using these alternative definitions of ROH, also recommended in the ACMG guidelines, we detected 115 (prevalence of ~1/3969; CI 95% : [1/4857–1/3355]) and 98 (prevalence of ~1/4658; CI 95% : [1/5807–1/3887]) cases of EI, respectively. We also estimated the prevalence of EI using allele-frequency based inbreeding measures or using ROHs detected on both autosome and X-chromosomes of female participants. (Supplementary Table 1 ). Given that the latter estimates of the prevalence of EI are not statistically distinct (paired t test: p > 0.05) from our first estimate based on ROHs > 1.5 Mb, we will hereafter only consider ROHs > 1.5 Mb. We then compared our estimate of the prevalence of EI with the prevalence of incest offences reported in the CSEW between April 2002 and March 2017. That survey reports a total of 11,196 cases of police-recorded incest offences over this time period (URLs). Relative<|im_end|> <|im_start|>assistant A team of researchers has found a way to gauge the rate of extreme inbreeding (EI) in the U.K. and its possible health repercussions. In their paper published in the journal Nature Communications, the group describes their study of data from the U.K. Biobank and what they found. The researchers began their study by noting that not a lot of research has been done surrounding EI, which they define as reproduction between people that are closely related, such as siblings or aunts or uncles. They note that EI is considered taboo in most societies, and is very often outlawed. This has led to limited information on the topic. To learn more about EI in the U.K., the researchers turned to the U.K. Biobank, which contains information from approximately 450,000 voluntary participants, all of whom have European ancestry. In sifting through the data in the Biobank, the researchers looked at genetic information, specifically, for large runs of homozygosity—an indicator of close family ties between parents. They report that they found 125 cases of individuals who they believed were the product of inbreeding—a rate of one in 3,652. That number differs significantly from police incest reports, which show a rate of one in 5,247. The researchers then looked at the health histories of those individuals and compared them with people in society at large. They report that they found that such individuals were at a slightly higher risk of a variety of health effects. They were on average slightly shorter, were less smart, and were less able to reproduce. They also were more likely to have lung function problems and were more likely to contract diseases than the average person. The researchers acknowledge that their dataset might have been somewhat limited—people who volunteer to be tested and have their data added to the Biobank tend to be wealthy, healthy and more highly educated. That could have skewed the results. If so, the researchers suggest it likely skews low, because those with more health problems due to inbreeding would not volunteer to as participants. They conclude by claiming that their study backs up claims of the ill health effects of inbreeding. <|im_end|>

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1,965

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Coral microbial flora has been attracting attention because of their potential to protect corals from environmental stresses or pathogens. Although coral-associated bacteria are considered to be acquired from seawater, little is known about the relationships between microbial composition in corals and its surrounding seawater. Here, we tested several methods to identify coral-associated bacteria in coral and its surrounding seawater to detect specific types of Ruegeria species, some of which exhibit growth inhibition activities against the coral pathogen Vibrio coralliilyticus . We first isolated coral-associated bacteria from the reef-building coral Galaxea fascicularis collected at Sesoko Island, Okinawa, Japan, via random colony picking, which showed the existence of varieties of bacteria including Ruegeria species. Using newly constructed primers for colony PCR, several Ruegeria species were successfully isolated from G. fascicularis and seawater. We further investigated the seawater microbiome in association with the distance from coral reefs. By seasonal sampling, it was suggested that the seawater microbiome is more affected by seasonality than the distance from coral reefs. These methods and results may contribute to investigating and understanding the relationships between the presence of corals and microbial diversity in seawater, in addition to the efficient isolation of specific bacterial species from coral or its surrounding seawater. Access provided by MPDL Services gGmbH c/o Max Planck Digital Library Working on a manuscript? Avoid the common mistakes Introduction Coral reefs are considered to play an essential role in maintaining marine biodiversity, including fish (Descombes 2015 ; Jones et al. 2004 ) and bacteria involved in the biogeochemical cycle of sulfur (Raina et al. 2009 ). Since corals are endangered (Carpenter 2008 ; Dietzel et al. 2021 ), extensive research has been conducted to understand the mechanisms of maintaining coral health. In recent years, coral microbiota have attracted attention from the viewpoint of relevance to coral health (Bourne et al. 2016 ; Peixoto et al. 2017 ; Peixoto 2021 ; Reshef et al. 2006 ; Rosenberg et al. 2007 ). It is well known that the microbiota in diseased coral changes compared to the healthy state (Meyer et al. 2019 ; Rosales et al. 2019 ; Sweet et al. 2019 ). Coral microbiota are also affected by bleaching (Pootakham 2018 ) or environmental stresses (Maher et al. 2019 ; Vega Thurber 2009 ), including heat stress (Pootakham 2019 ) and the combined stress of heat and acidification (Grottoli 2018 ). Conversely, the composition of microbial flora is considered to be related to coral resilience to environmental stresses (Grottoli et al. 2018 ; Ziegler et al. 2017 ). In fact, microbial mixtures extracted from corals have been shown to protect the reef-building coral Pocillopora damicornis from bleaching induced by heat stress as well as exposure to a coral pathogen, Vibrio coralliilyticus (Rosado 2019 ), suggesting that the composition of coral microbiota can assist in maintaining the healthy status of corals. Hence, monitoring coral microbiota is considered to be effective to predict risks of environmental or pathological coral bleaching. Coral-associated bacteria are considered to be acquired from seawater (Bernasconi et al. 2019 ). Previously, Glasl and colleagues suggested that the composition of the microbial flora in seawater around coral could be used as an environmental indicator (Glasl et al. 2019 ). However, whether the distribution of specific types of bacteria in seawater is related to the existence or status of coral reefs is not known. Recently, it has been suggested that specific types of bacteria can contribute to protecting coral health. For example, carotenoid-producing Muricauda sp. isolated from the reef-building coral Galaxea fascicularis has been shown to recover photosynthetic activities of the coral symbiont zooxanthellae under heat and higher-light stress (Motone et al. 2020 ), suggesting a role of Flavobacteriia in protecting corals from environmental stress. It has also been suggested that several bacterial species inhibit the growth of pathogens. Various bacterial species isolated from corals have been shown to inhibit the in vitro growth of V . coralliilyticus (Miura et al. 2019 ; Raina 2016 ; Tang et al. 2020 ), which is considered to be one of the coral pathogens (Ben-Haim et al. 2003 ). We have previously isolated several G . fascicularis -associated Ruegeria spp. that inhibit the in vitro growth of V . coralliilyticus P1 strain (Miura et al. 2019 ). Ruegeria spp. are known to play essential roles in marine ecosystems by supplying vitamin B 12 to phytoplankton and contributing to marine carbon and sulfur cycles (Durham 2015 ). Hence, Ruegeria spp. are not only potentially probiotic toward corals but also considered to be important bacterial lineages to protect marine ecosystems. Although Ruegeria spp. are known to be widely distributed in seawater (Sonnenschein 2017 ), their distribution and functions associated with corals are not well understood. In this study, we evaluated several methods, including classical techniques for isolation of coral-associated bacteria, direct colony polymerase chain reaction (colony PCR), real-time PCR using previously constructed Ruegeria -specific primer sets (Kitamura et al. 2020 ), in addition to the 16S metabarcoding analysis of seawater, to survey the distribution of Ruegeria spp. inhabiting the interior and exterior of corals. We investigated the distribution of coral-associated Ruegeria spp. near Sesoko Island, Okinawa, Japan, which harbor a variety of stony and soft corals (Loya et al. 2001 ), including G . fascicularis and Acropora tenuis (Yuyama et al. 2012 ). Although G . fascicularis is a relatively minor player among reef-building corals found around Sesoko Island, it is easily detectable and identifiable in the field. Here, we isolated several Ruegeria spp. from G . fascicularis , and tested methods to detect Ruegeria spp. in seawater from around Sesoko Island. Furthermore, we investigated microbial flora in seawater related to seasonality and distance from coral reefs. Materials and Methods Strains and Media Escherichia coli BW25113 ( rrnB DElacZ4787 hdR514 DE ( araBAD ) 567 DE ( rhaBAD ) 568 rph-1 ) was cultured in LB medium (Nacalai Tesque Inc., Kyoto, Japan). Vibrio coralliilyticus P1 was purchased from the Belgian Coordinated Collections of Microorganisms ( ). V . coralliilyticus P1 and", "role": "user" }, { "content": "The multi-institute research team developed a method to quickly and noninvasively test for bacteria species known to benefit coral—they test the seawater near the coral. Their approach, first published online on July 18 in Marine Biotechnology, was featured on the cover of the journal's August print edition. \"Some coral-associated bacteria are thought to protect coral as probiotics, and in order to develop coral probiotics, it is important to collect such bacteria for further study,\" said paper author Natsuko Miura, assistant professor in the Graduate School of Life and Environmental Sciences at Osaka Prefecture University. She also noted that detecting and identifying bacteria is key to checking the balance of the coral's bacterial flora, the collective balance of bacteria that exist on any organism. \"Previously, researchers suggested that the composition of the microbial flora in seawater around coral could be used as an environmental indicator,\" Miura said, explaining that the challenge is determining exactly how the distribution of bacteria in seawater reflects the coral health. \"To better understand this, we collect and analyze bacteria from coral. But, in previous collection methods, coral-associated bacteria were obtained by destroying the coral body. We thought it was problematic to destroy the coral in order to protect it.\" The researchers set out to develop a quick detection method to identify beneficial bacteria in seawater samples taken from around coral reefs. They focused on Galaxea fascicularis, a reef-building coral found off the coast of Sesoko Island in Okinawa, Japan. Species of Ruegeria bacteria are thought to offer probiotic benefits to this coral, such as B12 vitamin production and protection against some pathogens, according to Miura. In general, to identify specific species, researchers use two fragments of defined genetic code called primers to target and isolate desired longer genetic sequences. Once isolated, the sequence can be copied and amplified in quantities large enough to match to individual species. Frequently, potential primers are proposed based on various genetic factors but require verification. Seawater around the corals was collected using plastic containers for bacterial isolation and microbiota investigation. Credit: H.Yamashiro, The University of the Ryukyus In addition to newly developed primers, Miura and her team hypothesized that the physical characteristics of two primers from a set of 55 proposed in 2020 that were needed to verify the seawater contents during this development period, would reliably identify Ruegeria species in samples of seawater and coral from around Sesoko Island in just a few hours. They were right. \"Our results indicate that this specific primer set enables easy and rapid isolation of specific bacterial species, facilitating isolation of bacteria of interest,\" Miura said, adding that they found higher concentrations of the Ruegeria species in coral than in seawater, suggesting that the bacteria may be concentrated in coral. \"While further studies are needed to determine differences in the abundance of bacteria in corals and seawater, the newly developed method makes it easier to quickly check if seawater around the coral obtains beneficial coral-related bacteria without destroying the coral.\" The researchers are now supplying samples of the identified bacteria species to public repositories with the hope that others will be able to expand and accelerate the work to better understand and use coral probiotics, according to Miura. \"In the future, checking for bacteria in the seawater around the coral will allow us to quickly check the health of the coral,\" Miura said. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Coral microbial flora has been attracting attention because of their potential to protect corals from environmental stresses or pathogens. Although coral-associated bacteria are considered to be acquired from seawater, little is known about the relationships between microbial composition in corals and its surrounding seawater. Here, we tested several methods to identify coral-associated bacteria in coral and its surrounding seawater to detect specific types of Ruegeria species, some of which exhibit growth inhibition activities against the coral pathogen Vibrio coralliilyticus . We first isolated coral-associated bacteria from the reef-building coral Galaxea fascicularis collected at Sesoko Island, Okinawa, Japan, via random colony picking, which showed the existence of varieties of bacteria including Ruegeria species. Using newly constructed primers for colony PCR, several Ruegeria species were successfully isolated from G. fascicularis and seawater. We further investigated the seawater microbiome in association with the distance from coral reefs. By seasonal sampling, it was suggested that the seawater microbiome is more affected by seasonality than the distance from coral reefs. These methods and results may contribute to investigating and understanding the relationships between the presence of corals and microbial diversity in seawater, in addition to the efficient isolation of specific bacterial species from coral or its surrounding seawater. Access provided by MPDL Services gGmbH c/o Max Planck Digital Library Working on a manuscript? Avoid the common mistakes Introduction Coral reefs are considered to play an essential role in maintaining marine biodiversity, including fish (Descombes 2015 ; Jones et al. 2004 ) and bacteria involved in the biogeochemical cycle of sulfur (Raina et al. 2009 ). Since corals are endangered (Carpenter 2008 ; Dietzel et al. 2021 ), extensive research has been conducted to understand the mechanisms of maintaining coral health. In recent years, coral microbiota have attracted attention from the viewpoint of relevance to coral health (Bourne et al. 2016 ; Peixoto et al. 2017 ; Peixoto 2021 ; Reshef et al. 2006 ; Rosenberg et al. 2007 ). It is well known that the microbiota in diseased coral changes compared to the healthy state (Meyer et al. 2019 ; Rosales et al. 2019 ; Sweet et al. 2019 ). Coral microbiota are also affected by bleaching (Pootakham 2018 ) or environmental stresses (Maher et al. 2019 ; Vega Thurber 2009 ), including heat stress (Pootakham 2019 ) and the combined stress of heat and acidification (Grottoli 2018 ). Conversely, the composition of microbial flora is considered to be related to coral resilience to environmental stresses (Grottoli et al. 2018 ; Ziegler et al. 2017 ). In fact, microbial mixtures extracted from corals have been shown to protect the reef-building coral Pocillopora damicornis from bleaching induced by heat stress as well as exposure to a coral pathogen, Vibrio coralliilyticus (Rosado 2019 ), suggesting that the composition of coral microbiota can assist in maintaining the healthy status of corals. Hence, monitoring coral microbiota is considered to be effective to predict risks of environmental or pathological coral bleaching. Coral-associated bacteria are considered to be acquired from seawater (Bernasconi et al. 2019 ). Previously, Glasl and colleagues suggested that the composition of the microbial flora in seawater around coral could be used as an environmental indicator (Glasl et al. 2019 ). However, whether the distribution of specific types of bacteria in seawater is related to the existence or status of coral reefs is not known. Recently, it has been suggested that specific types of bacteria can contribute to protecting coral health. For example, carotenoid-producing Muricauda sp. isolated from the reef-building coral Galaxea fascicularis has been shown to recover photosynthetic activities of the coral symbiont zooxanthellae under heat and higher-light stress (Motone et al. 2020 ), suggesting a role of Flavobacteriia in protecting corals from environmental stress. It has also been suggested that several bacterial species inhibit the growth of pathogens. Various bacterial species isolated from corals have been shown to inhibit the in vitro growth of V . coralliilyticus (Miura et al. 2019 ; Raina 2016 ; Tang et al. 2020 ), which is considered to be one of the coral pathogens (Ben-Haim et al. 2003 ). We have previously isolated several G . fascicularis -associated Ruegeria spp. that inhibit the in vitro growth of V . coralliilyticus P1 strain (Miura et al. 2019 ). Ruegeria spp. are known to play essential roles in marine ecosystems by supplying vitamin B 12 to phytoplankton and contributing to marine carbon and sulfur cycles (Durham 2015 ). Hence, Ruegeria spp. are not only potentially probiotic toward corals but also considered to be important bacterial lineages to protect marine ecosystems. Although Ruegeria spp. are known to be widely distributed in seawater (Sonnenschein 2017 ), their distribution and functions associated with corals are not well understood. In this study, we evaluated several methods, including classical techniques for isolation of coral-associated bacteria, direct colony polymerase chain reaction (colony PCR), real-time PCR using previously constructed Ruegeria -specific primer sets (Kitamura et al. 2020 ), in addition to the 16S metabarcoding analysis of seawater, to survey the distribution of Ruegeria spp. inhabiting the interior and exterior of corals. We investigated the distribution of coral-associated Ruegeria spp. near Sesoko Island, Okinawa, Japan, which harbor a variety of stony and soft corals (Loya et al. 2001 ), including G . fascicularis and Acropora tenuis (Yuyama et al. 2012 ). Although G . fascicularis is a relatively minor player among reef-building corals found around Sesoko Island, it is easily detectable and identifiable in the field. Here, we isolated several Ruegeria spp. from G . fascicularis , and tested methods to detect Ruegeria spp. in seawater from around Sesoko Island. Furthermore, we investigated microbial flora in seawater related to seasonality and distance from coral reefs. Materials and Methods Strains and Media Escherichia coli BW25113 ( rrnB DElacZ4787 hdR514 DE ( araBAD ) 567 DE ( rhaBAD ) 568 rph-1 ) was cultured in LB medium (Nacalai Tesque Inc., Kyoto, Japan). Vibrio coralliilyticus P1 was purchased from the Belgian Coordinated Collections of Microorganisms ( ). V . coralliilyticus P1 and<|im_end|> <|im_start|>assistant The multi-institute research team developed a method to quickly and noninvasively test for bacteria species known to benefit coral—they test the seawater near the coral. Their approach, first published online on July 18 in Marine Biotechnology, was featured on the cover of the journal's August print edition. "Some coral-associated bacteria are thought to protect coral as probiotics, and in order to develop coral probiotics, it is important to collect such bacteria for further study," said paper author Natsuko Miura, assistant professor in the Graduate School of Life and Environmental Sciences at Osaka Prefecture University. She also noted that detecting and identifying bacteria is key to checking the balance of the coral's bacterial flora, the collective balance of bacteria that exist on any organism. "Previously, researchers suggested that the composition of the microbial flora in seawater around coral could be used as an environmental indicator," Miura said, explaining that the challenge is determining exactly how the distribution of bacteria in seawater reflects the coral health. "To better understand this, we collect and analyze bacteria from coral. But, in previous collection methods, coral-associated bacteria were obtained by destroying the coral body. We thought it was problematic to destroy the coral in order to protect it." The researchers set out to develop a quick detection method to identify beneficial bacteria in seawater samples taken from around coral reefs. They focused on Galaxea fascicularis, a reef-building coral found off the coast of Sesoko Island in Okinawa, Japan. Species of Ruegeria bacteria are thought to offer probiotic benefits to this coral, such as B12 vitamin production and protection against some pathogens, according to Miura. In general, to identify specific species, researchers use two fragments of defined genetic code called primers to target and isolate desired longer genetic sequences. Once isolated, the sequence can be copied and amplified in quantities large enough to match to individual species. Frequently, potential primers are proposed based on various genetic factors but require verification. Seawater around the corals was collected using plastic containers for bacterial isolation and microbiota investigation. Credit: H.Yamashiro, The University of the Ryukyus In addition to newly developed primers, Miura and her team hypothesized that the physical characteristics of two primers from a set of 55 proposed in 2020 that were needed to verify the seawater contents during this development period, would reliably identify Ruegeria species in samples of seawater and coral from around Sesoko Island in just a few hours. They were right. "Our results indicate that this specific primer set enables easy and rapid isolation of specific bacterial species, facilitating isolation of bacteria of interest," Miura said, adding that they found higher concentrations of the Ruegeria species in coral than in seawater, suggesting that the bacteria may be concentrated in coral. "While further studies are needed to determine differences in the abundance of bacteria in corals and seawater, the newly developed method makes it easier to quickly check if seawater around the coral obtains beneficial coral-related bacteria without destroying the coral." The researchers are now supplying samples of the identified bacteria species to public repositories with the hope that others will be able to expand and accelerate the work to better understand and use coral probiotics, according to Miura. "In the future, checking for bacteria in the seawater around the coral will allow us to quickly check the health of the coral," Miura said. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Luminous blue variables are massive, evolved stars that exhibit large variations in luminosity and size on timescales from months to years, with high associated rates of mass loss 1 , 2 , 3 , 4 , 5 . In addition to this on-going variability, these stars exhibit outburst phases, during which their size increases and as a result their effective temperature decreases, typically to about 9,000 kelvin 3 , 6 . Outbursts are believed to be caused by the radiation force on the cooler, more opaque, outer layers of the star balancing or even exceeding the force of gravity, although the exact mechanisms are unknown and cannot be determined using one-dimensional, spherically symmetric models of stars because such models cannot determine the physical processes that occur in this regime 7 . Here we report three-dimensional simulations of massive, radiation-dominated stars, which show that helium opacity has an important role in triggering outbursts and setting the observed effective temperature during outbursts of about 9,000 kelvin. It probably also triggers the episodic mass loss at rates of 10 −7 to 10 −5 solar masses per year. The peak in helium opacity is evident in our three-dimensional simulations only because the density and temperature of the stellar envelope (the outer part of the star near the photosphere) need to be determined self-consistently with convection, which cannot be done in one-dimensional models that assume spherical symmetry. The simulations reproduce observations of long-timescale variability, and predict that convection causes irregular oscillations in the radii of the stars and variations in brightness of 10–30 per cent on a typical timescale of a few days. The amplitudes of these short-timescale variations are predicted to be even larger for cooler stars (in the outburst phase). This short-timescale variability should be observable with high-cadence observations. Main We used 60 million CPU hours on the supercomputer Mira, awarded by the Argonne Leadership Computing Facility for the INCITE programme, as well as computational resources from NASA and NERSC (National Energy Research Scientific Computing Center), to solve the three-dimensional radiation hydrodynamic equations 8 and follow the physically realistic evolution of the stellar envelopes of luminous blue variables (LBVs; see Methods for the simulation set-up). These simulations take as inputs the fixed mass of the core of the star and its luminosity from the bottom (inner) boundary of the simulation area, and determine self-consistently the structure of the envelope, its effective temperature and the rate of mass loss. We performed three simulations: the first (which we refer to as T9L6.2) assumes an initial core mass of M i = 80 M ʘ , where M ʘ is the mass of the Sun, a luminosity relative to that of the Sun of log( L / L ʘ ) = 6.2 and an effective temperature of T eff = 9,000 K; the second (T19L6.4) assumes the same initial mass, M i = 80 M ʘ , log( L / L ʘ ) = 6.4 and T eff = 19,000 K; and the third (T19L6) assumes M i = 35 M ʘ , log( L / L ʘ ) = 6.0 and T eff = 19,000 K. Although the three simulations are based on one-dimensional models for stars with different initial masses and at different evolutionary stages (see Methods ), they share properties such as density and Eddington ratio (the ratio of radiation to gravitational acceleration) at the peak in opacity due to iron (at around 180,000 K). The main difference between our three simulations is the pressure scale height at the iron opacity peak, which results in different total stellar masses and optical depths above the convective region, and hence different surface temperatures 9 . The locations of the three models in the Hertzsprung–Russell diagram and the stellar-evolution tracks determined from the one-dimensional models are shown in Fig. 1 . The histories of spherically averaged radial profiles of density, turbulent velocity, radiation temperature and opacity for run T9L6.2 are shown in Fig. 2 . The envelope is convectively unstable at the iron opacity peak 7 , 9 , 10 , as indicated by the density increasing with radius around that region in the initial hydrostatic structure. Convection takes about 10 dynamical times (about 43 h; where one dynamical time is the time required for the radiation-supported sound waves to travel one pressure scale height in the convective region) to destroy the density inversion (density inversion means that the density increases rather than decreases with radius), which causes high-density clumps to rise, expand and cool to a temperature of less than about 6 × 10 4 K. Because the density of these cooled clumps is much greater than that of the unclumped gas at the same temperature before the onset of convection, a strong helium opacity peak appears (Fig. 2 , bottom). The local radiation acceleration after the helium opacity peak has formed is ten times larger than the gravitational acceleration, which causes a large fraction of the envelope to expand markedly, with most of the gas above that region blown away. The mass flux of unbound gas (positive total energy 11 ) leaving our simulation domain can reach an instantaneous rate of around 0.05 M ʘ yr −1 . After 400 h, the envelope settles to a steady state(Fig. 2 , right). Convection is still operating at around 80.90 R ʘ (where R ʘ is the radius of the Sun), with a second peak in helium opacity at around 200 R ʘ . Convection also causes envelope oscillations (that is, oscillations in the size or radius of the star) with a typical timescale of a day. The time-averaged location of the photosphere, at which the total Rosseland optical depth to the outer boundary of the simulation box is unity, is at 342.8 R ʘ , as indicated by the dashed blue lines in Fig. 2 . At this location, the average radiation temperature is 9.06 × 10 3 K. The mass-averaged turbulent velocity is only 1% of sound speed deep in the envelope, but", "role": "user" }, { "content": "Astrophysicists finally have an explanation for the violent mood swings of some of the biggest, brightest and rarest stars in the universe. The stars, called luminous blue variables, periodically erupt in dazzling outbursts nicknamed \"stellar geysers.\" These powerful eruptions launch entire planets' worth of material into space in a matter of days. The cause of this instability, however, has remained a mystery for decades. Now, new 3-D simulations by a team of astrophysicists suggest that turbulent motion in the outer layers of a massive star creates dense clumps of stellar material. These clumps catch the star's intense light like a solar sail, erupting material into space. After jettisoning enough mass, the star calms down until its outer layers re-form and the cycle begins anew, the astrophysicists report online September 26 in Nature. Identifying the cause of the stellar geysers is significant because every extremely massive star probably spends part of its life as a luminous blue variable, says study co-author Matteo Cantiello, an associate research scientist at the Center for Computational Astrophysics at the Flatiron Institute in New York City. A simulation of the turbulent gas that envelops a star 80 times the mass of the sun. Intense light from within the star pushes against dense pockets of helium-rich material in the star's outer layers, launching the material spaceward. The colors represent the density of the gas, with lighter colors signifying denser regions. Credit: Joseph Insley/Argonne Leadership Computing Facility \"This finding represents an important step forward in understanding the life and death of the biggest stars in the universe,\" says Cantiello. \"These massive stars, despite their small number, largely determine the evolution of galaxies through their stellar winds and supernova explosions. And when they die, they leave behind black holes.\" Luminous blue variables, or LBVs, are exceedingly rare, with only around a dozen spotted in and around the Milky Way galaxy. The gargantuan stars can exceed 100 times the mass of the sun and approach the theoretical limit of how massive stars can get. LBVs are also exceptionally radiant: The brightest ones shine with more than 1 million times the luminosity of the sun. That light pushes matter spaceward because absorption and re-emission of a photon by an atom results in a net outward shove. The tug of war between extreme gravity pulling material in and extreme luminosity pushing it out is responsible for the trademark outbursts of LBVs, scientists believe. The absorption of a photon by an atom, however, requires that electrons be bound in orbits around the atom's nucleus. In the deepest, hottest layers of a star, matter behaves as a plasma with electrons untethered from atoms. In the cooler outer layers, electrons begin rejoining their atoms and can therefore absorb photons again. Previously proposed explanations for the outbursts predicted that elements such as helium in the outer layers could absorb enough photons to overcome gravity and fly into space as an outburst. But simple, one-dimensional calculations didn't back up this hypothesis: The outer layers didn't seem sufficiently dense to catch enough light to overpower gravity. A simulation of the turbulent gas that envelops a star 80 times the mass of the sun. Intense light from within the star pushes against dense pockets of helium-rich material in the star's outer layers, launching the material spaceward. The solid colors denote radiation intensity, with bluer colors representing regions of larger intensity. The translucent purplish colors represent the gas density, with lighter colors denoting denser regions. Credit: Joseph Insley/Argonne Leadership Computing Facility Those simple calculations, however, didn't capture the full picture of the complex dynamics within a colossal star. Cantiello, along with Yan-Fei Jiang of the Kavli Institute for Theoretical Physics at the University of California, Santa Barbara, and colleagues took a more realistic approach. The researchers created a detailed, three-dimensional computer simulation of how matter, heat and light flow and interact within supersize stars. The calculations involved required more than 60 million computer processor hours to solve. In the simulation, the average density of the outer layers was too low for material to go flying—just as the one-dimensional calculations predicted. However, the new calculations revealed that convection and mixing in the outer layers resulted in some regions being denser than others, with some clumps opaque enough to be launched into space by the star's light. Such eruptions occur over timescales ranging from days to weeks as the star churns and its brightness fluctuates. The team estimates that such stars can shed around 10 billion trillion metric tons of material each year, roughly double the Earth's mass. The researchers plan to improve the accuracy of their simulations by incorporating other effects such as the star's rotation, which can make launching material into space easier near the star's fast-spinning equator than near the almost stationary poles. (This effect is the reason NASA launches its rockets from Florida and California rather than Maine or Alaska.) Improving the fidelity of star simulations is crucial to achieving astrophysical insights, Cantiello says. The move from simple, single-dimensional calculations to full 3-D simulations requires more computational muscle and more complex physics, but the results are well worth the trouble. \"We had to implement all of these physics to see, with our own eyes, that this process—that we didn't expect to be important—would turn out to be key to understanding these violent eruptions and the evolution of these massive stars,\" he says. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Luminous blue variables are massive, evolved stars that exhibit large variations in luminosity and size on timescales from months to years, with high associated rates of mass loss 1 , 2 , 3 , 4 , 5 . In addition to this on-going variability, these stars exhibit outburst phases, during which their size increases and as a result their effective temperature decreases, typically to about 9,000 kelvin 3 , 6 . Outbursts are believed to be caused by the radiation force on the cooler, more opaque, outer layers of the star balancing or even exceeding the force of gravity, although the exact mechanisms are unknown and cannot be determined using one-dimensional, spherically symmetric models of stars because such models cannot determine the physical processes that occur in this regime 7 . Here we report three-dimensional simulations of massive, radiation-dominated stars, which show that helium opacity has an important role in triggering outbursts and setting the observed effective temperature during outbursts of about 9,000 kelvin. It probably also triggers the episodic mass loss at rates of 10 −7 to 10 −5 solar masses per year. The peak in helium opacity is evident in our three-dimensional simulations only because the density and temperature of the stellar envelope (the outer part of the star near the photosphere) need to be determined self-consistently with convection, which cannot be done in one-dimensional models that assume spherical symmetry. The simulations reproduce observations of long-timescale variability, and predict that convection causes irregular oscillations in the radii of the stars and variations in brightness of 10–30 per cent on a typical timescale of a few days. The amplitudes of these short-timescale variations are predicted to be even larger for cooler stars (in the outburst phase). This short-timescale variability should be observable with high-cadence observations. Main We used 60 million CPU hours on the supercomputer Mira, awarded by the Argonne Leadership Computing Facility for the INCITE programme, as well as computational resources from NASA and NERSC (National Energy Research Scientific Computing Center), to solve the three-dimensional radiation hydrodynamic equations 8 and follow the physically realistic evolution of the stellar envelopes of luminous blue variables (LBVs; see Methods for the simulation set-up). These simulations take as inputs the fixed mass of the core of the star and its luminosity from the bottom (inner) boundary of the simulation area, and determine self-consistently the structure of the envelope, its effective temperature and the rate of mass loss. We performed three simulations: the first (which we refer to as T9L6.2) assumes an initial core mass of M i = 80 M ʘ , where M ʘ is the mass of the Sun, a luminosity relative to that of the Sun of log( L / L ʘ ) = 6.2 and an effective temperature of T eff = 9,000 K; the second (T19L6.4) assumes the same initial mass, M i = 80 M ʘ , log( L / L ʘ ) = 6.4 and T eff = 19,000 K; and the third (T19L6) assumes M i = 35 M ʘ , log( L / L ʘ ) = 6.0 and T eff = 19,000 K. Although the three simulations are based on one-dimensional models for stars with different initial masses and at different evolutionary stages (see Methods ), they share properties such as density and Eddington ratio (the ratio of radiation to gravitational acceleration) at the peak in opacity due to iron (at around 180,000 K). The main difference between our three simulations is the pressure scale height at the iron opacity peak, which results in different total stellar masses and optical depths above the convective region, and hence different surface temperatures 9 . The locations of the three models in the Hertzsprung–Russell diagram and the stellar-evolution tracks determined from the one-dimensional models are shown in Fig. 1 . The histories of spherically averaged radial profiles of density, turbulent velocity, radiation temperature and opacity for run T9L6.2 are shown in Fig. 2 . The envelope is convectively unstable at the iron opacity peak 7 , 9 , 10 , as indicated by the density increasing with radius around that region in the initial hydrostatic structure. Convection takes about 10 dynamical times (about 43 h; where one dynamical time is the time required for the radiation-supported sound waves to travel one pressure scale height in the convective region) to destroy the density inversion (density inversion means that the density increases rather than decreases with radius), which causes high-density clumps to rise, expand and cool to a temperature of less than about 6 × 10 4 K. Because the density of these cooled clumps is much greater than that of the unclumped gas at the same temperature before the onset of convection, a strong helium opacity peak appears (Fig. 2 , bottom). The local radiation acceleration after the helium opacity peak has formed is ten times larger than the gravitational acceleration, which causes a large fraction of the envelope to expand markedly, with most of the gas above that region blown away. The mass flux of unbound gas (positive total energy 11 ) leaving our simulation domain can reach an instantaneous rate of around 0.05 M ʘ yr −1 . After 400 h, the envelope settles to a steady state(Fig. 2 , right). Convection is still operating at around 80.90 R ʘ (where R ʘ is the radius of the Sun), with a second peak in helium opacity at around 200 R ʘ . Convection also causes envelope oscillations (that is, oscillations in the size or radius of the star) with a typical timescale of a day. The time-averaged location of the photosphere, at which the total Rosseland optical depth to the outer boundary of the simulation box is unity, is at 342.8 R ʘ , as indicated by the dashed blue lines in Fig. 2 . At this location, the average radiation temperature is 9.06 × 10 3 K. The mass-averaged turbulent velocity is only 1% of sound speed deep in the envelope, but<|im_end|> <|im_start|>assistant Astrophysicists finally have an explanation for the violent mood swings of some of the biggest, brightest and rarest stars in the universe. The stars, called luminous blue variables, periodically erupt in dazzling outbursts nicknamed "stellar geysers." These powerful eruptions launch entire planets' worth of material into space in a matter of days. The cause of this instability, however, has remained a mystery for decades. Now, new 3-D simulations by a team of astrophysicists suggest that turbulent motion in the outer layers of a massive star creates dense clumps of stellar material. These clumps catch the star's intense light like a solar sail, erupting material into space. After jettisoning enough mass, the star calms down until its outer layers re-form and the cycle begins anew, the astrophysicists report online September 26 in Nature. Identifying the cause of the stellar geysers is significant because every extremely massive star probably spends part of its life as a luminous blue variable, says study co-author Matteo Cantiello, an associate research scientist at the Center for Computational Astrophysics at the Flatiron Institute in New York City. A simulation of the turbulent gas that envelops a star 80 times the mass of the sun. Intense light from within the star pushes against dense pockets of helium-rich material in the star's outer layers, launching the material spaceward. The colors represent the density of the gas, with lighter colors signifying denser regions. Credit: Joseph Insley/Argonne Leadership Computing Facility "This finding represents an important step forward in understanding the life and death of the biggest stars in the universe," says Cantiello. "These massive stars, despite their small number, largely determine the evolution of galaxies through their stellar winds and supernova explosions. And when they die, they leave behind black holes." Luminous blue variables, or LBVs, are exceedingly rare, with only around a dozen spotted in and around the Milky Way galaxy. The gargantuan stars can exceed 100 times the mass of the sun and approach the theoretical limit of how massive stars can get. LBVs are also exceptionally radiant: The brightest ones shine with more than 1 million times the luminosity of the sun. That light pushes matter spaceward because absorption and re-emission of a photon by an atom results in a net outward shove. The tug of war between extreme gravity pulling material in and extreme luminosity pushing it out is responsible for the trademark outbursts of LBVs, scientists believe. The absorption of a photon by an atom, however, requires that electrons be bound in orbits around the atom's nucleus. In the deepest, hottest layers of a star, matter behaves as a plasma with electrons untethered from atoms. In the cooler outer layers, electrons begin rejoining their atoms and can therefore absorb photons again. Previously proposed explanations for the outbursts predicted that elements such as helium in the outer layers could absorb enough photons to overcome gravity and fly into space as an outburst. But simple, one-dimensional calculations didn't back up this hypothesis: The outer layers didn't seem sufficiently dense to catch enough light to overpower gravity. A simulation of the turbulent gas that envelops a star 80 times the mass of the sun. Intense light from within the star pushes against dense pockets of helium-rich material in the star's outer layers, launching the material spaceward. The solid colors denote radiation intensity, with bluer colors representing regions of larger intensity. The translucent purplish colors represent the gas density, with lighter colors denoting denser regions. Credit: Joseph Insley/Argonne Leadership Computing Facility Those simple calculations, however, didn't capture the full picture of the complex dynamics within a colossal star. Cantiello, along with Yan-Fei Jiang of the Kavli Institute for Theoretical Physics at the University of California, Santa Barbara, and colleagues took a more realistic approach. The researchers created a detailed, three-dimensional computer simulation of how matter, heat and light flow and interact within supersize stars. The calculations involved required more than 60 million computer processor hours to solve. In the simulation, the average density of the outer layers was too low for material to go flying—just as the one-dimensional calculations predicted. However, the new calculations revealed that convection and mixing in the outer layers resulted in some regions being denser than others, with some clumps opaque enough to be launched into space by the star's light. Such eruptions occur over timescales ranging from days to weeks as the star churns and its brightness fluctuates. The team estimates that such stars can shed around 10 billion trillion metric tons of material each year, roughly double the Earth's mass. The researchers plan to improve the accuracy of their simulations by incorporating other effects such as the star's rotation, which can make launching material into space easier near the star's fast-spinning equator than near the almost stationary poles. (This effect is the reason NASA launches its rockets from Florida and California rather than Maine or Alaska.) Improving the fidelity of star simulations is crucial to achieving astrophysical insights, Cantiello says. The move from simple, single-dimensional calculations to full 3-D simulations requires more computational muscle and more complex physics, but the results are well worth the trouble. "We had to implement all of these physics to see, with our own eyes, that this process—that we didn't expect to be important—would turn out to be key to understanding these violent eruptions and the evolution of these massive stars," he says. <|im_end|>

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2,492

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Diverse microbial ecosystems underpin life in the sea. Among these microbes are many unicellular eukaryotes that span the diversity of the eukaryotic tree of life. However, genetic tractability has been limited to a few species, which do not represent eukaryotic diversity or environmentally relevant taxa. Here, we report on the development of genetic tools in a range of protists primarily from marine environments. We present evidence for foreign DNA delivery and expression in 13 species never before transformed and for advancement of tools for eight other species, as well as potential reasons for why transformation of yet another 17 species tested was not achieved. Our resource in genetic manipulation will provide insights into the ancestral eukaryotic lifeforms, general eukaryote cell biology, protein diversification and the evolution of cellular pathways. Main The ocean represents the largest continuous planetary ecosystem, hosting an enormous variety of organisms, which include microscopic biota such as unicellular eukaryotes (protists). Despite their small size, protists play key roles in marine biogeochemical cycles and harbor tremendous evolutionary diversity 1 , 2 . Notwithstanding their significance for understanding the evolution of life on Earth and their role in marine food webs, as well as driving biogeochemical cycles to maintain habitability, little is known about their cell biology including reproduction, metabolism and signaling 3 . Most of the biological knowledge available is based on comparison of proteins from cultured species to homologs in genetically tractable model taxa 4 , 5 , 6 , 7 . A main impediment to understanding the cell biology of these diverse eukaryotes is that protocols for genetic modification are only available for a small number of species 8 , 9 that represent neither the most ecologically relevant protists nor the breadth of eukaryotic diversity. The development of genetic tools requires reliable information about gene organization and regulation of the emergent model species. Over the last decade, genome 4 , 5 , 6 and transcriptome sequencing initiatives 7 have resulted in nearly 120 million unigenes being identified in protists 10 , which facilitates the developments of genetic tools used for model species. Insights from these studies enabled the phylogenetically informed approach 7 for selecting and developing key marine protists into model systems in the Environmental Model Systems (EMS) Project presented herein. Forty-one research groups took part in the EMS Project, a collaborative effort resulting in the development of genetic tools that significantly expand the number of eukaryotic lineages that can be manipulated, and that encompass multiple ecologically important marine protists. Here, we summarize detailed methodological achievements and analyze results to provide a synthetic ‘transformation roadmap’ for creating new microeukaryotic model systems. Although the organisms reported here are diverse, the paths to overcome difficulties share similarities, highlighting the importance of building a well-connected community to overcome technical challenges and accelerate the development of genetic tools. The 13 emerging model species presented herein, and the collective set of genetic tools from the overall collaborative project, will not only extend our knowledge of marine cell biology, evolution and functional biodiversity, but also serve as platforms to advance protistan biotechnology. Results Overview of taxa in the EMS initiative Taxa were selected from multiple eukaryotic supergroups 1 , 7 to maximize the potential of cellular biology and to evaluate the numerous unigenes with unknown functions found in marine protists (Fig. 1 ). Before the EMS initiative, reproducible transformation of marine protists was limited to only a few species such as Thalassiosira pseudonana , Phaeodactylum tricornutum and Ostreococcus tauri (Supplementary Table 1 ). The EMS initiative included 39 species, specifically, 6 archaeplastids, 2 haptophytes, 2 rhizarians, 9 stramenopiles, 12 alveolates, 4 discobans and 4 opisthokonts (Fig. 1 ). Most of these taxa were isolated from coastal habitats, the focus area of several culture collections 7 . More than 50% of the selected species are considered photoautotrophs, with another 35% divided between heterotrophic osmotrophs and phagotrophs, the remainder being predatory mixotrophs. Almost 20% of the chosen species are symbionts and/or parasites of marine plants or animals, 5% are associated with detritus and several are responsible for harmful algal blooms (Supplementary Table 2 ). Fig. 1: Phylogenetic relationships and transformation status of marine protists. A schematic view of the eukaryotic tree of life with effigies of main representatives. Color-coordinated species we have attempted to genetically modify are listed below. Current transformability status is schematized in circles indicating: DNA delivered and shown to be expressed (yellow, for details see text and Table 1 ); DNA delivered, but no expression seen (gray) and no successful transformation achieved despite efforts (blue). The details of transformation of species that belong to ‘DNA delivered’ and ‘Not achieved yet’ categories are described in Supplementary Table 5 . mRNA, messenger RNA; FITC–dextran, fluorescein isothiocyanate (FITC)-conjugated dextran. Full size image While some transformation systems for protists have been developed in the past 8 , 9 , 11 , the challenge for this initiative was to develop genetic tools for species that not only require different cultivation conditions but are also phenotypically diverse. It should be noted that not all main lineages were explored. For example, amoebozoans did not feature in this aquatic-focused initiative, in part because they tend to be most important in soils, at least based on current knowledge, and manipulation systems exist for members of this eukaryotic supergroup, such as Dictyostelium discoideum 12 . The overall EMS initiative outcomes are summarized in Fig. 1 and Table 1 . We provide detailed protocols for 13 taxa, for which no transformation systems have been previously reported (category A) and eight taxa, for which existing protocols 9 , 11 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 were advanced (category B; Figs. 2 , 3 and 4 , Table 1 , Supplementary Tables 1 – 5 and Methods ). We also review an already published EMS transformation protocol 22 in one species (category C), and we discuss unsuccessful transformation attempts for 17 additional taxa (Fig. 1 and Methods ). Finally, we synthesize", "role": "user" }, { "content": "Throughout the world's oceans in global nutrient cycles, food chains, and climate, as well as increasingly in human-made industrial processes, a diverse set of planktonic microbes, such as algae, play an integral role. For nearly all of these planktonic microbes, however, little is known about them genetically beyond a few marker sequences, while their morphology, biological interactions, metabolism, and ecological significance remain a mystery. Algae produce half of the oxygen in earth's atmosphere and some forms of algae are used in industrial applications—such as producing high omega-3 fatty acids for baby formula or being used for biofuels—so there are many reasons a better understanding of algae could be beneficial. There is another side to algae, however, as some species can create harmful algal blooms (HABs), and those have been the focus of the research of University of Delaware's Kathryn Coyne. Advancing the study of microbes To help advance the understanding of the cellular instructions that underpin microbial life in the sea, Coyne joined more than 100 scientists from institutions around the globe to publish a compilation of methods, or protocols, for laboratory experiments that will help scientists gain a better understanding of the genetic underpinnings of marine algae as a resource article in the journal Nature Methods. The work was funded by the Gordon and Betty Moore Foundation's Marine Microbiology Initiative. For her contribution to the collaboration, Coyne worked specifically with Heterosigma akashiwo, a species of algae that can produce HABs. One of the mysteries about H. akashiwo is that while some strains produce toxins that can kill fish, other strains are non-toxic. \"We don't have a clear understanding of what kind of toxin they produce. We just know that when there are blooms of this algae in some areas of the world, they are associated with massive fish kills,\" said Coyne, an associate professor of marine biosciences in UD's College of Earth, Ocean, and Environment (CEOE), and director of the Delaware Sea Grant program. \"We also don't know why some strains produce toxins, or what stimulates this toxin production.\" Scientists often use genome manipulation to better understand how microbes respond to the environment or to identify genes that may be involved in a specific response, like production of toxins. Unlike other algal species that serve as models for genome manipulations, however, H. akashiwo doesn't have a cell wall, instead having only a thin membrane that holds the cell shape. Coyne explained that having a cell wall can be an impediment to genome manipulations and that these kinds of experiments usually entail some effort initially just to remove the cell wall or make it more porous. Because H. akashiwo lacked a cell wall, Coyne and her research team proposed that genome manipulation might be more straightforward with this species, and were able to demonstrate that using a couple of gene manipulation methods that have been successful on other model species. \"We created a piece of genetic material that could be introduced into Heterosigma cells that would make them resistant to a specific antibiotic,\" said Coyne. \"If we were successful, we would be able to grow them in this antibiotic and cells that had incorporated the resistance gene would survive.\" Coyne worked with Deepak Nanjappa, a postdoctoral researcher in her lab who is also an author on the paper, as well as Pam Green and her lab members, Vinay Nagarajan, a postdoctoral researcher, and Monica Accerbi, a research associate in Green's lab at the Delaware Biotechnology Institute (DBI). Together, they tried a handful of methods and optimized those that were successful for Heterosigma. One method in particular was replicated successfully several times, showing that they were able to produce a genetically modified strain of Heterosigma. Using this approach, scientists can now probe the genome of Heterosigma akashiwo to gain a better understanding of how this species responds to environmental cues, or what genes are responsible for its toxicity. One of the aims of the project was to make all of the methods developed freely available so that scientists can take that information and use it in their own research. \"The Moore Foundation funded this project with the expectation that all of the methods developed during this research would be published,\" said Coyne. \"Nothing is proprietary for this project, so we can share any of the protocols that we developed for Heterosigma.\" Immobilizing algicidal bacteria In addition, Coyne had another paper published in the scientific journal, Harmful Algae, that detailed her work with Yanfei Wang, a doctoral student in CEOE, studying the algicidal bacterium Shewanella and how it could be used to remediate HABs. Shewanella, which is an algicidal bacterium that has been isolated from the Delaware Inland Bays, is being developed as a biological control for HABs. It secretes water-soluble compounds that inhibit the growth of dinoflagellates, single-celled organisms that often produce toxins and contribute to HABs. Other research on this species of Shewanella shows that it has no negative effects on the growth of other species of algae, or on fish or shellfish. Since it was isolated from local waters, it may be considered an \"environmentally neutral\" solution to controlling HABs. In order to use Shewanella in the natural environment to control HABs, there first needs to be a method to safely deploy the bacterium in areas that are at risk for HABs. To move this HAB control solution closer to reality, Coyne and Wang immobilized Shewanella into several porous materials. Funded by Delaware Sea Grant, this research determined how well each material retained the bacteria over time, and whether the immobilized form of Shewanella was effective at controlling the growth of dinoflagellates. Unlike other HAB control approaches, such as application of toxic chemicals like copper sulfate, the advantage of using immobilized algicidal bacteria is the potential for continuous control of HABs without the need for frequent reapplication. The immobilized bacteria can also be removed when it is no longer needed. This research found that an alginate hydrogel was the most successful of the porous materials used in the study, and had the best retention of Shewanella cells. This research also showed that Shewanella cells immobilized in alginate beads were as effective as free bacteria in controlling the growth of the harmful species while at the same time having no negative impacts on a non-harmful control species. Overall, the study suggests that immobilized Shewanella may be used as an environmentally friendly approach to prevent or mitigate the blooms of harmful dinoflagellates and provides insight and directions for future studies. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Diverse microbial ecosystems underpin life in the sea. Among these microbes are many unicellular eukaryotes that span the diversity of the eukaryotic tree of life. However, genetic tractability has been limited to a few species, which do not represent eukaryotic diversity or environmentally relevant taxa. Here, we report on the development of genetic tools in a range of protists primarily from marine environments. We present evidence for foreign DNA delivery and expression in 13 species never before transformed and for advancement of tools for eight other species, as well as potential reasons for why transformation of yet another 17 species tested was not achieved. Our resource in genetic manipulation will provide insights into the ancestral eukaryotic lifeforms, general eukaryote cell biology, protein diversification and the evolution of cellular pathways. Main The ocean represents the largest continuous planetary ecosystem, hosting an enormous variety of organisms, which include microscopic biota such as unicellular eukaryotes (protists). Despite their small size, protists play key roles in marine biogeochemical cycles and harbor tremendous evolutionary diversity 1 , 2 . Notwithstanding their significance for understanding the evolution of life on Earth and their role in marine food webs, as well as driving biogeochemical cycles to maintain habitability, little is known about their cell biology including reproduction, metabolism and signaling 3 . Most of the biological knowledge available is based on comparison of proteins from cultured species to homologs in genetically tractable model taxa 4 , 5 , 6 , 7 . A main impediment to understanding the cell biology of these diverse eukaryotes is that protocols for genetic modification are only available for a small number of species 8 , 9 that represent neither the most ecologically relevant protists nor the breadth of eukaryotic diversity. The development of genetic tools requires reliable information about gene organization and regulation of the emergent model species. Over the last decade, genome 4 , 5 , 6 and transcriptome sequencing initiatives 7 have resulted in nearly 120 million unigenes being identified in protists 10 , which facilitates the developments of genetic tools used for model species. Insights from these studies enabled the phylogenetically informed approach 7 for selecting and developing key marine protists into model systems in the Environmental Model Systems (EMS) Project presented herein. Forty-one research groups took part in the EMS Project, a collaborative effort resulting in the development of genetic tools that significantly expand the number of eukaryotic lineages that can be manipulated, and that encompass multiple ecologically important marine protists. Here, we summarize detailed methodological achievements and analyze results to provide a synthetic ‘transformation roadmap’ for creating new microeukaryotic model systems. Although the organisms reported here are diverse, the paths to overcome difficulties share similarities, highlighting the importance of building a well-connected community to overcome technical challenges and accelerate the development of genetic tools. The 13 emerging model species presented herein, and the collective set of genetic tools from the overall collaborative project, will not only extend our knowledge of marine cell biology, evolution and functional biodiversity, but also serve as platforms to advance protistan biotechnology. Results Overview of taxa in the EMS initiative Taxa were selected from multiple eukaryotic supergroups 1 , 7 to maximize the potential of cellular biology and to evaluate the numerous unigenes with unknown functions found in marine protists (Fig. 1 ). Before the EMS initiative, reproducible transformation of marine protists was limited to only a few species such as Thalassiosira pseudonana , Phaeodactylum tricornutum and Ostreococcus tauri (Supplementary Table 1 ). The EMS initiative included 39 species, specifically, 6 archaeplastids, 2 haptophytes, 2 rhizarians, 9 stramenopiles, 12 alveolates, 4 discobans and 4 opisthokonts (Fig. 1 ). Most of these taxa were isolated from coastal habitats, the focus area of several culture collections 7 . More than 50% of the selected species are considered photoautotrophs, with another 35% divided between heterotrophic osmotrophs and phagotrophs, the remainder being predatory mixotrophs. Almost 20% of the chosen species are symbionts and/or parasites of marine plants or animals, 5% are associated with detritus and several are responsible for harmful algal blooms (Supplementary Table 2 ). Fig. 1: Phylogenetic relationships and transformation status of marine protists. A schematic view of the eukaryotic tree of life with effigies of main representatives. Color-coordinated species we have attempted to genetically modify are listed below. Current transformability status is schematized in circles indicating: DNA delivered and shown to be expressed (yellow, for details see text and Table 1 ); DNA delivered, but no expression seen (gray) and no successful transformation achieved despite efforts (blue). The details of transformation of species that belong to ‘DNA delivered’ and ‘Not achieved yet’ categories are described in Supplementary Table 5 . mRNA, messenger RNA; FITC–dextran, fluorescein isothiocyanate (FITC)-conjugated dextran. Full size image While some transformation systems for protists have been developed in the past 8 , 9 , 11 , the challenge for this initiative was to develop genetic tools for species that not only require different cultivation conditions but are also phenotypically diverse. It should be noted that not all main lineages were explored. For example, amoebozoans did not feature in this aquatic-focused initiative, in part because they tend to be most important in soils, at least based on current knowledge, and manipulation systems exist for members of this eukaryotic supergroup, such as Dictyostelium discoideum 12 . The overall EMS initiative outcomes are summarized in Fig. 1 and Table 1 . We provide detailed protocols for 13 taxa, for which no transformation systems have been previously reported (category A) and eight taxa, for which existing protocols 9 , 11 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 were advanced (category B; Figs. 2 , 3 and 4 , Table 1 , Supplementary Tables 1 – 5 and Methods ). We also review an already published EMS transformation protocol 22 in one species (category C), and we discuss unsuccessful transformation attempts for 17 additional taxa (Fig. 1 and Methods ). Finally, we synthesize<|im_end|> <|im_start|>assistant Throughout the world's oceans in global nutrient cycles, food chains, and climate, as well as increasingly in human-made industrial processes, a diverse set of planktonic microbes, such as algae, play an integral role. For nearly all of these planktonic microbes, however, little is known about them genetically beyond a few marker sequences, while their morphology, biological interactions, metabolism, and ecological significance remain a mystery. Algae produce half of the oxygen in earth's atmosphere and some forms of algae are used in industrial applications—such as producing high omega-3 fatty acids for baby formula or being used for biofuels—so there are many reasons a better understanding of algae could be beneficial. There is another side to algae, however, as some species can create harmful algal blooms (HABs), and those have been the focus of the research of University of Delaware's Kathryn Coyne. Advancing the study of microbes To help advance the understanding of the cellular instructions that underpin microbial life in the sea, Coyne joined more than 100 scientists from institutions around the globe to publish a compilation of methods, or protocols, for laboratory experiments that will help scientists gain a better understanding of the genetic underpinnings of marine algae as a resource article in the journal Nature Methods. The work was funded by the Gordon and Betty Moore Foundation's Marine Microbiology Initiative. For her contribution to the collaboration, Coyne worked specifically with Heterosigma akashiwo, a species of algae that can produce HABs. One of the mysteries about H. akashiwo is that while some strains produce toxins that can kill fish, other strains are non-toxic. "We don't have a clear understanding of what kind of toxin they produce. We just know that when there are blooms of this algae in some areas of the world, they are associated with massive fish kills," said Coyne, an associate professor of marine biosciences in UD's College of Earth, Ocean, and Environment (CEOE), and director of the Delaware Sea Grant program. "We also don't know why some strains produce toxins, or what stimulates this toxin production." Scientists often use genome manipulation to better understand how microbes respond to the environment or to identify genes that may be involved in a specific response, like production of toxins. Unlike other algal species that serve as models for genome manipulations, however, H. akashiwo doesn't have a cell wall, instead having only a thin membrane that holds the cell shape. Coyne explained that having a cell wall can be an impediment to genome manipulations and that these kinds of experiments usually entail some effort initially just to remove the cell wall or make it more porous. Because H. akashiwo lacked a cell wall, Coyne and her research team proposed that genome manipulation might be more straightforward with this species, and were able to demonstrate that using a couple of gene manipulation methods that have been successful on other model species. "We created a piece of genetic material that could be introduced into Heterosigma cells that would make them resistant to a specific antibiotic," said Coyne. "If we were successful, we would be able to grow them in this antibiotic and cells that had incorporated the resistance gene would survive." Coyne worked with Deepak Nanjappa, a postdoctoral researcher in her lab who is also an author on the paper, as well as Pam Green and her lab members, Vinay Nagarajan, a postdoctoral researcher, and Monica Accerbi, a research associate in Green's lab at the Delaware Biotechnology Institute (DBI). Together, they tried a handful of methods and optimized those that were successful for Heterosigma. One method in particular was replicated successfully several times, showing that they were able to produce a genetically modified strain of Heterosigma. Using this approach, scientists can now probe the genome of Heterosigma akashiwo to gain a better understanding of how this species responds to environmental cues, or what genes are responsible for its toxicity. One of the aims of the project was to make all of the methods developed freely available so that scientists can take that information and use it in their own research. "The Moore Foundation funded this project with the expectation that all of the methods developed during this research would be published," said Coyne. "Nothing is proprietary for this project, so we can share any of the protocols that we developed for Heterosigma." Immobilizing algicidal bacteria In addition, Coyne had another paper published in the scientific journal, Harmful Algae, that detailed her work with Yanfei Wang, a doctoral student in CEOE, studying the algicidal bacterium Shewanella and how it could be used to remediate HABs. Shewanella, which is an algicidal bacterium that has been isolated from the Delaware Inland Bays, is being developed as a biological control for HABs. It secretes water-soluble compounds that inhibit the growth of dinoflagellates, single-celled organisms that often produce toxins and contribute to HABs. Other research on this species of Shewanella shows that it has no negative effects on the growth of other species of algae, or on fish or shellfish. Since it was isolated from local waters, it may be considered an "environmentally neutral" solution to controlling HABs. In order to use Shewanella in the natural environment to control HABs, there first needs to be a method to safely deploy the bacterium in areas that are at risk for HABs. To move this HAB control solution closer to reality, Coyne and Wang immobilized Shewanella into several porous materials. Funded by Delaware Sea Grant, this research determined how well each material retained the bacteria over time, and whether the immobilized form of Shewanella was effective at controlling the growth of dinoflagellates. Unlike other HAB control approaches, such as application of toxic chemicals like copper sulfate, the advantage of using immobilized algicidal bacteria is the potential for continuous control of HABs without the need for frequent reapplication. The immobilized bacteria can also be removed when it is no longer needed. This research found that an alginate hydrogel was the most successful of the porous materials used in the study, and had the best retention of Shewanella cells. This research also showed that Shewanella cells immobilized in alginate beads were as effective as free bacteria in controlling the growth of the harmful species while at the same time having no negative impacts on a non-harmful control species. Overall, the study suggests that immobilized Shewanella may be used as an environmentally friendly approach to prevent or mitigate the blooms of harmful dinoflagellates and provides insight and directions for future studies. <|im_end|>

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71165, 5907, 11, 264, 40806, 5149, 13239, 304, 279, 4500, 315, 19465, 7526, 430, 12207, 9407, 279, 1396, 315, 384, 3178, 661, 14546, 1584, 1154, 430, 649, 387, 55315, 11, 323, 430, 38632, 5361, 12208, 30450, 3062, 29691, 1760, 1705, 13, 5810, 11, 584, 63179, 11944, 1749, 5848, 33997, 323, 24564, 3135, 311, 3493, 264, 28367, 3451, 1485, 1659, 69917, 529, 369, 6968, 502, 8162, 68, 3178, 661, 14546, 1646, 6067, 13, 10541, 279, 44304, 5068, 1618, 527, 17226, 11, 279, 13006, 311, 23075, 27129, 4430, 43874, 11, 39686, 279, 12939, 315, 4857, 264, 1664, 73288, 4029, 311, 23075, 11156, 11774, 323, 43880, 279, 4500, 315, 19465, 7526, 13, 578, 220, 1032, 24084, 1646, 9606, 10666, 36881, 11, 323, 279, 22498, 743, 315, 19465, 7526, 505, 279, 8244, 40806, 2447, 11, 690, 539, 1193, 13334, 1057, 6677, 315, 29691, 2849, 34458, 11, 15740, 323, 16003, 73119, 11, 719, 1101, 8854, 439, 15771, 311, 12178, 1760, 9121, 6160, 52536, 13, 18591, 35907, 315, 77314, 304, 279, 71165, 20770, 15545, 64, 1051, 4183, 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34786, 6067, 3073, 369, 3697, 315, 420, 384, 3178, 661, 14546, 2307, 4166, 11, 1778, 439, 30226, 88, 117700, 2411, 54969, 579, 372, 220, 717, 662, 578, 8244, 71165, 20770, 20124, 527, 69729, 304, 23966, 13, 220, 16, 323, 6771, 220, 16, 662, 1226, 3493, 11944, 32885, 369, 220, 1032, 77314, 11, 369, 902, 912, 18475, 6067, 617, 1027, 8767, 5068, 320, 5588, 362, 8, 323, 8223, 77314, 11, 369, 902, 6484, 32885, 220, 24, 1174, 220, 806, 1174, 220, 1032, 1174, 220, 975, 1174, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 1174, 220, 777, 1174, 220, 508, 1174, 220, 1691, 1051, 11084, 320, 5588, 426, 26, 435, 14801, 13, 220, 17, 1174, 220, 18, 323, 220, 19, 1174, 6771, 220, 16, 1174, 99371, 43252, 220, 16, 1389, 220, 20, 323, 19331, 7609, 1226, 1101, 3477, 459, 2736, 4756, 71165, 18475, 11766, 220, 1313, 304, 832, 9606, 320, 5588, 356, 705, 323, 584, 4358, 46025, 18475, 13865, 369, 220, 1114, 5217, 77314, 320, 30035, 13, 220, 16, 323, 19331, 7609, 17830, 11, 584, 6925, 27985, 128257, 198, 128256, 78191, 198, 60105, 279, 1917, 596, 54280, 304, 3728, 50123, 25492, 11, 3691, 27271, 11, 323, 10182, 11, 439, 1664, 439, 15098, 304, 3823, 27975, 13076, 11618, 11, 264, 17226, 743, 315, 73187, 783, 292, 80727, 11, 1778, 439, 68951, 11, 1514, 459, 26154, 3560, 13, 1789, 7154, 682, 315, 1521, 73187, 783, 292, 80727, 11, 4869, 11, 2697, 374, 3967, 922, 1124, 52033, 7953, 264, 2478, 11381, 24630, 11, 1418, 872, 79612, 11, 24156, 22639, 11, 39097, 11, 323, 50953, 26431, 7293, 264, 23347, 13, 1708, 67378, 8356, 4376, 315, 279, 24463, 304, 9578, 596, 16975, 323, 1063, 7739, 315, 68951, 527, 1511, 304, 13076, 8522, 2345, 21470, 439, 17843, 1579, 34998, 12, 18, 40085, 33969, 369, 8945, 15150, 477, 1694, 1511, 369, 17332, 33721, 2053, 2345, 708, 1070, 527, 1690, 8125, 264, 2731, 8830, 315, 68951, 1436, 387, 24629, 13, 2684, 374, 2500, 3185, 311, 68951, 11, 4869, 11, 439, 1063, 9606, 649, 1893, 28856, 453, 16876, 92889, 320, 39, 1905, 82, 705, 323, 1884, 617, 1027, 279, 5357, 315, 279, 3495, 315, 3907, 315, 40838, 596, 92168, 63073, 818, 13, 12605, 9151, 279, 4007, 315, 80727, 2057, 1520, 12178, 279, 8830, 315, 279, 35693, 11470, 430, 1234, 13576, 75418, 2324, 304, 279, 9581, 11, 63073, 818, 11096, 810, 1109, 220, 1041, 14248, 505, 14673, 2212, 279, 24867, 311, 3498, 264, 29772, 315, 5528, 11, 477, 32885, 11, 369, 27692, 21896, 430, 690, 1520, 14248, 8895, 264, 2731, 8830, 315, 279, 19465, 1234, 79, 6258, 826, 315, 29691, 68951, 439, 264, 5211, 4652, 304, 279, 8486, 22037, 19331, 13, 578, 990, 574, 24853, 555, 279, 26952, 323, 56111, 20832, 5114, 596, 23820, 18654, 81162, 38756, 13, 1789, 1077, 19035, 311, 279, 20632, 11, 63073, 818, 6575, 11951, 449, 473, 1430, 437, 11750, 17774, 31478, 1146, 11, 264, 9606, 315, 68951, 430, 649, 8356, 473, 1905, 82, 13, 3861, 315, 279, 57700, 922, 473, 13, 17774, 31478, 1146, 374, 430, 1418, 1063, 42400, 8356, 62186, 430, 649, 5622, 7795, 11, 1023, 42400, 527, 2536, 4791, 14668, 13, 330, 1687, 1541, 956, 617, 264, 2867, 8830, 315, 1148, 3169, 315, 98534, 814, 8356, 13, 1226, 1120, 1440, 430, 994, 1070, 527, 92889, 315, 420, 68951, 304, 1063, 5789, 315, 279, 1917, 11, 814, 527, 5938, 449, 11191, 7795, 29910, 1359, 1071, 63073, 818, 11, 459, 22712, 14561, 315, 29691, 49554, 5979, 2436, 304, 79651, 596, 9304, 315, 9420, 11, 22302, 11, 323, 11847, 320, 2152, 53965, 705, 323, 7690, 315, 279, 40838, 15379, 24668, 2068, 13, 330, 1687, 1101, 1541, 956, 1440, 3249, 1063, 42400, 8356, 62186, 11, 477, 1148, 95455, 420, 98534, 5788, 1210, 57116, 3629, 1005, 33869, 34786, 311, 2731, 3619, 1268, 80727, 6013, 311, 279, 4676, 477, 311, 10765, 21389, 430, 1253, 387, 6532, 304, 264, 3230, 2077, 11, 1093, 5788, 315, 62186, 13, 27140, 1023, 453, 16876, 9606, 430, 8854, 439, 4211, 369, 33869, 14951, 7607, 11, 4869, 11, 473, 13, 17774, 31478, 1146, 3250, 956, 617, 264, 2849, 7147, 11, 4619, 3515, 1193, 264, 15792, 39654, 430, 10187, 279, 2849, 6211, 13, 63073, 818, 11497, 430, 3515, 264, 2849, 7147, 649, 387, 459, 50502, 3904, 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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Autonomous polymers that report damage prior to loss of function and simultaneously self-heal are highly relevant for preventing catastrophic failures and extending the lifetimes of materials. Here, we demonstrate mechanochromic and thermally reprocessable thermosets that can be used for autonomic damage reporting and self-healing coatings. A mechanochromic molecule, spiropyran (SP), is covalently incorporated into thermoreversible Diels–Alder (DA) cross-linking networks. Mechanical activation of SPs in DA networks is confirmed by computational simulations and mechanical testing. The damaged areas of the polymers change colour, emit fluorescence signals, and completely recover after heat treatment. Because of the thermoreversible covalent networks, these polymers can be recycled up to fifteen times without degrading their mechanical, damage-reporting, or self-healing properties. Our autonomic material systems provide a new way to enhance the lifespans and reliabilities of thermosetting coatings, which also expands the range for practical applications of force-induced chemical reactions in polymers. Introduction Thermosets are chemically cross-linked polymer networks formed by irreversible chemical reactions of soft solids or viscous liquid prepolymers. Owing to their superior mechanical properties, high thermal stabilities, and outstanding chemical resistance, thermosets are used in a wide range of applications, including coatings, adhesives, composites, electronic packaging, etc. 1 , 2 . As a key element in the modern plastic industry, thermosets comprise 20% of total polymer production today, with worldwide annual production of more than 65 million tons 3 . Although permanent cross-links endow thermosets with desirable properties, their high stability precludes repair, reshaping, and reprocessing of thermosets even at high temperatures; hence, they are among the most difficult materials to recycle 4 . With increased interest in sustainability and environmental responsibility, dynamic and exchangeable chemical reactions have been investigated for developing reprocessable thermosets known as covalent adaptable networks (CANs) 5 , 6 , 7 , 8 . This type of polymer behaves like a classical thermoset under ambient conditions, but the network topology can be rearranged repeatedly in response to external stimuli. Since every reaction rate is dependent on temperature, thermal treatment is a universal stimulus used to trigger or control dynamic chemical reactions 9 , 10 , 11 . In particular, thermoreversible Diels–Alder (DA) reactions have been employed for syntheses of CANs due to their relatively fast kinetics and catalyst-free mild reaction conditions 12 , 13 . The DA reaction involves a [4 + 2] cycloaddition between an electron-rich diene and an electron-poor dienophile to form a stable cyclohexene derivative. The use of furan as the diene and maleimide as the dienophile constitutes an excellent combination for CANs since this DA reaction has relatively low coupling and high decoupling temperatures 14 . Specifically, multifunctional maleimides and furans have been used as cross-linking agents with several furan- and maleimide-containing polymers, respectively 15 , 16 . Therefore, we chose to use DA chemistry as a thermoreversible cross-linking tool for self-healing and reprocessable thermosets. Autonomous polymers that report damage prior to loss of function and simultaneously self-heal are highly relevant for preventing catastrophic failures and extending the lifetimes of materials, thus ultimately keeping us on the path to sustainability 17 , 18 . In particular, damage visualization has been achieved by incorporating mechanochromic molecules that change optical properties in response to mechanical stresses into polymeric materials. Spiropyran (SP) is a well-studied mechanochromic molecule that undergoes a force-induced reversible 6π electrocyclic ring-opening reaction to produce a merocyanine (MC) form 19 . Different strategies have been used to synthesize SP-linked mechanochromic polymers: Homo and block copolymers, including polyacrylates 20 , 21 and polystyrenes 22 , 23 , were prepared by using SP as a bifunctional initiator via atom transfer radical polymerization (ATRP). Dihydroxy-terminated SPs were incorporated into polyurethanes 24 , 25 , polyesters 26 , 27 and polycarbonates 28 through step-growth or ring-opening polymerization. SP-linked silicone rubbers were fabricated using bis-alkene functionalized SP as a cross-linker 29 , 30 . However, there has been no attempt to integrate SP molecules into CANs, especially those prepared with DA chemistry. Since some DA isomers undergo force-induced retro-DA (rDA) reactions 31 , SP-incorporated DA networks would be useful for studying how two different force-sensitive molecules can be mechanically activated in a single polymeric system. Here, we demonstrate self-healing and reprocessable thermosets that indicate damage with optical changes involving mechanochromic SPs and thermoreversible DA chemistry (Scheme 1 ). Linear random copolymers containing furfuryl functionalities are synthesized from bifunctional SP initiators through ATRP. We discuss in detail how polymerization kinetics and comonomer compositions are influenced by reaction conditions. Then, tris-maleimide cross-linkers are mixed with SP-linked linear polymers to prepare a thermally reversible cross-linked network. When the thermoset is mechanically deformed or damaged, the affected areas change colour and emit fluorescence during the SP to MC transition. Upon thermal treatment, the coloured MC reverts to the colourless SP, and reversible DA–rDA reactions reorganize the polymer network, which results in self-healing and reprocessing. Mechanical activation of SPs in DA polymeric networks is investigated with both ab initio steered molecular dynamics simulations and mechanical testing. We also evaluate the self-healing abilities and thermomechanical properties of mechanochromic thermosets after multiple recycling processes. Scheme 1 Mechanochromic, self-healing and reprocessable thermosets based on SP mechanophores and Diels–Alder adducts. Full size image Materials and methods Materials Unless otherwise states, all reagents were purchased from commercial source and used as received. Lauryl methacrylate (LMA) (96%) and furfuryl methacrylate (FMA) (97%) were passed through a column of basic alumina before use to remove the inhibitors. Copper(I) bromide (98%) was purified by stirring with glacial acetic acid, rinsed with ethanol, and dried under vacuum. Syntheses of mechanically active spiropyran (SP), control spiropyran (Ctrl) and cross-linkers SP, Ctrl and tris-maleimide cross-linkers were prepared according to literature procedures or with some modification. Details of their syntheses and characterization data are provided in the Supplementary material. SP-linked poly(LMA- co -FMA) ( P ) and Ctrl-linked poly(LMA- co -FMA) ( C M3 ) Nine types of SP-linked copolymers ( P ) containing SP mechanophores near the chain midpoint were synthesized by changing the molecular weights and FMA molar contents. Ctrl-linked copolymer ( C M3 )", "role": "user" }, { "content": "Skin-like polymeric coatings are applied to the surfaces of automobiles, ships, and buildings to protect them from the external environment. As it is difficult to determine whether the currently used coatings are already damaged or not, these non-reusable coatings must be regularly replaced, leading to a large amount of waste generation and high disposal costs. The Korea Institute of Science and Technology (KIST) announced that Dr. Tae Ann Kim's team at the Soft Hybrid Materials Research Center has developed a polymeric coating wherein the damaged area changes color, enabling immediate detection and high temperature self-healing. Existing studies on damage-reporting and self-healing polymeric coatings involve the use of extremely small capsules containing functional agents. However, these capsules cannot be used again for subsequent damage detection and self-healing if broken. The KIST research team has developed a thermoset polymer that can recover its original chemical structure after being disrupted by an external stimulus, thereby allowing this material to self-report damage and self-heal multiple times. In this study, a mechanochromic molecule, which changes color when an external force is applied due to a specific bond cleavage, and a thermoset polymer containing a molecule that can be separated and re-formed by temperature were synthesized. When a force is applied to a mechanochromic molecule, a certain bond is broken, thus changing into a form that can exhibit color. The damaged part of the synthesized polymeric coating changed to purple. When a temperature of 100°C or higher was applied, the material became processable and was physically healed and became colorless. The research team used molecular dynamics simulations to predict and confirm that only certain desired chemical bonds are selectively cleaved when a mechanical force is applied to yield a colored structure; the functionality was implemented by synthesizing the actual coating agent. Mechanochromic and self-healing coatings on diverse substrates. Credit: Korea Institute of Science and Technology (KIST) The novel multifunctional polymeric coating developed herein can be extensively used in automotive, marine, defense, timber, railway, highway, and aerospace industries, and can significantly contribute toward the reduction of industrial waste. In addition, it can be used as an artificial skin for robots, such as humanoids, since its functionality is similar to that of skin and it does not require an external energy source. Dr. Tae Ann Kim of KIST said, \"This study reports a method for the simultaneous realization of damage detection and self-healing technology without any external agents such as capsules.\" He added, \"However, even if repeated self-healing is possible, it cannot be used permanently. Therefore, additional research is underway to transition materials that have reached their lifespan into materials that are harmless to the environment or convert them into a re-cyclable form.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Autonomous polymers that report damage prior to loss of function and simultaneously self-heal are highly relevant for preventing catastrophic failures and extending the lifetimes of materials. Here, we demonstrate mechanochromic and thermally reprocessable thermosets that can be used for autonomic damage reporting and self-healing coatings. A mechanochromic molecule, spiropyran (SP), is covalently incorporated into thermoreversible Diels–Alder (DA) cross-linking networks. Mechanical activation of SPs in DA networks is confirmed by computational simulations and mechanical testing. The damaged areas of the polymers change colour, emit fluorescence signals, and completely recover after heat treatment. Because of the thermoreversible covalent networks, these polymers can be recycled up to fifteen times without degrading their mechanical, damage-reporting, or self-healing properties. Our autonomic material systems provide a new way to enhance the lifespans and reliabilities of thermosetting coatings, which also expands the range for practical applications of force-induced chemical reactions in polymers. Introduction Thermosets are chemically cross-linked polymer networks formed by irreversible chemical reactions of soft solids or viscous liquid prepolymers. Owing to their superior mechanical properties, high thermal stabilities, and outstanding chemical resistance, thermosets are used in a wide range of applications, including coatings, adhesives, composites, electronic packaging, etc. 1 , 2 . As a key element in the modern plastic industry, thermosets comprise 20% of total polymer production today, with worldwide annual production of more than 65 million tons 3 . Although permanent cross-links endow thermosets with desirable properties, their high stability precludes repair, reshaping, and reprocessing of thermosets even at high temperatures; hence, they are among the most difficult materials to recycle 4 . With increased interest in sustainability and environmental responsibility, dynamic and exchangeable chemical reactions have been investigated for developing reprocessable thermosets known as covalent adaptable networks (CANs) 5 , 6 , 7 , 8 . This type of polymer behaves like a classical thermoset under ambient conditions, but the network topology can be rearranged repeatedly in response to external stimuli. Since every reaction rate is dependent on temperature, thermal treatment is a universal stimulus used to trigger or control dynamic chemical reactions 9 , 10 , 11 . In particular, thermoreversible Diels–Alder (DA) reactions have been employed for syntheses of CANs due to their relatively fast kinetics and catalyst-free mild reaction conditions 12 , 13 . The DA reaction involves a [4 + 2] cycloaddition between an electron-rich diene and an electron-poor dienophile to form a stable cyclohexene derivative. The use of furan as the diene and maleimide as the dienophile constitutes an excellent combination for CANs since this DA reaction has relatively low coupling and high decoupling temperatures 14 . Specifically, multifunctional maleimides and furans have been used as cross-linking agents with several furan- and maleimide-containing polymers, respectively 15 , 16 . Therefore, we chose to use DA chemistry as a thermoreversible cross-linking tool for self-healing and reprocessable thermosets. Autonomous polymers that report damage prior to loss of function and simultaneously self-heal are highly relevant for preventing catastrophic failures and extending the lifetimes of materials, thus ultimately keeping us on the path to sustainability 17 , 18 . In particular, damage visualization has been achieved by incorporating mechanochromic molecules that change optical properties in response to mechanical stresses into polymeric materials. Spiropyran (SP) is a well-studied mechanochromic molecule that undergoes a force-induced reversible 6π electrocyclic ring-opening reaction to produce a merocyanine (MC) form 19 . Different strategies have been used to synthesize SP-linked mechanochromic polymers: Homo and block copolymers, including polyacrylates 20 , 21 and polystyrenes 22 , 23 , were prepared by using SP as a bifunctional initiator via atom transfer radical polymerization (ATRP). Dihydroxy-terminated SPs were incorporated into polyurethanes 24 , 25 , polyesters 26 , 27 and polycarbonates 28 through step-growth or ring-opening polymerization. SP-linked silicone rubbers were fabricated using bis-alkene functionalized SP as a cross-linker 29 , 30 . However, there has been no attempt to integrate SP molecules into CANs, especially those prepared with DA chemistry. Since some DA isomers undergo force-induced retro-DA (rDA) reactions 31 , SP-incorporated DA networks would be useful for studying how two different force-sensitive molecules can be mechanically activated in a single polymeric system. Here, we demonstrate self-healing and reprocessable thermosets that indicate damage with optical changes involving mechanochromic SPs and thermoreversible DA chemistry (Scheme 1 ). Linear random copolymers containing furfuryl functionalities are synthesized from bifunctional SP initiators through ATRP. We discuss in detail how polymerization kinetics and comonomer compositions are influenced by reaction conditions. Then, tris-maleimide cross-linkers are mixed with SP-linked linear polymers to prepare a thermally reversible cross-linked network. When the thermoset is mechanically deformed or damaged, the affected areas change colour and emit fluorescence during the SP to MC transition. Upon thermal treatment, the coloured MC reverts to the colourless SP, and reversible DA–rDA reactions reorganize the polymer network, which results in self-healing and reprocessing. Mechanical activation of SPs in DA polymeric networks is investigated with both ab initio steered molecular dynamics simulations and mechanical testing. We also evaluate the self-healing abilities and thermomechanical properties of mechanochromic thermosets after multiple recycling processes. Scheme 1 Mechanochromic, self-healing and reprocessable thermosets based on SP mechanophores and Diels–Alder adducts. Full size image Materials and methods Materials Unless otherwise states, all reagents were purchased from commercial source and used as received. Lauryl methacrylate (LMA) (96%) and furfuryl methacrylate (FMA) (97%) were passed through a column of basic alumina before use to remove the inhibitors. Copper(I) bromide (98%) was purified by stirring with glacial acetic acid, rinsed with ethanol, and dried under vacuum. Syntheses of mechanically active spiropyran (SP), control spiropyran (Ctrl) and cross-linkers SP, Ctrl and tris-maleimide cross-linkers were prepared according to literature procedures or with some modification. Details of their syntheses and characterization data are provided in the Supplementary material. SP-linked poly(LMA- co -FMA) ( P ) and Ctrl-linked poly(LMA- co -FMA) ( C M3 ) Nine types of SP-linked copolymers ( P ) containing SP mechanophores near the chain midpoint were synthesized by changing the molecular weights and FMA molar contents. Ctrl-linked copolymer ( C M3 )<|im_end|> <|im_start|>assistant Skin-like polymeric coatings are applied to the surfaces of automobiles, ships, and buildings to protect them from the external environment. As it is difficult to determine whether the currently used coatings are already damaged or not, these non-reusable coatings must be regularly replaced, leading to a large amount of waste generation and high disposal costs. The Korea Institute of Science and Technology (KIST) announced that Dr. Tae Ann Kim's team at the Soft Hybrid Materials Research Center has developed a polymeric coating wherein the damaged area changes color, enabling immediate detection and high temperature self-healing. Existing studies on damage-reporting and self-healing polymeric coatings involve the use of extremely small capsules containing functional agents. However, these capsules cannot be used again for subsequent damage detection and self-healing if broken. The KIST research team has developed a thermoset polymer that can recover its original chemical structure after being disrupted by an external stimulus, thereby allowing this material to self-report damage and self-heal multiple times. In this study, a mechanochromic molecule, which changes color when an external force is applied due to a specific bond cleavage, and a thermoset polymer containing a molecule that can be separated and re-formed by temperature were synthesized. When a force is applied to a mechanochromic molecule, a certain bond is broken, thus changing into a form that can exhibit color. The damaged part of the synthesized polymeric coating changed to purple. When a temperature of 100°C or higher was applied, the material became processable and was physically healed and became colorless. The research team used molecular dynamics simulations to predict and confirm that only certain desired chemical bonds are selectively cleaved when a mechanical force is applied to yield a colored structure; the functionality was implemented by synthesizing the actual coating agent. Mechanochromic and self-healing coatings on diverse substrates. Credit: Korea Institute of Science and Technology (KIST) The novel multifunctional polymeric coating developed herein can be extensively used in automotive, marine, defense, timber, railway, highway, and aerospace industries, and can significantly contribute toward the reduction of industrial waste. In addition, it can be used as an artificial skin for robots, such as humanoids, since its functionality is similar to that of skin and it does not require an external energy source. Dr. Tae Ann Kim of KIST said, "This study reports a method for the simultaneous realization of damage detection and self-healing technology without any external agents such as capsules." He added, "However, even if repeated self-healing is possible, it cannot be used permanently. Therefore, additional research is underway to transition materials that have reached their lifespan into materials that are harmless to the environment or convert them into a re-cyclable form." <|im_end|>

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2,109

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Cells sense their environment and adapt to it by fine-tuning their transcriptome. Wired into this network of gene expression control are mechanisms to compensate for gene dosage. The increasing use of reverse genetics in zebrafish, and other model systems, has revealed profound differences between the phenotypes caused by genetic mutations and those caused by gene knockdowns at many loci 1 , 2 , 3 , an observation previously reported in mouse and Arabidopsis 4 , 5 , 6 , 7 . To identify the reasons underlying the phenotypic differences between mutants and knockdowns, we generated mutations in zebrafish egfl7 , an endothelial extracellular matrix gene of therapeutic interest, as well as in vegfaa . Here we show that egfl7 mutants do not show any obvious phenotypes while animals injected with egfl7 morpholino (morphants) exhibit severe vascular defects. We further observe that egfl7 mutants are less sensitive than their wild-type siblings to Egfl7 knockdown, arguing against residual protein function in the mutants or significant off-target effects of the morpholinos when used at a moderate dose. Comparing egfl7 mutant and morphant proteomes and transcriptomes, we identify a set of proteins and genes that are upregulated in mutants but not in morphants. Among them are extracellular matrix genes that can rescue egfl7 morphants, indicating that they could be compensating for the loss of Egfl7 function in the phenotypically wild-type egfl7 mutants. Moreover, egfl7 CRISPR interference, which obstructs transcript elongation and causes severe vascular defects, does not cause the upregulation of these genes. Similarly, vegfaa mutants but not morphants show an upregulation of vegfab . Taken together, these data reveal the activation of a compensatory network to buffer against deleterious mutations, which was not observed after translational or transcriptional knockdown. Main Interfering with a gene’s function is a widely used strategy to decipher its role. Several different approaches have been developed over the years to achieve this goal. Yet, despite having the same goal of functional inactivation, different strategies, namely knockdown (via antisense) and knockout (via genetic inactivation), often lead to different phenotypes. These discrepancies could be caused by off-target effects of the knockdown reagents, the generation and use of hypomorphic alleles, or other and more fundamental reasons. The recent development of new genome engineering techniques, such as TAL effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPRs), is allowing the facile generation of mutations and has revived concerns over the lack of specificity of knockdown reagents 1 , 2 , 3 . In several cases, toxicity due to off-target effects, induction of p53 (also known as tp53 ) transcription, interferon response, engagement of toll-like receptors and/or saturation of the RNA interference machinery can lead to phenotypes unrelated to the silencing of the target gene 8 , 9 . To investigate further whether toxicity effects are the main reason for the differences between genetic mutation and gene knockdown phenotypes, we analysed the EGF-like-domain, multiple 7 ( egfl7 ) gene. The egfl7 gene is a good candidate to address this question because of the lack of obvious phenotypes in the mouse mutants 10 , 11 and the severe vascular tube formation defects observed in knockdown experiments in zebrafish, frogs and human cells 12 , 13 , 14 . We first generated egfl7 mutants using TALENs 15 targeting exon 3, which encodes part of the EMI domain ( Fig. 1a and Extended Data Fig. 1 ). This domain precedes other domains critical for Egfl7 activity, including EGF domains and the leucine–valine-rich carboxy (C) terminus ( Fig. 1a ) 16 . We identified several deletion alleles including a Δ3 and a Δ4 ( Fig. 1b ). The egfl7 Δ3 (hereafter egfl7 s980 ) allele encodes a protein that lacks a non-conserved proline at position 50 (p.P50del) while the egfl7 Δ4 allele (hereafter egfl7 s981 ) is predicted to encode a truncated polypeptide containing a stretch of 29 incorrect amino acids starting with a Gln to Leu substitution at position 49 (p.Gln49Leufs*30) ( Fig. 1b ). To investigate the severity of these mutant alleles, we first examined egfl7 transcript levels by quantitative PCR (qPCR). The premature stop codon in egfl7 s981 led to a decrease of approximately 50% in transcript levels compared with wild-type (WT) and egfl7 s980 mutant embryos, indicating an increased messenger RNA (mRNA) degradation rate ( Extended Data Fig. 2a ). To characterize the different egfl7 mutant alleles further, we cloned the egfl7 WT, s980 and s981 complementary DNAs (cDNAs) in a mammalian expression vector and transfected HUVEC cells. Unlike Egfl7 WT and Egfl7 s980 , the Egfl7 s981 protein was mostly absent in the medium or the cells, suggesting that this truncated polypeptide is rapidly degraded and/or poorly translated and secreted ( Extended Data Fig. 2b ). Altogether, these data indicate that egfl7 s981 is a severe mutant allele, possibly even a null. Figure 1: Generation of zebrafish egfl7 mutant alleles and sporadic brain haemorrhage in mutant larvae. a , Top: egfl7 consists of 9 exons and mir126b is embedded in intron 6. The protein is encoded by exons 2–9 (grey boxes). a , Bottom: Egfl7, 277 amino acids (aa) long, contains a signal peptide (blue), an EMI domain (yellow), an EGF domain that contains a Delta-Serrate-LAG-2 (DSL) motif (orange) and a Ca 2+ -binding EGF domain (red). b , Top: the egfl7 s980 lesion (Δ3) leads to the deletion of proline at position 50 (p.P50del). b , Bottom: the egfl7 s981 allele (Δ4) encodes a truncated 77-amino-acid-long polypeptide (p.Gln49Leufs*30) that contains a signal peptide (blue) and a partial EMI domain (yellow) followed by a frameshift leading to a premature stop codon. c , d , Brightfield micrographs of 72 hpf WT and egfl7 s981/s981 larvae in lateral and ventral views. Arrows point to area of haemorrhage. e , f , Confocal micrographs of 72 hpf Tg(kdrl:HRAS-mCherry) WT and egfl7 s981/s981 larvae in lateral and dorsal views. PowerPoint slide Full size image To analyse Egfl7 function during vascular development, the egfl7 s981 mutant fish were crossed into the Tg(kdrl:HRAS-mCherry) 17 and", "role": "user" }, { "content": "New methods for modifying the genome are currently widely discussed: Using CRISPR/Cas for instance, scientists can remove parts of the genetic code of a gene, thereby knocking it out. Furthermore, there are ways to inhibit translation of a gene into a protein. Both methods have in common that they impede production of a protein and should therefore have comparable consequences for an organism. However, it has been shown that consequences can differ, after a gene is either knocked, out or only blocked. Scientist from the MPI for Heart and Lung Research in Bad Nauheim now found that additional genes compensate for a knocked out gene and either attenuate consequences or completely compensate deficits. The results suggest caution when interpreting data from molecular biological studies or developing gene therapies to treat various diseases. To analyse function of an unkown gene, scientists often extinguish the gene and investigate the consequences of this treatment for the organism. To do so, they cut DNA-fragments from the gene using enzymes deleting the genetic information for a functioning protein. Such method is called \"Gene knockout\". In contrast, in a \"gene knockdown\" scientists block protein production using particular substances, e.g. microRNAs. Recent studies, however, have shown that results may vary between knockout- and knockdown animals. Scientists from Didier Stainier's group at the Max Planck Institute for Heart and Lung Research have now identified the reason for this. The Bad Nauheim based researchers have investigated a gene called egfl7 in zebrafish. The gene is involved in the production of connective tissue in blood vessel walls, thereby stabilizing them. Doing so, egfl7 regulates blood vessel growth. Developmental biologists, however, are not sure, what happens in a fish organism, after the egfl7 gene has been deleted. \"If the gene has been blocked in a knockdown, blood vessels do not develop normally\", explains Andrea Rossi, together with Zacharias Kontarakis first author of the study. In contrast, if the gene itself is deleted by a genetic manipulation, blood vessel growth is not affected. In the beginning, Max Planck researchers excluded potential side effects of the knockdown substance being responsible for interference in vascular development. To this end, they injected the substance into fish larvae in which the egfl7 gene had already been deleted. However, the larvae almost developed normally. \"Since the substance did not cause disturbances in blood vessel growth, we thought of a different mechanism: The gene loss could be compensated by another gene taking over the function\", Kontarakis says. \"Therefore, we were looking for rescue genes, which might have been produced in animals without a functional egfl7 gene.\" The researchers compared the mRNA molecules and proteins in fish with or without a functional egfl7 gene and detected several mRNAs and proteins being present in higher amounts in fish without egfl7. An example is emilin 3B. When \"knockdown\" animals are treated with emilin 3B after egfl7 has been blocked, blood vessels develop almost normally. \"This tells us that emilin 3B can compensate for the loss of egfl7. In egfl7 knockout fish, emilin production is getting upregulated. This is not the case in knockdown fish\", Stainier explains. As the next step, the group plans to analyse how genes \"know\" that another gene has been deleted and then compensate for the loss. Several researchers worldwide are trying to delete disease genes for therapeutic reasons. Before we establish such therapies, we have to fully understand the consequences the loss or blockade of a gene might have. \"In addition, our study illustrates the power of comparing knockouts and knockdowns to identify modifier genes, a goal that remains a major challenge in the field of human genetics\" says Stainier. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Cells sense their environment and adapt to it by fine-tuning their transcriptome. Wired into this network of gene expression control are mechanisms to compensate for gene dosage. The increasing use of reverse genetics in zebrafish, and other model systems, has revealed profound differences between the phenotypes caused by genetic mutations and those caused by gene knockdowns at many loci 1 , 2 , 3 , an observation previously reported in mouse and Arabidopsis 4 , 5 , 6 , 7 . To identify the reasons underlying the phenotypic differences between mutants and knockdowns, we generated mutations in zebrafish egfl7 , an endothelial extracellular matrix gene of therapeutic interest, as well as in vegfaa . Here we show that egfl7 mutants do not show any obvious phenotypes while animals injected with egfl7 morpholino (morphants) exhibit severe vascular defects. We further observe that egfl7 mutants are less sensitive than their wild-type siblings to Egfl7 knockdown, arguing against residual protein function in the mutants or significant off-target effects of the morpholinos when used at a moderate dose. Comparing egfl7 mutant and morphant proteomes and transcriptomes, we identify a set of proteins and genes that are upregulated in mutants but not in morphants. Among them are extracellular matrix genes that can rescue egfl7 morphants, indicating that they could be compensating for the loss of Egfl7 function in the phenotypically wild-type egfl7 mutants. Moreover, egfl7 CRISPR interference, which obstructs transcript elongation and causes severe vascular defects, does not cause the upregulation of these genes. Similarly, vegfaa mutants but not morphants show an upregulation of vegfab . Taken together, these data reveal the activation of a compensatory network to buffer against deleterious mutations, which was not observed after translational or transcriptional knockdown. Main Interfering with a gene’s function is a widely used strategy to decipher its role. Several different approaches have been developed over the years to achieve this goal. Yet, despite having the same goal of functional inactivation, different strategies, namely knockdown (via antisense) and knockout (via genetic inactivation), often lead to different phenotypes. These discrepancies could be caused by off-target effects of the knockdown reagents, the generation and use of hypomorphic alleles, or other and more fundamental reasons. The recent development of new genome engineering techniques, such as TAL effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPRs), is allowing the facile generation of mutations and has revived concerns over the lack of specificity of knockdown reagents 1 , 2 , 3 . In several cases, toxicity due to off-target effects, induction of p53 (also known as tp53 ) transcription, interferon response, engagement of toll-like receptors and/or saturation of the RNA interference machinery can lead to phenotypes unrelated to the silencing of the target gene 8 , 9 . To investigate further whether toxicity effects are the main reason for the differences between genetic mutation and gene knockdown phenotypes, we analysed the EGF-like-domain, multiple 7 ( egfl7 ) gene. The egfl7 gene is a good candidate to address this question because of the lack of obvious phenotypes in the mouse mutants 10 , 11 and the severe vascular tube formation defects observed in knockdown experiments in zebrafish, frogs and human cells 12 , 13 , 14 . We first generated egfl7 mutants using TALENs 15 targeting exon 3, which encodes part of the EMI domain ( Fig. 1a and Extended Data Fig. 1 ). This domain precedes other domains critical for Egfl7 activity, including EGF domains and the leucine–valine-rich carboxy (C) terminus ( Fig. 1a ) 16 . We identified several deletion alleles including a Δ3 and a Δ4 ( Fig. 1b ). The egfl7 Δ3 (hereafter egfl7 s980 ) allele encodes a protein that lacks a non-conserved proline at position 50 (p.P50del) while the egfl7 Δ4 allele (hereafter egfl7 s981 ) is predicted to encode a truncated polypeptide containing a stretch of 29 incorrect amino acids starting with a Gln to Leu substitution at position 49 (p.Gln49Leufs*30) ( Fig. 1b ). To investigate the severity of these mutant alleles, we first examined egfl7 transcript levels by quantitative PCR (qPCR). The premature stop codon in egfl7 s981 led to a decrease of approximately 50% in transcript levels compared with wild-type (WT) and egfl7 s980 mutant embryos, indicating an increased messenger RNA (mRNA) degradation rate ( Extended Data Fig. 2a ). To characterize the different egfl7 mutant alleles further, we cloned the egfl7 WT, s980 and s981 complementary DNAs (cDNAs) in a mammalian expression vector and transfected HUVEC cells. Unlike Egfl7 WT and Egfl7 s980 , the Egfl7 s981 protein was mostly absent in the medium or the cells, suggesting that this truncated polypeptide is rapidly degraded and/or poorly translated and secreted ( Extended Data Fig. 2b ). Altogether, these data indicate that egfl7 s981 is a severe mutant allele, possibly even a null. Figure 1: Generation of zebrafish egfl7 mutant alleles and sporadic brain haemorrhage in mutant larvae. a , Top: egfl7 consists of 9 exons and mir126b is embedded in intron 6. The protein is encoded by exons 2–9 (grey boxes). a , Bottom: Egfl7, 277 amino acids (aa) long, contains a signal peptide (blue), an EMI domain (yellow), an EGF domain that contains a Delta-Serrate-LAG-2 (DSL) motif (orange) and a Ca 2+ -binding EGF domain (red). b , Top: the egfl7 s980 lesion (Δ3) leads to the deletion of proline at position 50 (p.P50del). b , Bottom: the egfl7 s981 allele (Δ4) encodes a truncated 77-amino-acid-long polypeptide (p.Gln49Leufs*30) that contains a signal peptide (blue) and a partial EMI domain (yellow) followed by a frameshift leading to a premature stop codon. c , d , Brightfield micrographs of 72 hpf WT and egfl7 s981/s981 larvae in lateral and ventral views. Arrows point to area of haemorrhage. e , f , Confocal micrographs of 72 hpf Tg(kdrl:HRAS-mCherry) WT and egfl7 s981/s981 larvae in lateral and dorsal views. PowerPoint slide Full size image To analyse Egfl7 function during vascular development, the egfl7 s981 mutant fish were crossed into the Tg(kdrl:HRAS-mCherry) 17 and<|im_end|> <|im_start|>assistant New methods for modifying the genome are currently widely discussed: Using CRISPR/Cas for instance, scientists can remove parts of the genetic code of a gene, thereby knocking it out. Furthermore, there are ways to inhibit translation of a gene into a protein. Both methods have in common that they impede production of a protein and should therefore have comparable consequences for an organism. However, it has been shown that consequences can differ, after a gene is either knocked, out or only blocked. Scientist from the MPI for Heart and Lung Research in Bad Nauheim now found that additional genes compensate for a knocked out gene and either attenuate consequences or completely compensate deficits. The results suggest caution when interpreting data from molecular biological studies or developing gene therapies to treat various diseases. To analyse function of an unkown gene, scientists often extinguish the gene and investigate the consequences of this treatment for the organism. To do so, they cut DNA-fragments from the gene using enzymes deleting the genetic information for a functioning protein. Such method is called "Gene knockout". In contrast, in a "gene knockdown" scientists block protein production using particular substances, e.g. microRNAs. Recent studies, however, have shown that results may vary between knockout- and knockdown animals. Scientists from Didier Stainier's group at the Max Planck Institute for Heart and Lung Research have now identified the reason for this. The Bad Nauheim based researchers have investigated a gene called egfl7 in zebrafish. The gene is involved in the production of connective tissue in blood vessel walls, thereby stabilizing them. Doing so, egfl7 regulates blood vessel growth. Developmental biologists, however, are not sure, what happens in a fish organism, after the egfl7 gene has been deleted. "If the gene has been blocked in a knockdown, blood vessels do not develop normally", explains Andrea Rossi, together with Zacharias Kontarakis first author of the study. In contrast, if the gene itself is deleted by a genetic manipulation, blood vessel growth is not affected. In the beginning, Max Planck researchers excluded potential side effects of the knockdown substance being responsible for interference in vascular development. To this end, they injected the substance into fish larvae in which the egfl7 gene had already been deleted. However, the larvae almost developed normally. "Since the substance did not cause disturbances in blood vessel growth, we thought of a different mechanism: The gene loss could be compensated by another gene taking over the function", Kontarakis says. "Therefore, we were looking for rescue genes, which might have been produced in animals without a functional egfl7 gene." The researchers compared the mRNA molecules and proteins in fish with or without a functional egfl7 gene and detected several mRNAs and proteins being present in higher amounts in fish without egfl7. An example is emilin 3B. When "knockdown" animals are treated with emilin 3B after egfl7 has been blocked, blood vessels develop almost normally. "This tells us that emilin 3B can compensate for the loss of egfl7. In egfl7 knockout fish, emilin production is getting upregulated. This is not the case in knockdown fish", Stainier explains. As the next step, the group plans to analyse how genes "know" that another gene has been deleted and then compensate for the loss. Several researchers worldwide are trying to delete disease genes for therapeutic reasons. Before we establish such therapies, we have to fully understand the consequences the loss or blockade of a gene might have. "In addition, our study illustrates the power of comparing knockouts and knockdowns to identify modifier genes, a goal that remains a major challenge in the field of human genetics" says Stainier. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Tumors have evolved mechanisms to escape anti-tumor immunosurveillance. They limit humoral and cellular immune activities in the stroma and render tumors resistant to immunotherapy. Sensitizing tumor cells to immune attack is an important strategy to revert immunosuppression. However, the underlying mechanisms of immune escape are still poorly understood. Here we discover Indoleamine-2,3-dioxygenase-1 (IDO1) + Paneth cells in the stem cell niche of intestinal crypts and tumors, which promoted immune escape of colorectal cancer (CRC). Ido1 expression in Paneth cells was strictly Stat1 dependent. Loss of IDO1 + Paneth cells in murine intestinal adenomas with tumor cell-specific Stat1 deletion had profound effects on the intratumoral immune cell composition. Patient samples and TCGA expression data suggested corresponding cells in human colorectal tumors. Thus, our data uncovered an immune escape mechanism of CRC and identify IDO1 + Paneth cells as a target for immunotherapy. Introduction Colorectal cancer (CRC) is the third most common cancer worldwide and patients with metastases in distant organs have a 5-year survival rate below 13% 1 . Metastatic CRC is currently treated with several combinations of cytotoxic agents. They improved overall survival of patients, treated initially with fluoropyrimidine monotherapy, from 12 to 30 months 2 . However, chemotherapy reached its limits 3 , which fostered clinical trials for immunotherapies 4 . The importance of immunosurveillance in CRC is emphasized by the good prognostic value of CD3 + , CD8 + , and CD45RO + T-cell infiltration (Immunoscore) 5 , 6 , 7 . Unfortunately, immunotherapy with checkpoint inhibitors showed clinical benefits only in mismatch-repair-deficient CRC with high neo-antigen load. Durable responses in CRC with different etiologies remained scarce, which is due to immune escape mechanisms 8 . The transcription factor signal transducer and activator of transcription 1 (Stat1) is a key effector in tumor immunosurveillance mediated by natural killer (NK)- and T cells 9 , 10 . Consistently, Stat1 is part of the immunologic constant of rejection gene expression signature, which correlates with good prognosis of CRC 7 . In cancer cells, Stat1 inhibits proliferation and promotes apoptosis via induction of cyclin-dependent kinase inhibitors and pro-apoptotic proteins 9 . Stat1 also regulates the expression of tissue antigens and proteins of the antigen presentation machinery, which enhance the immunogenicity of tumors 11 . Therefore, it is generally considered that Stat1 expression and activation in immune cells and in cancer cells suppresses tumorigenesis. Type I and II interferon (IFN) are the major activators of canonical Stat1 signaling, which relies on Tyr701 phosphorylation (pY-STAT1) and mediates tumor suppressive effects of IFN 12 . However, the tumor cell-intrinsic role of Stat1 in CRC is not well defined. Lgr5 + stem cells at the bottom of intestinal crypts have been identified as possible precursor cells for CRC 13 . However, non-stem cells can also acquire tumor-initiating capacity 14 and Lgr5 + cancer stem cells are not essential for growth of primary tumors 15 . These cells are separated by Lysozyme + Paneth cells in the small intestine, which provide essential niche factors for stem cell proliferation and self-renewal 16 . In the colon, Lysozyme − deep crypt base secretory cells support Lgr5 + stem cells 16 but colonic Paneth cells can appear through epithelial metaplasia 17 . Paneth cells have been identified in intestinal tumors of Apc Min mice 18 and in sporadic CRC of humans, albeit at varying frequencies ranging from 0.2% to 39% 19 . However, intestinal tumors from familial adenomatous polyposis (FAP) patients with inherited Apc mutations harbored more than 90% of Paneth cells 20 . The role of Paneth cells is unclear but CRC developed predominantly in colonic mucosal tissue with Paneth cell metaplasia 21 and the presence of Paneth cell-containing adenomas increased the risk for synchronous CRC 19 . Therefore, Paneth cells might promote CRC formation. Here we identified a subset of Paneth cells that displayed Stat1-dependent expression of the immune checkpoint molecule IDO1. Loss of these cells in Stat1-deficient intestinal tumors of Apc Min mice resulted in reduced tumor load and increased infiltration of anti-tumor immune cells. Results Epithelial Stat1 promotes formation of intestinal tumors We used Apc Min mice 22 with conditional deletion of Stat1 in intestinal epithelial cells ( Stat1 ∆IEC Apc Min ) 23 , 24 to identify Stat1 functions in intestinal tumorigenesis. Deletion of Stat1 was confirmed by PCR (Supplementary Fig. 1a ), quantitative PCR (qPCR) of purified intestinal epithelial cells (Supplementary Fig. 1b ) and immunohistochemistry (IHC, Supplementary Fig. 1c ). Lamina propria cells of Stat1 ∆IEC Apc Min mice displayed STAT1 expression, which demonstrated specific ablation in intestinal epithelial cells (Supplementary Fig. 1c ). Goblet, enteroendocrine, Paneth, and proliferating cells in the intestinal crypts were present at normal numbers in Stat1 ∆IEC Apc Min mice (Supplementary Fig. 1d-h ). These data show that epithelial cell-specific deletion of Stat1 does not affect intestinal cell differentiation and crypt proliferation of Apc Min mice. Four-month-old Stat1 flox/flox Apc Min and Stat1 ∆IEC Apc Min mice were used to investigate epithelial cell-intrinsic functions of Stat1 in intestinal tumorigenesis. Tumor formation was reduced in Stat1 ∆IEC Apc Min male and female mice (Fig. 1a–c ). Angiogenesis (Supplementary Fig. 2a ), tumor cell proliferation, and apoptosis (Supplementary Fig. 2b ) were not affected but numbers of low-grade adenomas were increased (Fig. 1d ). These data show that epithelial cell-intrinsic Stat1 promotes the formation and progression of intestinal tumors in Apc Min mice. Fig. 1: Reduced intestinal tumor burden in Stat1 ∆IEC Apc Min mice. a – c Quantification of tumor load ( a ), number ( b ), and mean area ( c ) in Stat1 flox/flox Apc Min (7♀, 9♂) and Stat1 ∆IEC Apc Min (6♀, 13♂) mice. d Grading of tumors in Stat1 flox/flox Apc Min (115 tumors, 9 mice) and Stat1 ∆IEC Apc Min (68 tumors, 9 mice) mice. Low grade: p < 0.001; high grade: p < 0.001; carcinoma: p = 0.473. e IHC staining demonstrating STAT1 + tumor cells (arrowheads) in Stat1 flox/flox Apc Min colon tumors. STAT1 expression was not detectable", "role": "user" }, { "content": "A MedUni Vienna study group has identified a previously unknown mechanism involved in the development of intestinal cancer: The bacterial microbiome activates the so-called immune checkpoint Ido1 in Paneth cells, a special cell that is only found in the gastrointestinal tract, thereby preventing local intestinal inflammation. However, this also gives rise to immunosuppressed areas, in which intestinal tumors can develop. The Paneth cells are therefore a new cellular target for immune-based therapies against intestinal tumors. The study was recently published in the Nature journal Communications Biology. Cancer cells have developed mechanisms that allow them to go undetected by the body's immune system and so avoid their destruction. These mechanisms restrict humoral and cell-mediated immune activity in the surrounding connective tissue (stroma) and make cancers resistant to treatment. Sensitizing cancer cells for an immune attack is therefore an important strategy in ensuring the success of immunotherapy techniques. However, little is yet known about the underlying mechanisms by which cancers escape the immune system. Paneth cells are gland cells in the gastrointestinal area and support the division of intestinal stem cells. MedUni Vienna researchers, led by Robert Eferl from the Institute of Cancer Research (member of the Comprehensive Cancer Center CCC of MedUni Vienna and Vienna University Hospital) discovered that Paneth cells, which produce the enzyme Ido1 (indoleamine-2,3-dioxygenase-1), inhibit the action of the immune system against intestinal cancer in the stem cell area of intestinal crypts and tumors. The researchers knocked-out the transcription factor Stat1 in intestinal epithelial cells of so-called ApcMin mice, which develop intestinal tumors due to a mutation in the Apc gene. The result was that they developed smaller and less aggressive tumors. Moreover, these tumors were infiltrated by immune cells that play a role in tumor defense. These included cytotoxic T lymphocytes. The study group then studied these tumors in more detail using RNA sequencing and found that the Stat1-deficient tumors exhibit reduced expression of the Ido1 gene. Ido1 encodes an enzyme that produces the metabolite kynurenine. Kynurenine suppresses the immune response in the tumor, thereby promoting tumor growth. Further studies have shown that ApcMin tumors with an intact Stat1 gene contain special cells that express Ido1. Similar cells were also discovered in human intestinal polyps. These cells were not present in the Stat1-deficient ApcMin tumors. Further characterisation revealed that these special cells are Paneth-like cells. Paneth cells are also found in the normal intestine, in the stem cell areas that are responsible for regeneration of the intestinal mucosa. Ido1 expression in the Paneth cells is stimulated by interaction with the bacterial microbiome. Eferl explains: \"According to our hypothesis, the bacterial microbiome induces the Ido1 immune checkpoint in the Paneth cells, thereby preventing local intestinal inflammation. However, this also gives rise to immunosuppressed areas, in which intestinal tumors can develop. Ido1-expressing Paneth cells are therefore a cellular target for immune-based therapies.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Tumors have evolved mechanisms to escape anti-tumor immunosurveillance. They limit humoral and cellular immune activities in the stroma and render tumors resistant to immunotherapy. Sensitizing tumor cells to immune attack is an important strategy to revert immunosuppression. However, the underlying mechanisms of immune escape are still poorly understood. Here we discover Indoleamine-2,3-dioxygenase-1 (IDO1) + Paneth cells in the stem cell niche of intestinal crypts and tumors, which promoted immune escape of colorectal cancer (CRC). Ido1 expression in Paneth cells was strictly Stat1 dependent. Loss of IDO1 + Paneth cells in murine intestinal adenomas with tumor cell-specific Stat1 deletion had profound effects on the intratumoral immune cell composition. Patient samples and TCGA expression data suggested corresponding cells in human colorectal tumors. Thus, our data uncovered an immune escape mechanism of CRC and identify IDO1 + Paneth cells as a target for immunotherapy. Introduction Colorectal cancer (CRC) is the third most common cancer worldwide and patients with metastases in distant organs have a 5-year survival rate below 13% 1 . Metastatic CRC is currently treated with several combinations of cytotoxic agents. They improved overall survival of patients, treated initially with fluoropyrimidine monotherapy, from 12 to 30 months 2 . However, chemotherapy reached its limits 3 , which fostered clinical trials for immunotherapies 4 . The importance of immunosurveillance in CRC is emphasized by the good prognostic value of CD3 + , CD8 + , and CD45RO + T-cell infiltration (Immunoscore) 5 , 6 , 7 . Unfortunately, immunotherapy with checkpoint inhibitors showed clinical benefits only in mismatch-repair-deficient CRC with high neo-antigen load. Durable responses in CRC with different etiologies remained scarce, which is due to immune escape mechanisms 8 . The transcription factor signal transducer and activator of transcription 1 (Stat1) is a key effector in tumor immunosurveillance mediated by natural killer (NK)- and T cells 9 , 10 . Consistently, Stat1 is part of the immunologic constant of rejection gene expression signature, which correlates with good prognosis of CRC 7 . In cancer cells, Stat1 inhibits proliferation and promotes apoptosis via induction of cyclin-dependent kinase inhibitors and pro-apoptotic proteins 9 . Stat1 also regulates the expression of tissue antigens and proteins of the antigen presentation machinery, which enhance the immunogenicity of tumors 11 . Therefore, it is generally considered that Stat1 expression and activation in immune cells and in cancer cells suppresses tumorigenesis. Type I and II interferon (IFN) are the major activators of canonical Stat1 signaling, which relies on Tyr701 phosphorylation (pY-STAT1) and mediates tumor suppressive effects of IFN 12 . However, the tumor cell-intrinsic role of Stat1 in CRC is not well defined. Lgr5 + stem cells at the bottom of intestinal crypts have been identified as possible precursor cells for CRC 13 . However, non-stem cells can also acquire tumor-initiating capacity 14 and Lgr5 + cancer stem cells are not essential for growth of primary tumors 15 . These cells are separated by Lysozyme + Paneth cells in the small intestine, which provide essential niche factors for stem cell proliferation and self-renewal 16 . In the colon, Lysozyme − deep crypt base secretory cells support Lgr5 + stem cells 16 but colonic Paneth cells can appear through epithelial metaplasia 17 . Paneth cells have been identified in intestinal tumors of Apc Min mice 18 and in sporadic CRC of humans, albeit at varying frequencies ranging from 0.2% to 39% 19 . However, intestinal tumors from familial adenomatous polyposis (FAP) patients with inherited Apc mutations harbored more than 90% of Paneth cells 20 . The role of Paneth cells is unclear but CRC developed predominantly in colonic mucosal tissue with Paneth cell metaplasia 21 and the presence of Paneth cell-containing adenomas increased the risk for synchronous CRC 19 . Therefore, Paneth cells might promote CRC formation. Here we identified a subset of Paneth cells that displayed Stat1-dependent expression of the immune checkpoint molecule IDO1. Loss of these cells in Stat1-deficient intestinal tumors of Apc Min mice resulted in reduced tumor load and increased infiltration of anti-tumor immune cells. Results Epithelial Stat1 promotes formation of intestinal tumors We used Apc Min mice 22 with conditional deletion of Stat1 in intestinal epithelial cells ( Stat1 ∆IEC Apc Min ) 23 , 24 to identify Stat1 functions in intestinal tumorigenesis. Deletion of Stat1 was confirmed by PCR (Supplementary Fig. 1a ), quantitative PCR (qPCR) of purified intestinal epithelial cells (Supplementary Fig. 1b ) and immunohistochemistry (IHC, Supplementary Fig. 1c ). Lamina propria cells of Stat1 ∆IEC Apc Min mice displayed STAT1 expression, which demonstrated specific ablation in intestinal epithelial cells (Supplementary Fig. 1c ). Goblet, enteroendocrine, Paneth, and proliferating cells in the intestinal crypts were present at normal numbers in Stat1 ∆IEC Apc Min mice (Supplementary Fig. 1d-h ). These data show that epithelial cell-specific deletion of Stat1 does not affect intestinal cell differentiation and crypt proliferation of Apc Min mice. Four-month-old Stat1 flox/flox Apc Min and Stat1 ∆IEC Apc Min mice were used to investigate epithelial cell-intrinsic functions of Stat1 in intestinal tumorigenesis. Tumor formation was reduced in Stat1 ∆IEC Apc Min male and female mice (Fig. 1a–c ). Angiogenesis (Supplementary Fig. 2a ), tumor cell proliferation, and apoptosis (Supplementary Fig. 2b ) were not affected but numbers of low-grade adenomas were increased (Fig. 1d ). These data show that epithelial cell-intrinsic Stat1 promotes the formation and progression of intestinal tumors in Apc Min mice. Fig. 1: Reduced intestinal tumor burden in Stat1 ∆IEC Apc Min mice. a – c Quantification of tumor load ( a ), number ( b ), and mean area ( c ) in Stat1 flox/flox Apc Min (7♀, 9♂) and Stat1 ∆IEC Apc Min (6♀, 13♂) mice. d Grading of tumors in Stat1 flox/flox Apc Min (115 tumors, 9 mice) and Stat1 ∆IEC Apc Min (68 tumors, 9 mice) mice. Low grade: p < 0.001; high grade: p < 0.001; carcinoma: p = 0.473. e IHC staining demonstrating STAT1 + tumor cells (arrowheads) in Stat1 flox/flox Apc Min colon tumors. STAT1 expression was not detectable<|im_end|> <|im_start|>assistant A MedUni Vienna study group has identified a previously unknown mechanism involved in the development of intestinal cancer: The bacterial microbiome activates the so-called immune checkpoint Ido1 in Paneth cells, a special cell that is only found in the gastrointestinal tract, thereby preventing local intestinal inflammation. However, this also gives rise to immunosuppressed areas, in which intestinal tumors can develop. The Paneth cells are therefore a new cellular target for immune-based therapies against intestinal tumors. The study was recently published in the Nature journal Communications Biology. Cancer cells have developed mechanisms that allow them to go undetected by the body's immune system and so avoid their destruction. These mechanisms restrict humoral and cell-mediated immune activity in the surrounding connective tissue (stroma) and make cancers resistant to treatment. Sensitizing cancer cells for an immune attack is therefore an important strategy in ensuring the success of immunotherapy techniques. However, little is yet known about the underlying mechanisms by which cancers escape the immune system. Paneth cells are gland cells in the gastrointestinal area and support the division of intestinal stem cells. MedUni Vienna researchers, led by Robert Eferl from the Institute of Cancer Research (member of the Comprehensive Cancer Center CCC of MedUni Vienna and Vienna University Hospital) discovered that Paneth cells, which produce the enzyme Ido1 (indoleamine-2,3-dioxygenase-1), inhibit the action of the immune system against intestinal cancer in the stem cell area of intestinal crypts and tumors. The researchers knocked-out the transcription factor Stat1 in intestinal epithelial cells of so-called ApcMin mice, which develop intestinal tumors due to a mutation in the Apc gene. The result was that they developed smaller and less aggressive tumors. Moreover, these tumors were infiltrated by immune cells that play a role in tumor defense. These included cytotoxic T lymphocytes. The study group then studied these tumors in more detail using RNA sequencing and found that the Stat1-deficient tumors exhibit reduced expression of the Ido1 gene. Ido1 encodes an enzyme that produces the metabolite kynurenine. Kynurenine suppresses the immune response in the tumor, thereby promoting tumor growth. Further studies have shown that ApcMin tumors with an intact Stat1 gene contain special cells that express Ido1. Similar cells were also discovered in human intestinal polyps. These cells were not present in the Stat1-deficient ApcMin tumors. Further characterisation revealed that these special cells are Paneth-like cells. Paneth cells are also found in the normal intestine, in the stem cell areas that are responsible for regeneration of the intestinal mucosa. Ido1 expression in the Paneth cells is stimulated by interaction with the bacterial microbiome. Eferl explains: "According to our hypothesis, the bacterial microbiome induces the Ido1 immune checkpoint in the Paneth cells, thereby preventing local intestinal inflammation. However, this also gives rise to immunosuppressed areas, in which intestinal tumors can develop. Ido1-expressing Paneth cells are therefore a cellular target for immune-based therapies." <|im_end|>

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2,182

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Diet is commonly assumed to affect the evolution of species, but few studies have directly tested its effect at macroevolutionary scales. Here we use Bayesian models of trait-dependent diversification and a comprehensive dietary database of all birds worldwide to assess speciation and extinction dynamics of avian dietary guilds (carnivores, frugivores, granivores, herbivores, insectivores, nectarivores, omnivores and piscivores). Our results suggest that omnivory is associated with higher extinction rates and lower speciation rates than other guilds, and that overall net diversification is negative. Trait-dependent models, dietary similarity and network analyses show that transitions into omnivory occur at higher rates than into any other guild. We suggest that omnivory acts as macroevolutionary sink, where its ephemeral nature is retrieved through transitions from other guilds rather than from omnivore speciation. We propose that these dynamics result from competition within and among dietary guilds, influenced by the deep-time availability and predictability of food resources. Introduction Variation of biodiversity across space and time is a trademark of the history of life on Earth and ultimately determined by speciation and extinction rates 1 , 2 . To better understand the dynamics of biodiversity we need to understand the roles of biotic and abiotic factors in determining speciation and extinction dynamics 3 . While examples of abiotic factors affecting diversification dynamics are numerous (for example, ref. 4 and references therein), few studies have explored biotic influences on macroevolutionary rates across large spatio-temporal scales 5 , 6 , 7 . Hence, the relevance of biotic interactions for diversification dynamics across deep timescales is still an open question. Understanding the role of biotic interactions is a daunting task, given the myriad of interactions (for example, antagonistic, mutualistic and competitive) that individuals of a given species can have with individuals of other species. However, characterizing and understanding the trophic habits of species is tractable and may also be of great importance to understand potential adaptive responses to food availability, (for example, ref. 8 ), as well as the effects of biotic interactions on macroevolutionary dynamics 9 . As such, the diet of a given species can be used as a first-order proxy to biotic interactions. It summarizes distinct morphological, physiological and behavioural traits of an organism, which jointly determine the way it interacts with the biotic and abiotic environment 10 , 11 , 12 . For example, birds that attend army ant raids have to deal with the unpredictability of those raids, and have developed cognitive and behavioural adaptations to surpass these challenges 11 . Similarly, many nectar-feeding species have evolved beaks that suit the morphology of the flowers on which they feed, (for example, ref. 12 ). Since flowering phenology is strongly constrained by seasonality, the variability in climate (for example, in temperature) strongly determines geographic distributions of guilds such as nectarivores 13 . More generally, the long-term availability of particular climates 14 , as well as the spatio-temporal predictability of food resources, (for example, refs 15 , 16 ), might influence evolutionary radiations and diversity dynamics 14 , 15 , with environmental instability setting a potential limit to the degree of specialization 17 . Dietary strategies have been crucial for understanding species formation because interspecific competition for similar food resources can explain character displacement and the evolutionary divergence of species 18 , 19 . Nevertheless, to date only few studies at macroevolutionary scales have tested how diets might affect diversification dynamics across whole clades, (for example, refs 9 , 20 , 21 ). The paucity of whole-clade investigations relating diet to macroevolutionary dynamics is partly due to the lack of data, but also due to methodological limitations. However, recently developed methods now allow us to explicitly address 22 , 23 , 24 or indirectly assess 25 , 26 the relationship between trait evolution and diversification rates, and various authors have therefore analysed this relationship. Collectively, those studies revealed the effects of numerous traits on diversification dynamics, including self-incompatibility in Solanaceae 27 , tank formation and photosynthesis type in bromeliads 28 , migratory behaviour in birds 29 and diet in mammals 9 , 20 . Hence, ecological and life history traits play a critical role for understanding macroevolutionary dynamics and broad-scale patterns of species coexistence 24 , 30 . One of the few papers that explicitly addressed the effect of diet on macroevolutionary dynamics has shown that coarse trophic levels (that is, herbivores, carnivores and omnivores) are characterized by different diversification rates in mammals 9 . These results suggest that omnivorous mammals have lower net diversification rates than carnivores and herbivores, and that transitions into omnivory are more frequent than into other trophic levels. Using a finer diet classification within ruminants (that is, giraffes, deer, buffaloes, antelope and relatives), it has further been shown that different feeding styles underwent differential diversification rates 21 . However, this analysis suggested that grazing and mixed feeding (a combination of browsing and grazing) have both higher diversification rates and more transitions into and from these diets than browsing. Overall, these studies highlight the potential association between dietary guilds and diversification dynamics, but they also suggest that a more generalist diet (for example, omnivory or mixed feeding) might not have the same straightforward macroevolutionary outcomes at different lineages or hierarchical levels. Birds represent a good model system for investigating the role of diet on speciation and extinction 18 , 19 , and more broadly, to understand the interplay between ecology and diversification. The clade Aves has an enormous taxonomic diversity (c. 10,300 species) with a large variability in ecological and life history traits 13 , 30 , 31 . The recently published whole-clade bird phylogeny 32 and the abundance of ecological information for Aves have allowed biologists to assess the evolutionary dynamics (either trait-dependent or trait-independent) of many bird lineages at different taxonomic levels, (for example, refs 29 , 33 , 34 ). Moreover, different types of diet have evolved multiple times within the clade 13 . Dietary adaptations range from specialized feeders such as some insectivores (for example, swifts and swallows), frugivores", "role": "user" }, { "content": "How diet has affected the evolution of the 10,000 bird species in the world is still a mystery to evolutionary biology. A study by Daniel Kissling of the Institute for Biodiversity and Ecosystem Dynamics (UvA) and colleagues from the University of São Paulo and the University of Utah shows how diet preferences have influenced bird diversification over millions of years. The findings were published in Nature Communications. Since the seminal work by Charles Darwin, it is know that dietary habits of birds can affect the evolution of species, such as the beak sizes of Galapagos finches. However, birds show an astonishing diversity of species and dietary adaptations, ranging from very small nectar-feeding hummingbirds to large carnivorous eagles. How such diverse dietary preferences ultimately lead to differences in diversification dynamics (i.e. the balance between speciation and extinction) of different birds has not yet been examined. Diet dataset The researchers compiled an impressive diet dataset of almost all bird species in the world together with a large phylogenetic tree that represent the relatedness of all bird species. Using models of trait-dependent diversification, they then showed that omnivorous bird lineages (with species that feed on many different food items) have lower rates of speciation (i.e. generating less new species) and higher rates of extinction (i.e. losing more existing species) than species which prefer specific food items such as fruits, nectar, or insects. Furthermore, the researchers also found that over deep evolutionary time birds which are specialized on a particular food item often add other food items to their diets, resulting in evolving transitions into omnivory. Surprised 'I was really surprised to find that omnivores preferentially originate via transitions, and not through speciation', says lead author and PhD student Gustavo Burin from the University of São Paulo. Together with the low speciation rates and high extinction rates, these high transition rates indicate that omnivores originate from more specialized birds that expand their diets, rather than directly through speciation of omnivorous bird clades. 'We suggest that this is caused by resource competition, climate instability, and deep-time availability of food resources', says Burin. High transition rates towards omnivory may arise in times when food is harder to find or when it is temporally unavailable. Human activities Expanding these findings to the current human-driven changes on our planet the researchers expect that shifts in competitive dynamics between generalists and specialists will occur. 'Human activities such as habitat destruction and other global change drivers eliminate the resources of many specialist species', says Daniel Kissling from University of Amsterdam. This means that specialists are currently at higher risk of extinction than generalists. 'This will dramatically change the ecology and evolution of life on Earth because generalists are now favoured at the expense of specialists', explains Kissling. Ultimately, this will affect the functioning of ecosystems and the services that nature provides to humanity. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Diet is commonly assumed to affect the evolution of species, but few studies have directly tested its effect at macroevolutionary scales. Here we use Bayesian models of trait-dependent diversification and a comprehensive dietary database of all birds worldwide to assess speciation and extinction dynamics of avian dietary guilds (carnivores, frugivores, granivores, herbivores, insectivores, nectarivores, omnivores and piscivores). Our results suggest that omnivory is associated with higher extinction rates and lower speciation rates than other guilds, and that overall net diversification is negative. Trait-dependent models, dietary similarity and network analyses show that transitions into omnivory occur at higher rates than into any other guild. We suggest that omnivory acts as macroevolutionary sink, where its ephemeral nature is retrieved through transitions from other guilds rather than from omnivore speciation. We propose that these dynamics result from competition within and among dietary guilds, influenced by the deep-time availability and predictability of food resources. Introduction Variation of biodiversity across space and time is a trademark of the history of life on Earth and ultimately determined by speciation and extinction rates 1 , 2 . To better understand the dynamics of biodiversity we need to understand the roles of biotic and abiotic factors in determining speciation and extinction dynamics 3 . While examples of abiotic factors affecting diversification dynamics are numerous (for example, ref. 4 and references therein), few studies have explored biotic influences on macroevolutionary rates across large spatio-temporal scales 5 , 6 , 7 . Hence, the relevance of biotic interactions for diversification dynamics across deep timescales is still an open question. Understanding the role of biotic interactions is a daunting task, given the myriad of interactions (for example, antagonistic, mutualistic and competitive) that individuals of a given species can have with individuals of other species. However, characterizing and understanding the trophic habits of species is tractable and may also be of great importance to understand potential adaptive responses to food availability, (for example, ref. 8 ), as well as the effects of biotic interactions on macroevolutionary dynamics 9 . As such, the diet of a given species can be used as a first-order proxy to biotic interactions. It summarizes distinct morphological, physiological and behavioural traits of an organism, which jointly determine the way it interacts with the biotic and abiotic environment 10 , 11 , 12 . For example, birds that attend army ant raids have to deal with the unpredictability of those raids, and have developed cognitive and behavioural adaptations to surpass these challenges 11 . Similarly, many nectar-feeding species have evolved beaks that suit the morphology of the flowers on which they feed, (for example, ref. 12 ). Since flowering phenology is strongly constrained by seasonality, the variability in climate (for example, in temperature) strongly determines geographic distributions of guilds such as nectarivores 13 . More generally, the long-term availability of particular climates 14 , as well as the spatio-temporal predictability of food resources, (for example, refs 15 , 16 ), might influence evolutionary radiations and diversity dynamics 14 , 15 , with environmental instability setting a potential limit to the degree of specialization 17 . Dietary strategies have been crucial for understanding species formation because interspecific competition for similar food resources can explain character displacement and the evolutionary divergence of species 18 , 19 . Nevertheless, to date only few studies at macroevolutionary scales have tested how diets might affect diversification dynamics across whole clades, (for example, refs 9 , 20 , 21 ). The paucity of whole-clade investigations relating diet to macroevolutionary dynamics is partly due to the lack of data, but also due to methodological limitations. However, recently developed methods now allow us to explicitly address 22 , 23 , 24 or indirectly assess 25 , 26 the relationship between trait evolution and diversification rates, and various authors have therefore analysed this relationship. Collectively, those studies revealed the effects of numerous traits on diversification dynamics, including self-incompatibility in Solanaceae 27 , tank formation and photosynthesis type in bromeliads 28 , migratory behaviour in birds 29 and diet in mammals 9 , 20 . Hence, ecological and life history traits play a critical role for understanding macroevolutionary dynamics and broad-scale patterns of species coexistence 24 , 30 . One of the few papers that explicitly addressed the effect of diet on macroevolutionary dynamics has shown that coarse trophic levels (that is, herbivores, carnivores and omnivores) are characterized by different diversification rates in mammals 9 . These results suggest that omnivorous mammals have lower net diversification rates than carnivores and herbivores, and that transitions into omnivory are more frequent than into other trophic levels. Using a finer diet classification within ruminants (that is, giraffes, deer, buffaloes, antelope and relatives), it has further been shown that different feeding styles underwent differential diversification rates 21 . However, this analysis suggested that grazing and mixed feeding (a combination of browsing and grazing) have both higher diversification rates and more transitions into and from these diets than browsing. Overall, these studies highlight the potential association between dietary guilds and diversification dynamics, but they also suggest that a more generalist diet (for example, omnivory or mixed feeding) might not have the same straightforward macroevolutionary outcomes at different lineages or hierarchical levels. Birds represent a good model system for investigating the role of diet on speciation and extinction 18 , 19 , and more broadly, to understand the interplay between ecology and diversification. The clade Aves has an enormous taxonomic diversity (c. 10,300 species) with a large variability in ecological and life history traits 13 , 30 , 31 . The recently published whole-clade bird phylogeny 32 and the abundance of ecological information for Aves have allowed biologists to assess the evolutionary dynamics (either trait-dependent or trait-independent) of many bird lineages at different taxonomic levels, (for example, refs 29 , 33 , 34 ). Moreover, different types of diet have evolved multiple times within the clade 13 . Dietary adaptations range from specialized feeders such as some insectivores (for example, swifts and swallows), frugivores<|im_end|> <|im_start|>assistant How diet has affected the evolution of the 10,000 bird species in the world is still a mystery to evolutionary biology. A study by Daniel Kissling of the Institute for Biodiversity and Ecosystem Dynamics (UvA) and colleagues from the University of São Paulo and the University of Utah shows how diet preferences have influenced bird diversification over millions of years. The findings were published in Nature Communications. Since the seminal work by Charles Darwin, it is know that dietary habits of birds can affect the evolution of species, such as the beak sizes of Galapagos finches. However, birds show an astonishing diversity of species and dietary adaptations, ranging from very small nectar-feeding hummingbirds to large carnivorous eagles. How such diverse dietary preferences ultimately lead to differences in diversification dynamics (i.e. the balance between speciation and extinction) of different birds has not yet been examined. Diet dataset The researchers compiled an impressive diet dataset of almost all bird species in the world together with a large phylogenetic tree that represent the relatedness of all bird species. Using models of trait-dependent diversification, they then showed that omnivorous bird lineages (with species that feed on many different food items) have lower rates of speciation (i.e. generating less new species) and higher rates of extinction (i.e. losing more existing species) than species which prefer specific food items such as fruits, nectar, or insects. Furthermore, the researchers also found that over deep evolutionary time birds which are specialized on a particular food item often add other food items to their diets, resulting in evolving transitions into omnivory. Surprised 'I was really surprised to find that omnivores preferentially originate via transitions, and not through speciation', says lead author and PhD student Gustavo Burin from the University of São Paulo. Together with the low speciation rates and high extinction rates, these high transition rates indicate that omnivores originate from more specialized birds that expand their diets, rather than directly through speciation of omnivorous bird clades. 'We suggest that this is caused by resource competition, climate instability, and deep-time availability of food resources', says Burin. High transition rates towards omnivory may arise in times when food is harder to find or when it is temporally unavailable. Human activities Expanding these findings to the current human-driven changes on our planet the researchers expect that shifts in competitive dynamics between generalists and specialists will occur. 'Human activities such as habitat destruction and other global change drivers eliminate the resources of many specialist species', says Daniel Kissling from University of Amsterdam. This means that specialists are currently at higher risk of extinction than generalists. 'This will dramatically change the ecology and evolution of life on Earth because generalists are now favoured at the expense of specialists', explains Kissling. Ultimately, this will affect the functioning of ecosystems and the services that nature provides to humanity. <|im_end|>

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25078, 13, 27304, 10550, 578, 12074, 20276, 459, 16358, 10173, 10550, 315, 4661, 682, 12224, 9606, 304, 279, 1917, 3871, 449, 264, 3544, 37555, 86945, 5411, 5021, 430, 4097, 279, 5552, 2136, 315, 682, 12224, 9606, 13, 12362, 4211, 315, 18027, 43918, 21797, 2461, 11, 814, 1243, 8710, 430, 50197, 344, 20857, 12224, 1584, 1154, 320, 4291, 9606, 430, 5510, 389, 1690, 2204, 3691, 3673, 8, 617, 4827, 7969, 315, 1424, 7246, 320, 72, 1770, 13, 24038, 2753, 502, 9606, 8, 323, 5190, 7969, 315, 52609, 320, 72, 1770, 13, 13490, 810, 6484, 9606, 8, 1109, 9606, 902, 10932, 3230, 3691, 3673, 1778, 439, 26390, 11, 308, 39916, 11, 477, 41911, 13, 24296, 11, 279, 12074, 1101, 1766, 430, 927, 5655, 41993, 892, 20229, 902, 527, 28175, 389, 264, 4040, 3691, 1537, 3629, 923, 1023, 3691, 3673, 311, 872, 41943, 11, 13239, 304, 42028, 34692, 1139, 50197, 344, 683, 13, 8242, 652, 4147, 364, 40, 574, 2216, 14792, 311, 1505, 430, 50197, 344, 4692, 10932, 31668, 82316, 4669, 34692, 11, 323, 539, 1555, 1424, 7246, 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1,979

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract An important technique for discovering and characterizing planets beyond our solar system relies upon measurement of weak Doppler shifts in the spectra of host stars induced by the influence of orbiting planets. A recent advance has been the introduction of optical frequency combs as frequency references. Frequency combs produce a series of equally spaced reference frequencies and they offer extreme accuracy and spectral grasp that can potentially revolutionize exoplanet detection. Here we demonstrate a laser frequency comb using an alternate comb generation method based on electro-optical modulation, with the comb centre wavelength stabilized to a molecular or atomic reference. In contrast to mode-locked combs, the line spacing is readily resolvable using typical astronomical grating spectrographs. Built using commercial off-the-shelf components, the instrument is relatively simple and reliable. Proof of concept experiments operated at near-infrared wavelengths were carried out at the NASA Infrared Telescope Facility and the Keck-II telescope. Introduction The earliest technique for the discovery and characterization of planets orbiting other stars (exoplanets) is the Doppler or radial velocity (RV) method whereby small periodic changes in the motion of a star orbited by a planet are detected via careful spectroscopic measurements 1 . The RV technique has identified hundreds of planets ranging in mass from a few times the mass of Jupiter to less than an Earth mass, and in orbital periods from less than a day to over 10 years (ref. 2 ). However, the detection of Earth-analogues at orbital separations suitable for the presence of liquid water at the planet’s surface, that is, in the ‘habitable zone’ 3 , remains challenging for stars like the Sun with RV signatures <0.1 m s −1 (Δ V / c <3 × 10 −10 ) and periods of a year ( ∼ 10 8 sec to measure three complete periods). For cooler, lower luminosity stars (spectral class M), however, the habitable zone moves closer to the star which, by application of Kepler’s laws, implies that a planet’s RV signature increases, ∼ 0.5 m s −1 (Δ V / c <1.5 × 10 −9 ), and its orbital period decreases, ∼ 30 days ( ∼ 10 7 s to measure three periods). Both of these effects make the detection easier. But for M stars, the bulk of the radiation shifts from the visible wavelengths, where most RV measurements have been made to date, into the near-infrared. Thus, there is considerable interest among astronomers in developing precise RV capabilities at longer wavelengths. Critical to precision RV measurements is a highly stable wavelength reference 4 . Recently a number of groups have undertaken to provide a broadband calibration standard that consists of a ‘comb’ of evenly spaced laser lines accurately anchored to a stable frequency standard and injected directly into the spectrometer along with the stellar spectrum 5 , 6 , 7 , 8 , 9 . While this effort has mostly been focused on visible wavelengths, there have been successful efforts at near-IR wavelengths as well 10 , 11 , 12 . In all of these earlier studies, the comb has been based on a femtosecond mode-locked laser that is self-referenced 13 , 14 , 15 , such that the spectral line spacing and common offset frequency of all lines are both locked to a radio frequency standard. Thus, laser combs potentially represent an ideal tool for spectroscopic and RV measurements. However, in the case of mode-locked laser combs, the line spacing is typically in the range of 0.1–1 GHz, which is too small to be resolved by most astronomical spectrographs. As a result, the output spectrum of the comb must be spectrally filtered to create a calibration grid spaced by >10 GHz, which is more commensurate with the resolving power of a high-resolution astronomical spectrograph 8 . While this approach has led to spectrograph characterization at the cm s −1 level 16 , it nonetheless increases the complexity and cost of the system. In light of this, there is interest in developing photonic tools that possess many of the benefits of mode-locked laser combs, but that might be simpler, less expensive and more amenable to ‘hands-off’ operation at remote telescope sites. Indeed, in many RV measurements, other system-induced errors and uncertainties can limit the achievable precision, such that a frequency comb of lesser precision could still be equally valuable. For example, one alternative technique recently reported is to use a series of spectroscopic peaks induced in a broad continuum spectrum using a compact Fabry–Perot interferometer 17 , 18 , 19 . While the technique must account for temperature-induced tuning of the interferometer, it has the advantage of simplicity and low cost. Another interesting alternative is the so-called Kerr comb or microcomb, which has the distinct advantage of directly providing a comb with spacing in the range of 10–100 GHz, without the need for filtering 20 . While this new type of laser comb is still under development, there have been promising demonstrations of full microcomb frequency control 21 , 22 and in the future it could be possible to fully integrate such a microcomb on only a few square centimetres of silicon, making a very robust and inexpensive calibrator. Another approach that has been proposed is to create a comb through electro-optical modulation of a frequency-stabilized laser 23 , 24 . In the following, we describe a successful effort to implement this approach. We produce a line-referenced, electro-optical modulation frequency comb (LR-EOFC) ∼ 1559.9 nm in the astronomical H band (1,500–1,800 nm). We discuss the experimental set-up, laboratory results and proof of concept demonstrations at the NASA Infrared Telescope Facility (IRTF) and the W. M. Keck observatory (Keck) 10 m telescope. Results Comb generation A LR-EOFC is a spectrum of lines generated by electro-optical modulation of a continuous-wave laser source 25 , 26 , 27 , 28 , 29 which has been stabilized to a molecular or atomic reference (for example, f 0 = f atom ). The position of the comb teeth ( f N = f 0 ± Nf", "role": "user" }, { "content": "Promising new calibration tools, called laser frequency combs, could allow astronomers to take a major step in discovering and characterizing earthlike planets around other stars. These devices generate evenly spaced lines of light, much like the teeth on a comb for styling hair or the tick marks on a ruler—hence their nickname of \"optical rulers.\" The tick marks serve as stable reference points when making precision measurements such as those of the small shifts in starlight caused by planets pulling gravitationally on their parent stars. Yet today's commercially available combs have a significant drawback. Because their tick marks are so finely spaced, the light output of these combs must be filtered to produce useful reference lines. This extra step adds complexity to the system and requires costly additional equipment. To resolve these kinds of issues, Caltech researchers looked to a kind of comb not previously deployed for astronomy. The novel comb produces easily resolvable lines, without any need for filtering. Furthermore, the Caltech comb is built from off-the-shelf components developed by the telecommunications industry. \"We have demonstrated an alternative approach that is simple, reliable, and relatively inexpensive,\" says paper coauthor Kerry Vahala, the Ted and Ginger Jenkins Professor of Information Science and Technology and Applied Physics as well as the executive officer for Applied Physics and Materials Science in Caltech's Division of Engineering and Applied Science. The kind of frequency comb used by the researchers previously has been studied in the Vahala group in a different application, the generation of high-stability microwaves. \"We believe members of the astronomical community could greatly benefit in their exoplanet hunting and characterization studies with this new laser frequency comb instrument,\" says Xu Yi, a graduate student in Vahala's lab and the lead author of a paper describing the work published in the January 27, 2016, issue of the journal Nature Communications. Scientists first began widely using laser frequency combs as precision rulers in the late 1990s in fields like metrology and spectroscopy; for their work, the technology's developers (John L. Hall of JILA and the National Institute of Standards and Technology (NIST) and Theodor Hänsch of the Max Planck Institute of Quantum Optics and Ludwig Maximilians University Munich) were awarded half of the Nobel Prize in Physics in 2005. In astronomy, the combs are starting to be utilized in the radial velocity, or \"wobble\" method, the earliest and among the most successful methods for identifying exoplanets. The \"wobble\" refers to the periodic changes in a star's motion, accompanied by starlight shifts owing to the Doppler effect, that are induced by the gravitational pull of an exoplanet orbiting around the star. The magnitude of the shift in the starlight's wavelength—on the order of quadrillionths of a meter—together with the period of the wobble can be used to determine an exoplanet's mass and orbital distance from its star. These details are critical for assessing habitability parameters such as surface temperature and the eccentricity of the exoplanet's orbit. With exoplanets that pass directly in front of (or \"transit\") their host star, allowing their radius to be determined directly, it is even possible to determine the bulk composition—for example, if the planet is built up primarily of gas, ice, or rock. In recent years, so-called mode-locked laser combs have proven useful in this task. These lasers generate a periodic stream of ultrashort light pulses to create the comb. With such combs, however, approximately 49 out of every 50 tick marks must be blocked out. This requires temperature- and vibration-insensitive filtering equipment. The new electro-optical comb that the Caltech team studied relies on microwave modulation of a continuous laser source, rather than a pulsed laser. It produces comb lines spaced by tens of gigahertz. These lines have from 10 to 100 times wider spacing than the tick marks of pulsed laser combs. To see how well a prototype would work in the field, the researchers took their comb to Mauna Kea in Hawaii. In September 2014, the instrument was tested at the NASA Infrared Telescope Facility (IRTF); in March 2015, it was tested with the Near Infrared Spectrometer on the W. M. Keck Observatory's Keck II telescope with the assistance of UCLA astronomer Mike Fitzgerald (BS '00) and UCLA graduate student Emily Martin, coauthors on the paper. The researchers found that their simplified comb (the entire electro-optical comb apparatus requires only half of the space available on a standard 19-inch instrumentation rack) provided steady calibration at room temperature for more than five days at IRTF. The comb also operated flawlessly during the second test—despite having been disassembled, stored for six months, and reassembled. \"From a technological maturity point of view, the frequency comb we have developed is already basically ready to go and could be installed at many telescopes,\" says paper coauthor Scott Diddams of NIST. The Caltech comb produces spectral lines in the infrared, making it ideal for studying red dwarf stars, the most common stars in the Milky Way. Red dwarf stars are brightest in infrared wavelengths. Because red dwarfs are small, cool, and dim, planets orbiting these types of stars are easier to detect and analyze than those orbiting hotter sun-like stars. NASA's Kepler space observatory has shown that almost all red dwarf stars host planets in the range of one to four times the size of Earth, with up to 25 percent of these planets located in the temperate, or \"habitable,\" zone around their host stars. Thus, many astronomers predict that red dwarfs provide the best chance for the first discovery of a world capable of supporting life. \"Our goal is to make these laser frequency combs simple and sturdy enough that you can slap them onto every telescope, and you don't have to think about them anymore,\" says paper coauthor Charles Beichman, senior faculty associate in astronomy and the executive director of the NASA ExoPlanet Science Institute at Caltech. \"Having these combs routinely available as a modest add-on to current and future instrumentation really will expand our ability to find potentially habitable planets, particularly around very cool red dwarf stars,\" he says. The research team is planning to double the frequency of the prototype comb's light output—now centered around 1,550 nanometers, in the infrared—to reach into the visible light range. Doing so would allow the comb also to calibrate spectra from sun-like stars, whose light output is at shorter, visible wavelengths, and thus seek out planets that are Earth's \"twins.\" Other authors of the paper are Jiang Li, a visitor in applied physics and materials science, graduate students Peter Gao and Michael Bottom, and scientific research assistant Elise Furlan, all from Caltech; Stephanie Leifer, Jagmit Sandhu, Gautam Vasisht, and Pin Chen of JPL; Peter Plavchan (BS '01), formerly at Caltech and now a professor at Missouri State University; G. Ycas of NIST; Jonathan Gagne of the University of Montréal; and Greg Doppmann of the Keck Observatory. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract An important technique for discovering and characterizing planets beyond our solar system relies upon measurement of weak Doppler shifts in the spectra of host stars induced by the influence of orbiting planets. A recent advance has been the introduction of optical frequency combs as frequency references. Frequency combs produce a series of equally spaced reference frequencies and they offer extreme accuracy and spectral grasp that can potentially revolutionize exoplanet detection. Here we demonstrate a laser frequency comb using an alternate comb generation method based on electro-optical modulation, with the comb centre wavelength stabilized to a molecular or atomic reference. In contrast to mode-locked combs, the line spacing is readily resolvable using typical astronomical grating spectrographs. Built using commercial off-the-shelf components, the instrument is relatively simple and reliable. Proof of concept experiments operated at near-infrared wavelengths were carried out at the NASA Infrared Telescope Facility and the Keck-II telescope. Introduction The earliest technique for the discovery and characterization of planets orbiting other stars (exoplanets) is the Doppler or radial velocity (RV) method whereby small periodic changes in the motion of a star orbited by a planet are detected via careful spectroscopic measurements 1 . The RV technique has identified hundreds of planets ranging in mass from a few times the mass of Jupiter to less than an Earth mass, and in orbital periods from less than a day to over 10 years (ref. 2 ). However, the detection of Earth-analogues at orbital separations suitable for the presence of liquid water at the planet’s surface, that is, in the ‘habitable zone’ 3 , remains challenging for stars like the Sun with RV signatures <0.1 m s −1 (Δ V / c <3 × 10 −10 ) and periods of a year ( ∼ 10 8 sec to measure three complete periods). For cooler, lower luminosity stars (spectral class M), however, the habitable zone moves closer to the star which, by application of Kepler’s laws, implies that a planet’s RV signature increases, ∼ 0.5 m s −1 (Δ V / c <1.5 × 10 −9 ), and its orbital period decreases, ∼ 30 days ( ∼ 10 7 s to measure three periods). Both of these effects make the detection easier. But for M stars, the bulk of the radiation shifts from the visible wavelengths, where most RV measurements have been made to date, into the near-infrared. Thus, there is considerable interest among astronomers in developing precise RV capabilities at longer wavelengths. Critical to precision RV measurements is a highly stable wavelength reference 4 . Recently a number of groups have undertaken to provide a broadband calibration standard that consists of a ‘comb’ of evenly spaced laser lines accurately anchored to a stable frequency standard and injected directly into the spectrometer along with the stellar spectrum 5 , 6 , 7 , 8 , 9 . While this effort has mostly been focused on visible wavelengths, there have been successful efforts at near-IR wavelengths as well 10 , 11 , 12 . In all of these earlier studies, the comb has been based on a femtosecond mode-locked laser that is self-referenced 13 , 14 , 15 , such that the spectral line spacing and common offset frequency of all lines are both locked to a radio frequency standard. Thus, laser combs potentially represent an ideal tool for spectroscopic and RV measurements. However, in the case of mode-locked laser combs, the line spacing is typically in the range of 0.1–1 GHz, which is too small to be resolved by most astronomical spectrographs. As a result, the output spectrum of the comb must be spectrally filtered to create a calibration grid spaced by >10 GHz, which is more commensurate with the resolving power of a high-resolution astronomical spectrograph 8 . While this approach has led to spectrograph characterization at the cm s −1 level 16 , it nonetheless increases the complexity and cost of the system. In light of this, there is interest in developing photonic tools that possess many of the benefits of mode-locked laser combs, but that might be simpler, less expensive and more amenable to ‘hands-off’ operation at remote telescope sites. Indeed, in many RV measurements, other system-induced errors and uncertainties can limit the achievable precision, such that a frequency comb of lesser precision could still be equally valuable. For example, one alternative technique recently reported is to use a series of spectroscopic peaks induced in a broad continuum spectrum using a compact Fabry–Perot interferometer 17 , 18 , 19 . While the technique must account for temperature-induced tuning of the interferometer, it has the advantage of simplicity and low cost. Another interesting alternative is the so-called Kerr comb or microcomb, which has the distinct advantage of directly providing a comb with spacing in the range of 10–100 GHz, without the need for filtering 20 . While this new type of laser comb is still under development, there have been promising demonstrations of full microcomb frequency control 21 , 22 and in the future it could be possible to fully integrate such a microcomb on only a few square centimetres of silicon, making a very robust and inexpensive calibrator. Another approach that has been proposed is to create a comb through electro-optical modulation of a frequency-stabilized laser 23 , 24 . In the following, we describe a successful effort to implement this approach. We produce a line-referenced, electro-optical modulation frequency comb (LR-EOFC) ∼ 1559.9 nm in the astronomical H band (1,500–1,800 nm). We discuss the experimental set-up, laboratory results and proof of concept demonstrations at the NASA Infrared Telescope Facility (IRTF) and the W. M. Keck observatory (Keck) 10 m telescope. Results Comb generation A LR-EOFC is a spectrum of lines generated by electro-optical modulation of a continuous-wave laser source 25 , 26 , 27 , 28 , 29 which has been stabilized to a molecular or atomic reference (for example, f 0 = f atom ). The position of the comb teeth ( f N = f 0 ± Nf<|im_end|> <|im_start|>assistant Promising new calibration tools, called laser frequency combs, could allow astronomers to take a major step in discovering and characterizing earthlike planets around other stars. These devices generate evenly spaced lines of light, much like the teeth on a comb for styling hair or the tick marks on a ruler—hence their nickname of "optical rulers." The tick marks serve as stable reference points when making precision measurements such as those of the small shifts in starlight caused by planets pulling gravitationally on their parent stars. Yet today's commercially available combs have a significant drawback. Because their tick marks are so finely spaced, the light output of these combs must be filtered to produce useful reference lines. This extra step adds complexity to the system and requires costly additional equipment. To resolve these kinds of issues, Caltech researchers looked to a kind of comb not previously deployed for astronomy. The novel comb produces easily resolvable lines, without any need for filtering. Furthermore, the Caltech comb is built from off-the-shelf components developed by the telecommunications industry. "We have demonstrated an alternative approach that is simple, reliable, and relatively inexpensive," says paper coauthor Kerry Vahala, the Ted and Ginger Jenkins Professor of Information Science and Technology and Applied Physics as well as the executive officer for Applied Physics and Materials Science in Caltech's Division of Engineering and Applied Science. The kind of frequency comb used by the researchers previously has been studied in the Vahala group in a different application, the generation of high-stability microwaves. "We believe members of the astronomical community could greatly benefit in their exoplanet hunting and characterization studies with this new laser frequency comb instrument," says Xu Yi, a graduate student in Vahala's lab and the lead author of a paper describing the work published in the January 27, 2016, issue of the journal Nature Communications. Scientists first began widely using laser frequency combs as precision rulers in the late 1990s in fields like metrology and spectroscopy; for their work, the technology's developers (John L. Hall of JILA and the National Institute of Standards and Technology (NIST) and Theodor Hänsch of the Max Planck Institute of Quantum Optics and Ludwig Maximilians University Munich) were awarded half of the Nobel Prize in Physics in 2005. In astronomy, the combs are starting to be utilized in the radial velocity, or "wobble" method, the earliest and among the most successful methods for identifying exoplanets. The "wobble" refers to the periodic changes in a star's motion, accompanied by starlight shifts owing to the Doppler effect, that are induced by the gravitational pull of an exoplanet orbiting around the star. The magnitude of the shift in the starlight's wavelength—on the order of quadrillionths of a meter—together with the period of the wobble can be used to determine an exoplanet's mass and orbital distance from its star. These details are critical for assessing habitability parameters such as surface temperature and the eccentricity of the exoplanet's orbit. With exoplanets that pass directly in front of (or "transit") their host star, allowing their radius to be determined directly, it is even possible to determine the bulk composition—for example, if the planet is built up primarily of gas, ice, or rock. In recent years, so-called mode-locked laser combs have proven useful in this task. These lasers generate a periodic stream of ultrashort light pulses to create the comb. With such combs, however, approximately 49 out of every 50 tick marks must be blocked out. This requires temperature- and vibration-insensitive filtering equipment. The new electro-optical comb that the Caltech team studied relies on microwave modulation of a continuous laser source, rather than a pulsed laser. It produces comb lines spaced by tens of gigahertz. These lines have from 10 to 100 times wider spacing than the tick marks of pulsed laser combs. To see how well a prototype would work in the field, the researchers took their comb to Mauna Kea in Hawaii. In September 2014, the instrument was tested at the NASA Infrared Telescope Facility (IRTF); in March 2015, it was tested with the Near Infrared Spectrometer on the W. M. Keck Observatory's Keck II telescope with the assistance of UCLA astronomer Mike Fitzgerald (BS '00) and UCLA graduate student Emily Martin, coauthors on the paper. The researchers found that their simplified comb (the entire electro-optical comb apparatus requires only half of the space available on a standard 19-inch instrumentation rack) provided steady calibration at room temperature for more than five days at IRTF. The comb also operated flawlessly during the second test—despite having been disassembled, stored for six months, and reassembled. "From a technological maturity point of view, the frequency comb we have developed is already basically ready to go and could be installed at many telescopes," says paper coauthor Scott Diddams of NIST. The Caltech comb produces spectral lines in the infrared, making it ideal for studying red dwarf stars, the most common stars in the Milky Way. Red dwarf stars are brightest in infrared wavelengths. Because red dwarfs are small, cool, and dim, planets orbiting these types of stars are easier to detect and analyze than those orbiting hotter sun-like stars. NASA's Kepler space observatory has shown that almost all red dwarf stars host planets in the range of one to four times the size of Earth, with up to 25 percent of these planets located in the temperate, or "habitable," zone around their host stars. Thus, many astronomers predict that red dwarfs provide the best chance for the first discovery of a world capable of supporting life. "Our goal is to make these laser frequency combs simple and sturdy enough that you can slap them onto every telescope, and you don't have to think about them anymore," says paper coauthor Charles Beichman, senior faculty associate in astronomy and the executive director of the NASA ExoPlanet Science Institute at Caltech. "Having these combs routinely available as a modest add-on to current and future instrumentation really will expand our ability to find potentially habitable planets, particularly around very cool red dwarf stars," he says. The research team is planning to double the frequency of the prototype comb's light output—now centered around 1,550 nanometers, in the infrared—to reach into the visible light range. Doing so would allow the comb also to calibrate spectra from sun-like stars, whose light output is at shorter, visible wavelengths, and thus seek out planets that are Earth's "twins." Other authors of the paper are Jiang Li, a visitor in applied physics and materials science, graduate students Peter Gao and Michael Bottom, and scientific research assistant Elise Furlan, all from Caltech; Stephanie Leifer, Jagmit Sandhu, Gautam Vasisht, and Pin Chen of JPL; Peter Plavchan (BS '01), formerly at Caltech and now a professor at Missouri State University; G. Ycas of NIST; Jonathan Gagne of the University of Montréal; and Greg Doppmann of the Keck Observatory. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Objective To evaluate the effect of intensive care unit (ICU) admission on mortality among patients with ST elevation myocardial infarction (STEMI). Design Retrospective cohort study. Setting 1727 acute care hospitals in the United States. Participants Medicare beneficiaries (aged 65 years or older) admitted with STEMI to either an ICU or a non-ICU unit (general/telemetry ward or intermediate care) between January 2014 and October 2015. Main outcome measure 30 day mortality. An instrumental variable analysis was done to account for confounding, using as an instrument the additional distance that a patient with STEMI would need to travel beyond the closest hospital to arrive at a hospital in the top quarter of ICU admission rates for STEMI. Results The analysis included 109 375 patients admitted to hospital with STEMI. Hospitals in the top quarter of ICU admission rates admitted 85% or more of STEMI patients to an ICU. Among patients who received ICU care dependent on their proximity to a hospital in the top quarter of ICU admission rates, ICU admission was associated with lower 30 day mortality than non-ICU admission (absolute decrease 6.1 (95% confidence interval −11.9 to −0.3) percentage points). In a separate analysis among patients with non-STEMI, a group for whom evidence suggests that routine ICU care does not improve outcomes, ICU admission was not associated with differences in mortality (absolute increase 1.3 (−0.9 to 3.4) percentage points). Conclusions ICU care for STEMI is associated with improved mortality among patients who could be treated in an ICU or non-ICU unit. An urgent need exists to identify which patients with STEMI benefit from ICU admission and what about ICU care is beneficial. Introduction Survival after ST elevation myocardial infarction (STEMI) has increased by nearly 20% over the past two decades. 1 Complications from STEMI, such as cardiogenic shock or life threatening arrhythmias, have also fallen markedly. 2 This improvement is usually attributed to the accessibility and implementation of early reperfusion therapy, which typically occurs before patients are admitted to an intensive or coronary care unit (ICU). Nevertheless, 75% of patients with STEMI in the US are admitted to an ICU. 3 The costs of this practice are enormous. ICU admissions are on average 2.5 times more costly than non-ICU admissions, and critical care services now account for almost 1% of the US gross domestic product. 4 Whether ICU care for patients with STEMI provides a benefit over lower levels of care, such as general, telemetry, or intermediate care, is poorly understood. 5 Guidelines for STEMI care also provide conflicting advice. Recent European guidelines recommended admitting all patients with STEMI to an ICU. 6 Previous American guidelines suggested that STEMI patients at low risk may not need ICU level care, 7 but recent guideline updates did not specifically discuss the role of ICU care for STEMI. 1 This uncertainty is reflected in practice. Wide variation exists among hospitals in the use of ICUs for STEMI, both in the US and worldwide. 3 8 In this context, we sought to evaluate the effect of ICU admission on mortality for patients with STEMI in the US. As the decision to use an ICU is inherently linked to a patient’s severity of illness, previous observational studies were limited by confounding by indication. 9 To overcome this, we used an instrumental variable analysis to examine the effect of ICU admission on patients with borderline or discretionary ICU needs (that is, those patients who could reasonably receive care in an ICU or non-ICU unit). As mortality after STEMI is declining owing to broader use of reperfusion therapy, 10 we hypothesized that ICU admission would not be associated with a mortality benefit. Methods Study cohort We did a retrospective cohort study of all fee-for-service Medicare beneficiaries aged 65 years and older who were admitted to a hospital in the US for STEMI between January 2014 and October 2015. We identified patients with STEMI by using international classification of diseases, ninth revision, clinical modification (ICD-9-CM) primary diagnosis codes for STEMI (supplementary table A). 10 We excluded patients with STEMI admitted to hospitals without ICU capabilities or admitted directly (that is, transferred in) from other acute care hospitals. We also excluded patients for whom data necessary for analyses were missing (such as ZIP codes (n=1415), hospital characteristics (n=805), or hospital identifiers (n=2)) (supplementary figure A). Data source We linked inpatient claims from the Medicare Provider Analysis and Review File to mortality data in the Medicare Beneficiary Summary File. 11 Characteristics of hospitals came from the American Hospital Association’s Annual Surveys and the Healthcare Cost Reporting Information Systems. 12 13 We obtained population and geographic information by linking the patient’s ZIP code of residence to 2010 US census data. Patient and public involvement Patients were not involved in the development of the research question, study design, or outcome measures. Patients were not involved in the recruitment, conduct, or interpretation of the study. There are no specific plans to disseminate the results of the research to study participants or to relevant patients beyond the usual channels of publication. Exposure variable, outcome variable, and covariate definitions We used room and board charges for each Medicare beneficiary to establish the level of care for which the patient was billed. Thus, we relied on the US Centers for Medicare and Medicaid Services’ definition of an ICU, which is based on two criteria. 14 Firstly, an ICU must have lifesaving equipment available for immediate use and be geographically and identifiably separate from general routine care areas. Secondly, a single nurse must take care of no more than two patients, and nursing staff cannot be shared between an ICU and other units that provide lower levels of care. The exposure variable was admission to ICU (the presence of an ICU or coronary care unit (CCU) revenue center code in the administrative billing record). 15 We defined non-ICU admission as any admission to a general/telemetry (the lack of any ICU or CCU revenue center code) or intermediate care ward (the presence of an intermediate ICU or", "role": "user" }, { "content": "A trip to an intensive care unit can be more than twice as costly as a stay in a non-ICU hospital room, but a new study finds intensive care is still the right option for some vulnerable patients after a severe heart attack. The difficulty lies in determining which people are best served in the ICU while they recover. The new Michigan Medicine (University of Michigan) research, published in The BMJ, found ICU admission was associated with improved 30-day mortality rates for patients who had a STEMI heart attack and weren't clearly indicated for an ICU or non-ICU unit. \"For these patients who could reasonably be cared for in either place, ICU admission was beneficial,\" says lead author Thomas Valley, M.D., M.Sc., an assistant professor of internal medicine at Michigan Medicine, who cares for patients in the intensive care unit. But Valley cautions against simply continuing to send nearly everyone to the ICU. \"ICU care is a treatment just like any medication,\" Valley says. \"Providers need to know whether it's right for an individual person just like we try to do with a prescription drug.\" The researchers analyzed Medicare data from more than 100,000 patients hospitalized with STEMI, or ST-elevation myocardial infarction, a dangerous heart attack that requires quick opening of the blocked blood vessel to restore blood flow. Those patients were hospitalized at 1,727 acute care hospitals across the U.S. in a nearly two-year period from January 2014 to October 2015, and most were sent to the ICU after treatment. \"A lot of the focus is on getting these people to the cardiac catheterization lab as soon as possible to open up the blood vessel, but less is known about what you do after that,\" Valley says. Current U.S. guidelines don't address whether to send patients to the ICU, while European guidelines recommend the ICU. Valley says providers could use more clear guidance on how to make these decisions. In this study, the mortality rate was 6.1% lower after 30 days for those admitted to their hospital's ICU. Valley says the surprising results—in the face of other studies that show ICU overuse—demonstrate that ICU care is misdirected. 'An important debate in cardiology' This study addresses an important issue in ICU care, says Michael Thomas, M.D., an assistant professor of internal medicine who runs the Cardiac ICU at Michigan Medicine's Cardiovascular Center. \"At Michigan Medicine, all of our STEMI patients are admitted to the Cardiac ICU,\" says Thomas, who was not involved with the BMJ paper. \"However, knowing where to send these patients after STEMI is an important debate in cardiology right now.\" \"Some recent studies suggest many patients don't need ICU level of care and that it wastes resources. But before we pull back from this model, we need to understand this problem more fully,\" he says. Across the nation, 75% of STEMI heart attack patients are sent to the ICU, most of the time after reperfusion treatment in the cath lab to open up the blocked vessel. ICU vs. non-ICU care People recovering from a STEMI are some of the very sick patients ICUs were originally designed for, so providers may not even think about disrupting the longtime status quo, Valley says. \"The historical thinking was, 'Why not send everyone to the ICU?' Now, we see that there are risks associated,\" Valley says. \"For example, in the ICU, you're more likely to have a procedure, whether you need it more or not. \"We must also consider the risk of infection, sending someone to a unit full of really sick patients who might have C. diff or other serious infections.\" The sleep quality as people are recovering from their heart attacks may also be lower in the ICU, because patients are given such close nursing care, Valley says. That's necessary for the sickest patients, but it might be disruptive to those people on the bubble who could be getting better rest on a regular floor, he says. Medicare has requirements for what constitutes ICU care, such as high nurse staffing levels and access to lifesaving care. \"Because of Medicare requirements, ICUs tend to be more similar across hospitals than non-ICUs,\" Valley says. \"Perhaps some hospitals can take care of patients anywhere, while others really need to use the ICU at high rates in order to provide safe care.\" A clear benefit for some, increased cost for others Valley says these data show a clear benefit of ICU care for vulnerable patients, as opposed to non-STEMI patients studied who did not have a significant difference in mortality rates with or without ICU admission. \"Physicians might look at STEMI patients and wonder, 'Do they really need the ICU? Could it harm them? Is it a good use of resources?'\" Valley says. Valley, a member of U-M's Institute for Healthcare Policy and Innovation, has previously found ICU overuse occurred for less critical patients hospitalized for a flare-up of chronic obstructive pulmonary disease (COPD) or heart failure. In that study, ICU admission dramatically increased cost of care without an increased survival benefit. The next step, according to Valley, is to determine what is beneficial about the ICU for those patients who benefit from it. He says that could lead to hospitals adopting some ICU care practices on non-ICU floors. Valley hopes making non-ICU floors more similar to the ICU in some ways could improve outcomes while reducing cost of care and infection risk. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Objective To evaluate the effect of intensive care unit (ICU) admission on mortality among patients with ST elevation myocardial infarction (STEMI). Design Retrospective cohort study. Setting 1727 acute care hospitals in the United States. Participants Medicare beneficiaries (aged 65 years or older) admitted with STEMI to either an ICU or a non-ICU unit (general/telemetry ward or intermediate care) between January 2014 and October 2015. Main outcome measure 30 day mortality. An instrumental variable analysis was done to account for confounding, using as an instrument the additional distance that a patient with STEMI would need to travel beyond the closest hospital to arrive at a hospital in the top quarter of ICU admission rates for STEMI. Results The analysis included 109 375 patients admitted to hospital with STEMI. Hospitals in the top quarter of ICU admission rates admitted 85% or more of STEMI patients to an ICU. Among patients who received ICU care dependent on their proximity to a hospital in the top quarter of ICU admission rates, ICU admission was associated with lower 30 day mortality than non-ICU admission (absolute decrease 6.1 (95% confidence interval −11.9 to −0.3) percentage points). In a separate analysis among patients with non-STEMI, a group for whom evidence suggests that routine ICU care does not improve outcomes, ICU admission was not associated with differences in mortality (absolute increase 1.3 (−0.9 to 3.4) percentage points). Conclusions ICU care for STEMI is associated with improved mortality among patients who could be treated in an ICU or non-ICU unit. An urgent need exists to identify which patients with STEMI benefit from ICU admission and what about ICU care is beneficial. Introduction Survival after ST elevation myocardial infarction (STEMI) has increased by nearly 20% over the past two decades. 1 Complications from STEMI, such as cardiogenic shock or life threatening arrhythmias, have also fallen markedly. 2 This improvement is usually attributed to the accessibility and implementation of early reperfusion therapy, which typically occurs before patients are admitted to an intensive or coronary care unit (ICU). Nevertheless, 75% of patients with STEMI in the US are admitted to an ICU. 3 The costs of this practice are enormous. ICU admissions are on average 2.5 times more costly than non-ICU admissions, and critical care services now account for almost 1% of the US gross domestic product. 4 Whether ICU care for patients with STEMI provides a benefit over lower levels of care, such as general, telemetry, or intermediate care, is poorly understood. 5 Guidelines for STEMI care also provide conflicting advice. Recent European guidelines recommended admitting all patients with STEMI to an ICU. 6 Previous American guidelines suggested that STEMI patients at low risk may not need ICU level care, 7 but recent guideline updates did not specifically discuss the role of ICU care for STEMI. 1 This uncertainty is reflected in practice. Wide variation exists among hospitals in the use of ICUs for STEMI, both in the US and worldwide. 3 8 In this context, we sought to evaluate the effect of ICU admission on mortality for patients with STEMI in the US. As the decision to use an ICU is inherently linked to a patient’s severity of illness, previous observational studies were limited by confounding by indication. 9 To overcome this, we used an instrumental variable analysis to examine the effect of ICU admission on patients with borderline or discretionary ICU needs (that is, those patients who could reasonably receive care in an ICU or non-ICU unit). As mortality after STEMI is declining owing to broader use of reperfusion therapy, 10 we hypothesized that ICU admission would not be associated with a mortality benefit. Methods Study cohort We did a retrospective cohort study of all fee-for-service Medicare beneficiaries aged 65 years and older who were admitted to a hospital in the US for STEMI between January 2014 and October 2015. We identified patients with STEMI by using international classification of diseases, ninth revision, clinical modification (ICD-9-CM) primary diagnosis codes for STEMI (supplementary table A). 10 We excluded patients with STEMI admitted to hospitals without ICU capabilities or admitted directly (that is, transferred in) from other acute care hospitals. We also excluded patients for whom data necessary for analyses were missing (such as ZIP codes (n=1415), hospital characteristics (n=805), or hospital identifiers (n=2)) (supplementary figure A). Data source We linked inpatient claims from the Medicare Provider Analysis and Review File to mortality data in the Medicare Beneficiary Summary File. 11 Characteristics of hospitals came from the American Hospital Association’s Annual Surveys and the Healthcare Cost Reporting Information Systems. 12 13 We obtained population and geographic information by linking the patient’s ZIP code of residence to 2010 US census data. Patient and public involvement Patients were not involved in the development of the research question, study design, or outcome measures. Patients were not involved in the recruitment, conduct, or interpretation of the study. There are no specific plans to disseminate the results of the research to study participants or to relevant patients beyond the usual channels of publication. Exposure variable, outcome variable, and covariate definitions We used room and board charges for each Medicare beneficiary to establish the level of care for which the patient was billed. Thus, we relied on the US Centers for Medicare and Medicaid Services’ definition of an ICU, which is based on two criteria. 14 Firstly, an ICU must have lifesaving equipment available for immediate use and be geographically and identifiably separate from general routine care areas. Secondly, a single nurse must take care of no more than two patients, and nursing staff cannot be shared between an ICU and other units that provide lower levels of care. The exposure variable was admission to ICU (the presence of an ICU or coronary care unit (CCU) revenue center code in the administrative billing record). 15 We defined non-ICU admission as any admission to a general/telemetry (the lack of any ICU or CCU revenue center code) or intermediate care ward (the presence of an intermediate ICU or<|im_end|> <|im_start|>assistant A trip to an intensive care unit can be more than twice as costly as a stay in a non-ICU hospital room, but a new study finds intensive care is still the right option for some vulnerable patients after a severe heart attack. The difficulty lies in determining which people are best served in the ICU while they recover. The new Michigan Medicine (University of Michigan) research, published in The BMJ, found ICU admission was associated with improved 30-day mortality rates for patients who had a STEMI heart attack and weren't clearly indicated for an ICU or non-ICU unit. "For these patients who could reasonably be cared for in either place, ICU admission was beneficial," says lead author Thomas Valley, M.D., M.Sc., an assistant professor of internal medicine at Michigan Medicine, who cares for patients in the intensive care unit. But Valley cautions against simply continuing to send nearly everyone to the ICU. "ICU care is a treatment just like any medication," Valley says. "Providers need to know whether it's right for an individual person just like we try to do with a prescription drug." The researchers analyzed Medicare data from more than 100,000 patients hospitalized with STEMI, or ST-elevation myocardial infarction, a dangerous heart attack that requires quick opening of the blocked blood vessel to restore blood flow. Those patients were hospitalized at 1,727 acute care hospitals across the U.S. in a nearly two-year period from January 2014 to October 2015, and most were sent to the ICU after treatment. "A lot of the focus is on getting these people to the cardiac catheterization lab as soon as possible to open up the blood vessel, but less is known about what you do after that," Valley says. Current U.S. guidelines don't address whether to send patients to the ICU, while European guidelines recommend the ICU. Valley says providers could use more clear guidance on how to make these decisions. In this study, the mortality rate was 6.1% lower after 30 days for those admitted to their hospital's ICU. Valley says the surprising results—in the face of other studies that show ICU overuse—demonstrate that ICU care is misdirected. 'An important debate in cardiology' This study addresses an important issue in ICU care, says Michael Thomas, M.D., an assistant professor of internal medicine who runs the Cardiac ICU at Michigan Medicine's Cardiovascular Center. "At Michigan Medicine, all of our STEMI patients are admitted to the Cardiac ICU," says Thomas, who was not involved with the BMJ paper. "However, knowing where to send these patients after STEMI is an important debate in cardiology right now." "Some recent studies suggest many patients don't need ICU level of care and that it wastes resources. But before we pull back from this model, we need to understand this problem more fully," he says. Across the nation, 75% of STEMI heart attack patients are sent to the ICU, most of the time after reperfusion treatment in the cath lab to open up the blocked vessel. ICU vs. non-ICU care People recovering from a STEMI are some of the very sick patients ICUs were originally designed for, so providers may not even think about disrupting the longtime status quo, Valley says. "The historical thinking was, 'Why not send everyone to the ICU?' Now, we see that there are risks associated," Valley says. "For example, in the ICU, you're more likely to have a procedure, whether you need it more or not. "We must also consider the risk of infection, sending someone to a unit full of really sick patients who might have C. diff or other serious infections." The sleep quality as people are recovering from their heart attacks may also be lower in the ICU, because patients are given such close nursing care, Valley says. That's necessary for the sickest patients, but it might be disruptive to those people on the bubble who could be getting better rest on a regular floor, he says. Medicare has requirements for what constitutes ICU care, such as high nurse staffing levels and access to lifesaving care. "Because of Medicare requirements, ICUs tend to be more similar across hospitals than non-ICUs," Valley says. "Perhaps some hospitals can take care of patients anywhere, while others really need to use the ICU at high rates in order to provide safe care." A clear benefit for some, increased cost for others Valley says these data show a clear benefit of ICU care for vulnerable patients, as opposed to non-STEMI patients studied who did not have a significant difference in mortality rates with or without ICU admission. "Physicians might look at STEMI patients and wonder, 'Do they really need the ICU? Could it harm them? Is it a good use of resources?'" Valley says. Valley, a member of U-M's Institute for Healthcare Policy and Innovation, has previously found ICU overuse occurred for less critical patients hospitalized for a flare-up of chronic obstructive pulmonary disease (COPD) or heart failure. In that study, ICU admission dramatically increased cost of care without an increased survival benefit. The next step, according to Valley, is to determine what is beneficial about the ICU for those patients who benefit from it. He says that could lead to hospitals adopting some ICU care practices on non-ICU floors. Valley hopes making non-ICU floors more similar to the ICU in some ways could improve outcomes while reducing cost of care and infection risk. <|im_end|>

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85015, 323, 1023, 8316, 430, 3493, 4827, 5990, 315, 2512, 13, 578, 14675, 3977, 574, 26360, 311, 85015, 320, 1820, 9546, 315, 459, 85015, 477, 66298, 2512, 5089, 320, 3791, 52, 8, 13254, 4219, 2082, 304, 279, 23541, 34631, 3335, 570, 220, 868, 1226, 4613, 2536, 12, 1341, 52, 26360, 439, 904, 26360, 311, 264, 4689, 14, 668, 37058, 320, 1820, 6996, 315, 904, 85015, 477, 13844, 52, 13254, 4219, 2082, 8, 477, 29539, 2512, 26741, 320, 1820, 9546, 315, 459, 29539, 85015, 477, 128257, 198, 128256, 78191, 198, 32, 8577, 311, 459, 37295, 2512, 5089, 649, 387, 810, 1109, 11157, 439, 34348, 439, 264, 4822, 304, 264, 2536, 12, 1341, 52, 8952, 3130, 11, 719, 264, 502, 4007, 14035, 37295, 2512, 374, 2103, 279, 1314, 3072, 369, 1063, 20134, 6978, 1306, 264, 15748, 4851, 3440, 13, 578, 17250, 15812, 304, 26679, 902, 1274, 527, 1888, 10434, 304, 279, 85015, 1418, 814, 11993, 13, 578, 502, 14972, 19152, 320, 31272, 315, 14972, 8, 3495, 11, 4756, 304, 578, 20387, 41, 11, 1766, 85015, 26360, 574, 5938, 449, 13241, 220, 966, 11477, 29528, 7969, 369, 6978, 889, 1047, 264, 27597, 9972, 4851, 3440, 323, 15058, 956, 9539, 16717, 369, 459, 85015, 477, 2536, 12, 1341, 52, 5089, 13, 330, 2520, 1521, 6978, 889, 1436, 29546, 387, 42777, 369, 304, 3060, 2035, 11, 85015, 26360, 574, 24629, 1359, 2795, 3063, 3229, 11355, 13345, 11, 386, 920, 2637, 386, 18832, 2637, 459, 18328, 14561, 315, 5419, 16088, 520, 14972, 19152, 11, 889, 34672, 369, 6978, 304, 279, 37295, 2512, 5089, 13, 2030, 13345, 2211, 4065, 2403, 5042, 14691, 311, 3708, 7154, 5127, 311, 279, 85015, 13, 330, 1341, 52, 2512, 374, 264, 6514, 1120, 1093, 904, 24099, 1359, 13345, 2795, 13, 330, 38451, 1205, 311, 1440, 3508, 433, 596, 1314, 369, 459, 3927, 1732, 1120, 1093, 584, 1456, 311, 656, 449, 264, 22866, 5623, 1210, 578, 12074, 30239, 31822, 828, 505, 810, 1109, 220, 1041, 11, 931, 6978, 70340, 449, 27597, 9972, 11, 477, 4015, 5773, 44857, 95736, 532, 4225, 277, 407, 11, 264, 11660, 4851, 3440, 430, 7612, 4062, 8736, 315, 279, 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71015, 430, 85015, 2512, 374, 5906, 20384, 291, 13, 364, 2127, 3062, 11249, 304, 3786, 31226, 6, 1115, 4007, 14564, 459, 3062, 4360, 304, 85015, 2512, 11, 2795, 8096, 11355, 11, 386, 920, 2637, 459, 18328, 14561, 315, 5419, 16088, 889, 8640, 279, 6938, 18029, 85015, 520, 14972, 19152, 596, 92976, 33945, 5955, 13, 330, 1688, 14972, 19152, 11, 682, 315, 1057, 27597, 9972, 6978, 527, 16584, 311, 279, 6938, 18029, 85015, 1359, 2795, 11355, 11, 889, 574, 539, 6532, 449, 279, 20387, 41, 5684, 13, 330, 11458, 11, 14392, 1405, 311, 3708, 1521, 6978, 1306, 27597, 9972, 374, 459, 3062, 11249, 304, 3786, 31226, 1314, 1457, 1210, 330, 8538, 3293, 7978, 4284, 1690, 6978, 1541, 956, 1205, 85015, 2237, 315, 2512, 323, 430, 433, 82320, 5070, 13, 2030, 1603, 584, 6958, 1203, 505, 420, 1646, 11, 584, 1205, 311, 3619, 420, 3575, 810, 7373, 1359, 568, 2795, 13, 58237, 279, 7140, 11, 220, 2075, 4, 315, 27597, 9972, 4851, 3440, 6978, 527, 3288, 311, 279, 85015, 11, 1455, 315, 279, 892, 1306, 312, 716, 55665, 6514, 304, 279, 31747, 10278, 311, 1825, 709, 279, 19857, 27274, 13, 85015, 6296, 13, 2536, 12, 1341, 52, 2512, 9029, 42386, 505, 264, 27597, 9972, 527, 1063, 315, 279, 1633, 14363, 6978, 19845, 3642, 1051, 13517, 6319, 369, 11, 779, 12850, 1253, 539, 1524, 1781, 922, 87843, 279, 36504, 2704, 41608, 11, 13345, 2795, 13, 330, 791, 13970, 7422, 574, 11, 364, 10445, 539, 3708, 5127, 311, 279, 85015, 20837, 4800, 11, 584, 1518, 430, 1070, 527, 15635, 5938, 1359, 13345, 2795, 13, 330, 2520, 3187, 11, 304, 279, 85015, 11, 499, 2351, 810, 4461, 311, 617, 264, 10537, 11, 3508, 499, 1205, 433, 810, 477, 539, 13, 330, 1687, 2011, 1101, 2980, 279, 5326, 315, 19405, 11, 11889, 4423, 311, 264, 5089, 2539, 315, 2216, 14363, 6978, 889, 2643, 617, 356, 13, 3722, 477, 1023, 6129, 30020, 1210, 578, 6212, 4367, 439, 1274, 527, 42386, 505, 872, 4851, 8951, 1253, 1101, 387, 4827, 304, 279, 85015, 11, 1606, 6978, 527, 2728, 1778, 3345, 28456, 2512, 11, 13345, 2795, 13, 3011, 596, 5995, 369, 279, 53747, 40423, 6978, 11, 719, 433, 2643, 387, 62642, 311, 1884, 1274, 389, 279, 24529, 889, 1436, 387, 3794, 2731, 2800, 389, 264, 5912, 6558, 11, 568, 2795, 13, 31822, 706, 8670, 369, 1148, 42675, 85015, 2512, 11, 1778, 439, 1579, 29198, 65151, 5990, 323, 2680, 311, 49785, 2370, 2512, 13, 330, 18433, 315, 31822, 8670, 11, 19845, 3642, 8541, 311, 387, 810, 4528, 4028, 24461, 1109, 2536, 12, 1341, 3642, 1359, 13345, 2795, 13, 330, 32576, 1063, 24461, 649, 1935, 2512, 315, 6978, 12660, 11, 1418, 3885, 2216, 1205, 311, 1005, 279, 85015, 520, 1579, 7969, 304, 2015, 311, 3493, 6220, 2512, 1210, 362, 2867, 8935, 369, 1063, 11, 7319, 2853, 369, 3885, 13345, 2795, 1521, 828, 1501, 264, 2867, 8935, 315, 85015, 2512, 369, 20134, 6978, 11, 439, 16475, 311, 2536, 12, 15642, 40, 6978, 20041, 889, 1550, 539, 617, 264, 5199, 6811, 304, 29528, 7969, 449, 477, 2085, 85015, 26360, 13, 330, 67171, 9818, 2643, 1427, 520, 27597, 9972, 6978, 323, 5895, 11, 364, 5519, 814, 2216, 1205, 279, 85015, 30, 16910, 433, 11682, 1124, 30, 2209, 433, 264, 1695, 1005, 315, 5070, 30, 15260, 13345, 2795, 13, 13345, 11, 264, 4562, 315, 549, 5364, 596, 10181, 369, 39435, 11216, 323, 38710, 11, 706, 8767, 1766, 85015, 927, 817, 10222, 369, 2753, 9200, 6978, 70340, 369, 264, 61363, 5352, 315, 21249, 54292, 535, 70524, 8624, 320, 34, 3143, 35, 8, 477, 4851, 8060, 13, 763, 430, 4007, 11, 85015, 26360, 29057, 7319, 2853, 315, 2512, 2085, 459, 7319, 20237, 8935, 13, 578, 1828, 3094, 11, 4184, 311, 13345, 11, 374, 311, 8417, 1148, 374, 24629, 922, 279, 85015, 369, 1884, 6978, 889, 8935, 505, 433, 13, 1283, 2795, 430, 1436, 3063, 311, 24461, 48810, 1063, 85015, 2512, 12659, 389, 2536, 12, 1341, 52, 27035, 13, 13345, 16388, 3339, 2536, 12, 1341, 52, 27035, 810, 4528, 311, 279, 85015, 304, 1063, 5627, 1436, 7417, 20124, 1418, 18189, 2853, 315, 2512, 323, 19405, 5326, 13, 220, 128257, 198 ]

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Previous studies of the central United States Cordillera have indicated that a high-elevation orogenic plateau, the Nevadaplano, was present in Late Cretaceous to early Paleogene time. The southern United States Cordillera and northern Mexican Cordillera share a similar geologic history and many of the same tectonic features (e.g., metamorphic core complexes) as the central United States Cordillera, raising the possibility that a similar plateau may have been present at lower latitudes. To test the hypothesis of an elevated plateau, we examined Laramide-age continental-arc geochemistry and employed an empirical relation between whole-rock La/Yb and Moho depth as a proxy for crustal thickness. Calculations of crustal thickness from individual data points range between 45 and 72 km, with an average of 57 ± 12 km (2σ) for the entire data set, which corresponds to 3 ± 1.8 km paleoelevation assuming simple Airy isostasy. These crustal thickness and paleoaltimetry estimates are similar to previous estimates for the Nevadaplano and are interpreted to suggest that an analogous high-elevation plateau may have been present in the southern United States Cordillera. This result raises questions about the mechanisms that thickened the crust, because shortening in the Sevier thrust belt is generally not thought to have extended into the southern United States Cordillera, south of ∼35°N latitude. INTRODUCTION High-elevation orogenic plateaus like the modern Tibetan, Anatolian, and Altiplano-Puna plateaus commonly develop in the interior, or hinterland, of convergent orogenic systems. Construction of such plateaus is arguably among the most significant tectonic phenomena of Cenozoic time. The plateaus influence Earth systems in a wide variety of ways, including disrupting atmospheric circulation patterns ( Molnar et al., 1993 ), driving past climate change ( Raymo and Ruddiman, 1992 ; Strecker et al., 2007 ), concentrating metallic and other natural resources ( Hou and Cook, 2009 ), and altering plate motions ( Patriat and Achache, 1984 ; Iaffaldano et al., 2006 ). A similar plateau—the Nevadaplano, analogous to the Altiplano in the central Andes—was present in the Great Basin region of the central United States Cordillera (∼35°N–45°N latitude; Fig. 1 ) during Late Cretaceous to early Paleogene time ( DeCelles, 2004 ; Best et al., 2009 ; Snell et al., 2014 ). The Nevadaplano was isostatically supported by thickened continental crust formed by retroarc shortening in the Sevier thrust belt and in precursor thrust belts such as the Luning-Fencemaker ( Jones et al., 1998 ; DeCelles, 2004 ). Previous estimates for crustal thickness in the Nevadaplano using igneous geochemical proxies, similar to the technique employed in this study, range from 55 to 65 km ( Chapman et al., 2015 ). Structural restoration of late Paleogene to Holocene extension, including zones of high-magnitude extension associated with the Cordilleran metamorphic core complexes ( Fig. 1 ), also suggests that the Nevadaplano was supported by thick (40–65 km) crust ( Coney and Harms, 1984 ). Some researchers have suggested that the Nevadaplano may have extended farther southeast ( Whitney et al., 2004 ; Copeland et al., 2017 ). This idea is contentious, however, because the Sevier thrust belt does not extend into the southern United States Cordillera and northern Mexican Cordillera ( Fig. 1 ; Yonkee and Weil, 2015 ; Fitz-Díaz et al., 2018 ). Instead, Late Cretaceous to Paleogene contractional strain in these areas is generally characterized by basement-involved uplifts accompanying high-angle reverse faulting, formed during the Laramide orogeny ( Krantz et al., 1989 ; Clinkscales and Lawton, 2017 ; Fitz-Díaz et al., 2018 ). Horizontal shortening recorded by these high-angle reverse faults is insufficient to have significantly thickened the crust ( Davis, 1979 ). Thus, if the Laramide orogeny in southern Arizona and northern Sonora resulted in thickened crust, mechanisms in addition to tectonic shortening are required. To evaluate the possibility of thick crust supporting an orogenic plateau in the southern United States and northern Mexican Cordillera, we used whole-rock La/Yb ratios in Laramide-age, intermediate-composition continental-arc rocks as a proxy for crustal thickness ( Fig. 2 ), following the method of Profeta et al. (2015) . As crustal thickness increases, whole-rock heavy rare earth element (HREE) concentrations decrease and light rare earth element (LREE) concentrations increase, due to the high-pressure stabilization of HREE-enriched phases such as amphibole and garnet at the expense of LREE-enriched phases such as plagioclase ( Hu et al., 2017 ; Müntener and Ulmer, 2018 ). Despite the low concentration of LREE in plagioclase, the mineral is important because of its abundance in continental-arc rocks and because it is unstable at higher pressure, in contrast to other LREE-bearing accessory phases such as monazite. GEOLOGIC BACKGROUND Some early studies of the southern United States Cordillera suggested that the Sevier thrust belt was continuous from southern Nevada to northern Chihuahua ( Drewes, 1978 ). However, subsequent research has demonstrated that many of the thrust faults used to support a thrust belt interpretation are low-angle normal faults or other types of geologic contacts such as unconformities ( Dickinson, 1984 ; Krantz et al., 1989 ; Clinkscales and Lawton, 2017 ). As a result, most researchers now believe that the Sevier thrust belt terminates in the Mojave region of southern California ( DeCelles, 2004 ; Yonkee and Weil, 2015 ) and that shortening in southern Arizona and northern Sonora was temporally restricted to the Laramide orogeny and predominantly occurred along high-angle reverse faults, in part reactivating Late Jurassic to Early Cretaceous rift-related structures ( Davis, 1979 ; Krantz et al., 1989 ; Lawton, 2000 ; Favorito and Seedorff, 2018 ; Fitz-Díaz et al., 2018 ). Continental-arc magmatism migrated eastward through the study area ( Fig. 2 ) during the Laramide orogeny as the subduction angle of the Farallon slab shallowed ( Coney and Reynolds, 1977 ). Laramide igneous rocks in southern Arizona and northern Sonora are mainly intermediate, metaluminous, and calc-alkaline rocks that have radiogenic isotopic compositions inherited from the lithospheric province into which they were emplaced ( Lang and Titley, 1998 ; González-León et al., 2011 ; Chapman et al., 2018 ). During mid-Eocene time, toward the end of the", "role": "user" }, { "content": "A University of Wyoming researcher and his colleagues have shown that much of the southwestern United States was once a vast high-elevation plateau, similar to Tibet today. This work has implications for the distribution of natural resources, such as copper, and provides insight into the formation of mountains during the subduction of tectonic plates. \"We normally think of southern Arizona and the surrounding areas as hot, cactus-laden deserts with relatively low base elevations, below 3,000 feet,\" says Jay Chapman, an assistant professor in UW's Department of Geology and Geophysics. \"However, our recent research suggests that, during the Late Cretaceous to Early Paleogene period (80-50 million years ago), the region may have had elevations in excess of 10,000 feet and looked more like the Tibetan plateau north of the Himalayan Mountains or the Altiplano in the Andes Mountains in South America.\" Chapman is lead author of a paper, titled \"Geochemical evidence for an orogenic plateau in the southern U.S. and northern Mexican Cordillera during the Laramide Orogeny,\" which was published online Nov. 22 in the journal Geology. The print version will be published in February. Roy Greig, a Ph.D. student in the Department of Geosciences at the University of Arizona, and Gordon Haxel, a U.S. Geological Survey scientist based in Flagstaff, Ariz., are co-authors of the paper. Chapman and his colleagues analyzed the chemistry of igneous rocks to determine how thick Earth's crust was in the past and then related the thickness to elevation. \"Earth's crust floats in the mantle just like an iceberg floats in the water, with a little bit sticking out above the surface,\" Chapman says. \"When the crust is thicker, the height of mountains and the elevation of the land surface are higher, just like the height of an iceberg sticking out of the water is taller if the overall iceberg is larger.\" The study determined that the crust in southern Arizona was once almost 60 kilometers thick, which is twice as thick as it is today—and comparable to how thick the crust is in parts of the Himalayas. \"While the ancient mountains were forming, magma intruded into the crust and formed rocks like granite,\" Chapman says. \"When the crust was really thick, the magmas experienced extreme pressure from the weight of all the rocks above them, which caused distinctive changes in the types and the chemistry of the minerals that formed those rocks.\" One of the interesting questions the study raises is how the crust in southern Arizona became so thick in the past. \"The most common way to make really thick crust is for tectonic plates to converge or collide, which produces large earthquakes and faults that stack rock masses overtop one another,\" he says. \"The prevailing view of southern Arizona is that there was never enough faulting in the area to make the thickness of crust we observe. It is a bit of a conundrum as to how such thick crust was generated.\" Adam Trzinski, a first-year Ph.D. student at UW, is now tackling this problem and searching for ancient faults in southern Arizona that could help explain how the thick crust became so thick. In addition to helping understand plate tectonic processes, the study may help explain why copper is so abundant in southern Arizona. \"Several previous studies have noted a correlation between large copper ore deposits and regions of thick crust,\" Chapman says. \"For example, there are many copper mines in the Andes Mountains in Chile. The results of this study strengthen that correlation and may aid in exploration efforts.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Previous studies of the central United States Cordillera have indicated that a high-elevation orogenic plateau, the Nevadaplano, was present in Late Cretaceous to early Paleogene time. The southern United States Cordillera and northern Mexican Cordillera share a similar geologic history and many of the same tectonic features (e.g., metamorphic core complexes) as the central United States Cordillera, raising the possibility that a similar plateau may have been present at lower latitudes. To test the hypothesis of an elevated plateau, we examined Laramide-age continental-arc geochemistry and employed an empirical relation between whole-rock La/Yb and Moho depth as a proxy for crustal thickness. Calculations of crustal thickness from individual data points range between 45 and 72 km, with an average of 57 ± 12 km (2σ) for the entire data set, which corresponds to 3 ± 1.8 km paleoelevation assuming simple Airy isostasy. These crustal thickness and paleoaltimetry estimates are similar to previous estimates for the Nevadaplano and are interpreted to suggest that an analogous high-elevation plateau may have been present in the southern United States Cordillera. This result raises questions about the mechanisms that thickened the crust, because shortening in the Sevier thrust belt is generally not thought to have extended into the southern United States Cordillera, south of ∼35°N latitude. INTRODUCTION High-elevation orogenic plateaus like the modern Tibetan, Anatolian, and Altiplano-Puna plateaus commonly develop in the interior, or hinterland, of convergent orogenic systems. Construction of such plateaus is arguably among the most significant tectonic phenomena of Cenozoic time. The plateaus influence Earth systems in a wide variety of ways, including disrupting atmospheric circulation patterns ( Molnar et al., 1993 ), driving past climate change ( Raymo and Ruddiman, 1992 ; Strecker et al., 2007 ), concentrating metallic and other natural resources ( Hou and Cook, 2009 ), and altering plate motions ( Patriat and Achache, 1984 ; Iaffaldano et al., 2006 ). A similar plateau—the Nevadaplano, analogous to the Altiplano in the central Andes—was present in the Great Basin region of the central United States Cordillera (∼35°N–45°N latitude; Fig. 1 ) during Late Cretaceous to early Paleogene time ( DeCelles, 2004 ; Best et al., 2009 ; Snell et al., 2014 ). The Nevadaplano was isostatically supported by thickened continental crust formed by retroarc shortening in the Sevier thrust belt and in precursor thrust belts such as the Luning-Fencemaker ( Jones et al., 1998 ; DeCelles, 2004 ). Previous estimates for crustal thickness in the Nevadaplano using igneous geochemical proxies, similar to the technique employed in this study, range from 55 to 65 km ( Chapman et al., 2015 ). Structural restoration of late Paleogene to Holocene extension, including zones of high-magnitude extension associated with the Cordilleran metamorphic core complexes ( Fig. 1 ), also suggests that the Nevadaplano was supported by thick (40–65 km) crust ( Coney and Harms, 1984 ). Some researchers have suggested that the Nevadaplano may have extended farther southeast ( Whitney et al., 2004 ; Copeland et al., 2017 ). This idea is contentious, however, because the Sevier thrust belt does not extend into the southern United States Cordillera and northern Mexican Cordillera ( Fig. 1 ; Yonkee and Weil, 2015 ; Fitz-Díaz et al., 2018 ). Instead, Late Cretaceous to Paleogene contractional strain in these areas is generally characterized by basement-involved uplifts accompanying high-angle reverse faulting, formed during the Laramide orogeny ( Krantz et al., 1989 ; Clinkscales and Lawton, 2017 ; Fitz-Díaz et al., 2018 ). Horizontal shortening recorded by these high-angle reverse faults is insufficient to have significantly thickened the crust ( Davis, 1979 ). Thus, if the Laramide orogeny in southern Arizona and northern Sonora resulted in thickened crust, mechanisms in addition to tectonic shortening are required. To evaluate the possibility of thick crust supporting an orogenic plateau in the southern United States and northern Mexican Cordillera, we used whole-rock La/Yb ratios in Laramide-age, intermediate-composition continental-arc rocks as a proxy for crustal thickness ( Fig. 2 ), following the method of Profeta et al. (2015) . As crustal thickness increases, whole-rock heavy rare earth element (HREE) concentrations decrease and light rare earth element (LREE) concentrations increase, due to the high-pressure stabilization of HREE-enriched phases such as amphibole and garnet at the expense of LREE-enriched phases such as plagioclase ( Hu et al., 2017 ; Müntener and Ulmer, 2018 ). Despite the low concentration of LREE in plagioclase, the mineral is important because of its abundance in continental-arc rocks and because it is unstable at higher pressure, in contrast to other LREE-bearing accessory phases such as monazite. GEOLOGIC BACKGROUND Some early studies of the southern United States Cordillera suggested that the Sevier thrust belt was continuous from southern Nevada to northern Chihuahua ( Drewes, 1978 ). However, subsequent research has demonstrated that many of the thrust faults used to support a thrust belt interpretation are low-angle normal faults or other types of geologic contacts such as unconformities ( Dickinson, 1984 ; Krantz et al., 1989 ; Clinkscales and Lawton, 2017 ). As a result, most researchers now believe that the Sevier thrust belt terminates in the Mojave region of southern California ( DeCelles, 2004 ; Yonkee and Weil, 2015 ) and that shortening in southern Arizona and northern Sonora was temporally restricted to the Laramide orogeny and predominantly occurred along high-angle reverse faults, in part reactivating Late Jurassic to Early Cretaceous rift-related structures ( Davis, 1979 ; Krantz et al., 1989 ; Lawton, 2000 ; Favorito and Seedorff, 2018 ; Fitz-Díaz et al., 2018 ). Continental-arc magmatism migrated eastward through the study area ( Fig. 2 ) during the Laramide orogeny as the subduction angle of the Farallon slab shallowed ( Coney and Reynolds, 1977 ). Laramide igneous rocks in southern Arizona and northern Sonora are mainly intermediate, metaluminous, and calc-alkaline rocks that have radiogenic isotopic compositions inherited from the lithospheric province into which they were emplaced ( Lang and Titley, 1998 ; González-León et al., 2011 ; Chapman et al., 2018 ). During mid-Eocene time, toward the end of the<|im_end|> <|im_start|>assistant A University of Wyoming researcher and his colleagues have shown that much of the southwestern United States was once a vast high-elevation plateau, similar to Tibet today. This work has implications for the distribution of natural resources, such as copper, and provides insight into the formation of mountains during the subduction of tectonic plates. "We normally think of southern Arizona and the surrounding areas as hot, cactus-laden deserts with relatively low base elevations, below 3,000 feet," says Jay Chapman, an assistant professor in UW's Department of Geology and Geophysics. "However, our recent research suggests that, during the Late Cretaceous to Early Paleogene period (80-50 million years ago), the region may have had elevations in excess of 10,000 feet and looked more like the Tibetan plateau north of the Himalayan Mountains or the Altiplano in the Andes Mountains in South America." Chapman is lead author of a paper, titled "Geochemical evidence for an orogenic plateau in the southern U.S. and northern Mexican Cordillera during the Laramide Orogeny," which was published online Nov. 22 in the journal Geology. The print version will be published in February. Roy Greig, a Ph.D. student in the Department of Geosciences at the University of Arizona, and Gordon Haxel, a U.S. Geological Survey scientist based in Flagstaff, Ariz., are co-authors of the paper. Chapman and his colleagues analyzed the chemistry of igneous rocks to determine how thick Earth's crust was in the past and then related the thickness to elevation. "Earth's crust floats in the mantle just like an iceberg floats in the water, with a little bit sticking out above the surface," Chapman says. "When the crust is thicker, the height of mountains and the elevation of the land surface are higher, just like the height of an iceberg sticking out of the water is taller if the overall iceberg is larger." The study determined that the crust in southern Arizona was once almost 60 kilometers thick, which is twice as thick as it is today—and comparable to how thick the crust is in parts of the Himalayas. "While the ancient mountains were forming, magma intruded into the crust and formed rocks like granite," Chapman says. "When the crust was really thick, the magmas experienced extreme pressure from the weight of all the rocks above them, which caused distinctive changes in the types and the chemistry of the minerals that formed those rocks." One of the interesting questions the study raises is how the crust in southern Arizona became so thick in the past. "The most common way to make really thick crust is for tectonic plates to converge or collide, which produces large earthquakes and faults that stack rock masses overtop one another," he says. "The prevailing view of southern Arizona is that there was never enough faulting in the area to make the thickness of crust we observe. It is a bit of a conundrum as to how such thick crust was generated." Adam Trzinski, a first-year Ph.D. student at UW, is now tackling this problem and searching for ancient faults in southern Arizona that could help explain how the thick crust became so thick. In addition to helping understand plate tectonic processes, the study may help explain why copper is so abundant in southern Arizona. "Several previous studies have noted a correlation between large copper ore deposits and regions of thick crust," Chapman says. "For example, there are many copper mines in the Andes Mountains in Chile. The results of this study strengthen that correlation and may aid in exploration efforts." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Increasing the capability of automated driving vehicles is motivated by environmental, productivity, and traffic safety benefits. But over-reliance on the automation system is known to cause accidents. The role of the driver cannot be underestimated as it will ultimately be the most relevant aspect for trust building and social acceptance of this technology. Here we introduce a driver-oriented automation strategy to achieve collaborative steering. Our approach relies on three major functionalities: interaction, arbitration, and inclusion. The proposed control strategy is grounded in the concept of shared control enabling driver intervention over the automation without deactivation. Well-defined physical human-robot interaction types are made available with the arbitration strategy. The automated driving trajectory is adapted to include the driver intent into the tactical level of trajectory planning. This enables driver initiated rerouting and consistent coordination of all vehicle actuators. In this way, automated vehicles, which rely on sight only, are augmented with the incorporation of the driver intent. The driver is neither replaced by nor excluded from the automation, rather their role remains active to the benefit of trust building and driving safety. Introduction Advanced driver assistance systems (ADAS) used in partial automation are intended to reduce the driver workload without causing disengagement. Level-2 automation splits the responsibility of the real-time operational and tactical functions to operate a vehicle safely in on-road traffic 1 , where the driver is responsible for the ‘object and event detection and response (OEDR)’, while the vehicle operates the sustained lateral and longitudinal motion control 2 . A combination of two ADAS is used to comply with this definition. Active cruise control regulates the vehicle to a predefined speed and slows down to maintain a preset distance with any slower moving vehicles ahead. Lane centering assistance (LCA) operates the steering system to track the trajectory computed by the automation (or AD trajectory), which typically is the center position of the lane in which the vehicle is traveling. Moreover, assistance for lane change is available in some vehicles. The automated lane change (ALC) function provides guidance to support the driver when the traffic condition is safe. Level-0 ADAS functions, such as automatic emergency braking for the longitudinal displacement or lane keeping assistance (LKA) for the lateral deviation complete the active safety envelope. Providing an interactive environment with the steering system, where manual and automated inputs can coexist alleviates the risk of disengagement. Hence, lateral control of the vehicle is often shared so that manual steering over the guidance torque of the automation is possible without deactivation. Here, shared control is defined following 3 : ‘human(s) and robot(s) are interacting congruently in a perception-action cycle to perform a dynamic task that either the human or the robot could execute individually under ideal circumstances. This definition excludes full automation (where there is no human) or manual control (where there is no automation)’. The concept of haptic shared control (HSC) has received significant attention due to the anticipated benefits to safety for partial and conditional automation levels 4 , 5 , 6 , 7 , 8 . Haptic communication through the steering interface is suggested to be the most practical channel to bond driver and vehicle because of its bilateral and dynamic characteristics 4 , 6 , 9 . Most partially automated vehicles use a blended control scheme for HSC (Fig. 1 a). It finds its origin in robotic force control under the name of ‘parallel force/position control’ 10 , 11 and is based on the idea that the driver and the automation can apply a torque command independently to the same actuator. In terms of control, the automation is a feedback loop of the steering displacement, in which a manual torque input is seen as an external disturbance to be rejected. Conceptually, blended control consists in modulating the angle controller impedance to enable driver intervention. The ADAS functions are realized through conditional operation of the blended control scheme. Typically, the gain G t and eventually the angle controller gains are programmed to satisfy the operating condition of each ADAS function. For example, the assistance provided from the LCA function is obtained by operating the steering system in shared control mode with 0 < G t < 1. The reaction torque to the driver is proportional to the tracking error and its derivative. This angular error is caused by manual intervention or variation of the tracking reference. Therefore, the reaction torque of the LCA represents haptic guidance directed towards the AD trajectory, which is intended to reduce the driver workload. Fig. 1: Two configurations of steering HSC between human driver and automation and overview of an automated driving control framework including the proposed collaborative steering control. The dashed lines represent the human driver control. a Blended control: The driver torque T d and the automation torque T a track their target angles θ d and θ a with the feedback of the measured angle θ p . The respective tracking efforts are superposed to form an electric power steering (EPS) motor torque command. The gain G t is used for attenuating the automation effort and enabling driver intervention in shared mode. G t is set to zero when operating the EPS in manual mode in the event of an override. b Admittance control: A virtual plant is used to estimate the manual deviation θ m from the measured driver torque input T t b . The angle control attempts to enforce the superposition angle of θ a and θ m by applying the command torque T m o t to the EPS. The reaction torque perceived by the driver is designed with the virtual plant and its load T a . Similarly to blended control, the gain G t is set to zero for manual steering. c The black blocks with the vision loops illustrate the typical structure of an automated vehicle control system. The proposed control is represented with the turquoise blocks. Arbitration allocates the control authority of the automation based on the interaction type. The driver and the", "role": "user" }, { "content": "Researchers from EPFL and JTEKT Corporation have developed an automated driving system based on the concept of \"collaborative steering,\" which aims to increase transportation safety, efficiency, and comfort by encouraging active interaction between autonomous vehicles and their human drivers. Autonomous driving technologies have already been integrated into many mass-produced vehicles, providing human drivers with steering assistance in tasks like centering a vehicle in its lane. But the little data available on automated driving safety shows that placing too much control of a vehicle in the hands of automation can do more harm than good, as disengagement by human drivers can increase the risk of accidents. \"Current vehicles on the market are either manual or automated, and there is no clear way of making their control a truly shared experience. This is dangerous, because it tends to lead to driver over-reliance on automation,\" explains Jürg Schiffmann, head of the Laboratory for Applied Mechanical Design in the School of Engineering. Now, researchers from the lab have collaborated with Japanese steering system supplier JTEKT Corporation to develop and successfully road-test a haptics-based automated driving system that integrates different modes of human-robot interaction. The researchers hope that their approach will increase not only the safety of automated driving, but also social acceptance of it. \"This research was based on the idea that automation systems should adapt to human drivers, and not vice versa,\" says EPFL Ph.D. student and JTEKT researcher Tomohiro Nakade, who is also the first author on a recent paper describing the system published in the journal Communications Engineering. Credit: Ecole Polytechnique Federale de Lausanne Nakade adds that a good metaphor for the new system can be drawn from a transportation mode that predates automation: \"A vehicle must be open to negotiation with a human driver, just as a horseback rider conveys his or her intention to the horse through the reins.\" Interaction, arbitration, and inclusion Unlike current automated driving systems, which use only cameras for sensory input, the researchers' more holistic approach integrates information from a car's steering column. It also encourages continuous engagement between driver and automation, as opposed to current automated systems, which are typically either switched on or off. \"In automation in general, when humans are just monitoring a system but not actively involved, they lose the ability to react,\" says Robert Fuchs, a former EPFL Ph.D. student who is now an R&D general manager at JTEKT Corporation. \"That's why we wanted to actively improve driver engagement through automation.\" The researchers' system achieves this thanks to three functionalities: interaction, arbitration, and inclusion. First, the system distinguishes between four different types of human-robot interaction: cooperation (the automation supports the human in achieving a goal); coactivity (the human and automation have different goals, but their actions impact one another); collaboration (human and automation assist one another in achieving different goals); and competition (human and automation activities are in opposition). Next, as the driver operates the vehicle, the system arbitrates, or moves between different interaction modes depending on the evolving situation on the road. For example, the car might switch from collaboration to competition mode to avoid a sudden collision threat. Finally, and still within the same control framework, the system integrates an 'inclusion' function: it recomputes the vehicle's trajectory whenever the driver intervenes—by turning the steering wheel, for example—rather than perceiving it as an override and switching off. A practical solution To test their system, the researchers developed experiments involving a simulated virtual driver and a human driver using a detached power steering system, a full driving simulator, and even field tests with a modified test vehicle. The field tests were carried out with the participation of five drivers on a JTEKT test course in Japan's Mie prefecture, by connecting the researchers' system to a standard sedan via an external controller. The researchers specifically tested drivers' experiences of steering smoothness and lane-changing ease, and their results confirmed the system's significant potential for increasing comfort and reducing effort for drivers through collaborative steering. \"This is a very practical concept—it's not just research for research's sake,\" says Schiffmann, adding that the software-based system can be integrated into standard mass-produced cars without any special equipment. \"It's also a beautiful example of a fruitful partnership between our lab and JTEKT, with whom EPFL has collaborated since 1998.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Increasing the capability of automated driving vehicles is motivated by environmental, productivity, and traffic safety benefits. But over-reliance on the automation system is known to cause accidents. The role of the driver cannot be underestimated as it will ultimately be the most relevant aspect for trust building and social acceptance of this technology. Here we introduce a driver-oriented automation strategy to achieve collaborative steering. Our approach relies on three major functionalities: interaction, arbitration, and inclusion. The proposed control strategy is grounded in the concept of shared control enabling driver intervention over the automation without deactivation. Well-defined physical human-robot interaction types are made available with the arbitration strategy. The automated driving trajectory is adapted to include the driver intent into the tactical level of trajectory planning. This enables driver initiated rerouting and consistent coordination of all vehicle actuators. In this way, automated vehicles, which rely on sight only, are augmented with the incorporation of the driver intent. The driver is neither replaced by nor excluded from the automation, rather their role remains active to the benefit of trust building and driving safety. Introduction Advanced driver assistance systems (ADAS) used in partial automation are intended to reduce the driver workload without causing disengagement. Level-2 automation splits the responsibility of the real-time operational and tactical functions to operate a vehicle safely in on-road traffic 1 , where the driver is responsible for the ‘object and event detection and response (OEDR)’, while the vehicle operates the sustained lateral and longitudinal motion control 2 . A combination of two ADAS is used to comply with this definition. Active cruise control regulates the vehicle to a predefined speed and slows down to maintain a preset distance with any slower moving vehicles ahead. Lane centering assistance (LCA) operates the steering system to track the trajectory computed by the automation (or AD trajectory), which typically is the center position of the lane in which the vehicle is traveling. Moreover, assistance for lane change is available in some vehicles. The automated lane change (ALC) function provides guidance to support the driver when the traffic condition is safe. Level-0 ADAS functions, such as automatic emergency braking for the longitudinal displacement or lane keeping assistance (LKA) for the lateral deviation complete the active safety envelope. Providing an interactive environment with the steering system, where manual and automated inputs can coexist alleviates the risk of disengagement. Hence, lateral control of the vehicle is often shared so that manual steering over the guidance torque of the automation is possible without deactivation. Here, shared control is defined following 3 : ‘human(s) and robot(s) are interacting congruently in a perception-action cycle to perform a dynamic task that either the human or the robot could execute individually under ideal circumstances. This definition excludes full automation (where there is no human) or manual control (where there is no automation)’. The concept of haptic shared control (HSC) has received significant attention due to the anticipated benefits to safety for partial and conditional automation levels 4 , 5 , 6 , 7 , 8 . Haptic communication through the steering interface is suggested to be the most practical channel to bond driver and vehicle because of its bilateral and dynamic characteristics 4 , 6 , 9 . Most partially automated vehicles use a blended control scheme for HSC (Fig. 1 a). It finds its origin in robotic force control under the name of ‘parallel force/position control’ 10 , 11 and is based on the idea that the driver and the automation can apply a torque command independently to the same actuator. In terms of control, the automation is a feedback loop of the steering displacement, in which a manual torque input is seen as an external disturbance to be rejected. Conceptually, blended control consists in modulating the angle controller impedance to enable driver intervention. The ADAS functions are realized through conditional operation of the blended control scheme. Typically, the gain G t and eventually the angle controller gains are programmed to satisfy the operating condition of each ADAS function. For example, the assistance provided from the LCA function is obtained by operating the steering system in shared control mode with 0 < G t < 1. The reaction torque to the driver is proportional to the tracking error and its derivative. This angular error is caused by manual intervention or variation of the tracking reference. Therefore, the reaction torque of the LCA represents haptic guidance directed towards the AD trajectory, which is intended to reduce the driver workload. Fig. 1: Two configurations of steering HSC between human driver and automation and overview of an automated driving control framework including the proposed collaborative steering control. The dashed lines represent the human driver control. a Blended control: The driver torque T d and the automation torque T a track their target angles θ d and θ a with the feedback of the measured angle θ p . The respective tracking efforts are superposed to form an electric power steering (EPS) motor torque command. The gain G t is used for attenuating the automation effort and enabling driver intervention in shared mode. G t is set to zero when operating the EPS in manual mode in the event of an override. b Admittance control: A virtual plant is used to estimate the manual deviation θ m from the measured driver torque input T t b . The angle control attempts to enforce the superposition angle of θ a and θ m by applying the command torque T m o t to the EPS. The reaction torque perceived by the driver is designed with the virtual plant and its load T a . Similarly to blended control, the gain G t is set to zero for manual steering. c The black blocks with the vision loops illustrate the typical structure of an automated vehicle control system. The proposed control is represented with the turquoise blocks. Arbitration allocates the control authority of the automation based on the interaction type. The driver and the<|im_end|> <|im_start|>assistant Researchers from EPFL and JTEKT Corporation have developed an automated driving system based on the concept of "collaborative steering," which aims to increase transportation safety, efficiency, and comfort by encouraging active interaction between autonomous vehicles and their human drivers. Autonomous driving technologies have already been integrated into many mass-produced vehicles, providing human drivers with steering assistance in tasks like centering a vehicle in its lane. But the little data available on automated driving safety shows that placing too much control of a vehicle in the hands of automation can do more harm than good, as disengagement by human drivers can increase the risk of accidents. "Current vehicles on the market are either manual or automated, and there is no clear way of making their control a truly shared experience. This is dangerous, because it tends to lead to driver over-reliance on automation," explains Jürg Schiffmann, head of the Laboratory for Applied Mechanical Design in the School of Engineering. Now, researchers from the lab have collaborated with Japanese steering system supplier JTEKT Corporation to develop and successfully road-test a haptics-based automated driving system that integrates different modes of human-robot interaction. The researchers hope that their approach will increase not only the safety of automated driving, but also social acceptance of it. "This research was based on the idea that automation systems should adapt to human drivers, and not vice versa," says EPFL Ph.D. student and JTEKT researcher Tomohiro Nakade, who is also the first author on a recent paper describing the system published in the journal Communications Engineering. Credit: Ecole Polytechnique Federale de Lausanne Nakade adds that a good metaphor for the new system can be drawn from a transportation mode that predates automation: "A vehicle must be open to negotiation with a human driver, just as a horseback rider conveys his or her intention to the horse through the reins." Interaction, arbitration, and inclusion Unlike current automated driving systems, which use only cameras for sensory input, the researchers' more holistic approach integrates information from a car's steering column. It also encourages continuous engagement between driver and automation, as opposed to current automated systems, which are typically either switched on or off. "In automation in general, when humans are just monitoring a system but not actively involved, they lose the ability to react," says Robert Fuchs, a former EPFL Ph.D. student who is now an R&D general manager at JTEKT Corporation. "That's why we wanted to actively improve driver engagement through automation." The researchers' system achieves this thanks to three functionalities: interaction, arbitration, and inclusion. First, the system distinguishes between four different types of human-robot interaction: cooperation (the automation supports the human in achieving a goal); coactivity (the human and automation have different goals, but their actions impact one another); collaboration (human and automation assist one another in achieving different goals); and competition (human and automation activities are in opposition). Next, as the driver operates the vehicle, the system arbitrates, or moves between different interaction modes depending on the evolving situation on the road. For example, the car might switch from collaboration to competition mode to avoid a sudden collision threat. Finally, and still within the same control framework, the system integrates an 'inclusion' function: it recomputes the vehicle's trajectory whenever the driver intervenes—by turning the steering wheel, for example—rather than perceiving it as an override and switching off. A practical solution To test their system, the researchers developed experiments involving a simulated virtual driver and a human driver using a detached power steering system, a full driving simulator, and even field tests with a modified test vehicle. The field tests were carried out with the participation of five drivers on a JTEKT test course in Japan's Mie prefecture, by connecting the researchers' system to a standard sedan via an external controller. The researchers specifically tested drivers' experiences of steering smoothness and lane-changing ease, and their results confirmed the system's significant potential for increasing comfort and reducing effort for drivers through collaborative steering. "This is a very practical concept—it's not just research for research's sake," says Schiffmann, adding that the software-based system can be integrated into standard mass-produced cars without any special equipment. "It's also a beautiful example of a fruitful partnership between our lab and JTEKT, with whom EPFL has collaborated since 1998." <|im_end|>

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2,106

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [ 11 C]DASB and [ 11 C]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response. Introduction Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety but it has been widely debated to what extent SSRI efficacy can be attributed to expectancies of improvement—a key mechanism of placebo effects [ 1 , 2 , 3 , 4 , 5 , 6 ]. This question has been discussed extensively in the field of depression, but it is relevant also for anxiety conditions [ 7 , 8 ] including social anxiety disorder (SAD) [ 9 ]. Meta-analyses support that SSRIs are efficacious for these disorders [ 10 , 11 ] but the clinical effect of SSRIs in double-blind RCTs may, at least partly, reflect an enhanced placebo response because of perceived side effects by participants in the active drug arm, compromising the integrity of the blind and increasing response expectancies [ 12 ]. While this notion has been questioned [ 6 , 13 ], it is supported by trials using active placebo, mimicking the side effects of the active substance, and by experimental research demonstrating that expectancies affect therapeutic outcomes [ 14 , 15 , 16 ]. Further research is needed to clarify the magnitude of the SSRI clinicial effect, to what extent it can be attributed to the drug itself, and the neural mechanisms underlying symptom remission with SSRIs. Research designs involving deception have been used to separate drug from expectancy effects in clinical as well as neuroimaging trials [ 9 , 15 , 16 , 17 , 18 ]. We previously demonstrated enhanced anti-anxiety effects of overt as compared to covert SSRI treatment with escitalopram in patients with SAD [ 9 ]. Patients were treated with equivalent clinical doses of escitalopram for 9 weeks, but only one group was correctly informed about the treatment received and its effectiveness. Using a credible cover story, the other group was led to believe that they were treated with an “active placebo” (a neurokinin-1 receptor antagonist) expected to induce similar side effects as the SSRI while lacking anxiolytic properties. In the present study, we further investigated the therapeutic mechanisms underlying SSRI efficacy by analyzing how serotonin and dopamine transporters (DATs) are affected by response expectancies. The SSRIs are held to exert their therapeutic effects by blocking serotonin uptake via the serotonin transporter (SERT) [ 19 ] and clinical doses typically result in 76–85% SERT occupancy in the striatum [ 20 ]. However, the downstream therapeutic mechanisms of action are still not elucidated, and in this respect dopaminergic mechanisms may also be important as the serotonin and dopamine systems have reciprocal functional influences on each other [ 21 , 22 ]. SAD patients show increased expression and co-expression of SERTs and DATs in comparison to healthy controls [ 23 ]. Molecular neuroimaging studies suggest that SSRIs exert effects also on the DAT [ 24 , 25 , 26 , 27 , 28 ]. It is, however, unclear to what extent SERTs and DATs are affected by the SSRI itself or by psychological processes like expectancies. Here, in a subsample of our previous SSRI deception study of SAD [ 9 ], we examined if giving correct or incorrect information about the drug affects serotonergic and dopaminergic neurotransmission as assessed with positron emission tomography (PET) and the highly selective radioligands [ 11 C]DASB and [ 11 C]PE2I, probing SERTs and DATs respectively. Effects on monoamine transporter proteins and clinical responsiveness were evaluated when escitalopram was administered with and without clear expectations of improvement, i.e., overt vs. covert SSRI treatment. Methods Participants We studied a PET subsample of a previously reported SAD treatment cohort, and for methodological details, we refer to that paper [ 9 ]. Also, PET baseline comparisons of SAD patients vs. healthy controls have been reported elsewhere [ 23 ]. Here, 27 right-handed patients with SAD (17 men, 10 women; mean ± SD age, 31.1 ± 10.3 years) underwent [ 11 C]DASB and [ 11 C]PE2I PET imaging before and after 9 weeks of escitalopram treatment—see Fig. S1 and Table S1 in the Supplementary. Of these, one female participant could not be included in posttreatment [ 11 C]DASB analyses due to scanner failure. In addition to the included sample, two patients were assessed by PET at baseline but were excluded from analyses due to magnetic resonance imaging (MRI) contraindications, and withdrawal from the study before completed MRI, respectively. Between March 17th 2014 and May 22nd 2015, participants were recruited through advertisements in newspapers, public", "role": "user" }, { "content": "Levels of dopamine and the placebo effect can determine whether patients with social anxieties improve when treated with SSRIs. A new study shows the effect was four times higher for patients with high expectations of the medication compared with patients with low expectations. This was true even though the groups received the same medical treatment. Although SSRIs influence levels of serotonin in the brain, the effects on dopamine had the greatest impact for improvement. Selective serotonin reuptake inhibitors (SSRIs) are an established and effective medication for treating depression and anxiety. The placebo effect, where the positive effects of a treatment can increase when a patient expects to be helped, is a well-known phenomenon. The effect can be significant, and it is unclear how much of the improvement results from expectations of the SSRI treatment. It is also unclear whether the expectations use the same mechanism in the brain as SSRI medications (the inhibiting of the transporter protein for serotonin) or whether other neurotransmitters are involved. The new study points to the transporter protein for dopamine being the key. Researchers at Uppsala University confirmed in a study on social anxiety published in Translational Psychiatry that the placebo effect had a major impact on the anti-anxiety effect of the SSRI drug escitalopram. The surprising finding in the study was that the improvement after SSRI treatment can largely be linked to effects on dopamine rather than to the serotonin transporters. In the study, all the participants were treated with the same clinical dose of escitalopram for nine weeks, but they had different expectations. Half received accurate information about the drug and its effectiveness, while a cover story was used for the other half. Participants in the second group were told that the drug was an 'active placebo' that causes similar side effects as SSRIs but was not expected to alleviate their social anxiety. \"The results showed that almost four times as many patients responded to the treatment when correct information about the drug was given. This is consistent with previous research showing that expectations affect treatment outcome,\" says researcher Olof Hjorth. Positron emission tomography (PET) brain scanning showed that the SSRI drug had the same effect on serotonin and blocked about 80 per cent of serotonin transporters in both groups. This was true even for the group that had low expectations and did not improve. \"This indicates that the pharmacological effect was identical in both groups and that this cannot explain why correct information gave better treatment results. So, inhibiting serotonin transporters is insufficient for achieving good clinical relief from social anxiety using SSRI drugs.\" When assessing the transporter protein for dopamine after treatment, however, a clear difference between the groups was observed. Participants who began the treatment knowing that it was an effective drug showed a reduced availability of dopamine transporters in the striatum, a part of the cerebrum, while the opposite was true in the group that was given the cover story. One explanation may be that expectations affected the release of dopamine in the brain's reward pathways. This may have led to differences in the two groups in the proportion of dopamine transporters available after treatment. \"The results indicate that positive expectations arising in the relationship between doctor and patient affect dopamine and enhance the effect of SSRI treatment,\" says Professor Tomas Furmark, who led the study. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract It has been extensively debated whether selective serotonin reuptake inhibitors (SSRIs) are more efficacious than placebo in affective disorders, and it is not fully understood how SSRIs exert their beneficial effects. Along with serotonin transporter blockade, altered dopamine signaling and psychological factors may contribute. In this randomized clinical trial of participants with social anxiety disorder (SAD) we investigated how manipulation of verbally-induced expectancies, vital for placebo response, affect brain monoamine transporters and symptom improvement during SSRI treatment. Twenty-seven participants with SAD (17 men, 10 women), were randomized, to 9 weeks of overt or covert treatment with escitalopram 20 mg. The overt group received correct treatment information whereas the covert group was treated deceptively with escitalopram, described as an active placebo in a cover story. Before and after treatment, patients underwent positron emission tomography (PET) assessments with the [ 11 C]DASB and [ 11 C]PE2I radiotracers, probing brain serotonin (SERT) and dopamine (DAT) transporters. SAD symptoms were measured by the Liebowitz Social Anxiety Scale. Overt was superior to covert SSRI treatment, resulting in almost a fourfold higher rate of responders. PET results showed that SERT occupancy after treatment was unrelated to anxiety reduction and equally high in both groups. In contrast, DAT binding decreased in the right putamen, pallidum, and the left thalamus with overt SSRI treatment, and increased with covert treatment, resulting in significant group differences. DAT binding potential changes in these regions correlated negatively with symptom improvement. Findings support that the anxiolytic effects of SSRIs involve psychological factors contingent on dopaminergic neurotransmission while serotonin transporter blockade alone is insufficient for clinical response. Introduction Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed for depression and anxiety but it has been widely debated to what extent SSRI efficacy can be attributed to expectancies of improvement—a key mechanism of placebo effects [ 1 , 2 , 3 , 4 , 5 , 6 ]. This question has been discussed extensively in the field of depression, but it is relevant also for anxiety conditions [ 7 , 8 ] including social anxiety disorder (SAD) [ 9 ]. Meta-analyses support that SSRIs are efficacious for these disorders [ 10 , 11 ] but the clinical effect of SSRIs in double-blind RCTs may, at least partly, reflect an enhanced placebo response because of perceived side effects by participants in the active drug arm, compromising the integrity of the blind and increasing response expectancies [ 12 ]. While this notion has been questioned [ 6 , 13 ], it is supported by trials using active placebo, mimicking the side effects of the active substance, and by experimental research demonstrating that expectancies affect therapeutic outcomes [ 14 , 15 , 16 ]. Further research is needed to clarify the magnitude of the SSRI clinicial effect, to what extent it can be attributed to the drug itself, and the neural mechanisms underlying symptom remission with SSRIs. Research designs involving deception have been used to separate drug from expectancy effects in clinical as well as neuroimaging trials [ 9 , 15 , 16 , 17 , 18 ]. We previously demonstrated enhanced anti-anxiety effects of overt as compared to covert SSRI treatment with escitalopram in patients with SAD [ 9 ]. Patients were treated with equivalent clinical doses of escitalopram for 9 weeks, but only one group was correctly informed about the treatment received and its effectiveness. Using a credible cover story, the other group was led to believe that they were treated with an “active placebo” (a neurokinin-1 receptor antagonist) expected to induce similar side effects as the SSRI while lacking anxiolytic properties. In the present study, we further investigated the therapeutic mechanisms underlying SSRI efficacy by analyzing how serotonin and dopamine transporters (DATs) are affected by response expectancies. The SSRIs are held to exert their therapeutic effects by blocking serotonin uptake via the serotonin transporter (SERT) [ 19 ] and clinical doses typically result in 76–85% SERT occupancy in the striatum [ 20 ]. However, the downstream therapeutic mechanisms of action are still not elucidated, and in this respect dopaminergic mechanisms may also be important as the serotonin and dopamine systems have reciprocal functional influences on each other [ 21 , 22 ]. SAD patients show increased expression and co-expression of SERTs and DATs in comparison to healthy controls [ 23 ]. Molecular neuroimaging studies suggest that SSRIs exert effects also on the DAT [ 24 , 25 , 26 , 27 , 28 ]. It is, however, unclear to what extent SERTs and DATs are affected by the SSRI itself or by psychological processes like expectancies. Here, in a subsample of our previous SSRI deception study of SAD [ 9 ], we examined if giving correct or incorrect information about the drug affects serotonergic and dopaminergic neurotransmission as assessed with positron emission tomography (PET) and the highly selective radioligands [ 11 C]DASB and [ 11 C]PE2I, probing SERTs and DATs respectively. Effects on monoamine transporter proteins and clinical responsiveness were evaluated when escitalopram was administered with and without clear expectations of improvement, i.e., overt vs. covert SSRI treatment. Methods Participants We studied a PET subsample of a previously reported SAD treatment cohort, and for methodological details, we refer to that paper [ 9 ]. Also, PET baseline comparisons of SAD patients vs. healthy controls have been reported elsewhere [ 23 ]. Here, 27 right-handed patients with SAD (17 men, 10 women; mean ± SD age, 31.1 ± 10.3 years) underwent [ 11 C]DASB and [ 11 C]PE2I PET imaging before and after 9 weeks of escitalopram treatment—see Fig. S1 and Table S1 in the Supplementary. Of these, one female participant could not be included in posttreatment [ 11 C]DASB analyses due to scanner failure. In addition to the included sample, two patients were assessed by PET at baseline but were excluded from analyses due to magnetic resonance imaging (MRI) contraindications, and withdrawal from the study before completed MRI, respectively. Between March 17th 2014 and May 22nd 2015, participants were recruited through advertisements in newspapers, public<|im_end|> <|im_start|>assistant Levels of dopamine and the placebo effect can determine whether patients with social anxieties improve when treated with SSRIs. A new study shows the effect was four times higher for patients with high expectations of the medication compared with patients with low expectations. This was true even though the groups received the same medical treatment. Although SSRIs influence levels of serotonin in the brain, the effects on dopamine had the greatest impact for improvement. Selective serotonin reuptake inhibitors (SSRIs) are an established and effective medication for treating depression and anxiety. The placebo effect, where the positive effects of a treatment can increase when a patient expects to be helped, is a well-known phenomenon. The effect can be significant, and it is unclear how much of the improvement results from expectations of the SSRI treatment. It is also unclear whether the expectations use the same mechanism in the brain as SSRI medications (the inhibiting of the transporter protein for serotonin) or whether other neurotransmitters are involved. The new study points to the transporter protein for dopamine being the key. Researchers at Uppsala University confirmed in a study on social anxiety published in Translational Psychiatry that the placebo effect had a major impact on the anti-anxiety effect of the SSRI drug escitalopram. The surprising finding in the study was that the improvement after SSRI treatment can largely be linked to effects on dopamine rather than to the serotonin transporters. In the study, all the participants were treated with the same clinical dose of escitalopram for nine weeks, but they had different expectations. Half received accurate information about the drug and its effectiveness, while a cover story was used for the other half. Participants in the second group were told that the drug was an 'active placebo' that causes similar side effects as SSRIs but was not expected to alleviate their social anxiety. "The results showed that almost four times as many patients responded to the treatment when correct information about the drug was given. This is consistent with previous research showing that expectations affect treatment outcome," says researcher Olof Hjorth. Positron emission tomography (PET) brain scanning showed that the SSRI drug had the same effect on serotonin and blocked about 80 per cent of serotonin transporters in both groups. This was true even for the group that had low expectations and did not improve. "This indicates that the pharmacological effect was identical in both groups and that this cannot explain why correct information gave better treatment results. So, inhibiting serotonin transporters is insufficient for achieving good clinical relief from social anxiety using SSRI drugs." When assessing the transporter protein for dopamine after treatment, however, a clear difference between the groups was observed. Participants who began the treatment knowing that it was an effective drug showed a reduced availability of dopamine transporters in the striatum, a part of the cerebrum, while the opposite was true in the group that was given the cover story. One explanation may be that expectations affected the release of dopamine in the brain's reward pathways. This may have led to differences in the two groups in the proportion of dopamine transporters available after treatment. "The results indicate that positive expectations arising in the relationship between doctor and patient affect dopamine and enhance the effect of SSRI treatment," says Professor Tomas Furmark, who led the study. <|im_end|>

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510, 220, 24, 1174, 220, 868, 1174, 220, 845, 1174, 220, 1114, 1174, 220, 972, 21087, 1226, 8767, 21091, 24872, 7294, 19415, 16708, 6372, 315, 43661, 439, 7863, 311, 57593, 18679, 4403, 6514, 449, 3920, 2223, 454, 2453, 304, 6978, 449, 328, 1846, 510, 220, 24, 21087, 44430, 1051, 12020, 449, 13890, 14830, 35130, 315, 3920, 2223, 454, 2453, 369, 220, 24, 5672, 11, 719, 1193, 832, 1912, 574, 12722, 16369, 922, 279, 6514, 4036, 323, 1202, 27375, 13, 12362, 264, 43010, 3504, 3446, 11, 279, 1023, 1912, 574, 6197, 311, 4510, 430, 814, 1051, 12020, 449, 459, 1054, 3104, 43715, 863, 320, 64, 18247, 8148, 258, 12, 16, 35268, 82159, 8, 3685, 311, 49853, 4528, 3185, 6372, 439, 279, 18679, 4403, 1418, 32161, 459, 11927, 5849, 29150, 6012, 13, 763, 279, 3118, 4007, 11, 584, 4726, 27313, 279, 37471, 24717, 16940, 18679, 4403, 41265, 555, 42118, 1268, 77130, 323, 66128, 7710, 388, 320, 48992, 82, 8, 527, 11754, 555, 2077, 1755, 32737, 13, 578, 96404, 3957, 527, 5762, 311, 43844, 872, 37471, 6372, 555, 22978, 77130, 69575, 4669, 279, 77130, 73565, 320, 50, 3481, 8, 510, 220, 777, 2331, 323, 14830, 35130, 11383, 1121, 304, 220, 4767, 4235, 5313, 4, 328, 3481, 66419, 304, 279, 6076, 27349, 510, 220, 508, 21087, 4452, 11, 279, 52452, 37471, 24717, 315, 1957, 527, 2103, 539, 97298, 660, 11, 323, 304, 420, 5201, 27420, 8778, 75439, 24717, 1253, 1101, 387, 3062, 439, 279, 77130, 323, 66128, 6067, 617, 87298, 16003, 34453, 389, 1855, 1023, 510, 220, 1691, 1174, 220, 1313, 21087, 328, 1846, 6978, 1501, 7319, 7645, 323, 1080, 82593, 315, 328, 3481, 82, 323, 40462, 82, 304, 12593, 311, 9498, 11835, 510, 220, 1419, 21087, 60825, 18247, 318, 4210, 7978, 4284, 430, 96404, 3957, 43844, 6372, 1101, 389, 279, 40462, 510, 220, 1187, 1174, 220, 914, 1174, 220, 1627, 1174, 220, 1544, 1174, 220, 1591, 21087, 1102, 374, 11, 4869, 11, 25420, 311, 1148, 13112, 328, 3481, 82, 323, 40462, 82, 527, 11754, 555, 279, 18679, 4403, 5196, 477, 555, 24064, 11618, 1093, 1755, 32737, 13, 5810, 11, 304, 264, 5258, 1545, 315, 1057, 3766, 18679, 4403, 64575, 4007, 315, 328, 1846, 510, 220, 24, 10881, 584, 25078, 422, 7231, 4495, 477, 15465, 2038, 922, 279, 5623, 22223, 1446, 26934, 75439, 323, 27420, 8778, 75439, 90351, 2796, 439, 32448, 449, 20940, 2298, 41353, 10390, 5814, 320, 80504, 8, 323, 279, 7701, 44010, 12164, 337, 343, 2914, 510, 220, 806, 356, 60, 35, 1950, 33, 323, 510, 220, 806, 356, 60, 1777, 17, 40, 11, 84072, 328, 3481, 82, 323, 40462, 82, 15947, 13, 30246, 389, 40774, 20588, 73565, 28896, 323, 14830, 100039, 1051, 26126, 994, 3920, 2223, 454, 2453, 574, 38018, 449, 323, 2085, 2867, 17078, 315, 16048, 11, 602, 1770, 2637, 43661, 6296, 13, 57593, 18679, 4403, 6514, 13, 19331, 52878, 1226, 20041, 264, 50359, 5258, 1545, 315, 264, 8767, 5068, 328, 1846, 6514, 41944, 11, 323, 369, 1749, 5848, 3649, 11, 584, 8464, 311, 430, 5684, 510, 220, 24, 21087, 7429, 11, 50359, 26954, 36595, 315, 328, 1846, 6978, 6296, 13, 9498, 11835, 617, 1027, 5068, 18403, 510, 220, 1419, 21087, 5810, 11, 220, 1544, 1314, 37240, 6978, 449, 328, 1846, 320, 1114, 3026, 11, 220, 605, 3278, 26, 3152, 20903, 8189, 4325, 11, 220, 2148, 13, 16, 20903, 220, 605, 13, 18, 1667, 8, 55093, 510, 220, 806, 356, 60, 35, 1950, 33, 323, 510, 220, 806, 356, 60, 1777, 17, 40, 50359, 32758, 1603, 323, 1306, 220, 24, 5672, 315, 3920, 2223, 454, 2453, 6514, 2345, 4151, 23966, 13, 328, 16, 323, 6771, 328, 16, 304, 279, 99371, 13, 5046, 1521, 11, 832, 8954, 25923, 1436, 539, 387, 5343, 304, 1772, 83, 35320, 510, 220, 806, 356, 60, 35, 1950, 33, 29060, 4245, 311, 21438, 8060, 13, 763, 5369, 311, 279, 5343, 6205, 11, 1403, 6978, 1051, 32448, 555, 50359, 520, 26954, 719, 1051, 28544, 505, 29060, 4245, 311, 24924, 58081, 32758, 320, 79770, 8, 6155, 467, 30780, 811, 11, 323, 30836, 505, 279, 4007, 1603, 8308, 52460, 11, 15947, 13, 28232, 5587, 220, 1114, 339, 220, 679, 19, 323, 3297, 220, 1313, 303, 220, 679, 20, 11, 13324, 1051, 45425, 1555, 43749, 304, 32594, 11, 586, 128257, 198, 128256, 78191, 198, 48091, 315, 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96404, 3957, 719, 574, 539, 3685, 311, 61705, 872, 3674, 18547, 13, 330, 791, 3135, 8710, 430, 4661, 3116, 3115, 439, 1690, 6978, 16846, 311, 279, 6514, 994, 4495, 2038, 922, 279, 5623, 574, 2728, 13, 1115, 374, 13263, 449, 3766, 3495, 9204, 430, 17078, 7958, 6514, 15632, 1359, 2795, 32185, 507, 385, 69, 473, 73, 2419, 13, 19408, 275, 2298, 41353, 10390, 5814, 320, 80504, 8, 8271, 36201, 8710, 430, 279, 18679, 4403, 5623, 1047, 279, 1890, 2515, 389, 77130, 323, 19857, 922, 220, 1490, 824, 2960, 315, 77130, 7710, 388, 304, 2225, 5315, 13, 1115, 574, 837, 1524, 369, 279, 1912, 430, 1047, 3428, 17078, 323, 1550, 539, 7417, 13, 330, 2028, 15151, 430, 279, 36449, 5848, 2515, 574, 20086, 304, 2225, 5315, 323, 430, 420, 4250, 10552, 3249, 4495, 2038, 6688, 2731, 6514, 3135, 13, 2100, 11, 20747, 5977, 77130, 7710, 388, 374, 39413, 369, 32145, 1695, 14830, 16337, 505, 3674, 18547, 1701, 18679, 4403, 11217, 1210, 3277, 47614, 279, 73565, 13128, 369, 66128, 1306, 6514, 11, 4869, 11, 264, 2867, 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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Granulomas are organized immune cell aggregates formed in response to chronic infection or antigen persistence. The bacterial pathogen Yersinia pseudotuberculosis ( Yp ) blocks innate inflammatory signalling and immune defence, inducing neutrophil-rich pyogranulomas (PGs) within lymphoid tissues. Here we uncover that Yp also triggers PG formation within the murine intestinal mucosa. Mice lacking circulating monocytes fail to form defined PGs, have defects in neutrophil activation and succumb to Yp infection. Yersinia lacking virulence factors that target actin polymerization to block phagocytosis and reactive oxygen burst do not induce PGs, indicating that intestinal PGs form in response to Yp disruption of cytoskeletal dynamics. Notably, mutation of the virulence factor YopH restores PG formation and control of Yp in mice lacking circulating monocytes, demonstrating that monocytes override YopH-dependent blockade of innate immune defence. This work reveals an unappreciated site of Yersinia intestinal invasion and defines host and pathogen drivers of intestinal granuloma formation. Main Microbial pathogens utilize diverse mechanisms to subvert host immunity to replicate and spread to new hosts. While acute infections can be cleared rapidly by the immune system, some pathogens evade immune defences to cause chronic disease. Chronic infections often result in formation of structures termed granulomas that limit pathogen dissemination and tissue damage 1 . Granulomas are characterized by the presence of activated phagocytes, notably monocytes and macrophages, and form in response to a wide variety of infections 2 . Monocytes are rapidly recruited to infected tissues, where they produce inflammatory cytokines and antimicrobial effector molecules, contributing to defence against multiple pathogens 3 , 4 , 5 , 6 . Some pathogens, however, exploit monocytes as a means of dissemination, including Salmonella enterica , Yersinia pestis and Mycobacterium species 7 , 8 , 9 . The pathogen-specific signals that induce granuloma formation remain poorly defined. Enteropathogenic Yersinia , including Y. pseudotuberculosis ( Yp ) and Y. enterocolitica ( Ye ), cause self-limiting gastroenteritis and mesenteric lymphadenopathy following enteric infection 10 , 11 . In immune-compromised patients, however, bacteria disseminate and cause a systemic plague-like disease, indicating that the intestinal immune system is critical for control of acute infection. Indeed, the intestine constitutes a bottleneck against Yersinia dissemination, as bacteria in systemic organs are thought to originate predominantly from the intestinal lumen rather than gut-associated lymphoid tissues 12 . A hallmark of Yersinia infections is the presence of chronic pyogranulomas (PGs) in lymphoid tissue, characterized by nodular infiltrates of activated monocytes and macrophages surrounding a core of activated neutrophils 13 . Notably, the contribution of monocytes to PG formation and their role in Yersinia restriction are unclear 14 , 15 . In this Article, we report that PGs form acutely in the murine intestinal mucosa during enteric Yersinia infection. PGs are enriched in neutrophils and inflammatory monocytes, and contain live bacteria at levels comparable to Peyer’s patches (PPs). Notably, CCR2-deficient mice, which lack circulating inflammatory monocytes 16 , 17 , form disorganized necrosuppurative lesions rather than defined PGs, are unable to contain bacteria within the lesions and succumb rapidly to infection. Moreover, mice lacking circulating monocytes exhibit reduced levels of interleukin (IL)-1 cytokines and surface expression of the neutrophil activation marker CD11b within intestinal PGs. Yp lacking either the virulence plasmid (pYV) encoding the type III secreted Yersinia Outer Proteins (Yops), or lacking Yops that block phagocytosis and the reactive oxygen burst, do not induce detectable PGs, indicating that PGs are induced in response to Yersinia blockade of innate immune defence. Notably, CCR2-deficient mice infected with bacteria lacking the virulence factor YopH, which blocks actin cytoskeleton dynamics, were able to restrict bacterial burdens and form defined granulomatous lesions, accompanied by restored neutrophil CD11b surface expression. Neutrophil depletion in CCR2-deficient animals abrogates control of YopH-mutant Yersinia , demonstrating that inflammatory monocytes overcome YopH-mediated disruption of neutrophil function. Altogether, our study identifies an unappreciated site of Yersinia colonization within the murine intestinal mucosa, and reveals an essential function for inflammatory monocytes in maintainance of PG architecture during Yp infection. Results Intestinal PGs form upon oral Yersinia infection Yp colonizes gut-associated lymphoid tissues, resulting in acute PG formation following oral infection 18 . Interactions between Yersinia and immune cells within systemic tissues have been extensively documented 19 , 20 , 21 . In our efforts to dissect intestinal immune responses to Yp , we observed numerous macroscopically visible nodular lesions in the gastrointestinal tract 5 days post infection, which appeared as punctate areas of increased opacity (Fig. 1a ). Lesions were most prevalent in the jejunum and ileum, ranged in number from two to over 40 in individual mice and also formed in response to Ye infection (Fig. 1b,c ). Histology of Yp- infected intestines revealed focal inflammation characterized by crypt hyperplasia, oedema and submucosal to transmural cellular infiltration, whereas non-lesional areas of infected intestines appeared largely unaffected (Fig. 1d ). The lesions contained infiltrates of macrophages and neutrophils surrounding colonies of coccobacilli, similar to structures that we and others observed in lymphoid tissues and have termed PGs (Fig. 1e ) (refs. 15 , 18 , 22 ). Consistently, flow cytometric analysis of intestinal punch biopsies containing PGs (PG+), adjacent non-granulomatous tissue (PG−), and uninfected control tissue revealed that neutrophils were the most enriched cell type within PG+ tissue, followed by macrophages and inflammatory monocytes (Fig. 1f,g ). We also observed increases in eosinophils, dendritic cells and CD4 + T cells in PG+ tissue, although the relative frequencies of these populations were decreased, due to even larger increases in neutrophils, monocytes and macrophages (Extended Data Fig. 1a,b ). Fig. 1: Intestinal PGs form upon oral Yersinia infection. a , Small intestinal segments from uninfected (uninf) and Yp -infected mice with arrows depicting lesions, and a magnified lesion with dotted circle depicting size of punch biopsies. Scale bars, 3 mm (left) and 0.5 mm (right). Representative of more than three independent experiments. b , Frequency distribution of lesions along the intestine, with graphical key of anatomical segments. Each coloured bar represents the mean frequency of lesions in a given segment ( n", "role": "user" }, { "content": "Yersinia bacteria cause a variety of human and animal diseases, the most notorious being the plague, caused by Yersinia pestis. A relative, Yersinia pseudotuberculosis, causes gastrointestinal illness and is less deadly, but naturally infects both mice and humans, making it a useful model for studying its interactions with the immune system. These two pathogens, as well as a third close cousin, Y. enterocolitica, which affects swine and can cause food-borne illness if people consume infected meat, have many traits in common, particularly their knack for interfering with the immune system's ability to respond to infection. The plague pathogen is blood-borne and transmitted by infected fleas. Infection with the other two depends on ingestion. Yet the focus of much of the work in the field had been on interactions of Yersinia with lymphoid tissues, rather than the intestine. A new study of Y. pseudotuberculosis, led by a team from Penn's School of Veterinary Medicine and published in Nature Microbiology demonstrates that in response to infection, the host immune system forms small, walled-off lesions in the intestines called granulomas. It's the first time these organized collections of immune cells have been found in the intestines in response to Yersinia infections. The team went on to show that monocytes, a type of immune cell, sustain these granulomas. Without them, the granulomas deteriorated, allowing the mice to be overtaken by Yersinia. \"Our data reveal a previously unappreciated site where Yersinia can colonize and the immune system is engaged,\" says Igor Brodsky, senior author on the work and a professor and chair of pathobiology at Penn Vet. \"These granulomas form in order to control the bacterial infection in the intestines. And we show that if they don't form or fail to be maintained, the bacteria are able to overcome the control of the immune system and cause greater systemic infection.\" The findings have implications for developing new therapies that leverage the host immune system, Brodsky says. A drug that harnessed the power of immune cells to not only keep Yersinia in check but to overcome its defenses, the researchers say, could potentially eliminate the pathogen altogether. A novel battlefield Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica share a keen ability to evade immune detection. \"In all three Yersinia infections, a hallmark is that they colonize lymphoid tissues and are able to escape immune control and replicate, cause disease, and spread,\" Brodsky says. Earlier studies had shown that Yersinia prompted the formation of granulomas in the lymph nodes and spleen but had never observed them in the intestines until Daniel Sorobetea, a research fellow in Brodsky's group, took a closer look at the intestines of mice infected with Y. pseudotuberculosis. \"Because it's an orally acquired pathogen, we were interested in how the bacteria behaved in the intestines,\" Brodsky says. \"Daniel made this initial observation that following Yersinia pseudotuberculosis infection, there were macroscopically visible lesions all along the length of the gut that had never been described before.\" The research team, including Sorobetea and later Rina Matsuda, a doctoral student in the lab, saw that these same lesions were present when mice were infected with Y. enterocolitica, forming within five days after an infection. A biopsy of the intestinal tissues confirmed that the lesions were a type of granuloma, known as a pyogranuloma, composed of a variety of immune cells, including monocytes and neutrophils, another type of white blood cell that is part of the body's front line in fighting bacteria and viruses. Granulomas form in other diseases that involve chronic infection, including tuberculosis, for which Y. pseudotuberculosis is named. Somewhat paradoxically, these granulomas—while key in controlling infection by walling off the infectious agent—also sustain a population of the pathogen within those walls. The team wanted to understand how these granulomas were both formed and maintained, working with mice lacking monocytes as well as animals treated with an antibody that depletes monocytes. In the animals lacking monocytes \"these granulomas, with their distinct architecture, wouldn't form,\" Brodsky says. Instead, a more disorganized and necrotic abscess developed, neutrophils failed to be activated, and the mice were less able to control the invading bacteria. These animals experienced higher levels of bacteria in their intestines and succumbed to their infections. Groundwork for the future The researchers believe the monocytes are responsible for recruiting neutrophils to the site of infection and thus launching the formation of the granuloma, helping to control the bacteria. This leading role for monocytes may exist beyond the intestines, the researchers believe. \"We hypothesize that it's a general role for the monocytes in other tissues as well,\" Brodsky says. But the discoveries also point to the intestines as a key site of engagement between the immune system and Yersinia. \"Previous to this study, we knew of Peyer's patches to be the primary site where the body interacts with the outside environment through the mucosal tissue of the intestines,\" says Brodsky. Peyer's patches are small areas of lymphoid tissue present in the intestines that serve to regulate the microbiome and fend off infection. In future work, Brodsky and colleagues hope to continue to piece together the mechanism by which monocytes and neutrophils contain the bacteria, an effort they're pursing in collaboration with Sunny Shin's lab in the Perelman School of Medicine's microbiology department. A deeper understanding of the molecular pathways that regulate this immune response could one day offer inroads into host-directed immune therapies, by which a drug could tip the scales in favor of the host immune system, unleashing its might to fully eradicate the bacteria rather than simply corralling them in granulomas. \"These therapies have caused an explosion of excitement in the cancer field,\" Brodsky says, \"the idea of reinvigorating the immune system. Conceptually we can also think about how to coax the immune system to be reinvigorated to attack pathogens in these settings of chronic infection as well.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Granulomas are organized immune cell aggregates formed in response to chronic infection or antigen persistence. The bacterial pathogen Yersinia pseudotuberculosis ( Yp ) blocks innate inflammatory signalling and immune defence, inducing neutrophil-rich pyogranulomas (PGs) within lymphoid tissues. Here we uncover that Yp also triggers PG formation within the murine intestinal mucosa. Mice lacking circulating monocytes fail to form defined PGs, have defects in neutrophil activation and succumb to Yp infection. Yersinia lacking virulence factors that target actin polymerization to block phagocytosis and reactive oxygen burst do not induce PGs, indicating that intestinal PGs form in response to Yp disruption of cytoskeletal dynamics. Notably, mutation of the virulence factor YopH restores PG formation and control of Yp in mice lacking circulating monocytes, demonstrating that monocytes override YopH-dependent blockade of innate immune defence. This work reveals an unappreciated site of Yersinia intestinal invasion and defines host and pathogen drivers of intestinal granuloma formation. Main Microbial pathogens utilize diverse mechanisms to subvert host immunity to replicate and spread to new hosts. While acute infections can be cleared rapidly by the immune system, some pathogens evade immune defences to cause chronic disease. Chronic infections often result in formation of structures termed granulomas that limit pathogen dissemination and tissue damage 1 . Granulomas are characterized by the presence of activated phagocytes, notably monocytes and macrophages, and form in response to a wide variety of infections 2 . Monocytes are rapidly recruited to infected tissues, where they produce inflammatory cytokines and antimicrobial effector molecules, contributing to defence against multiple pathogens 3 , 4 , 5 , 6 . Some pathogens, however, exploit monocytes as a means of dissemination, including Salmonella enterica , Yersinia pestis and Mycobacterium species 7 , 8 , 9 . The pathogen-specific signals that induce granuloma formation remain poorly defined. Enteropathogenic Yersinia , including Y. pseudotuberculosis ( Yp ) and Y. enterocolitica ( Ye ), cause self-limiting gastroenteritis and mesenteric lymphadenopathy following enteric infection 10 , 11 . In immune-compromised patients, however, bacteria disseminate and cause a systemic plague-like disease, indicating that the intestinal immune system is critical for control of acute infection. Indeed, the intestine constitutes a bottleneck against Yersinia dissemination, as bacteria in systemic organs are thought to originate predominantly from the intestinal lumen rather than gut-associated lymphoid tissues 12 . A hallmark of Yersinia infections is the presence of chronic pyogranulomas (PGs) in lymphoid tissue, characterized by nodular infiltrates of activated monocytes and macrophages surrounding a core of activated neutrophils 13 . Notably, the contribution of monocytes to PG formation and their role in Yersinia restriction are unclear 14 , 15 . In this Article, we report that PGs form acutely in the murine intestinal mucosa during enteric Yersinia infection. PGs are enriched in neutrophils and inflammatory monocytes, and contain live bacteria at levels comparable to Peyer’s patches (PPs). Notably, CCR2-deficient mice, which lack circulating inflammatory monocytes 16 , 17 , form disorganized necrosuppurative lesions rather than defined PGs, are unable to contain bacteria within the lesions and succumb rapidly to infection. Moreover, mice lacking circulating monocytes exhibit reduced levels of interleukin (IL)-1 cytokines and surface expression of the neutrophil activation marker CD11b within intestinal PGs. Yp lacking either the virulence plasmid (pYV) encoding the type III secreted Yersinia Outer Proteins (Yops), or lacking Yops that block phagocytosis and the reactive oxygen burst, do not induce detectable PGs, indicating that PGs are induced in response to Yersinia blockade of innate immune defence. Notably, CCR2-deficient mice infected with bacteria lacking the virulence factor YopH, which blocks actin cytoskeleton dynamics, were able to restrict bacterial burdens and form defined granulomatous lesions, accompanied by restored neutrophil CD11b surface expression. Neutrophil depletion in CCR2-deficient animals abrogates control of YopH-mutant Yersinia , demonstrating that inflammatory monocytes overcome YopH-mediated disruption of neutrophil function. Altogether, our study identifies an unappreciated site of Yersinia colonization within the murine intestinal mucosa, and reveals an essential function for inflammatory monocytes in maintainance of PG architecture during Yp infection. Results Intestinal PGs form upon oral Yersinia infection Yp colonizes gut-associated lymphoid tissues, resulting in acute PG formation following oral infection 18 . Interactions between Yersinia and immune cells within systemic tissues have been extensively documented 19 , 20 , 21 . In our efforts to dissect intestinal immune responses to Yp , we observed numerous macroscopically visible nodular lesions in the gastrointestinal tract 5 days post infection, which appeared as punctate areas of increased opacity (Fig. 1a ). Lesions were most prevalent in the jejunum and ileum, ranged in number from two to over 40 in individual mice and also formed in response to Ye infection (Fig. 1b,c ). Histology of Yp- infected intestines revealed focal inflammation characterized by crypt hyperplasia, oedema and submucosal to transmural cellular infiltration, whereas non-lesional areas of infected intestines appeared largely unaffected (Fig. 1d ). The lesions contained infiltrates of macrophages and neutrophils surrounding colonies of coccobacilli, similar to structures that we and others observed in lymphoid tissues and have termed PGs (Fig. 1e ) (refs. 15 , 18 , 22 ). Consistently, flow cytometric analysis of intestinal punch biopsies containing PGs (PG+), adjacent non-granulomatous tissue (PG−), and uninfected control tissue revealed that neutrophils were the most enriched cell type within PG+ tissue, followed by macrophages and inflammatory monocytes (Fig. 1f,g ). We also observed increases in eosinophils, dendritic cells and CD4 + T cells in PG+ tissue, although the relative frequencies of these populations were decreased, due to even larger increases in neutrophils, monocytes and macrophages (Extended Data Fig. 1a,b ). Fig. 1: Intestinal PGs form upon oral Yersinia infection. a , Small intestinal segments from uninfected (uninf) and Yp -infected mice with arrows depicting lesions, and a magnified lesion with dotted circle depicting size of punch biopsies. Scale bars, 3 mm (left) and 0.5 mm (right). Representative of more than three independent experiments. b , Frequency distribution of lesions along the intestine, with graphical key of anatomical segments. Each coloured bar represents the mean frequency of lesions in a given segment ( n<|im_end|> <|im_start|>assistant Yersinia bacteria cause a variety of human and animal diseases, the most notorious being the plague, caused by Yersinia pestis. A relative, Yersinia pseudotuberculosis, causes gastrointestinal illness and is less deadly, but naturally infects both mice and humans, making it a useful model for studying its interactions with the immune system. These two pathogens, as well as a third close cousin, Y. enterocolitica, which affects swine and can cause food-borne illness if people consume infected meat, have many traits in common, particularly their knack for interfering with the immune system's ability to respond to infection. The plague pathogen is blood-borne and transmitted by infected fleas. Infection with the other two depends on ingestion. Yet the focus of much of the work in the field had been on interactions of Yersinia with lymphoid tissues, rather than the intestine. A new study of Y. pseudotuberculosis, led by a team from Penn's School of Veterinary Medicine and published in Nature Microbiology demonstrates that in response to infection, the host immune system forms small, walled-off lesions in the intestines called granulomas. It's the first time these organized collections of immune cells have been found in the intestines in response to Yersinia infections. The team went on to show that monocytes, a type of immune cell, sustain these granulomas. Without them, the granulomas deteriorated, allowing the mice to be overtaken by Yersinia. "Our data reveal a previously unappreciated site where Yersinia can colonize and the immune system is engaged," says Igor Brodsky, senior author on the work and a professor and chair of pathobiology at Penn Vet. "These granulomas form in order to control the bacterial infection in the intestines. And we show that if they don't form or fail to be maintained, the bacteria are able to overcome the control of the immune system and cause greater systemic infection." The findings have implications for developing new therapies that leverage the host immune system, Brodsky says. A drug that harnessed the power of immune cells to not only keep Yersinia in check but to overcome its defenses, the researchers say, could potentially eliminate the pathogen altogether. A novel battlefield Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica share a keen ability to evade immune detection. "In all three Yersinia infections, a hallmark is that they colonize lymphoid tissues and are able to escape immune control and replicate, cause disease, and spread," Brodsky says. Earlier studies had shown that Yersinia prompted the formation of granulomas in the lymph nodes and spleen but had never observed them in the intestines until Daniel Sorobetea, a research fellow in Brodsky's group, took a closer look at the intestines of mice infected with Y. pseudotuberculosis. "Because it's an orally acquired pathogen, we were interested in how the bacteria behaved in the intestines," Brodsky says. "Daniel made this initial observation that following Yersinia pseudotuberculosis infection, there were macroscopically visible lesions all along the length of the gut that had never been described before." The research team, including Sorobetea and later Rina Matsuda, a doctoral student in the lab, saw that these same lesions were present when mice were infected with Y. enterocolitica, forming within five days after an infection. A biopsy of the intestinal tissues confirmed that the lesions were a type of granuloma, known as a pyogranuloma, composed of a variety of immune cells, including monocytes and neutrophils, another type of white blood cell that is part of the body's front line in fighting bacteria and viruses. Granulomas form in other diseases that involve chronic infection, including tuberculosis, for which Y. pseudotuberculosis is named. Somewhat paradoxically, these granulomas—while key in controlling infection by walling off the infectious agent—also sustain a population of the pathogen within those walls. The team wanted to understand how these granulomas were both formed and maintained, working with mice lacking monocytes as well as animals treated with an antibody that depletes monocytes. In the animals lacking monocytes "these granulomas, with their distinct architecture, wouldn't form," Brodsky says. Instead, a more disorganized and necrotic abscess developed, neutrophils failed to be activated, and the mice were less able to control the invading bacteria. These animals experienced higher levels of bacteria in their intestines and succumbed to their infections. Groundwork for the future The researchers believe the monocytes are responsible for recruiting neutrophils to the site of infection and thus launching the formation of the granuloma, helping to control the bacteria. This leading role for monocytes may exist beyond the intestines, the researchers believe. "We hypothesize that it's a general role for the monocytes in other tissues as well," Brodsky says. But the discoveries also point to the intestines as a key site of engagement between the immune system and Yersinia. "Previous to this study, we knew of Peyer's patches to be the primary site where the body interacts with the outside environment through the mucosal tissue of the intestines," says Brodsky. Peyer's patches are small areas of lymphoid tissue present in the intestines that serve to regulate the microbiome and fend off infection. In future work, Brodsky and colleagues hope to continue to piece together the mechanism by which monocytes and neutrophils contain the bacteria, an effort they're pursing in collaboration with Sunny Shin's lab in the Perelman School of Medicine's microbiology department. A deeper understanding of the molecular pathways that regulate this immune response could one day offer inroads into host-directed immune therapies, by which a drug could tip the scales in favor of the host immune system, unleashing its might to fully eradicate the bacteria rather than simply corralling them in granulomas. "These therapies have caused an explosion of excitement in the cancer field," Brodsky says, "the idea of reinvigorating the immune system. Conceptually we can also think about how to coax the immune system to be reinvigorated to attack pathogens in these settings of chronic infection as well." <|im_end|>

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2015, 311, 2585, 279, 45964, 19405, 304, 279, 39408, 1572, 13, 1628, 584, 1501, 430, 422, 814, 1541, 956, 1376, 477, 3775, 311, 387, 18908, 11, 279, 24032, 527, 3025, 311, 23075, 279, 2585, 315, 279, 22852, 1887, 323, 5353, 7191, 46417, 19405, 1210, 578, 14955, 617, 25127, 369, 11469, 502, 52312, 430, 33164, 279, 3552, 22852, 1887, 11, 6031, 67, 27782, 2795, 13, 362, 5623, 430, 305, 1923, 22456, 279, 2410, 315, 22852, 7917, 311, 539, 1193, 2567, 816, 388, 91550, 304, 1817, 719, 311, 23075, 1202, 46616, 11, 279, 12074, 2019, 11, 1436, 13893, 22472, 279, 1853, 11968, 31155, 13, 362, 11775, 38486, 816, 13, 44885, 285, 11, 816, 13, 51743, 354, 392, 74554, 11, 323, 816, 13, 3810, 4650, 275, 3074, 4430, 264, 27989, 5845, 311, 77753, 22852, 18468, 13, 330, 644, 682, 2380, 816, 388, 91550, 30020, 11, 264, 98799, 374, 430, 814, 15235, 553, 43745, 590, 39881, 323, 527, 3025, 311, 12731, 22852, 2585, 323, 46113, 11, 5353, 8624, 11, 323, 9041, 1359, 6031, 67, 27782, 2795, 13, 47993, 7978, 1047, 6982, 430, 816, 388, 91550, 29746, 279, 18488, 315, 16109, 360, 23063, 304, 279, 43745, 7954, 323, 87450, 268, 719, 1047, 2646, 13468, 1124, 304, 279, 39408, 1572, 3156, 15469, 30631, 677, 7870, 64, 11, 264, 3495, 12637, 304, 6031, 67, 27782, 596, 1912, 11, 3952, 264, 12401, 1427, 520, 279, 39408, 1572, 315, 24548, 29374, 449, 816, 13, 51743, 354, 392, 74554, 13, 330, 18433, 433, 596, 459, 98122, 19426, 1853, 11968, 11, 584, 1051, 8173, 304, 1268, 279, 24032, 89831, 304, 279, 39408, 1572, 1359, 6031, 67, 27782, 2795, 13, 330, 41686, 1903, 420, 2926, 22695, 430, 2768, 816, 388, 91550, 51743, 354, 392, 74554, 19405, 11, 1070, 1051, 18563, 2445, 454, 2740, 9621, 63324, 682, 3235, 279, 3160, 315, 279, 18340, 430, 1047, 2646, 1027, 7633, 1603, 1210, 578, 3495, 2128, 11, 2737, 30631, 677, 7870, 64, 323, 3010, 432, 2259, 68279, 8213, 11, 264, 74657, 5575, 304, 279, 10278, 11, 5602, 430, 1521, 1890, 63324, 1051, 3118, 994, 24548, 1051, 29374, 449, 816, 13, 3810, 4650, 275, 3074, 11, 30164, 2949, 4330, 2919, 1306, 459, 19405, 13, 362, 99647, 315, 279, 63900, 39881, 11007, 430, 279, 63324, 1051, 264, 955, 315, 16109, 360, 7942, 11, 3967, 439, 264, 4611, 540, 6713, 360, 7942, 11, 24306, 315, 264, 8205, 315, 22852, 7917, 11, 2737, 1647, 57878, 323, 26878, 22761, 8839, 11, 2500, 955, 315, 4251, 6680, 2849, 430, 374, 961, 315, 279, 2547, 596, 4156, 1584, 304, 11039, 24032, 323, 42068, 13, 27622, 360, 23063, 1376, 304, 1023, 19338, 430, 21736, 21249, 19405, 11, 2737, 88234, 11, 369, 902, 816, 13, 51743, 354, 392, 74554, 374, 7086, 13, 18024, 81575, 52313, 2740, 11, 1521, 16109, 360, 23063, 2345, 3556, 1401, 304, 26991, 19405, 555, 7147, 287, 1022, 279, 50600, 8479, 2345, 19171, 14201, 264, 7187, 315, 279, 1853, 11968, 2949, 1884, 14620, 13, 578, 2128, 4934, 311, 3619, 1268, 1521, 16109, 360, 23063, 1051, 2225, 14454, 323, 18908, 11, 3318, 449, 24548, 32161, 1647, 57878, 439, 1664, 439, 10099, 12020, 449, 459, 63052, 430, 409, 698, 2392, 1647, 57878, 13, 763, 279, 10099, 32161, 1647, 57878, 330, 45010, 16109, 360, 23063, 11, 449, 872, 12742, 18112, 11, 8434, 956, 1376, 1359, 6031, 67, 27782, 2795, 13, 12361, 11, 264, 810, 834, 63316, 323, 19591, 4744, 292, 3731, 1140, 8040, 11, 26878, 22761, 8839, 4745, 311, 387, 22756, 11, 323, 279, 24548, 1051, 2753, 3025, 311, 2585, 279, 83631, 24032, 13, 4314, 10099, 10534, 5190, 5990, 315, 24032, 304, 872, 39408, 1572, 323, 20639, 99696, 311, 872, 30020, 13, 26486, 1816, 369, 279, 3938, 578, 12074, 4510, 279, 1647, 57878, 527, 8647, 369, 32959, 26878, 22761, 8839, 311, 279, 2816, 315, 19405, 323, 8617, 28818, 279, 18488, 315, 279, 16109, 360, 7942, 11, 10695, 311, 2585, 279, 24032, 13, 1115, 6522, 3560, 369, 1647, 57878, 1253, 3073, 7953, 279, 39408, 1572, 11, 279, 12074, 4510, 13, 330, 1687, 22601, 27985, 430, 433, 596, 264, 4689, 3560, 369, 279, 1647, 57878, 304, 1023, 39881, 439, 1664, 1359, 6031, 67, 27782, 2795, 13, 2030, 279, 54098, 1101, 1486, 311, 279, 39408, 1572, 439, 264, 1401, 2816, 315, 20392, 1990, 279, 22852, 1887, 323, 816, 388, 91550, 13, 330, 21994, 311, 420, 4007, 11, 584, 7020, 315, 393, 35472, 596, 29760, 311, 387, 279, 6156, 2816, 1405, 279, 2547, 84261, 449, 279, 4994, 4676, 1555, 279, 65104, 33656, 20438, 315, 279, 39408, 1572, 1359, 2795, 6031, 67, 27782, 13, 393, 35472, 596, 29760, 527, 2678, 5789, 315, 43745, 590, 20438, 3118, 304, 279, 39408, 1572, 430, 8854, 311, 37377, 279, 53499, 638, 323, 95127, 1022, 19405, 13, 763, 3938, 990, 11, 6031, 67, 27782, 323, 18105, 3987, 311, 3136, 311, 6710, 3871, 279, 17383, 555, 902, 1647, 57878, 323, 26878, 22761, 8839, 6782, 279, 24032, 11, 459, 5149, 814, 2351, 10037, 287, 304, 20632, 449, 56138, 35549, 596, 10278, 304, 279, 3700, 64641, 6150, 315, 19152, 596, 53499, 2508, 9476, 13, 362, 19662, 8830, 315, 279, 31206, 44014, 430, 37377, 420, 22852, 2077, 1436, 832, 1938, 3085, 304, 43791, 1139, 3552, 86855, 22852, 52312, 11, 555, 902, 264, 5623, 1436, 11813, 279, 29505, 304, 4799, 315, 279, 3552, 22852, 1887, 11, 38826, 19587, 1202, 2643, 311, 7373, 89514, 279, 24032, 4856, 1109, 5042, 45453, 17157, 1124, 304, 16109, 360, 23063, 13, 330, 9673, 52312, 617, 9057, 459, 25176, 315, 28361, 304, 279, 9572, 2115, 1359, 6031, 67, 27782, 2795, 11, 330, 1820, 4623, 315, 312, 14386, 71070, 1113, 279, 22852, 1887, 13, 35455, 1870, 584, 649, 1101, 1781, 922, 1268, 311, 91966, 279, 22852, 1887, 311, 387, 312, 14386, 71070, 660, 311, 3440, 78284, 304, 1521, 5110, 315, 21249, 19405, 439, 1664, 1210, 220, 128257, 198 ]

2,852

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Defining drivers of tumour initiation can provide opportunities to control cancer progression. Here we report that lysophosphatidic acid receptor 4 (LPAR4) becomes transiently upregulated on pancreatic cancer cells exposed to environmental stress or chemotherapy where it promotes stress tolerance, drug resistance, self-renewal and tumour initiation. Pancreatic cancer cells gain LPAR4 expression in response to stress by downregulating a tumour suppressor, miR-139-5p. Even in the absence of exogenous lysophosphatidic acid, LPAR4-expressing tumour cells display an enrichment of extracellular matrix genes that are established drivers of cancer stemness. Mechanistically, upregulation of fibronectin via an LPAR4/AKT/CREB axis is indispensable for LPAR4-induced tumour initiation and stress tolerance. Moreover, ligation of this fibronectin-containing matrix via integrins α5β1 or αVβ3 can transfer stress tolerance to LPAR4-negative cells. Therefore, stress- or drug-induced LPAR4 enhances cell-autonomous production of a fibronectin-rich extracellular matrix, allowing cells to survive ‘isolation stress’ and compensate for the absence of stromal-derived factors by creating their own tumour-initiating niche. Main Tumour-initiating cells (TICs) are critical contributors to tumour growth, recurrence and metastatic spread by virtue of their capacity to overcome various forms of stress 1 , 2 . Such features are not only derived from intrinsic stem-like traits but can be influenced by tumour stroma-derived immune cell factors within a cancer stem cell (CSC) niche 3 . One such factor is lysophosphatidic acid (LPA) 4 , a bioactive lipid that regulates cell fate transitions for a variety of stem cell types, including CSCs 5 , 6 . We are particularly interested in how TIC properties may fluctuate in response to external cues 7 , such as changes in vascularization that impact oxygenation and access to nutrients, or application of therapeutic pressures designed to eliminate vulnerable populations of tumour cells. At the earliest stage of tumour formation or during seeding of metastatic cells in distant organs, individual tumour cells must overcome the challenging consequences of isolation-induced stresses such as hypoxia, nutrient deprivation and oxidative stress, while compensating for the loss of matrix adhesion, cell–cell contact or immune cell and stromal-produced survival factors 8 , 9 . While TICs may inherently possess resistance to such stresses, we considered whether non-TICs may undergo adaptive reprogramming to overcome isolation stress and thereby gain tumour-initiating properties. Pancreatic cancer is a lethal cancer that is notoriously resilient to therapy due in part to poor vascularization and dense stroma in the tumour microenvironment 10 . LPA and the enzyme that produces LPA, autotaxin, are particularly enriched in pancreatic cancer 11 , 12 , which can exploit LPA produced by neighbouring pancreatic stellate cells to drive pacreatic ductal adenocarcinoma (PDAC) growth in vivo 12 . Functions of the six G-protein-coupled LPA receptors (LPAR1–6) do not appear to overlap in pancreatic cancer cells. LPAR1 promotes cell migration and metastasis 13 , 14 , while LPAR2 suppresses migration 15 . Interestingly, LPAR4 suppresses mobility in PANC1 cells 16 but is also necessary for cardiac dedifferentiation and heart tissue repair 17 , suggesting a context-dependent role. In this Article, we discovered that LPAR4 becomes upregulated by the stress-induced loss of a tumour-suppressive microRNA (miRNA) and is capable of conferring TIC properties, stress tolerance and drug resistance. Mechanistically, LPAR4 expression endows solitary tumour cells with the ability to create their own fibronectin-containing niche to support tumour initiation. The molecular basis for this adaptive reprogramming mechanism may provide therapeutic opportunities to slow pancreatic cancer progression and sensitize tumours to therapeutic intervention. Results Pancreatic cancer cells upregulate LPAR4 in response to stress Tumour cells must overcome various stressors during tumour initiation and progression, including hypoxia, nutrient stress, loss of adhesion, oxidative stress and therapeutic stress. Given the role of autotaxin/LPA in pancreatic cancer progression 12 , we asked whether one or more LPA receptor(s) are linked to tumour initiation. To create tumour growth conditions that would selectively favour the survival of TICs in vivo, nu/nu mice received a subcutaneous injection of 300 pancreatic cancer cells, a cell number we established produces palpable tumours in approximately 50% of the injection sites after 14 days (Fig. 1a ). Compared with an injection of 1 million cells resulting in tumour growth at all injection sites, we propose that tumours formed from a limiting number of cells create a state of ‘isolation stress’ that highlights the contribution of tumour-initiating and/or self-renewing cells. Among the six LPA receptors, only LPAR4 was enriched in isolation-stressed tumours formed by 300 cells (Fig. 1a,b ). Interestingly, LPAR4 expression was significantly higher in early-stage (day 20) lesions versus established (day 35) tumours (Fig. 1c ), indicating that LPAR4 is transiently expressed when tumour cells are experiencing ‘isolation stress’ but downregulated as tumours become established. Compared with cells grown in 2D adherent culture conditions, LPAR4 messenger RNA (mRNA) was highly enriched in the self-renewing cells that form secondary tumourspheres (Fig. 1d ). Thus, LPAR4 is upregulated under in vitro and in vivo conditions that enrich for TICs. Fig. 1: Pancreatic cancer cells selectively upregulate LPAR4 in response to isolation stress. a , log 2 fold change (log 2 FC) for all LPAR s mRNA expression in ‘self-renewing’ tumours formed by subcutaneous injection of 300 cells of Colo-357 (pink dots, n = 6 biologically independent samples), 79E (black dots, n = 4 biologically independent samples) or 34E (blue dots, n = 6 biologically independent samples) with respect to ‘bulk’ tumours formed by injection of 1 million (1 M) cells of Colo-357 ( n = 6 biologically independent samples), 79E ( n = 6 biologically independent samples) or 34E ( n = 5 biologically independent samples). b , Representative images of immunohistochemistry staining of LPAR4 in 79E xenograft tumours derived from 1 M cells ( n = 5 biologically independent samples) or 300 cells ( n = 4 biologically independent samples). Scale bar is 50 µm or 10 µm as indicated. c , Relative LPAR4 mRNA level (normalized to housekeeping genes) in xenograft tumours collected at early timepoint (day 20, early lesions) versus late timepoint (day 35, established tumours). Data are mean ± standard deviation (s.d.) ( n = 3,", "role": "user" }, { "content": "Researchers at University of California San Diego School of Medicine have discovered a molecular pathway critical to the initiation of pancreatic tumors. The mechanism could also contribute to the disease's high resistance to chemotherapy and its propensity for metastasis. The study, published on January 16, 2023, in Nature Cell Biology, found that pancreatic tumor-initiating cells must first overcome local \"isolation stress\" by creating their own tumor-promoting microenvironment, and then recruit surrounding cells into this network. By targeting this tumor-initiating pathway, new therapeutics could limit the progression, relapse and spread of pancreatic cancer. Pancreatic cancer is one of the most lethal cancers, notoriously resistant to treatment. Almost all patients experience cancer recurrence or metastasis. In the early stages of tumor formation, cancer cells (those with cancerous mutations, called oncogenes) experience a loss of adhesion to other cells and the extracellular matrix—the web of macromolecules that encase and support all cells. This isolation leads to a local lack of oxygen and nutrients. Most cells do not survive such isolation stress, but a certain group of cells can. Tumor-initiating cells (TIC) play a major role in the formation, recurrence and metastatic spread of tumors. What sets them apart from other cancer cells is their resilience to these early substandard conditions. Like cacti in a desert, they can adapt to the harsh environment and set the scene for further tumor progression. \"Our goal was to understand what special properties these tumor-initiating cells have and whether we can control the growth and spread of cancer by disrupting them,\" said senior study author David Cheresh, Ph.D., Distinguished Professor and vice chair of the Department of Pathology at UC San Diego School of Medicine and a member of the UC San Diego Moores Cancer Center. To answer these questions, first author Chengsheng Wu, Ph.D., a postdoctoral fellow in Cheresh's lab, subjected pancreatic cell lines to various forms of stress, including low oxygen and sugar levels. He then identified which cells could adapt to the harsh conditions and observed which genes and molecules were modified in these cells. The stress-tolerant tumor-initiating cells showed reduced levels of a tumor-suppressive microRNA, miR-139-5p. This in turn led to the upregulation of lysophosphatidic acid receptor 4 (LPAR4), a G-protein-coupled receptor on the cell surface. \"LPAR4 is not normally found on happy cells, but it gets turned on in stressful environments to help the cells survive, which is particularly advantageous for tumor-initiating cells,\" said Cheresh. Schematic: When a tumor-initiating cell experiences isolation stress, it begins expressing LPAR4. This leads to the production of a new extracellular matrix full of fibronectin (FN1), which keeps the cell safe and recruits other cells into the niche to begin tumor formation. Credit: UC San Diego Health Sciences The researchers found that LPAR4 expression promoted the production of new extracellular matrix proteins, allowing the solitary cancer cells to start building their own tumor-supporting microenvironment. The new extracellular matrix was particularly rich in fibronectin, a protein that binds to transmembrane receptors called integrins on surrounding cells. Once the integrins on these cells sensed the fibronectin, they began signaling the cells to express their own tumor-initiating genes. Eventually, these other cells were recruited into the fibronectin matrix laid by the tumor-initiating cells and a tumor started to form. \"Our findings establish a critical role for LPAR4 in pancreatic tumor initiation, and a likely role in other epithelial cancers, such as lung cancer,\" said Cheresh. \"It is central to tumor-initiating cells' ability to overcome isolation stress and build their own niche in which tumors can form.\" But isolation stress is not the only way this signaling pathway can be triggered, the researchers said. Chemotherapy drugs are also designed to put cancer cells under stress. Indeed, Cheresh's team found that treating cultured tumor cells and pancreatic tumors in mice with standard-of-care chemotherapeutics also led to the upregulation of LPAR4. The researchers said this might explain how such tumor cells could develop a stress tolerance and resistance to the drugs. Further experiments also showed that using integrin antagonists to block cells' ability to utilize the fibronectin matrix reversed the stress tolerance benefit of LPAR4 expression. Thus, the authors suggest targeting the LPAR4 pathway or disrupting the fibronectin/integrin interaction could be effective in preventing the growth, spread and drug resistance of pancreatic tumors. \"We can think of tumor-initiating cells as being in a transient state that can be induced by different stressors, so our clinical goal would be to prevent oncogenic cells from ever entering this state,\" said Cheresh. \"Now that we've identified the pathway, we can assess all the different ways we can intervene.\" The researchers suggested a new drug targeting this pathway could be used as a prophylactic in patients at high risk of developing the disease, or to prevent new tumors from forming in cancer cases with a high likelihood of metastasis. Pairing the new drug with existing chemotherapeutics that put stress on mature tumor cells could also mitigate the effects of drug resistance and make cancer treatments more effective, authors said. \"Treating cancer can feel a little like whack-a-mole,\" said Cheresh, \"but if we have two or three hammers and we know where the moles are going to pop up next, we can beat the game.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Defining drivers of tumour initiation can provide opportunities to control cancer progression. Here we report that lysophosphatidic acid receptor 4 (LPAR4) becomes transiently upregulated on pancreatic cancer cells exposed to environmental stress or chemotherapy where it promotes stress tolerance, drug resistance, self-renewal and tumour initiation. Pancreatic cancer cells gain LPAR4 expression in response to stress by downregulating a tumour suppressor, miR-139-5p. Even in the absence of exogenous lysophosphatidic acid, LPAR4-expressing tumour cells display an enrichment of extracellular matrix genes that are established drivers of cancer stemness. Mechanistically, upregulation of fibronectin via an LPAR4/AKT/CREB axis is indispensable for LPAR4-induced tumour initiation and stress tolerance. Moreover, ligation of this fibronectin-containing matrix via integrins α5β1 or αVβ3 can transfer stress tolerance to LPAR4-negative cells. Therefore, stress- or drug-induced LPAR4 enhances cell-autonomous production of a fibronectin-rich extracellular matrix, allowing cells to survive ‘isolation stress’ and compensate for the absence of stromal-derived factors by creating their own tumour-initiating niche. Main Tumour-initiating cells (TICs) are critical contributors to tumour growth, recurrence and metastatic spread by virtue of their capacity to overcome various forms of stress 1 , 2 . Such features are not only derived from intrinsic stem-like traits but can be influenced by tumour stroma-derived immune cell factors within a cancer stem cell (CSC) niche 3 . One such factor is lysophosphatidic acid (LPA) 4 , a bioactive lipid that regulates cell fate transitions for a variety of stem cell types, including CSCs 5 , 6 . We are particularly interested in how TIC properties may fluctuate in response to external cues 7 , such as changes in vascularization that impact oxygenation and access to nutrients, or application of therapeutic pressures designed to eliminate vulnerable populations of tumour cells. At the earliest stage of tumour formation or during seeding of metastatic cells in distant organs, individual tumour cells must overcome the challenging consequences of isolation-induced stresses such as hypoxia, nutrient deprivation and oxidative stress, while compensating for the loss of matrix adhesion, cell–cell contact or immune cell and stromal-produced survival factors 8 , 9 . While TICs may inherently possess resistance to such stresses, we considered whether non-TICs may undergo adaptive reprogramming to overcome isolation stress and thereby gain tumour-initiating properties. Pancreatic cancer is a lethal cancer that is notoriously resilient to therapy due in part to poor vascularization and dense stroma in the tumour microenvironment 10 . LPA and the enzyme that produces LPA, autotaxin, are particularly enriched in pancreatic cancer 11 , 12 , which can exploit LPA produced by neighbouring pancreatic stellate cells to drive pacreatic ductal adenocarcinoma (PDAC) growth in vivo 12 . Functions of the six G-protein-coupled LPA receptors (LPAR1–6) do not appear to overlap in pancreatic cancer cells. LPAR1 promotes cell migration and metastasis 13 , 14 , while LPAR2 suppresses migration 15 . Interestingly, LPAR4 suppresses mobility in PANC1 cells 16 but is also necessary for cardiac dedifferentiation and heart tissue repair 17 , suggesting a context-dependent role. In this Article, we discovered that LPAR4 becomes upregulated by the stress-induced loss of a tumour-suppressive microRNA (miRNA) and is capable of conferring TIC properties, stress tolerance and drug resistance. Mechanistically, LPAR4 expression endows solitary tumour cells with the ability to create their own fibronectin-containing niche to support tumour initiation. The molecular basis for this adaptive reprogramming mechanism may provide therapeutic opportunities to slow pancreatic cancer progression and sensitize tumours to therapeutic intervention. Results Pancreatic cancer cells upregulate LPAR4 in response to stress Tumour cells must overcome various stressors during tumour initiation and progression, including hypoxia, nutrient stress, loss of adhesion, oxidative stress and therapeutic stress. Given the role of autotaxin/LPA in pancreatic cancer progression 12 , we asked whether one or more LPA receptor(s) are linked to tumour initiation. To create tumour growth conditions that would selectively favour the survival of TICs in vivo, nu/nu mice received a subcutaneous injection of 300 pancreatic cancer cells, a cell number we established produces palpable tumours in approximately 50% of the injection sites after 14 days (Fig. 1a ). Compared with an injection of 1 million cells resulting in tumour growth at all injection sites, we propose that tumours formed from a limiting number of cells create a state of ‘isolation stress’ that highlights the contribution of tumour-initiating and/or self-renewing cells. Among the six LPA receptors, only LPAR4 was enriched in isolation-stressed tumours formed by 300 cells (Fig. 1a,b ). Interestingly, LPAR4 expression was significantly higher in early-stage (day 20) lesions versus established (day 35) tumours (Fig. 1c ), indicating that LPAR4 is transiently expressed when tumour cells are experiencing ‘isolation stress’ but downregulated as tumours become established. Compared with cells grown in 2D adherent culture conditions, LPAR4 messenger RNA (mRNA) was highly enriched in the self-renewing cells that form secondary tumourspheres (Fig. 1d ). Thus, LPAR4 is upregulated under in vitro and in vivo conditions that enrich for TICs. Fig. 1: Pancreatic cancer cells selectively upregulate LPAR4 in response to isolation stress. a , log 2 fold change (log 2 FC) for all LPAR s mRNA expression in ‘self-renewing’ tumours formed by subcutaneous injection of 300 cells of Colo-357 (pink dots, n = 6 biologically independent samples), 79E (black dots, n = 4 biologically independent samples) or 34E (blue dots, n = 6 biologically independent samples) with respect to ‘bulk’ tumours formed by injection of 1 million (1 M) cells of Colo-357 ( n = 6 biologically independent samples), 79E ( n = 6 biologically independent samples) or 34E ( n = 5 biologically independent samples). b , Representative images of immunohistochemistry staining of LPAR4 in 79E xenograft tumours derived from 1 M cells ( n = 5 biologically independent samples) or 300 cells ( n = 4 biologically independent samples). Scale bar is 50 µm or 10 µm as indicated. c , Relative LPAR4 mRNA level (normalized to housekeeping genes) in xenograft tumours collected at early timepoint (day 20, early lesions) versus late timepoint (day 35, established tumours). Data are mean ± standard deviation (s.d.) ( n = 3,<|im_end|> <|im_start|>assistant Researchers at University of California San Diego School of Medicine have discovered a molecular pathway critical to the initiation of pancreatic tumors. The mechanism could also contribute to the disease's high resistance to chemotherapy and its propensity for metastasis. The study, published on January 16, 2023, in Nature Cell Biology, found that pancreatic tumor-initiating cells must first overcome local "isolation stress" by creating their own tumor-promoting microenvironment, and then recruit surrounding cells into this network. By targeting this tumor-initiating pathway, new therapeutics could limit the progression, relapse and spread of pancreatic cancer. Pancreatic cancer is one of the most lethal cancers, notoriously resistant to treatment. Almost all patients experience cancer recurrence or metastasis. In the early stages of tumor formation, cancer cells (those with cancerous mutations, called oncogenes) experience a loss of adhesion to other cells and the extracellular matrix—the web of macromolecules that encase and support all cells. This isolation leads to a local lack of oxygen and nutrients. Most cells do not survive such isolation stress, but a certain group of cells can. Tumor-initiating cells (TIC) play a major role in the formation, recurrence and metastatic spread of tumors. What sets them apart from other cancer cells is their resilience to these early substandard conditions. Like cacti in a desert, they can adapt to the harsh environment and set the scene for further tumor progression. "Our goal was to understand what special properties these tumor-initiating cells have and whether we can control the growth and spread of cancer by disrupting them," said senior study author David Cheresh, Ph.D., Distinguished Professor and vice chair of the Department of Pathology at UC San Diego School of Medicine and a member of the UC San Diego Moores Cancer Center. To answer these questions, first author Chengsheng Wu, Ph.D., a postdoctoral fellow in Cheresh's lab, subjected pancreatic cell lines to various forms of stress, including low oxygen and sugar levels. He then identified which cells could adapt to the harsh conditions and observed which genes and molecules were modified in these cells. The stress-tolerant tumor-initiating cells showed reduced levels of a tumor-suppressive microRNA, miR-139-5p. This in turn led to the upregulation of lysophosphatidic acid receptor 4 (LPAR4), a G-protein-coupled receptor on the cell surface. "LPAR4 is not normally found on happy cells, but it gets turned on in stressful environments to help the cells survive, which is particularly advantageous for tumor-initiating cells," said Cheresh. Schematic: When a tumor-initiating cell experiences isolation stress, it begins expressing LPAR4. This leads to the production of a new extracellular matrix full of fibronectin (FN1), which keeps the cell safe and recruits other cells into the niche to begin tumor formation. Credit: UC San Diego Health Sciences The researchers found that LPAR4 expression promoted the production of new extracellular matrix proteins, allowing the solitary cancer cells to start building their own tumor-supporting microenvironment. The new extracellular matrix was particularly rich in fibronectin, a protein that binds to transmembrane receptors called integrins on surrounding cells. Once the integrins on these cells sensed the fibronectin, they began signaling the cells to express their own tumor-initiating genes. Eventually, these other cells were recruited into the fibronectin matrix laid by the tumor-initiating cells and a tumor started to form. "Our findings establish a critical role for LPAR4 in pancreatic tumor initiation, and a likely role in other epithelial cancers, such as lung cancer," said Cheresh. "It is central to tumor-initiating cells' ability to overcome isolation stress and build their own niche in which tumors can form." But isolation stress is not the only way this signaling pathway can be triggered, the researchers said. Chemotherapy drugs are also designed to put cancer cells under stress. Indeed, Cheresh's team found that treating cultured tumor cells and pancreatic tumors in mice with standard-of-care chemotherapeutics also led to the upregulation of LPAR4. The researchers said this might explain how such tumor cells could develop a stress tolerance and resistance to the drugs. Further experiments also showed that using integrin antagonists to block cells' ability to utilize the fibronectin matrix reversed the stress tolerance benefit of LPAR4 expression. Thus, the authors suggest targeting the LPAR4 pathway or disrupting the fibronectin/integrin interaction could be effective in preventing the growth, spread and drug resistance of pancreatic tumors. "We can think of tumor-initiating cells as being in a transient state that can be induced by different stressors, so our clinical goal would be to prevent oncogenic cells from ever entering this state," said Cheresh. "Now that we've identified the pathway, we can assess all the different ways we can intervene." The researchers suggested a new drug targeting this pathway could be used as a prophylactic in patients at high risk of developing the disease, or to prevent new tumors from forming in cancer cases with a high likelihood of metastasis. Pairing the new drug with existing chemotherapeutics that put stress on mature tumor cells could also mitigate the effects of drug resistance and make cancer treatments more effective, authors said. "Treating cancer can feel a little like whack-a-mole," said Cheresh, "but if we have two or three hammers and we know where the moles are going to pop up next, we can beat the game." <|im_end|>

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2,699

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract New neuronal recruitment in an adult animal’s brain is presumed to contribute to brain plasticity and increase the animal’s ability to contend with new and changing environments. During long-distance migration, birds migrating greater distances are exposed to more diverse spatial information. Thus, we hypothesized that greater migration distance in birds would correlate with the recruitment of new neurons into the brain regions involved with migratory navigation. We tested this hypothesis on two Palearctic migrants - reed warblers ( Acrocephalus scirpaceus ) and turtle doves ( Streptopelia turtur ), caught in Israel while returning from Africa in spring and summer. Birds were injected with a neuronal birth marker and later inspected for new neurons in brain regions known to play a role in navigation - the hippocampus and nidopallium caudolateral. We calculated the migration distance of each individual by matching feather isotopic values (δ 2 H and δ 13 C) to winter base-maps of these isotopes in Africa. Our findings suggest a positive correlation between migration distance and new neuronal recruitment in two brain regions - the hippocampus in reed warblers and nidopallium caudolateral in turtle doves. This multidisciplinary approach provides new insights into the ability of the avian brain to adapt to different migration challenges. Introduction Exposure to new information in adult animals has been positively correlated with the magnitude of new neuronal recruitment in their brains 1 , 2 . This exposure, linked to new neuronal recruitment, could be manifested in many ways throughout an animal’s life history and the challenges it faces 3 , 4 , 5 . The recruitment of new neurons is considered to be promoted by an elevated need to acquire new information in relevant brain regions 6 . Such recruitment may serve this purpose by facilitating brain plasticity and has been suggested to play an important role in acquiring new memories in both invertebrates 7 , 8 and vertebrates 1 , 9 . Birds have been used as model animals in studies linking new neuronal recruitment with various behaviors, such as social complexity 10 , food hoarding 4 , 11 , song learning 12 , the reproductive cycle 13 and others. Long-distance migration is highly demanding in many aspects of a bird’s life cycle. Beyond the immense physiological effort required in traveling large geographical distances, birds also have to avoid predation, minimize resource competition, overcome adverse weather and accurately navigate and orient 14 . The mortality rate of young avian migrants is far higher than that of their adult counterparts which suggests that learned experience is of great importance for migratory birds 15 . Indeed, several studies have explored the importance of learning and experience for accurate navigation in migratory birds 16 , 17 . Learning could be key to improved navigation ability; identification of suitable stop-over sites en-route; avoidance of harsh weather or potential predators; and for outcompeting both fellow migrants and local birds. Such needs for increased learning ability during migration may be answered by a greater neuronal recruitment in the relevant brain regions of migratory birds. To date, only two studies of passerines 18 , 19 have directly investigated the possible relationship between neuronal recruitment and migratory behavior in birds. Those studies revealed that, for passerines, migrant species or sub-species possessed more new neurons than resident species in the brain regions that play a role in spatial information processing. During the past century, great advances have been made in tracking and monitoring migratory birds. In addition to the increased use of recovery-based ringing and tagging, researchers nowadays have access to radio transmitters and satellite or GPS tracking to monitor individual birds 20 . Recently, the use of stable isotopes has been shown to be effective in quantifying individual or population migratory connectivity 21 , 22 . The use of stable isotopes to track migratory movement is based on the predictable global spatial patterns for hydrogen (H) and carbon (C) isotopes. Wherever a bird grows its feathers (often at its natal or overwintering site), the local isotopic patterns are translated through diet along the trophic cascade and are fixed into the growing feathers, thereby reflecting the region the feathers were grown 23 . When a bird is caught later, its feathers’ 2 H/H and 13 C/ 12 C ratios can be non-lethally analyzed and compared to known H and C isotopic distribution base-maps (e.g. isoscapes). This tissue-to-isoscape comparison is used to obtain estimates of the region where a bird had molted or grown its feathers. One of the primary advantages of the isotope technique is that every bird captured provides intrinsic spatial information about its migration route, without the need for the mark-recapture used in ringing and marking techniques 24 . In this study we hypothesized a possible link between an increase in new neuronal recruitment and the distances traveled by migrant birds. We explored this phenomenon in reed warblers ( Acrocephalus scirpaceus ) and turtle doves ( Streptopelia turtur ), which are summer visitors in Israel and winter and molt in Africa 25 . Migration distance estimates were determined using feather isotopic ratios as an indicator of molt locality in the wintering grounds. New neuronal recruitment was evaluated in two brain regions known to take part in navigation and spatial orientation tasks-the Hippocampal complex (HC) 26 , 27 and the nidopallium caudolateral (NCL) 27 . Results Migration distance and recruitment of new neurons When exploring links between migration distance and new neuronal recruitment in turtle doves we found marginally significant increase in recruitment into the NCL for birds flying longer distances (P = 0.07; ρ = 0.53; N = 12; Fig. 1 ), but not in the HC (P = 0.96; ρ = −0.01; N = 11). In the reed warbler we found a similar but opposite trend, with increased neuronal recruitment into the HC (P = 0.12; ρ = 0.69; N = 6; Fig. 2 ), but not into the NCL (P = 0.8; ρ = −0.13; N = 6) of birds flying longer distances. Notably, these marginally significant", "role": "user" }, { "content": "Birds that migrate the greatest distances have more new neurons in the regions of the brain responsible for navigation and spatial orientation, suggests a new paper published in Scientific Reports. For some time scholars have widely accepted the view that neurons, the cells that specialise in processing and transmitting information and contribute to brain plasticity, continue to be generated in the brains of animals even when they are adults. After being created in one part of the brain, the neurons then migrate to those regions of the brain that need them most. The international research team, which included scientists from the University of Oxford, focused on the role played by neurons in two species, turtle doves and reed warblers, making their way from Africa to the Middle East or Europe. In both species, the researchers found that the proportion of new neurons increased in line with the migration distance. Interestingly, however, there was a distinct difference between the two species in the areas of the brain that incorporated the new neurons. In reed warblers, birds that migrate as individuals at night, new neurons were found mainly in the hippocampus—a region associated with navigation. In turtle doves, a species that migrates as a group, the new neurons were found mainly in the nidopallium caudolateral, an area associated with communication skills. A Turtle dove. Credit: Guy Barkan The researchers caught 12 turtle doves and six reed warblers in nets in the Jordan Rift Valley in Israel. All the birds were on a migratory flight from Africa, but the researchers were able to estimate the flight distance already taken by each individual by measuring the isotopic signatures on the birds' feathers. The known values of isotopes of carbon and hydrogen, found in the water, soil and plants, differ according to which part of the world they are located. The researchers matched the known local values of isotopes with the particular values found on the feathers when the bird was captured. When birds lose their old feathers (through moulting) and grow new ones, they incorporate the isotopic signature of where they have been through the food and water they have ingested. Then, these migration distances were compared with the amount of new neurons incorporated into the birds' brains. This was done by selectively colouring brain cells in several relevant regions: once—for identifying new cells, and then a few weeks again for identifying neuron cells. Those coloured twice were identified as new neurons. The researchers discovered that both species show a trend of increasing new neurons in line with migration distance and that different brain regions were affected. A Reed warbler. Credit: Asaf Rahamim Researcher Dr Uri Roll, from the School of Geography and the Environment at the University of Oxford, said: \"These preliminary findings suggest a potentially exciting, new avenue of research. What we humans do during the day may actually make us more \"brainy\" as our regular activities may actually determine how our brains adapt and in which areas. In the long term, there are implications for how species evolve. For example, other research already suggests that birds that hoard food in particular periods incorporate new neurons in brain regions responsible for memory and spatial orientation. This latest paper builds on that work, suggesting that birds that need greater navigational help have more new neurons in that part of the brain while those that need to keep up with the flock incorporate new neurons in a different area.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract New neuronal recruitment in an adult animal’s brain is presumed to contribute to brain plasticity and increase the animal’s ability to contend with new and changing environments. During long-distance migration, birds migrating greater distances are exposed to more diverse spatial information. Thus, we hypothesized that greater migration distance in birds would correlate with the recruitment of new neurons into the brain regions involved with migratory navigation. We tested this hypothesis on two Palearctic migrants - reed warblers ( Acrocephalus scirpaceus ) and turtle doves ( Streptopelia turtur ), caught in Israel while returning from Africa in spring and summer. Birds were injected with a neuronal birth marker and later inspected for new neurons in brain regions known to play a role in navigation - the hippocampus and nidopallium caudolateral. We calculated the migration distance of each individual by matching feather isotopic values (δ 2 H and δ 13 C) to winter base-maps of these isotopes in Africa. Our findings suggest a positive correlation between migration distance and new neuronal recruitment in two brain regions - the hippocampus in reed warblers and nidopallium caudolateral in turtle doves. This multidisciplinary approach provides new insights into the ability of the avian brain to adapt to different migration challenges. Introduction Exposure to new information in adult animals has been positively correlated with the magnitude of new neuronal recruitment in their brains 1 , 2 . This exposure, linked to new neuronal recruitment, could be manifested in many ways throughout an animal’s life history and the challenges it faces 3 , 4 , 5 . The recruitment of new neurons is considered to be promoted by an elevated need to acquire new information in relevant brain regions 6 . Such recruitment may serve this purpose by facilitating brain plasticity and has been suggested to play an important role in acquiring new memories in both invertebrates 7 , 8 and vertebrates 1 , 9 . Birds have been used as model animals in studies linking new neuronal recruitment with various behaviors, such as social complexity 10 , food hoarding 4 , 11 , song learning 12 , the reproductive cycle 13 and others. Long-distance migration is highly demanding in many aspects of a bird’s life cycle. Beyond the immense physiological effort required in traveling large geographical distances, birds also have to avoid predation, minimize resource competition, overcome adverse weather and accurately navigate and orient 14 . The mortality rate of young avian migrants is far higher than that of their adult counterparts which suggests that learned experience is of great importance for migratory birds 15 . Indeed, several studies have explored the importance of learning and experience for accurate navigation in migratory birds 16 , 17 . Learning could be key to improved navigation ability; identification of suitable stop-over sites en-route; avoidance of harsh weather or potential predators; and for outcompeting both fellow migrants and local birds. Such needs for increased learning ability during migration may be answered by a greater neuronal recruitment in the relevant brain regions of migratory birds. To date, only two studies of passerines 18 , 19 have directly investigated the possible relationship between neuronal recruitment and migratory behavior in birds. Those studies revealed that, for passerines, migrant species or sub-species possessed more new neurons than resident species in the brain regions that play a role in spatial information processing. During the past century, great advances have been made in tracking and monitoring migratory birds. In addition to the increased use of recovery-based ringing and tagging, researchers nowadays have access to radio transmitters and satellite or GPS tracking to monitor individual birds 20 . Recently, the use of stable isotopes has been shown to be effective in quantifying individual or population migratory connectivity 21 , 22 . The use of stable isotopes to track migratory movement is based on the predictable global spatial patterns for hydrogen (H) and carbon (C) isotopes. Wherever a bird grows its feathers (often at its natal or overwintering site), the local isotopic patterns are translated through diet along the trophic cascade and are fixed into the growing feathers, thereby reflecting the region the feathers were grown 23 . When a bird is caught later, its feathers’ 2 H/H and 13 C/ 12 C ratios can be non-lethally analyzed and compared to known H and C isotopic distribution base-maps (e.g. isoscapes). This tissue-to-isoscape comparison is used to obtain estimates of the region where a bird had molted or grown its feathers. One of the primary advantages of the isotope technique is that every bird captured provides intrinsic spatial information about its migration route, without the need for the mark-recapture used in ringing and marking techniques 24 . In this study we hypothesized a possible link between an increase in new neuronal recruitment and the distances traveled by migrant birds. We explored this phenomenon in reed warblers ( Acrocephalus scirpaceus ) and turtle doves ( Streptopelia turtur ), which are summer visitors in Israel and winter and molt in Africa 25 . Migration distance estimates were determined using feather isotopic ratios as an indicator of molt locality in the wintering grounds. New neuronal recruitment was evaluated in two brain regions known to take part in navigation and spatial orientation tasks-the Hippocampal complex (HC) 26 , 27 and the nidopallium caudolateral (NCL) 27 . Results Migration distance and recruitment of new neurons When exploring links between migration distance and new neuronal recruitment in turtle doves we found marginally significant increase in recruitment into the NCL for birds flying longer distances (P = 0.07; ρ = 0.53; N = 12; Fig. 1 ), but not in the HC (P = 0.96; ρ = −0.01; N = 11). In the reed warbler we found a similar but opposite trend, with increased neuronal recruitment into the HC (P = 0.12; ρ = 0.69; N = 6; Fig. 2 ), but not into the NCL (P = 0.8; ρ = −0.13; N = 6) of birds flying longer distances. Notably, these marginally significant<|im_end|> <|im_start|>assistant Birds that migrate the greatest distances have more new neurons in the regions of the brain responsible for navigation and spatial orientation, suggests a new paper published in Scientific Reports. For some time scholars have widely accepted the view that neurons, the cells that specialise in processing and transmitting information and contribute to brain plasticity, continue to be generated in the brains of animals even when they are adults. After being created in one part of the brain, the neurons then migrate to those regions of the brain that need them most. The international research team, which included scientists from the University of Oxford, focused on the role played by neurons in two species, turtle doves and reed warblers, making their way from Africa to the Middle East or Europe. In both species, the researchers found that the proportion of new neurons increased in line with the migration distance. Interestingly, however, there was a distinct difference between the two species in the areas of the brain that incorporated the new neurons. In reed warblers, birds that migrate as individuals at night, new neurons were found mainly in the hippocampus—a region associated with navigation. In turtle doves, a species that migrates as a group, the new neurons were found mainly in the nidopallium caudolateral, an area associated with communication skills. A Turtle dove. Credit: Guy Barkan The researchers caught 12 turtle doves and six reed warblers in nets in the Jordan Rift Valley in Israel. All the birds were on a migratory flight from Africa, but the researchers were able to estimate the flight distance already taken by each individual by measuring the isotopic signatures on the birds' feathers. The known values of isotopes of carbon and hydrogen, found in the water, soil and plants, differ according to which part of the world they are located. The researchers matched the known local values of isotopes with the particular values found on the feathers when the bird was captured. When birds lose their old feathers (through moulting) and grow new ones, they incorporate the isotopic signature of where they have been through the food and water they have ingested. Then, these migration distances were compared with the amount of new neurons incorporated into the birds' brains. This was done by selectively colouring brain cells in several relevant regions: once—for identifying new cells, and then a few weeks again for identifying neuron cells. Those coloured twice were identified as new neurons. The researchers discovered that both species show a trend of increasing new neurons in line with migration distance and that different brain regions were affected. A Reed warbler. Credit: Asaf Rahamim Researcher Dr Uri Roll, from the School of Geography and the Environment at the University of Oxford, said: "These preliminary findings suggest a potentially exciting, new avenue of research. What we humans do during the day may actually make us more "brainy" as our regular activities may actually determine how our brains adapt and in which areas. In the long term, there are implications for how species evolve. For example, other research already suggests that birds that hoard food in particular periods incorporate new neurons in brain regions responsible for memory and spatial orientation. This latest paper builds on that work, suggesting that birds that need greater navigational help have more new neurons in that part of the brain while those that need to keep up with the flock incorporate new neurons in a different area." <|im_end|>

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2,006

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract A previously unexplored property of two-dimensional electronic materials is their ability to graft electronic functionality onto colloidal particles to access local hydrodynamics in fluids to impart mobility and enter spaces inaccessible to larger electronic systems. Here, we demonstrate the design and fabrication of fully autonomous state machines built onto SU-8 particles powered by a two-dimensional material-based photodiode. The on-board circuit connects a chemiresistor circuit element and a memristor element, enabling the detection and storage of information after aerosolization, hydrodynamic propulsion to targets over 0.6 m away, and large-area surface sensing of triethylamine, ammonia and aerosolized soot in inaccessible locations. An incorporated retroreflector design allows for facile position location using laser-scanning optical detection. Such state machines may find widespread application as probes in confined environments, such as the human digestive tract, oil and gas conduits, chemical and biosynthetic reactors, and autonomous environmental sensors. Main Two-dimensional (2D) materials, such as graphene and transition metal dichalcogenides, can be fashioned into novel planar circuit elements, including photodiodes 1 , transistors 2 , chemiresistor sensors 3 , memory elements 4 and capacitors 5 , 6 . This has enabled the transfer and construction of nanoelectronic circuits grafted onto unique surfaces. However, one surface that has yet to be explored for this purpose is a fluid dispersible colloid. This could extend nanoelectronics to remote and inaccessible spaces and volumes. As on-board circuit elements increase in number and complexity, access independent sources of power, and manifest input and output information sources, a threshold is reached where the colloid constitutes a finite-state machine or computational device for handling informational flows. Nanofabrication and synthesis methods have allowed researchers to create sophisticated colloidal devices (single particles or assemblies that serve a particular function), but not ones possessing autonomous circuitry, logic manipulation or information storage. In particular, state-of-the-art multifunctional micro/nanoparticles do not process information in an autonomous way when decoupled from their environment 7 , 8 . Similarly, conceptual devices referred to as ‘molecular machines’ rely on the stochastic thermodynamics of their environment 9 (for example, the Brownian ratchet). Directed self-assembly methods are still in their infancy and are only able to create rather simple geometries—and not yet autonomous function 10 , 11 ; on the other hand, nanoelectronics has enabled several state machine implementations, although not in the form of autonomous colloidal particles 12 , 13 , 14 . DNA electronics has been proposed in ref. 15 , but the formation of electronic, DNA-based, colloidal state machines has not been realized. Finally, there has been recent progress in creating so-called ‘biorobots’, or biological state machines (a natural organism whose genome has been modified to manifest diverse, non-natural functions) 16 , 17 , 18 . However, biorobots can only exist under specific biological conditions, requiring limitations to the environment, temperature, pH and salinity, and protection against wild-type organisms. This constrains the envisioned applications compared to purely synthetic state machines, which could bring both digital and analog electronics to harsh environments in a scalable way. For example, the large-area monitoring of environmental bacteria, biological spores, particulates and volatile organic compounds (VOCs) requires significant resources 19 that could be more efficiently deployed using synthetic state machines (Supplementary Note 1 ). The concept of cubic millimetre-sized devices, previously called ‘smart dust’, was not implemented for fluid dispersion, but nevertheless constituted an early attempt towards achieving miniaturized autonomous electronics 20 . However, it is clear that the power density limits further downward scaling. Batteries with typical energy capacities up to 0.1 nW µm − 3 (ref. 21 ) and with power harvesting techniques that can deliver between 0.1 and 10 nW (10 4 µm 2 ) −1 (ref. 22 , 23 , 24 ) remain insufficient for conventional electronics at the microscale (Supplementary Note 2 ). Fortunately, 2D material devices are predicted to bypass these difficulties 25 because they have a number of advantages 26 , such as low-power performance compared to Si (<0.5 V), acceptable gate control with subthreshold swings ≪ 60 mV dec −1 , and large turn-on currents (>10 3 μA μm −1 ). In this work we create a new class of submillimetre colloidal particles with 2D electronic materials (graphene, hexagonal boron nitride (hBN), MoS 2 and WSe 2 ) grafted onto them. Top-down fabrication can pattern them into functional electronic circuits, transistors, memory and sensors, creating what we call colloidal state machines (CSMs), or particles capable of collecting, manipulating and storing information autonomously. Such CSMs can access local fluid hydrodynamics to enter spaces inaccessible to conventional electronics. Our designs include circuits with 2D material p–n heterojunctions of MoS 2 and WSe 2 , powering MoS 2 chemiresistor circuit elements. Such CSMs can be aerosolized and detect VOCs or carbon nanoparticulates along their trajectories, storing the detection in a non-volatile memristor device consisting of a Au–MoS 2 –Ag junction shielded from the environment by an inert hBN monolayer. These state machines exploit a unique property of 2D electronic materials in their ability to impart fundamentally new functions to highly mobile colloids. We demonstrate several specific applications, such as remote sensing of ammonia in constricted pipelines, as well as large-area sensing of aerosolized soot via standoff deployment and retrieval of surface-dispersed state machines. Because of their high aspect ratio, micrometre-scale 2D materials have low mechanical stability (necessary to sustain off-substrate applications). To circumvent this, we first designed a CSM base that plays the role of a carrier substrate for the 2D devices. We chose the photoresponsive polymer SU-8, as it can be processed with micrometre precision via conventional photolithography, becomes mechanically and chemically stable after cross-linking, even during various fabrication stages (Supplementary Fig. 1 ), and has a smooth surface (Supplementary Fig. 2 ). We also designed an electrical state machine with functional elements of combinational logic on this polymer base (Fig. 1a ). Specifically, this has three components—a power source, a switch and a memory element—implemented by a photodiode, chemiresistor and memristor, respectively (Fig. 1b ). The photodiode is built on a p–n heterojunction of MoS 2 and WSe 2", "role": "user" }, { "content": "Researchers at MIT have created what may be the smallest robots yet that can sense their environment, store data, and even carry out computational tasks. These devices, which are about the size of a human egg cell, consist of tiny electronic circuits made of two-dimensional materials, piggybacking on minuscule particles called colloids. Colloids, which insoluble particles or molecules anywhere from a billionth to a millionth of a meter across, are so small they can stay suspended indefinitely in a liquid or even in air. By coupling these tiny objects to complex circuitry, the researchers hope to lay the groundwork for devices that could be dispersed to carry out diagnostic journeys through anything from the human digestive system to oil and gas pipelines, or perhaps to waft through air to measure compounds inside a chemical processor or refinery. \"We wanted to figure out methods to graft complete, intact electronic circuits onto colloidal particles,\" explains Michael Strano, the Carbon C. Dubbs Professor of Chemical Engineering at MIT and senior author of the study, which was published today in the journal Nature Nanotechnology. MIT postdoc Volodymyr Koman is the paper's lead author. \"Colloids can access environments and travel in ways that other materials can't,\" Strano says. Dust particles, for example, can float indefinitely in the air because they are small enough that the random motions imparted by colliding air molecules are stronger than the pull of gravity. Similarly, colloids suspended in liquid will never settle out. Researchers produced tiny electronic circuits, just 100 micrometers across,on a substrate material which was then dissolved away to leave the individual devices floating freely in solution. These were later attached to tiny colloidal particles. Credit: Massachusetts Institute of Technology Strano says that while other groups have worked on the creation of similarly tiny robotic devices, their emphasis has been on developing ways to control movement, for example by replicating the tail-like flagellae that some microbial organisms use to propel themselves. But Strano suggests that may not be the most fruitful approach, since flagellae and other cellular movement systems are primarily used for local-scale positioning, rather than for significant movement. For most purposes, making such devices more functional is more important than making them mobile, he says. Tiny robots made by the MIT team are self-powered, requiring no external power source or even internal batteries. A simple photodiode provides the trickle of electricity that the tiny robots' circuits require to power their computation and memory circuits. That's enough to let them sense information about their environment, store those data in their memory, and then later have the data read out after accomplishing their mission. Such devices could ultimately be a boon for the oil and gas industry, Strano says. Currently, the main way of checking for leaks or other issues in pipelines is to have a crew physically drive along the pipe and inspect it with expensive instruments. In principle, the new devices could be inserted into one end of the pipeline, carried along with the flow, and then removed at the other end, providing a record of the conditions they encountered along the way, including the presence of contaminants that could indicate the location of problem areas. The initial proof-of-concept devices didn't have a timing circuit that would indicate the location of particular data readings, but adding that is part of ongoing work. Similarly, such particles could potentially be used for diagnostic purposes in the body, for example to pass through the digestive tract searching for signs of inflammation or other disease indicators, the researchers say. As a demonstration of how such particles might be used to test biological samples, the team placed a solution containing the devices on a leaf, and then used the devices’ internal reflectors to locate them for testing by shining a laser at the leaf. Credit: Massachusetts Institute of Technology Most conventional microchips, such as silicon-based or CMOS, have a flat, rigid substrate and would not perform properly when attached to colloids that can experience complex mechanical stresses while travelling through the environment. In addition, all such chips are \"very energy-thirsty,\" Strano says. That's why Koman decided to try out two-dimensional electronic materials, including graphene and transition-metal dichalcogenides, which he found could be attached to colloid surfaces, remaining operational even after after being launched into air or water. And such thin-film electronics require only tiny amounts of energy. \"They can be powered by nanowatts with subvolt voltages,\" Koman says. Why not just use the 2-D electronics alone? Without some substrate to carry them, these tiny materials are too fragile to hold together and function. \"They can't exist without a substrate,\" Strano says. \"We need to graft them to the particles to give them mechanical rigidity and to make them large enough to get entrained in the flow.\" But the 2-D materials \"are strong enough, robust enough to maintain their functionality even on unconventional substrates\" such as the colloids, Koman says. The nanodevices they produced with this method are autonomous particles that contain electronics for power generation, computation, logic, and memory storage. They are powered by light and contain tiny retroreflectors that allow them to be easily located after their travels. They can then be interrogated through probes to deliver their data. In ongoing work, the team hopes to add communications capabilities to allow the particles to deliver their data without the need for physical contact. Other efforts at nanoscale robotics \"haven't reached that level\" of creating complex electronics that are sufficiently small and energy efficient to be aerosolized or suspended in a colloidal liquid. These are \"very smart particles, by current standards,\" Strano says, adding, \"We see this paper as the introduction of a new field\" in robotics. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract A previously unexplored property of two-dimensional electronic materials is their ability to graft electronic functionality onto colloidal particles to access local hydrodynamics in fluids to impart mobility and enter spaces inaccessible to larger electronic systems. Here, we demonstrate the design and fabrication of fully autonomous state machines built onto SU-8 particles powered by a two-dimensional material-based photodiode. The on-board circuit connects a chemiresistor circuit element and a memristor element, enabling the detection and storage of information after aerosolization, hydrodynamic propulsion to targets over 0.6 m away, and large-area surface sensing of triethylamine, ammonia and aerosolized soot in inaccessible locations. An incorporated retroreflector design allows for facile position location using laser-scanning optical detection. Such state machines may find widespread application as probes in confined environments, such as the human digestive tract, oil and gas conduits, chemical and biosynthetic reactors, and autonomous environmental sensors. Main Two-dimensional (2D) materials, such as graphene and transition metal dichalcogenides, can be fashioned into novel planar circuit elements, including photodiodes 1 , transistors 2 , chemiresistor sensors 3 , memory elements 4 and capacitors 5 , 6 . This has enabled the transfer and construction of nanoelectronic circuits grafted onto unique surfaces. However, one surface that has yet to be explored for this purpose is a fluid dispersible colloid. This could extend nanoelectronics to remote and inaccessible spaces and volumes. As on-board circuit elements increase in number and complexity, access independent sources of power, and manifest input and output information sources, a threshold is reached where the colloid constitutes a finite-state machine or computational device for handling informational flows. Nanofabrication and synthesis methods have allowed researchers to create sophisticated colloidal devices (single particles or assemblies that serve a particular function), but not ones possessing autonomous circuitry, logic manipulation or information storage. In particular, state-of-the-art multifunctional micro/nanoparticles do not process information in an autonomous way when decoupled from their environment 7 , 8 . Similarly, conceptual devices referred to as ‘molecular machines’ rely on the stochastic thermodynamics of their environment 9 (for example, the Brownian ratchet). Directed self-assembly methods are still in their infancy and are only able to create rather simple geometries—and not yet autonomous function 10 , 11 ; on the other hand, nanoelectronics has enabled several state machine implementations, although not in the form of autonomous colloidal particles 12 , 13 , 14 . DNA electronics has been proposed in ref. 15 , but the formation of electronic, DNA-based, colloidal state machines has not been realized. Finally, there has been recent progress in creating so-called ‘biorobots’, or biological state machines (a natural organism whose genome has been modified to manifest diverse, non-natural functions) 16 , 17 , 18 . However, biorobots can only exist under specific biological conditions, requiring limitations to the environment, temperature, pH and salinity, and protection against wild-type organisms. This constrains the envisioned applications compared to purely synthetic state machines, which could bring both digital and analog electronics to harsh environments in a scalable way. For example, the large-area monitoring of environmental bacteria, biological spores, particulates and volatile organic compounds (VOCs) requires significant resources 19 that could be more efficiently deployed using synthetic state machines (Supplementary Note 1 ). The concept of cubic millimetre-sized devices, previously called ‘smart dust’, was not implemented for fluid dispersion, but nevertheless constituted an early attempt towards achieving miniaturized autonomous electronics 20 . However, it is clear that the power density limits further downward scaling. Batteries with typical energy capacities up to 0.1 nW µm − 3 (ref. 21 ) and with power harvesting techniques that can deliver between 0.1 and 10 nW (10 4 µm 2 ) −1 (ref. 22 , 23 , 24 ) remain insufficient for conventional electronics at the microscale (Supplementary Note 2 ). Fortunately, 2D material devices are predicted to bypass these difficulties 25 because they have a number of advantages 26 , such as low-power performance compared to Si (<0.5 V), acceptable gate control with subthreshold swings ≪ 60 mV dec −1 , and large turn-on currents (>10 3 μA μm −1 ). In this work we create a new class of submillimetre colloidal particles with 2D electronic materials (graphene, hexagonal boron nitride (hBN), MoS 2 and WSe 2 ) grafted onto them. Top-down fabrication can pattern them into functional electronic circuits, transistors, memory and sensors, creating what we call colloidal state machines (CSMs), or particles capable of collecting, manipulating and storing information autonomously. Such CSMs can access local fluid hydrodynamics to enter spaces inaccessible to conventional electronics. Our designs include circuits with 2D material p–n heterojunctions of MoS 2 and WSe 2 , powering MoS 2 chemiresistor circuit elements. Such CSMs can be aerosolized and detect VOCs or carbon nanoparticulates along their trajectories, storing the detection in a non-volatile memristor device consisting of a Au–MoS 2 –Ag junction shielded from the environment by an inert hBN monolayer. These state machines exploit a unique property of 2D electronic materials in their ability to impart fundamentally new functions to highly mobile colloids. We demonstrate several specific applications, such as remote sensing of ammonia in constricted pipelines, as well as large-area sensing of aerosolized soot via standoff deployment and retrieval of surface-dispersed state machines. Because of their high aspect ratio, micrometre-scale 2D materials have low mechanical stability (necessary to sustain off-substrate applications). To circumvent this, we first designed a CSM base that plays the role of a carrier substrate for the 2D devices. We chose the photoresponsive polymer SU-8, as it can be processed with micrometre precision via conventional photolithography, becomes mechanically and chemically stable after cross-linking, even during various fabrication stages (Supplementary Fig. 1 ), and has a smooth surface (Supplementary Fig. 2 ). We also designed an electrical state machine with functional elements of combinational logic on this polymer base (Fig. 1a ). Specifically, this has three components—a power source, a switch and a memory element—implemented by a photodiode, chemiresistor and memristor, respectively (Fig. 1b ). The photodiode is built on a p–n heterojunction of MoS 2 and WSe 2<|im_end|> <|im_start|>assistant Researchers at MIT have created what may be the smallest robots yet that can sense their environment, store data, and even carry out computational tasks. These devices, which are about the size of a human egg cell, consist of tiny electronic circuits made of two-dimensional materials, piggybacking on minuscule particles called colloids. Colloids, which insoluble particles or molecules anywhere from a billionth to a millionth of a meter across, are so small they can stay suspended indefinitely in a liquid or even in air. By coupling these tiny objects to complex circuitry, the researchers hope to lay the groundwork for devices that could be dispersed to carry out diagnostic journeys through anything from the human digestive system to oil and gas pipelines, or perhaps to waft through air to measure compounds inside a chemical processor or refinery. "We wanted to figure out methods to graft complete, intact electronic circuits onto colloidal particles," explains Michael Strano, the Carbon C. Dubbs Professor of Chemical Engineering at MIT and senior author of the study, which was published today in the journal Nature Nanotechnology. MIT postdoc Volodymyr Koman is the paper's lead author. "Colloids can access environments and travel in ways that other materials can't," Strano says. Dust particles, for example, can float indefinitely in the air because they are small enough that the random motions imparted by colliding air molecules are stronger than the pull of gravity. Similarly, colloids suspended in liquid will never settle out. Researchers produced tiny electronic circuits, just 100 micrometers across,on a substrate material which was then dissolved away to leave the individual devices floating freely in solution. These were later attached to tiny colloidal particles. Credit: Massachusetts Institute of Technology Strano says that while other groups have worked on the creation of similarly tiny robotic devices, their emphasis has been on developing ways to control movement, for example by replicating the tail-like flagellae that some microbial organisms use to propel themselves. But Strano suggests that may not be the most fruitful approach, since flagellae and other cellular movement systems are primarily used for local-scale positioning, rather than for significant movement. For most purposes, making such devices more functional is more important than making them mobile, he says. Tiny robots made by the MIT team are self-powered, requiring no external power source or even internal batteries. A simple photodiode provides the trickle of electricity that the tiny robots' circuits require to power their computation and memory circuits. That's enough to let them sense information about their environment, store those data in their memory, and then later have the data read out after accomplishing their mission. Such devices could ultimately be a boon for the oil and gas industry, Strano says. Currently, the main way of checking for leaks or other issues in pipelines is to have a crew physically drive along the pipe and inspect it with expensive instruments. In principle, the new devices could be inserted into one end of the pipeline, carried along with the flow, and then removed at the other end, providing a record of the conditions they encountered along the way, including the presence of contaminants that could indicate the location of problem areas. The initial proof-of-concept devices didn't have a timing circuit that would indicate the location of particular data readings, but adding that is part of ongoing work. Similarly, such particles could potentially be used for diagnostic purposes in the body, for example to pass through the digestive tract searching for signs of inflammation or other disease indicators, the researchers say. As a demonstration of how such particles might be used to test biological samples, the team placed a solution containing the devices on a leaf, and then used the devices’ internal reflectors to locate them for testing by shining a laser at the leaf. Credit: Massachusetts Institute of Technology Most conventional microchips, such as silicon-based or CMOS, have a flat, rigid substrate and would not perform properly when attached to colloids that can experience complex mechanical stresses while travelling through the environment. In addition, all such chips are "very energy-thirsty," Strano says. That's why Koman decided to try out two-dimensional electronic materials, including graphene and transition-metal dichalcogenides, which he found could be attached to colloid surfaces, remaining operational even after after being launched into air or water. And such thin-film electronics require only tiny amounts of energy. "They can be powered by nanowatts with subvolt voltages," Koman says. Why not just use the 2-D electronics alone? Without some substrate to carry them, these tiny materials are too fragile to hold together and function. "They can't exist without a substrate," Strano says. "We need to graft them to the particles to give them mechanical rigidity and to make them large enough to get entrained in the flow." But the 2-D materials "are strong enough, robust enough to maintain their functionality even on unconventional substrates" such as the colloids, Koman says. The nanodevices they produced with this method are autonomous particles that contain electronics for power generation, computation, logic, and memory storage. They are powered by light and contain tiny retroreflectors that allow them to be easily located after their travels. They can then be interrogated through probes to deliver their data. In ongoing work, the team hopes to add communications capabilities to allow the particles to deliver their data without the need for physical contact. Other efforts at nanoscale robotics "haven't reached that level" of creating complex electronics that are sufficiently small and energy efficient to be aerosolized or suspended in a colloidal liquid. These are "very smart particles, by current standards," Strano says, adding, "We see this paper as the introduction of a new field" in robotics. <|im_end|>

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2,625

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The constituents of the gut microbiome are determined by the local habitat, which itself is shaped by immunological pressures, such as mucosal IgA. Using a mouse model of restricted antibody repertoire, we identified a role for antibody–microbe interactions in shaping a community of bacteria with an enhanced capacity to metabolize l -tyrosine. This model led to increased concentrations of p -cresol sulfate (PCS), which protected the host against allergic airway inflammation. PCS selectively reduced CCL20 production by airway epithelial cells due to an uncoupling of epidermal growth factor receptor (EGFR) and Toll-like receptor 4 (TLR4) signaling. Together, these data reveal a gut microbe–derived metabolite pathway that acts distally on the airway epithelium to reduce allergic airway responses, such as those underpinning asthma. Main Allergic asthma is a chronic airway disease characterized by the production of type 2 cytokines, synthesis of IgE, goblet cell metaplasia, influx of inflammatory cells and, ultimately, airway remodeling. Initiation of allergic asthma is a consequence of a dysregulated interplay between airway epithelium and immune cells, including dendritic cells (DCs), in response to allergen exposure 1 , 2 . In support of this, sensing of house dust mite (HDM) extract via TLR4 expressed on airway epithelial cells was shown to be necessary for the activation of pulmonary DCs and the initiation of allergic sensitization 3 , 4 . However, the immunomodulatory properties of other receptors (and ligands) upon epithelium-driven DC activation that could underpin differences in susceptibility to asthma remain obscure. A previous study identified the involvement of a deubiquitinating enzyme, A20, where its expression was reduced in airway epithelial cells of individuals with asthma 5 . Experimentally, induction of A20 by chronic exposure to endotoxin was sufficient to protect mice against allergic airway disease 5 . Exposure to endotoxins might mimic exposure to a rural environment, a setting associated with protection against asthma. Diet, including consumption of unpasteurized cow’s milk, fibers or breastfeeding, has been reported to confer similar benefits 6 . In the case of fibers, the effect relies on production of short-chain fatty acids in the gut that are released systemically and influence hematopoiesis 7 . Interestingly, both the farm effect and diet involve changes in the microbiome; yet, the impact of microbes or their metabolites on the airway epithelium is currently unknown. In addition to environmental cues, host-intrinsic factors contribute to diversification of the microbiota (a feature usually associated with health benefits 8 ), for example, via the generation of a diverse antibody repertoire 9 . We aimed to explore the impact of a restricted antibody repertoire on the composition of the gut microbiome and assess its capacity to influence airway inflammation. Results MD4 mice do not develop allergic airway disease To model a lack of antibody diversity, we utilized a B cell antigen receptor-transgenic mouse strain, ‘MD4’, with a restricted antibody repertoire such that >99% of its B cells are specific to a single antigen, hen egg lysozyme (HEL). Given the positive correlation between diversification of the antibody repertoire and a diverse microbiota 9 , a characteristic associated with health benefits 8 , we hypothesized that MD4 mice would have reduced microbial diversity and, consequently, an increased susceptibility to inflammation such as allergic airway inflammation, a mouse model of asthma. On the contrary, intranasal exposure of MD4 mice to HDM extract (as indicated in the Methods ) resulted in an almost complete absence of the allergic airway disease seen in wild-type controls, including eosinophilia (Fig. 1a ), recruitment and activation of pulmonary DCs (Fig. 1b ), mucus production (Fig. 1c ), peribronchial and perivascular inflammatory cell infiltrates (Fig. 1d ) and production of the type 2 helper T cell (T H 2)-associated cytokines interleukin (IL)-5 and IL-13 (Fig. 1e ). These immunological differences only manifested following HDM exposure, as no differences were observed in the immune profiles of these mouse strains at steady state. However, because the cellular composition of mediastinal lymph nodes differed markedly between wild-type and MD4 mice exposed to HDM (as a consequence of the lack of B cell proliferation in the latter), we sorted CD4 + T cells from the lymph nodes of both groups and co-cultured them with DCs in the presence of HDM. Consistent with these observations, we failed to detect type 2 cytokines in culture supernatants of MD4 T cells (Extended Data Fig. 1a ). Recruitment of CD4 + T cells was only moderately decreased, with a slight reduction in the proportion of FoxP3 + regulatory T (T reg ) cells (Fig. 1f ). B cell-deficient mice (J H T –/– ) mounted an allergic response similar to that seen in wild-type mice (Extended Data Fig. 1b ), indicating that the lack of an allergic response in the MD4 mouse strain was not due to the absence of antigen-specific B cells. Fig. 1: MD4 mice with a restricted antibody repertoire to HEL fail to mount allergic responses to HDM extract. a , Differential cell counts in the bronchoalveolar lavage fluid (BALF). Mac, macrophages; Neutr, neutrophils; Eos, eosinophils; Lymph, lymphocytes; WT, wild type. b , Total number of DCs in the lungs and their surface expression of PD-L2. GMFI, geometric mean fluorescence intensity. c , Representative periodic acid–Schiff (PAS)-stained lung tissue from WT or MD4 mice and quantification of the frequency of PAS + bronchi in histological sections. Scale bars, 100 μm; P = 0.0074. d , Representative hematoxylin and eosin (H&E)-stained lung tissue from WT or MD4 mice. Scale bars, 100 μm. e , Concentrations of IL-5 and IL-13 in culture supernatants of mediastinal lymph node cells restimulated with the indicated concentrations of HDM for 4 d; *** P = 0.0005 (IL-5), ** P = 0.0012 (IL-13). f , Total number of CD4 + T cells and the frequency of T reg cells (expressed as the percentage of CD4 + T cells) in the lung tissue; ** P = 0.0063 (CD4 + T cells), * P = 0.0495 (T reg cells). g , Principal-coordinate analysis (PCoA) plot (based on Bray–Curtis distance) of the bacterial", "role": "user" }, { "content": "A study designed to study how the immune system impacts gut bacteria—has led to the extraordinary discovery of two molecules that can not only provide profound protection in experimental models of asthma but can also substantially reduce the severity of an attack. Neither of these molecules, one of which is already commercially available as a dietary supplement, were previously known to have an effect on asthma—and they also appear, from animal studies, to have a role in treating the respiratory illness that is prevalent, and often fatal, in people with serious COVID-19. The researchers aim to test one of the molecules in a clinical trial in 2021 in asthmatics. As further evidence that these two molecules could potentially protect against asthma the Monash University researchers found, through studying the literature, that these metabolites are present in higher amounts in two studies of children without asthma compared to those with the disease, according to Professor Benjamin Marsland from the Monash University Central Clinical School, whose paper is published today in Nature Immunology. Asthma is one of the most common major non-communicable diseases and it impacts 300 million people globally. The global asthma treatment market size stood at over $18 billion US in 2019. The team led by VESKI innovation fellow, Professor Marsland, wanted to understand how the immune system impacts the gut microbiome. While it is known that gut bacteria have an effect on the immune system, \"how the immune system influences the gut microbiome has to date been under studied,\" he said. Studying a mouse that had a limited immune system, consisting of a single type of antibody, the researchers found the gut microbiome was changed. By transferring these gut bacteria into 'normal' mice they could identify which bacteria had an impact on the mouse immune system. In what was an enormous surprise the researchers found that the production of a particular gut bacteria by-product, called p-cresol sulfate (PCS), led to a \"profound and striking protection against asthma.\" Part of the serendipity of the finding is that Professor Marsland's area of expertise is in the immunology of asthma, though he suspects this metabolite may have a role in other inflammatory diseases. The researchers found that the PCS was produced by enhanced bacterial metabolism of L-tyrosine; a well-known amino acid found in dietary supplements aimed at improving attention and alertness. \"We found that giving mice either L-tyrosine or PCS, provided significant protection against lung inflammation. PCS travels all the way from the gut, to the lungs, and acts on epithelial cells lining the airways to prevent the allergic asthma response\" The researchers also tested the metabolites in animal models of acute respiratory distress syndrome (ARDS), and found it to be protective. ARDS is a common killer of people with serious COVID-19. While L-tyrosine has a long history of use in the clinic, as mentioned in dietary supplements, its potential use as a therapy could be fast tracked into clinical trials because it is known to be safe. Professor Marsland commented \"It's very important that a thorough clinical study is performed in order to determine whether L-tyrosine is effective in people with asthma, and for us to determine what is the correct dose and treatment regime.\" PCS however is known to be in high levels in people with chronic kidney disease and it's suspected to be toxic because of these patient's inability to clear it. The research group has started developing a form of PCS that is a potent protector against asthma without the potential toxic side effects. More importantly the scientists have found that inhaling PCS provides a direct protective effect against lung inflammation, opening the way for a novel inhaled preventive therapy. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The constituents of the gut microbiome are determined by the local habitat, which itself is shaped by immunological pressures, such as mucosal IgA. Using a mouse model of restricted antibody repertoire, we identified a role for antibody–microbe interactions in shaping a community of bacteria with an enhanced capacity to metabolize l -tyrosine. This model led to increased concentrations of p -cresol sulfate (PCS), which protected the host against allergic airway inflammation. PCS selectively reduced CCL20 production by airway epithelial cells due to an uncoupling of epidermal growth factor receptor (EGFR) and Toll-like receptor 4 (TLR4) signaling. Together, these data reveal a gut microbe–derived metabolite pathway that acts distally on the airway epithelium to reduce allergic airway responses, such as those underpinning asthma. Main Allergic asthma is a chronic airway disease characterized by the production of type 2 cytokines, synthesis of IgE, goblet cell metaplasia, influx of inflammatory cells and, ultimately, airway remodeling. Initiation of allergic asthma is a consequence of a dysregulated interplay between airway epithelium and immune cells, including dendritic cells (DCs), in response to allergen exposure 1 , 2 . In support of this, sensing of house dust mite (HDM) extract via TLR4 expressed on airway epithelial cells was shown to be necessary for the activation of pulmonary DCs and the initiation of allergic sensitization 3 , 4 . However, the immunomodulatory properties of other receptors (and ligands) upon epithelium-driven DC activation that could underpin differences in susceptibility to asthma remain obscure. A previous study identified the involvement of a deubiquitinating enzyme, A20, where its expression was reduced in airway epithelial cells of individuals with asthma 5 . Experimentally, induction of A20 by chronic exposure to endotoxin was sufficient to protect mice against allergic airway disease 5 . Exposure to endotoxins might mimic exposure to a rural environment, a setting associated with protection against asthma. Diet, including consumption of unpasteurized cow’s milk, fibers or breastfeeding, has been reported to confer similar benefits 6 . In the case of fibers, the effect relies on production of short-chain fatty acids in the gut that are released systemically and influence hematopoiesis 7 . Interestingly, both the farm effect and diet involve changes in the microbiome; yet, the impact of microbes or their metabolites on the airway epithelium is currently unknown. In addition to environmental cues, host-intrinsic factors contribute to diversification of the microbiota (a feature usually associated with health benefits 8 ), for example, via the generation of a diverse antibody repertoire 9 . We aimed to explore the impact of a restricted antibody repertoire on the composition of the gut microbiome and assess its capacity to influence airway inflammation. Results MD4 mice do not develop allergic airway disease To model a lack of antibody diversity, we utilized a B cell antigen receptor-transgenic mouse strain, ‘MD4’, with a restricted antibody repertoire such that >99% of its B cells are specific to a single antigen, hen egg lysozyme (HEL). Given the positive correlation between diversification of the antibody repertoire and a diverse microbiota 9 , a characteristic associated with health benefits 8 , we hypothesized that MD4 mice would have reduced microbial diversity and, consequently, an increased susceptibility to inflammation such as allergic airway inflammation, a mouse model of asthma. On the contrary, intranasal exposure of MD4 mice to HDM extract (as indicated in the Methods ) resulted in an almost complete absence of the allergic airway disease seen in wild-type controls, including eosinophilia (Fig. 1a ), recruitment and activation of pulmonary DCs (Fig. 1b ), mucus production (Fig. 1c ), peribronchial and perivascular inflammatory cell infiltrates (Fig. 1d ) and production of the type 2 helper T cell (T H 2)-associated cytokines interleukin (IL)-5 and IL-13 (Fig. 1e ). These immunological differences only manifested following HDM exposure, as no differences were observed in the immune profiles of these mouse strains at steady state. However, because the cellular composition of mediastinal lymph nodes differed markedly between wild-type and MD4 mice exposed to HDM (as a consequence of the lack of B cell proliferation in the latter), we sorted CD4 + T cells from the lymph nodes of both groups and co-cultured them with DCs in the presence of HDM. Consistent with these observations, we failed to detect type 2 cytokines in culture supernatants of MD4 T cells (Extended Data Fig. 1a ). Recruitment of CD4 + T cells was only moderately decreased, with a slight reduction in the proportion of FoxP3 + regulatory T (T reg ) cells (Fig. 1f ). B cell-deficient mice (J H T –/– ) mounted an allergic response similar to that seen in wild-type mice (Extended Data Fig. 1b ), indicating that the lack of an allergic response in the MD4 mouse strain was not due to the absence of antigen-specific B cells. Fig. 1: MD4 mice with a restricted antibody repertoire to HEL fail to mount allergic responses to HDM extract. a , Differential cell counts in the bronchoalveolar lavage fluid (BALF). Mac, macrophages; Neutr, neutrophils; Eos, eosinophils; Lymph, lymphocytes; WT, wild type. b , Total number of DCs in the lungs and their surface expression of PD-L2. GMFI, geometric mean fluorescence intensity. c , Representative periodic acid–Schiff (PAS)-stained lung tissue from WT or MD4 mice and quantification of the frequency of PAS + bronchi in histological sections. Scale bars, 100 μm; P = 0.0074. d , Representative hematoxylin and eosin (H&E)-stained lung tissue from WT or MD4 mice. Scale bars, 100 μm. e , Concentrations of IL-5 and IL-13 in culture supernatants of mediastinal lymph node cells restimulated with the indicated concentrations of HDM for 4 d; *** P = 0.0005 (IL-5), ** P = 0.0012 (IL-13). f , Total number of CD4 + T cells and the frequency of T reg cells (expressed as the percentage of CD4 + T cells) in the lung tissue; ** P = 0.0063 (CD4 + T cells), * P = 0.0495 (T reg cells). g , Principal-coordinate analysis (PCoA) plot (based on Bray–Curtis distance) of the bacterial<|im_end|> <|im_start|>assistant A study designed to study how the immune system impacts gut bacteria—has led to the extraordinary discovery of two molecules that can not only provide profound protection in experimental models of asthma but can also substantially reduce the severity of an attack. Neither of these molecules, one of which is already commercially available as a dietary supplement, were previously known to have an effect on asthma—and they also appear, from animal studies, to have a role in treating the respiratory illness that is prevalent, and often fatal, in people with serious COVID-19. The researchers aim to test one of the molecules in a clinical trial in 2021 in asthmatics. As further evidence that these two molecules could potentially protect against asthma the Monash University researchers found, through studying the literature, that these metabolites are present in higher amounts in two studies of children without asthma compared to those with the disease, according to Professor Benjamin Marsland from the Monash University Central Clinical School, whose paper is published today in Nature Immunology. Asthma is one of the most common major non-communicable diseases and it impacts 300 million people globally. The global asthma treatment market size stood at over $18 billion US in 2019. The team led by VESKI innovation fellow, Professor Marsland, wanted to understand how the immune system impacts the gut microbiome. While it is known that gut bacteria have an effect on the immune system, "how the immune system influences the gut microbiome has to date been under studied," he said. Studying a mouse that had a limited immune system, consisting of a single type of antibody, the researchers found the gut microbiome was changed. By transferring these gut bacteria into 'normal' mice they could identify which bacteria had an impact on the mouse immune system. In what was an enormous surprise the researchers found that the production of a particular gut bacteria by-product, called p-cresol sulfate (PCS), led to a "profound and striking protection against asthma." Part of the serendipity of the finding is that Professor Marsland's area of expertise is in the immunology of asthma, though he suspects this metabolite may have a role in other inflammatory diseases. The researchers found that the PCS was produced by enhanced bacterial metabolism of L-tyrosine; a well-known amino acid found in dietary supplements aimed at improving attention and alertness. "We found that giving mice either L-tyrosine or PCS, provided significant protection against lung inflammation. PCS travels all the way from the gut, to the lungs, and acts on epithelial cells lining the airways to prevent the allergic asthma response" The researchers also tested the metabolites in animal models of acute respiratory distress syndrome (ARDS), and found it to be protective. ARDS is a common killer of people with serious COVID-19. While L-tyrosine has a long history of use in the clinic, as mentioned in dietary supplements, its potential use as a therapy could be fast tracked into clinical trials because it is known to be safe. Professor Marsland commented "It's very important that a thorough clinical study is performed in order to determine whether L-tyrosine is effective in people with asthma, and for us to determine what is the correct dose and treatment regime." PCS however is known to be in high levels in people with chronic kidney disease and it's suspected to be toxic because of these patient's inability to clear it. The research group has started developing a form of PCS that is a potent protector against asthma without the potential toxic side effects. More importantly the scientists have found that inhaling PCS provides a direct protective effect against lung inflammation, opening the way for a novel inhaled preventive therapy. <|im_end|>

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2,223

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Interferon-α (IFNα), a type I interferon, is expressed in the islets of type 1 diabetic individuals, and its expression and signaling are regulated by T1D genetic risk variants and viral infections associated with T1D. We presently characterize human beta cell responses to IFNα by combining ATAC-seq, RNA-seq and proteomics assays. The initial response to IFNα is characterized by chromatin remodeling, followed by changes in transcriptional and translational regulation. IFNα induces changes in alternative splicing (AS) and first exon usage, increasing the diversity of transcripts expressed by the beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may expand antigens presented by beta cells to the immune system. Beta cells also up-regulate the checkpoint proteins PDL1 and HLA-E that may exert a protective role against the autoimmune assault. Data mining of the present multi-omics analysis identifies two compound classes that antagonize IFNα effects on human beta cells. Introduction Type 1 diabetes (T1D) is a chronic autoimmune disease leading to pancreatic islet inflammation (insulitis) and progressive beta cell loss 1 . Type I interferons (IFN-I), a class of cytokines involved in antiviral immune responses 2 , are involved in insulitis. Viral infections are a risk factor associated with T1D development 3 and individuals at risk of T1D show a type I interferon signature 4 . The type I interferon, interferon-α (IFNα), is expressed in islets of T1D patients 5 , and antibodies neutralizing different isoforms of IFNα prevent T1D development in individuals with polyglandular autoimmune syndrome type 1 6 . Exposure of human pancreatic beta cells to IFNα recapitulates three key findings observed in human insulitis, namely HLA class I overexpression, endoplasmic reticulum (ER) stress and beta cell apoptosis 7 . Combination of genome-wide association studies (GWAS) 8 and studies using the ImmunoChip 9 have identified around 60 loci associated with the risk of developing T1D. Transcriptomic studies revealed that >70% of the T1D risk genes are expressed in human pancreatic beta cells 10 , and many of these genes regulate innate immunity and type I IFN signaling 11 . Type I IFN signaling is often cell-specific, an effect mediated by differences in cell surface receptor expression, and activation of downstream kinases and transcription factors 12 . Thus, and considering the potential relevance of this cytokine to the pathogenesis of T1D, it is crucial to characterize its effects on human beta cells. To define the global impact of IFNα on human beta cells, we presently performed an integrative multi-omics analysis (ATAC-seq, RNA-seq and proteomics) of IFNα-treated human beta cells to determine the early, intermediate and late responses to the cytokine. The findings obtained indicate that IFNα promotes early changes in chromatin accessibility, activating distant regulatory elements (RE) that control gene expression and protein abundance. IFNα activates key transcription factors (TFs), including IRF1, which act as a mediator of the crosstalk between beta cells and immune cells via the expression of the checkpoint proteins PDL1 and HLA-E. Furthermore, IFNα induces modules of co-expressed mRNA and proteins that physically interact and have relevance to T1D pathogenesis. The integration of high-coverage RNA-seq and ATAC-seq indicates regulatory gene networks and reveals that alternative splicing and different first exon usage are key mechanisms expanding the repertoire of mRNAs and proteins expressed by stressed beta cells. Finally, mining the modules of co-expressed genes and the IFNα beta cell signature against the most recent catalogs of experimental and clinical drugs identifies two potentially interesting therapeutic targets for future trials. Results IFNα modifies beta cell mRNA expression similarly to T1D We performed a time course multi-omics experiment combining ATAC-seq, RNA-seq and proteomics of the human beta cell line EndoC-βH1 exposed or not to IFNα. The data were integrated to determine the dynamics of chromatin accessibility, gene/transcript expression and protein translation, respectively (Fig. 1a ). We also performed RNA-seq of 6 independent human pancreatic islet preparations exposed or not to the cytokine at similar time points (Supplementary Fig. 1a ). To assess whether our in vitro model is relevant for the in vivo islet inflammation (insulitis) in T1D, we took two approaches: (1) Examine whether candidate genes for T1D expressed in human islets are involved in IFN signaling (Supplementary Fig. 2a ); and (2) Compare our in vitro data of IFNα-treated EndoC-βH1 cells and human islets with available RNA-seq data of human beta cells from T1D patients. In line with previous findings suggesting a role for IFNs on the pathogenesis of T1D 13 , we found that T1D risk genes expressed in human islets 10 , 14 are significantly enriched in immune-related pathways, including type I and II interferon regulation/signaling (Supplementary Fig. 2b ). Next, we performed a Rank–Rank Hypergeometric Overlap (RRHO) analysis (which estimates the similarities between two ranked lists 15 ) comparing the log 2 fold-change (FC) ranked list from RNA-seqs of EndoC-βH1 cells and human islets (IFNα-treated vs untreated) against an equally ranked list of genes obtained from RNA-seq of purified primary beta cells 16 from T1D and healthy individuals (Supplementary Fig. 2c and Supplementary Data 1 ). There was a significant intersection between upregulated genes induced by IFNα in both, EndoC-βH1 cells (362 overlapping genes) and human islets (850 overlapping genes), and genes induced by the local pro-inflammatory environment affecting primary beta cells from T1D individuals (Supplementary Fig. 2d, f ). We also compared these two IFNα-treated datasets against beta cells from T2D patients 17 , a condition mostly characterized by metabolic stress 18 . By contrast with the observations made in beta cells from T1D individuals, there was no statistically significant correlation between IFNα-regulated genes in EndoC-βH1 cells and human islets and the gene expression profile present in T2D beta cells (Supplementary Fig. 2e, g ). Fig. 1: Exposure of EndoC-βH1 cells to interferon-α promotes changes in chromatin accessibility, which are correlated with gene transcription and translation. a EndoC-βH1 cells were exposed or not to IFNα (2000 U/ml) for the indicated time points and different high-throughput techniques were performed to study chromatin accessibility (ATAC-seq, n = 4), transcription", "role": "user" }, { "content": "Researchers from the Indiana Biosciences Research Institute (IBRI), a leading independent, industry-inspired applied research institute, and Université Libre de Bruxelles (ULB) Center for Diabetes Research, identified two classes of compounds that prevent most of the effects of interferon-α (IFNα) on human beta cells, paving the way for potential future clinical trials of treatments for type 1 diabetes (T1D). Dr. Decio Eizirik, scientific director of the IBRI Diabetes Center and Professor at the ULB Center for Diabetes Research, and Dr. Maikel Colli, a researcher at the ULB Center for Diabetes Research, used an innovative \"multi-omics\" approach, funded by JDRF, the European IMI consortium INNODIA and the Belgian Funding Agency Welbio, that combined genomic, transcriptomic and proteomic techniques with advanced bioinformatic tools to analyze the initial changes present in human beta cells exposed to IFNα. \"This is a beautiful example of international collaboration and translational research led by scientists at the IBRI and the ULB,\" said Eizirik. \"Indeed, it started with use of complex omics technology and bioinformatics and ended up with the identification of two agents that may be one day re-purposed for the early treatment of T1D.\" T1D is a chronic autoimmune disease resulting in the destruction of the insulin-producing beta cells. Nearly 1.6 million Americans are affected by T1D. The early steps of the disease involve local release of pro-inflammatory mediators (cytokines) at the pancreatic islet level. One of these mediators is IFNα. In line with this, pancreatic islets obtained from living donors with recent onset T1D have a significant increase in the expression of IFN-stimulated genes, while inhibition of IFNα signaling prevents the development of T1D in animal models. There are currently no effective treatments to prevent T1D. \"JDRF's mission is to cure, treat and prevent T1D. To do so, we must validate key biological pathways as integral in T1D disease processes. Dr. Eizirik's work provides excellent justification for IFNα as a contributing factor in the development and progression of T1D,\" said Sanjoy Dutta, Ph.D., JDRF vice president of research. \"Importantly, his work identifies two drug candidates that, based on his findings, should be beneficial to those at risk of or living with T1D. We look forward to clinical testing of such drugs in people with T1D.\" The study, which was recently published in Nature Communications (\"An integrated multi-omics approach identifies the landscape of interferon-α mediated responses of human pancreatic beta cells\"), is based on collaborations with colleagues from Belgium, Spain, UK, Italy and USA. The changes induced by IFNα were similar to observations made in beta cells obtained from patients affected by T1D. IFNα promotes rapid changes in chromatin (the complex DNA+protein present in the nucleus) accessibility. These changes are probably required to enable gene expression to fight local viral infections but may contribute to trigger autoimmunity and T1D in genetically susceptible individuals. Furthermore, beta cells exposed to IFNα increased expression of proteins inhibiting the immune system, such as PDL1 and HLA-E, which may help to decrease and/or delay the autoimmune assault. This latest finding may explain why cancer immunotherapies using PDL1 blockers causes T1D in some patients. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Interferon-α (IFNα), a type I interferon, is expressed in the islets of type 1 diabetic individuals, and its expression and signaling are regulated by T1D genetic risk variants and viral infections associated with T1D. We presently characterize human beta cell responses to IFNα by combining ATAC-seq, RNA-seq and proteomics assays. The initial response to IFNα is characterized by chromatin remodeling, followed by changes in transcriptional and translational regulation. IFNα induces changes in alternative splicing (AS) and first exon usage, increasing the diversity of transcripts expressed by the beta cells. This, combined with changes observed on protein modification/degradation, ER stress and MHC class I, may expand antigens presented by beta cells to the immune system. Beta cells also up-regulate the checkpoint proteins PDL1 and HLA-E that may exert a protective role against the autoimmune assault. Data mining of the present multi-omics analysis identifies two compound classes that antagonize IFNα effects on human beta cells. Introduction Type 1 diabetes (T1D) is a chronic autoimmune disease leading to pancreatic islet inflammation (insulitis) and progressive beta cell loss 1 . Type I interferons (IFN-I), a class of cytokines involved in antiviral immune responses 2 , are involved in insulitis. Viral infections are a risk factor associated with T1D development 3 and individuals at risk of T1D show a type I interferon signature 4 . The type I interferon, interferon-α (IFNα), is expressed in islets of T1D patients 5 , and antibodies neutralizing different isoforms of IFNα prevent T1D development in individuals with polyglandular autoimmune syndrome type 1 6 . Exposure of human pancreatic beta cells to IFNα recapitulates three key findings observed in human insulitis, namely HLA class I overexpression, endoplasmic reticulum (ER) stress and beta cell apoptosis 7 . Combination of genome-wide association studies (GWAS) 8 and studies using the ImmunoChip 9 have identified around 60 loci associated with the risk of developing T1D. Transcriptomic studies revealed that >70% of the T1D risk genes are expressed in human pancreatic beta cells 10 , and many of these genes regulate innate immunity and type I IFN signaling 11 . Type I IFN signaling is often cell-specific, an effect mediated by differences in cell surface receptor expression, and activation of downstream kinases and transcription factors 12 . Thus, and considering the potential relevance of this cytokine to the pathogenesis of T1D, it is crucial to characterize its effects on human beta cells. To define the global impact of IFNα on human beta cells, we presently performed an integrative multi-omics analysis (ATAC-seq, RNA-seq and proteomics) of IFNα-treated human beta cells to determine the early, intermediate and late responses to the cytokine. The findings obtained indicate that IFNα promotes early changes in chromatin accessibility, activating distant regulatory elements (RE) that control gene expression and protein abundance. IFNα activates key transcription factors (TFs), including IRF1, which act as a mediator of the crosstalk between beta cells and immune cells via the expression of the checkpoint proteins PDL1 and HLA-E. Furthermore, IFNα induces modules of co-expressed mRNA and proteins that physically interact and have relevance to T1D pathogenesis. The integration of high-coverage RNA-seq and ATAC-seq indicates regulatory gene networks and reveals that alternative splicing and different first exon usage are key mechanisms expanding the repertoire of mRNAs and proteins expressed by stressed beta cells. Finally, mining the modules of co-expressed genes and the IFNα beta cell signature against the most recent catalogs of experimental and clinical drugs identifies two potentially interesting therapeutic targets for future trials. Results IFNα modifies beta cell mRNA expression similarly to T1D We performed a time course multi-omics experiment combining ATAC-seq, RNA-seq and proteomics of the human beta cell line EndoC-βH1 exposed or not to IFNα. The data were integrated to determine the dynamics of chromatin accessibility, gene/transcript expression and protein translation, respectively (Fig. 1a ). We also performed RNA-seq of 6 independent human pancreatic islet preparations exposed or not to the cytokine at similar time points (Supplementary Fig. 1a ). To assess whether our in vitro model is relevant for the in vivo islet inflammation (insulitis) in T1D, we took two approaches: (1) Examine whether candidate genes for T1D expressed in human islets are involved in IFN signaling (Supplementary Fig. 2a ); and (2) Compare our in vitro data of IFNα-treated EndoC-βH1 cells and human islets with available RNA-seq data of human beta cells from T1D patients. In line with previous findings suggesting a role for IFNs on the pathogenesis of T1D 13 , we found that T1D risk genes expressed in human islets 10 , 14 are significantly enriched in immune-related pathways, including type I and II interferon regulation/signaling (Supplementary Fig. 2b ). Next, we performed a Rank–Rank Hypergeometric Overlap (RRHO) analysis (which estimates the similarities between two ranked lists 15 ) comparing the log 2 fold-change (FC) ranked list from RNA-seqs of EndoC-βH1 cells and human islets (IFNα-treated vs untreated) against an equally ranked list of genes obtained from RNA-seq of purified primary beta cells 16 from T1D and healthy individuals (Supplementary Fig. 2c and Supplementary Data 1 ). There was a significant intersection between upregulated genes induced by IFNα in both, EndoC-βH1 cells (362 overlapping genes) and human islets (850 overlapping genes), and genes induced by the local pro-inflammatory environment affecting primary beta cells from T1D individuals (Supplementary Fig. 2d, f ). We also compared these two IFNα-treated datasets against beta cells from T2D patients 17 , a condition mostly characterized by metabolic stress 18 . By contrast with the observations made in beta cells from T1D individuals, there was no statistically significant correlation between IFNα-regulated genes in EndoC-βH1 cells and human islets and the gene expression profile present in T2D beta cells (Supplementary Fig. 2e, g ). Fig. 1: Exposure of EndoC-βH1 cells to interferon-α promotes changes in chromatin accessibility, which are correlated with gene transcription and translation. a EndoC-βH1 cells were exposed or not to IFNα (2000 U/ml) for the indicated time points and different high-throughput techniques were performed to study chromatin accessibility (ATAC-seq, n = 4), transcription<|im_end|> <|im_start|>assistant Researchers from the Indiana Biosciences Research Institute (IBRI), a leading independent, industry-inspired applied research institute, and Université Libre de Bruxelles (ULB) Center for Diabetes Research, identified two classes of compounds that prevent most of the effects of interferon-α (IFNα) on human beta cells, paving the way for potential future clinical trials of treatments for type 1 diabetes (T1D). Dr. Decio Eizirik, scientific director of the IBRI Diabetes Center and Professor at the ULB Center for Diabetes Research, and Dr. Maikel Colli, a researcher at the ULB Center for Diabetes Research, used an innovative "multi-omics" approach, funded by JDRF, the European IMI consortium INNODIA and the Belgian Funding Agency Welbio, that combined genomic, transcriptomic and proteomic techniques with advanced bioinformatic tools to analyze the initial changes present in human beta cells exposed to IFNα. "This is a beautiful example of international collaboration and translational research led by scientists at the IBRI and the ULB," said Eizirik. "Indeed, it started with use of complex omics technology and bioinformatics and ended up with the identification of two agents that may be one day re-purposed for the early treatment of T1D." T1D is a chronic autoimmune disease resulting in the destruction of the insulin-producing beta cells. Nearly 1.6 million Americans are affected by T1D. The early steps of the disease involve local release of pro-inflammatory mediators (cytokines) at the pancreatic islet level. One of these mediators is IFNα. In line with this, pancreatic islets obtained from living donors with recent onset T1D have a significant increase in the expression of IFN-stimulated genes, while inhibition of IFNα signaling prevents the development of T1D in animal models. There are currently no effective treatments to prevent T1D. "JDRF's mission is to cure, treat and prevent T1D. To do so, we must validate key biological pathways as integral in T1D disease processes. Dr. Eizirik's work provides excellent justification for IFNα as a contributing factor in the development and progression of T1D," said Sanjoy Dutta, Ph.D., JDRF vice president of research. "Importantly, his work identifies two drug candidates that, based on his findings, should be beneficial to those at risk of or living with T1D. We look forward to clinical testing of such drugs in people with T1D." The study, which was recently published in Nature Communications ("An integrated multi-omics approach identifies the landscape of interferon-α mediated responses of human pancreatic beta cells"), is based on collaborations with colleagues from Belgium, Spain, UK, Italy and USA. The changes induced by IFNα were similar to observations made in beta cells obtained from patients affected by T1D. IFNα promotes rapid changes in chromatin (the complex DNA+protein present in the nucleus) accessibility. These changes are probably required to enable gene expression to fight local viral infections but may contribute to trigger autoimmunity and T1D in genetically susceptible individuals. Furthermore, beta cells exposed to IFNα increased expression of proteins inhibiting the immune system, such as PDL1 and HLA-E, which may help to decrease and/or delay the autoimmune assault. This latest finding may explain why cancer immunotherapies using PDL1 blockers causes T1D in some patients. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Transdifferentiation is a complete and stable change in cell identity that serves as an alternative to stem-cell-mediated organ regeneration. In adult mammals, findings of transdifferentiation have been limited to the replenishment of cells lost from preexisting structures, in the presence of a fully developed scaffold and niche 1 . Here we show that transdifferentiation of hepatocytes in the mouse liver can build a structure that failed to form in development—the biliary system in a mouse model that mimics the hepatic phenotype of human Alagille syndrome (ALGS) 2 . In these mice, hepatocytes convert into mature cholangiocytes and form bile ducts that are effective in draining bile and persist after the cholestatic liver injury is reversed, consistent with transdifferentiation. These findings redefine hepatocyte plasticity, which appeared to be limited to metaplasia, that is, incomplete and transient biliary differentiation as an adaptation to cell injury, based on previous studies in mice with a fully developed biliary system 3 , 4 , 5 , 6 . In contrast to bile duct development 7 , 8 , 9 , we show that de novo bile duct formation by hepatocyte transdifferentiation is independent of NOTCH signalling. We identify TGFβ signalling as the driver of this compensatory mechanism and show that it is active in some patients with ALGS. Furthermore, we show that TGFβ signalling can be targeted to enhance the formation of the biliary system from hepatocytes, and that the transdifferentiation-inducing signals and remodelling capacity of the bile-duct-deficient liver can be harnessed with transplanted hepatocytes. Our results define the regenerative potential of mammalian transdifferentiation and reveal opportunities for the treatment of ALGS and other cholestatic liver diseases. Main In regenerating organs of adult mammals, differentiated cells can replenish other types of differentiated cells by transdifferentiation, as in the pancreatic islet 10 , gastric gland 11 , lung alveolus 12 and intestinal crypt 13 . Whether mammalian transdifferentiation can build these or other structures de novo is unknown. In the liver, hepatocytes can undergo biliary differentiation to form reactive ductules both in humans 14 , 15 , 16 , 17 and animals with cholestatic liver injury 3 , 4 , 5 , 6 , 18 , 19 , 20 , 21 . However, hepatocyte-derived biliary cells exhibit incomplete biliary and residual hepatocyte differentiation, that is, they are not mature cholangiocytes, and revert back to their original identity after the injury is reversed 3 , 4 , 5 , 6 . Moreover, hepatocyte-derived ductules do not contribute to bile drainage 5 . These findings are consistent with metaplasia, but not with transdifferentiation, and call into question the functional importance of hepatocyte plasticity. However, all studies of hepatocyte plasticity published so far used animals with a fully developed biliary system in which residual cholangiocytes are available to regenerate injured bile ducts, probably leading to insufficient pressure for transdifferentiation. To determine the full extent of hepatocyte plasticity, we used mice that lack the intrahepatic biliary system. Specifically, we used mice that mimic the hepatic phenotype of ALGS—a human disease caused by impaired NOTCH signalling 22 , 23 , 24 —generated by deletion of floxed alleles of the NOTCH signalling effector RBPJ and, to prevent compensation 25 , the transcription factor HNF6 (also known as ONECUT1) in embryonic liver progenitors using Cre expressed from an albumin ( Alb ) promoter 2 . These Alb-cre +/− Rbpj f/f Hnf6 f/f mice are severely cholestatic because they lack peripheral bile ducts (pBDs), the branches of the intrahepatic biliary tree, at birth; however, more than 90% of the mice survive and form pBDs and a functional biliary tree by postnatal day (P) 120 26 (Fig. 1a ). Although Alb-cre +/− Rbpj f/f Hnf6 f/f mice have hilar bile ducts (hBDs), the trunk of the biliary tree, we hypothesized that the new pBDs originate from hepatocytes because the livers of Alb-cre +/− Rbpj f/f Hnf6 f/f mice contain hybrid cells that express hepatocyte and biliary markers 2 , 26 . To test this hypothesis, we developed Cre-independent hepatocyte fate tracing. For this, we activated the Flp-reporter (GFP) in R26ZG +/+ mice specifically in hepatocytes by intravenous injection of an adeno-associated virus (AAV) serotype 8 vector expressing Flp from the transthyretin ( Ttr ) promoter (AAV8-Ttr-Flp) (Fig. 1a and Extended Data Fig. 1a–g ). Fig. 1: Hepatocytes can convert into peripheral cholangiocytes and form pBDs contiguous with preexisting hBDs. a , De novo pBD formation and hepatocyte fate tracing in Alb-cre +/− Rbpj f/f Hnf6 f/f R26ZG +/+ mice. Cells identified by dolichos biflorus agglutinin (DBA) lectin labelling and wsCK and GFP immunofluorescence. b , Immunofluorescence of hepatocyte-fate-traced P120 Alb-cre +/− Rbpj f/f Hnf6 f/f R26ZG +/+ mouse liver ( n = 7). c , Biliary tree visualized by retrograde ink injection into the common bile duct of P30 ( n = 6), P120–P138 ( n = 6) and ≥P334 ( n = 6) Alb-cre +/− Rbpj f/f Hnf6 f/f mice, and P30 ( n = 3) and P120–P138 ( n = 5) Rbpj f/f Hnf6 f/f mice. d , Maximum projection (top) and 3D reconstruction (bottom) of z -stack image of hepatocyte-fate-traced P120 Alb-cre +/− Rbpj f/f Hnf6 f/f R26ZG +/+ mouse liver ( n = 2). e , Immunofluorescence and bright-field images of hepatocyte-fate-traced P468 Alb-cre +/− Rbpj f/f Hnf6 f/f R26ZG +/+ mouse liver after retrograde ink injection into the common bile duct (≥P334, n = 3). Scale bars, 2 mm ( c , P30, P395 left), 500 µm ( c , P138 left), 250 µm ( c , P138 right), 100 µm ( b , c , P395 right, d , e , left), 25 µm ( e , middle). Full size image To trace hepatocytes during pBD formation, we intravenously injected Alb-cre +/− Rbpj f/f Hnf6 f/f R26ZG +/+ mice with AAV8-Ttr-Flp at P17, which is before cells expressing biliary markers emerge in the liver periphery 2 , 26 . At P120, the newly formed pBDs, identified by wide-spectrum (ws) cytokeratin (CK) immunofluorescence, were GFP positive, indicating hepatocyte origin", "role": "user" }, { "content": "By studying a rare liver disease called Alagille syndrome, scientists from Cincinnati Children's and the University of California San Francisco (UCSF) have discovered the mechanism behind an unusual form of tissue regeneration that may someday reduce the need for expensive and difficult-to-obtain organ transplants. The team's findings, published in the journal Nature, show that when disease or injury causes a shortage in one critical type of liver cell, the organ can instruct another type of liver cell to change identities to provide replacement supplies. This discovery was made in mice but in years to come may lead to a viable treatment for human disease. If ongoing follow-up studies succeed, the medical world may gain an alternative method for repairing tissue damage that does not require manipulating stem cells to grow organs from scratch in a lab dish. \"We have known for a long time that the liver has more ability to regenerate than other organs. Only recently have we had the tools to study this ability in depth. Now we have a high-level understanding,\" says Stacey Huppert, PhD, a developmental biologist in the Division of Gastroenterology, Hepatology and Nutrition at Cincinnati Children's, and one of two leading co-authors of the paper. \"Our study shows that the form and function of hepatocytes—the cell type that provides most of the liver's functions—are remarkably flexible. This flexibility provides an opportunity for therapy for a large group of liver diseases,\" says Holger Willenbring, MD, PhD, the study's other senior co-author and a member of the Department of Surgery, the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and the Liver Center at UCSF. What is Alagille syndrome? Alagille syndrome (ALGS) is a rare, inherited genetic disorder due to deficiencies in the Notch pathway, which plays an important role in cell development. ALGS is best known for disrupting the liver's plumbing system, which consists of tubes called bile ducts that deliver bile made in the liver to the intestine. The disorder occurs in about 1 in 30,000 people, and in most cases, the problems caused by the condition emerge during infancy or early childhood. The extent of the condition can range from having too few or too narrow bile ducts to missing all bile ducts in the liver. As a result, the bile that normally helps the body digest fat and carry away toxins backs up inside the liver where it causes severe damage. In many patients with ALGS, bile duct function can be managed and sustained. However, up to 50 percent of patients eventually need a liver transplant, often during childhood. A Quicker Method of Self-Repair Every day, the liver takes a beating as it processes everything from medications to alcohol consumption. All these \"insults\" have prompted the liver to develop a rapid healing ability that does not rely on stem cells, the co-authors say. \"In addition to making more of themselves, liver cells can switch their identity to produce a liver cell type that is lost or, in the case of severe ALGS, never formed,\" Willenbring says. \"Previous research has detected adaptive reprogramming in other organs, but it typically involves only a few cells at a time. Our study shows that cells switch their identity at a massive rate in the liver,\" Huppert says. Discovering this phenomenon and learning how it works took nearly five years. The team included co-first authors Johanna Schaub and Simone Kurial from UCSF and Kari Huppert from Cincinnati Children's. The researchers generated mice that lack cholangiocytes, the type of liver cell that forms bile ducts. Like patients with severe ALGS, these mice quickly developed signs of liver injury. However, over time the mice's symptoms improved because hepatocytes converted into cholangiocytes and formed fully functional bile ducts. In July 2017, another study published in Nature reported that cholangiocytes can become hepatocytes if their ability to regenerate is impaired. Viewed together, the two studies suggest that switching of cell identity is the main backup mechanism for liver repair. The new study further shows that the Notch pathway, which is essential for forming bile ducts but defective in patients with ALGS, can be replaced by another pathway. This process is regulated in the injured liver by transforming growth factor beta (TGFβ), a protein that controls cell growth. This discovery is a vital step in identifying targets for therapies that might control this process. Next Steps Now the research team is working to determine the precise set of proteins, called transcription factors, that work together to carry out the identity-switching process. \"Using transcription factors to make bile ducts from hepatocytes has potential as a safe and effective therapy,\" Willenbring says. \"With our finding that an entire biliary system can be 'retrofitted' in the mouse liver, I am encouraged that this eventually will work in patients.\" In addition to developing a therapy for ALGS, the team hopes to determine whether liver cell switching can benefit other types of liver disease. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Transdifferentiation is a complete and stable change in cell identity that serves as an alternative to stem-cell-mediated organ regeneration. In adult mammals, findings of transdifferentiation have been limited to the replenishment of cells lost from preexisting structures, in the presence of a fully developed scaffold and niche 1 . Here we show that transdifferentiation of hepatocytes in the mouse liver can build a structure that failed to form in development—the biliary system in a mouse model that mimics the hepatic phenotype of human Alagille syndrome (ALGS) 2 . In these mice, hepatocytes convert into mature cholangiocytes and form bile ducts that are effective in draining bile and persist after the cholestatic liver injury is reversed, consistent with transdifferentiation. These findings redefine hepatocyte plasticity, which appeared to be limited to metaplasia, that is, incomplete and transient biliary differentiation as an adaptation to cell injury, based on previous studies in mice with a fully developed biliary system 3 , 4 , 5 , 6 . In contrast to bile duct development 7 , 8 , 9 , we show that de novo bile duct formation by hepatocyte transdifferentiation is independent of NOTCH signalling. We identify TGFβ signalling as the driver of this compensatory mechanism and show that it is active in some patients with ALGS. Furthermore, we show that TGFβ signalling can be targeted to enhance the formation of the biliary system from hepatocytes, and that the transdifferentiation-inducing signals and remodelling capacity of the bile-duct-deficient liver can be harnessed with transplanted hepatocytes. Our results define the regenerative potential of mammalian transdifferentiation and reveal opportunities for the treatment of ALGS and other cholestatic liver diseases. Main In regenerating organs of adult mammals, differentiated cells can replenish other types of differentiated cells by transdifferentiation, as in the pancreatic islet 10 , gastric gland 11 , lung alveolus 12 and intestinal crypt 13 . Whether mammalian transdifferentiation can build these or other structures de novo is unknown. In the liver, hepatocytes can undergo biliary differentiation to form reactive ductules both in humans 14 , 15 , 16 , 17 and animals with cholestatic liver injury 3 , 4 , 5 , 6 , 18 , 19 , 20 , 21 . However, hepatocyte-derived biliary cells exhibit incomplete biliary and residual hepatocyte differentiation, that is, they are not mature cholangiocytes, and revert back to their original identity after the injury is reversed 3 , 4 , 5 , 6 . Moreover, hepatocyte-derived ductules do not contribute to bile drainage 5 . These findings are consistent with metaplasia, but not with transdifferentiation, and call into question the functional importance of hepatocyte plasticity. However, all studies of hepatocyte plasticity published so far used animals with a fully developed biliary system in which residual cholangiocytes are available to regenerate injured bile ducts, probably leading to insufficient pressure for transdifferentiation. To determine the full extent of hepatocyte plasticity, we used mice that lack the intrahepatic biliary system. Specifically, we used mice that mimic the hepatic phenotype of ALGS—a human disease caused by impaired NOTCH signalling 22 , 23 , 24 —generated by deletion of floxed alleles of the NOTCH signalling effector RBPJ and, to prevent compensation 25 , the transcription factor HNF6 (also known as ONECUT1) in embryonic liver progenitors using Cre expressed from an albumin ( Alb ) promoter 2 . These Alb-cre +/− Rbpj f/f Hnf6 f/f mice are severely cholestatic because they lack peripheral bile ducts (pBDs), the branches of the intrahepatic biliary tree, at birth; however, more than 90% of the mice survive and form pBDs and a functional biliary tree by postnatal day (P) 120 26 (Fig. 1a ). Although Alb-cre +/− Rbpj f/f Hnf6 f/f mice have hilar bile ducts (hBDs), the trunk of the biliary tree, we hypothesized that the new pBDs originate from hepatocytes because the livers of Alb-cre +/− Rbpj f/f Hnf6 f/f mice contain hybrid cells that express hepatocyte and biliary markers 2 , 26 . To test this hypothesis, we developed Cre-independent hepatocyte fate tracing. For this, we activated the Flp-reporter (GFP) in R26ZG +/+ mice specifically in hepatocytes by intravenous injection of an adeno-associated virus (AAV) serotype 8 vector expressing Flp from the transthyretin ( Ttr ) promoter (AAV8-Ttr-Flp) (Fig. 1a and Extended Data Fig. 1a–g ). Fig. 1: Hepatocytes can convert into peripheral cholangiocytes and form pBDs contiguous with preexisting hBDs. a , De novo pBD formation and hepatocyte fate tracing in Alb-cre +/− Rbpj f/f Hnf6 f/f R26ZG +/+ mice. Cells identified by dolichos biflorus agglutinin (DBA) lectin labelling and wsCK and GFP immunofluorescence. b , Immunofluorescence of hepatocyte-fate-traced P120 Alb-cre +/− Rbpj f/f Hnf6 f/f R26ZG +/+ mouse liver ( n = 7). c , Biliary tree visualized by retrograde ink injection into the common bile duct of P30 ( n = 6), P120–P138 ( n = 6) and ≥P334 ( n = 6) Alb-cre +/− Rbpj f/f Hnf6 f/f mice, and P30 ( n = 3) and P120–P138 ( n = 5) Rbpj f/f Hnf6 f/f mice. d , Maximum projection (top) and 3D reconstruction (bottom) of z -stack image of hepatocyte-fate-traced P120 Alb-cre +/− Rbpj f/f Hnf6 f/f R26ZG +/+ mouse liver ( n = 2). e , Immunofluorescence and bright-field images of hepatocyte-fate-traced P468 Alb-cre +/− Rbpj f/f Hnf6 f/f R26ZG +/+ mouse liver after retrograde ink injection into the common bile duct (≥P334, n = 3). Scale bars, 2 mm ( c , P30, P395 left), 500 µm ( c , P138 left), 250 µm ( c , P138 right), 100 µm ( b , c , P395 right, d , e , left), 25 µm ( e , middle). Full size image To trace hepatocytes during pBD formation, we intravenously injected Alb-cre +/− Rbpj f/f Hnf6 f/f R26ZG +/+ mice with AAV8-Ttr-Flp at P17, which is before cells expressing biliary markers emerge in the liver periphery 2 , 26 . At P120, the newly formed pBDs, identified by wide-spectrum (ws) cytokeratin (CK) immunofluorescence, were GFP positive, indicating hepatocyte origin<|im_end|> <|im_start|>assistant By studying a rare liver disease called Alagille syndrome, scientists from Cincinnati Children's and the University of California San Francisco (UCSF) have discovered the mechanism behind an unusual form of tissue regeneration that may someday reduce the need for expensive and difficult-to-obtain organ transplants. The team's findings, published in the journal Nature, show that when disease or injury causes a shortage in one critical type of liver cell, the organ can instruct another type of liver cell to change identities to provide replacement supplies. This discovery was made in mice but in years to come may lead to a viable treatment for human disease. If ongoing follow-up studies succeed, the medical world may gain an alternative method for repairing tissue damage that does not require manipulating stem cells to grow organs from scratch in a lab dish. "We have known for a long time that the liver has more ability to regenerate than other organs. Only recently have we had the tools to study this ability in depth. Now we have a high-level understanding," says Stacey Huppert, PhD, a developmental biologist in the Division of Gastroenterology, Hepatology and Nutrition at Cincinnati Children's, and one of two leading co-authors of the paper. "Our study shows that the form and function of hepatocytes—the cell type that provides most of the liver's functions—are remarkably flexible. This flexibility provides an opportunity for therapy for a large group of liver diseases," says Holger Willenbring, MD, PhD, the study's other senior co-author and a member of the Department of Surgery, the Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, and the Liver Center at UCSF. What is Alagille syndrome? Alagille syndrome (ALGS) is a rare, inherited genetic disorder due to deficiencies in the Notch pathway, which plays an important role in cell development. ALGS is best known for disrupting the liver's plumbing system, which consists of tubes called bile ducts that deliver bile made in the liver to the intestine. The disorder occurs in about 1 in 30,000 people, and in most cases, the problems caused by the condition emerge during infancy or early childhood. The extent of the condition can range from having too few or too narrow bile ducts to missing all bile ducts in the liver. As a result, the bile that normally helps the body digest fat and carry away toxins backs up inside the liver where it causes severe damage. In many patients with ALGS, bile duct function can be managed and sustained. However, up to 50 percent of patients eventually need a liver transplant, often during childhood. A Quicker Method of Self-Repair Every day, the liver takes a beating as it processes everything from medications to alcohol consumption. All these "insults" have prompted the liver to develop a rapid healing ability that does not rely on stem cells, the co-authors say. "In addition to making more of themselves, liver cells can switch their identity to produce a liver cell type that is lost or, in the case of severe ALGS, never formed," Willenbring says. "Previous research has detected adaptive reprogramming in other organs, but it typically involves only a few cells at a time. Our study shows that cells switch their identity at a massive rate in the liver," Huppert says. Discovering this phenomenon and learning how it works took nearly five years. The team included co-first authors Johanna Schaub and Simone Kurial from UCSF and Kari Huppert from Cincinnati Children's. The researchers generated mice that lack cholangiocytes, the type of liver cell that forms bile ducts. Like patients with severe ALGS, these mice quickly developed signs of liver injury. However, over time the mice's symptoms improved because hepatocytes converted into cholangiocytes and formed fully functional bile ducts. In July 2017, another study published in Nature reported that cholangiocytes can become hepatocytes if their ability to regenerate is impaired. Viewed together, the two studies suggest that switching of cell identity is the main backup mechanism for liver repair. The new study further shows that the Notch pathway, which is essential for forming bile ducts but defective in patients with ALGS, can be replaced by another pathway. This process is regulated in the injured liver by transforming growth factor beta (TGFβ), a protein that controls cell growth. This discovery is a vital step in identifying targets for therapies that might control this process. Next Steps Now the research team is working to determine the precise set of proteins, called transcription factors, that work together to carry out the identity-switching process. "Using transcription factors to make bile ducts from hepatocytes has potential as a safe and effective therapy," Willenbring says. "With our finding that an entire biliary system can be 'retrofitted' in the mouse liver, I am encouraged that this eventually will work in patients." In addition to developing a therapy for ALGS, the team hopes to determine whether liver cell switching can benefit other types of liver disease. <|im_end|>

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4595, 315, 26587, 8624, 13, 220, 128257, 198 ]

2,648

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract IRAS 04368+2557 is a solar-type (low-mass) protostar embedded in a protostellar core (L1527) in the Taurus molecular cloud 1 , 2 , which is only 140 parsecs away from Earth, making it the closest large star-forming region. The protostellar envelope has a flattened shape with a diameter of a thousand astronomical units (1 au is the distance from Earth to the Sun), and is infalling and rotating 3 , 4 , 5 . It also has a protostellar disk with a radius of 90 au (ref. 6 ), from which a planetary system is expected to form 7 , 8 . The interstellar gas, mainly consisting of hydrogen molecules, undergoes a change in density of about three orders of magnitude as it collapses from the envelope into the disk, while being heated from 10 kelvin to over 100 kelvin in the mid-plane, but it has hitherto not been possible to explore changes in chemical composition associated with this collapse. Here we report that the unsaturated hydrocarbon molecule cyclic-C 3 H 2 resides in the infalling rotating envelope, whereas sulphur monoxide (SO) is enhanced in the transition zone at the radius of the centrifugal barrier (100 ± 20 au ), which is the radius at which the kinetic energy of the infalling gas is converted to rotational energy. Such a drastic change in chemistry at the centrifugal barrier was not anticipated, but is probably caused by the discontinuous infalling motion at the centrifugal barrier and local heating processes there. Main We have conducted high-spatial-resolution observations of the millimetre and submillimetre wave lines of cyclic-C 3 H 2 and SO in the 500 au region around IRAS 04368+2557 (Methods). Figure 1a shows the observed integrated-intensity map of the 5 23 –4 32 rotational line of cyclic-C 3 H 2 (where J KK′ represents the rotational energy level of an asymmetric top molecule; see the footnote of Extended Data Table 1 ). The intensity distribution shows a double-peaked structure, where the southern and northern peaks are separated from the protostar position (the continuum peak position: Extended Data Fig. 1 ) by 1′′ (140 au ). Figure 1b shows the position–velocity (PV) diagram along the north–south line centred at the protostar’s position. A rotation signature is clearly seen outward of 100 au from the protostar, where the brightest velocity component is redshifted and blueshifted for the northern and southern parts, respectively. This situation is schematically illustrated in Fig. 1c . Such a rotation signature abruptly disappears inward of 100 au from the protostar. In addition to this signature, weak blueshifted and redshifted components can also be recognized in the northern and southern parts, respectively ( Fig. 1b ). The existence of such counter-velocity components indicates that the gas motion is not simple rotation but accompanies infalling motion, as shown in Fig. 2a . Most importantly, only the infalling (counter-velocity) components are seen towards the protostar position. This means that cyclic-C 3 H 2 is almost absent inward of 100 au . The other cyclic-C 3 H 2 lines (5 51– 4 40 , 9 18 –8 27 /9 28 –8 17 and 10 0,10– 9 19 /10 1,10 –9 09 ) also show similar distributions ( Extended Data Fig. 2 ). Figure 1: IRAS 04368+2557 in the cyclic-C 3 H 2 (5 23– 4 32 ) and SO ( J N = 7 8 –6 7 ) lines. a , Integrated intensity distributions of cyclic-C 3 H 2 (colour) and SO (contours). Contours are every 10 σ (90 mJy beam −1 km s −1 ), starting from 5 σ (the outermost contour). The red and white ellipses represent the synthesized beam sizes for cyclic-C 3 H 2 and SO, respectively. b , The PV diagram of cyclic-C 3 H 2 along a north–south line passing through the protostar position. Contours are every 3 σ (12 mJy beam −1 ), starting from 3 σ . The white rectangle represents the resolution. c , A schematic of the envelope geometry. d , The PV diagram of SO along the same line as b . Contours are every 4 σ (28 mJy beam −1 ), starting from 2 σ . White contours represent negative values. V LSR denotes the velocity with respect to the local standard of rest. The white rectangle represents the resolution. PowerPoint slide Full size image Figure 2: A model of an infalling rotating envelope. a , A schematic illustration of the infalling rotating envelope. The observer is on the left-hand side, looking at the envelope in an edge-on configuration. b , The highest and lowest velocities calculated with the toy model (Methods). The emissions of the coloured closed circles come from the corresponding coloured closed circles in a . c , Here the highest and lowest velocities shown in b (thick blue lines) are superposed on the PV diagram of cyclic-C 3 H 2 . The thick black lines indicate the Keplerian velocity expected for the disk. They trace the broad line profile of SO (thin grey contours) well. White and red rectangles represent the resolutions for SO and cyclic-C 3 H 2 , respectively. PowerPoint slide Full size image To account for this kinematic feature, we developed a toy model describing an infalling rotating envelope, where the gas motion is approximated by the motion of a particle for simplicity ( Fig. 2a ) (Methods and Extended Data Fig. 3 ). According to this model, the maximum infalling velocity towards the protostar position is half of the maximum rotation velocity at the centrifugal barrier of the infalling gas (that is, half the centrifugal radius). In fact, the observed maximum infalling velocity of cyclic-C 3 H 2 towards the protostar position is just half of the maximum rotation velocity ( Fig. 1b ). Therefore, the radius that gives the maximum rotation velocity in the cyclic-C 3 H 2 emission is the position of the centrifugal barrier. We simulate the PV diagram by using the radius of the centrifugal barrier and the maximum rotation", "role": "user" }, { "content": "A new star is formed by gravitational contraction of an interstellar molecular cloud consisting of gas and dust. In the course of this process, a gas disk (protoplanetary disk), whose size is on the order of 100 AU, forms around the protostar and evolves into a planetary system. The solar system was also formed in this way about 4.6 billion years ago, and life was eventually born on the Earth. How unique in the universe is the situation which happened for the solar system? In order to answer this question, understanding the formation of protoplanetary disks as well as the associated chemical evolution in various star forming regions is essential. There have been extensive observational efforts made toward this goal. So far, most of them have focused on changes in the physical structure and the kinematics during the formation process. However, it was very difficult to distinguish the protoplanetary disk from the infalling envelope clearly with such conventional approaches. On the other hand, the chemical evolution associated with disk formation has scarcely been studied observationally because of the insufficient sensitivity and spatial resolution of previous radio telescopes. As a result, a chemical model calculation with many assumptions is the only approach. Naturally, the physical and chemical changes in the disk formation should be coupled with each other. The disk formation around a young protostar has been explored from a novel point of view looking at physics and chemistry simultaneously. L1527 in the Taurus molecular cloud is a molecular cloud core which harbors a young protostar. A global team led by Dr. Nami Sakai, the University of Tokyo, conducted high-sensitivity, high-spatial-resolution observations of L1527 with ALMA (Atacama Large Millimeter/submillimeter Array) newly constructed in the Atacama desert in Chile, and investigated the disk formation process by using the spectral lines of several molecules. As a result, Sakai al. have found that carbon-chain molecules and their related species such as cyclic-C5H2 almost completely disappear from the gas phase inside a raius of 100 AU around the protostar (Figure1, top left; top right). Figure 1. An infrared image of the protostar L1527 taken by the Spitzer Space Telescope. Credit: J. Tobin/NASA/JPL-Caltech Precise measurements of the motion of the gas using the Doppler shift in the spectral lines of the gas components revealed that 100 AU corresponds to the radius of the centrifugal barrier (Figure 2). Figure 2. L1527 observed by Spitzer (Left) and the distributions of cyclic-C3H2 (center) and SO (right) observed by ALMA. ALMA reveals the gas distribution just close to the protostar. Emission from cyclic-C3H2 is weak toward the protostar but strong at the northern and southern parts. Meanwhile, SO has its emission peak near the protostar. Credit: J. Tobin/NASA/JPL-Caltech, N. Sakai/The University of Tokyo At this radius, infalling gas is stopped and accumulated due to the centrifugal force, and then is gradually transferred to the inner disk. Namely, this is the edge of the disk forming region. It has clearly been indentified with the spectral line of cycle-C5H2. On the other hand, the distribution of sulfur monoxide molecules (SO) is found to be localized in a ring structure located at the radius of the centrifugal barrier (100 AU) (Figure 1, bottom left; bottom right). Furthermore, the temperature of the SO molecules is found to be higher than that of the infalling gas. This means that the infalling gas probably causes a weak shock when in rushes into the outer edge of the disk at the centrifugal barrier. The gas temperature is raised around this radius, and the SO molecules frozen on dust grains are liberated into the gas phase. Hence, the spectral line of SO also highlights the disk-formation front. Since the density of the disk is 108 cm-5 or higher, most of the molecules are frozen out onto dust grains in the disk after they pass through the front. It is not at all anticipated that such a drastic chemical change occurs in the transition zone between the infalling envelope and the inner disk. The disk formation and the associated chemical change have successfully been detected by observations of the two chemical species, cyclic-C5H2 and SO. This study has demonstrated a drastic change in chemical composition associated with disk formation around the young protostar (cf; Figure 3). With a coupled view of physics and chemistry, it has also succeeded in highlighting the outermost part of the disk where the gas is still accreting. This success was realized by high-sensitivity and high-spatial-resolution observations with ALMA, and such a study will be extended to other various star-forming regions. In particular, it is very interesting to examine how widely applicable the picture seen in L1527 is to other star-forming regions. Although many observational efforts aimed at understanding planetary-system formation have been made, this study is novel in focusing on the chemical change. By extending this new method to various solar-type protostars using ALMA, the diversity and generality of the chemical evolution from interstellar matter to planetary matter will be unveiled within the next few years. Then, we can critically examine whether the solar system experienced this drastic chemical change. In parallel to the astronomical approach, the origin of the solar system is being investigated by exploring the solar system itself through microanalyses of meteorites, spectroscopy of comets, sample return missions to the asteroids, and so on. The present study will also have a strong impact on these studies by tracing the origins back to interstellar clouds. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract IRAS 04368+2557 is a solar-type (low-mass) protostar embedded in a protostellar core (L1527) in the Taurus molecular cloud 1 , 2 , which is only 140 parsecs away from Earth, making it the closest large star-forming region. The protostellar envelope has a flattened shape with a diameter of a thousand astronomical units (1 au is the distance from Earth to the Sun), and is infalling and rotating 3 , 4 , 5 . It also has a protostellar disk with a radius of 90 au (ref. 6 ), from which a planetary system is expected to form 7 , 8 . The interstellar gas, mainly consisting of hydrogen molecules, undergoes a change in density of about three orders of magnitude as it collapses from the envelope into the disk, while being heated from 10 kelvin to over 100 kelvin in the mid-plane, but it has hitherto not been possible to explore changes in chemical composition associated with this collapse. Here we report that the unsaturated hydrocarbon molecule cyclic-C 3 H 2 resides in the infalling rotating envelope, whereas sulphur monoxide (SO) is enhanced in the transition zone at the radius of the centrifugal barrier (100 ± 20 au ), which is the radius at which the kinetic energy of the infalling gas is converted to rotational energy. Such a drastic change in chemistry at the centrifugal barrier was not anticipated, but is probably caused by the discontinuous infalling motion at the centrifugal barrier and local heating processes there. Main We have conducted high-spatial-resolution observations of the millimetre and submillimetre wave lines of cyclic-C 3 H 2 and SO in the 500 au region around IRAS 04368+2557 (Methods). Figure 1a shows the observed integrated-intensity map of the 5 23 –4 32 rotational line of cyclic-C 3 H 2 (where J KK′ represents the rotational energy level of an asymmetric top molecule; see the footnote of Extended Data Table 1 ). The intensity distribution shows a double-peaked structure, where the southern and northern peaks are separated from the protostar position (the continuum peak position: Extended Data Fig. 1 ) by 1′′ (140 au ). Figure 1b shows the position–velocity (PV) diagram along the north–south line centred at the protostar’s position. A rotation signature is clearly seen outward of 100 au from the protostar, where the brightest velocity component is redshifted and blueshifted for the northern and southern parts, respectively. This situation is schematically illustrated in Fig. 1c . Such a rotation signature abruptly disappears inward of 100 au from the protostar. In addition to this signature, weak blueshifted and redshifted components can also be recognized in the northern and southern parts, respectively ( Fig. 1b ). The existence of such counter-velocity components indicates that the gas motion is not simple rotation but accompanies infalling motion, as shown in Fig. 2a . Most importantly, only the infalling (counter-velocity) components are seen towards the protostar position. This means that cyclic-C 3 H 2 is almost absent inward of 100 au . The other cyclic-C 3 H 2 lines (5 51– 4 40 , 9 18 –8 27 /9 28 –8 17 and 10 0,10– 9 19 /10 1,10 –9 09 ) also show similar distributions ( Extended Data Fig. 2 ). Figure 1: IRAS 04368+2557 in the cyclic-C 3 H 2 (5 23– 4 32 ) and SO ( J N = 7 8 –6 7 ) lines. a , Integrated intensity distributions of cyclic-C 3 H 2 (colour) and SO (contours). Contours are every 10 σ (90 mJy beam −1 km s −1 ), starting from 5 σ (the outermost contour). The red and white ellipses represent the synthesized beam sizes for cyclic-C 3 H 2 and SO, respectively. b , The PV diagram of cyclic-C 3 H 2 along a north–south line passing through the protostar position. Contours are every 3 σ (12 mJy beam −1 ), starting from 3 σ . The white rectangle represents the resolution. c , A schematic of the envelope geometry. d , The PV diagram of SO along the same line as b . Contours are every 4 σ (28 mJy beam −1 ), starting from 2 σ . White contours represent negative values. V LSR denotes the velocity with respect to the local standard of rest. The white rectangle represents the resolution. PowerPoint slide Full size image Figure 2: A model of an infalling rotating envelope. a , A schematic illustration of the infalling rotating envelope. The observer is on the left-hand side, looking at the envelope in an edge-on configuration. b , The highest and lowest velocities calculated with the toy model (Methods). The emissions of the coloured closed circles come from the corresponding coloured closed circles in a . c , Here the highest and lowest velocities shown in b (thick blue lines) are superposed on the PV diagram of cyclic-C 3 H 2 . The thick black lines indicate the Keplerian velocity expected for the disk. They trace the broad line profile of SO (thin grey contours) well. White and red rectangles represent the resolutions for SO and cyclic-C 3 H 2 , respectively. PowerPoint slide Full size image To account for this kinematic feature, we developed a toy model describing an infalling rotating envelope, where the gas motion is approximated by the motion of a particle for simplicity ( Fig. 2a ) (Methods and Extended Data Fig. 3 ). According to this model, the maximum infalling velocity towards the protostar position is half of the maximum rotation velocity at the centrifugal barrier of the infalling gas (that is, half the centrifugal radius). In fact, the observed maximum infalling velocity of cyclic-C 3 H 2 towards the protostar position is just half of the maximum rotation velocity ( Fig. 1b ). Therefore, the radius that gives the maximum rotation velocity in the cyclic-C 3 H 2 emission is the position of the centrifugal barrier. We simulate the PV diagram by using the radius of the centrifugal barrier and the maximum rotation<|im_end|> <|im_start|>assistant A new star is formed by gravitational contraction of an interstellar molecular cloud consisting of gas and dust. In the course of this process, a gas disk (protoplanetary disk), whose size is on the order of 100 AU, forms around the protostar and evolves into a planetary system. The solar system was also formed in this way about 4.6 billion years ago, and life was eventually born on the Earth. How unique in the universe is the situation which happened for the solar system? In order to answer this question, understanding the formation of protoplanetary disks as well as the associated chemical evolution in various star forming regions is essential. There have been extensive observational efforts made toward this goal. So far, most of them have focused on changes in the physical structure and the kinematics during the formation process. However, it was very difficult to distinguish the protoplanetary disk from the infalling envelope clearly with such conventional approaches. On the other hand, the chemical evolution associated with disk formation has scarcely been studied observationally because of the insufficient sensitivity and spatial resolution of previous radio telescopes. As a result, a chemical model calculation with many assumptions is the only approach. Naturally, the physical and chemical changes in the disk formation should be coupled with each other. The disk formation around a young protostar has been explored from a novel point of view looking at physics and chemistry simultaneously. L1527 in the Taurus molecular cloud is a molecular cloud core which harbors a young protostar. A global team led by Dr. Nami Sakai, the University of Tokyo, conducted high-sensitivity, high-spatial-resolution observations of L1527 with ALMA (Atacama Large Millimeter/submillimeter Array) newly constructed in the Atacama desert in Chile, and investigated the disk formation process by using the spectral lines of several molecules. As a result, Sakai al. have found that carbon-chain molecules and their related species such as cyclic-C5H2 almost completely disappear from the gas phase inside a raius of 100 AU around the protostar (Figure1, top left; top right). Figure 1. An infrared image of the protostar L1527 taken by the Spitzer Space Telescope. Credit: J. Tobin/NASA/JPL-Caltech Precise measurements of the motion of the gas using the Doppler shift in the spectral lines of the gas components revealed that 100 AU corresponds to the radius of the centrifugal barrier (Figure 2). Figure 2. L1527 observed by Spitzer (Left) and the distributions of cyclic-C3H2 (center) and SO (right) observed by ALMA. ALMA reveals the gas distribution just close to the protostar. Emission from cyclic-C3H2 is weak toward the protostar but strong at the northern and southern parts. Meanwhile, SO has its emission peak near the protostar. Credit: J. Tobin/NASA/JPL-Caltech, N. Sakai/The University of Tokyo At this radius, infalling gas is stopped and accumulated due to the centrifugal force, and then is gradually transferred to the inner disk. Namely, this is the edge of the disk forming region. It has clearly been indentified with the spectral line of cycle-C5H2. On the other hand, the distribution of sulfur monoxide molecules (SO) is found to be localized in a ring structure located at the radius of the centrifugal barrier (100 AU) (Figure 1, bottom left; bottom right). Furthermore, the temperature of the SO molecules is found to be higher than that of the infalling gas. This means that the infalling gas probably causes a weak shock when in rushes into the outer edge of the disk at the centrifugal barrier. The gas temperature is raised around this radius, and the SO molecules frozen on dust grains are liberated into the gas phase. Hence, the spectral line of SO also highlights the disk-formation front. Since the density of the disk is 108 cm-5 or higher, most of the molecules are frozen out onto dust grains in the disk after they pass through the front. It is not at all anticipated that such a drastic chemical change occurs in the transition zone between the infalling envelope and the inner disk. The disk formation and the associated chemical change have successfully been detected by observations of the two chemical species, cyclic-C5H2 and SO. This study has demonstrated a drastic change in chemical composition associated with disk formation around the young protostar (cf; Figure 3). With a coupled view of physics and chemistry, it has also succeeded in highlighting the outermost part of the disk where the gas is still accreting. This success was realized by high-sensitivity and high-spatial-resolution observations with ALMA, and such a study will be extended to other various star-forming regions. In particular, it is very interesting to examine how widely applicable the picture seen in L1527 is to other star-forming regions. Although many observational efforts aimed at understanding planetary-system formation have been made, this study is novel in focusing on the chemical change. By extending this new method to various solar-type protostars using ALMA, the diversity and generality of the chemical evolution from interstellar matter to planetary matter will be unveiled within the next few years. Then, we can critically examine whether the solar system experienced this drastic chemical change. In parallel to the astronomical approach, the origin of the solar system is being investigated by exploring the solar system itself through microanalyses of meteorites, spectroscopy of comets, sample return missions to the asteroids, and so on. The present study will also have a strong impact on these studies by tracing the origins back to interstellar clouds. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Objectives To investigate whether outcomes of patients who were admitted to hospital differ between those treated by younger and older physicians. Design Observational study. Setting US acute care hospitals. Participants 20% random sample of Medicare fee-for-service beneficiaries aged ≥65 admitted to hospital with a medical condition in 2011-14 and treated by hospitalist physicians to whom they were assigned based on scheduled work shifts. To assess the generalizability of findings, analyses also included patients treated by general internists including both hospitalists and non-hospitalists. Main outcome measures 30 day mortality and readmissions and costs of care. Results 736 537 admissions managed by 18 854 hospitalist physicians (median age 41) were included. Patients’ characteristics were similar across physician ages. After adjustment for characteristics of patients and physicians and hospital fixed effects (effectively comparing physicians within the same hospital), patients’ adjusted 30 day mortality rates were 10.8% for physicians aged <40 (95% confidence interval 10.7% to 10.9%), 11.1% for physicians aged 40-49 (11.0% to 11.3%), 11.3% for physicians aged 50-59 (11.1% to 11.5%), and 12.1% for physicians aged ≥60 (11.6% to 12.5%). Among physicians with a high volume of patients, however, there was no association between physician age and patient mortality. Readmissions did not vary with physician age, while costs of care were slightly higher among older physicians. Similar patterns were observed among general internists and in several sensitivity analyses. Conclusions Within the same hospital, patients treated by older physicians had higher mortality than patients cared for by younger physicians, except those physicians treating high volumes of patients. Introduction The relation between physician age and performance remains largely unknown, particularly with respect to patient outcomes. Clinical skills and knowledge accumulated by more experienced physicians can lead to improved quality of care. Physicians’ skills, however, can also become outdated as scientific knowledge, technology, and clinical guidelines change. Incorporating these changes into clinical practice is time consuming and can at times be overwhelming. 1 2 3 Interest in how quality of care evolves over a physician’s career has revived in recent years, with debates over how best to structure programs for continuing medical education, including recent controversy in the US regarding maintenance of certification programs. A systematic review of the relation between physician experience and quality of care found that older physicians might perform worse—older physicians have decreased clinical knowledge, adhere less often to standards of appropriate treatment, and perform worse on process measures of quality with respect to diagnosis, screening, and preventive care. 4 Data on patient outcomes, which arguably are most important, have been scarce. 4 Existing studies have also been limited in size or disease scope and have not been nationally representative. 5 6 7 As a result, whether physician age is associated with patient outcomes remains largely unknown. Using nationally representative data on Medicare beneficiaries admitted to hospital with a medical condition during 2011-14, we sought answers to three questions. First, what is the association between age of the treating physician and patient mortality after admission? Second, does this association vary with the volume of patients a physician treats? Finally, given national efforts to improve the efficiency of healthcare, is physician age associated with readmissions and costs of care? Methods Data We linked multiple data sources: the 20% Medicare Inpatient Carrier and Medicare Beneficiary Summary Files (2011-14); physician data collected by Doximity (an online professional network for physicians); and the American Hospital Association (AHA) annual survey of hospital characteristics (2012). Doximity has assembled data on all US physicians (both those who are registered members of the service as well as those who are not) from multiple sources and data partnerships, including the national plan and provider enumeration system national provider identifier registry, state medical boards, specialty societies such as the American Board of Medical Specialties, and collaborating hospitals and medical schools. The database includes information on physician age, sex, year of completion and name of medical school, residency, and board certification. 8 9 10 11 12 Previous studies have validated data for a random sample of physicians in the Doximity database by using manual audits. 8 9 We were able to match about 95% of physicians in the Medicare database to the Doximity database. Patients We identified beneficiaries of Medicare fee-for-service aged ≥65 who were admitted to hospital with a medical condition (as defined by the presence of a medical diagnosis related group on admission) from 1 January 2011 to 31 December 2014. We restricted our sample to patients treated in acute care hospitals and excluded elective admissions and those in which a patient left against medical advice. To allow sufficient follow-up, we excluded patients admitted in December 2014 from 30 day mortality analyses and patients discharged in December 2014 from readmission analyses. Medicare hospital spending and method of assigning physicians to patients In the US, Medicare spending on patients in hospital mainly consists of two components: parts A and B. Part A spending is a fixed payment to a hospital per patient that is determined by the final diagnosis or diagnoses of the patient (categorized into diagnosis related groups) and broadly reflects hospital costs other than professional services. Within each hospital the part A payment does not vary for patients within the same diagnosis related group (with a few exceptions). Part B uses fee-for-service payment, and spending varies with the intensity of services delivered, including visits, procedures, and interpretation of tests and images. Based on previous studies, 10 11 12 we defined the responsible physician for a given admission as the physician who billed the largest share of part B costs during that admission. 13 In a sensitivity analysis, we used alternative assignment methods to assess the robustness of our findings to this attribution rule. We restricted our analyses to admissions for which the highest spending physicians were hospitalists (described below) or general internists. For patients transferred to other acute care hospitals (1.2% of admissions), we attributed the multi-hospital episode of care and associated outcomes to the assigned physician of the initial admissions. 14 15 On average, 51%, 22%, and", "role": "user" }, { "content": "Patients in US hospitals treated by older physicians have higher mortality than patients cared for by younger physicians, except those physicians treating high volumes of patients, finds a study published by The BMJ today. If the results are causal, they suggest that for every 77 patients treated by doctors aged 60 or over, one fewer patient would die within 30 days of admission if those patients were cared for by physicians aged less than 40. However, the researchers stress that their findings should be regarded as exploratory. Clinical skills and knowledge accumulated by more experienced physicians can lead to improved quality of care. It is possible, however, that physicians' skills may become outdated as scientific knowledge, technology, and clinical guidelines evolve. Whether quality of care differs between younger and older physicians remains largely unknown, so a team led by Yusuke Tsugawa at Harvard T H Chan School of Public Health in Boston, set out to investigate whether outcomes of patients who were admitted to hospital differ between those treated by younger and older physicians. They analysed 30 day mortality, readmissions and costs of care for a random sample of 736,537 elderly Medicare patients (aged 65 or over) managed by 18,854 hospital physicians (average age 41) at US acute care hospitals from 2011 to 2014. Patients were assigned a physician based on scheduled work shifts and patients'characteristics were similar across physician ages. After adjusting for patient, physician, and hospital characteristics that could have affected the results, patients' 30 day mortality rates were 10.8% for physicians aged less than 40, 11.1% for physicians aged 40-49, 11.3% for physicians aged 50-59, and 12.1% for physicians aged 60 or over. Among physicians with a high volume of patients, however, there was no associationbetween physician age and patient mortality, suggesting that high volumes could be \"protective\" of clinical skills, say the authors. Readmissions did not vary with physician age, while costs of care were slightly higher among older physicians. And similar patterns were observed after further analyses to test the strength of the results. The researchers say this is an observational study, so no firm conclusions can be drawn about cause and effect, and they outline some limitations could have introduced bias. Nevertheless, they conclude that \"within the same hospital, patients treated by older physicians had higher mortality than patients cared for by younger physicians, except those physicians treating high volumes of patient volumes.\" In a linked editorial, researchers at the University of Pennsylvania ask what are the options for ensuring that quality and safety of care is optimized for patients. They point out that patient outcomes research \"is providing much needed evidence to inform clinical practice, educational innovation, organizational redesign, and healthcare policy.\" The challenge, they say, \"is to integrate findings across multiple studies within an overarching framework of health system responsibility, as recommended by the Institute of Medicine, which holds promise of safe care and good patient outcomes despite diversity of performance by individuals.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Objectives To investigate whether outcomes of patients who were admitted to hospital differ between those treated by younger and older physicians. Design Observational study. Setting US acute care hospitals. Participants 20% random sample of Medicare fee-for-service beneficiaries aged ≥65 admitted to hospital with a medical condition in 2011-14 and treated by hospitalist physicians to whom they were assigned based on scheduled work shifts. To assess the generalizability of findings, analyses also included patients treated by general internists including both hospitalists and non-hospitalists. Main outcome measures 30 day mortality and readmissions and costs of care. Results 736 537 admissions managed by 18 854 hospitalist physicians (median age 41) were included. Patients’ characteristics were similar across physician ages. After adjustment for characteristics of patients and physicians and hospital fixed effects (effectively comparing physicians within the same hospital), patients’ adjusted 30 day mortality rates were 10.8% for physicians aged <40 (95% confidence interval 10.7% to 10.9%), 11.1% for physicians aged 40-49 (11.0% to 11.3%), 11.3% for physicians aged 50-59 (11.1% to 11.5%), and 12.1% for physicians aged ≥60 (11.6% to 12.5%). Among physicians with a high volume of patients, however, there was no association between physician age and patient mortality. Readmissions did not vary with physician age, while costs of care were slightly higher among older physicians. Similar patterns were observed among general internists and in several sensitivity analyses. Conclusions Within the same hospital, patients treated by older physicians had higher mortality than patients cared for by younger physicians, except those physicians treating high volumes of patients. Introduction The relation between physician age and performance remains largely unknown, particularly with respect to patient outcomes. Clinical skills and knowledge accumulated by more experienced physicians can lead to improved quality of care. Physicians’ skills, however, can also become outdated as scientific knowledge, technology, and clinical guidelines change. Incorporating these changes into clinical practice is time consuming and can at times be overwhelming. 1 2 3 Interest in how quality of care evolves over a physician’s career has revived in recent years, with debates over how best to structure programs for continuing medical education, including recent controversy in the US regarding maintenance of certification programs. A systematic review of the relation between physician experience and quality of care found that older physicians might perform worse—older physicians have decreased clinical knowledge, adhere less often to standards of appropriate treatment, and perform worse on process measures of quality with respect to diagnosis, screening, and preventive care. 4 Data on patient outcomes, which arguably are most important, have been scarce. 4 Existing studies have also been limited in size or disease scope and have not been nationally representative. 5 6 7 As a result, whether physician age is associated with patient outcomes remains largely unknown. Using nationally representative data on Medicare beneficiaries admitted to hospital with a medical condition during 2011-14, we sought answers to three questions. First, what is the association between age of the treating physician and patient mortality after admission? Second, does this association vary with the volume of patients a physician treats? Finally, given national efforts to improve the efficiency of healthcare, is physician age associated with readmissions and costs of care? Methods Data We linked multiple data sources: the 20% Medicare Inpatient Carrier and Medicare Beneficiary Summary Files (2011-14); physician data collected by Doximity (an online professional network for physicians); and the American Hospital Association (AHA) annual survey of hospital characteristics (2012). Doximity has assembled data on all US physicians (both those who are registered members of the service as well as those who are not) from multiple sources and data partnerships, including the national plan and provider enumeration system national provider identifier registry, state medical boards, specialty societies such as the American Board of Medical Specialties, and collaborating hospitals and medical schools. The database includes information on physician age, sex, year of completion and name of medical school, residency, and board certification. 8 9 10 11 12 Previous studies have validated data for a random sample of physicians in the Doximity database by using manual audits. 8 9 We were able to match about 95% of physicians in the Medicare database to the Doximity database. Patients We identified beneficiaries of Medicare fee-for-service aged ≥65 who were admitted to hospital with a medical condition (as defined by the presence of a medical diagnosis related group on admission) from 1 January 2011 to 31 December 2014. We restricted our sample to patients treated in acute care hospitals and excluded elective admissions and those in which a patient left against medical advice. To allow sufficient follow-up, we excluded patients admitted in December 2014 from 30 day mortality analyses and patients discharged in December 2014 from readmission analyses. Medicare hospital spending and method of assigning physicians to patients In the US, Medicare spending on patients in hospital mainly consists of two components: parts A and B. Part A spending is a fixed payment to a hospital per patient that is determined by the final diagnosis or diagnoses of the patient (categorized into diagnosis related groups) and broadly reflects hospital costs other than professional services. Within each hospital the part A payment does not vary for patients within the same diagnosis related group (with a few exceptions). Part B uses fee-for-service payment, and spending varies with the intensity of services delivered, including visits, procedures, and interpretation of tests and images. Based on previous studies, 10 11 12 we defined the responsible physician for a given admission as the physician who billed the largest share of part B costs during that admission. 13 In a sensitivity analysis, we used alternative assignment methods to assess the robustness of our findings to this attribution rule. We restricted our analyses to admissions for which the highest spending physicians were hospitalists (described below) or general internists. For patients transferred to other acute care hospitals (1.2% of admissions), we attributed the multi-hospital episode of care and associated outcomes to the assigned physician of the initial admissions. 14 15 On average, 51%, 22%, and<|im_end|> <|im_start|>assistant Patients in US hospitals treated by older physicians have higher mortality than patients cared for by younger physicians, except those physicians treating high volumes of patients, finds a study published by The BMJ today. If the results are causal, they suggest that for every 77 patients treated by doctors aged 60 or over, one fewer patient would die within 30 days of admission if those patients were cared for by physicians aged less than 40. However, the researchers stress that their findings should be regarded as exploratory. Clinical skills and knowledge accumulated by more experienced physicians can lead to improved quality of care. It is possible, however, that physicians' skills may become outdated as scientific knowledge, technology, and clinical guidelines evolve. Whether quality of care differs between younger and older physicians remains largely unknown, so a team led by Yusuke Tsugawa at Harvard T H Chan School of Public Health in Boston, set out to investigate whether outcomes of patients who were admitted to hospital differ between those treated by younger and older physicians. They analysed 30 day mortality, readmissions and costs of care for a random sample of 736,537 elderly Medicare patients (aged 65 or over) managed by 18,854 hospital physicians (average age 41) at US acute care hospitals from 2011 to 2014. Patients were assigned a physician based on scheduled work shifts and patients'characteristics were similar across physician ages. After adjusting for patient, physician, and hospital characteristics that could have affected the results, patients' 30 day mortality rates were 10.8% for physicians aged less than 40, 11.1% for physicians aged 40-49, 11.3% for physicians aged 50-59, and 12.1% for physicians aged 60 or over. Among physicians with a high volume of patients, however, there was no associationbetween physician age and patient mortality, suggesting that high volumes could be "protective" of clinical skills, say the authors. Readmissions did not vary with physician age, while costs of care were slightly higher among older physicians. And similar patterns were observed after further analyses to test the strength of the results. The researchers say this is an observational study, so no firm conclusions can be drawn about cause and effect, and they outline some limitations could have introduced bias. Nevertheless, they conclude that "within the same hospital, patients treated by older physicians had higher mortality than patients cared for by younger physicians, except those physicians treating high volumes of patient volumes." In a linked editorial, researchers at the University of Pennsylvania ask what are the options for ensuring that quality and safety of care is optimized for patients. They point out that patient outcomes research "is providing much needed evidence to inform clinical practice, educational innovation, organizational redesign, and healthcare policy." The challenge, they say, "is to integrate findings across multiple studies within an overarching framework of health system responsibility, as recommended by the Institute of Medicine, which holds promise of safe care and good patient outcomes despite diversity of performance by individuals." <|im_end|>

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1,928

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Single-photon emitters (SPEs) in hexagonal boron nitride (hBN) have garnered increasing attention over the last few years due to their superior optical properties. However, despite the vast range of experimental results and theoretical calculations, the defect structure responsible for the observed emission has remained elusive. Here, by controlling the incorporation of impurities into hBN via various bottom-up synthesis methods and directly through ion implantation, we provide direct evidence that the visible SPEs are carbon related. Room-temperature optically detected magnetic resonance is demonstrated on ensembles of these defects. We perform ion-implantation experiments and confirm that only carbon implantation creates SPEs in the visible spectral range. Computational analysis of the simplest 12 carbon-containing defect species suggest the negatively charged \${\\rm{V}}_{\\rm{B}}{\\rm{C}}_{\\rm{N}}^ -\$ defect as a viable candidate and predict that out-of-plane deformations make the defect environmentally sensitive. Our results resolve a long-standing debate about the origin of single emitters at the visible range in hBN and will be key to the deterministic engineering of these defects for quantum photonic devices. Main Single defects in solids have become some of the most promising front-runner hardware constituents of applications in quantum information technologies and integrated quantum photonics 1 . Substantial effort has been devoted to isolate and deterministically engineer such defects in wide-band-gap materials such as diamond and silicon carbide 2 , 3 . This collective effort resulted in spectacular proof-of-principle demonstrations ranging from quantum networks to spin–photon interfaces 3 , while simultaneously and steadily leading to understanding the fundamental-level structures of these defects. Recently, hexagonal boron nitride (hBN) has emerged as a promising host material for defects which display ultrabright single-photon emission (SPE) 4 , 5 , 6 , 7 , 8 . They exhibit remarkable properties: a strong response to applied strain and electric fields (Stark shifts) 9 , 10 , 11 , stability under high pressure and elevated temperatures 12 , 13 , potential for resonant excitation above cryogenic temperatures 14 , 15 , 16 and addressability via spin-selective optical transitions 17 , 18 . Yet, despite the numerous experimental characterizations and in-depth theoretical attempts to model their possible crystalline structure 6 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , the nature of these defects remains unknown. Part of the challenge stems from standard hBN bulk crystal synthesis via high pressure and high temperature not being amenable to the deterministic control of impurity incorporation. This is aggravated by the induced impurities often segregating and forming regions of inhomogeneous defect concentration 26 . In addition, the two-dimensional, layered nature of hBN makes ion implantation difficult to control. These limitations have precluded identifying the exact origin of the single-photon emission in the material. Here we address this problem by carrying out a detailed study surveying various hBN samples grown in different laboratories by metal–organic vapour-phase epitaxy (MOVPE) and molecular beam epitaxy (MBE). We find compelling evidence that to observe photoluminescence from SPEs the inclusion of carbon atoms in hBN is required. By systematically growing samples with different carbon concentrations, we show that the carbon content determines whether the photoluminescence signal originates from an ensemble of emitters (high carbon concentration) or isolated defects (low carbon concentration). Defect ensembles are demonstrated to display room-temperature optically detected magnetic resonance (ODMR). We carry out multispecies ion-implantation experiments on both MOVPE films and exfoliated hBN, showing that only carbon implantation creates SPEs and that the density of emitters scales directly with the implantation dose of carbon. Our results are supported by rigorous modelling analysis of carbon-related defects. Optical properties of carbon-doped hBN Table 1 summarizes the materials analysed. They are epitaxial hBN samples grown by different methods and under various conditions. The rationale was to understand whether the single defects are intrinsic to hBN (for example, substitutional or interstitial nitrogen or boron complexes) or involve foreign atoms (for example, carbon). We investigated hBN samples grown by four methods: (1) MOVPE with varying flow rates of the precursor triethylboron (TEB)—a parameter known to systematically alter the levels of incorporated carbon; (2) high-temperature MBE on sapphire with and without a source of carbon; (3) high-temperature MBE on SiC with a varying orientation of the Si face to explore the possibility of carbon incorporation occurring from the substrate; (4) growth by the conversion of highly oriented pyrolytic graphite (HOPG) into hBN. Note that in the current work we focus on bottom-up growth of hBN as it offers an opportunity for large (centimetre) scale films of desired thickness (down to ~1 nm), as well as better control over the inclusions of impurities. Table 1 Epitaxial hBN samples with varying carbon concentrations Full size table We first explore the photoluminescence (PL) from a series of hBN samples grown by MOVPE 27 as the TEB flow rate is increased and the ammonia flow is kept constant (Fig. 1a ). The aim of this measurement is to engineer an ensemble of hBN emitters, and to compare their properties with isolated SPEs grown using the same growth technique. A region of the TEB 10 (µmol min −1 ) sample with the lowest percentage of carbon shows negligible fluorescence. Increasing the flow rate to TEB 20 is accompanied by the appearance of a bright fluorescence signal with two clear peaks appearing at ~585 and ~635 nm. Further increasing the flow rate to TEB 30 and 60 provides a similarly structured PL signature, with higher fluorescence intensity, confirming that higher PL intensity directly correlates with higher TEB flux. Moderate fluctuations in the peak positions and the intensity ratio of the 585 and 635 nm peaks at different sample locations are consistent with emission from dense ensembles of hBN emitters. This also confirms previous findings showing that hBN emitters possess zero-phonon line (ZPL) wavelengths clustered at ~585 nm when the sample is grown epitaxially 28 , 29 . The energy detuning between the ZPL of the ensemble and phonon sideband (PSB) peak is ~176 meV on average (Extended Data Fig. 1 ) 30 , 31 . Fig. 1: Photoluminescence from MOVPE hBN", "role": "user" }, { "content": "Systems which can emit a stream of single photons, referred to as quantum light sources, are critical hardware components for emerging technologies such as quantum computing, the quantum internet, and quantum communications. In many cases the ability to generate quantum light on-demand requires the manipulation and control of single atoms or molecules, pushing the limit of modern fabrication techniques, and making the development of these systems a cross-disciplinary challenge. In new research, published in Nature Materials, an international multidisciplinary collaboration led by the University of Technology Sydney (UTS), has uncovered the chemical structure behind defects in white graphene (hexagonal boron nitride, hBN), a two dimensional nanomaterial that shows great promise as a platform for generating quantum light. The defects, or crystal imperfections, can act as single photon sources and an understanding of their chemical structure is critical to being able to fabricate them in a controlled way. \"hBN single photon emitters display outstanding optical properties, among the best from any solid state material system, however, to make practical use of them we need to understand the nature of the defect and we have finally started to unravel this riddle,\" says UTS Ph.D. candidate Noah Mendelson and first author of the study. \"Unfortunately, we cannot simply combine powerful techniques to visualize single atoms directly with quantum optics measurements, so obtaining this structural information is very challenging. Instead we attacked this problem from a different angle, by controlling the incorporation of dopants, like carbon, into hBN during growth and then directly comparing the optical properties for each, \" he said. To realise this comprehensive study, the team, led by Professor Igor Aharonovich, chief investigator of the UTS node of the ARC Centre of Excellence for Transformative Meta-Optical Materials (TMOS), turned to collaborators in Australia and around the world to provide the array of samples needed. The researchers were able to observe, for the first time, a direct link between carbon incorporation into the hBN lattice and quantum emission. \"Determining the structure of material defects is an incredibly challenging problem and requires experts from many disciplines. This is not something we could have done within our group alone. Only by teaming up with collaborators from across the world whose expertise lies in different materials growth techniques could we study this issue comprehensively. Working together were we finally able to provide the clarity needed for the research community as a whole,\" said Professor Aharonovich. \"It was particularly exciting as this study was enabled by the new collaborative efforts with collaborators Dipankar Chugh, Hark Hoe Tan and Chennupati Jagadish from the TMOS node at the Australian National University, \" he said. The scientists also identified another intriguing feature in their study, that the defects carry spin, a fundamental quantum mechanical property, and a key element to encode and retrieve quantum information stored on single photons. \"Confirming these defects carry spin opens up exciting possibilities for future quantum sensing applications, specifically with atomically thin materials.\" Professor Aharonovich said. The work brings to the forefront a novel research field, 2-D quantum spintronics, and lays the groundwork for further studies into quantum light emission from hBN. The authors anticipate their work will stimulate increased interest in the field and facilitate a range of follow up experiments such as the generation of entangled photon pairs from hBN, detailed studies of the spin properties of the system, and theoretical confirmation of the defect structure. \"This is just the beginning, and we anticipate our findings will accelerate the deployment of hBN quantum emitters for a range of emerging technologies,\" concludes Mr. Mendelson. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Single-photon emitters (SPEs) in hexagonal boron nitride (hBN) have garnered increasing attention over the last few years due to their superior optical properties. However, despite the vast range of experimental results and theoretical calculations, the defect structure responsible for the observed emission has remained elusive. Here, by controlling the incorporation of impurities into hBN via various bottom-up synthesis methods and directly through ion implantation, we provide direct evidence that the visible SPEs are carbon related. Room-temperature optically detected magnetic resonance is demonstrated on ensembles of these defects. We perform ion-implantation experiments and confirm that only carbon implantation creates SPEs in the visible spectral range. Computational analysis of the simplest 12 carbon-containing defect species suggest the negatively charged ${\rm{V}}_{\rm{B}}{\rm{C}}_{\rm{N}}^ -$ defect as a viable candidate and predict that out-of-plane deformations make the defect environmentally sensitive. Our results resolve a long-standing debate about the origin of single emitters at the visible range in hBN and will be key to the deterministic engineering of these defects for quantum photonic devices. Main Single defects in solids have become some of the most promising front-runner hardware constituents of applications in quantum information technologies and integrated quantum photonics 1 . Substantial effort has been devoted to isolate and deterministically engineer such defects in wide-band-gap materials such as diamond and silicon carbide 2 , 3 . This collective effort resulted in spectacular proof-of-principle demonstrations ranging from quantum networks to spin–photon interfaces 3 , while simultaneously and steadily leading to understanding the fundamental-level structures of these defects. Recently, hexagonal boron nitride (hBN) has emerged as a promising host material for defects which display ultrabright single-photon emission (SPE) 4 , 5 , 6 , 7 , 8 . They exhibit remarkable properties: a strong response to applied strain and electric fields (Stark shifts) 9 , 10 , 11 , stability under high pressure and elevated temperatures 12 , 13 , potential for resonant excitation above cryogenic temperatures 14 , 15 , 16 and addressability via spin-selective optical transitions 17 , 18 . Yet, despite the numerous experimental characterizations and in-depth theoretical attempts to model their possible crystalline structure 6 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , the nature of these defects remains unknown. Part of the challenge stems from standard hBN bulk crystal synthesis via high pressure and high temperature not being amenable to the deterministic control of impurity incorporation. This is aggravated by the induced impurities often segregating and forming regions of inhomogeneous defect concentration 26 . In addition, the two-dimensional, layered nature of hBN makes ion implantation difficult to control. These limitations have precluded identifying the exact origin of the single-photon emission in the material. Here we address this problem by carrying out a detailed study surveying various hBN samples grown in different laboratories by metal–organic vapour-phase epitaxy (MOVPE) and molecular beam epitaxy (MBE). We find compelling evidence that to observe photoluminescence from SPEs the inclusion of carbon atoms in hBN is required. By systematically growing samples with different carbon concentrations, we show that the carbon content determines whether the photoluminescence signal originates from an ensemble of emitters (high carbon concentration) or isolated defects (low carbon concentration). Defect ensembles are demonstrated to display room-temperature optically detected magnetic resonance (ODMR). We carry out multispecies ion-implantation experiments on both MOVPE films and exfoliated hBN, showing that only carbon implantation creates SPEs and that the density of emitters scales directly with the implantation dose of carbon. Our results are supported by rigorous modelling analysis of carbon-related defects. Optical properties of carbon-doped hBN Table 1 summarizes the materials analysed. They are epitaxial hBN samples grown by different methods and under various conditions. The rationale was to understand whether the single defects are intrinsic to hBN (for example, substitutional or interstitial nitrogen or boron complexes) or involve foreign atoms (for example, carbon). We investigated hBN samples grown by four methods: (1) MOVPE with varying flow rates of the precursor triethylboron (TEB)—a parameter known to systematically alter the levels of incorporated carbon; (2) high-temperature MBE on sapphire with and without a source of carbon; (3) high-temperature MBE on SiC with a varying orientation of the Si face to explore the possibility of carbon incorporation occurring from the substrate; (4) growth by the conversion of highly oriented pyrolytic graphite (HOPG) into hBN. Note that in the current work we focus on bottom-up growth of hBN as it offers an opportunity for large (centimetre) scale films of desired thickness (down to ~1 nm), as well as better control over the inclusions of impurities. Table 1 Epitaxial hBN samples with varying carbon concentrations Full size table We first explore the photoluminescence (PL) from a series of hBN samples grown by MOVPE 27 as the TEB flow rate is increased and the ammonia flow is kept constant (Fig. 1a ). The aim of this measurement is to engineer an ensemble of hBN emitters, and to compare their properties with isolated SPEs grown using the same growth technique. A region of the TEB 10 (µmol min −1 ) sample with the lowest percentage of carbon shows negligible fluorescence. Increasing the flow rate to TEB 20 is accompanied by the appearance of a bright fluorescence signal with two clear peaks appearing at ~585 and ~635 nm. Further increasing the flow rate to TEB 30 and 60 provides a similarly structured PL signature, with higher fluorescence intensity, confirming that higher PL intensity directly correlates with higher TEB flux. Moderate fluctuations in the peak positions and the intensity ratio of the 585 and 635 nm peaks at different sample locations are consistent with emission from dense ensembles of hBN emitters. This also confirms previous findings showing that hBN emitters possess zero-phonon line (ZPL) wavelengths clustered at ~585 nm when the sample is grown epitaxially 28 , 29 . The energy detuning between the ZPL of the ensemble and phonon sideband (PSB) peak is ~176 meV on average (Extended Data Fig. 1 ) 30 , 31 . Fig. 1: Photoluminescence from MOVPE hBN<|im_end|> <|im_start|>assistant Systems which can emit a stream of single photons, referred to as quantum light sources, are critical hardware components for emerging technologies such as quantum computing, the quantum internet, and quantum communications. In many cases the ability to generate quantum light on-demand requires the manipulation and control of single atoms or molecules, pushing the limit of modern fabrication techniques, and making the development of these systems a cross-disciplinary challenge. In new research, published in Nature Materials, an international multidisciplinary collaboration led by the University of Technology Sydney (UTS), has uncovered the chemical structure behind defects in white graphene (hexagonal boron nitride, hBN), a two dimensional nanomaterial that shows great promise as a platform for generating quantum light. The defects, or crystal imperfections, can act as single photon sources and an understanding of their chemical structure is critical to being able to fabricate them in a controlled way. "hBN single photon emitters display outstanding optical properties, among the best from any solid state material system, however, to make practical use of them we need to understand the nature of the defect and we have finally started to unravel this riddle," says UTS Ph.D. candidate Noah Mendelson and first author of the study. "Unfortunately, we cannot simply combine powerful techniques to visualize single atoms directly with quantum optics measurements, so obtaining this structural information is very challenging. Instead we attacked this problem from a different angle, by controlling the incorporation of dopants, like carbon, into hBN during growth and then directly comparing the optical properties for each, " he said. To realise this comprehensive study, the team, led by Professor Igor Aharonovich, chief investigator of the UTS node of the ARC Centre of Excellence for Transformative Meta-Optical Materials (TMOS), turned to collaborators in Australia and around the world to provide the array of samples needed. The researchers were able to observe, for the first time, a direct link between carbon incorporation into the hBN lattice and quantum emission. "Determining the structure of material defects is an incredibly challenging problem and requires experts from many disciplines. This is not something we could have done within our group alone. Only by teaming up with collaborators from across the world whose expertise lies in different materials growth techniques could we study this issue comprehensively. Working together were we finally able to provide the clarity needed for the research community as a whole," said Professor Aharonovich. "It was particularly exciting as this study was enabled by the new collaborative efforts with collaborators Dipankar Chugh, Hark Hoe Tan and Chennupati Jagadish from the TMOS node at the Australian National University, " he said. The scientists also identified another intriguing feature in their study, that the defects carry spin, a fundamental quantum mechanical property, and a key element to encode and retrieve quantum information stored on single photons. "Confirming these defects carry spin opens up exciting possibilities for future quantum sensing applications, specifically with atomically thin materials." Professor Aharonovich said. The work brings to the forefront a novel research field, 2-D quantum spintronics, and lays the groundwork for further studies into quantum light emission from hBN. The authors anticipate their work will stimulate increased interest in the field and facilitate a range of follow up experiments such as the generation of entangled photon pairs from hBN, detailed studies of the spin properties of the system, and theoretical confirmation of the defect structure. "This is just the beginning, and we anticipate our findings will accelerate the deployment of hBN quantum emitters for a range of emerging technologies," concludes Mr. Mendelson. <|im_end|>

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305, 15967, 10688, 15042, 555, 2204, 5528, 323, 1234, 5370, 4787, 13, 578, 57916, 574, 311, 3619, 3508, 279, 3254, 42655, 527, 47701, 311, 305, 15967, 320, 2000, 3187, 11, 50068, 278, 477, 958, 49270, 47503, 477, 32732, 263, 69125, 8, 477, 21736, 7362, 33299, 320, 2000, 3187, 11, 12782, 570, 1226, 27313, 305, 15967, 10688, 15042, 555, 3116, 5528, 25, 320, 16, 8, 38728, 1777, 449, 29865, 6530, 7969, 315, 279, 71261, 2463, 42972, 9552, 263, 320, 2505, 33, 68850, 64, 5852, 3967, 311, 60826, 11857, 279, 5990, 315, 32762, 12782, 26, 320, 17, 8, 1579, 12, 35658, 386, 11855, 389, 274, 56205, 449, 323, 2085, 264, 2592, 315, 12782, 26, 320, 18, 8, 1579, 12, 35658, 386, 11855, 389, 12095, 34, 449, 264, 29865, 17140, 315, 279, 12095, 3663, 311, 13488, 279, 13336, 315, 12782, 88465, 31965, 505, 279, 54057, 26, 320, 19, 8, 6650, 555, 279, 14747, 315, 7701, 42208, 4611, 299, 398, 29150, 95273, 320, 39, 3143, 38, 8, 1139, 305, 15967, 13, 7181, 430, 304, 279, 1510, 990, 584, 5357, 389, 5740, 5352, 6650, 315, 305, 15967, 439, 433, 6209, 459, 6776, 369, 3544, 320, 1189, 318, 47987, 8, 5569, 12631, 315, 12974, 26839, 320, 2996, 311, 4056, 16, 26807, 705, 439, 1664, 439, 2731, 2585, 927, 279, 304, 24436, 315, 3242, 38333, 13, 6771, 220, 16, 11266, 275, 710, 532, 305, 15967, 10688, 449, 29865, 12782, 32466, 8797, 1404, 2007, 1226, 1176, 13488, 279, 4604, 1152, 1572, 36634, 320, 2989, 8, 505, 264, 4101, 315, 305, 15967, 10688, 15042, 555, 38728, 1777, 220, 1544, 439, 279, 350, 8428, 6530, 4478, 374, 7319, 323, 279, 92003, 6530, 374, 8774, 6926, 320, 30035, 13, 220, 16, 64, 7609, 578, 9395, 315, 420, 19179, 374, 311, 24490, 459, 40126, 315, 305, 15967, 991, 29163, 11, 323, 311, 9616, 872, 6012, 449, 25181, 68835, 82, 15042, 1701, 279, 1890, 6650, 15105, 13, 362, 5654, 315, 279, 350, 8428, 220, 605, 320, 74148, 45444, 1332, 25173, 16, 883, 6205, 449, 279, 15821, 11668, 315, 12782, 5039, 82802, 97332, 13, 74540, 279, 6530, 4478, 311, 350, 8428, 220, 508, 374, 24895, 555, 279, 11341, 315, 264, 10107, 97332, 8450, 449, 1403, 2867, 40035, 26449, 520, 4056, 21535, 323, 4056, 22276, 26807, 13, 15903, 7859, 279, 6530, 4478, 311, 350, 8428, 220, 966, 323, 220, 1399, 5825, 264, 30293, 34030, 10528, 12223, 11, 449, 5190, 97332, 21261, 11, 50096, 430, 5190, 10528, 21261, 6089, 97303, 449, 5190, 350, 8428, 31405, 13, 96075, 65649, 304, 279, 16557, 10093, 323, 279, 21261, 11595, 315, 279, 220, 21535, 323, 220, 22276, 26807, 40035, 520, 2204, 6205, 10687, 527, 13263, 449, 41353, 505, 29050, 665, 41794, 315, 305, 15967, 991, 29163, 13, 1115, 1101, 43496, 3766, 14955, 9204, 430, 305, 15967, 991, 29163, 15575, 7315, 12, 52801, 263, 1584, 320, 57, 2989, 8, 93959, 93858, 520, 4056, 21535, 26807, 994, 279, 6205, 374, 15042, 67422, 710, 34575, 220, 1591, 1174, 220, 1682, 662, 578, 4907, 3474, 38302, 1990, 279, 1901, 2989, 315, 279, 40126, 323, 51923, 263, 3185, 7198, 320, 5119, 33, 8, 16557, 374, 4056, 10967, 757, 53, 389, 5578, 320, 54290, 2956, 23966, 13, 220, 16, 883, 220, 966, 1174, 220, 2148, 662, 23966, 13, 220, 16, 25, 18235, 1152, 1572, 36634, 505, 38728, 1777, 305, 15967, 128257, 198, 128256, 78191, 198, 49165, 902, 649, 17105, 264, 4365, 315, 3254, 89235, 11, 14183, 311, 439, 31228, 3177, 8336, 11, 527, 9200, 12035, 6956, 369, 24084, 14645, 1778, 439, 31228, 25213, 11, 279, 31228, 7757, 11, 323, 31228, 17320, 13, 763, 1690, 5157, 279, 5845, 311, 7068, 31228, 3177, 389, 57364, 7612, 279, 34786, 323, 2585, 315, 3254, 33299, 477, 35715, 11, 17919, 279, 4017, 315, 6617, 59251, 12823, 11, 323, 3339, 279, 4500, 315, 1521, 6067, 264, 5425, 52765, 44550, 8815, 13, 763, 502, 3495, 11, 4756, 304, 22037, 32009, 11, 459, 6625, 64486, 3510, 44550, 20632, 6197, 555, 279, 3907, 315, 12053, 21972, 320, 1406, 50, 705, 706, 43522, 279, 11742, 6070, 4920, 42655, 304, 4251, 66192, 320, 17757, 24346, 32732, 263, 25719, 1425, 11, 305, 15967, 705, 264, 1403, 56987, 20622, 316, 2229, 430, 5039, 2294, 11471, 439, 264, 5452, 369, 24038, 31228, 3177, 13, 578, 42655, 11, 477, 26110, 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2,133

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Background Genetic variants can modulate phenotypic outcomes via epigenetic intermediates, for example at methylation quantitative trait loci (mQTL). We present the first large-scale assessment of mQTL at human genomic regions selected for interindividual variation in CpG methylation, which we call correlated regions of systemic interindividual variation (CoRSIVs). These can be assayed in blood DNA and do not reflect interindividual variation in cellular composition. Results We use target-capture bisulfite sequencing to assess DNA methylation at 4086 CoRSIVs in multiple tissues from each of 188 donors in the NIH Gene-Tissue Expression (GTEx) program. At CoRSIVs, DNA methylation in peripheral blood correlates with methylation and gene expression in internal organs. We also discover unprecedented mQTL at these regions. Genetic influences on CoRSIV methylation are extremely strong (median R 2 =0.76), cumulatively comprising over 70-fold more human mQTL than detected in the most powerful previous study. Moreover, mQTL beta coefficients at CoRSIVs are highly skewed (i.e., the major allele predicts higher methylation). Both surprising findings are independently validated in a cohort of 47 non-GTEx individuals. Genomic regions flanking CoRSIVs show long-range enrichments for LINE-1 and LTR transposable elements; the skewed beta coefficients may therefore reflect evolutionary selection of genetic variants that promote their methylation and silencing. Analyses of GWAS summary statistics show that mQTL polymorphisms at CoRSIVs are associated with metabolic and other classes of disease. Conclusions A focus on systemic interindividual epigenetic variants, clearly enhanced in mQTL content, should likewise benefit studies attempting to link human epigenetic variation to the risk of disease. Introduction Genome-wide association studies (GWAS) have revolutionized the field of genetics by identifying genetic variants associated with a range of diseases and phenotypes [ 1 , 2 , 3 ]. Nearly 20 years into the GWAS era, however, most human disease risk and phenotypic variation remain unexplained by common genetic variants [ 2 ], fueling interest in the possibility that individual epigenetic variation is an important determinant of phenotype [ 4 , 5 ]. To test this, over the last decade myriad studies have performed genome-scale screens to identify genomic regions at which epigenetic variation is associated with disease. Nearly all these epigenome-wide association studies (EWAS) used commercial arrays manufactured by Illumina (predominantly the HM450 and subsequently the scaled-up EPIC850 array) to assess methylation at CpG dinucleotides (a highly stable epigenetic mark) in peripheral blood DNA [ 6 , 7 ]. EWAS have uncovered associations between blood DNA methylation and neurological outcomes including Alzheimer’s disease [ 8 ], neurodegenerative disorders [ 9 ], educational attainment [ 10 ], and psychiatric diseases [ 11 ]. The HM450 and EPIC arrays were instrumental in discoveries in epigenetic aging [ 12 , 13 , 14 ], smoking-induced DNA methylation alterations [ 15 ], and understanding how maternal smoking [ 16 ] and alcohol consumption [ 17 ] affect DNA methylation in newborns. Peripheral blood DNA methylation has been associated with birthweight [ 18 ] and body mass index [ 19 ]. The Illumina methylation arrays have also played a central role in advancing our understanding of genetic influences on CpG methylation. Genetic variants that correlate with methylation at a specific CpG site (usually in cis) are known as methylation quantitative trait loci (mQTL). Seminal observations of familial clustering of CpG methylation levels [ 20 ] led to the first formal study of mQTL [ 21 ], which utilized an early version of the Illumina methylation platform. Now, hundreds of studies, nearly all using Illumina methylation arrays, have investigated mQTL in humans [ 22 ], enabling estimates of methylation heritability and insights into how genetic effects on disease risk may be mediated by DNA methylation [ 23 ] and mechanisms of trans (inter-chromosomal) mQTL effects [ 24 ]. Despite these successes, existing and legacy Illumina methylation platforms are not ideal for population epigenetics. The success of GWAS was built upon the HapMap [ 25 ] and 1,000 Genomes [ 26 ] projects, which systematically mapped out human genome sequence variants so they could be assessed at the population level. So far, however, no “EpiHapMap” project has been conducted. Several large consortium projects, including the Roadmap Epigenome Project [ 27 ], the Blueprint Epigenome Project [ 28 ], and the International Human Epigenome Consortium [ 29 ], focused primarily on characterizing tissue- and cell type-specific epigenetic variation rather than mapping out human genomic regions of interindividual epigenetic variation. The EWAS field therefore relied almost exclusively on Illumina arrays [ 30 ] which were designed without consideration of interindividual variation in DNA methylation [ 31 , 32 ] and generally target CpGs that show little [ 33 , 34 , 35 , 36 ]. To address this lacuna, we recently conducted an unbiased screen for correlated regions of systemic (i.e., not tissue-specific) interindividual epigenetic variation (CoRSIVs) in the human genome [ 37 ]. Because that screen was based on only ten individuals, we set out to assess these regions in a larger cohort to characterize associations among interindividual genetic, epigenetic, and transcriptional variation. In addition to validating CoRSIVs as systemic epigenetic variants, assessing correlations with gene expression, and characterizing associations with transposable elements, we discovered that CoRSIVs exhibit much stronger mQTL than previously observed. Because interindividual variation is essential not just for mQTL detection but also for epigenetic epidemiology, our results have important implications for the EWAS field. Results Target-capture bisulfite sequencing confirms systemic interindividual variation in DNA methylation In collaboration with the NIH Genotype-Tissue Expression (GTEx) program [ 38 ], we conducted target-capture bisulfite sequencing to quantify DNA methylation at 4641 gene-associated CoRSIVs in multiple tissues representing the three embryonic germ layers from each of 188 GTEx donors (807 samples total) (Fig. 1 A, B). For donor and sample information and regions targeted, see Additional file 2 : Table S1 and S2, respectively. The raw data have been deposited in a controlled-access public repository (dbGaP accession phs001746.v2.p1) linked to GTEx identifiers. We achieved high capture efficiency (Additional file 1 : Fig. S1A, B, C); over 90% of targeted regions were covered at 30x sequencing", "role": "user" }, { "content": "Twenty years ago, after the human genome was first sequenced, geneticists began conducting large genome-wide association studies to identify genomic regions linked to human disease. In addition to DNA sequence, another stable level of molecular information—epigenetic modifications established during development—can affect one's risk of disease. For more than a decade, scientists have studied these epigenetic modifications to test associations with disease. Today more than 1,000 such epigenome-wide association studies have been published. Now, in a study published in the journal Genome Biology, a team led by researchers at Baylor College of Medicine reveals that the commercial tool that has been the workhorse for these studies is actually not appropriate for population epigenetics. \"Many people know that each person has a unique DNA sequence or genome. Less well known is that every cell in the body likewise has a unique level of molecular individuality called its epigenome,\" said co-corresponding author Dr. Robert A. Waterland, professor of pediatrics—nutrition at Baylor's USDA/ARS Children's Nutrition Research Center. The epigenome—meaning \"above\" the genome—is a system of molecular markings on DNA that tells different cells in the body which genes to turn on or off in that cell type. \"Epigenetic differences between people can affect their risk of disease,\" said Waterland, a member of the Dan L Duncan Comprehensive Cancer Center at Baylor. To look for such differences, epigeneticists study DNA methylation, which occurs at specific locations called CpG sites. The standard tool for population studies of DNA methylation is a commercial array that assays hundreds of thousands of CpG sites distributed throughout the genome. For the last 15 years, the Waterland lab and colleagues have focused on a different set of CpG sites: those at which DNA methylation differs substantially among people but is consistent across the different tissues of each person. They reasoned that these sites would be most useful for population studies, because DNA from a blood sample can be used to investigate epigenetic causes of disease in internal organs like the brain or heart. \"Three years ago we reported nearly 10,000 such regions in the human genome (named CoRSIVs for correlated regions of systemic interindividual variation) and proposed that studying them could be a novel way to uncover epigenetic causes of disease,\" Waterland said. As a step toward this, the current study investigated how DNA methylation at CoRSIVs is affected by genetics. Correlations between a genetic variant and methylation at a specific CpG site are called methylation quantitative trait loci (mQTL). More than 200 studies of human mQTL have been reported, nearly all using the commercial methylation arrays. The team developed an approach to target CoRSIVs and studied their methylation in DNA samples from multiple tissues of nearly 200 individuals. When they compared their results with those of the largest previous study, \"what we found was somewhat of a shock,\" said first author Dr. Chathura J. Gunasekara, a data analyst in the Waterland lab. \"Compared to the most powerful previous study including 33,000 people, our much smaller study focused on CoRSIVs discovered 72-times more mQTL.\" Looking to explain this surprising finding, the team discovered that around 95% of the CpG sites on the commercial methylation arrays do not show appreciable methylation differences among people. Interindividual variation, which scientists call variance, is the foundation for statistical associations. With no population variance, there is no possibility of detecting mQTL. This finding should also shock the field of epigenetic epidemiology. \"Population variance is essential not only for mQTL detection, but also for detecting associations between DNA methylation and risk of disease,\" said co-corresponding author Dr. Cristian Coarfa, associate professor of molecular and cellular biology and in the Dan L Duncan Comprehensive Cancer Center and the Center for Precision Environmental Health at Baylor. \"Compared to what the field has been doing, we anticipate that focusing on CoRSIVs will make epigenome-wide association studies about 70 times more powerful.\" Indeed, CoRSIVs have already been associated with diverse health outcomes including thyroid function, cognition, cleft palate, schizophrenia, childhood obesity and autism spectrum disorder. \"It's as if there's been this massive and very expensive fishing expedition for the last 10 years, but everyone's been fishing in the wrong place,\" Waterland said. \"We hope that the new tool we've developed will accelerate progress in understanding epigenetic causality of disease.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Background Genetic variants can modulate phenotypic outcomes via epigenetic intermediates, for example at methylation quantitative trait loci (mQTL). We present the first large-scale assessment of mQTL at human genomic regions selected for interindividual variation in CpG methylation, which we call correlated regions of systemic interindividual variation (CoRSIVs). These can be assayed in blood DNA and do not reflect interindividual variation in cellular composition. Results We use target-capture bisulfite sequencing to assess DNA methylation at 4086 CoRSIVs in multiple tissues from each of 188 donors in the NIH Gene-Tissue Expression (GTEx) program. At CoRSIVs, DNA methylation in peripheral blood correlates with methylation and gene expression in internal organs. We also discover unprecedented mQTL at these regions. Genetic influences on CoRSIV methylation are extremely strong (median R 2 =0.76), cumulatively comprising over 70-fold more human mQTL than detected in the most powerful previous study. Moreover, mQTL beta coefficients at CoRSIVs are highly skewed (i.e., the major allele predicts higher methylation). Both surprising findings are independently validated in a cohort of 47 non-GTEx individuals. Genomic regions flanking CoRSIVs show long-range enrichments for LINE-1 and LTR transposable elements; the skewed beta coefficients may therefore reflect evolutionary selection of genetic variants that promote their methylation and silencing. Analyses of GWAS summary statistics show that mQTL polymorphisms at CoRSIVs are associated with metabolic and other classes of disease. Conclusions A focus on systemic interindividual epigenetic variants, clearly enhanced in mQTL content, should likewise benefit studies attempting to link human epigenetic variation to the risk of disease. Introduction Genome-wide association studies (GWAS) have revolutionized the field of genetics by identifying genetic variants associated with a range of diseases and phenotypes [ 1 , 2 , 3 ]. Nearly 20 years into the GWAS era, however, most human disease risk and phenotypic variation remain unexplained by common genetic variants [ 2 ], fueling interest in the possibility that individual epigenetic variation is an important determinant of phenotype [ 4 , 5 ]. To test this, over the last decade myriad studies have performed genome-scale screens to identify genomic regions at which epigenetic variation is associated with disease. Nearly all these epigenome-wide association studies (EWAS) used commercial arrays manufactured by Illumina (predominantly the HM450 and subsequently the scaled-up EPIC850 array) to assess methylation at CpG dinucleotides (a highly stable epigenetic mark) in peripheral blood DNA [ 6 , 7 ]. EWAS have uncovered associations between blood DNA methylation and neurological outcomes including Alzheimer’s disease [ 8 ], neurodegenerative disorders [ 9 ], educational attainment [ 10 ], and psychiatric diseases [ 11 ]. The HM450 and EPIC arrays were instrumental in discoveries in epigenetic aging [ 12 , 13 , 14 ], smoking-induced DNA methylation alterations [ 15 ], and understanding how maternal smoking [ 16 ] and alcohol consumption [ 17 ] affect DNA methylation in newborns. Peripheral blood DNA methylation has been associated with birthweight [ 18 ] and body mass index [ 19 ]. The Illumina methylation arrays have also played a central role in advancing our understanding of genetic influences on CpG methylation. Genetic variants that correlate with methylation at a specific CpG site (usually in cis) are known as methylation quantitative trait loci (mQTL). Seminal observations of familial clustering of CpG methylation levels [ 20 ] led to the first formal study of mQTL [ 21 ], which utilized an early version of the Illumina methylation platform. Now, hundreds of studies, nearly all using Illumina methylation arrays, have investigated mQTL in humans [ 22 ], enabling estimates of methylation heritability and insights into how genetic effects on disease risk may be mediated by DNA methylation [ 23 ] and mechanisms of trans (inter-chromosomal) mQTL effects [ 24 ]. Despite these successes, existing and legacy Illumina methylation platforms are not ideal for population epigenetics. The success of GWAS was built upon the HapMap [ 25 ] and 1,000 Genomes [ 26 ] projects, which systematically mapped out human genome sequence variants so they could be assessed at the population level. So far, however, no “EpiHapMap” project has been conducted. Several large consortium projects, including the Roadmap Epigenome Project [ 27 ], the Blueprint Epigenome Project [ 28 ], and the International Human Epigenome Consortium [ 29 ], focused primarily on characterizing tissue- and cell type-specific epigenetic variation rather than mapping out human genomic regions of interindividual epigenetic variation. The EWAS field therefore relied almost exclusively on Illumina arrays [ 30 ] which were designed without consideration of interindividual variation in DNA methylation [ 31 , 32 ] and generally target CpGs that show little [ 33 , 34 , 35 , 36 ]. To address this lacuna, we recently conducted an unbiased screen for correlated regions of systemic (i.e., not tissue-specific) interindividual epigenetic variation (CoRSIVs) in the human genome [ 37 ]. Because that screen was based on only ten individuals, we set out to assess these regions in a larger cohort to characterize associations among interindividual genetic, epigenetic, and transcriptional variation. In addition to validating CoRSIVs as systemic epigenetic variants, assessing correlations with gene expression, and characterizing associations with transposable elements, we discovered that CoRSIVs exhibit much stronger mQTL than previously observed. Because interindividual variation is essential not just for mQTL detection but also for epigenetic epidemiology, our results have important implications for the EWAS field. Results Target-capture bisulfite sequencing confirms systemic interindividual variation in DNA methylation In collaboration with the NIH Genotype-Tissue Expression (GTEx) program [ 38 ], we conducted target-capture bisulfite sequencing to quantify DNA methylation at 4641 gene-associated CoRSIVs in multiple tissues representing the three embryonic germ layers from each of 188 GTEx donors (807 samples total) (Fig. 1 A, B). For donor and sample information and regions targeted, see Additional file 2 : Table S1 and S2, respectively. The raw data have been deposited in a controlled-access public repository (dbGaP accession phs001746.v2.p1) linked to GTEx identifiers. We achieved high capture efficiency (Additional file 1 : Fig. S1A, B, C); over 90% of targeted regions were covered at 30x sequencing<|im_end|> <|im_start|>assistant Twenty years ago, after the human genome was first sequenced, geneticists began conducting large genome-wide association studies to identify genomic regions linked to human disease. In addition to DNA sequence, another stable level of molecular information—epigenetic modifications established during development—can affect one's risk of disease. For more than a decade, scientists have studied these epigenetic modifications to test associations with disease. Today more than 1,000 such epigenome-wide association studies have been published. Now, in a study published in the journal Genome Biology, a team led by researchers at Baylor College of Medicine reveals that the commercial tool that has been the workhorse for these studies is actually not appropriate for population epigenetics. "Many people know that each person has a unique DNA sequence or genome. Less well known is that every cell in the body likewise has a unique level of molecular individuality called its epigenome," said co-corresponding author Dr. Robert A. Waterland, professor of pediatrics—nutrition at Baylor's USDA/ARS Children's Nutrition Research Center. The epigenome—meaning "above" the genome—is a system of molecular markings on DNA that tells different cells in the body which genes to turn on or off in that cell type. "Epigenetic differences between people can affect their risk of disease," said Waterland, a member of the Dan L Duncan Comprehensive Cancer Center at Baylor. To look for such differences, epigeneticists study DNA methylation, which occurs at specific locations called CpG sites. The standard tool for population studies of DNA methylation is a commercial array that assays hundreds of thousands of CpG sites distributed throughout the genome. For the last 15 years, the Waterland lab and colleagues have focused on a different set of CpG sites: those at which DNA methylation differs substantially among people but is consistent across the different tissues of each person. They reasoned that these sites would be most useful for population studies, because DNA from a blood sample can be used to investigate epigenetic causes of disease in internal organs like the brain or heart. "Three years ago we reported nearly 10,000 such regions in the human genome (named CoRSIVs for correlated regions of systemic interindividual variation) and proposed that studying them could be a novel way to uncover epigenetic causes of disease," Waterland said. As a step toward this, the current study investigated how DNA methylation at CoRSIVs is affected by genetics. Correlations between a genetic variant and methylation at a specific CpG site are called methylation quantitative trait loci (mQTL). More than 200 studies of human mQTL have been reported, nearly all using the commercial methylation arrays. The team developed an approach to target CoRSIVs and studied their methylation in DNA samples from multiple tissues of nearly 200 individuals. When they compared their results with those of the largest previous study, "what we found was somewhat of a shock," said first author Dr. Chathura J. Gunasekara, a data analyst in the Waterland lab. "Compared to the most powerful previous study including 33,000 people, our much smaller study focused on CoRSIVs discovered 72-times more mQTL." Looking to explain this surprising finding, the team discovered that around 95% of the CpG sites on the commercial methylation arrays do not show appreciable methylation differences among people. Interindividual variation, which scientists call variance, is the foundation for statistical associations. With no population variance, there is no possibility of detecting mQTL. This finding should also shock the field of epigenetic epidemiology. "Population variance is essential not only for mQTL detection, but also for detecting associations between DNA methylation and risk of disease," said co-corresponding author Dr. Cristian Coarfa, associate professor of molecular and cellular biology and in the Dan L Duncan Comprehensive Cancer Center and the Center for Precision Environmental Health at Baylor. "Compared to what the field has been doing, we anticipate that focusing on CoRSIVs will make epigenome-wide association studies about 70 times more powerful." Indeed, CoRSIVs have already been associated with diverse health outcomes including thyroid function, cognition, cleft palate, schizophrenia, childhood obesity and autism spectrum disorder. "It's as if there's been this massive and very expensive fishing expedition for the last 10 years, but everyone's been fishing in the wrong place," Waterland said. "We hope that the new tool we've developed will accelerate progress in understanding epigenetic causality of disease." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Background How microbes affect host fitness and environmental adaptation has become a fundamental research question in evolutionary biology. To better understand the role of microbial genomic variation for host fitness, we tested for associations of bacterial genomic variation and Drosophila melanogaster offspring number in a microbial Genome Wide Association Study (GWAS). Results We performed a microbial GWAS, leveraging strain variation in the genus Gluconobacter , a genus of bacteria that are commonly associated with Drosophila under natural conditions. We pinpoint the thiamine biosynthesis pathway (TBP) as contributing to differences in fitness conferred to the fly host. While an effect of thiamine on fly development has been described, we show that strain variation in TBP between bacterial isolates from wild-caught D. melanogaster contributes to variation in offspring production by the host. By tracing the evolutionary history of TBP genes in Gluconobacter , we find that TBP genes were most likely lost and reacquired by horizontal gene transfer (HGT). Conclusion Our study emphasizes the importance of strain variation and highlights that HGT can add to microbiome flexibility and potentially to host adaptation. Background Microbes are important drivers of host phenotype and evolution [ 1 ]. Benefits derived from microorganisms can facilitate the occupation of new ecological niches [ 2 , 3 , 4 , 5 ] and microbial effects on host phenotypes and fitness can spur adaptive processes [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Changes in the effects of microbes on host fitness can alter interactions along the parasitism mutualism continuum [ 6 , 15 , 16 , 17 , 18 ], thus affecting the evolutionary trajectories of the partners. The importance of microbes in evolution and health of higher organisms has sparked a search for the molecular underpinnings of how microbes affect host phenotype. In this search, microbial Genome Wide Association Studies (GWAS) are an important tool [ 19 , 20 , 21 , 22 , 23 ]. The principle behind a microbial GWAS is to establish a link between traits and genetic variation of microbes by the means of GWAS. By testing for association between host traits and microbial genomic variation, Chaston et al. [ 24 ] introduced a particularly helpful approach to unravel how microbes affect host phenotypes [ 22 , 24 ]. The authors measured host phenotypes, here from Drosophila melanogaster that were mono-associated with several microbial isolates. Differences in host phenotype were then associated with the presence and absence of genes in the microbial isolates. By applying this approach, it was found that genes that play a role in glucose oxidation in bacteria affect D. melanogaster triglyceride levels [ 24 ] and that bacterial methionine and B vitamins are important for starvation resistance [ 25 ] as well as life span [ 26 ]. For targeting host phenotypes with microbial GWAS, model systems that allow the generation of axenic hosts that can successively be associated with individual microbial isolates are particularly useful [ 24 ]. One such model system is D. melanogaster and its bacterial microbiome. Techniques for the generation of gnotobiotic flies are readily available and standardized measurements of phenotypes exist. Microbe-affected host phenotypes include the life history traits such as development time, fecundity, and life span as well as size of the adults [ 14 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. These traits are components of fitness, emphasizing the potential importance of microbes in host evolution and adaptation [ 14 , 32 ]. Microbes often affect fitness-related traits by provisioning nutrients. These nutrients include vitamins, amino acids, lipids, and trace elements [ 24 , 34 , 35 , 36 , 37 , 38 , 39 ]. Nutrient provisioning is a recurring theme in metazoan–microbe interactions that are adaptive for the host [ 40 , 41 , 42 ]. The acquisition of nutrients from microbes need not rely on microbes that live inside the host. Instead, nutrients can also be acquired by harvesting or preying upon microbes that live outside the fly and subsequent digestion [ 35 , 43 , 44 , 45 ]. Furthermore, bacteria have been identified that affect D. melanogaster phenotypes by increasing the ability for nutrient uptake [ 46 ] or metabolizing components of the food substrate, and thus modulating its nutrient content [ 24 ]. Interestingly, the metabolic potential to produce nutrients that affect fly fitness differs between closely related microbes and so do the effects on fly phenotype and fitness [ 26 , 29 , 32 , 47 , 48 , 49 , 50 , 51 ]. These findings contribute to the notion that microbial variation at taxonomically low levels is not only important for human [ 15 ], mouse [ 52 ], and plant [ 18 ] hosts, but also for Drosophila [ 53 ]. Because variation between closely related bacteria is important for the interaction of the host and its microbiome, it is also important to consider closely related microbes in studies that aim at elucidating the molecular underpinnings of host–microbe interaction. At the same time, limiting a GWAS to the pan-genome of closely related microbes might offer particular power to the approach: limitation to a narrower range of genes that vary in their presence-absence patterns in a similar genomic background, microbial genes that affect the host can be more precisely pinpointed. For studies that are aimed at better understanding host–microbe interaction in an evolutionary context, it is also important to consider microbes that are associated with the host under natural conditions and if possible, to measure evolutionary relevant host phenotypes in a natural or near natural environment. Finally, tracing the evolutionary changes of the genomic elements that affect host fitness can help us to gain deeper insights into how host–microbe interaction evolves. We aimed our study at better understanding whether and how fly fitness is affected by its natural microbiome by a microbial GWAS. In order to increase the resolution of the", "role": "user" }, { "content": "European wild rabbits are a 'keystone species' that hold together entire ecosystems—according to researchers at the University of East Anglia. Their grazing and digging activity keeps the ground in a condition that is perfect for sustaining other species that would otherwise move on—or die out. But their numbers are declining regionally, nationally and globally. And they are even being classed as endangered in their native region, the Iberian Peninsula. The findings come as efforts to save England's most threatened species from extinction are turning the tide for wildlife in Norfolk and Suffolk thanks to the Shifting Sands project. Shifting Sands is one of 19 projects across England that make up the national Back from the Brink initiative. Together, these projects aim to save 20 species from extinction and benefit over 200 more. Lead partner of the rabbit workstream and rabbit expert Prof Diana Bell, from UEA' School of Biology, said: \"The Breckland-based Shifting Sands project was set up to save some of the region's rarest wildlife. \"After several years of hard work by this multi-partner project, the fortunes of species classed as declining, rare, near-threatened or endangered are now improving in the Brecks. \"The project has seen species recover in record numbers—including endangered beetle and plants, one of which is found nowhere else in the world. \"Rabbits are incredibly important because their grazing and digging activity keeps the ground in a condition that is perfect for sustaining other species. \"Sadly, rabbit populations have declined dramatically in the UK and across Europe, and the European wild rabbit is now listed as endangered in its ancestral Iberian Peninsula range. Their decline is largely due to a spill-over of new viruses from commercially bred rabbits. \"The Shifting Sands project has shown us how important rabbits are to entire ecosystems, and it is vital that these habitats are conserved and protected. \"We encouraged a rabbit revolution in the Brecks and we have produced a toolkit in partnership with Natural England to help landowners of similar rabbit-dependent habitats to do the same.\" \"Simple cost-effective ways of encouraging rabbits include creating piles of felled branches, known as brush piles, and banks of soil.\" Monitoring over the past three years has shown the interventions are working, with evidence of significantly higher amounts of rabbit activity. Prof Bell said: \"Our work resulted in evidence of rabbit activity in significantly higher numbers. 91 percent of brush piles showed paw scrapes and 41 percent contained burrows. Even when burrows did not form, the brush piles helped expand the range of rabbit activity.\" The UEA research team worked in collaboration with Natural England, Forestry England, Plantlife, Breckland Flora Group, Norfolk Wildlife Trust, Suffolk Wildlife Trust, Butterfly Conservation, Buglife, the Elveden Estate and the RSPB to deliver this ambitious partnership project. It has seen five kilometers of 'wildlife highways' created, more than 100 specimens of rare plants re-introduced, habitat created and restored across 12 sites, species encouraged, and landscape-management practices improved. As a result, seven species of plant, bird and insect are increasing in number and many more are benefiting in turn. Among those species recovering are rare plants such as the prostrate perennial knawel that is unique to the Brecks, basil thyme and field wormwood. The endangered wormwood moonshiner beetle, lunar yellow underwing moth and five-banded digger tailed wasp are also increasing. All these species are identified in the UK's Biodiversity Action Plan as being priorities for conservation. The open habitat maintained by rabbits supports two rare plants: the prostrate perennial knawel—found nowhere else in the world—and field wormwood. Pip Mountjoy, Shifting Sands project manager at Natural England, said: \"The Brecks were described by Charles Dickens as \"barren.\" They are anything but. Their 370 square miles of sandy heathland, open grassland and forest support almost 13,000 species, making it one of the UK's most important areas for wildlife. \"That wildlife is under threat. Felling trees and encouraging a species that is often considered a pest may seem a strange solution. But in this instance, carefully managed 'disturbance' is exactly what this landscape and its biodiversity needs.\" \"The project's interventions have provided a lifeline for this unique landscape, and shown how biodiversity can be promoted by 'disturbing' places—not just by leaving them alone. \" \"These rare habitats are becoming overgrown and species are declining as a result of changing land management practices and human impacts. It's our responsibility to restore and maintain these spaces for nature. Some of these species exist only here and, if lost, will be lost forever.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Background How microbes affect host fitness and environmental adaptation has become a fundamental research question in evolutionary biology. To better understand the role of microbial genomic variation for host fitness, we tested for associations of bacterial genomic variation and Drosophila melanogaster offspring number in a microbial Genome Wide Association Study (GWAS). Results We performed a microbial GWAS, leveraging strain variation in the genus Gluconobacter , a genus of bacteria that are commonly associated with Drosophila under natural conditions. We pinpoint the thiamine biosynthesis pathway (TBP) as contributing to differences in fitness conferred to the fly host. While an effect of thiamine on fly development has been described, we show that strain variation in TBP between bacterial isolates from wild-caught D. melanogaster contributes to variation in offspring production by the host. By tracing the evolutionary history of TBP genes in Gluconobacter , we find that TBP genes were most likely lost and reacquired by horizontal gene transfer (HGT). Conclusion Our study emphasizes the importance of strain variation and highlights that HGT can add to microbiome flexibility and potentially to host adaptation. Background Microbes are important drivers of host phenotype and evolution [ 1 ]. Benefits derived from microorganisms can facilitate the occupation of new ecological niches [ 2 , 3 , 4 , 5 ] and microbial effects on host phenotypes and fitness can spur adaptive processes [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. Changes in the effects of microbes on host fitness can alter interactions along the parasitism mutualism continuum [ 6 , 15 , 16 , 17 , 18 ], thus affecting the evolutionary trajectories of the partners. The importance of microbes in evolution and health of higher organisms has sparked a search for the molecular underpinnings of how microbes affect host phenotype. In this search, microbial Genome Wide Association Studies (GWAS) are an important tool [ 19 , 20 , 21 , 22 , 23 ]. The principle behind a microbial GWAS is to establish a link between traits and genetic variation of microbes by the means of GWAS. By testing for association between host traits and microbial genomic variation, Chaston et al. [ 24 ] introduced a particularly helpful approach to unravel how microbes affect host phenotypes [ 22 , 24 ]. The authors measured host phenotypes, here from Drosophila melanogaster that were mono-associated with several microbial isolates. Differences in host phenotype were then associated with the presence and absence of genes in the microbial isolates. By applying this approach, it was found that genes that play a role in glucose oxidation in bacteria affect D. melanogaster triglyceride levels [ 24 ] and that bacterial methionine and B vitamins are important for starvation resistance [ 25 ] as well as life span [ 26 ]. For targeting host phenotypes with microbial GWAS, model systems that allow the generation of axenic hosts that can successively be associated with individual microbial isolates are particularly useful [ 24 ]. One such model system is D. melanogaster and its bacterial microbiome. Techniques for the generation of gnotobiotic flies are readily available and standardized measurements of phenotypes exist. Microbe-affected host phenotypes include the life history traits such as development time, fecundity, and life span as well as size of the adults [ 14 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. These traits are components of fitness, emphasizing the potential importance of microbes in host evolution and adaptation [ 14 , 32 ]. Microbes often affect fitness-related traits by provisioning nutrients. These nutrients include vitamins, amino acids, lipids, and trace elements [ 24 , 34 , 35 , 36 , 37 , 38 , 39 ]. Nutrient provisioning is a recurring theme in metazoan–microbe interactions that are adaptive for the host [ 40 , 41 , 42 ]. The acquisition of nutrients from microbes need not rely on microbes that live inside the host. Instead, nutrients can also be acquired by harvesting or preying upon microbes that live outside the fly and subsequent digestion [ 35 , 43 , 44 , 45 ]. Furthermore, bacteria have been identified that affect D. melanogaster phenotypes by increasing the ability for nutrient uptake [ 46 ] or metabolizing components of the food substrate, and thus modulating its nutrient content [ 24 ]. Interestingly, the metabolic potential to produce nutrients that affect fly fitness differs between closely related microbes and so do the effects on fly phenotype and fitness [ 26 , 29 , 32 , 47 , 48 , 49 , 50 , 51 ]. These findings contribute to the notion that microbial variation at taxonomically low levels is not only important for human [ 15 ], mouse [ 52 ], and plant [ 18 ] hosts, but also for Drosophila [ 53 ]. Because variation between closely related bacteria is important for the interaction of the host and its microbiome, it is also important to consider closely related microbes in studies that aim at elucidating the molecular underpinnings of host–microbe interaction. At the same time, limiting a GWAS to the pan-genome of closely related microbes might offer particular power to the approach: limitation to a narrower range of genes that vary in their presence-absence patterns in a similar genomic background, microbial genes that affect the host can be more precisely pinpointed. For studies that are aimed at better understanding host–microbe interaction in an evolutionary context, it is also important to consider microbes that are associated with the host under natural conditions and if possible, to measure evolutionary relevant host phenotypes in a natural or near natural environment. Finally, tracing the evolutionary changes of the genomic elements that affect host fitness can help us to gain deeper insights into how host–microbe interaction evolves. We aimed our study at better understanding whether and how fly fitness is affected by its natural microbiome by a microbial GWAS. In order to increase the resolution of the<|im_end|> <|im_start|>assistant European wild rabbits are a 'keystone species' that hold together entire ecosystems—according to researchers at the University of East Anglia. Their grazing and digging activity keeps the ground in a condition that is perfect for sustaining other species that would otherwise move on—or die out. But their numbers are declining regionally, nationally and globally. And they are even being classed as endangered in their native region, the Iberian Peninsula. The findings come as efforts to save England's most threatened species from extinction are turning the tide for wildlife in Norfolk and Suffolk thanks to the Shifting Sands project. Shifting Sands is one of 19 projects across England that make up the national Back from the Brink initiative. Together, these projects aim to save 20 species from extinction and benefit over 200 more. Lead partner of the rabbit workstream and rabbit expert Prof Diana Bell, from UEA' School of Biology, said: "The Breckland-based Shifting Sands project was set up to save some of the region's rarest wildlife. "After several years of hard work by this multi-partner project, the fortunes of species classed as declining, rare, near-threatened or endangered are now improving in the Brecks. "The project has seen species recover in record numbers—including endangered beetle and plants, one of which is found nowhere else in the world. "Rabbits are incredibly important because their grazing and digging activity keeps the ground in a condition that is perfect for sustaining other species. "Sadly, rabbit populations have declined dramatically in the UK and across Europe, and the European wild rabbit is now listed as endangered in its ancestral Iberian Peninsula range. Their decline is largely due to a spill-over of new viruses from commercially bred rabbits. "The Shifting Sands project has shown us how important rabbits are to entire ecosystems, and it is vital that these habitats are conserved and protected. "We encouraged a rabbit revolution in the Brecks and we have produced a toolkit in partnership with Natural England to help landowners of similar rabbit-dependent habitats to do the same." "Simple cost-effective ways of encouraging rabbits include creating piles of felled branches, known as brush piles, and banks of soil." Monitoring over the past three years has shown the interventions are working, with evidence of significantly higher amounts of rabbit activity. Prof Bell said: "Our work resulted in evidence of rabbit activity in significantly higher numbers. 91 percent of brush piles showed paw scrapes and 41 percent contained burrows. Even when burrows did not form, the brush piles helped expand the range of rabbit activity." The UEA research team worked in collaboration with Natural England, Forestry England, Plantlife, Breckland Flora Group, Norfolk Wildlife Trust, Suffolk Wildlife Trust, Butterfly Conservation, Buglife, the Elveden Estate and the RSPB to deliver this ambitious partnership project. It has seen five kilometers of 'wildlife highways' created, more than 100 specimens of rare plants re-introduced, habitat created and restored across 12 sites, species encouraged, and landscape-management practices improved. As a result, seven species of plant, bird and insect are increasing in number and many more are benefiting in turn. Among those species recovering are rare plants such as the prostrate perennial knawel that is unique to the Brecks, basil thyme and field wormwood. The endangered wormwood moonshiner beetle, lunar yellow underwing moth and five-banded digger tailed wasp are also increasing. All these species are identified in the UK's Biodiversity Action Plan as being priorities for conservation. The open habitat maintained by rabbits supports two rare plants: the prostrate perennial knawel—found nowhere else in the world—and field wormwood. Pip Mountjoy, Shifting Sands project manager at Natural England, said: "The Brecks were described by Charles Dickens as "barren." They are anything but. Their 370 square miles of sandy heathland, open grassland and forest support almost 13,000 species, making it one of the UK's most important areas for wildlife. "That wildlife is under threat. Felling trees and encouraging a species that is often considered a pest may seem a strange solution. But in this instance, carefully managed 'disturbance' is exactly what this landscape and its biodiversity needs." "The project's interventions have provided a lifeline for this unique landscape, and shown how biodiversity can be promoted by 'disturbing' places—not just by leaving them alone. " "These rare habitats are becoming overgrown and species are declining as a result of changing land management practices and human impacts. It's our responsibility to restore and maintain these spaces for nature. Some of these species exist only here and, if lost, will be lost forever." <|im_end|>

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2,261

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract How genetic information is modified to generate phenotypic variation within a species is one of the central questions in evolutionary biology. Here we focus on the striking intraspecific diversity of >200 aposematic elytral (forewing) colour patterns of the multicoloured Asian ladybird beetle, Harmonia axyridis , which is regulated by a tightly linked genetic locus h . Our loss-of-function analyses, genetic association studies, de novo genome assemblies, and gene expression data reveal that the GATA transcription factor gene pannier is the major regulatory gene located at the h locus, and suggest that repeated inversions and cis -regulatory modifications at pannier led to the expansion of colour pattern variation in H. axyridis . Moreover, we show that the colour-patterning function of pannier is conserved in the seven-spotted ladybird beetle, Coccinella septempunctata , suggesting that H. axyridis ’ extraordinary intraspecific variation may have arisen from ancient modifications in conserved elytral colour-patterning mechanisms in ladybird beetles. Introduction There are approximately 6000 ladybird beetle species described worldwide 1 . Charismatic and popular, ladybird beetles are famous for the red and black spot patterns on their elytra (forewings), thought to be a warning signal to predators that they store bitter alkaloids in their body fluids 2 , 3 and are unpalatable. This red/black warning signal is shared among many ladybird beetle species, and provides a model for colour pattern mimicry by other insect orders. While most ladybird beetle species have only a single spot pattern, a few display remarkable intraspecific diversities, such as the multicoloured Asian ladybird beetle, Harmonia axyridis , which exhibits >200 different elytral colour forms (Fig. 1 a). This striking intraspecific variation prompted us to investigate its genetic and evolutionary basis. Fig. 1 Intraspecific genetic polymorphisms of elytral colour patterns in H. axyridis . a Highly diverse elytral colour patterns of H. ayridis . b Four major alleles of the elytral colour patterns. h C , conspicua ; h Sp , spectabilis ; h A , axyridis ; h, succinea . c An example of inheritance of elytral colour forms. When h C / h C and h / h are crossed (P), all F1 progenies show the colour pattern of h C / h . Note the small black spots within the red spots in the F1 progeny. When the F1 heterozygotes are sibcrossed, F2 progeny shows three phenotypes ( h C / h C , h C / h and h / h ) at the 1:2:1 ratio predicted for Mendelian segregation of a single locus. Inheritance of any combination of colour patterns follows this segregation pattern. Images in Fig. 1a are used under license from Insect DNA Research Society Japan (newsletter, vol. 13, September 2010). All rights reserved Full size image The first predictions regarding the genetics underlying the highly diverse elytral colour patterns of H. axyridis and its relevance to speciation were made by the evolutionary biologist, Theodosius Dobzhansky based on his comprehensive classification of specimens collected from various regions in Asia 4 . Successive genetic analyses 5 , 6 , 7 revealed that many of these colour patterns are actually regulated by a tightly linked genetic locus, h , which segregates either as a single gene, or as strongly linked pseudoallelic genes (a supergene 8 , 9 ) (Fig. 1b, c ). The elytral colour patterns are assumed to be formed by the superposition of combinations of two of the four major allelic patterns and dozens of minor allelic colour patterns (>20 different allelic patterns in total). The major allelic patterns cover more than 95% of colour patterns in the natural population 4 . In the elytral regions where the different colour elements are overlapped in heterozygotes, black colour elements are invariably dominant against red colour elements (mosaic dominance 10 ). Whether all of the supposed alleles linked to the h locus correspond to a single gene or multiple genes is unknown. Elucidating the DNA structure and the mechanisms underlying the evolution of this tightly linked genetic locus that encodes such a strikingly diverse intraspecific colour pattern polymorphism would provide a case-study that bears upon a major evolutionary developmental biology question; how does morphology evolve? Here we show that the gene pannier is responsible for controlling the major four elytral colour patterns of H. axyridis . Moreover, we illustrate how modification to this ancient colour-patterning gene likely contributed to an explosive diversification of colour forms. Results Elytral pigmentation during H. axyridis pupal development To identify the gene regulating elytral colour pattern formation of H. axyridis , we first investigated the pigmentation processes during development. In the developing pupal elytra, red pigment (carotenoids 11 ) was accumulated in the future red-pigmented regions (Fig. 2a , pharate adult elytron). Red pigmentation occurred only in the thick ventral epidermal cells of the two layers of the elytral epidermis (Fig. 2b, c , red), and started at 80 h after pupation (80 h AP). Black pigmentation (melanin accumulation 11 ) occurred only in the dorsal cuticle of black-pigmented regions (Fig. 2d , black), and started approximately 2 h after eclosion. Although pharate adult elytra are not black, we detected a strong upregulation of enzymatic activity related to melanin synthesis 12 in the nascent dorsal cuticle in the future black regions from 80 h AP (Fig. 2a , lower panels; Fig. 2c , black; Supplementary Figure 1 ). Every black-pigmented region was deployed complementary to the red regions. Therefore, we concluded that the developmental programs for both red and black pigmentation started around 80 h AP. Fig. 2 Developmental programs for elytral pigmentation initiate at the late pupal stage. a Adult elytral colour patterns (upper panels), and localisation of carotenoid (middle panels, orange) and phenol oxidase (PO) activity (lower panels, black) in pharate adult elytra at 96 h AP. Proximal is up. Outer rims are to the left. b – d Cross sections of elytra at 96 h AP ( b , c ) and adult ( d ). Dorsal is up. b magenta, nuclei (propidium iodide); green, F-actin (phalloidin). c left,", "role": "user" }, { "content": "Many ladybirds have attractive color patterns consisting of black and red. This prominent color pattern is thought to function as a warning that indicates to predators that they are very bitter and unpalatable. A research team led by Professor Teruyuki Niimi at the National Institute for Basic Biology in Japan focused on the multicolored Asian ladybird beetle Harmonia axyridis (also known as the harlequin ladybird), which lives mainly in Siberia and East Asia, and shows >200 color patterns within a species. The team has identified a single gene that regulates such highly diverse ladybird color patterns. Their genetic and genomic analyses in H. axyridis identified a single gene: pannier. The pannier gene was expressed in the black pigmented regions where the red pigment is not deposited. Functional inhibition of the pannier gene during pupal development resulted in the loss of the black color patterns and ectopic red pattern formation in the forewing. Therefore, the pannier gene has dual functions: promotion of black pigmentation and suppression of red pigmentation in the forewing. A similar result was also obtained in the seven-spot ladybird (Coccinella septempunctata), which lives all over the world. Professor Niimi stated, \"The multicolored Asian lady beetle (Harmonia axyridis) shows extraordinary intraspecific variation in wing colour patterns (>200 described colour forms), and seemed to be the best model to elucidate how insects have generated the diverse traits during evolution at the molecular level. In order to investigate the cause of these diverse morphological patterns, we sequenced the genomes of the multicolored Asian ladybeetle (Harmonia axyridis), and the seven-spot ladybird (Coccinella septempunctata) in collaboration with the specialists at the National Institute of Genetics and others.\" In the genomic analyses of ladybird beetles, they found that the DNA sequences of the pannier gene in the multicolored Asian ladybird beetle was greater compared to other holometabolous insects including the seven-spot ladybird which shows a single color pattern. Genomic sequence comparison among ladybird beetles with different color patterns in H. axyridis revealed that the difference in color pattern is associated with the difference in the DNA sequence of the first intron of the pannier gene. In addition, they found traces of repeated chromosomal inversion within the pannier intron. Assistant Professor Toshiya Ando who performed genomic analysis said \"Until now, it has not been reported that morphological diversification within a species was associated with repeated inversions within a single developmental gene. Our findings have shed light on intragenic chromosomal inversions as a driving force for morphological evolution of organisms.\" A mechanism of color pattern formation in ladybird beetles Credit: NIBB ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract How genetic information is modified to generate phenotypic variation within a species is one of the central questions in evolutionary biology. Here we focus on the striking intraspecific diversity of >200 aposematic elytral (forewing) colour patterns of the multicoloured Asian ladybird beetle, Harmonia axyridis , which is regulated by a tightly linked genetic locus h . Our loss-of-function analyses, genetic association studies, de novo genome assemblies, and gene expression data reveal that the GATA transcription factor gene pannier is the major regulatory gene located at the h locus, and suggest that repeated inversions and cis -regulatory modifications at pannier led to the expansion of colour pattern variation in H. axyridis . Moreover, we show that the colour-patterning function of pannier is conserved in the seven-spotted ladybird beetle, Coccinella septempunctata , suggesting that H. axyridis ’ extraordinary intraspecific variation may have arisen from ancient modifications in conserved elytral colour-patterning mechanisms in ladybird beetles. Introduction There are approximately 6000 ladybird beetle species described worldwide 1 . Charismatic and popular, ladybird beetles are famous for the red and black spot patterns on their elytra (forewings), thought to be a warning signal to predators that they store bitter alkaloids in their body fluids 2 , 3 and are unpalatable. This red/black warning signal is shared among many ladybird beetle species, and provides a model for colour pattern mimicry by other insect orders. While most ladybird beetle species have only a single spot pattern, a few display remarkable intraspecific diversities, such as the multicoloured Asian ladybird beetle, Harmonia axyridis , which exhibits >200 different elytral colour forms (Fig. 1 a). This striking intraspecific variation prompted us to investigate its genetic and evolutionary basis. Fig. 1 Intraspecific genetic polymorphisms of elytral colour patterns in H. axyridis . a Highly diverse elytral colour patterns of H. ayridis . b Four major alleles of the elytral colour patterns. h C , conspicua ; h Sp , spectabilis ; h A , axyridis ; h, succinea . c An example of inheritance of elytral colour forms. When h C / h C and h / h are crossed (P), all F1 progenies show the colour pattern of h C / h . Note the small black spots within the red spots in the F1 progeny. When the F1 heterozygotes are sibcrossed, F2 progeny shows three phenotypes ( h C / h C , h C / h and h / h ) at the 1:2:1 ratio predicted for Mendelian segregation of a single locus. Inheritance of any combination of colour patterns follows this segregation pattern. Images in Fig. 1a are used under license from Insect DNA Research Society Japan (newsletter, vol. 13, September 2010). All rights reserved Full size image The first predictions regarding the genetics underlying the highly diverse elytral colour patterns of H. axyridis and its relevance to speciation were made by the evolutionary biologist, Theodosius Dobzhansky based on his comprehensive classification of specimens collected from various regions in Asia 4 . Successive genetic analyses 5 , 6 , 7 revealed that many of these colour patterns are actually regulated by a tightly linked genetic locus, h , which segregates either as a single gene, or as strongly linked pseudoallelic genes (a supergene 8 , 9 ) (Fig. 1b, c ). The elytral colour patterns are assumed to be formed by the superposition of combinations of two of the four major allelic patterns and dozens of minor allelic colour patterns (>20 different allelic patterns in total). The major allelic patterns cover more than 95% of colour patterns in the natural population 4 . In the elytral regions where the different colour elements are overlapped in heterozygotes, black colour elements are invariably dominant against red colour elements (mosaic dominance 10 ). Whether all of the supposed alleles linked to the h locus correspond to a single gene or multiple genes is unknown. Elucidating the DNA structure and the mechanisms underlying the evolution of this tightly linked genetic locus that encodes such a strikingly diverse intraspecific colour pattern polymorphism would provide a case-study that bears upon a major evolutionary developmental biology question; how does morphology evolve? Here we show that the gene pannier is responsible for controlling the major four elytral colour patterns of H. axyridis . Moreover, we illustrate how modification to this ancient colour-patterning gene likely contributed to an explosive diversification of colour forms. Results Elytral pigmentation during H. axyridis pupal development To identify the gene regulating elytral colour pattern formation of H. axyridis , we first investigated the pigmentation processes during development. In the developing pupal elytra, red pigment (carotenoids 11 ) was accumulated in the future red-pigmented regions (Fig. 2a , pharate adult elytron). Red pigmentation occurred only in the thick ventral epidermal cells of the two layers of the elytral epidermis (Fig. 2b, c , red), and started at 80 h after pupation (80 h AP). Black pigmentation (melanin accumulation 11 ) occurred only in the dorsal cuticle of black-pigmented regions (Fig. 2d , black), and started approximately 2 h after eclosion. Although pharate adult elytra are not black, we detected a strong upregulation of enzymatic activity related to melanin synthesis 12 in the nascent dorsal cuticle in the future black regions from 80 h AP (Fig. 2a , lower panels; Fig. 2c , black; Supplementary Figure 1 ). Every black-pigmented region was deployed complementary to the red regions. Therefore, we concluded that the developmental programs for both red and black pigmentation started around 80 h AP. Fig. 2 Developmental programs for elytral pigmentation initiate at the late pupal stage. a Adult elytral colour patterns (upper panels), and localisation of carotenoid (middle panels, orange) and phenol oxidase (PO) activity (lower panels, black) in pharate adult elytra at 96 h AP. Proximal is up. Outer rims are to the left. b – d Cross sections of elytra at 96 h AP ( b , c ) and adult ( d ). Dorsal is up. b magenta, nuclei (propidium iodide); green, F-actin (phalloidin). c left,<|im_end|> <|im_start|>assistant Many ladybirds have attractive color patterns consisting of black and red. This prominent color pattern is thought to function as a warning that indicates to predators that they are very bitter and unpalatable. A research team led by Professor Teruyuki Niimi at the National Institute for Basic Biology in Japan focused on the multicolored Asian ladybird beetle Harmonia axyridis (also known as the harlequin ladybird), which lives mainly in Siberia and East Asia, and shows >200 color patterns within a species. The team has identified a single gene that regulates such highly diverse ladybird color patterns. Their genetic and genomic analyses in H. axyridis identified a single gene: pannier. The pannier gene was expressed in the black pigmented regions where the red pigment is not deposited. Functional inhibition of the pannier gene during pupal development resulted in the loss of the black color patterns and ectopic red pattern formation in the forewing. Therefore, the pannier gene has dual functions: promotion of black pigmentation and suppression of red pigmentation in the forewing. A similar result was also obtained in the seven-spot ladybird (Coccinella septempunctata), which lives all over the world. Professor Niimi stated, "The multicolored Asian lady beetle (Harmonia axyridis) shows extraordinary intraspecific variation in wing colour patterns (>200 described colour forms), and seemed to be the best model to elucidate how insects have generated the diverse traits during evolution at the molecular level. In order to investigate the cause of these diverse morphological patterns, we sequenced the genomes of the multicolored Asian ladybeetle (Harmonia axyridis), and the seven-spot ladybird (Coccinella septempunctata) in collaboration with the specialists at the National Institute of Genetics and others." In the genomic analyses of ladybird beetles, they found that the DNA sequences of the pannier gene in the multicolored Asian ladybird beetle was greater compared to other holometabolous insects including the seven-spot ladybird which shows a single color pattern. Genomic sequence comparison among ladybird beetles with different color patterns in H. axyridis revealed that the difference in color pattern is associated with the difference in the DNA sequence of the first intron of the pannier gene. In addition, they found traces of repeated chromosomal inversion within the pannier intron. Assistant Professor Toshiya Ando who performed genomic analysis said "Until now, it has not been reported that morphological diversification within a species was associated with repeated inversions within a single developmental gene. Our findings have shed light on intragenic chromosomal inversions as a driving force for morphological evolution of organisms." A mechanism of color pattern formation in ladybird beetles Credit: NIBB <|im_end|>

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2,070

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Continuum scaling laws often break down when materials approach atomic length scales, reflecting changes in their underlying physics and the opportunities to access unconventional properties. These continuum limits are evident in two-dimensional materials, where there is no consensus on their bending stiffnesses or how they scale with thickness. Through combined computational and electron microscopy experiments, we measure the bending stiffness of graphene, obtaining 1.2–1.7 eV for a monolayer. Moreover, we find that the bending stiffness of few-layer graphene decreases sharply as a function of bending angle, tuning by almost 400% for trilayer graphene. This softening results from shear, slip and the onset of superlubricity between the atomic layers and corresponds with a gradual change in scaling power from cubic to linear. Our results provide a unified model for bending in two-dimensional materials and show that their multilayers can be orders of magnitude softer than previously thought, among the most flexible electronic materials currently known. Main Two-dimensional (2D) materials exhibit a host of unusual properties that arise from their anisotropic atomic structure and bonding. For example, the 3D Young’s modulus of few-layer graphene (FLG) is 1 TPa (ref. 1 ), three orders of magnitude larger than its 4.6 GPa shear modulus 2 . Bending, a process that couples in-plane and out-of-plane motion, provides an opportunity to test the effects of anisotropy on the mechanical properties of 2D materials. In particular, interlayer slip has been shown to be a dominant mechanism for relieving stress at van der Waals interfaces 3 , 4 and in multiwalled carbon nanotubes 5 and nanotube bundles 6 . Slip should have similarly important impacts on the bending properties of 2D materials. Bending stiffness takes on practical significance in a new generation of devices where 2D materials are highly curved and shaped into complex 3D architectures 7 , 8 , 9 , 10 , 11 . Highly curved 2D materials have promise across soft robotics and deformable electronics because they combine the high charge carrier mobilities of hard materials with the pliability of soft materials. In these systems, the bending stiffness governs the 3D nanoscale deformations of 2D materials, the structure and onset of folding 12 , rippling 13 , buckling 13 and crumpling 7 , as well as the interfacial mechanics 14 , 15 of deformed structures on surfaces. Yet, after more than a decade, there is still no single model that describes the widely divergent measurements of bending stiffness in monolayer graphene and FLG 2 , 12 , 16 , 17 , 18 . Unlike graphene’s well-known in-plane properties such as its Young’s modulus and breaking stress 1 , 19 , 20 , the small bending stiffness of FLG has proven difficult to characterize. FLG exhibits markedly different mechanical properties from bulk graphite 1 , 21 , 22 , 23 , 24 because structural imperfections in bulk systems overshadow the intrinsic properties of the individual atomic layers. In the few-layer limit, techniques such as nanoindentation, electrostatic actuation, atomistic simulations and measurements of nanoscale fold morphologies 12 , 17 , 18 , 25 , 26 , 27 , 28 , 29 have produced a broad range of bending stiffness for FLG, which appear to be in conflict. For monolayer graphene, literature values for its bending stiffness range from 0.83 to 10,000 eV (refs. 9 , 16 , 27 , 28 , 30 , 31 , 32 ). Furthermore, the reported bending stiffness of bilayer graphene ranges across two orders of magnitude, from 3.4 to 160 eV, while values for trilayer graphene range from 7 to 690 eV (refs. 12 , 17 , 18 , 27 , 31 ). There is also little agreement on the mechanisms and scaling laws that govern the bending of FLG: linear, quadratic and cubic scaling of bending stiffness with thickness have all been reported 2 , 12 , 16 , 17 , 18 . Some inconsistencies arise from the difficulty of measuring the intrinsic bending stiffness of FLG without the contributions from extrinsic stiffening from out-of-plane corrugations or in-plane strain. Another possibility is that these discrepancies reflect real differences in bending stiffness in different physical regimes. When highly bent, 2D materials may be governed by fundamentally different mechanics than in nearly flat geometries, and they may undergo dynamic transitions in bending properties as they are bent and flattened during operation. Yet, the mechanical behaviour of 2D materials spanning from low to high bending regimes is not well understood. In this work, we aim to produce a unified understanding of bending in few-layer 2D materials across curvature regimes. To tackle this challenge, we fabricated heterostructures of FLG draped over atomically sharp steps of hexagonal boron nitride (hBN), as illustrated in Fig. 1a . These structures allow us to systematically vary the thickness and degree of curvature of the graphene, then analyse their bending through cross-sectional imaging with aberration-corrected scanning transmission electron microscopy (STEM). As shown in Fig. 1b , the graphene is placed perpendicularly across hBN steps using established dry aligned transfer techniques (see Methods ). We confirmed the cleanliness and uniformity of the heterostructure with atomic force microscopy (AFM) and Raman spectroscopy (Supplementary Methods 1.1 and Supplementary Figs. 1 and 2 ), then prepared cross-sectional TEM samples using standard focused ion beam lift-out procedures (see Methods ). An example of a resulting sample is shown in the low-magnification STEM image in Fig. 1c ; each sample contains multiple hBN steps with varying heights. Figure 1d–i shows annular dark-field (ADF) STEM images of FLG on hBN steps with varying FLG thickness and hBN step height. Electron microscopy provides a powerful platform for measuring the mechanical properties of nanomaterials by enabling studies of their conformation and strain at atomic resolution 28 , 33 , 34 , 35 , 36 . We imaged 22 individual steps with FLG thicknesses of 1–12 layers and hBN step heights of 1–19 layers (for the raw images of each step see Supplementary Figs. 3–5 ). In these images, the bending profile of FLG and the corresponding mechanics are", "role": "user" }, { "content": "New research by engineers at the University of Illinois combines atomic-scale experimentation with computer modeling to determine how much energy it takes to bend multilayer graphene—a question that has eluded scientists since graphene was first isolated. The findings are reported in the journal Nature Materials. Graphene—a single layer of carbon atoms arranged in a lattice—is the strongest material in the world and so thin that it is flexible, the researchers said. It is considered one of the key ingredients of future technologies. Most of the current research on graphene targets the development of nanoscale electronic devices. Yet, researchers say that many technologies—from stretchable electronics to tiny robots so small that they cannot be seen with the naked eye—require an understanding of the mechanics of graphene, particularly how it flexes and bends, to unlock their potential. \"The bending stiffness of a material is one of its most fundamental mechanical properties,\" said Edmund Han, a materials science and engineering graduate student and study co-author. \"Even though we have been studying graphene for two decades, we have yet to resolve this very fundamental property. The reason is that different research groups have come up with different answers that span across orders of magnitude.\" The team discovered why previous research efforts disagreed. \"They were either bending the material a little or bending it a lot,\" said Jaehyung Yu, a mechanical science and engineering graduate student and study co-author. \"But we found that graphene behaves differently in these two situations. When you bend multilayer graphene a little, it acts more like a stiff plate or a piece of wood. When you bend it a lot, it acts like a stack of papers where the atomic layers can slide past each other.\" \"What is exciting about this work is that it shows that even though everyone disagreed, they were actually all correct,\" said Arend van der Zande, a professor of mechanical science and engineering and study co-author. \"Every group was measuring something different. What we have discovered is a model to explain all the disagreement by showing how they all relate together through different degrees of bending.\" To make the bent graphene, Yu fabricated individual atomic layers of hexagonal boron nitride, another 2-D material, into atomic-scale steps, then stamped the graphene over the top. Using a focused ion beam, Han cut a slice of material and imaged the atomic structure with an electron microscope to see where each graphene layer sat. The team then developed a set of equations and simulations to calculate the bending stiffness using the shape of the graphene bend. Graduate student Edmund Han, left, professor Elif Ertekin, graduate student Jaehyung Yu, professor Pinshane Y. Huang, front, and professor Arend M. van der Zande have determined how much energy it takes to bend multilayer graphene - a question that has long eluded scientists. Credit: Stephanie Adams By draping multiple layers of graphene over a step just one to five atoms high, the researchers created a controlled and precise way of measuring how the material would bend over the step in different configurations. \"In this simple structure, there are two kinds of forces involved in bending the graphene,\" said Pinshane Huang, a materials science and engineering professor and study co-author. \"Adhesion, or the attraction of atoms to the surface, tries to pull the material down. The stiffer the material, the more it will try to pop back up, resisting the pull of adhesion. The shape that the graphene takes over the atomic steps encodes all the information about the material's stiffness.\" The study systematically controlled exactly how much the material bent and how the properties of the graphene changed. \"Because we studied graphene bent by different amounts, we were able to see the transition from one regime to another, from rigid to flexible and from plate to sheet behavior,\" said mechanical science and engineering professor Elif Ertekin, who led the computer modeling portion of the research. \"We built atomic-scale models to show that the reason this could happen is that the individual layers can slip over each other. Once we had this idea, we were able use the electron microscope to confirm the slip between the individual layers.\" The new results have implications for the creation of machines that are small and flexible enough to interact with cells or biological material, the researchers said. \"Cells can change shape and respond to their environment, and if we want to move in the direction of microrobots or systems that have the capabilities of biological systems, we need to have electronic systems that can change their shapes and be very soft as well,\" van der Zande said. \"By taking advantage of interlayer slip, we have shown that the graphene can be orders of magnitude softer than conventional materials of the same thickness.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Continuum scaling laws often break down when materials approach atomic length scales, reflecting changes in their underlying physics and the opportunities to access unconventional properties. These continuum limits are evident in two-dimensional materials, where there is no consensus on their bending stiffnesses or how they scale with thickness. Through combined computational and electron microscopy experiments, we measure the bending stiffness of graphene, obtaining 1.2–1.7 eV for a monolayer. Moreover, we find that the bending stiffness of few-layer graphene decreases sharply as a function of bending angle, tuning by almost 400% for trilayer graphene. This softening results from shear, slip and the onset of superlubricity between the atomic layers and corresponds with a gradual change in scaling power from cubic to linear. Our results provide a unified model for bending in two-dimensional materials and show that their multilayers can be orders of magnitude softer than previously thought, among the most flexible electronic materials currently known. Main Two-dimensional (2D) materials exhibit a host of unusual properties that arise from their anisotropic atomic structure and bonding. For example, the 3D Young’s modulus of few-layer graphene (FLG) is 1 TPa (ref. 1 ), three orders of magnitude larger than its 4.6 GPa shear modulus 2 . Bending, a process that couples in-plane and out-of-plane motion, provides an opportunity to test the effects of anisotropy on the mechanical properties of 2D materials. In particular, interlayer slip has been shown to be a dominant mechanism for relieving stress at van der Waals interfaces 3 , 4 and in multiwalled carbon nanotubes 5 and nanotube bundles 6 . Slip should have similarly important impacts on the bending properties of 2D materials. Bending stiffness takes on practical significance in a new generation of devices where 2D materials are highly curved and shaped into complex 3D architectures 7 , 8 , 9 , 10 , 11 . Highly curved 2D materials have promise across soft robotics and deformable electronics because they combine the high charge carrier mobilities of hard materials with the pliability of soft materials. In these systems, the bending stiffness governs the 3D nanoscale deformations of 2D materials, the structure and onset of folding 12 , rippling 13 , buckling 13 and crumpling 7 , as well as the interfacial mechanics 14 , 15 of deformed structures on surfaces. Yet, after more than a decade, there is still no single model that describes the widely divergent measurements of bending stiffness in monolayer graphene and FLG 2 , 12 , 16 , 17 , 18 . Unlike graphene’s well-known in-plane properties such as its Young’s modulus and breaking stress 1 , 19 , 20 , the small bending stiffness of FLG has proven difficult to characterize. FLG exhibits markedly different mechanical properties from bulk graphite 1 , 21 , 22 , 23 , 24 because structural imperfections in bulk systems overshadow the intrinsic properties of the individual atomic layers. In the few-layer limit, techniques such as nanoindentation, electrostatic actuation, atomistic simulations and measurements of nanoscale fold morphologies 12 , 17 , 18 , 25 , 26 , 27 , 28 , 29 have produced a broad range of bending stiffness for FLG, which appear to be in conflict. For monolayer graphene, literature values for its bending stiffness range from 0.83 to 10,000 eV (refs. 9 , 16 , 27 , 28 , 30 , 31 , 32 ). Furthermore, the reported bending stiffness of bilayer graphene ranges across two orders of magnitude, from 3.4 to 160 eV, while values for trilayer graphene range from 7 to 690 eV (refs. 12 , 17 , 18 , 27 , 31 ). There is also little agreement on the mechanisms and scaling laws that govern the bending of FLG: linear, quadratic and cubic scaling of bending stiffness with thickness have all been reported 2 , 12 , 16 , 17 , 18 . Some inconsistencies arise from the difficulty of measuring the intrinsic bending stiffness of FLG without the contributions from extrinsic stiffening from out-of-plane corrugations or in-plane strain. Another possibility is that these discrepancies reflect real differences in bending stiffness in different physical regimes. When highly bent, 2D materials may be governed by fundamentally different mechanics than in nearly flat geometries, and they may undergo dynamic transitions in bending properties as they are bent and flattened during operation. Yet, the mechanical behaviour of 2D materials spanning from low to high bending regimes is not well understood. In this work, we aim to produce a unified understanding of bending in few-layer 2D materials across curvature regimes. To tackle this challenge, we fabricated heterostructures of FLG draped over atomically sharp steps of hexagonal boron nitride (hBN), as illustrated in Fig. 1a . These structures allow us to systematically vary the thickness and degree of curvature of the graphene, then analyse their bending through cross-sectional imaging with aberration-corrected scanning transmission electron microscopy (STEM). As shown in Fig. 1b , the graphene is placed perpendicularly across hBN steps using established dry aligned transfer techniques (see Methods ). We confirmed the cleanliness and uniformity of the heterostructure with atomic force microscopy (AFM) and Raman spectroscopy (Supplementary Methods 1.1 and Supplementary Figs. 1 and 2 ), then prepared cross-sectional TEM samples using standard focused ion beam lift-out procedures (see Methods ). An example of a resulting sample is shown in the low-magnification STEM image in Fig. 1c ; each sample contains multiple hBN steps with varying heights. Figure 1d–i shows annular dark-field (ADF) STEM images of FLG on hBN steps with varying FLG thickness and hBN step height. Electron microscopy provides a powerful platform for measuring the mechanical properties of nanomaterials by enabling studies of their conformation and strain at atomic resolution 28 , 33 , 34 , 35 , 36 . We imaged 22 individual steps with FLG thicknesses of 1–12 layers and hBN step heights of 1–19 layers (for the raw images of each step see Supplementary Figs. 3–5 ). In these images, the bending profile of FLG and the corresponding mechanics are<|im_end|> <|im_start|>assistant New research by engineers at the University of Illinois combines atomic-scale experimentation with computer modeling to determine how much energy it takes to bend multilayer graphene—a question that has eluded scientists since graphene was first isolated. The findings are reported in the journal Nature Materials. Graphene—a single layer of carbon atoms arranged in a lattice—is the strongest material in the world and so thin that it is flexible, the researchers said. It is considered one of the key ingredients of future technologies. Most of the current research on graphene targets the development of nanoscale electronic devices. Yet, researchers say that many technologies—from stretchable electronics to tiny robots so small that they cannot be seen with the naked eye—require an understanding of the mechanics of graphene, particularly how it flexes and bends, to unlock their potential. "The bending stiffness of a material is one of its most fundamental mechanical properties," said Edmund Han, a materials science and engineering graduate student and study co-author. "Even though we have been studying graphene for two decades, we have yet to resolve this very fundamental property. The reason is that different research groups have come up with different answers that span across orders of magnitude." The team discovered why previous research efforts disagreed. "They were either bending the material a little or bending it a lot," said Jaehyung Yu, a mechanical science and engineering graduate student and study co-author. "But we found that graphene behaves differently in these two situations. When you bend multilayer graphene a little, it acts more like a stiff plate or a piece of wood. When you bend it a lot, it acts like a stack of papers where the atomic layers can slide past each other." "What is exciting about this work is that it shows that even though everyone disagreed, they were actually all correct," said Arend van der Zande, a professor of mechanical science and engineering and study co-author. "Every group was measuring something different. What we have discovered is a model to explain all the disagreement by showing how they all relate together through different degrees of bending." To make the bent graphene, Yu fabricated individual atomic layers of hexagonal boron nitride, another 2-D material, into atomic-scale steps, then stamped the graphene over the top. Using a focused ion beam, Han cut a slice of material and imaged the atomic structure with an electron microscope to see where each graphene layer sat. The team then developed a set of equations and simulations to calculate the bending stiffness using the shape of the graphene bend. Graduate student Edmund Han, left, professor Elif Ertekin, graduate student Jaehyung Yu, professor Pinshane Y. Huang, front, and professor Arend M. van der Zande have determined how much energy it takes to bend multilayer graphene - a question that has long eluded scientists. Credit: Stephanie Adams By draping multiple layers of graphene over a step just one to five atoms high, the researchers created a controlled and precise way of measuring how the material would bend over the step in different configurations. "In this simple structure, there are two kinds of forces involved in bending the graphene," said Pinshane Huang, a materials science and engineering professor and study co-author. "Adhesion, or the attraction of atoms to the surface, tries to pull the material down. The stiffer the material, the more it will try to pop back up, resisting the pull of adhesion. The shape that the graphene takes over the atomic steps encodes all the information about the material's stiffness." The study systematically controlled exactly how much the material bent and how the properties of the graphene changed. "Because we studied graphene bent by different amounts, we were able to see the transition from one regime to another, from rigid to flexible and from plate to sheet behavior," said mechanical science and engineering professor Elif Ertekin, who led the computer modeling portion of the research. "We built atomic-scale models to show that the reason this could happen is that the individual layers can slip over each other. Once we had this idea, we were able use the electron microscope to confirm the slip between the individual layers." The new results have implications for the creation of machines that are small and flexible enough to interact with cells or biological material, the researchers said. "Cells can change shape and respond to their environment, and if we want to move in the direction of microrobots or systems that have the capabilities of biological systems, we need to have electronic systems that can change their shapes and be very soft as well," van der Zande said. "By taking advantage of interlayer slip, we have shown that the graphene can be orders of magnitude softer than conventional materials of the same thickness." <|im_end|>

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2,345

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Several studies reported a central role of the endothelin type A receptor (ETAR) in tumor progression leading to the formation of metastasis. Here, we investigated the in vitro and in vivo anti-tumor effects of the FDA-approved ETAR antagonist, Ambrisentan, which is currently used to treat patients with pulmonary arterial hypertension. In vitro, Ambrisentan inhibited both spontaneous and induced migration/invasion capacity of different tumor cells (COLO-357 metastatic pancreatic adenocarcinoma, OvCar3 ovarian carcinoma, MDA-MB-231 breast adenocarcinoma, and HL-60 promyelocytic leukemia). Whole transcriptome analysis using RNAseq indicated Ambrisentan’s inhibitory effects on the whole transcriptome of resting and PAR2-activated COLO-357 cells, which tended to normalize to an unstimulated profile. Finally, in a pre-clinical murine model of metastatic breast cancer, treatment with Ambrisentan was effective in decreasing metastasis into the lungs and liver. Importantly, this was associated with a significant enhancement in animal survival. Taken together, our work suggests a new therapeutic application for Ambrisentan in the treatment of cancer metastasis. Introduction The endothelin type A receptor (ETAR) is a G-protein coupled receptor (GPCRs) expressed on both non-immune (e.g., endothelial cells, vascular smooth muscle cells, fibroblasts) and immune cells such as neutrophils 1 , 2 , 3 , 4 , 5 . ETAR, present on vascular smooth muscle cells, has a well-known role in vasoconstriction, which upon agonist stimulation by Endothelin-1 (ET-1), induces cell contraction 6 , 7 . Beyond that, ETAR exerts pleiotropic effects on the progression of ovarian, prostate, colon, breast, bladder and lung primary tumors and tumor metastasis 8 , 9 , 10 , 11 , 12 , 13 . The expression of ETAR on tumor cells increases migration, proliferation, and survival 14 , 15 . ETAR has also been reported to be overexpressed on breast cancer tissue in comparison with non-neoplastic tissue 10 and tumor hypoxia induces breast carcinoma invasiveness in an ETAR-dependent manner 11 . Currently, there is a unique selective ETAR antagonist approved for clinical use, which is called Ambrisentan (Volibris). Ambrisentan has been successfully explored to treat pulmonary arterial hypertension (PAH), and its safety has been demonstrated by several clinical trials 16 , 17 , 18 . However, Ambrisentan remains to be explored as a potential therapy for cancer. Here, we aim to investigate the potential role of Ambrisentan for the treatment of cancer. Since Ambrisentan is a selective ETAR antagonist it does not interfere with the physiological vasodilator and clearance effects of the endothelin type B receptor (ETBR) 19 , 20 . This counterbalances the ETAR effects by transducing intracellular signals that result in the production of nitric oxide and vascular relaxation 21 . In the present study, we found that Ambrisentan inhibited tumor cell migration and invasion, while modulating the tumor transcriptome. Furthermore, in a pre-clinical breast cancer model, Ambrisentan reduced cancer cell metastasis to vital organs and decreased mortality. Taken together, our in vitro data using different tumor cell lines, and in vivo observations suggest a new application of Ambrisentan for the treatment of cancer. Results Ambrisentan demonstrates in vitro anti-tumor effects by impacting tumor cell migration and invasion In preliminary experiments, we tested the effect of exogenously added ET-1 on COLO-357 pancreatic carcinoma cells. However, the results showed no effect on migration (data not shown). It is well known that cancer cells secrete ET-1 constitutively. This could explain the lack of effect observed with exogenously added ET-1. We therefore assessed the effect of Ambrisentan on metastatic carcinoma cell lines in response to protease-activated receptor 2 (PAR2) activation, which is a GPCR that has been implicated in tumor progression 22 , 23 , 24 . For these experiments, we used the Oris Pro Cell assay, a technique employed to analyze the migration of adherent cells in real-time to a cell-free detection zone at the center of each well (Fig. 1 a). Ambrisentan reduced the migration capacity of COLO-357 pancreatic carcinoma cells in the presence or absence of PAR2 induction (Fig. 1 b). In concordance with these data, Ambrisentan also blocked the migration of other tumor cells such as OvCar3 ovarian carcinoma (Supplementary Fig. S1a ) and HL-60 promyelocytic leukemia cell line (Supplementary Fig. S1b ). We also analyzed the effect of Ambrisentan on the functional capacity of MDA‐MB231 breast adenocarcinoma, a cell line shown to be positive for ETAR expression (Fig. 2 a). The findings demonstrate that treatment with up to 100 µM Ambrisentan had no effect on viability of cancer cells (Fig. 2 b). However, the migration and invasion capacities of MDA-MB-231 cells, which are known to contribute to the tumorigenicity of these triple-negative breast cancer cells 25 were significantly inhibited after a 24 h-exposure to Ambrisentan in a dose-dependent manner (Fig. 2 c, d). Figure 1 The anti-tumor actions of Ambrisentan on metastatic pancreatic adenocarcinoma (COLO-357) cells. ( a ) Illustration of the Oris migration assay (left panel), which was used to assess cell migration. ( b ) Graphics (on the top) and representative images (on the bottom) of the inhibitory effect of Ambrisentan on migration of COLO 357 cells before and after stimulation by PAR2 agonist (PAR2 ag.). Assays were performed in quadruplicates. Error bars denote mean with SD; * p ≤ 0.05 (n = 3, Mann–Whitney test). Full size image Figure 2 Ambrisentan inhibits migration and invasion capacity of MDA-MB-231 cells without any impact on cell viability. (a) Flow cytometry histogram shows the extent of ETAR expression by MDA-MB-231 cells. (b) Impact of Ambrisentan on cellular vaibility of exponentially growing MDA-MB-231 cells treated with either vehicle (0.1% DMSO) or the indicated concentrations of Ambrisentan for 24 h. (c , d) Viable cells that were able to cross the 8-mm pores insert (migration assay; c ) and the matrigel matrix (invasion assay; d ) were quantified using the CellTiter-Glo luminescent cell viability assay. The data are expressed as means ± SD of 2–3 replicates per group and are pooled from 3 independent experiments. Asterisks denote statistically significant differences between Ambrisentan-treated cells compared to controls (*** p < 0.001; **** p < 0.0001). Full size image Since high toxicity towards immune cells", "role": "user" }, { "content": "A drug used to treat pulmonary hypertension significantly reduced the capacity of tumor cells to migrate and invade other tissues in trials involving pancreatic, ovarian, breast cancer, and leukemia cell lines. Furthermore, in mice with an aggressive form of breast cancer, the drug reduced the incidence of metastasis in the liver and lungs by 47% and lengthened survival compared with untreated animals. The study is published in Scientific Reports. \"The drug ambrisentan is an inhibitor of the endothelin type A receptor, which is known to play a role in vasoconstriction, so the drug is used to treat pulmonary hypertension [typically caused by autoimmune diseases such as lupus and systemic sclerosis]. In the laboratory, we found that the drug prevented migration of tumor cells to other tissues and had other effects we're still investigating,\" said Otávio Cabral Marques, a researcher at the University of São Paulo's Biomedical Sciences Institute (ICB-USP) in Brazil and principal investigator for the study, which was funded by FAPESP. Marques conducted the study while he was a postdoctoral fellow at the University of Freiburg in Germany, collaborating with researchers there and in the United Arab Emirates. He is currently principal investigator for a project supported by FAPESP via a Young Investigator Grant. Endothelin type A receptor is expressed in endothelium, the layer of cells that line the inner surface of blood vessels, and in the cells of the immune system. Other research has also shown its involvement in tumor growth and metastasis. \"The effects of the drug appear not to be confined to preventing tumor cell migration, but also to include inhibition of neoangiogenesis, the formation of new blood vessels required to sustain tumor growth,\" Marques said. \"We're currently doing experiments to confirm this. If so, the drug must have a systemic effect, preventing tumor migration to other tissues and inhibiting tumor growth by blocking the generation of new vessels.\" The drug's benefits in cancer treatment have yet to be proven. Its use without a physician's guidance can be harmful to health, especially in pregnancy. Experiments Using special techniques to measure cell migration, the researchers found that the drug significantly reduced both migration of tumor cells that received a stimulus and spontaneous migration. They tested ovarian, pancreatic, breast and leukemia cancer cell lines. Next, 4T1 cells derived from the mammary gland tissue of a mouse strain were injected into mice to mimic the initial stage of an aggressive form of breast cancer in humans. The mice were treated with the drug for two weeks before the injection and another two weeks afterward. In this experiment, the drug reduced metastasis by about 43% and enhanced median survival by about 30%. \"Metastasis of 4T1 cells is very fast in mice, so we began treatment earlier in order to approximate what happens in humans,\" Marques explained. Marques is now preparing to perform clinical trials with other researchers at ICB-USP. The drug will be tested on a group of cancer patients undergoing chemotherapy to see if they recover better than the control group that will not be given the drug. Although the drug can be administered by mouth, which is an advantage, Marques wants to test applying it directly to the tumor in order to enhance its effect. The type of cancer on which it will be tested has not yet been decided. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Several studies reported a central role of the endothelin type A receptor (ETAR) in tumor progression leading to the formation of metastasis. Here, we investigated the in vitro and in vivo anti-tumor effects of the FDA-approved ETAR antagonist, Ambrisentan, which is currently used to treat patients with pulmonary arterial hypertension. In vitro, Ambrisentan inhibited both spontaneous and induced migration/invasion capacity of different tumor cells (COLO-357 metastatic pancreatic adenocarcinoma, OvCar3 ovarian carcinoma, MDA-MB-231 breast adenocarcinoma, and HL-60 promyelocytic leukemia). Whole transcriptome analysis using RNAseq indicated Ambrisentan’s inhibitory effects on the whole transcriptome of resting and PAR2-activated COLO-357 cells, which tended to normalize to an unstimulated profile. Finally, in a pre-clinical murine model of metastatic breast cancer, treatment with Ambrisentan was effective in decreasing metastasis into the lungs and liver. Importantly, this was associated with a significant enhancement in animal survival. Taken together, our work suggests a new therapeutic application for Ambrisentan in the treatment of cancer metastasis. Introduction The endothelin type A receptor (ETAR) is a G-protein coupled receptor (GPCRs) expressed on both non-immune (e.g., endothelial cells, vascular smooth muscle cells, fibroblasts) and immune cells such as neutrophils 1 , 2 , 3 , 4 , 5 . ETAR, present on vascular smooth muscle cells, has a well-known role in vasoconstriction, which upon agonist stimulation by Endothelin-1 (ET-1), induces cell contraction 6 , 7 . Beyond that, ETAR exerts pleiotropic effects on the progression of ovarian, prostate, colon, breast, bladder and lung primary tumors and tumor metastasis 8 , 9 , 10 , 11 , 12 , 13 . The expression of ETAR on tumor cells increases migration, proliferation, and survival 14 , 15 . ETAR has also been reported to be overexpressed on breast cancer tissue in comparison with non-neoplastic tissue 10 and tumor hypoxia induces breast carcinoma invasiveness in an ETAR-dependent manner 11 . Currently, there is a unique selective ETAR antagonist approved for clinical use, which is called Ambrisentan (Volibris). Ambrisentan has been successfully explored to treat pulmonary arterial hypertension (PAH), and its safety has been demonstrated by several clinical trials 16 , 17 , 18 . However, Ambrisentan remains to be explored as a potential therapy for cancer. Here, we aim to investigate the potential role of Ambrisentan for the treatment of cancer. Since Ambrisentan is a selective ETAR antagonist it does not interfere with the physiological vasodilator and clearance effects of the endothelin type B receptor (ETBR) 19 , 20 . This counterbalances the ETAR effects by transducing intracellular signals that result in the production of nitric oxide and vascular relaxation 21 . In the present study, we found that Ambrisentan inhibited tumor cell migration and invasion, while modulating the tumor transcriptome. Furthermore, in a pre-clinical breast cancer model, Ambrisentan reduced cancer cell metastasis to vital organs and decreased mortality. Taken together, our in vitro data using different tumor cell lines, and in vivo observations suggest a new application of Ambrisentan for the treatment of cancer. Results Ambrisentan demonstrates in vitro anti-tumor effects by impacting tumor cell migration and invasion In preliminary experiments, we tested the effect of exogenously added ET-1 on COLO-357 pancreatic carcinoma cells. However, the results showed no effect on migration (data not shown). It is well known that cancer cells secrete ET-1 constitutively. This could explain the lack of effect observed with exogenously added ET-1. We therefore assessed the effect of Ambrisentan on metastatic carcinoma cell lines in response to protease-activated receptor 2 (PAR2) activation, which is a GPCR that has been implicated in tumor progression 22 , 23 , 24 . For these experiments, we used the Oris Pro Cell assay, a technique employed to analyze the migration of adherent cells in real-time to a cell-free detection zone at the center of each well (Fig. 1 a). Ambrisentan reduced the migration capacity of COLO-357 pancreatic carcinoma cells in the presence or absence of PAR2 induction (Fig. 1 b). In concordance with these data, Ambrisentan also blocked the migration of other tumor cells such as OvCar3 ovarian carcinoma (Supplementary Fig. S1a ) and HL-60 promyelocytic leukemia cell line (Supplementary Fig. S1b ). We also analyzed the effect of Ambrisentan on the functional capacity of MDA‐MB231 breast adenocarcinoma, a cell line shown to be positive for ETAR expression (Fig. 2 a). The findings demonstrate that treatment with up to 100 µM Ambrisentan had no effect on viability of cancer cells (Fig. 2 b). However, the migration and invasion capacities of MDA-MB-231 cells, which are known to contribute to the tumorigenicity of these triple-negative breast cancer cells 25 were significantly inhibited after a 24 h-exposure to Ambrisentan in a dose-dependent manner (Fig. 2 c, d). Figure 1 The anti-tumor actions of Ambrisentan on metastatic pancreatic adenocarcinoma (COLO-357) cells. ( a ) Illustration of the Oris migration assay (left panel), which was used to assess cell migration. ( b ) Graphics (on the top) and representative images (on the bottom) of the inhibitory effect of Ambrisentan on migration of COLO 357 cells before and after stimulation by PAR2 agonist (PAR2 ag.). Assays were performed in quadruplicates. Error bars denote mean with SD; * p ≤ 0.05 (n = 3, Mann–Whitney test). Full size image Figure 2 Ambrisentan inhibits migration and invasion capacity of MDA-MB-231 cells without any impact on cell viability. (a) Flow cytometry histogram shows the extent of ETAR expression by MDA-MB-231 cells. (b) Impact of Ambrisentan on cellular vaibility of exponentially growing MDA-MB-231 cells treated with either vehicle (0.1% DMSO) or the indicated concentrations of Ambrisentan for 24 h. (c , d) Viable cells that were able to cross the 8-mm pores insert (migration assay; c ) and the matrigel matrix (invasion assay; d ) were quantified using the CellTiter-Glo luminescent cell viability assay. The data are expressed as means ± SD of 2–3 replicates per group and are pooled from 3 independent experiments. Asterisks denote statistically significant differences between Ambrisentan-treated cells compared to controls (*** p < 0.001; **** p < 0.0001). Full size image Since high toxicity towards immune cells<|im_end|> <|im_start|>assistant A drug used to treat pulmonary hypertension significantly reduced the capacity of tumor cells to migrate and invade other tissues in trials involving pancreatic, ovarian, breast cancer, and leukemia cell lines. Furthermore, in mice with an aggressive form of breast cancer, the drug reduced the incidence of metastasis in the liver and lungs by 47% and lengthened survival compared with untreated animals. The study is published in Scientific Reports. "The drug ambrisentan is an inhibitor of the endothelin type A receptor, which is known to play a role in vasoconstriction, so the drug is used to treat pulmonary hypertension [typically caused by autoimmune diseases such as lupus and systemic sclerosis]. In the laboratory, we found that the drug prevented migration of tumor cells to other tissues and had other effects we're still investigating," said Otávio Cabral Marques, a researcher at the University of São Paulo's Biomedical Sciences Institute (ICB-USP) in Brazil and principal investigator for the study, which was funded by FAPESP. Marques conducted the study while he was a postdoctoral fellow at the University of Freiburg in Germany, collaborating with researchers there and in the United Arab Emirates. He is currently principal investigator for a project supported by FAPESP via a Young Investigator Grant. Endothelin type A receptor is expressed in endothelium, the layer of cells that line the inner surface of blood vessels, and in the cells of the immune system. Other research has also shown its involvement in tumor growth and metastasis. "The effects of the drug appear not to be confined to preventing tumor cell migration, but also to include inhibition of neoangiogenesis, the formation of new blood vessels required to sustain tumor growth," Marques said. "We're currently doing experiments to confirm this. If so, the drug must have a systemic effect, preventing tumor migration to other tissues and inhibiting tumor growth by blocking the generation of new vessels." The drug's benefits in cancer treatment have yet to be proven. Its use without a physician's guidance can be harmful to health, especially in pregnancy. Experiments Using special techniques to measure cell migration, the researchers found that the drug significantly reduced both migration of tumor cells that received a stimulus and spontaneous migration. They tested ovarian, pancreatic, breast and leukemia cancer cell lines. Next, 4T1 cells derived from the mammary gland tissue of a mouse strain were injected into mice to mimic the initial stage of an aggressive form of breast cancer in humans. The mice were treated with the drug for two weeks before the injection and another two weeks afterward. In this experiment, the drug reduced metastasis by about 43% and enhanced median survival by about 30%. "Metastasis of 4T1 cells is very fast in mice, so we began treatment earlier in order to approximate what happens in humans," Marques explained. Marques is now preparing to perform clinical trials with other researchers at ICB-USP. The drug will be tested on a group of cancer patients undergoing chemotherapy to see if they recover better than the control group that will not be given the drug. Although the drug can be administered by mouth, which is an advantage, Marques wants to test applying it directly to the tumor in order to enhance its effect. The type of cancer on which it will be tested has not yet been decided. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Maintaining long-term euglycemia after intraportal islet transplantation is hampered by the considerable islet loss in the peri-transplant period attributed to inflammation, ischemia and poor angiogenesis. Here, we show that viable and functional islet organoids can be successfully generated from dissociated islet cells (ICs) and human amniotic epithelial cells (hAECs). Incorporation of hAECs into islet organoids markedly enhances engraftment, viability and graft function in a mouse type 1 diabetes model. Our results demonstrate that the integration of hAECs into islet cell organoids has great potential in the development of cell-based therapies for type 1 diabetes. Engineering of functional mini-organs using this strategy will allow the exploration of more favorable implantation sites, and can be expanded to unlimited (stem-cell-derived or xenogeneic) sources of insulin-producing cells. Introduction Although intraportal islet transplantation is an established therapy for patients with type 1 diabetes, maintaining long-term glucose control with this approach remains challenging, mainly due to considerable islet loss in the peri-transplant period 1 . Among the reasons for early graft loss, inflammation at the site of implantation and impaired revascularization appear as key factors 2 , 3 , 4 . Pancreatic islets have a dense blood supply which is inevitably disrupted by the isolation process 5 . In the first weeks after transplantation, oxygen and nutrients are delivered to avascular islets exclusively by diffusion until they become revascularized 6 . Therefore, new strategies aiming at protecting the islets from inflammatory insults and/or promoting graft revascularization may be effective for improving clinical islet transplantation outcomes. Recent studies have demonstrated the functionality of three-dimensionally assembled β-cell aggregates, or multicellular islet spheroids 7 , 8 . Modulating the cell composition by combining different cell types of islet spheroids leads to improvement of function and viability due to heterotypic cell–cell interactions and reproduction of the complex natural morphology of the islet 9 , 10 . This strategy could be brought further, by generating multicellular hybrid organoids consisting of several cell types, i.e., endocrine cells for regulated hormone release, and other cell types with cytoprotective and immunomodulatory properties with the aim to increase islet survival and function after transplantation. Over the last decades, human amniotic epithelial cells (hAECs) have gained interest in regenerative medicine due to their high proliferative capacity, multilineage differentiation, ease of access, and safety 11 . hAECs express surface markers found on human embryonic stem cells and secrete considerable amounts of proangiogenic and anti-inflammatory growth factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin (ANG), insulin-like growth factors (IGF), and their binding proteins (IGFBPs) 12 , 13 , 14 . In addition, hAECs secrete high levels of hyaluronic acid, which suppresses tumor growth factor β (TGFβ)—a potent profibrogenic cytokine 15 . Decreased levels of TGFβ expression were observed after AEC transplantation in mice with bleomycin- and CCl 4 -induced lung or liver injury 16 , 17 . This growth factor secretion profile and antifibrotic properties make hAECs attractive cells for a construct designed to enhance the engraftment and vascularization of islet cells. In this study we successfully generated viable and functional insulin-secreting organoids composed of hAECs and dissociated islet cells (ICs) and have shown that incorporation of hAECs into islet-cell constructs markedly enhances engraftment, viability and graft function in model of cell therapy for type 1 diabetes. Results Characterization of hAECs After initial seeding, hAECs rapidly formed proliferating clusters and grew within 5 days into a confluent cobblestone-shaped monolayer (Fig. 1a ). After culture, hAECs were characterized by flow cytometry and were positive for epithelial (CD326), mesenchymal (CD90, CD105), embryonic stem-cell (SSEA-4) and pluripotency (Oct-4) markers. Most importantly, the hAECs expressed non-classical class Ib histocompatibility antigens HLA-G and HLA-E (Fig. 1b, c , Supplementary Fig. 8 ). Human amniotic epithelial cells were negative for hematopoietic cell markers CD34, CD31, and CD45 (Fig. 1b ). Our results are consistent with previously reported findings 14 . Fig. 1 Characterization of hAECs. a Phase-contrast microscopic images of cultured hAECs at days 2 (left panel) and 5 (right panel) after seeding. Scale bar = 100 μm. b hAECs were characterized for various surface markers by FACS. Data are the means ± SEM, of cells obtained from sixteen different donors labeled with specific antibodies (% positive cells). c Immunohistochemical detection of cytokeratin (red) and OCT-4 (green) in cultured hAECs; nuclei are labeled by DAPI (blue). Scale bar = 50 μm Full size image Generation and in vitro assessment of organoids Figure 2a describes the process used herein to generate islet organoids by mixing ICs and hAECs. Both IC- and IC-hAEC aggregates formed round-shaped spheroids of uniform size with well-defined smooth borders within 5 days (Fig. 2b ). The average diameter of IC-hAEC organoids and IC spheroids were 139 ± 4 μm and 202 ± 2 μm (data are mean ± SEM, n = 12), respectively (Fig. 2c ). Although ICs and hAECs formed small monocellular islands within the organoid, most ICs were in contact with both cell types as shown by confocal laser scanning microscopy (Fig. 2d ). No evidence of cell loss was detected. There was no significant difference in cell viability between IC spheroids and IC-hAEC organoids (Supplementary Fig. 1 ). Fig. 2 In vitro characterization of islet organoids. a Schematic representation of islet organoid engineering. After labeling with Dio and DiI, ICs and hAECs were mixed, seeded and incubated several days on 3D agarose-patterned microwells to generate islet organoids. b Phase-contrast and corresponding fluorescence views of spheroids in one microwell on days 1 and 5. After 5 day culture (bottom), cells undergo compaction and spheroids appear to acquire a smooth border as compared with aggregated cells at day 1. Scale bar = 50 μm. c Diameters of IC spheroids and IC-hAEC organoids ( n = 12). **** p > 0.0001, unpaired Student’s t test. d Confocal views of islet-cell construct. Cell arrangement and composition of the islet organoid on day 14. Islet-derived cells stained for Insulin (green) and hAECs for human nuclear factor (red). Every ninth section of a z -stacked and the entire", "role": "user" }, { "content": "To save patients with a severe form of type 1 diabetes (characterized by the absence of functional insulin-producing cells), pancreatic cell transplantation is sometimes the last resort. The pancreas contains cell clusters—called islets of Langerhans—where cells that produce blood glucose regulating hormones are grouped together. However, the transplant process is long and complex: a significant part of the grafted cells die quickly without being able to engraft. By adding amniotic epithelial cells to these cell clusters, researchers at the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG), Switzerland, have succeeded in creating much more robust \"super-islets\" of Langerhans. Once transplanted, more of them engraft; they then start producing insulin much more rapidly. These results, to be discovered in Nature Communications, would not only improve the success of cell transplants, but also offer new perspectives for other types of transplants, including stem cell transplantation. Today, islet transplantation is one of the last-chance options for patients with a particularly severe form of type 1 diabetes. The islets are removed from a donor's pancreas, isolated and then re-injected into the patient's liver. \"The procedure is well controlled—about fifteen patients benefit from it every year in Switzerland—but nevertheless complex, says Ekaterine Berishvili, a researcher in the Department of Surgery at UNIGE Faculty of Medicine, who led this work. Many of the islets die along the way. It often takes several donors to treat one person, whereas we are in desperate need of donors.\" Placental cells to help grafts To improve the success of islet transplantation and the survival of transplanted cells, researchers in Geneva have sought to create new, more robust islets that would withstand the stress of transplantation better than natural islets. To do this, they came up with the idea of adding amniotic epithelial cells, taken from the wall of the inner placenta membrane, to the pancreatic cells. \"These cells, very similar to stem cells, are already used in other therapies, such as corneal repair for example,\" says Thierry Berney, Professor in the Department of Surgery at UNIGE Faculty of Medicine and Head of HUG Transplant Division, who co-directed this work. \"In our case, we found that they can promote the function of pancreatic cells, which is to produce hormones according to fluctuations in sugar levels.\" First step, in vitro: the addition of amniotic epithelial cells allowed the cell clusters to form regular spheres, indicating better intracellular communication and connectivity. Second step in vivo: the scientists transplanted their \"super-islets\" of Langerhans into diabetic mice, which quickly began to produce insulin. \"Even with few cell clusters, our super islets adapted very well to their new environment and quickly became vascularized,\" says Fanny Lebreton, a researcher in the Department of Surgery at UNIGE Faculty of Medicine and the first author of this work. A good vascularization is indeed the key element of any transplantation: it allows to supply the new organ with oxygen and nutrients and guarantees their survival. In addition, the artificial islets quickly began to produce insulin. Improving oxygenation and protecting islets Amniotic epithelial cells are thus essential to islet survival and seem to act on two vital elements: the lack of oxygen, which usually kills a large number of transplanted islets, and the modulation of the host immune system to limit the risk of rejection. \"In any transplant, the first step is to lower the recipient's immunity to limit the risk of rejection, says Ekaterine Berishvili. Amniotic epithelial cells have the unique characteristic of protecting the foetus, which is also a \"non-self,\" from attacks by its mother's immune system. We believe that the same mechanism is at work to protect the grafts.\" The protective mechanism, observed here on cell transplants, could also take place in other types of transplants or even in xenotransplantation—where non-human cells or organs are transplanted into humans. These discoveries now need to be confirmed on human subjects. Since the use of amniotic epithelial cells is already common in other clinical settings without adverse side effects, this could be done relatively quickly. An important hope for all those awaiting a transplant. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Maintaining long-term euglycemia after intraportal islet transplantation is hampered by the considerable islet loss in the peri-transplant period attributed to inflammation, ischemia and poor angiogenesis. Here, we show that viable and functional islet organoids can be successfully generated from dissociated islet cells (ICs) and human amniotic epithelial cells (hAECs). Incorporation of hAECs into islet organoids markedly enhances engraftment, viability and graft function in a mouse type 1 diabetes model. Our results demonstrate that the integration of hAECs into islet cell organoids has great potential in the development of cell-based therapies for type 1 diabetes. Engineering of functional mini-organs using this strategy will allow the exploration of more favorable implantation sites, and can be expanded to unlimited (stem-cell-derived or xenogeneic) sources of insulin-producing cells. Introduction Although intraportal islet transplantation is an established therapy for patients with type 1 diabetes, maintaining long-term glucose control with this approach remains challenging, mainly due to considerable islet loss in the peri-transplant period 1 . Among the reasons for early graft loss, inflammation at the site of implantation and impaired revascularization appear as key factors 2 , 3 , 4 . Pancreatic islets have a dense blood supply which is inevitably disrupted by the isolation process 5 . In the first weeks after transplantation, oxygen and nutrients are delivered to avascular islets exclusively by diffusion until they become revascularized 6 . Therefore, new strategies aiming at protecting the islets from inflammatory insults and/or promoting graft revascularization may be effective for improving clinical islet transplantation outcomes. Recent studies have demonstrated the functionality of three-dimensionally assembled β-cell aggregates, or multicellular islet spheroids 7 , 8 . Modulating the cell composition by combining different cell types of islet spheroids leads to improvement of function and viability due to heterotypic cell–cell interactions and reproduction of the complex natural morphology of the islet 9 , 10 . This strategy could be brought further, by generating multicellular hybrid organoids consisting of several cell types, i.e., endocrine cells for regulated hormone release, and other cell types with cytoprotective and immunomodulatory properties with the aim to increase islet survival and function after transplantation. Over the last decades, human amniotic epithelial cells (hAECs) have gained interest in regenerative medicine due to their high proliferative capacity, multilineage differentiation, ease of access, and safety 11 . hAECs express surface markers found on human embryonic stem cells and secrete considerable amounts of proangiogenic and anti-inflammatory growth factors, including vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin (ANG), insulin-like growth factors (IGF), and their binding proteins (IGFBPs) 12 , 13 , 14 . In addition, hAECs secrete high levels of hyaluronic acid, which suppresses tumor growth factor β (TGFβ)—a potent profibrogenic cytokine 15 . Decreased levels of TGFβ expression were observed after AEC transplantation in mice with bleomycin- and CCl 4 -induced lung or liver injury 16 , 17 . This growth factor secretion profile and antifibrotic properties make hAECs attractive cells for a construct designed to enhance the engraftment and vascularization of islet cells. In this study we successfully generated viable and functional insulin-secreting organoids composed of hAECs and dissociated islet cells (ICs) and have shown that incorporation of hAECs into islet-cell constructs markedly enhances engraftment, viability and graft function in model of cell therapy for type 1 diabetes. Results Characterization of hAECs After initial seeding, hAECs rapidly formed proliferating clusters and grew within 5 days into a confluent cobblestone-shaped monolayer (Fig. 1a ). After culture, hAECs were characterized by flow cytometry and were positive for epithelial (CD326), mesenchymal (CD90, CD105), embryonic stem-cell (SSEA-4) and pluripotency (Oct-4) markers. Most importantly, the hAECs expressed non-classical class Ib histocompatibility antigens HLA-G and HLA-E (Fig. 1b, c , Supplementary Fig. 8 ). Human amniotic epithelial cells were negative for hematopoietic cell markers CD34, CD31, and CD45 (Fig. 1b ). Our results are consistent with previously reported findings 14 . Fig. 1 Characterization of hAECs. a Phase-contrast microscopic images of cultured hAECs at days 2 (left panel) and 5 (right panel) after seeding. Scale bar = 100 μm. b hAECs were characterized for various surface markers by FACS. Data are the means ± SEM, of cells obtained from sixteen different donors labeled with specific antibodies (% positive cells). c Immunohistochemical detection of cytokeratin (red) and OCT-4 (green) in cultured hAECs; nuclei are labeled by DAPI (blue). Scale bar = 50 μm Full size image Generation and in vitro assessment of organoids Figure 2a describes the process used herein to generate islet organoids by mixing ICs and hAECs. Both IC- and IC-hAEC aggregates formed round-shaped spheroids of uniform size with well-defined smooth borders within 5 days (Fig. 2b ). The average diameter of IC-hAEC organoids and IC spheroids were 139 ± 4 μm and 202 ± 2 μm (data are mean ± SEM, n = 12), respectively (Fig. 2c ). Although ICs and hAECs formed small monocellular islands within the organoid, most ICs were in contact with both cell types as shown by confocal laser scanning microscopy (Fig. 2d ). No evidence of cell loss was detected. There was no significant difference in cell viability between IC spheroids and IC-hAEC organoids (Supplementary Fig. 1 ). Fig. 2 In vitro characterization of islet organoids. a Schematic representation of islet organoid engineering. After labeling with Dio and DiI, ICs and hAECs were mixed, seeded and incubated several days on 3D agarose-patterned microwells to generate islet organoids. b Phase-contrast and corresponding fluorescence views of spheroids in one microwell on days 1 and 5. After 5 day culture (bottom), cells undergo compaction and spheroids appear to acquire a smooth border as compared with aggregated cells at day 1. Scale bar = 50 μm. c Diameters of IC spheroids and IC-hAEC organoids ( n = 12). **** p > 0.0001, unpaired Student’s t test. d Confocal views of islet-cell construct. Cell arrangement and composition of the islet organoid on day 14. Islet-derived cells stained for Insulin (green) and hAECs for human nuclear factor (red). Every ninth section of a z -stacked and the entire<|im_end|> <|im_start|>assistant To save patients with a severe form of type 1 diabetes (characterized by the absence of functional insulin-producing cells), pancreatic cell transplantation is sometimes the last resort. The pancreas contains cell clusters—called islets of Langerhans—where cells that produce blood glucose regulating hormones are grouped together. However, the transplant process is long and complex: a significant part of the grafted cells die quickly without being able to engraft. By adding amniotic epithelial cells to these cell clusters, researchers at the University of Geneva (UNIGE) and the Geneva University Hospitals (HUG), Switzerland, have succeeded in creating much more robust "super-islets" of Langerhans. Once transplanted, more of them engraft; they then start producing insulin much more rapidly. These results, to be discovered in Nature Communications, would not only improve the success of cell transplants, but also offer new perspectives for other types of transplants, including stem cell transplantation. Today, islet transplantation is one of the last-chance options for patients with a particularly severe form of type 1 diabetes. The islets are removed from a donor's pancreas, isolated and then re-injected into the patient's liver. "The procedure is well controlled—about fifteen patients benefit from it every year in Switzerland—but nevertheless complex, says Ekaterine Berishvili, a researcher in the Department of Surgery at UNIGE Faculty of Medicine, who led this work. Many of the islets die along the way. It often takes several donors to treat one person, whereas we are in desperate need of donors." Placental cells to help grafts To improve the success of islet transplantation and the survival of transplanted cells, researchers in Geneva have sought to create new, more robust islets that would withstand the stress of transplantation better than natural islets. To do this, they came up with the idea of adding amniotic epithelial cells, taken from the wall of the inner placenta membrane, to the pancreatic cells. "These cells, very similar to stem cells, are already used in other therapies, such as corneal repair for example," says Thierry Berney, Professor in the Department of Surgery at UNIGE Faculty of Medicine and Head of HUG Transplant Division, who co-directed this work. "In our case, we found that they can promote the function of pancreatic cells, which is to produce hormones according to fluctuations in sugar levels." First step, in vitro: the addition of amniotic epithelial cells allowed the cell clusters to form regular spheres, indicating better intracellular communication and connectivity. Second step in vivo: the scientists transplanted their "super-islets" of Langerhans into diabetic mice, which quickly began to produce insulin. "Even with few cell clusters, our super islets adapted very well to their new environment and quickly became vascularized," says Fanny Lebreton, a researcher in the Department of Surgery at UNIGE Faculty of Medicine and the first author of this work. A good vascularization is indeed the key element of any transplantation: it allows to supply the new organ with oxygen and nutrients and guarantees their survival. In addition, the artificial islets quickly began to produce insulin. Improving oxygenation and protecting islets Amniotic epithelial cells are thus essential to islet survival and seem to act on two vital elements: the lack of oxygen, which usually kills a large number of transplanted islets, and the modulation of the host immune system to limit the risk of rejection. "In any transplant, the first step is to lower the recipient's immunity to limit the risk of rejection, says Ekaterine Berishvili. Amniotic epithelial cells have the unique characteristic of protecting the foetus, which is also a "non-self," from attacks by its mother's immune system. We believe that the same mechanism is at work to protect the grafts." The protective mechanism, observed here on cell transplants, could also take place in other types of transplants or even in xenotransplantation—where non-human cells or organs are transplanted into humans. These discoveries now need to be confirmed on human subjects. Since the use of amniotic epithelial cells is already common in other clinical settings without adverse side effects, this could be done relatively quickly. An important hope for all those awaiting a transplant. <|im_end|>

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2,486

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The exchange bias effect refers to the shift of the hysteresis loop of a ferromagnet in direct contact to an antiferromagnet. For applications in spintronics a robust and tunable exchange bias is required. Here we show experimental evidence for a perpendicular exchange bias in a prototypical ferrimagnetic spin valve consisting of DyCo 5 /Ta/Fe 76 Gd 24 , where the DyCo 5 alloy has the role of a hard ferrimagnet and Fe 76 Gd 24 is a soft ferrimagnet. Taking advantage of the tunability of the exchange coupling between the ferrimagnetic layers by means of thickness variation of an interlayer spacer, we demonstrate that perpendicular unidirectional anisotropy can be induced with desirable absolute values at room temperature, without making use of a field-cooling procedure. Moreover, the shift of the hysteresis loop can be reversed with relatively low magnetic fields of several hundred Oersteds. This flexibility in controlling a robust perpendicular exchange bias at room temperature may be of crucial importance for applications. Introduction After the discovery of the giant magnetoresistance 1 , 2 , the exchange bias (EB) effect has become an integral part of spintronics with implications for basic research and for numerous device applications like random access magnetic storage units and spin valves. Although its observation has been made only 60 years ago by Meiklejohn and Bean 3 when studying Co particles embedded in their natural oxide (CoO) matrix, the first EB system was engineered by nature long before, a few billion years ago, in grains of titanohaematite 4 . The origin of the EB effect is related to the magnetic coupling across the common interface shared by a ferromagnetic (FM) and an antiferromagnetic (AF) layer, when the system is cooled through the Néel temperature of the AF layer. The magnetic properties of the AF layer and the interface are crucial for understanding the magnetic properties of the EB systems 5 . Yet, these two magnetic components are difficult to access experimentally with laboratory tools because of a virtually vanishing magnetization of AF layers and a small volume of the magnetic interface. Important progress has been made by involving neutron and X-ray techniques to study the bulk part of the pinning layer and the interfacial magnetism 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 . For instance, in an archetypal CoO/FM bilayer, neutron scattering has revealed the origin of reduced EB. It was shown to be related to the anisotropic domain state of the AF system 12 . Using soft X-ray techniques, the frozen and rotatable spins 12 , 14 , 15 were observed in several systems, leading to a deeper understanding of the enhanced coercivity and the origin of the EB for systems with uncompensated AF interfaces. Larger efforts were dedicated to the understanding of the FM/AF EB systems with in-plane anisotropy of the ferromagnet 16 . Notably, Mangin and colleagues 17 , 18 , 19 , 20 have performed significant work on GdFe/TbFe ferrimagnetic soft/hard bilayers with in-plane anisotropy in which EB effects occur. EB was also studied in all coupled FM films with in-plane magnetized ferromagnets acting as pinning layers 21 , 22 . However, for applications, perpendicular uniaxial and unidirectional anisotropies are more desirable owing to a larger thermal stability of encoded information 23 . For instance, antiferromagnets in contact to ferromagnets with perpendicular anisotropy like Co/Pt multilayers and CoPt 3 layers have been shown to exhibit EB and all other macroscopic behaviour of EB systems, like training effect, enhanced coercivity and blocking temperature for the onset of the EB 23 , 24 , 25 , 26 . More recently, the perpendicular EB (PEB) was demonstrated in a novel exchange-coupled system Sm 1−0.028 Gd 0.028 Al 2 /SmAl 2 based on the zero magnetization ferromagnet Sm 1−0.028 Gd 0.028 Al 2 as the pinning layer 27 . The latter exhibits a compensation temperature where the antiparallel oriented spin and orbital moments cancel one another leading to a vanishing macroscopic magnetization of the ferromagnet 28 . In nearly all cases, the PEB is set through field-cooling or by in situ field growth procedures, similar to the AF/FM systems with in-plane anisotropy. In this article, we demonstrate that PEB can be set, controlled and reversed at room temperature in exchange-coupled ferrimagnetic systems, by making use of an interlayer exchange decoupling mechanism. As a prototype system, we have chosen artificial DyCo 5 /Ta(x)/Fe 76 Gd 24 spin-valve (SV) trilayers, where the hard ferrimagnet (HFi) DyCo 5 serves as a single magnetic domain pinning layer. In bulk form 29 and in thin films 30 , it has a magnetization compensation temperature and a spin reorientation temperature. As the orbital moment of Dy is nearly as large as the spin moment 31 , it is expected that DyCo 5 exhibits a large perpendicular anisotropy 32 , which qualifies it as a robust pinning layer. Owing to the vanishing orbital moment of Gd, the perpendicular magnetic anisotropy of Fe 76 Gd 24 (FeGd) is weak. Therefore, it acts as a soft ferrimagnetic layer (SFi). To induce a perpendicular unidirectional anisotropy, in a first step the soft and the hard ferrimagnets are partially decoupled by a Ta interlayer spacer, and in a second step hysteresis loops are measured, reversing the SFi magnetization while keeping the HFi magnetically saturated. In this way, the PEB can be set and even reversed without involving a field-cooling procedure. Results Perpendicular anisotropy with ferrimagnetic pinning layer The origin of EB in FM/AF and X/HFi (with X =FM or SFi) bilayers is related to the coupling across the interface shared by two adjacent magnetic layers. The magnetic state of the pinning layer interface has a crucial role in establishing a robust EB 5 . We exemplify below that, as a prerequisite for the occurrence of a strong PEB, the magnetic state of the interface of HFi pinning layer must be compensated. This contrasts the case of an AF pinning layer, where the magnetic state of the interface has to", "role": "user" }, { "content": "In close collaboration with colleagues from Bochum, Germany, and the Netherlands, researchers from the Helmholtz-Zentrum Berlin, Germany, have developed a novel, extremely thin structure made of various magnetic materials. It is suitable as a kind of magnetic valve for data-storage units of the most recent generation and makes use of effects in the context of so-called spintronics, with which, in addition to the (re-)charging process, magnetic characteristics of the electrons can also be used for information-processing and -storage. The advantage of the new structure: data remain intact even after the electric current has been switched off and the memory can be re-written more or less indefinitely. The scientists published their results in Nature Communications. Everything began with basic academic curiosity. \"First of all we just wanted to create a defined anisotropy with two thin, stacked ferrimagnetic layers\", says Florin Radu, physicist at the Institute for Complex Magnetic Materials of the Helmholtz-Zentrum Berlin (HZB) and principal author of the research paper. In other words, the researchers just wanted to create a structure in which a magnetic characteristic within the material changes in a well defined way. Experts in this field define this as magnetic hysteresis. It describes the behaviour of magnetic substances vis-à-vis an externally-applied magnetic field. However, the task proved to be much more difficult; the magnetic energies at the interfaces turned out to be so powerful that the magnetization of the films reverses together. It was necessary to place an additional, non-magnetic layer made of tantalum between the ferrimagnetic layers in order to diminish this effect. What the scientists saw next was truly astounding; the system behaved fundamentally differently as compared to the conventional systems made of ferromagnetic and anti-ferromagnetic layers. The ferrimagnet described as magnetically \"soft\", which consists of the chemical elements iron and gadolinium, unexpectedly indicated an alteration in the hysteresis, while the existing magnetism remained unaltered for the \"hard\" ferrimagnetic film that consists of the chemical elements dysprosium and cobalt. This discovery paves the way for an even more vigorous research in the field of spintronics.. \"Know how, Show how!!\", thus proclaims the research maxim of Radu. \"I would not be surprised to see this discovery implemented into PC's, smart phones and tablets in the future\", he predicts. For his invention the so-called spin-valve the HZB filed a patent application this week. Nowadays, the data storage units are either volatile or non-volatile. For the former, the information is lost as soon as the device is switched off, and for the latter the information remain intact for many years. Due to thermal effects, they are also practically unusable after about ten years. In particular, when the bits are only a few nanometres in size, they lose stability. Once lost, the magnetization direction of the hard magnetic layer cannot easily be set again in the original direction.. This leads irretrievably loss of data. This stability issue can now be addressed with the new spin-valve concept. By tunning the magnetic properties of the hard ferrimagnetic layer, the so-called RAM memory building-blocks (RAM stands for random access memory) can be manufactured with controlled life-time of the stored information of weeks, months or years.. Thereafter, the magnetic orientation can be resettedin the original state, which increases considerably the overall life expectancy of the information as compared to the existing non-volatile MRAM (Magnetoresistive Random Access Memory). These memory building-blocks are now certainly highly sought-after in the field of micro-electronics, but have not been able, to date, to be established in the markets due to high costs and technical problems. With the spin-valve concept by Radu and his colleagues, electronic devices can now be developed that, similar to the MRAM technology, are operable immediately after being switched on and allow their data storage units to be re-written more or less indefinitely. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The exchange bias effect refers to the shift of the hysteresis loop of a ferromagnet in direct contact to an antiferromagnet. For applications in spintronics a robust and tunable exchange bias is required. Here we show experimental evidence for a perpendicular exchange bias in a prototypical ferrimagnetic spin valve consisting of DyCo 5 /Ta/Fe 76 Gd 24 , where the DyCo 5 alloy has the role of a hard ferrimagnet and Fe 76 Gd 24 is a soft ferrimagnet. Taking advantage of the tunability of the exchange coupling between the ferrimagnetic layers by means of thickness variation of an interlayer spacer, we demonstrate that perpendicular unidirectional anisotropy can be induced with desirable absolute values at room temperature, without making use of a field-cooling procedure. Moreover, the shift of the hysteresis loop can be reversed with relatively low magnetic fields of several hundred Oersteds. This flexibility in controlling a robust perpendicular exchange bias at room temperature may be of crucial importance for applications. Introduction After the discovery of the giant magnetoresistance 1 , 2 , the exchange bias (EB) effect has become an integral part of spintronics with implications for basic research and for numerous device applications like random access magnetic storage units and spin valves. Although its observation has been made only 60 years ago by Meiklejohn and Bean 3 when studying Co particles embedded in their natural oxide (CoO) matrix, the first EB system was engineered by nature long before, a few billion years ago, in grains of titanohaematite 4 . The origin of the EB effect is related to the magnetic coupling across the common interface shared by a ferromagnetic (FM) and an antiferromagnetic (AF) layer, when the system is cooled through the Néel temperature of the AF layer. The magnetic properties of the AF layer and the interface are crucial for understanding the magnetic properties of the EB systems 5 . Yet, these two magnetic components are difficult to access experimentally with laboratory tools because of a virtually vanishing magnetization of AF layers and a small volume of the magnetic interface. Important progress has been made by involving neutron and X-ray techniques to study the bulk part of the pinning layer and the interfacial magnetism 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 . For instance, in an archetypal CoO/FM bilayer, neutron scattering has revealed the origin of reduced EB. It was shown to be related to the anisotropic domain state of the AF system 12 . Using soft X-ray techniques, the frozen and rotatable spins 12 , 14 , 15 were observed in several systems, leading to a deeper understanding of the enhanced coercivity and the origin of the EB for systems with uncompensated AF interfaces. Larger efforts were dedicated to the understanding of the FM/AF EB systems with in-plane anisotropy of the ferromagnet 16 . Notably, Mangin and colleagues 17 , 18 , 19 , 20 have performed significant work on GdFe/TbFe ferrimagnetic soft/hard bilayers with in-plane anisotropy in which EB effects occur. EB was also studied in all coupled FM films with in-plane magnetized ferromagnets acting as pinning layers 21 , 22 . However, for applications, perpendicular uniaxial and unidirectional anisotropies are more desirable owing to a larger thermal stability of encoded information 23 . For instance, antiferromagnets in contact to ferromagnets with perpendicular anisotropy like Co/Pt multilayers and CoPt 3 layers have been shown to exhibit EB and all other macroscopic behaviour of EB systems, like training effect, enhanced coercivity and blocking temperature for the onset of the EB 23 , 24 , 25 , 26 . More recently, the perpendicular EB (PEB) was demonstrated in a novel exchange-coupled system Sm 1−0.028 Gd 0.028 Al 2 /SmAl 2 based on the zero magnetization ferromagnet Sm 1−0.028 Gd 0.028 Al 2 as the pinning layer 27 . The latter exhibits a compensation temperature where the antiparallel oriented spin and orbital moments cancel one another leading to a vanishing macroscopic magnetization of the ferromagnet 28 . In nearly all cases, the PEB is set through field-cooling or by in situ field growth procedures, similar to the AF/FM systems with in-plane anisotropy. In this article, we demonstrate that PEB can be set, controlled and reversed at room temperature in exchange-coupled ferrimagnetic systems, by making use of an interlayer exchange decoupling mechanism. As a prototype system, we have chosen artificial DyCo 5 /Ta(x)/Fe 76 Gd 24 spin-valve (SV) trilayers, where the hard ferrimagnet (HFi) DyCo 5 serves as a single magnetic domain pinning layer. In bulk form 29 and in thin films 30 , it has a magnetization compensation temperature and a spin reorientation temperature. As the orbital moment of Dy is nearly as large as the spin moment 31 , it is expected that DyCo 5 exhibits a large perpendicular anisotropy 32 , which qualifies it as a robust pinning layer. Owing to the vanishing orbital moment of Gd, the perpendicular magnetic anisotropy of Fe 76 Gd 24 (FeGd) is weak. Therefore, it acts as a soft ferrimagnetic layer (SFi). To induce a perpendicular unidirectional anisotropy, in a first step the soft and the hard ferrimagnets are partially decoupled by a Ta interlayer spacer, and in a second step hysteresis loops are measured, reversing the SFi magnetization while keeping the HFi magnetically saturated. In this way, the PEB can be set and even reversed without involving a field-cooling procedure. Results Perpendicular anisotropy with ferrimagnetic pinning layer The origin of EB in FM/AF and X/HFi (with X =FM or SFi) bilayers is related to the coupling across the interface shared by two adjacent magnetic layers. The magnetic state of the pinning layer interface has a crucial role in establishing a robust EB 5 . We exemplify below that, as a prerequisite for the occurrence of a strong PEB, the magnetic state of the interface of HFi pinning layer must be compensated. This contrasts the case of an AF pinning layer, where the magnetic state of the interface has to<|im_end|> <|im_start|>assistant In close collaboration with colleagues from Bochum, Germany, and the Netherlands, researchers from the Helmholtz-Zentrum Berlin, Germany, have developed a novel, extremely thin structure made of various magnetic materials. It is suitable as a kind of magnetic valve for data-storage units of the most recent generation and makes use of effects in the context of so-called spintronics, with which, in addition to the (re-)charging process, magnetic characteristics of the electrons can also be used for information-processing and -storage. The advantage of the new structure: data remain intact even after the electric current has been switched off and the memory can be re-written more or less indefinitely. The scientists published their results in Nature Communications. Everything began with basic academic curiosity. "First of all we just wanted to create a defined anisotropy with two thin, stacked ferrimagnetic layers", says Florin Radu, physicist at the Institute for Complex Magnetic Materials of the Helmholtz-Zentrum Berlin (HZB) and principal author of the research paper. In other words, the researchers just wanted to create a structure in which a magnetic characteristic within the material changes in a well defined way. Experts in this field define this as magnetic hysteresis. It describes the behaviour of magnetic substances vis-à-vis an externally-applied magnetic field. However, the task proved to be much more difficult; the magnetic energies at the interfaces turned out to be so powerful that the magnetization of the films reverses together. It was necessary to place an additional, non-magnetic layer made of tantalum between the ferrimagnetic layers in order to diminish this effect. What the scientists saw next was truly astounding; the system behaved fundamentally differently as compared to the conventional systems made of ferromagnetic and anti-ferromagnetic layers. The ferrimagnet described as magnetically "soft", which consists of the chemical elements iron and gadolinium, unexpectedly indicated an alteration in the hysteresis, while the existing magnetism remained unaltered for the "hard" ferrimagnetic film that consists of the chemical elements dysprosium and cobalt. This discovery paves the way for an even more vigorous research in the field of spintronics.. "Know how, Show how!!", thus proclaims the research maxim of Radu. "I would not be surprised to see this discovery implemented into PC's, smart phones and tablets in the future", he predicts. For his invention the so-called spin-valve the HZB filed a patent application this week. Nowadays, the data storage units are either volatile or non-volatile. For the former, the information is lost as soon as the device is switched off, and for the latter the information remain intact for many years. Due to thermal effects, they are also practically unusable after about ten years. In particular, when the bits are only a few nanometres in size, they lose stability. Once lost, the magnetization direction of the hard magnetic layer cannot easily be set again in the original direction.. This leads irretrievably loss of data. This stability issue can now be addressed with the new spin-valve concept. By tunning the magnetic properties of the hard ferrimagnetic layer, the so-called RAM memory building-blocks (RAM stands for random access memory) can be manufactured with controlled life-time of the stored information of weeks, months or years.. Thereafter, the magnetic orientation can be resettedin the original state, which increases considerably the overall life expectancy of the information as compared to the existing non-volatile MRAM (Magnetoresistive Random Access Memory). These memory building-blocks are now certainly highly sought-after in the field of micro-electronics, but have not been able, to date, to be established in the markets due to high costs and technical problems. With the spin-valve concept by Radu and his colleagues, electronic devices can now be developed that, similar to the MRAM technology, are operable immediately after being switched on and allow their data storage units to be re-written more or less indefinitely. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Soil Carbon Storage has emerged as a feasible strategy for removing carbon dioxide from the atmosphere, raising important questions regarding whether the general public supports the strategy as a means to address climate change. We analyzed data from a national probability survey of 1222 US adults who reported believing in climate change at least “somewhat” to estimate public support for Soil Carbon Storage and how it compares to other leading Carbon Dioxide Removal (CDR) strategies. Overall, a majority of the sample expressed support for Soil Carbon Storage—regardless of whether the strategy involved the use of biochar (a form of charcoal made from organic matter) or not (55% and 62%, respectively)—placing Soil Carbon Storage ahead of Bioenergy plus Carbon Capture and Storage (32%) and Direct Air Capture (25%), and behind only Afforestation and Reforestation (73%), in terms of public support. In addition, perceiving Soil Carbon Storage as “natural” strongly predicted individual-level support, a pattern that held for every CDR strategy featured on the survey. Results demonstrate broad US public support for Soil Carbon Storage as a climate change mitigation strategy at a time when scientists and policymakers are actively considering the political, not just technical, feasibility of different climate solutions. Access provided by MPDL Services gGmbH c/o Max Planck Digital Library Working on a manuscript? Avoid the common mistakes 1 Introduction 1.1 Carbon Dioxide Removal (CDR) strategies According to the Intergovernmental Panel on Climate Change (IPCC 2018 ), anthropogenic climate change—due largely to carbon dioxide emissions (Cox et al. 2000 ; Solomon et al. 2009 )—increased the global average temperature to 1 °C above pre-industrial levels in 2017. However, the same IPCC report concluded that maintaining a global temperature increase of less than 1.5 °C would substantially reduce risks to ecosystems and humans relative to 2 °C of warming (IPCC 2018 ). There is a growing consensus that meeting this target will be difficult to achieve via reductions in greenhouse gas emissions alone. In addition to reducing emissions, strategies that create “negative emissions” scenarios—for example, Carbon Dioxide Removal (CDR) strategies—will likely also be needed (Van Vuuren et al. 2018 ). CDR strategies remove carbon dioxide from the atmosphere using chemical and/or biological solutions to capture and store carbon dioxide (Corner and Pidgeon 2014 ; Field and Mach 2017 ; Lawrence et al. 2018 ; Rogelj et al. 2018 , Smith et al. 2016 ). As several CDR strategies have emerged in recent years, scholars have recognized that gaining policy traction in this area will require not only demonstrating the scientific feasibility of these techniques (Caldeira et al. 2013 ; Fuss et al. 2018 ) but also understanding public opinion on the issue, including the psychological factors that predict support for different strategies (Campbell and Kay 2014 ; Minx et al. 2018 ; Shrum et al. 2020 ). This may be particularly important in the USA, where the issue of climate change and proposed policy solutions have been politically polarized for decades (Dunlap et al. 2016 ; McCright and Dunlap 2011 ). Although recent public opinion data reveal that a majority of the US public is concerned about climate change and its implications for society (Borick and Rabe 2012 ; Brulle et al. 2012 ; Leiserowitz et al. 2019 ; Schuldt et al. 2020 ; Van Boven and Sherman 2018 ), there is limited consensus on which strategies should be used to address the issue (Corner et al. 2013 ; Faran and Olsson 2018 ; Kahan et al. 2015 ; Preston 2013 ). This is partly because public opinion is often shaped by subjective risk perceptions, whether it regards a global pandemic (Dryhurst et al. 2020 ; Walter et al. 2012 ; van der Weerd et al. 2011 ) or new technological breakthroughs (Bassarak et al. 2017 ; Sjöberg 2000 ; Slovic 2000 ). When it comes to CDR strategies in particular, members of the public and key stakeholder groups may not yet have strongly formed opinions. As a consequence, they may rely on pre-existing mental schemas and cognitive associations in deciding whether or not to support a given strategy for removing carbon dioxide from the atmosphere (Shrum et al. 2020 ). 1.2 Soil Carbon Storage As CDR strategies have gained attention in scientific circles, a growing number of studies suggest that sequestering carbon in soils may be a worthwhile approach to addressing climate change (Christoff 2016 ; García-Tejero et al. 2020 ; Lal 2004; Minasny et al. 2017 ; Vermeulen et al. 2019 ). One such approach involves managing land, such as farm and grazing lands, forests, and wetlands, in ways that store increased amounts of carbon in the soil, thus keeping it out of the atmosphere (i.e., Soil Carbon Storage) (Bossio et al. 2020 ; Doetterl et al. 2015 ). Another approach receiving recent attention (Minx et al. 2017 ) involves the same land management approaches mentioned above plus the use of heat to convert unused plant material or manure on farms into a form of charcoal called biochar (Demirbas and Arin 2002 ; Gurwick et al. 2012 ; Lehmann and Joseph 2015 ), which is then mixed into the soil in order to store carbon for long periods of time (i.e., Soil Carbon Storage with Biochar) (Winsley 2007 ; Laird 2008 ; Woolf et al. 2010 ). Although sequestering carbon in soil to mitigate climate change is scientifically feasible (Lal et al. 2003 ; Sykes et al. 2020 ), some have argued there may be significant political barriers to implementing Soil Carbon Storage in the USA, given that key stakeholders, such as farmers, tend to be lean politically conservative and may be resistant to government regulations aimed at addressing climate change (Amundson and Biardeau 2018 ; Amelung et al. 2020 ). Also, while a small number of studies have investigated public perceptions of Soil Carbon Storage as a climate change mitigation strategy (Glenk and Colombo 2011 ; Kragt et al. 2016 ; Shrum et al. 2020 ), few have examined how the public reacts to the use of", "role": "user" }, { "content": "Soil carbon storage, carbon capture and storage, biochar—mention these terms to most people, and a blank stare might be the response. But frame these climate change mitigation strategies as being clean and green approaches to reversing the dangerous warming of our planet, and people might be more inclined to at least listen—and even to back these efforts. A cross-disciplinary collaboration led by Jonathon Schuldt, associate professor of communication at Cornell University, found that a majority of the U.S. public is supportive of soil carbon storage as a climate change mitigation strategy, particularly when that and similar approaches are seen as \"natural\" strategies. \"To me, that psychology part—that's really interesting,\" Schuldt said. \"What would lead people, especially if they're unfamiliar with these different strategies, to support one more than the other? Our study and others suggest that a big part of it is whether people see it as natural.\" The group's paper, \"Perceptions of Naturalness Predict U.S. Public Support for Soil Carbon Storage as a Climate Solution,\" published May 26 in the journal Climatic Change. Co-authors include Johannes Lehmann, the Liberty Hyde Bailey Professor in the School of Integrative Plant Science (SIPS), Soil and Crop Sciences Section (CALS); Dominic Woolf, senior research associate in SIPS; Shannan Sweet, postdoctoral associate in the Lehmann Lab; and Deborah Bossio of the Nature Conservancy. Schuldt's team analyzed results from a survey of 1,222 U.S. adults who reported believing in climate change at least \"somewhat,\" to estimate public support for soil carbon storage and how it compares to other leading carbon dioxide removal strategies. Mitigation strategies—solar and wind power, electric vehicles and sustainable land use and biodiversity, to name a few—are already capturing much attention as the world grapples with rising temperatures, melting ice caps and increasingly violent weather events. Survey data came from an online poll conducted Sept. 19 to Oct. 4, 2019, by NORC at the University of Chicago, a leading survey research firm. The team solicited respondents' perceptions of naturalness and policy support for five CO2 removal strategies: afforestation and reforestation; bioenergy plus carbon capture and storage; direct air capture; soil carbon storage; and soil carbon storage with biochar. Each respondent viewed a randomized group of three options and was asked to estimate the likelihood that they'd support that strategy. They were also asked to rate their level of agreement with each of five statements related to humans' tampering with nature. In the final analysis, perceived naturalness was a strong indicator of support for soil carbon storage as a climate change mitigation strategy. Of the five CO2 removal strategies, support was highest (73%) for afforestation and reforestation; soil carbon storage ranked second, supported by 62% of those polled. And in this politically divided time, Schuldt said, support for soil carbon storage crossed the aisle. A total of 72% who identified as Democrats supported the strategy; among Republicans, 52% were in support. \"We expected, and found, that Democrats support all kinds of climate strategies more than Republicans do,\" Schuldt said. \"But the error I think we sometimes make is that we categorize all Democrats as being for it, and all Republicans as being against it. That's not true.\" Ultimately, Schuldt said, the goal is to allow policymakers to present the public with palatable options for addressing climate change. \"There is a whole range of solutions out there,\" he said. \"Then the question politically becomes, where do you start? Which one has the most buy-in? I think our data help speak to that.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Soil Carbon Storage has emerged as a feasible strategy for removing carbon dioxide from the atmosphere, raising important questions regarding whether the general public supports the strategy as a means to address climate change. We analyzed data from a national probability survey of 1222 US adults who reported believing in climate change at least “somewhat” to estimate public support for Soil Carbon Storage and how it compares to other leading Carbon Dioxide Removal (CDR) strategies. Overall, a majority of the sample expressed support for Soil Carbon Storage—regardless of whether the strategy involved the use of biochar (a form of charcoal made from organic matter) or not (55% and 62%, respectively)—placing Soil Carbon Storage ahead of Bioenergy plus Carbon Capture and Storage (32%) and Direct Air Capture (25%), and behind only Afforestation and Reforestation (73%), in terms of public support. In addition, perceiving Soil Carbon Storage as “natural” strongly predicted individual-level support, a pattern that held for every CDR strategy featured on the survey. Results demonstrate broad US public support for Soil Carbon Storage as a climate change mitigation strategy at a time when scientists and policymakers are actively considering the political, not just technical, feasibility of different climate solutions. Access provided by MPDL Services gGmbH c/o Max Planck Digital Library Working on a manuscript? Avoid the common mistakes 1 Introduction 1.1 Carbon Dioxide Removal (CDR) strategies According to the Intergovernmental Panel on Climate Change (IPCC 2018 ), anthropogenic climate change—due largely to carbon dioxide emissions (Cox et al. 2000 ; Solomon et al. 2009 )—increased the global average temperature to 1 °C above pre-industrial levels in 2017. However, the same IPCC report concluded that maintaining a global temperature increase of less than 1.5 °C would substantially reduce risks to ecosystems and humans relative to 2 °C of warming (IPCC 2018 ). There is a growing consensus that meeting this target will be difficult to achieve via reductions in greenhouse gas emissions alone. In addition to reducing emissions, strategies that create “negative emissions” scenarios—for example, Carbon Dioxide Removal (CDR) strategies—will likely also be needed (Van Vuuren et al. 2018 ). CDR strategies remove carbon dioxide from the atmosphere using chemical and/or biological solutions to capture and store carbon dioxide (Corner and Pidgeon 2014 ; Field and Mach 2017 ; Lawrence et al. 2018 ; Rogelj et al. 2018 , Smith et al. 2016 ). As several CDR strategies have emerged in recent years, scholars have recognized that gaining policy traction in this area will require not only demonstrating the scientific feasibility of these techniques (Caldeira et al. 2013 ; Fuss et al. 2018 ) but also understanding public opinion on the issue, including the psychological factors that predict support for different strategies (Campbell and Kay 2014 ; Minx et al. 2018 ; Shrum et al. 2020 ). This may be particularly important in the USA, where the issue of climate change and proposed policy solutions have been politically polarized for decades (Dunlap et al. 2016 ; McCright and Dunlap 2011 ). Although recent public opinion data reveal that a majority of the US public is concerned about climate change and its implications for society (Borick and Rabe 2012 ; Brulle et al. 2012 ; Leiserowitz et al. 2019 ; Schuldt et al. 2020 ; Van Boven and Sherman 2018 ), there is limited consensus on which strategies should be used to address the issue (Corner et al. 2013 ; Faran and Olsson 2018 ; Kahan et al. 2015 ; Preston 2013 ). This is partly because public opinion is often shaped by subjective risk perceptions, whether it regards a global pandemic (Dryhurst et al. 2020 ; Walter et al. 2012 ; van der Weerd et al. 2011 ) or new technological breakthroughs (Bassarak et al. 2017 ; Sjöberg 2000 ; Slovic 2000 ). When it comes to CDR strategies in particular, members of the public and key stakeholder groups may not yet have strongly formed opinions. As a consequence, they may rely on pre-existing mental schemas and cognitive associations in deciding whether or not to support a given strategy for removing carbon dioxide from the atmosphere (Shrum et al. 2020 ). 1.2 Soil Carbon Storage As CDR strategies have gained attention in scientific circles, a growing number of studies suggest that sequestering carbon in soils may be a worthwhile approach to addressing climate change (Christoff 2016 ; García-Tejero et al. 2020 ; Lal 2004; Minasny et al. 2017 ; Vermeulen et al. 2019 ). One such approach involves managing land, such as farm and grazing lands, forests, and wetlands, in ways that store increased amounts of carbon in the soil, thus keeping it out of the atmosphere (i.e., Soil Carbon Storage) (Bossio et al. 2020 ; Doetterl et al. 2015 ). Another approach receiving recent attention (Minx et al. 2017 ) involves the same land management approaches mentioned above plus the use of heat to convert unused plant material or manure on farms into a form of charcoal called biochar (Demirbas and Arin 2002 ; Gurwick et al. 2012 ; Lehmann and Joseph 2015 ), which is then mixed into the soil in order to store carbon for long periods of time (i.e., Soil Carbon Storage with Biochar) (Winsley 2007 ; Laird 2008 ; Woolf et al. 2010 ). Although sequestering carbon in soil to mitigate climate change is scientifically feasible (Lal et al. 2003 ; Sykes et al. 2020 ), some have argued there may be significant political barriers to implementing Soil Carbon Storage in the USA, given that key stakeholders, such as farmers, tend to be lean politically conservative and may be resistant to government regulations aimed at addressing climate change (Amundson and Biardeau 2018 ; Amelung et al. 2020 ). Also, while a small number of studies have investigated public perceptions of Soil Carbon Storage as a climate change mitigation strategy (Glenk and Colombo 2011 ; Kragt et al. 2016 ; Shrum et al. 2020 ), few have examined how the public reacts to the use of<|im_end|> <|im_start|>assistant Soil carbon storage, carbon capture and storage, biochar—mention these terms to most people, and a blank stare might be the response. But frame these climate change mitigation strategies as being clean and green approaches to reversing the dangerous warming of our planet, and people might be more inclined to at least listen—and even to back these efforts. A cross-disciplinary collaboration led by Jonathon Schuldt, associate professor of communication at Cornell University, found that a majority of the U.S. public is supportive of soil carbon storage as a climate change mitigation strategy, particularly when that and similar approaches are seen as "natural" strategies. "To me, that psychology part—that's really interesting," Schuldt said. "What would lead people, especially if they're unfamiliar with these different strategies, to support one more than the other? Our study and others suggest that a big part of it is whether people see it as natural." The group's paper, "Perceptions of Naturalness Predict U.S. Public Support for Soil Carbon Storage as a Climate Solution," published May 26 in the journal Climatic Change. Co-authors include Johannes Lehmann, the Liberty Hyde Bailey Professor in the School of Integrative Plant Science (SIPS), Soil and Crop Sciences Section (CALS); Dominic Woolf, senior research associate in SIPS; Shannan Sweet, postdoctoral associate in the Lehmann Lab; and Deborah Bossio of the Nature Conservancy. Schuldt's team analyzed results from a survey of 1,222 U.S. adults who reported believing in climate change at least "somewhat," to estimate public support for soil carbon storage and how it compares to other leading carbon dioxide removal strategies. Mitigation strategies—solar and wind power, electric vehicles and sustainable land use and biodiversity, to name a few—are already capturing much attention as the world grapples with rising temperatures, melting ice caps and increasingly violent weather events. Survey data came from an online poll conducted Sept. 19 to Oct. 4, 2019, by NORC at the University of Chicago, a leading survey research firm. The team solicited respondents' perceptions of naturalness and policy support for five CO2 removal strategies: afforestation and reforestation; bioenergy plus carbon capture and storage; direct air capture; soil carbon storage; and soil carbon storage with biochar. Each respondent viewed a randomized group of three options and was asked to estimate the likelihood that they'd support that strategy. They were also asked to rate their level of agreement with each of five statements related to humans' tampering with nature. In the final analysis, perceived naturalness was a strong indicator of support for soil carbon storage as a climate change mitigation strategy. Of the five CO2 removal strategies, support was highest (73%) for afforestation and reforestation; soil carbon storage ranked second, supported by 62% of those polled. And in this politically divided time, Schuldt said, support for soil carbon storage crossed the aisle. A total of 72% who identified as Democrats supported the strategy; among Republicans, 52% were in support. "We expected, and found, that Democrats support all kinds of climate strategies more than Republicans do," Schuldt said. "But the error I think we sometimes make is that we categorize all Democrats as being for it, and all Republicans as being against it. That's not true." Ultimately, Schuldt said, the goal is to allow policymakers to present the public with palatable options for addressing climate change. "There is a whole range of solutions out there," he said. "Then the question politically becomes, where do you start? Which one has the most buy-in? I think our data help speak to that." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Neuronal activities underlying a percept are constrained by the physics of sensory signals. In the tactile sense such constraints are frictional stick–slip events, occurring, amongst other vibrotactile features, when tactile sensors are in contact with objects. We reveal new biomechanical phenomena about the transmission of these microNewton forces at the tip of a rat’s whisker, where they occur, to the base where they engage primary afferents. Using high resolution videography and accurate measurement of axial and normal forces at the follicle, we show that the conical and curved rat whisker acts as a sign-converting amplification filter for moment to robustly engage primary afferents. Furthermore, we present a model based on geometrically nonlinear Cosserat rod theory and a friction model that recreates the observed whole-beam whisker dynamics. The model quantifies the relation between kinematics (positions and velocities) and dynamic variables (forces and moments). Thus, only videographic assessment of acceleration is required to estimate forces and moments measured by the primary afferents. Our study highlights how sensory systems deal with complex physical constraints of perceptual targets and sensors. Introduction The study of perception needs to consider the special physical (and chemical) properties of the sensory objects and their interaction with the sensors. In the tactile system, and most prominently in texture discrimination, such physical constraints include friction, arising with moving mechanical contact of integument (hair and skin) and touched object. Frictional phenomena with presumptive high impact on tactile coding are the so-called ‘stick–slip events’ (slips), short jerky movements that originate from storing and releasing energy into elastic object deformations on the microscopic level 1 . Here, we focus on rats’ vibrissae, or whiskers, tactile hairs that the animals actively move across textures. Rodent vibrissae are tapered giving them extraordinary elasticity 2 , 3 , and pliability 4 , 5 , 6 . Vibrissae movements vary in characteristic ways 7 , 8 , 9 , such that, in principle, the animal could choose to vary properties of the whisking motion, in order to optimize its performance in a challenging perceptual context. Tracking a point on the vibrissae shaft when rats touched textured surfaces 10 , 11 has demonstrated that sequences of frictional stick–slip events can carry a substantial amount of texture information, as well as information about the context, e.g. speed and distance to the texture surface 12 . System identification methods have identified that microslip-like features in the vibrotactile domain are well encoded on the tactile neural pathway 13 , 14 , 15 , 16 , 17 , 18 , 19 . Finally, behavioural studies suggest that such stick–slip signals determine perception 20 , 21 . From the study of biomechanical properties of whiskers, it has been suggested that dynamical variables, such as force and moment, are likely to be the definitive factors for stimulation of the mechanoreceptors in the follicle 2 , 4 . Unfortunately, observations of motion of intact whiskers used by a behaving animal are largely limited to whisker kinematics. It is therefore crucial to find out how kinematic variables associated with the whisker’s tip relate to dynamical variables. Moreover, it remains to establish the principles of mechanical transmission of signals along the whisker beam, from the highly pliable tip towards the much stiffer follicle, where neural signals are generated. It would seem that mathematical modelling is necessary to faithfully translate measured whisker kinematics into dynamics. At present, whisker mechanics has mainly been studied using either linear beam theory 4 , 22 or using a quasi-static approximation of a Euler elastica with non-uniform axial properties 23 , 24 , 25 . These approaches are useful for establishing the linear vibration frequencies in contactless whisking, and the quasi-static nonlinear deformations, like buckling, that likely occur when the pliable tip 6 is in continuous contact with a surface. For example, Goss and Chaouki 25 , using elastic beam theory, worked out criteria for the establishment of tip and line contacts, depending on the distance of the beam to the surface (see also 26 , 27 ). Also, the quasi-static Elastica2D code introduced in 24 has been successfully used by 28 to measure the axial follicle force. But none of these techniques can be used to measure the rapid dynamic forces in the transmission of stick–slip waves from the tip to the follicle. In the spirit of this earlier work, we therefore adapt the elastica formulation to include rapid dynamical deformation while the whisker is in contact with a surface. To do this we employ Cosserat rod-mechanics formulation (e.g. 29 ), to model the dynamics of velocity, force and moment at every position along the central axis of the whisker, with complex boundary conditions that can capture the impulsive forces caused by transitions between stick and slip contact. The earlier models likely capture the DC component of the forces at the follicle (which is likely to sense proximity and hardness) whereas our model is able to capture the rapid AC component of these forces, which we argue is how texture is likely to be coded. In the present work we include the case of tip contact only, but following the approach outlined in 25 it is straightforward in principle to extend our mathematical formulation to include line contact. In particular, a simple mechanical argument shows that the forces transmitted in the presence of line contact are dynamically equivalent to those of a shorter rod undergoing tip contact. We combine modelling with a limited number of biomechanical measurements to identify new biomechanical phenomena about how slip-stick transitions at the whisker tip are transmitted to force and moment information at its base. We will show that deflections at the tip, characterized by low moments and large excursions, are rapidly transmitted and result in large moment / short excursion movements at the base, and we will demonstrate that the non-linear modelling can recreate these observed characteristics. Our results strongly suggest that slips generated at the tip are presented in robust fashion to the base, the location of the neurites. Results For videography, the follicle", "role": "user" }, { "content": "How we sense texture has long been a mystery. It is known that nerves attached to the fingertip skin are responsible for sensing different surfaces, but how they do it is not well understood. Rodents perform texture sensing through their whiskers. Like human fingertips, whiskers perform multiple tasks, sensing proximity and shape of objects, as well as surface textures. Mathematicians from the University of Bristol's Department of Engineering Mathematics, worked with neuroscientists from the University of Tuebingen in Germany, to understand how the motion of a whisker across a surface translates texture information into neural signals that can be perceived by the brain. By carrying out high precision laboratory tests on a real rat whisker, combined with computation models, the researchers found that whiskers act like antennae, tuned to sense the tiny stick-slip motions caused by friction between the surface and the tip of the whisker. \"One of the most striking things we found both in the experiments and the theory was the thousand-fold amplification of tiny force signals perceived by the tip of the whisker to that received by the neurons at the whiskers base. Suddenly we realized that the whisker is acting like an amplifier, taking micro-scale stick-slip events and rapidly turning them into clean pulses that can be picked up and processed by the brain,\" said Professor Alan Champneys from the University of Bristol, co-lead of the modeling work with colleague, Dr. Robert Szalai. Dr. Thibaut Putelat carried out the detailed numerical modeling. The research Conveyance of texture signals along a rat whisker, published in the journal Scientific Reports from the publisher Nature, reveals the tapering of the whisker has the effect of amplifying tiny high-frequency motions into appreciable pulse-like changes in forces and movement at the whisker follicle. In turn, the nerve cells in the follicle sense these changes and transmit them to the brain. \"It is almost as if the morphology of the whisker is designed to convey these friction-induced signals as \"AC\" waves on top of the \"DC\" motion of the whisker that conveys the information on surface proximity and hardness. \"These AC waves are too small and too rapid to be perceived by the human eye. However, in approaching this problem in a multidisciplinary fashion, we have been able to reveal these waves with clarity for the first time,\" said Professor Champneys. \"The findings have implications for human touch too, where the morphology of finger-print ridges is more complex, but might similarly distinguish between AC and DC signals as our brain tries to disentangle multiple information streams about what we are feeling,\" said Dr. Maysam Oladazimi, who carried out the experiments as part of his Ph.D. The findings could have far-reaching benefits including how textures could be designed to provide optimal cues for the visually impaired, for human safety operation in low light environments, or for immersive artistic installations. \"This research opens several avenues for future work. As neuroscientists, we are interested in developing a more detailed understanding of neural signaling pathways in texture discrimination, while our colleagues in Bristol are keen to explore implications for the design of future robotic sensing systems,\" said Professor Cornelius Schwarz, who led the experiments at the University of Tuebingen. Professor Champneys said the research was of particular value to haptic-sensing in the field of robotics, where robots literally feel their environment and is the focus of much current research, especially for robots that need to act autonomously in the dark, such as in search and rescue missions. Professor Nathan Lepora and colleagues at the Bristol Robotics Laboratory are pioneers in this field. \"This transnational interdisciplinary collaboration between experimentalists and mathematical modelers was exciting. The results from the computer models and from the laboratory experiments went hand in hand—it was only through a combination of the two that we were able to make our breakthrough,\" said Professor Champneys. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Neuronal activities underlying a percept are constrained by the physics of sensory signals. In the tactile sense such constraints are frictional stick–slip events, occurring, amongst other vibrotactile features, when tactile sensors are in contact with objects. We reveal new biomechanical phenomena about the transmission of these microNewton forces at the tip of a rat’s whisker, where they occur, to the base where they engage primary afferents. Using high resolution videography and accurate measurement of axial and normal forces at the follicle, we show that the conical and curved rat whisker acts as a sign-converting amplification filter for moment to robustly engage primary afferents. Furthermore, we present a model based on geometrically nonlinear Cosserat rod theory and a friction model that recreates the observed whole-beam whisker dynamics. The model quantifies the relation between kinematics (positions and velocities) and dynamic variables (forces and moments). Thus, only videographic assessment of acceleration is required to estimate forces and moments measured by the primary afferents. Our study highlights how sensory systems deal with complex physical constraints of perceptual targets and sensors. Introduction The study of perception needs to consider the special physical (and chemical) properties of the sensory objects and their interaction with the sensors. In the tactile system, and most prominently in texture discrimination, such physical constraints include friction, arising with moving mechanical contact of integument (hair and skin) and touched object. Frictional phenomena with presumptive high impact on tactile coding are the so-called ‘stick–slip events’ (slips), short jerky movements that originate from storing and releasing energy into elastic object deformations on the microscopic level 1 . Here, we focus on rats’ vibrissae, or whiskers, tactile hairs that the animals actively move across textures. Rodent vibrissae are tapered giving them extraordinary elasticity 2 , 3 , and pliability 4 , 5 , 6 . Vibrissae movements vary in characteristic ways 7 , 8 , 9 , such that, in principle, the animal could choose to vary properties of the whisking motion, in order to optimize its performance in a challenging perceptual context. Tracking a point on the vibrissae shaft when rats touched textured surfaces 10 , 11 has demonstrated that sequences of frictional stick–slip events can carry a substantial amount of texture information, as well as information about the context, e.g. speed and distance to the texture surface 12 . System identification methods have identified that microslip-like features in the vibrotactile domain are well encoded on the tactile neural pathway 13 , 14 , 15 , 16 , 17 , 18 , 19 . Finally, behavioural studies suggest that such stick–slip signals determine perception 20 , 21 . From the study of biomechanical properties of whiskers, it has been suggested that dynamical variables, such as force and moment, are likely to be the definitive factors for stimulation of the mechanoreceptors in the follicle 2 , 4 . Unfortunately, observations of motion of intact whiskers used by a behaving animal are largely limited to whisker kinematics. It is therefore crucial to find out how kinematic variables associated with the whisker’s tip relate to dynamical variables. Moreover, it remains to establish the principles of mechanical transmission of signals along the whisker beam, from the highly pliable tip towards the much stiffer follicle, where neural signals are generated. It would seem that mathematical modelling is necessary to faithfully translate measured whisker kinematics into dynamics. At present, whisker mechanics has mainly been studied using either linear beam theory 4 , 22 or using a quasi-static approximation of a Euler elastica with non-uniform axial properties 23 , 24 , 25 . These approaches are useful for establishing the linear vibration frequencies in contactless whisking, and the quasi-static nonlinear deformations, like buckling, that likely occur when the pliable tip 6 is in continuous contact with a surface. For example, Goss and Chaouki 25 , using elastic beam theory, worked out criteria for the establishment of tip and line contacts, depending on the distance of the beam to the surface (see also 26 , 27 ). Also, the quasi-static Elastica2D code introduced in 24 has been successfully used by 28 to measure the axial follicle force. But none of these techniques can be used to measure the rapid dynamic forces in the transmission of stick–slip waves from the tip to the follicle. In the spirit of this earlier work, we therefore adapt the elastica formulation to include rapid dynamical deformation while the whisker is in contact with a surface. To do this we employ Cosserat rod-mechanics formulation (e.g. 29 ), to model the dynamics of velocity, force and moment at every position along the central axis of the whisker, with complex boundary conditions that can capture the impulsive forces caused by transitions between stick and slip contact. The earlier models likely capture the DC component of the forces at the follicle (which is likely to sense proximity and hardness) whereas our model is able to capture the rapid AC component of these forces, which we argue is how texture is likely to be coded. In the present work we include the case of tip contact only, but following the approach outlined in 25 it is straightforward in principle to extend our mathematical formulation to include line contact. In particular, a simple mechanical argument shows that the forces transmitted in the presence of line contact are dynamically equivalent to those of a shorter rod undergoing tip contact. We combine modelling with a limited number of biomechanical measurements to identify new biomechanical phenomena about how slip-stick transitions at the whisker tip are transmitted to force and moment information at its base. We will show that deflections at the tip, characterized by low moments and large excursions, are rapidly transmitted and result in large moment / short excursion movements at the base, and we will demonstrate that the non-linear modelling can recreate these observed characteristics. Our results strongly suggest that slips generated at the tip are presented in robust fashion to the base, the location of the neurites. Results For videography, the follicle<|im_end|> <|im_start|>assistant How we sense texture has long been a mystery. It is known that nerves attached to the fingertip skin are responsible for sensing different surfaces, but how they do it is not well understood. Rodents perform texture sensing through their whiskers. Like human fingertips, whiskers perform multiple tasks, sensing proximity and shape of objects, as well as surface textures. Mathematicians from the University of Bristol's Department of Engineering Mathematics, worked with neuroscientists from the University of Tuebingen in Germany, to understand how the motion of a whisker across a surface translates texture information into neural signals that can be perceived by the brain. By carrying out high precision laboratory tests on a real rat whisker, combined with computation models, the researchers found that whiskers act like antennae, tuned to sense the tiny stick-slip motions caused by friction between the surface and the tip of the whisker. "One of the most striking things we found both in the experiments and the theory was the thousand-fold amplification of tiny force signals perceived by the tip of the whisker to that received by the neurons at the whiskers base. Suddenly we realized that the whisker is acting like an amplifier, taking micro-scale stick-slip events and rapidly turning them into clean pulses that can be picked up and processed by the brain," said Professor Alan Champneys from the University of Bristol, co-lead of the modeling work with colleague, Dr. Robert Szalai. Dr. Thibaut Putelat carried out the detailed numerical modeling. The research Conveyance of texture signals along a rat whisker, published in the journal Scientific Reports from the publisher Nature, reveals the tapering of the whisker has the effect of amplifying tiny high-frequency motions into appreciable pulse-like changes in forces and movement at the whisker follicle. In turn, the nerve cells in the follicle sense these changes and transmit them to the brain. "It is almost as if the morphology of the whisker is designed to convey these friction-induced signals as "AC" waves on top of the "DC" motion of the whisker that conveys the information on surface proximity and hardness. "These AC waves are too small and too rapid to be perceived by the human eye. However, in approaching this problem in a multidisciplinary fashion, we have been able to reveal these waves with clarity for the first time," said Professor Champneys. "The findings have implications for human touch too, where the morphology of finger-print ridges is more complex, but might similarly distinguish between AC and DC signals as our brain tries to disentangle multiple information streams about what we are feeling," said Dr. Maysam Oladazimi, who carried out the experiments as part of his Ph.D. The findings could have far-reaching benefits including how textures could be designed to provide optimal cues for the visually impaired, for human safety operation in low light environments, or for immersive artistic installations. "This research opens several avenues for future work. As neuroscientists, we are interested in developing a more detailed understanding of neural signaling pathways in texture discrimination, while our colleagues in Bristol are keen to explore implications for the design of future robotic sensing systems," said Professor Cornelius Schwarz, who led the experiments at the University of Tuebingen. Professor Champneys said the research was of particular value to haptic-sensing in the field of robotics, where robots literally feel their environment and is the focus of much current research, especially for robots that need to act autonomously in the dark, such as in search and rescue missions. Professor Nathan Lepora and colleagues at the Bristol Robotics Laboratory are pioneers in this field. "This transnational interdisciplinary collaboration between experimentalists and mathematical modelers was exciting. The results from the computer models and from the laboratory experiments went hand in hand—it was only through a combination of the two that we were able to make our breakthrough," said Professor Champneys. <|im_end|>

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2,103

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Quantum walks have been employed widely to develop new tools for quantum information processing recently. A natural quantum walk dynamics of interacting particles can be used to implement efficiently the universal quantum computation. In this work quantum walks of electrons on a graph are studied. The graph is composed of semiconductor quantum dots arranged in a circle. Electrons can tunnel between adjacent dots and interact via Coulomb repulsion, which leads to entanglement. Fermionic entanglement dynamics is obtained and evaluated. Introduction Quantum walks are quantum counterparts of classical random walks 1 , 2 . Unlike the state of classical walker, quantum walker’s state can be a coherent superposition of several positions. Quantum walks found applications to various fields, for example, to the development of a new family of quantum algorithms 3 , 4 , 5 , 6 or to the efficient energy transfer in proteins 7 . And recently, quantum walk dynamics is used as an underlying mechanism for quantum-enhanced decision-making process in reinforcement learning 8 , 9 , for which schemes of experimental realization in systems of trapped ions and superconducting transmon qubits were proposed 10 , 11 . There are plenty of theoretical and experimental results in the field of single-particle quantum walks 12 , 13 , but walks with multiple identical walkers, in both non-interacting and interacting cases, are less explored. In this paper we study quantum walks of identical particles for quantum information processing purposes. It is known that entanglement creation plays a pivotal role in most of the branches of quantum information. Here we introduce a method for generating a two-qudit (two d-level systems) entangled state by implementing continuous-time quantum walks on a cycle graph. This technique allows us to observe diverse structures of entangled subsystems of high dimensions, a preparation of which is of importance 14 , 15 . To relate theoretical study with feasible experimental implementations we consider realistic models of quantum walks 16 . The physical system we choose as a suitable candidate for quantum walks implementation is an array of tunnel-coupled semiconductor quantum dots. Quantum dots in semiconductors can be used as building blocks for a construction of a quantum computer, where quantum dots positions provide a spatial degree of freedom of a quantum particle 17 , 18 , 19 , 20 . It was shown that a spatial location of an electron in one of two semiconductor quantum dots can serve for encoding a qubit 17 , 18 and errors that occur mostly because of the interaction with acoustic phonons can be corrected 21 , 22 . In this paper we study quantum dots arranged in a circle, where each quantum dot can be populated by no more than one electron. By placing two identical particles in this system, one can define higher dimensional quantum states, qudits. If electrons are close enough they can also influence each other via Coulomb interaction. First, we analyze dynamics of non-interacting particles, and then we proceed to the case of interacting electrons. Results The remainder of the paper has the following structure: first, we introduce the model of symmetrical two-electron quantum walk on a cycle graph of arbitrary size. After the introduction of the model we study the dynamics of electrons in the cases with and without an interaction between them. The case of interacting electrons is studied in details and the scheme for entangling gate between two qudits, represented by two electrons, is proposed. Then we summarize the results and discuss possible applications of the proposed scheme. Framework The system under consideration contains two electrons. Each electron can sit in one of N quantum dots arranged in a circle 23 . Dots themselves can be formed from the two-dimensional electron gas by field of gates and the population of electrons in these dots can be controlled by potentials on gates. Each position in the circle can be occupied by at most one electron. The position of an electron can be measured by quantum point contact detectors, which are placed near quantum dots such that an electron in a certain quantum dot decreases an electric current in the detector by increasing a potential barrier. Therefore a lower current detects an electron and a higher current indicates an absence of an electron (an empty quantum dot), correspondingly. Experimentally, lateral structures of this geometry with different number of quantum dots were realized. Among them, a double quantum dot, which can be viewed as a circle with N = 2 sites, is the most studied configuration and is used to create a solid state qubit 24 , 25 , 26 , 27 . Beyond this, triple quantum dots with circular and linear geometries were studied in detail both theoretically and experimentally 28 . A concept of a scalable architecture was demonstrated by fabricating quadruple 29 , 30 , 31 and quintuple 32 quantum dots. In all experiments, a high degree of control over the precise number of electrons in each quantum dot was demonstrated by measuring stability diagrams. Moreover, it was shown that it is possible to tune the tunnel coupling between neighbouring quantum dots by changing the voltage on the gate that spatially separates these dots, see e.g. ref. 26 , where the tunnel coupling was shown to be an exponential function of the gate voltage. Similar techniques and technologies could be used for a fabrication of circles of larger sizes. The described circle of semiconductor quantum dots is mathematically represented as a cycle graph with quantum dots being vertices of this graph. Edges of the cycle graph connect only nearest neighbours and represent possible tunnel transitions of electrons. We enumerate the vertices within the graph, from 0 to N − 1. The localization of an electron in the 0-th, 1-st, … or ( N − 1)-th quantum dot is described by corresponding quantum states |0〉, |1〉, … or | N − 1〉, as shown in Fig. 1 for N = 2 K , . As a straightforward result, the states |0〉, |1〉, … and |", "role": "user" }, { "content": "Scientists from the Institute of Physics and Technology of the Russian Academy of Sciences and MIPT have let two electrons loose in a system of quantum dots to create a quantum computer memory cell of a higher dimension than a qubit (a quantum bit). In their study published in Scientific Reports, the researchers demonstrate for the first time how quantum walks of several electrons can help to implement quantum computation. \"By studying the system with two electrons, we solved the problems faced in the general case of two identical interacting particles. This paves the way toward compact high-level quantum structures,\" says Leonid Fedichkin, associate professor at MIPT's Department of Theoretical Physics. In a matter of hours, a quantum computer would be able to hack through the most popular cryptosystem used by web browsers. As far as more benevolent applications are concerned, a quantum computer would be capable of molecular modeling that accounts for all interactions between the particles involved. This in turn would enable the development of highly efficient solar cells and new drugs. To have practical applications, a quantum computer needs to incorporate hundreds or even thousands of qubits. And that is where it gets tricky. As it turns out, the unstable nature of the connection between qubits remains the major obstacle preventing the use of quantum walks of particles for quantum computation. Unlike their classical analogs, quantum structures are extremely sensitive to external noise. To prevent a system of several qubits from losing the information stored in it, liquid nitrogen (or helium) needs to be used for cooling. Plenty of schemes have been proposed for the experimental realization of a separate qubit. In an earlier study, a research team led by Prof. Fedichkin demonstrated that a qubit could be physically implemented as a particle \"taking a quantum walk\" between two extremely small semiconductors known as quantum dots, which are connected by a \"quantum tunnel.\" From the perspective of an electron, the quantum dots represent potential wells. Thus, the position of the electron can be used to encode the two basis states of the qubit—|0? and |1?—depending on whether the particle is in one well or the other. Rather than sit in one of the two wells, the electron is smeared out between the two different states, taking up a definite position only when its coordinates are measured. In other words, it is in a superposition of two states. The blue and purple dots in the diagrams are the states of the two connected qudits (qutrits and ququarts are shown in (a) and (b) respectively). Each cell in the square diagrams on the right side of each figure (a-d) represents the position of one electron (i = 0, 1, 2, ... along the horizontal axis) versus the position of the other electron (j = 0, 1, 2, ... along the vertical axis). The cells color-code the probability of finding the two electrons in the corresponding dots with numbers i and j when a measurement of the system is made. Warmer colors denote higher probabilities. Credit: MIPT If an entangled state is created between several qubits, their individual states can no longer be described separately from one another, and any valid description must refer to the state of the whole system. This means that a system of three qubits has a total of eight basis states and is in a superposition of them: A|000⟩+B|001⟩+C|010⟩+D|100⟩+E|011⟩+F|101⟩+G|110⟩+H|111⟩. By influencing the system, one inevitably affects all of the eight coefficients, whereas influencing a system of regular bits only affects their individual states. By implication, n bits can store n variables, while n qubits can store 2n variables. Qudits offer an even greater advantage, since n four-level qudits (aka ququarts) can encode 4n, or 2n×2n variables. To put this into perspective, 10 ququarts store approximately 100,000 times more information than 10 bits. With greater values of n, the zeros in this number start to pile up very quickly. In this study, Alexey Melnikov and Leonid Fedichkin obtain a system of two qudits implemented as two entangled electrons quantum-walking around the so-called cycle graph. To make one, the scientists had to \"connect the dots,\" forming a circle (once again, these are quantum dots, and they are connected by quantum tunneling). The entanglement of the two electrons is caused by the mutual electrostatic repulsion experienced by like charges. It is possible to create a system of even more qudits in the same volume of semiconductor material. To do this, it is necessary to connect quantum dots in a pattern of winding paths and have more wandering electrons. The quantum walks approach to quantum computation is convenient because it is based on a natural process. Nevertheless, the presence of two identical electrons in the same structure was a source of additional difficulties that had remained unsolved. The phenomenon of particle entanglement plays a pivotal role in quantum information processing. However, in experiments with identical particles, false entanglement can arise between electrons that are not interacting, which must be distinguished from genuine entanglement. To do this, the scientists performed mathematical calculations for both cases, viz., with and without entanglement. They observed the changing distribution of probabilities for the cases with six, eight, 10, and 12 dots, i.e., for a system of two qudits with three, four, five, and six levels each. The scientists demonstrated that their proposed system is characterized by a relatively high degree of stability. The qubit is the basic element of a quantum computer. It has two basis states, viz., |0⟩ and |1⟩. The distinction between the classical bit and its quantum counterpart lies in more than just fancy brackets (these are the standard quantum mechanical notation for a state). The essential property of a qubit is its ability to be in a superposition of the two basis states: A|0⟩+B|1⟩. A classical bit, on the other hand, can only have one of the two values (0 or 1). The term “qudit” can be used to refer to higher-level quantum systems with more than two states. Credit: MIPT So far, scientists have been unable to connect a sufficient number of qubits for the development of a quantum computer. The work of the Russian researchers brings computer science one step closer to a future when quantum computations are commonplace. And although there are algorithms that quantum computers could never accelerate, others would still benefit enormously from devices able to exploit the potential of large numbers of qubits (or qudits). These alone would be enough to save us a couple of thousand years. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Quantum walks have been employed widely to develop new tools for quantum information processing recently. A natural quantum walk dynamics of interacting particles can be used to implement efficiently the universal quantum computation. In this work quantum walks of electrons on a graph are studied. The graph is composed of semiconductor quantum dots arranged in a circle. Electrons can tunnel between adjacent dots and interact via Coulomb repulsion, which leads to entanglement. Fermionic entanglement dynamics is obtained and evaluated. Introduction Quantum walks are quantum counterparts of classical random walks 1 , 2 . Unlike the state of classical walker, quantum walker’s state can be a coherent superposition of several positions. Quantum walks found applications to various fields, for example, to the development of a new family of quantum algorithms 3 , 4 , 5 , 6 or to the efficient energy transfer in proteins 7 . And recently, quantum walk dynamics is used as an underlying mechanism for quantum-enhanced decision-making process in reinforcement learning 8 , 9 , for which schemes of experimental realization in systems of trapped ions and superconducting transmon qubits were proposed 10 , 11 . There are plenty of theoretical and experimental results in the field of single-particle quantum walks 12 , 13 , but walks with multiple identical walkers, in both non-interacting and interacting cases, are less explored. In this paper we study quantum walks of identical particles for quantum information processing purposes. It is known that entanglement creation plays a pivotal role in most of the branches of quantum information. Here we introduce a method for generating a two-qudit (two d-level systems) entangled state by implementing continuous-time quantum walks on a cycle graph. This technique allows us to observe diverse structures of entangled subsystems of high dimensions, a preparation of which is of importance 14 , 15 . To relate theoretical study with feasible experimental implementations we consider realistic models of quantum walks 16 . The physical system we choose as a suitable candidate for quantum walks implementation is an array of tunnel-coupled semiconductor quantum dots. Quantum dots in semiconductors can be used as building blocks for a construction of a quantum computer, where quantum dots positions provide a spatial degree of freedom of a quantum particle 17 , 18 , 19 , 20 . It was shown that a spatial location of an electron in one of two semiconductor quantum dots can serve for encoding a qubit 17 , 18 and errors that occur mostly because of the interaction with acoustic phonons can be corrected 21 , 22 . In this paper we study quantum dots arranged in a circle, where each quantum dot can be populated by no more than one electron. By placing two identical particles in this system, one can define higher dimensional quantum states, qudits. If electrons are close enough they can also influence each other via Coulomb interaction. First, we analyze dynamics of non-interacting particles, and then we proceed to the case of interacting electrons. Results The remainder of the paper has the following structure: first, we introduce the model of symmetrical two-electron quantum walk on a cycle graph of arbitrary size. After the introduction of the model we study the dynamics of electrons in the cases with and without an interaction between them. The case of interacting electrons is studied in details and the scheme for entangling gate between two qudits, represented by two electrons, is proposed. Then we summarize the results and discuss possible applications of the proposed scheme. Framework The system under consideration contains two electrons. Each electron can sit in one of N quantum dots arranged in a circle 23 . Dots themselves can be formed from the two-dimensional electron gas by field of gates and the population of electrons in these dots can be controlled by potentials on gates. Each position in the circle can be occupied by at most one electron. The position of an electron can be measured by quantum point contact detectors, which are placed near quantum dots such that an electron in a certain quantum dot decreases an electric current in the detector by increasing a potential barrier. Therefore a lower current detects an electron and a higher current indicates an absence of an electron (an empty quantum dot), correspondingly. Experimentally, lateral structures of this geometry with different number of quantum dots were realized. Among them, a double quantum dot, which can be viewed as a circle with N = 2 sites, is the most studied configuration and is used to create a solid state qubit 24 , 25 , 26 , 27 . Beyond this, triple quantum dots with circular and linear geometries were studied in detail both theoretically and experimentally 28 . A concept of a scalable architecture was demonstrated by fabricating quadruple 29 , 30 , 31 and quintuple 32 quantum dots. In all experiments, a high degree of control over the precise number of electrons in each quantum dot was demonstrated by measuring stability diagrams. Moreover, it was shown that it is possible to tune the tunnel coupling between neighbouring quantum dots by changing the voltage on the gate that spatially separates these dots, see e.g. ref. 26 , where the tunnel coupling was shown to be an exponential function of the gate voltage. Similar techniques and technologies could be used for a fabrication of circles of larger sizes. The described circle of semiconductor quantum dots is mathematically represented as a cycle graph with quantum dots being vertices of this graph. Edges of the cycle graph connect only nearest neighbours and represent possible tunnel transitions of electrons. We enumerate the vertices within the graph, from 0 to N − 1. The localization of an electron in the 0-th, 1-st, … or ( N − 1)-th quantum dot is described by corresponding quantum states |0〉, |1〉, … or | N − 1〉, as shown in Fig. 1 for N = 2 K , . As a straightforward result, the states |0〉, |1〉, … and |<|im_end|> <|im_start|>assistant Scientists from the Institute of Physics and Technology of the Russian Academy of Sciences and MIPT have let two electrons loose in a system of quantum dots to create a quantum computer memory cell of a higher dimension than a qubit (a quantum bit). In their study published in Scientific Reports, the researchers demonstrate for the first time how quantum walks of several electrons can help to implement quantum computation. "By studying the system with two electrons, we solved the problems faced in the general case of two identical interacting particles. This paves the way toward compact high-level quantum structures," says Leonid Fedichkin, associate professor at MIPT's Department of Theoretical Physics. In a matter of hours, a quantum computer would be able to hack through the most popular cryptosystem used by web browsers. As far as more benevolent applications are concerned, a quantum computer would be capable of molecular modeling that accounts for all interactions between the particles involved. This in turn would enable the development of highly efficient solar cells and new drugs. To have practical applications, a quantum computer needs to incorporate hundreds or even thousands of qubits. And that is where it gets tricky. As it turns out, the unstable nature of the connection between qubits remains the major obstacle preventing the use of quantum walks of particles for quantum computation. Unlike their classical analogs, quantum structures are extremely sensitive to external noise. To prevent a system of several qubits from losing the information stored in it, liquid nitrogen (or helium) needs to be used for cooling. Plenty of schemes have been proposed for the experimental realization of a separate qubit. In an earlier study, a research team led by Prof. Fedichkin demonstrated that a qubit could be physically implemented as a particle "taking a quantum walk" between two extremely small semiconductors known as quantum dots, which are connected by a "quantum tunnel." From the perspective of an electron, the quantum dots represent potential wells. Thus, the position of the electron can be used to encode the two basis states of the qubit—|0? and |1?—depending on whether the particle is in one well or the other. Rather than sit in one of the two wells, the electron is smeared out between the two different states, taking up a definite position only when its coordinates are measured. In other words, it is in a superposition of two states. The blue and purple dots in the diagrams are the states of the two connected qudits (qutrits and ququarts are shown in (a) and (b) respectively). Each cell in the square diagrams on the right side of each figure (a-d) represents the position of one electron (i = 0, 1, 2, ... along the horizontal axis) versus the position of the other electron (j = 0, 1, 2, ... along the vertical axis). The cells color-code the probability of finding the two electrons in the corresponding dots with numbers i and j when a measurement of the system is made. Warmer colors denote higher probabilities. Credit: MIPT If an entangled state is created between several qubits, their individual states can no longer be described separately from one another, and any valid description must refer to the state of the whole system. This means that a system of three qubits has a total of eight basis states and is in a superposition of them: A|000⟩+B|001⟩+C|010⟩+D|100⟩+E|011⟩+F|101⟩+G|110⟩+H|111⟩. By influencing the system, one inevitably affects all of the eight coefficients, whereas influencing a system of regular bits only affects their individual states. By implication, n bits can store n variables, while n qubits can store 2n variables. Qudits offer an even greater advantage, since n four-level qudits (aka ququarts) can encode 4n, or 2n×2n variables. To put this into perspective, 10 ququarts store approximately 100,000 times more information than 10 bits. With greater values of n, the zeros in this number start to pile up very quickly. In this study, Alexey Melnikov and Leonid Fedichkin obtain a system of two qudits implemented as two entangled electrons quantum-walking around the so-called cycle graph. To make one, the scientists had to "connect the dots," forming a circle (once again, these are quantum dots, and they are connected by quantum tunneling). The entanglement of the two electrons is caused by the mutual electrostatic repulsion experienced by like charges. It is possible to create a system of even more qudits in the same volume of semiconductor material. To do this, it is necessary to connect quantum dots in a pattern of winding paths and have more wandering electrons. The quantum walks approach to quantum computation is convenient because it is based on a natural process. Nevertheless, the presence of two identical electrons in the same structure was a source of additional difficulties that had remained unsolved. The phenomenon of particle entanglement plays a pivotal role in quantum information processing. However, in experiments with identical particles, false entanglement can arise between electrons that are not interacting, which must be distinguished from genuine entanglement. To do this, the scientists performed mathematical calculations for both cases, viz., with and without entanglement. They observed the changing distribution of probabilities for the cases with six, eight, 10, and 12 dots, i.e., for a system of two qudits with three, four, five, and six levels each. The scientists demonstrated that their proposed system is characterized by a relatively high degree of stability. The qubit is the basic element of a quantum computer. It has two basis states, viz., |0⟩ and |1⟩. The distinction between the classical bit and its quantum counterpart lies in more than just fancy brackets (these are the standard quantum mechanical notation for a state). The essential property of a qubit is its ability to be in a superposition of the two basis states: A|0⟩+B|1⟩. A classical bit, on the other hand, can only have one of the two values (0 or 1). The term “qudit” can be used to refer to higher-level quantum systems with more than two states. Credit: MIPT So far, scientists have been unable to connect a sufficient number of qubits for the development of a quantum computer. The work of the Russian researchers brings computer science one step closer to a future when quantum computations are commonplace. And although there are algorithms that quantum computers could never accelerate, others would still benefit enormously from devices able to exploit the potential of large numbers of qubits (or qudits). These alone would be enough to save us a couple of thousand years. <|im_end|>

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2,639

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Particle–hole symmetry plays an important role in the characterization of topological phases in solid-state systems 1 . It is found, for example, in free-fermion systems at half filling and it is closely related to the notion of antiparticles in relativistic field theories 2 . In the low-energy limit, graphene is a prime example of a gapless particle–hole symmetric system described by an effective Dirac equation 3 , 4 in which topological phases can be understood by studying ways to open a gap by preserving (or breaking) symmetries 5 , 6 . An important example is the intrinsic Kane–Mele spin-orbit gap of graphene, which leads to a lifting of the spin-valley degeneracy and renders graphene a topological insulator in a quantum spin Hall phase 7 while preserving particle–hole symmetry. Here we show that bilayer graphene allows the realization of electron–hole double quantum dots that exhibit near-perfect particle–hole symmetry, in which transport occurs via the creation and annihilation of single electron–hole pairs with opposite quantum numbers. Moreover, we show that particle–hole symmetric spin and valley textures lead to a protected single-particle spin-valley blockade. The latter will allow robust spin-to-charge and valley-to-charge conversion, which are essential for the operation of spin and valley qubits. Main Carbon-based materials, such as monolayer and bilayer graphene, are interesting hosts for spin and spin-valley qubits thanks to their weak spin-orbit (SO) coupling 7 , 8 , 9 , 10 and weak hyperfine interaction 11 , 12 . Bilayer graphene (BLG) is attracting particular attention because it presents a gate-tuneable band gap 13 , E g , that can be used to electrostatically confine charge carriers into quantum point contacts and quantum dots (QDs) 9 , 10 , 14 , 15 . The small size of this gap (up to around 120 meV) allows the formation of ambipolar QDs, which is difficult to achieve with standard semiconductors 16 , 17 , 18 . Another attractive feature is that, at low energy, charge carriers have an orbital magnetic moment caused by a finite Berry curvature 3 , 19 . These orbital magnetic moments are aligned perpendicular to the BLG plane and allow control over the valley degree of freedom because they have opposite signs for the two valleys ( K and K ′) and for electrons and holes, as illustrated in Fig. 1a . This property is a consequence of the particle–hole symmetry that is imprinted on the low-energy Hamiltonian of bilayer graphene, $${H}_{{\\rm{BLG}}}=-\\,\\frac{1}{2m}{\\Psi }^{\\dagger }\\left[\\left({p}_{x}^{2}-{p}_{y}^{2}\\right){\\sigma }_{x}+2{p}_{x}{p}_{y}{\\sigma }_{y}{\\tau }_{z}\\right]\\Psi +\\frac{{E}_{{\\rm{g}}}}{2}{\\Psi }^{\\dagger }{\\sigma }_{z}\\Psi ,$$ as well as on the intrinsic Kane–Mele SO coupling term \${H}_{{\\rm{SO}}}\\,=\$ \$\\frac{1}{2}{\\Delta }_{{\\rm{SO}}}{\\Psi }^{\\dagger }{\\sigma }_{z}{\\tau }_{z}{s}_{z}\\Psi \$ 7 , 8 . Here, m = 0.033 m e is the effective mass of the charge carriers in BLG with free electron mass m e , momentum operators p i and s i , τ i and σ i being Pauli matrices ( i = x , y , z ) acting on the spin, valley and sublattice space, respectively. Both H BLG and H SO are invariant under particle–hole transformation \${\\rm{K}}\$ , which effectively flips the sublattice, valley and spin indices, \${\\rm{K}}{\\Psi }^{\\dagger }{{\\rm{K}}}^{-1}={\\sigma }_{y}{\\tau }_{x}{s}_{y}\\Psi \$ . As a consequence, the hole spectrum in BLG mirrors the electron spectrum around the K and K ′ points. Fig. 1: Particle–hole symmetry in BLG and the formation of electron–hole DQDs. a , Low-energy dispersion relation of gapped BLG at the K and K ′ points. Arrows indicate the orientation of the valley-dependent orbital magnetic moment of electrons (blue) and holes (red). b , Each orbital state in the electron and hole QDs holds four single-particle states due to the spin and valley degree of freedom. The SO gap, Δ SO , splits the fourfold degeneracy of each orbital into two Kramers’ pairs. Black (coloured) arrows indicate the orientation of the spin (valley) magnetic moment. The first electron shell in the conduction band is separated from the first hole shell in the valence band by E g and the confinement energy of the QD. c , Schematic cross-section of the device. The van der Waals heterostructure consists of a hBN–BLG–hBN–graphite stack. The gate pattern comprises a layer of SGs, forming a narrow channel, and two layers of FGs to define and control the QDs. d , Schematic of the valence and conduction band-edge profiles along the p-type channel. Finger gates (L, C and R) form an e–h DQD. e , Charge stability diagram of the device at V SD = 1 mV. Red dashed lines indicate charging lines of a hole QD and black dashed lines indicate charging lines of electron QDs, with the electron (hole) occupation number labelled in black (white). Dashed circles mark the formation of single e–h DQDs. The position of the QDs along the channel is interchanged for the red and black circles (see Extended Data Fig. 1 ). Full size image This symmetry remains preserved in BLG QDs, where the orbital states are quantized and form shells of four states grouped by the SO coupling into Kramers’ doublets, \$\\left|K\\uparrow \\right\\rangle ,\\left|{K}^{{\\prime} }\\downarrow \\right\\rangle \$ and \$\\left|{K}^{{\\prime} }\\uparrow \\right\\rangle ,\\left|K\\downarrow \\right\\rangle \$ . Every electron state in the energetically lower (higher) Kramers’ pair in the conduction band has a corresponding hole state in the energetically higher (lower) Kramers’ pair in the valence band, as illustrated in Fig. 1b . This is in stark contrast to the single-particle spectrum of QDs in carbon nanotubes, where the SO coupling caused by the curvature breaks particle–hole symmetry 20 . Here we show that this symmetry is almost perfectly preserved also when electrons and holes are physically separated into different QDs, and that the resulting ordering of electron and hole states leads to a very strong single-particle blockade in the transport through electron–hole (e–h) double quantum dots (DQDs). Bilayer graphene electron–hole DQD devices The DQD devices are fabricated as shown schematically in Fig. 1c . They consist of BLG encapsulated between two crystals of hexagonal boron nitride (hBN) resting on a graphite crystal that acts as", "role": "user" }, { "content": "Quantum dots in semiconductors such as silicon or gallium arsenide have long been considered hot candidates for hosting quantum bits in future quantum processors. Scientists at Forschungszentrum Jülich and RWTH Aachen University have now shown that bilayer graphene has even more to offer here than other materials. The double quantum dots they have created are characterized by a nearly perfect electron-hole-symmetry that allows a robust read-out mechanism—one of the necessary criteria for quantum computing. The results were published in Nature. The development of robust semiconductor spin qubits could help the realization of large-scale quantum computers in the future. However, current quantum dot based qubit systems are still in their infancy. In 2022, researchers at QuTech in the Netherlands were able to create 6 silicon-based spin qubits for the first time. With graphene, there is still a long way to go. The material, which was first isolated in 2004, is highly attractive to many scientists. But the realization of the first quantum bit has yet to come. \"Bilayer graphene is a unique semiconductor,\" explains Prof. Christoph Stampfer of Forschungszentrum Jülich and RWTH Aachen University. \"It shares several properties with single-layer graphene and also has some other special features. This makes it very interesting for quantum technologies.\" One of these features is that it has a bandgap that can be tuned by an external electric field from zero to about 120 milli-electronvolt. The band gap can be used to confine charge carriers in individual areas, so-called quantum dots. Depending on the applied voltage, these can trap a single electron or its counterpart, a hole—basically a missing electron in the solid-state structure. The possibility of using the same gate structure to trap both electrons and holes is a feature that has no counter part in conventional semiconductors. \"Bilayer graphene is still a fairly new material. So far, mainly experiments that have already been realized with other semiconductors have been carried out with it. Our current experiment now goes really beyond this for the first time,\" Christoph Stampfer says. He and his colleagues have created a so-called double quantum dot: two opposing quantum dots, each housing an electron and a hole whose spin properties mirror each other almost perfectly. The double quantum dots were produced at the Helmholtz Nano Facility, the central technology platform for the production of nanostructures and circuits in the Helmholtz Association. Credit: Forschungszentrum Jülich / Sascha Kreklau Wide range of applications \"This symmetry has two remarkable consequences: it is almost perfectly preserved even when electrons and holes are spatially separated in different quantum dots,\" Stampfer said. This mechanism can be used to couple qubits to other qubits over a longer distance. And what's more, \"the symmetry results in a very robust blockade mechanism which could be used to read out the spin state of the dot with high fidelity.\" \"This goes beyond what can be done in conventional semiconductors or any other two-dimensional electron systems,\" says Prof. Fabian Hassler of the JARA Institute for Quantum Information at Forschungszentrum Jülich and RWTH Aachen University, co-author of the study. \"The near-perfect symmetry and strong selection rules are very attractive not only for operating qubits, but also for realizing single-particle terahertz detectors. In addition, it lends itself to coupling quantum dots of bilayer graphene with superconductors, two systems in which electron-hole symmetry plays an important role. These hybrid systems could be used to create efficient sources of entangled particle pairs or artificial topological systems, bringing us one step closer to realizing topological quantum computers.\" The research results were published in the journal Nature. The data supporting the results and the codes used for the analysis are available in a Zenodo repository. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Particle–hole symmetry plays an important role in the characterization of topological phases in solid-state systems 1 . It is found, for example, in free-fermion systems at half filling and it is closely related to the notion of antiparticles in relativistic field theories 2 . In the low-energy limit, graphene is a prime example of a gapless particle–hole symmetric system described by an effective Dirac equation 3 , 4 in which topological phases can be understood by studying ways to open a gap by preserving (or breaking) symmetries 5 , 6 . An important example is the intrinsic Kane–Mele spin-orbit gap of graphene, which leads to a lifting of the spin-valley degeneracy and renders graphene a topological insulator in a quantum spin Hall phase 7 while preserving particle–hole symmetry. Here we show that bilayer graphene allows the realization of electron–hole double quantum dots that exhibit near-perfect particle–hole symmetry, in which transport occurs via the creation and annihilation of single electron–hole pairs with opposite quantum numbers. Moreover, we show that particle–hole symmetric spin and valley textures lead to a protected single-particle spin-valley blockade. The latter will allow robust spin-to-charge and valley-to-charge conversion, which are essential for the operation of spin and valley qubits. Main Carbon-based materials, such as monolayer and bilayer graphene, are interesting hosts for spin and spin-valley qubits thanks to their weak spin-orbit (SO) coupling 7 , 8 , 9 , 10 and weak hyperfine interaction 11 , 12 . Bilayer graphene (BLG) is attracting particular attention because it presents a gate-tuneable band gap 13 , E g , that can be used to electrostatically confine charge carriers into quantum point contacts and quantum dots (QDs) 9 , 10 , 14 , 15 . The small size of this gap (up to around 120 meV) allows the formation of ambipolar QDs, which is difficult to achieve with standard semiconductors 16 , 17 , 18 . Another attractive feature is that, at low energy, charge carriers have an orbital magnetic moment caused by a finite Berry curvature 3 , 19 . These orbital magnetic moments are aligned perpendicular to the BLG plane and allow control over the valley degree of freedom because they have opposite signs for the two valleys ( K and K ′) and for electrons and holes, as illustrated in Fig. 1a . This property is a consequence of the particle–hole symmetry that is imprinted on the low-energy Hamiltonian of bilayer graphene, $${H}_{{\rm{BLG}}}=-\,\frac{1}{2m}{\Psi }^{\dagger }\left[\left({p}_{x}^{2}-{p}_{y}^{2}\right){\sigma }_{x}+2{p}_{x}{p}_{y}{\sigma }_{y}{\tau }_{z}\right]\Psi +\frac{{E}_{{\rm{g}}}}{2}{\Psi }^{\dagger }{\sigma }_{z}\Psi ,$$ as well as on the intrinsic Kane–Mele SO coupling term ${H}_{{\rm{SO}}}\,=$ $\frac{1}{2}{\Delta }_{{\rm{SO}}}{\Psi }^{\dagger }{\sigma }_{z}{\tau }_{z}{s}_{z}\Psi $ 7 , 8 . Here, m = 0.033 m e is the effective mass of the charge carriers in BLG with free electron mass m e , momentum operators p i and s i , τ i and σ i being Pauli matrices ( i = x , y , z ) acting on the spin, valley and sublattice space, respectively. Both H BLG and H SO are invariant under particle–hole transformation ${\rm{K}}$ , which effectively flips the sublattice, valley and spin indices, ${\rm{K}}{\Psi }^{\dagger }{{\rm{K}}}^{-1}={\sigma }_{y}{\tau }_{x}{s}_{y}\Psi $ . As a consequence, the hole spectrum in BLG mirrors the electron spectrum around the K and K ′ points. Fig. 1: Particle–hole symmetry in BLG and the formation of electron–hole DQDs. a , Low-energy dispersion relation of gapped BLG at the K and K ′ points. Arrows indicate the orientation of the valley-dependent orbital magnetic moment of electrons (blue) and holes (red). b , Each orbital state in the electron and hole QDs holds four single-particle states due to the spin and valley degree of freedom. The SO gap, Δ SO , splits the fourfold degeneracy of each orbital into two Kramers’ pairs. Black (coloured) arrows indicate the orientation of the spin (valley) magnetic moment. The first electron shell in the conduction band is separated from the first hole shell in the valence band by E g and the confinement energy of the QD. c , Schematic cross-section of the device. The van der Waals heterostructure consists of a hBN–BLG–hBN–graphite stack. The gate pattern comprises a layer of SGs, forming a narrow channel, and two layers of FGs to define and control the QDs. d , Schematic of the valence and conduction band-edge profiles along the p-type channel. Finger gates (L, C and R) form an e–h DQD. e , Charge stability diagram of the device at V SD = 1 mV. Red dashed lines indicate charging lines of a hole QD and black dashed lines indicate charging lines of electron QDs, with the electron (hole) occupation number labelled in black (white). Dashed circles mark the formation of single e–h DQDs. The position of the QDs along the channel is interchanged for the red and black circles (see Extended Data Fig. 1 ). Full size image This symmetry remains preserved in BLG QDs, where the orbital states are quantized and form shells of four states grouped by the SO coupling into Kramers’ doublets, $\left|K\uparrow \right\rangle ,\left|{K}^{{\prime} }\downarrow \right\rangle $ and $\left|{K}^{{\prime} }\uparrow \right\rangle ,\left|K\downarrow \right\rangle $ . Every electron state in the energetically lower (higher) Kramers’ pair in the conduction band has a corresponding hole state in the energetically higher (lower) Kramers’ pair in the valence band, as illustrated in Fig. 1b . This is in stark contrast to the single-particle spectrum of QDs in carbon nanotubes, where the SO coupling caused by the curvature breaks particle–hole symmetry 20 . Here we show that this symmetry is almost perfectly preserved also when electrons and holes are physically separated into different QDs, and that the resulting ordering of electron and hole states leads to a very strong single-particle blockade in the transport through electron–hole (e–h) double quantum dots (DQDs). Bilayer graphene electron–hole DQD devices The DQD devices are fabricated as shown schematically in Fig. 1c . They consist of BLG encapsulated between two crystals of hexagonal boron nitride (hBN) resting on a graphite crystal that acts as<|im_end|> <|im_start|>assistant Quantum dots in semiconductors such as silicon or gallium arsenide have long been considered hot candidates for hosting quantum bits in future quantum processors. Scientists at Forschungszentrum Jülich and RWTH Aachen University have now shown that bilayer graphene has even more to offer here than other materials. The double quantum dots they have created are characterized by a nearly perfect electron-hole-symmetry that allows a robust read-out mechanism—one of the necessary criteria for quantum computing. The results were published in Nature. The development of robust semiconductor spin qubits could help the realization of large-scale quantum computers in the future. However, current quantum dot based qubit systems are still in their infancy. In 2022, researchers at QuTech in the Netherlands were able to create 6 silicon-based spin qubits for the first time. With graphene, there is still a long way to go. The material, which was first isolated in 2004, is highly attractive to many scientists. But the realization of the first quantum bit has yet to come. "Bilayer graphene is a unique semiconductor," explains Prof. Christoph Stampfer of Forschungszentrum Jülich and RWTH Aachen University. "It shares several properties with single-layer graphene and also has some other special features. This makes it very interesting for quantum technologies." One of these features is that it has a bandgap that can be tuned by an external electric field from zero to about 120 milli-electronvolt. The band gap can be used to confine charge carriers in individual areas, so-called quantum dots. Depending on the applied voltage, these can trap a single electron or its counterpart, a hole—basically a missing electron in the solid-state structure. The possibility of using the same gate structure to trap both electrons and holes is a feature that has no counter part in conventional semiconductors. "Bilayer graphene is still a fairly new material. So far, mainly experiments that have already been realized with other semiconductors have been carried out with it. Our current experiment now goes really beyond this for the first time," Christoph Stampfer says. He and his colleagues have created a so-called double quantum dot: two opposing quantum dots, each housing an electron and a hole whose spin properties mirror each other almost perfectly. The double quantum dots were produced at the Helmholtz Nano Facility, the central technology platform for the production of nanostructures and circuits in the Helmholtz Association. Credit: Forschungszentrum Jülich / Sascha Kreklau Wide range of applications "This symmetry has two remarkable consequences: it is almost perfectly preserved even when electrons and holes are spatially separated in different quantum dots," Stampfer said. This mechanism can be used to couple qubits to other qubits over a longer distance. And what's more, "the symmetry results in a very robust blockade mechanism which could be used to read out the spin state of the dot with high fidelity." "This goes beyond what can be done in conventional semiconductors or any other two-dimensional electron systems," says Prof. Fabian Hassler of the JARA Institute for Quantum Information at Forschungszentrum Jülich and RWTH Aachen University, co-author of the study. "The near-perfect symmetry and strong selection rules are very attractive not only for operating qubits, but also for realizing single-particle terahertz detectors. In addition, it lends itself to coupling quantum dots of bilayer graphene with superconductors, two systems in which electron-hole symmetry plays an important role. These hybrid systems could be used to create efficient sources of entangled particle pairs or artificial topological systems, bringing us one step closer to realizing topological quantum computers." The research results were published in the journal Nature. The data supporting the results and the codes used for the analysis are available in a Zenodo repository. <|im_end|>

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1144, 1315, 12285, 4134, 1144, 8, 662, 7357, 17130, 1614, 304, 279, 38556, 456, 2740, 4827, 320, 90447, 8, 735, 2453, 388, 529, 6857, 304, 279, 390, 23985, 7200, 706, 264, 12435, 14512, 1614, 304, 279, 38556, 456, 2740, 5190, 320, 15115, 8, 735, 2453, 388, 529, 6857, 304, 279, 1062, 768, 7200, 11, 439, 36762, 304, 23966, 13, 220, 16, 65, 662, 1115, 374, 304, 38246, 13168, 311, 279, 3254, 2320, 7203, 20326, 315, 1229, 68050, 304, 12782, 20622, 354, 51725, 11, 1405, 279, 5745, 59086, 9057, 555, 279, 83233, 18808, 19320, 4235, 31520, 46220, 220, 508, 662, 5810, 584, 1501, 430, 420, 46220, 374, 4661, 14268, 34683, 1101, 994, 57678, 323, 20349, 527, 22655, 19180, 1139, 2204, 1229, 68050, 11, 323, 430, 279, 13239, 22106, 315, 17130, 323, 14512, 5415, 11767, 311, 264, 1633, 3831, 3254, 2320, 7203, 77237, 304, 279, 7710, 1555, 17130, 4235, 31520, 320, 68, 4235, 71, 8, 2033, 31228, 32094, 320, 35, 48, 68050, 570, 39158, 1155, 66192, 17130, 4235, 31520, 423, 48, 35, 7766, 578, 423, 48, 35, 7766, 527, 70554, 439, 6982, 20225, 7167, 304, 23966, 13, 220, 16, 66, 662, 2435, 6824, 315, 15195, 38, 43669, 7913, 1990, 1403, 48473, 315, 12651, 24346, 32732, 263, 25719, 1425, 320, 71, 15967, 8, 41219, 389, 264, 95273, 26110, 430, 14385, 439, 128257, 198, 128256, 78191, 198, 45320, 372, 32094, 304, 5347, 1965, 1076, 1105, 1778, 439, 51692, 477, 19754, 2411, 87364, 579, 617, 1317, 1027, 6646, 4106, 11426, 369, 20256, 31228, 9660, 304, 3938, 31228, 37686, 13, 57116, 520, 50990, 331, 2234, 14694, 306, 10952, 622, 2448, 6915, 323, 47306, 3701, 362, 46799, 3907, 617, 1457, 6982, 430, 20934, 1155, 66192, 706, 1524, 810, 311, 3085, 1618, 1109, 1023, 7384, 13, 578, 2033, 31228, 32094, 814, 617, 3549, 527, 32971, 555, 264, 7154, 4832, 17130, 87693, 1355, 1631, 33342, 430, 6276, 264, 22514, 1373, 9994, 17383, 87671, 315, 279, 5995, 13186, 369, 31228, 25213, 13, 578, 3135, 1051, 4756, 304, 22037, 13, 578, 4500, 315, 22514, 87836, 12903, 2874, 82502, 1436, 1520, 279, 49803, 315, 3544, 13230, 31228, 19002, 304, 279, 3938, 13, 4452, 11, 1510, 31228, 13046, 3196, 2874, 60320, 6067, 527, 2103, 304, 872, 86617, 13, 763, 220, 2366, 17, 11, 12074, 520, 3489, 35197, 304, 279, 26746, 1051, 3025, 311, 1893, 220, 21, 51692, 6108, 12903, 2874, 82502, 369, 279, 1176, 892, 13, 3161, 66192, 11, 1070, 374, 2103, 264, 1317, 1648, 311, 733, 13, 578, 3769, 11, 902, 574, 1176, 25181, 304, 220, 1049, 19, 11, 374, 7701, 19411, 311, 1690, 14248, 13, 2030, 279, 49803, 315, 279, 1176, 31228, 2766, 706, 3686, 311, 2586, 13, 330, 33, 321, 1155, 66192, 374, 264, 5016, 87836, 1359, 15100, 8626, 13, 95693, 55887, 809, 315, 50990, 331, 2234, 14694, 306, 10952, 622, 2448, 6915, 323, 47306, 3701, 362, 46799, 3907, 13, 330, 2181, 13551, 3892, 6012, 449, 3254, 48435, 66192, 323, 1101, 706, 1063, 1023, 3361, 4519, 13, 1115, 3727, 433, 1633, 7185, 369, 31228, 14645, 1210, 3861, 315, 1521, 4519, 374, 430, 433, 706, 264, 7200, 42510, 430, 649, 387, 33519, 555, 459, 9434, 9249, 2115, 505, 7315, 311, 922, 220, 4364, 117825, 37081, 2298, 97371, 13, 578, 7200, 13225, 649, 387, 1511, 311, 2389, 483, 6900, 35991, 304, 3927, 5789, 11, 779, 19434, 31228, 32094, 13, 40730, 389, 279, 9435, 22465, 11, 1521, 649, 23709, 264, 3254, 17130, 477, 1202, 45116, 11, 264, 14512, 2345, 18275, 2740, 264, 7554, 17130, 304, 279, 6573, 21395, 6070, 13, 578, 13336, 315, 1701, 279, 1890, 18618, 6070, 311, 23709, 2225, 57678, 323, 20349, 374, 264, 4668, 430, 706, 912, 5663, 961, 304, 21349, 5347, 1965, 1076, 1105, 13, 330, 33, 321, 1155, 66192, 374, 2103, 264, 14470, 502, 3769, 13, 2100, 3117, 11, 14918, 21896, 430, 617, 2736, 1027, 15393, 449, 1023, 5347, 1965, 1076, 1105, 617, 1027, 11953, 704, 449, 433, 13, 5751, 1510, 9526, 1457, 5900, 2216, 7953, 420, 369, 279, 1176, 892, 1359, 95693, 55887, 809, 2795, 13, 1283, 323, 813, 18105, 617, 3549, 264, 779, 19434, 2033, 31228, 13046, 25, 1403, 31322, 31228, 32094, 11, 1855, 11983, 459, 17130, 323, 264, 14512, 6832, 12903, 6012, 18327, 1855, 1023, 4661, 14268, 13, 578, 2033, 31228, 32094, 1051, 9124, 520, 279, 16183, 53016, 6312, 89, 64051, 47750, 11, 279, 8792, 5557, 5452, 369, 279, 5788, 315, 51593, 47194, 323, 46121, 304, 279, 16183, 53016, 6312, 89, 10229, 13, 16666, 25, 50990, 331, 2234, 14694, 306, 10952, 622, 2448, 6915, 611, 62189, 6583, 30718, 10784, 2933, 33845, 2134, 315, 8522, 330, 2028, 46220, 706, 1403, 23649, 16296, 25, 433, 374, 4661, 14268, 34683, 1524, 994, 57678, 323, 20349, 527, 29079, 398, 19180, 304, 2204, 31228, 32094, 1359, 55887, 809, 1071, 13, 1115, 17383, 649, 387, 1511, 311, 5743, 2874, 82502, 311, 1023, 2874, 82502, 927, 264, 5129, 6138, 13, 1628, 1148, 596, 810, 11, 330, 1820, 46220, 3135, 304, 264, 1633, 22514, 77237, 17383, 902, 1436, 387, 1511, 311, 1373, 704, 279, 12903, 1614, 315, 279, 13046, 449, 1579, 83604, 1210, 330, 2028, 5900, 7953, 1148, 649, 387, 2884, 304, 21349, 5347, 1965, 1076, 1105, 477, 904, 1023, 1403, 33520, 17130, 6067, 1359, 2795, 8626, 13, 19797, 1122, 43122, 1565, 315, 279, 622, 55062, 10181, 369, 56413, 8245, 520, 50990, 331, 2234, 14694, 306, 10952, 622, 2448, 6915, 323, 47306, 3701, 362, 46799, 3907, 11, 1080, 43802, 315, 279, 4007, 13, 330, 791, 3221, 17453, 3836, 46220, 323, 3831, 6727, 5718, 527, 1633, 19411, 539, 1193, 369, 10565, 2874, 82502, 11, 719, 1101, 369, 44114, 3254, 2320, 7203, 2024, 1494, 59037, 69087, 13, 763, 5369, 11, 433, 79018, 5196, 311, 59086, 31228, 32094, 315, 20934, 1155, 66192, 449, 2307, 77752, 1105, 11, 1403, 6067, 304, 902, 17130, 87693, 46220, 11335, 459, 3062, 3560, 13, 4314, 26038, 6067, 1436, 387, 1511, 311, 1893, 11297, 8336, 315, 1218, 40040, 19320, 13840, 477, 21075, 1948, 5848, 6067, 11, 12967, 603, 832, 3094, 12401, 311, 44114, 1948, 5848, 31228, 19002, 1210, 578, 3495, 3135, 1051, 4756, 304, 279, 8486, 22037, 13, 578, 828, 12899, 279, 3135, 323, 279, 14236, 1511, 369, 279, 6492, 527, 2561, 304, 264, 32889, 6132, 12827, 13, 220, 128257, 198 ]

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract We mapped the inferred long-distance migrations of four species of Amazonian goliath catfishes ( Brachyplatystoma rousseauxii, B. platynemum, B. juruense and B. vaillantii ) based on the presence of individuals with mature gonads and conducted statistical analysis of the expected long-distance downstream migrations of their larvae and juveniles. By linking the distribution of larval, juvenile and mature adult size classes across the Amazon, the results showed: (i) that the main spawning regions of these goliath catfish species are in the western Amazon; (ii) at least three species— B. rousseauxii, B. platynemum, and B. juruense —spawn partially or mainly as far upstream as the Andes; (iii) the main spawning area of B. rousseauxii is in or near the Andes; and (iv) the life history migration distances of B. rousseauxii are the longest strictly freshwater fish migrations in the world. These results provide an empirical baseline for tagging experiments, life histories extrapolated from otolith microchemistry interpretations and other methods to establish goliath catfish migratory routes, their seasonal timing and possible return (homing) to western headwater tributaries where they were born. Introduction The Amazon has two main groups of migratory fish species, and they belong to the orders Siluriformes (catfishes) and Characiformes (characins) 1 , 2 , 3 . Major fisheries in the Amazon are based on knowledge of the seasonal upstream and downstream movements of fish, although the life cycles are poorly known by fishermen because the species enter and leave local fishing areas 4 , 5 , 6 . Long-distance fish migrations (>1,000 km) that exclusively or partially involve freshwater are known for salmon 7 and eels 8 but have also been inferred for Amazon goliath catfishes of the family Pimelodidae 9 , 10 , 11 , 12 . Although the migrations of most catfish species are poorly known, the general pattern reported is upstream movement to spawn, downstream passive drifting and even active migration of young juveniles to enter nursery habitats in river channels, floodplains or estuaries 7 , 13 , 14 , 15 . In the Amazon, goliath catfishes are major river channel and estuarine predators that are represented by a paraphyletic group of six extant and one fossil species of the genus Brachyplatystoma 16 , 17 , 18 with a maximum known adult fork length (FL) of 60–280 cm 9 ( Fig. 1 ). Figure 1: Migratory goliath catfishes ( Brachyplatystoma , Pimelodidae). ( A ) B. vaillantii (piramutaba in Portuguese, pirabutón in Spanish); ( B ) B. rousseauxii (dourada in Portuguese, dorado in Spanish); ( C ) B. platynemum (babão in Portuguese, mota flemosa in Spanish); ( D ) B. juruense (zebra in Portuguese, zebra in Spanish); ( E ) Dorado migrations exploited by fishermen. The Santo Antônio Dam on the Madeira River now drowns the Teotônio Rapids (shown here) where B. rousseauxii (species in photo) and B. platynemum were previously exploited and easily detected when migrating. Photos by M. Goulding. Full size image The first hypotheses of goliath catfish migration focused on B. rousseauxii and B. vaillantii , the most important commercial species, and their dependence on the Amazon River estuary as their nursery and inland rivers as feeding and spawning areas 9 . The spawning areas, however, were only identified as being located in the western Amazon, a vast region of at least 2 million km 2 that includes parts of Colombia, Ecuador, Peru, Bolivia and Brazil. More recent biological studies based on commercial fisheries in all major western Andes-Amazon tributary basins 19 , 20 , 21 , 22 , 23 established the seasonal, and in some cases year-round, presence of mature goliath catfishes in the western Amazon to at least a few hundred km downstream of the Andes. However, these investigations could not verify the spawning areas, leaving the possibility that they are located farther upriver and closer to the Andes. We present data on the distribution of goliath catfish ( Brachyplatystoma ) adults, larvae and juveniles across the Amazon Basin, including areas in or near the Andes. Even without tagging experiments, the general differential distribution of sub-adult (downstream) and adult (upstream) goliath catfish size-classes 9 , as well as otolith microchemistry data 10 , strongly indicates that long-distance upstream goliath catfish migration occurs. Seasonal upstream goliath catfish movements are also visually obvious at some cataracts, such as those of the Madeira River ( Fig. 1 ) in Brazil, before dams were built 4 , and those of the Caquetá River in Colombia 6 . Therefore, it is reasonable to hypothesize that long-distance downstream migrations of young fish occurs, otherwise there would be no recruitment to nurseries, in some cases as far downstream as the Amazon River estuary. To test the goliath catfish migratory hypothesis related to western spawning regions, we mapped the presence of mature adults complemented by the seasonal and geographical variation in abundance and length of larvae and juveniles in river channels across the Amazon, including in the estuary. Two complementary geographical and temporal perspectives were used. The first focused on the Madeira Basin, the Amazon’s largest sub-basin with headwaters in the Andes, and where year-round collections were performed. The second included most of the Amazon and available data from all years. Our study shows that spawning for at least B. rousseauxii, B. juruense and B. platynemum occurs in or near the Andes and demonstrates conclusively that long-distance downstream migration of their larvae and juveniles occurs. The great variation in B. platynemum larvae size across the Amazon indicates a much wider nursery area than just the Andean region. Size-class data for B. vaillantii indicate long-distance migration and spawning in the western Amazon but do not confirm it near the Andes. Our results are also discussed in light of published goliath life history hypotheses derived from genetic and otolith isotope signatures. Results Adult Distribution and Gonadal Stage Fish length and gonadal data derived from specimens captured in fisheries in major Andes-Amazon sub-basins in Brazil, Bolivia and Peru, complemented by published data from studies based in Colombia 19 , 23 and Ecuador", "role": "user" }, { "content": "An international team of scientists has confirmed that the dorado catfish (Brachyplatystoma rousseauxii) of the Amazon River basin holds the record for the world's longest exclusively freshwater fish migration, an epic life-cycle journey stretching nearly the entire width of the South America continent. The finding, published today in the journal Scientific Reports-Nature, is an output of WCS's Amazon Waters Initiative, sponsored by the Science for Nature and People Partnership (SNAPP) led by WCS (Wildlife Conservation Society), The Nature Conservancy (TNC) and the National Center for Ecological Analysis and Synthesis (NCEAS). The study reveals the amazing life histories of the dorado and three other \"goliath\" catfish species that spawn in the western headwaters of the Amazon. The journey of the dorado catfish specifically begins with adults and pre-adults traveling thousands of kilometers upriver from the Amazon River estuary to spawning areas in or near the Andes Mountains. The breeding fish never return to their nursery areas, but the newborn catfish do, migrating thousands of kilometers in the opposite direction to complete the cycle. The dorado catfish was found to have a life-cycle migration of approximately 11,600 kilometers (more than 7,200 miles). Growing up to nearly 6 feet in length, the dorado catfish is sometimes called the gilded catfish due to its silver and gold skin with no scales. The dorado and the other three closely related species are widely distributed in the Amazon River basin and are among the most important commercialized species. The paper's authors warn that looming development plans for proposed dams, mining operations, and deforestation—especially in the Amazon's headwaters where these fish spawn—could imperil these long-distance migrants and the fishing industries that rely on them. Growing up to six feet in length, the dorado catfish is sometimes called the gilded catfish due to its silver and gold skin. Credit: Michael Goulding/WCS. \"This is the first time that scientific research has linked the full range of these fish species, some of which stretch from the Andes to the Amazon River estuary abutting the Atlantic Ocean,\" said lead author Ronaldo Barthem of Museu Paraense Emílio Goeldi of Brazil. \"These findings can now inform effective management strategies for these fish, some of which are important for fishing industries in the region.\" \"One of the biggest threats to the dorado catfish and other fish species is headwater infrastructure development in the Andes that could heavily impact the spawning grounds of the world's longest freshwater migrants,\" said WCS aquatic scientist Michael Goulding, a co-author on the study. Whereas the journeys of fish such as salmon and eels are well known, the migratory movements of goliath catfish have been less understood and poorly documented, although it was suspected that goliath catfish make the longest freshwater fish migrations in the world. A map of dorado's life-cycle migration range. Credit: WCS. To confirm this hypothesis, the research team mapped the long-distance movements of four goliath catfish species (Brachyplatystoma rousseauxii, B. platynemum, B. juruense, and B. vaillantii) using information on the presence of adult fish, juveniles, and larvae across the Amazon. The scientists also statistically analyzed the downstream migrations of juvenile fish and larvae from the headwaters of the Amazon's tributaries to the nurseries. The study results revealed that adult dorado catfish traveling upstream from the Amazon estuary may take as long as 1-2 years to reach their spawning grounds in or near the Andes. The scientists also confirmed that at least two other goliath catfish species (B. platynemum, and B. juruense) spawn near or in the Andean foothills, and suspect that there are other species as well. The researchers added that the newly published goliath catfish study will serve as a foundation for later research. Tagging experiments and analyses of isotopes in calcium deposits in the inner ear of fish can both be used to study the migratory pathways of goliath catfish and the seasonal timing of those movements. \"Many questions remain about these incredible fish, such as why they travel so far to reproduce and do they return to place of birth to spawn,\" said Goulding. \"Now we have a baseline that will help direct the trajectory of future research and conservation efforts.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract We mapped the inferred long-distance migrations of four species of Amazonian goliath catfishes ( Brachyplatystoma rousseauxii, B. platynemum, B. juruense and B. vaillantii ) based on the presence of individuals with mature gonads and conducted statistical analysis of the expected long-distance downstream migrations of their larvae and juveniles. By linking the distribution of larval, juvenile and mature adult size classes across the Amazon, the results showed: (i) that the main spawning regions of these goliath catfish species are in the western Amazon; (ii) at least three species— B. rousseauxii, B. platynemum, and B. juruense —spawn partially or mainly as far upstream as the Andes; (iii) the main spawning area of B. rousseauxii is in or near the Andes; and (iv) the life history migration distances of B. rousseauxii are the longest strictly freshwater fish migrations in the world. These results provide an empirical baseline for tagging experiments, life histories extrapolated from otolith microchemistry interpretations and other methods to establish goliath catfish migratory routes, their seasonal timing and possible return (homing) to western headwater tributaries where they were born. Introduction The Amazon has two main groups of migratory fish species, and they belong to the orders Siluriformes (catfishes) and Characiformes (characins) 1 , 2 , 3 . Major fisheries in the Amazon are based on knowledge of the seasonal upstream and downstream movements of fish, although the life cycles are poorly known by fishermen because the species enter and leave local fishing areas 4 , 5 , 6 . Long-distance fish migrations (>1,000 km) that exclusively or partially involve freshwater are known for salmon 7 and eels 8 but have also been inferred for Amazon goliath catfishes of the family Pimelodidae 9 , 10 , 11 , 12 . Although the migrations of most catfish species are poorly known, the general pattern reported is upstream movement to spawn, downstream passive drifting and even active migration of young juveniles to enter nursery habitats in river channels, floodplains or estuaries 7 , 13 , 14 , 15 . In the Amazon, goliath catfishes are major river channel and estuarine predators that are represented by a paraphyletic group of six extant and one fossil species of the genus Brachyplatystoma 16 , 17 , 18 with a maximum known adult fork length (FL) of 60–280 cm 9 ( Fig. 1 ). Figure 1: Migratory goliath catfishes ( Brachyplatystoma , Pimelodidae). ( A ) B. vaillantii (piramutaba in Portuguese, pirabutón in Spanish); ( B ) B. rousseauxii (dourada in Portuguese, dorado in Spanish); ( C ) B. platynemum (babão in Portuguese, mota flemosa in Spanish); ( D ) B. juruense (zebra in Portuguese, zebra in Spanish); ( E ) Dorado migrations exploited by fishermen. The Santo Antônio Dam on the Madeira River now drowns the Teotônio Rapids (shown here) where B. rousseauxii (species in photo) and B. platynemum were previously exploited and easily detected when migrating. Photos by M. Goulding. Full size image The first hypotheses of goliath catfish migration focused on B. rousseauxii and B. vaillantii , the most important commercial species, and their dependence on the Amazon River estuary as their nursery and inland rivers as feeding and spawning areas 9 . The spawning areas, however, were only identified as being located in the western Amazon, a vast region of at least 2 million km 2 that includes parts of Colombia, Ecuador, Peru, Bolivia and Brazil. More recent biological studies based on commercial fisheries in all major western Andes-Amazon tributary basins 19 , 20 , 21 , 22 , 23 established the seasonal, and in some cases year-round, presence of mature goliath catfishes in the western Amazon to at least a few hundred km downstream of the Andes. However, these investigations could not verify the spawning areas, leaving the possibility that they are located farther upriver and closer to the Andes. We present data on the distribution of goliath catfish ( Brachyplatystoma ) adults, larvae and juveniles across the Amazon Basin, including areas in or near the Andes. Even without tagging experiments, the general differential distribution of sub-adult (downstream) and adult (upstream) goliath catfish size-classes 9 , as well as otolith microchemistry data 10 , strongly indicates that long-distance upstream goliath catfish migration occurs. Seasonal upstream goliath catfish movements are also visually obvious at some cataracts, such as those of the Madeira River ( Fig. 1 ) in Brazil, before dams were built 4 , and those of the Caquetá River in Colombia 6 . Therefore, it is reasonable to hypothesize that long-distance downstream migrations of young fish occurs, otherwise there would be no recruitment to nurseries, in some cases as far downstream as the Amazon River estuary. To test the goliath catfish migratory hypothesis related to western spawning regions, we mapped the presence of mature adults complemented by the seasonal and geographical variation in abundance and length of larvae and juveniles in river channels across the Amazon, including in the estuary. Two complementary geographical and temporal perspectives were used. The first focused on the Madeira Basin, the Amazon’s largest sub-basin with headwaters in the Andes, and where year-round collections were performed. The second included most of the Amazon and available data from all years. Our study shows that spawning for at least B. rousseauxii, B. juruense and B. platynemum occurs in or near the Andes and demonstrates conclusively that long-distance downstream migration of their larvae and juveniles occurs. The great variation in B. platynemum larvae size across the Amazon indicates a much wider nursery area than just the Andean region. Size-class data for B. vaillantii indicate long-distance migration and spawning in the western Amazon but do not confirm it near the Andes. Our results are also discussed in light of published goliath life history hypotheses derived from genetic and otolith isotope signatures. Results Adult Distribution and Gonadal Stage Fish length and gonadal data derived from specimens captured in fisheries in major Andes-Amazon sub-basins in Brazil, Bolivia and Peru, complemented by published data from studies based in Colombia 19 , 23 and Ecuador<|im_end|> <|im_start|>assistant An international team of scientists has confirmed that the dorado catfish (Brachyplatystoma rousseauxii) of the Amazon River basin holds the record for the world's longest exclusively freshwater fish migration, an epic life-cycle journey stretching nearly the entire width of the South America continent. The finding, published today in the journal Scientific Reports-Nature, is an output of WCS's Amazon Waters Initiative, sponsored by the Science for Nature and People Partnership (SNAPP) led by WCS (Wildlife Conservation Society), The Nature Conservancy (TNC) and the National Center for Ecological Analysis and Synthesis (NCEAS). The study reveals the amazing life histories of the dorado and three other "goliath" catfish species that spawn in the western headwaters of the Amazon. The journey of the dorado catfish specifically begins with adults and pre-adults traveling thousands of kilometers upriver from the Amazon River estuary to spawning areas in or near the Andes Mountains. The breeding fish never return to their nursery areas, but the newborn catfish do, migrating thousands of kilometers in the opposite direction to complete the cycle. The dorado catfish was found to have a life-cycle migration of approximately 11,600 kilometers (more than 7,200 miles). Growing up to nearly 6 feet in length, the dorado catfish is sometimes called the gilded catfish due to its silver and gold skin with no scales. The dorado and the other three closely related species are widely distributed in the Amazon River basin and are among the most important commercialized species. The paper's authors warn that looming development plans for proposed dams, mining operations, and deforestation—especially in the Amazon's headwaters where these fish spawn—could imperil these long-distance migrants and the fishing industries that rely on them. Growing up to six feet in length, the dorado catfish is sometimes called the gilded catfish due to its silver and gold skin. Credit: Michael Goulding/WCS. "This is the first time that scientific research has linked the full range of these fish species, some of which stretch from the Andes to the Amazon River estuary abutting the Atlantic Ocean," said lead author Ronaldo Barthem of Museu Paraense Emílio Goeldi of Brazil. "These findings can now inform effective management strategies for these fish, some of which are important for fishing industries in the region." "One of the biggest threats to the dorado catfish and other fish species is headwater infrastructure development in the Andes that could heavily impact the spawning grounds of the world's longest freshwater migrants," said WCS aquatic scientist Michael Goulding, a co-author on the study. Whereas the journeys of fish such as salmon and eels are well known, the migratory movements of goliath catfish have been less understood and poorly documented, although it was suspected that goliath catfish make the longest freshwater fish migrations in the world. A map of dorado's life-cycle migration range. Credit: WCS. To confirm this hypothesis, the research team mapped the long-distance movements of four goliath catfish species (Brachyplatystoma rousseauxii, B. platynemum, B. juruense, and B. vaillantii) using information on the presence of adult fish, juveniles, and larvae across the Amazon. The scientists also statistically analyzed the downstream migrations of juvenile fish and larvae from the headwaters of the Amazon's tributaries to the nurseries. The study results revealed that adult dorado catfish traveling upstream from the Amazon estuary may take as long as 1-2 years to reach their spawning grounds in or near the Andes. The scientists also confirmed that at least two other goliath catfish species (B. platynemum, and B. juruense) spawn near or in the Andean foothills, and suspect that there are other species as well. The researchers added that the newly published goliath catfish study will serve as a foundation for later research. Tagging experiments and analyses of isotopes in calcium deposits in the inner ear of fish can both be used to study the migratory pathways of goliath catfish and the seasonal timing of those movements. "Many questions remain about these incredible fish, such as why they travel so far to reproduce and do they return to place of birth to spawn," said Goulding. "Now we have a baseline that will help direct the trajectory of future research and conservation efforts." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Summertime wildfire activity is increasing in boreal forest and tundra ecosystems in the Northern Hemisphere. However, the impact of long range transport and deposition of wildfire aerosols on biogeochemical cycles in the Arctic Ocean is unknown. Here, we use satellite-based ocean color data, atmospheric modeling and back trajectory analysis to investigate the transport and fate of aerosols emitted from Siberian wildfires in summer 2014 and their potential impact on phytoplankton dynamics in the Arctic Ocean. We detect large phytoplankton blooms near the North Pole (up to 82°N in the eastern Eurasian Basin). Our analysis indicates that these blooms were induced by the northward plume transport and deposition of nutrient-bearing wildfire aerosols. We estimate that these highly stratified surface waters received large amounts of wildfire-derived nitrogen, which alleviated nutrient stress in the phytoplankton community and triggered an unusually large bloom event. Our findings suggest that changes in wildfire activity may strongly influence summertime productivity in the Arctic Ocean. Introduction The intensity, frequency, and duration of fires is rapidly changing globally 1 , altering the global carbon cycle and climate 1 , 2 , 3 . High latitude regions of the Northern Hemisphere (>50°N) have dense boreal forests and peatlands subject to major wildfire activity, emissions from which have approximately doubled (north of 60°) over the last decade 4 . The Arctic Oscillation-induced temperature increase appears to be critical for driving earlier snowmelt and fire activity, particularly in southeastern Siberia 5 . Aerosols and gases emitted from wildfires are predominantly carbonaceous in composition, but smoke plumes also carry significant amounts of bio-essential nutrients such as phosphorus 6 , 7 , nitrogen (N) 8 , and iron 9 , 10 . Although Russian observation stations do not routinely record information about N species, N deposition in other northern high latitude regions (e.g., North American High Arctic) is enhanced by wildfire smoke 11 , 12 . Consequently, wildfires can impact the Earth’s biosphere by altering plant productivity, biodiversity, and ultimately ecosystem carbon storage 13 , 14 . Over the past two decades, wildfires have released substantial amounts of carbon in North America (60 Tg C year −1 ) and Asia (124 Tg C year −1 ) 15 . Major Arctic wildfire source regions include Canada, Scandinavia, and Russia 4 , but also Greenland 16 . Russia accounts for approximately two-thirds of the total burnt area within these countries 4 , highlighting the importance of understanding how changing fire activity in Russia under a warming climate could impact marine biogeochemical processes 17 . Depending on the type of vegetation burned, the return interval for boreal forest fires ranges from a few decades to many centuries 18 . Return intervals are projected to decrease in the future, leading to more frequent and severe fires. More severe fires have the potential to release more aerosol to the atmosphere per unit time burned, and thus nutrients deposited within their plumes can be expected to increase. The coupling of wildfires and marine biogeochemical cycles is a recent development in our understanding of the Earth System 19 , 20 , and the impact of increasing boreal wildfires is yet to be assessed for Arctic Ocean marine primary production. Here, we suggest that boreal wildfires directly affect Arctic Ocean primary production by providing a new source of N, the macronutrient primarily limiting biological productivity in these waters 21 , 22 , and thus stimulating phytoplankton growth 23 . Results In summer 2014, ocean color satellites captured one prolonged, or several short, phytoplankton blooms (reaching 1–2 mg chlorophyll a m −3 , Fig. 1 ) up to 850 km south of the North Pole in the eastern Eurasian Basin. The pervasive cloud cover did not allow for continuous characterization of bloom dynamics, but snapshots of the ocean surface clearly revealed anomalously high chlorophyll a concentrations in the eastern Eurasian Basin, north of the Laptev Sea interior shelf. Given the spatial extent and short periods between missing retrievals, it was likely one single prolonged summer bloom. Also captured by satellite remote sensing were the exceptional sea ice conditions; although the onset of melt was two weeks later than the climatological mean, the consolidated ice pack disappeared in July and August at the most rapid rate ever recorded for this region and much further north (Fig. S1 ). Fig. 1: Large summer phytoplankton bloom near the North Pole (eastern Eurasian Basin) in summer 2014. Satellite-derived mean chlorophyll a concentration within the region of the bloom (28–155°E, 80–85°N) during the summer of 2014 ( a ). Dot color represents which satellite sensor (MODIS Aqua, Terra, or VIIRS) is used. Dot size is relative to the number of observations obtained (i.e., pixels). The blue line is the climatological daily average of surface chlorophyll a concentration over the period 2003–2019 (except 2014) with the shading envelope corresponding to the interval between the first and third quartiles. Sea-ice concentration and sea surface temperature, for the full period July 28–August 31 ( b ), and for the three time periods July 27–28, August 13 –15, and August 29–31 ( c – e , respectively). Sea-ice concentration and chlorophyll a concentration, for the same dates as b – e , shown in panels f – i . For b – i : location of the bloom is within the dotted box (28–155°E, 80–85°N) and the continental shelf (bottom depth <50 m) is shown by cross-hatching. Full size image To ascertain the potential source of new nutrients fueling this high latitude bloom we assessed several plausible mechanisms (see the supplementary results for a comprehensive evaluation of all potential mechanisms) of new N supply to the N-depleted surface ocean in summer (Fig. S2 ). Summarizing, storm events can mix N-rich deeper waters to the surface; however, winds remained weaker than the 10 m s −1 threshold generally required to induce rigorous vertical mixing 24 , 25 (Fig. S3 ). Likewise, upwelling in the Arctic can transport deep nutrient-rich waters to the surface that support intense marine production 26 , 27 ,", "role": "user" }, { "content": "Smoke from a Siberian wildfire may have transported enough nitrogen to parts of the Arctic Ocean to amplify a phytoplankton bloom, according to new research from North Carolina State University and the International Research Laboratory Takuvik (CNRS/Laval University) in Canada. The work, which appears in Communications Earth & Environment, sheds light on some potential ecological effects from Northern Hemisphere wildfires, particularly as these fires become larger, longer and more intense. In the summer of 2014, satellite imagery detected a larger than normal algal bloom in the Laptev Sea, located in the Arctic Ocean approximately 850 kilometers (528 miles) south of the North Pole. \"For a bloom that large to occur, the area would need a substantial influx of new nitrogen supply, as the Arctic Ocean is nitrogen-depleted,\" says Douglas Hamilton, assistant professor of marine, earth and atmospheric sciences at NC State and co-first author of a paper describing the work. Hamilton was formerly a research associate at Cornell University, where the research was conducted. \"So we needed to figure out where that nitrogen was coming from.\" First, the researchers looked at the \"usual suspects\" for nitrogen input, such as sea ice melt, river discharge and ocean upwelling, but didn't find anything that would account for the amount of nitrogen necessary for the bloom to occur. But during that same time period, exceptionally large wildfires in Siberia, Russia, located directly upwind of the bloom, had burned approximately 1.5 million hectares (or about 3.5 million acres) of land. So the researchers turned their attention to atmospheric composition. They used the Community Earth System Model (CESM), a computer model that can simulate what happens to emissions from natural and human sources as they enter and leave the atmosphere. The model was fed information about wind, temperature and atmospheric composition—including the composition of wildfire smoke—from the time period in question. The model simulations showed that during late July and August of 2014—when the bloom was detected and the Siberian wildfire was burning—nitrogen deposition from the atmosphere was almost double that of the preceding and following years. \"The wildfires were located in rapidly warming boreal regions, which have a lot of peat in the thawing permafrost,\" Hamilton says. \"Peat is very nitrogen rich and the smoke from the burning peat was hypothesized as the most likely source of much of the additional nitrogen.\" \"We've known that fires can impact phytoplankton blooms, though it is unexpected to see something like this in the Arctic Ocean,\" says Mathieu Ardyna, co-first author and CNRS researcher at the International Research Laboratory Takuvik (CNRS/Laval University). \"Most likely, since fires are locality-specific and difficult to predict, blooms like this won't be the norm—but when these wildfires do occur the nutrients they bring in could lead to sustained or multiple blooms.\" The researchers' next steps could include reviewing the historical satellite record and further characterizing the chemical composition of the particles within the smoke to get a clearer picture of how wildfires like these might impact different ecosystems. \"A one-off bloom like this won't change ecosystem structure, but both Siberia and high arctic Canada are getting more wildfires,\" Hamilton says. \"So it may be interesting to explore potential downstream effects if fire activity and nutrient supply remain high.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Summertime wildfire activity is increasing in boreal forest and tundra ecosystems in the Northern Hemisphere. However, the impact of long range transport and deposition of wildfire aerosols on biogeochemical cycles in the Arctic Ocean is unknown. Here, we use satellite-based ocean color data, atmospheric modeling and back trajectory analysis to investigate the transport and fate of aerosols emitted from Siberian wildfires in summer 2014 and their potential impact on phytoplankton dynamics in the Arctic Ocean. We detect large phytoplankton blooms near the North Pole (up to 82°N in the eastern Eurasian Basin). Our analysis indicates that these blooms were induced by the northward plume transport and deposition of nutrient-bearing wildfire aerosols. We estimate that these highly stratified surface waters received large amounts of wildfire-derived nitrogen, which alleviated nutrient stress in the phytoplankton community and triggered an unusually large bloom event. Our findings suggest that changes in wildfire activity may strongly influence summertime productivity in the Arctic Ocean. Introduction The intensity, frequency, and duration of fires is rapidly changing globally 1 , altering the global carbon cycle and climate 1 , 2 , 3 . High latitude regions of the Northern Hemisphere (>50°N) have dense boreal forests and peatlands subject to major wildfire activity, emissions from which have approximately doubled (north of 60°) over the last decade 4 . The Arctic Oscillation-induced temperature increase appears to be critical for driving earlier snowmelt and fire activity, particularly in southeastern Siberia 5 . Aerosols and gases emitted from wildfires are predominantly carbonaceous in composition, but smoke plumes also carry significant amounts of bio-essential nutrients such as phosphorus 6 , 7 , nitrogen (N) 8 , and iron 9 , 10 . Although Russian observation stations do not routinely record information about N species, N deposition in other northern high latitude regions (e.g., North American High Arctic) is enhanced by wildfire smoke 11 , 12 . Consequently, wildfires can impact the Earth’s biosphere by altering plant productivity, biodiversity, and ultimately ecosystem carbon storage 13 , 14 . Over the past two decades, wildfires have released substantial amounts of carbon in North America (60 Tg C year −1 ) and Asia (124 Tg C year −1 ) 15 . Major Arctic wildfire source regions include Canada, Scandinavia, and Russia 4 , but also Greenland 16 . Russia accounts for approximately two-thirds of the total burnt area within these countries 4 , highlighting the importance of understanding how changing fire activity in Russia under a warming climate could impact marine biogeochemical processes 17 . Depending on the type of vegetation burned, the return interval for boreal forest fires ranges from a few decades to many centuries 18 . Return intervals are projected to decrease in the future, leading to more frequent and severe fires. More severe fires have the potential to release more aerosol to the atmosphere per unit time burned, and thus nutrients deposited within their plumes can be expected to increase. The coupling of wildfires and marine biogeochemical cycles is a recent development in our understanding of the Earth System 19 , 20 , and the impact of increasing boreal wildfires is yet to be assessed for Arctic Ocean marine primary production. Here, we suggest that boreal wildfires directly affect Arctic Ocean primary production by providing a new source of N, the macronutrient primarily limiting biological productivity in these waters 21 , 22 , and thus stimulating phytoplankton growth 23 . Results In summer 2014, ocean color satellites captured one prolonged, or several short, phytoplankton blooms (reaching 1–2 mg chlorophyll a m −3 , Fig. 1 ) up to 850 km south of the North Pole in the eastern Eurasian Basin. The pervasive cloud cover did not allow for continuous characterization of bloom dynamics, but snapshots of the ocean surface clearly revealed anomalously high chlorophyll a concentrations in the eastern Eurasian Basin, north of the Laptev Sea interior shelf. Given the spatial extent and short periods between missing retrievals, it was likely one single prolonged summer bloom. Also captured by satellite remote sensing were the exceptional sea ice conditions; although the onset of melt was two weeks later than the climatological mean, the consolidated ice pack disappeared in July and August at the most rapid rate ever recorded for this region and much further north (Fig. S1 ). Fig. 1: Large summer phytoplankton bloom near the North Pole (eastern Eurasian Basin) in summer 2014. Satellite-derived mean chlorophyll a concentration within the region of the bloom (28–155°E, 80–85°N) during the summer of 2014 ( a ). Dot color represents which satellite sensor (MODIS Aqua, Terra, or VIIRS) is used. Dot size is relative to the number of observations obtained (i.e., pixels). The blue line is the climatological daily average of surface chlorophyll a concentration over the period 2003–2019 (except 2014) with the shading envelope corresponding to the interval between the first and third quartiles. Sea-ice concentration and sea surface temperature, for the full period July 28–August 31 ( b ), and for the three time periods July 27–28, August 13 –15, and August 29–31 ( c – e , respectively). Sea-ice concentration and chlorophyll a concentration, for the same dates as b – e , shown in panels f – i . For b – i : location of the bloom is within the dotted box (28–155°E, 80–85°N) and the continental shelf (bottom depth <50 m) is shown by cross-hatching. Full size image To ascertain the potential source of new nutrients fueling this high latitude bloom we assessed several plausible mechanisms (see the supplementary results for a comprehensive evaluation of all potential mechanisms) of new N supply to the N-depleted surface ocean in summer (Fig. S2 ). Summarizing, storm events can mix N-rich deeper waters to the surface; however, winds remained weaker than the 10 m s −1 threshold generally required to induce rigorous vertical mixing 24 , 25 (Fig. S3 ). Likewise, upwelling in the Arctic can transport deep nutrient-rich waters to the surface that support intense marine production 26 , 27 ,<|im_end|> <|im_start|>assistant Smoke from a Siberian wildfire may have transported enough nitrogen to parts of the Arctic Ocean to amplify a phytoplankton bloom, according to new research from North Carolina State University and the International Research Laboratory Takuvik (CNRS/Laval University) in Canada. The work, which appears in Communications Earth & Environment, sheds light on some potential ecological effects from Northern Hemisphere wildfires, particularly as these fires become larger, longer and more intense. In the summer of 2014, satellite imagery detected a larger than normal algal bloom in the Laptev Sea, located in the Arctic Ocean approximately 850 kilometers (528 miles) south of the North Pole. "For a bloom that large to occur, the area would need a substantial influx of new nitrogen supply, as the Arctic Ocean is nitrogen-depleted," says Douglas Hamilton, assistant professor of marine, earth and atmospheric sciences at NC State and co-first author of a paper describing the work. Hamilton was formerly a research associate at Cornell University, where the research was conducted. "So we needed to figure out where that nitrogen was coming from." First, the researchers looked at the "usual suspects" for nitrogen input, such as sea ice melt, river discharge and ocean upwelling, but didn't find anything that would account for the amount of nitrogen necessary for the bloom to occur. But during that same time period, exceptionally large wildfires in Siberia, Russia, located directly upwind of the bloom, had burned approximately 1.5 million hectares (or about 3.5 million acres) of land. So the researchers turned their attention to atmospheric composition. They used the Community Earth System Model (CESM), a computer model that can simulate what happens to emissions from natural and human sources as they enter and leave the atmosphere. The model was fed information about wind, temperature and atmospheric composition—including the composition of wildfire smoke—from the time period in question. The model simulations showed that during late July and August of 2014—when the bloom was detected and the Siberian wildfire was burning—nitrogen deposition from the atmosphere was almost double that of the preceding and following years. "The wildfires were located in rapidly warming boreal regions, which have a lot of peat in the thawing permafrost," Hamilton says. "Peat is very nitrogen rich and the smoke from the burning peat was hypothesized as the most likely source of much of the additional nitrogen." "We've known that fires can impact phytoplankton blooms, though it is unexpected to see something like this in the Arctic Ocean," says Mathieu Ardyna, co-first author and CNRS researcher at the International Research Laboratory Takuvik (CNRS/Laval University). "Most likely, since fires are locality-specific and difficult to predict, blooms like this won't be the norm—but when these wildfires do occur the nutrients they bring in could lead to sustained or multiple blooms." The researchers' next steps could include reviewing the historical satellite record and further characterizing the chemical composition of the particles within the smoke to get a clearer picture of how wildfires like these might impact different ecosystems. "A one-off bloom like this won't change ecosystem structure, but both Siberia and high arctic Canada are getting more wildfires," Hamilton says. "So it may be interesting to explore potential downstream effects if fire activity and nutrient supply remain high." <|im_end|>

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2,022

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The unmatched catalytic turnover rates of [FeFe]-hydrogenases require an exceptionally efficient proton-transfer (PT) pathway to shuttle protons as substrates or products between bulk water and catalytic center. For clostridial [FeFe]-hydrogenase CpI such a pathway has been proposed and analyzed, but mainly on a theoretical basis. Here, eleven enzyme variants of two different [FeFe]-hydrogenases (CpI and HydA1) with substitutions in the presumptive PT-pathway are examined kinetically, spectroscopically, and crystallographically to provide solid experimental proof for its role in hydrogen-turnover. Targeting key residues of the PT-pathway by site directed mutagenesis significantly alters the pH-activity profile of these variants and in presence of H 2 their cofactor is trapped in an intermediate state indicative of precluded proton-transfer. Furthermore, crystal structures coherently explain the individual levels of residual activity, demonstrating e.g. how trapped H 2 O molecules rescue the interrupted PT-pathway. These features provide conclusive evidence that the targeted positions are indeed vital for catalytic proton-transfer. Introduction [FeFe]-hydrogenases represent one of natures’ most effective classes of redox enzymes catalyzing the reversible reduction of protons to dihydrogen (H 2 ) at turnover frequencies of up to 9000 s -1 1 , 2 , 3 . Most [FeFe]-hydrogenases favor proton reduction while [NiFe]-hydrogenases are usually more biased toward H 2 oxidation 4 . With their low catalytic over-potential 5 , [FeFe]-hydrogenases represent excellent models for a regenerative and likewise economically feasible H 2 production. Their active center (“H-cluster”) can be structured into a standard [4Fe-4S]-cluster ([4Fe] H ) and a diiron site ([2Fe] H ). The latter is uniquely coordinated by three carbonmonoxide (CO) and two cyanide (CN − ) ligands. They stabilize the cofactor in its protein environment 6 and fine-tune its redox features 7 . An azadithiolate ligand (adt) further bridges the proximal (Fe p ) and the distal (Fe d ) iron center, which are differentiated according to their location relative to the [4Fe] H -cluster. To achieve the extraordinary high turnover frequencies of [FeFe]-hydrogenases 8 , it can be implied that proton transfer (PT) is facilitated by distinct and optimized pathways. PT pathways span large distances through protein scaffolds, e.g. to enable proton-coupled electron transfer or proton translocation 9 , 10 , 11 , 12 . They usually comprise of a succession of protonatable or polar residues and protein-bound water molecules aligned at hydrogen-bonding distance 13 , 14 . Based on the crystal structures of [FeFe]-hydrogenases CpΙ from Clostridium pasteurianum and DdH from Desulfovibrio desulfuricans , several putative PT pathways have been discussed 15 , 16 , 17 , 18 . Theoretical studies suggest that the most probable PT pathway comprises of strictly conserved residues E282, S319, E279, and C299 (from surface to H-cluster, numbering corresponds to CpI), including two protein-bound water molecules (Wat826, Wat1120 4XDC 19 , chain B) located between E279 and C299 15 , 16 , 20 . This pathway ends with C299 located in hydrogen-bonding distance to the amine head-group of the adt-ligand. Its identity and importance as a proton relay was verified in comparative studies on cofactor variants of HydA1 from Chlamydomonas reinhardtii 21 . Cornish and co-workers could show that amino-acid substitutions along the putative PT pathway dramatically decreased the catalytic activities. In particular, their study indicated a participation of surface-exposed residue E282 in catalytic PT 15 . In a second study they suggested a regulative function for positions R286 and S320 in the PT of CpI 22 . Furthermore, Morra and co-workers described that the pH optimum of variant C298D of [FeFe]-hydrogenase CaI from Clostridium acetobutylicum (corresponding to C299D in CpI) is shifted from pH 8 to pH 7, indicative for the involvement of C298 in PT 23 , 24 . Although several studies were conducted, immediate experimental evidence for the relevance of residues in the putative PT pathway is missing, leaving an essential aspect of enzymatic performance opaque. In this study, site-directed mutagenesis (SDM) is used to investigate the PT pathway of two [FeFe]-hydrogenases, namely CpI and HydA1, which represent the largest (M3) and smallest (M1) type of monomeric [FeFe]-hydrogenases, respectively 25 . Most of the 22 SDM variants show strongly affected H 2 release activities and pH optima. For 11 of these variants the crystal structure is solved, which facilitates a correlation of individual structural features (i.e. hydrogen-bonding distances) and catalytic performance. This provides insight into the minutiae of PT on the molecular level. Catalytically hampered SDM variants are analyzed by in situ attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. When flushed with H 2 , these enzymes are found to adopt a key intermediate of hydrogen turnover, the recently described H hyd state 26 , 27 , 28 , 29 , 30 . H hyd accumulation under H 2 clearly correlates with the diminished PT efficiency of the enzyme 29 . Herein we provide complementary kinetic, structural, and spectroscopic data, which allow to verify the PT pathway discussed above as the key route of catalytic PT in [FeFe]-hydrogenases. Results H 2 release assays and pH-dependent enzyme activities For both CpI and HydA1, 11 SDM variants were generated to target residues along the putative PT pathway applying conservative and non-conservative exchanges (Fig. 1 ). Conservative exchanges (e.g. E → D) maintain the functional group of the targeted position, but due to other structural differences in the substitute residue, will affect the precise spatial placement and configuration of the functional group. In a highly ordered system such as the well-distanced H-bond chain of an evolutionarily optimized PT pathway, this should at least affect the efficiency of the functional aspect. Non-conservative exchanges (e.g. E → Q/A) delete the functional group entirely and therefore prohibit these substitute residues from rescuing the targeted function. For wild-type (wt) enzyme, H 2 release activities of about 860 (HydA1) and 2600 (CpI) µmol H 2 per mg per min were measured and defined as 100% activity 29 , 31 , 32 , 33 . Corresponding substitutions in CpI and HydA1 had similar effects on H 2 -release activity, except for variants E282Q CpI (8.2%) and E144Q HydA1 (0.4%).", "role": "user" }, { "content": "In their catalytic center, hydrogenases manufacture molecular hydrogen (H2) from two protons and two electrons. They extract the protons required for this process from the surrounding water and transfer them – via a transport chain – into their catalytic core. The exact proton pathway through the hydrogenase had as yet not been understood. \"This transfer pathway is a jigsaw piece, crucial for understanding the interplay of cofactor and protein which is the reason why biocatalysts are so much more efficient than hydrogen-producing chemical complexes,\" explains Dr. Martin Winkler, one of the authors of this study from the Photobiotechnology research group at RUB. In order to figure out which of the hydrogenase building blocks are involved in proton transfer, the researchers substituted them individually. They replaced each either by an amino acid with a similar function or by a dysfunctional amino acid. Thus, 22 variants of two different hydrogenases were created. Subsequently, the researchers compared those variants with regard to different aspects, including their spectroscopic properties and their enzyme activity. \"The molecular structures of twelve protein variants, which were solved using X-ray structure analysis, proved particularly informative,\" says Winkler. Amino acids with no function shut down hydrogenases Depending on where and how the researchers had changed the hydrogenase, hydrogen production became less efficient or stopped altogether. \"Thus, we ascertained why some variants are severely impaired in terms of enzyme activity and why others are hardly impaired at all – against all expectations,\" says Martin Winkler. The closer to the catalytic centre the replaced amino acids were located, the less able the hydrogenase was to compensate for these modifications. If building blocks with no function were embedded in sensitive locations, hydrogen production was shut down. \"The thus generated state resembles an oversaturation due to proton stress where protons as well as hydrogen are simultaneously introduced into the hydrogenase,\" elaborates Martin Winkler. \"In the course of our project, we were for the first time able to stabilise and analyse this highly transient state that we had already encountered in experiments.\" Valuable baseline information This study has made it possible to assign the functions of individual amino acids to the proton transfer pathway for the enzyme group of [FeFe] hydrogenases. \"Moreover, it provides valuable information on the molecular mechanism of proton transfer by redox-active proteins and the structural requirements thereof,\" concludes Thomas Happe. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The unmatched catalytic turnover rates of [FeFe]-hydrogenases require an exceptionally efficient proton-transfer (PT) pathway to shuttle protons as substrates or products between bulk water and catalytic center. For clostridial [FeFe]-hydrogenase CpI such a pathway has been proposed and analyzed, but mainly on a theoretical basis. Here, eleven enzyme variants of two different [FeFe]-hydrogenases (CpI and HydA1) with substitutions in the presumptive PT-pathway are examined kinetically, spectroscopically, and crystallographically to provide solid experimental proof for its role in hydrogen-turnover. Targeting key residues of the PT-pathway by site directed mutagenesis significantly alters the pH-activity profile of these variants and in presence of H 2 their cofactor is trapped in an intermediate state indicative of precluded proton-transfer. Furthermore, crystal structures coherently explain the individual levels of residual activity, demonstrating e.g. how trapped H 2 O molecules rescue the interrupted PT-pathway. These features provide conclusive evidence that the targeted positions are indeed vital for catalytic proton-transfer. Introduction [FeFe]-hydrogenases represent one of natures’ most effective classes of redox enzymes catalyzing the reversible reduction of protons to dihydrogen (H 2 ) at turnover frequencies of up to 9000 s -1 1 , 2 , 3 . Most [FeFe]-hydrogenases favor proton reduction while [NiFe]-hydrogenases are usually more biased toward H 2 oxidation 4 . With their low catalytic over-potential 5 , [FeFe]-hydrogenases represent excellent models for a regenerative and likewise economically feasible H 2 production. Their active center (“H-cluster”) can be structured into a standard [4Fe-4S]-cluster ([4Fe] H ) and a diiron site ([2Fe] H ). The latter is uniquely coordinated by three carbonmonoxide (CO) and two cyanide (CN − ) ligands. They stabilize the cofactor in its protein environment 6 and fine-tune its redox features 7 . An azadithiolate ligand (adt) further bridges the proximal (Fe p ) and the distal (Fe d ) iron center, which are differentiated according to their location relative to the [4Fe] H -cluster. To achieve the extraordinary high turnover frequencies of [FeFe]-hydrogenases 8 , it can be implied that proton transfer (PT) is facilitated by distinct and optimized pathways. PT pathways span large distances through protein scaffolds, e.g. to enable proton-coupled electron transfer or proton translocation 9 , 10 , 11 , 12 . They usually comprise of a succession of protonatable or polar residues and protein-bound water molecules aligned at hydrogen-bonding distance 13 , 14 . Based on the crystal structures of [FeFe]-hydrogenases CpΙ from Clostridium pasteurianum and DdH from Desulfovibrio desulfuricans , several putative PT pathways have been discussed 15 , 16 , 17 , 18 . Theoretical studies suggest that the most probable PT pathway comprises of strictly conserved residues E282, S319, E279, and C299 (from surface to H-cluster, numbering corresponds to CpI), including two protein-bound water molecules (Wat826, Wat1120 4XDC 19 , chain B) located between E279 and C299 15 , 16 , 20 . This pathway ends with C299 located in hydrogen-bonding distance to the amine head-group of the adt-ligand. Its identity and importance as a proton relay was verified in comparative studies on cofactor variants of HydA1 from Chlamydomonas reinhardtii 21 . Cornish and co-workers could show that amino-acid substitutions along the putative PT pathway dramatically decreased the catalytic activities. In particular, their study indicated a participation of surface-exposed residue E282 in catalytic PT 15 . In a second study they suggested a regulative function for positions R286 and S320 in the PT of CpI 22 . Furthermore, Morra and co-workers described that the pH optimum of variant C298D of [FeFe]-hydrogenase CaI from Clostridium acetobutylicum (corresponding to C299D in CpI) is shifted from pH 8 to pH 7, indicative for the involvement of C298 in PT 23 , 24 . Although several studies were conducted, immediate experimental evidence for the relevance of residues in the putative PT pathway is missing, leaving an essential aspect of enzymatic performance opaque. In this study, site-directed mutagenesis (SDM) is used to investigate the PT pathway of two [FeFe]-hydrogenases, namely CpI and HydA1, which represent the largest (M3) and smallest (M1) type of monomeric [FeFe]-hydrogenases, respectively 25 . Most of the 22 SDM variants show strongly affected H 2 release activities and pH optima. For 11 of these variants the crystal structure is solved, which facilitates a correlation of individual structural features (i.e. hydrogen-bonding distances) and catalytic performance. This provides insight into the minutiae of PT on the molecular level. Catalytically hampered SDM variants are analyzed by in situ attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. When flushed with H 2 , these enzymes are found to adopt a key intermediate of hydrogen turnover, the recently described H hyd state 26 , 27 , 28 , 29 , 30 . H hyd accumulation under H 2 clearly correlates with the diminished PT efficiency of the enzyme 29 . Herein we provide complementary kinetic, structural, and spectroscopic data, which allow to verify the PT pathway discussed above as the key route of catalytic PT in [FeFe]-hydrogenases. Results H 2 release assays and pH-dependent enzyme activities For both CpI and HydA1, 11 SDM variants were generated to target residues along the putative PT pathway applying conservative and non-conservative exchanges (Fig. 1 ). Conservative exchanges (e.g. E → D) maintain the functional group of the targeted position, but due to other structural differences in the substitute residue, will affect the precise spatial placement and configuration of the functional group. In a highly ordered system such as the well-distanced H-bond chain of an evolutionarily optimized PT pathway, this should at least affect the efficiency of the functional aspect. Non-conservative exchanges (e.g. E → Q/A) delete the functional group entirely and therefore prohibit these substitute residues from rescuing the targeted function. For wild-type (wt) enzyme, H 2 release activities of about 860 (HydA1) and 2600 (CpI) µmol H 2 per mg per min were measured and defined as 100% activity 29 , 31 , 32 , 33 . Corresponding substitutions in CpI and HydA1 had similar effects on H 2 -release activity, except for variants E282Q CpI (8.2%) and E144Q HydA1 (0.4%).<|im_end|> <|im_start|>assistant In their catalytic center, hydrogenases manufacture molecular hydrogen (H2) from two protons and two electrons. They extract the protons required for this process from the surrounding water and transfer them – via a transport chain – into their catalytic core. The exact proton pathway through the hydrogenase had as yet not been understood. "This transfer pathway is a jigsaw piece, crucial for understanding the interplay of cofactor and protein which is the reason why biocatalysts are so much more efficient than hydrogen-producing chemical complexes," explains Dr. Martin Winkler, one of the authors of this study from the Photobiotechnology research group at RUB. In order to figure out which of the hydrogenase building blocks are involved in proton transfer, the researchers substituted them individually. They replaced each either by an amino acid with a similar function or by a dysfunctional amino acid. Thus, 22 variants of two different hydrogenases were created. Subsequently, the researchers compared those variants with regard to different aspects, including their spectroscopic properties and their enzyme activity. "The molecular structures of twelve protein variants, which were solved using X-ray structure analysis, proved particularly informative," says Winkler. Amino acids with no function shut down hydrogenases Depending on where and how the researchers had changed the hydrogenase, hydrogen production became less efficient or stopped altogether. "Thus, we ascertained why some variants are severely impaired in terms of enzyme activity and why others are hardly impaired at all – against all expectations," says Martin Winkler. The closer to the catalytic centre the replaced amino acids were located, the less able the hydrogenase was to compensate for these modifications. If building blocks with no function were embedded in sensitive locations, hydrogen production was shut down. "The thus generated state resembles an oversaturation due to proton stress where protons as well as hydrogen are simultaneously introduced into the hydrogenase," elaborates Martin Winkler. "In the course of our project, we were for the first time able to stabilise and analyse this highly transient state that we had already encountered in experiments." Valuable baseline information This study has made it possible to assign the functions of individual amino acids to the proton transfer pathway for the enzyme group of [FeFe] hydrogenases. "Moreover, it provides valuable information on the molecular mechanism of proton transfer by redox-active proteins and the structural requirements thereof," concludes Thomas Happe. <|im_end|>

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2,046

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Acute pain represents a crucial alarm signal to protect us from injury 1 . Whereas the nociceptive neurons that convey pain signals were described more than a century ago 2 , the molecular sensors that detect noxious thermal or mechanical insults have yet to be fully identified 3 , 4 , 5 , 6 . Here we show that acute noxious heat sensing in mice depends on a triad of transient receptor potential (TRP) ion channels: TRPM3, TRPV1, and TRPA1. We found that robust somatosensory heat responsiveness at the cellular and behavioural levels is observed only if at least one of these TRP channels is functional. However, combined genetic or pharmacological elimination of all three channels largely and selectively prevents heat responses in both isolated sensory neurons and rapidly firing C and Aδ sensory nerve fibres that innervate the skin. Strikingly, Trpv1 −/− Trpm3 −/− Trpa1 −/− triple knockout (TKO) mice lack the acute withdrawal response to noxious heat that is necessary to avoid burn injury, while showing normal nociceptive responses to cold or mechanical stimuli and a preserved preference for moderate temperatures. These findings indicate that the initiation of the acute heat-evoked pain response in sensory nerve endings relies on three functionally redundant TRP channels, representing a fault-tolerant mechanism to avoid burn injury. Main Nociceptors involved in acute heat sensing have cell bodies in the dorsal root and trigeminal ganglia and extend their sensory endings into the skin, mucosa and internal organs 4 , 6 . In these nociceptor endings, a rise in temperature induces the firing of action potentials, which propagate towards the dorsal horn or sensory nucleus in the brain, where the sensory information is relayed to second-order neurons 4 . Heat-activated nociceptors are characterized by the expression of the heat- and capsaicin-activated TRP channel TRPV1 7 . However, although ablation 8 or silencing 9 of TRPV1-expressing neurons in mice result in almost complete absence of heat nociception, Trpv1 -knockout mice display only minor deficits in acute noxious heat sensing 10 , 11 , indicating that heat-sensitive nociceptors express additional molecular heat sensors. Although various other ion channels, including several other TRP channels and calcium-activated chloride channels of the Anoctamin/TMEM16 family 4 , 6 , have been put forward as molecular heat sensors, mice deficient in these various channels showed either no or relatively mild deficits in acute heat sensing 12 , 13 , 14 , 15 . Thus, the molecular basis of acute heat sensing has remained unresolved 4 . The heat-sensitive TRP channel TRPM3 is expressed in a large subset of TRPV1-expressing sensory neurons, and Trpm3 −/− knockout mice exhibit reduced heat sensitivity at cellular and behavioural levels 14 , 16 . To investigate the consequences of combined elimination of TRPV1 and TRPM3, we analysed the heat responsiveness of Trpm3 −/− Trpv1 −/− double knockout (DKO M3/V1 ) mice. Using calcium imaging, we probed the thermal and chemical responsiveness of sensory neurons isolated from the trigeminal ganglia in primary cultures. Whereas responses to the TRPM3 agonist pregnenolone sulfate and to the TRPV1 agonist capsaicin were largely eliminated, the proportion of heat-responsive neurons was reduced only slightly compared to that of wild-type mice, with approximately 40% of the DKO M3/V1 neurons still exhibiting a robust heat-induced calcium response ( Fig. 1a ; Extended Data Fig. 1a ; see Methods for identification of heat responders). We used a skin-nerve preparation to measure action potentials upon stimulation of the receptive fields of single nerve fibres 17 , and recorded robust heat-evoked responses in 33% (6/18) of the mechanosensitive C fibres from DKO M3/V1 mice, as compared to 49% (17/35) in wild-type mice ( P = 0.38; Fisher’s exact test; Extended Data Fig. 1b ). At the behavioural level, DKO M3/V1 mice exhibited vigorous heat avoidance responses in the tail-immersion and hot-plate assays, although withdrawal latencies were prolonged compared to the wild type ( Extended Data Fig. 1c ). Thus, combined elimination of TRPM3 and TRPV1 results in only very mild deficits in heat responsiveness, implying the existence of one or more additional heat sensors in somatosensory neurons. Figure 1: TRPA1 mediates TRPM3- and TRPV1-independent heat responses. a , b , Responses to heat (45 °C) and AITC (50 μM) in sensory neurons from DKO M3/V1 mice in the absence and presence of the TRPA1 antagonist HC030031 (100 μM). WT, wild-type; PS, pregnenolone sulfate; Caps, capsaicin. c , Example of a HC030031-sensitive heat-activated inward current in an AITC-sensitive DKO M3/V1 neuron. d , Mean (± s.e.m.) current densities for experiments as in c ( n = 9 cells). e , f , Heat and ligand responses in sensory neurons from TKO and indicated DKO mice. Scale bars in a , b , e , f , 60 s/100 nM. g , Percentages of heat-responding sensory neurons in mice of the indicated genotypes, in the absence or presence of HC030031. The experiments in a , b , e , f and summary data in g are representative of the following numbers ( n ) of tested trigeminal neurons from N mice: wild-type: n = 296, N = 6; DKO M3/A1 : n = 613, N = 5; DKO V1/A1 : n = 725, N = 7; DKO M3/V1 : n = 1,353, N = 9; TKO: n = 720, N = 11; WT+HC030031: n = 208, N = 3; DKO M3/V1 + HC030031: n = 293, N = 3; DRG neurons from wild-type: n = 133, N = 3; TKO: n = 181, N = 3. *** P < 0.00001; Fisher’s exact test with Holm–Bonferroni correction. PowerPoint slide Full size image We observed that most residual heat-sensitive neurons in the DKO M3/V1 mice also responded to allyl isothiocyanate (AITC, 50 μM; Fig. 1a ), a pungent chemical that at this concentration causes selective activation of TRPA1 18 . Moreover, in wild-type heat-sensitive neurons, we found extensive overlap of functional expression of TRPA1 with both TRPM3 and TRPV1 ( Extended Data Fig. 1d ). To test whether TRPA1 contributes to", "role": "user" }, { "content": "Researchers at VIB and KU Leuven have uncovered a trio of complementary ion channels in sensory neurons that mediate detection of acute, harmful heat. Having three redundant molecular heat-sensing mechanisms provides a powerful fail-safe mechanism that protects against burn injuries. The seminal findings have been published today in Nature. Although the sensory neurons involved in acute pain signaling in mammals were described more than a century ago, the molecular mechanisms whereby these neurons detect harmful signals have remained largely unresolved. A research team jointly led by prof. Thomas Voets (VIB - KU Leuven) and prof. Joris Vriens (KU Leuven) used genetic knockout models to pinpoint which molecular partners are involved. \"We already knew several potential molecular heat sensors, but none of them, when deactivated, resulted in severe loss of acute noxious heat sensing,\" explains Ine Vandewauw, postdoctoral scientist in the lab of Thomas Voets. The researchers started by eliminating two different heat-activated TRP ion channels, including one known to be also activated by capsaicin, the active component of chili peppers. But this only resulted in very mild deficits in heat sensing. Interestingly, most residual heat-sensitive neurons in the double knockout mice also responded to allyl isothiocyanate, responsible for the pungent sensation of mustard, radish and wasabi. This chemical selectively activates a third TRP channel, which prompted the scientists to go one step further and generate a triple knockout. Mice with all three TRP channels eliminated showed a complete loss of heat-induced pain responses. Reintroduction of the receptors via transient transfection restored sensitivity to heat, and conversely, heat responses could also be suppressed by an inhibitor cocktail for all three TRP channels. The signaling was specific for the pain response to heat, as the animals responded normally to other painful stimuli such as cold, pressure or pinpricks, and their overall thermal preference was not affected. This triple knock out mouse represents the first demonstration in mammals of elimination of the pain response to a physical stimulus at the level of the signal-transducing ion channel. \"Acute pain in response to heat is a crucial alarm signal in all mammals,\" explains Thomas Voets. \"The presence of three redundant molecular heat-sensing mechanisms with overlapping expression in pain-sensing neurons creates a powerful fail-safe mechanism. It ensures we avoid dangerous heat, even if one or even two heat sensors are compromised.\" Next, the researchers want to investigate how these channels can be targeted to treat chronic pain. Thomas Voets says, \"Millions of people worldwide suffer from ongoing, burning pain caused for instance by nerve damage or inflammation, and the currently available drugs to treat chronic pain often don't work well or cause addiction. In such conditions, the three heat-activated TRP channels can get deregulated, signaling painful heat even when there is no risk of burning. By developing new drugs that specifically temper the activity of these molecular heat detectors, we hope to be able to provide effective and safe means to treat chronic pain in patients.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Acute pain represents a crucial alarm signal to protect us from injury 1 . Whereas the nociceptive neurons that convey pain signals were described more than a century ago 2 , the molecular sensors that detect noxious thermal or mechanical insults have yet to be fully identified 3 , 4 , 5 , 6 . Here we show that acute noxious heat sensing in mice depends on a triad of transient receptor potential (TRP) ion channels: TRPM3, TRPV1, and TRPA1. We found that robust somatosensory heat responsiveness at the cellular and behavioural levels is observed only if at least one of these TRP channels is functional. However, combined genetic or pharmacological elimination of all three channels largely and selectively prevents heat responses in both isolated sensory neurons and rapidly firing C and Aδ sensory nerve fibres that innervate the skin. Strikingly, Trpv1 −/− Trpm3 −/− Trpa1 −/− triple knockout (TKO) mice lack the acute withdrawal response to noxious heat that is necessary to avoid burn injury, while showing normal nociceptive responses to cold or mechanical stimuli and a preserved preference for moderate temperatures. These findings indicate that the initiation of the acute heat-evoked pain response in sensory nerve endings relies on three functionally redundant TRP channels, representing a fault-tolerant mechanism to avoid burn injury. Main Nociceptors involved in acute heat sensing have cell bodies in the dorsal root and trigeminal ganglia and extend their sensory endings into the skin, mucosa and internal organs 4 , 6 . In these nociceptor endings, a rise in temperature induces the firing of action potentials, which propagate towards the dorsal horn or sensory nucleus in the brain, where the sensory information is relayed to second-order neurons 4 . Heat-activated nociceptors are characterized by the expression of the heat- and capsaicin-activated TRP channel TRPV1 7 . However, although ablation 8 or silencing 9 of TRPV1-expressing neurons in mice result in almost complete absence of heat nociception, Trpv1 -knockout mice display only minor deficits in acute noxious heat sensing 10 , 11 , indicating that heat-sensitive nociceptors express additional molecular heat sensors. Although various other ion channels, including several other TRP channels and calcium-activated chloride channels of the Anoctamin/TMEM16 family 4 , 6 , have been put forward as molecular heat sensors, mice deficient in these various channels showed either no or relatively mild deficits in acute heat sensing 12 , 13 , 14 , 15 . Thus, the molecular basis of acute heat sensing has remained unresolved 4 . The heat-sensitive TRP channel TRPM3 is expressed in a large subset of TRPV1-expressing sensory neurons, and Trpm3 −/− knockout mice exhibit reduced heat sensitivity at cellular and behavioural levels 14 , 16 . To investigate the consequences of combined elimination of TRPV1 and TRPM3, we analysed the heat responsiveness of Trpm3 −/− Trpv1 −/− double knockout (DKO M3/V1 ) mice. Using calcium imaging, we probed the thermal and chemical responsiveness of sensory neurons isolated from the trigeminal ganglia in primary cultures. Whereas responses to the TRPM3 agonist pregnenolone sulfate and to the TRPV1 agonist capsaicin were largely eliminated, the proportion of heat-responsive neurons was reduced only slightly compared to that of wild-type mice, with approximately 40% of the DKO M3/V1 neurons still exhibiting a robust heat-induced calcium response ( Fig. 1a ; Extended Data Fig. 1a ; see Methods for identification of heat responders). We used a skin-nerve preparation to measure action potentials upon stimulation of the receptive fields of single nerve fibres 17 , and recorded robust heat-evoked responses in 33% (6/18) of the mechanosensitive C fibres from DKO M3/V1 mice, as compared to 49% (17/35) in wild-type mice ( P = 0.38; Fisher’s exact test; Extended Data Fig. 1b ). At the behavioural level, DKO M3/V1 mice exhibited vigorous heat avoidance responses in the tail-immersion and hot-plate assays, although withdrawal latencies were prolonged compared to the wild type ( Extended Data Fig. 1c ). Thus, combined elimination of TRPM3 and TRPV1 results in only very mild deficits in heat responsiveness, implying the existence of one or more additional heat sensors in somatosensory neurons. Figure 1: TRPA1 mediates TRPM3- and TRPV1-independent heat responses. a , b , Responses to heat (45 °C) and AITC (50 μM) in sensory neurons from DKO M3/V1 mice in the absence and presence of the TRPA1 antagonist HC030031 (100 μM). WT, wild-type; PS, pregnenolone sulfate; Caps, capsaicin. c , Example of a HC030031-sensitive heat-activated inward current in an AITC-sensitive DKO M3/V1 neuron. d , Mean (± s.e.m.) current densities for experiments as in c ( n = 9 cells). e , f , Heat and ligand responses in sensory neurons from TKO and indicated DKO mice. Scale bars in a , b , e , f , 60 s/100 nM. g , Percentages of heat-responding sensory neurons in mice of the indicated genotypes, in the absence or presence of HC030031. The experiments in a , b , e , f and summary data in g are representative of the following numbers ( n ) of tested trigeminal neurons from N mice: wild-type: n = 296, N = 6; DKO M3/A1 : n = 613, N = 5; DKO V1/A1 : n = 725, N = 7; DKO M3/V1 : n = 1,353, N = 9; TKO: n = 720, N = 11; WT+HC030031: n = 208, N = 3; DKO M3/V1 + HC030031: n = 293, N = 3; DRG neurons from wild-type: n = 133, N = 3; TKO: n = 181, N = 3. *** P < 0.00001; Fisher’s exact test with Holm–Bonferroni correction. PowerPoint slide Full size image We observed that most residual heat-sensitive neurons in the DKO M3/V1 mice also responded to allyl isothiocyanate (AITC, 50 μM; Fig. 1a ), a pungent chemical that at this concentration causes selective activation of TRPA1 18 . Moreover, in wild-type heat-sensitive neurons, we found extensive overlap of functional expression of TRPA1 with both TRPM3 and TRPV1 ( Extended Data Fig. 1d ). To test whether TRPA1 contributes to<|im_end|> <|im_start|>assistant Researchers at VIB and KU Leuven have uncovered a trio of complementary ion channels in sensory neurons that mediate detection of acute, harmful heat. Having three redundant molecular heat-sensing mechanisms provides a powerful fail-safe mechanism that protects against burn injuries. The seminal findings have been published today in Nature. Although the sensory neurons involved in acute pain signaling in mammals were described more than a century ago, the molecular mechanisms whereby these neurons detect harmful signals have remained largely unresolved. A research team jointly led by prof. Thomas Voets (VIB - KU Leuven) and prof. Joris Vriens (KU Leuven) used genetic knockout models to pinpoint which molecular partners are involved. "We already knew several potential molecular heat sensors, but none of them, when deactivated, resulted in severe loss of acute noxious heat sensing," explains Ine Vandewauw, postdoctoral scientist in the lab of Thomas Voets. The researchers started by eliminating two different heat-activated TRP ion channels, including one known to be also activated by capsaicin, the active component of chili peppers. But this only resulted in very mild deficits in heat sensing. Interestingly, most residual heat-sensitive neurons in the double knockout mice also responded to allyl isothiocyanate, responsible for the pungent sensation of mustard, radish and wasabi. This chemical selectively activates a third TRP channel, which prompted the scientists to go one step further and generate a triple knockout. Mice with all three TRP channels eliminated showed a complete loss of heat-induced pain responses. Reintroduction of the receptors via transient transfection restored sensitivity to heat, and conversely, heat responses could also be suppressed by an inhibitor cocktail for all three TRP channels. The signaling was specific for the pain response to heat, as the animals responded normally to other painful stimuli such as cold, pressure or pinpricks, and their overall thermal preference was not affected. This triple knock out mouse represents the first demonstration in mammals of elimination of the pain response to a physical stimulus at the level of the signal-transducing ion channel. "Acute pain in response to heat is a crucial alarm signal in all mammals," explains Thomas Voets. "The presence of three redundant molecular heat-sensing mechanisms with overlapping expression in pain-sensing neurons creates a powerful fail-safe mechanism. It ensures we avoid dangerous heat, even if one or even two heat sensors are compromised." Next, the researchers want to investigate how these channels can be targeted to treat chronic pain. Thomas Voets says, "Millions of people worldwide suffer from ongoing, burning pain caused for instance by nerve damage or inflammation, and the currently available drugs to treat chronic pain often don't work well or cause addiction. In such conditions, the three heat-activated TRP channels can get deregulated, signaling painful heat even when there is no risk of burning. By developing new drugs that specifically temper the activity of these molecular heat detectors, we hope to be able to provide effective and safe means to treat chronic pain in patients." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract High pressure represents extreme environments and provides opportunities for materials discovery 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 . Thermal transport under high hydrostatic pressure has been investigated for more than 100 years and all measurements of crystals so far have indicated a monotonically increasing lattice thermal conductivity. Here we report in situ thermal transport measurements in the newly discovered semiconductor crystal boron arsenide, and observe an anomalous pressure dependence of the thermal conductivity. We use ultrafast optics, Raman spectroscopy and inelastic X-ray scattering measurements to examine the phonon bandstructure evolution of the optical and acoustic branches, as well as thermal conductivity under varied temperatures and pressures up to 32 gigapascals. Using atomistic theory, we attribute the anomalous high-pressure behaviour to competitive heat conduction channels from interactive high-order anharmonicity physics inherent to the unique phonon bandstructure. Our study verifies ab initio theory calculations and we show that the phonon dynamics—resulting from competing three-phonon and four-phonon scattering processes—are beyond those expected from classical models and seen in common materials. This work uses high-pressure spectroscopy combined with atomistic theory as a powerful approach to probe complex phonon physics and provide fundamental insights for understanding microscopic energy transport in materials of extreme properties. Main Understanding materials properties under high pressure is critical to many areas, from planetary science, geophysics and condensed-matter theory, to new chemical bonding and superconductivity 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 . Over 100 years of literature studies of high pressure thermal transport, from the first experiment 9 , to additional analysis 10 , 11 , 12 , 13 , the lattice thermal conductivity of crystals has been found to increase monotonically with hydrostatic pressure, unless a phase transition takes place. From a theoretical perspective 9 , 14 , the crystal lattice symmetry remains under hydrostatic pressure, and therefore such a universal increase of thermal conductivity can be well understood as a result of volume shrink under pressure that leads to increased atom density and atomic bonding strength. Classical theories 15 , 16 , 17 , 18 , 19 use parameterized models to link with the Debye temperature, bulk modulus and Grüneisen parameters to predict that thermal conductivity must increase with pressure 20 . Although a quantum mechanical picture for this governing rule is missing, it has shown consistency with all experimental reports in the literature so far. Here we measured high-pressure thermal transport in a recently discovered semiconductor material, cubic boron arsenide (BAs), and observed anomalous pressure dependence of the thermal conductivity that has not, to our knowledge, been measured in any other materials 9 , 10 , 11 , 12 , 13 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 (see summary in Fig. 1a ). On the basis of our experimental characterizations, and in combination with ab initio atomistic theory, we attribute this anomalous behaviour to competitive heat conduction channels that are inherent and arise from the unique bandstructure and high-order phonon physics. We verified ab initio calculations and the unique competition mechanisms from interactive high-order anharmonic scattering processes that are beyond understanding using classical theories. Fig. 1: Anomalous thermal conductivity of BAs under high pressure compared to literature studies. a , Summary of thermal conductivities of non-metal crystals as a function of hydrostatic pressure (CsCl 21 , CsBr 21 , NaCl 22 , NaI 22 , quartz 23 , mica 24 , ice 25 , MgSiO 3 26 , diamond 27 , MgO 28 , BN 29 , GaAs 30 ). Results from existing literature indicate a ubiquitous increase in lattice thermal conductivity under a single phase, whereas BAs is an exception. b , Zinc blende crystal structure of cubic BAs. c , High-resolution transmission electron microscopy image showing atomically resolved lattices of BAs. Scale bar, 2 nm. Full size image BAs with high thermal conductivity To experimentally measure the high-pressure transport behaviour, we synthesized high-quality, single-crystal BAs and performed ultrafast pump–probe measurements under high pressure and temperature dependence. Cubic BAs (Fig. 1b ) is a semiconductor that was recently discovered to have an ultrahigh thermal conductivity 31 , 32 , 33 , 34 beyond most common materials and demonstrates high promise for electronics thermal management 35 , 36 . Importantly, these recent theoretical studies indicate that BAs can be an exception and showcase material for higher-order phonon anharmonicity. Ab initio theory expects anomalous thermal transport at high pressure 37 ; however, this has yet to be experimentally explored. Here we synthesized BAs crystals through chemical vapour deposition in a customized three-zone furnace as described in our recent reports 32 , 38 . The high crystal quality of BAs was carefully verified with structural characterizations (Fig. 1c ) and measurement of a room-temperature (298 K) thermal conductivity of approximately 1,300 W m − 1 K −1 (ref. 32 ). Our experimental set-up uses a diamond anvil cell (DAC) to provide high pressure, which was installed in a cryostat chamber for temperature control; pump–probe and optical measurements are applied to measure the sample through the optical window (Fig. 2a ). The DAC can generate tens of GPa of pressure on the loaded BAs crystals, as shown in Fig. 2b . Importantly, we performed synchrotron X-ray diffraction measurements up to 32.6 GPa and verified that BAs crystal remains stable in the cubic phase and that there is no phase transition under all pressures. We use pump–probe measurements based on ultrafast optics (Fig. 2c ) to perform in situ characterizations of the phonon properties under varied pressures and temperatures. The ultrafast set-up is configured for varied measurements, as discussed in the following. Fig. 2: Experimental set-up for in situ ultrafast optical measurements under high pressure. a , Schematic of DAC loaded with the sample for pump–probe measurements. b , BAs crystal in the DAC sample chamber from", "role": "user" }, { "content": "UCLA researchers and their colleagues have discovered a new physics principle governing how heat transfers through materials, and the finding contradicts the conventional wisdom that heat always moves faster as pressure increases. Up until now, the common belief has held true in recorded observations and scientific experiments involving different materials such as gases, liquids and solids. The researchers detailed their discovery in a study published last week by Nature. They have found that boron arsenide, which has already been viewed as a highly promising material for heat management and advanced electronics, also has a unique property. After reaching an extremely high pressure that is hundreds of times greater than the pressure found at the bottom of the ocean, boron arsenide's thermal conductivity actually begins to decrease. The results suggest that there might be other materials experiencing the same phenomenon under extreme conditions. The advance may also lead to novel materials that could be developed for smart energy systems with built-in \"pressure windows\" so that the system only switches on within a certain pressure range before shutting off automatically after reaching a maximum pressure point. \"This fundamental research finding shows that the general rule of pressure dependence starts to fail under extreme conditions,\" said study leader Yongjie Hu, an associate professor of mechanical and aerospace engineering at the UCLA Samueli School of Engineering. \"We expect that this study will not only provide a benchmark for potentially revising current understanding of heat movement, but it could also impact established modeling predictions for extreme conditions, such as those found in the Earth's interior, where direct measurements are not possible.\" According to Hu, the research breakthrough may also lead to retooling of standard techniques used in shock wave studies. Thermal conductivity measured from in-situ spectroscopy experiment showing the activity slowing down under high pressure. Credit: The H-Lab/UCLA Similar to how a sound wave travels through a rung bell, heat travels through most materials by way of atomic vibrations. As pressure squeezes closer together the atoms inside a material, it enables heat to move through the material faster, atom by atom, until its structure breaks down or transforms to another phase. That is not the case, however, with boron arsenide. The research team observed that heat started to move slower under extreme pressure, suggesting a possible interference caused by different ways the heat vibrates through the structure as pressure mounts, similar to overlapping waves canceling each other out. Such interference involves higher-order interactions that cannot be explained by textbook physics. The results also suggest that the thermal conductivity of minerals can reach a maximum after a certain pressure range. \"If applicable to planetary interiors, this may suggest a mechanism for an internal 'thermal window'—an internal layer within the planet where the mechanisms of heat flow are different from those below and above it,\" says co-author Abby Kavner, a professor of earth, planetary and space sciences at UCLA. \"A layer like this may generate interesting dynamic behavior in the interiors of large planets.\" To achieve the extremely high-pressure environment for their heat-transfer demonstrations, the researchers placed and compressed a boron arsenide crystal between two diamonds in a controlled chamber. They then utilized quantum theory and several advanced imaging techniques, including ultrafast optics and inelastic X-ray scattering measurements, to observe and validate the previously unknown phenomenon. Mechanical engineering graduate students Suixuan Li, Zihao Qin, Huan Wu and Man Li from Hu's research group are the study's co-lead authors. Other authors are Kavner, Martin Kunz of Lawrence Berkeley National Laboratory and Ahmet Alatas of Argonne National Laboratory. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract High pressure represents extreme environments and provides opportunities for materials discovery 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 . Thermal transport under high hydrostatic pressure has been investigated for more than 100 years and all measurements of crystals so far have indicated a monotonically increasing lattice thermal conductivity. Here we report in situ thermal transport measurements in the newly discovered semiconductor crystal boron arsenide, and observe an anomalous pressure dependence of the thermal conductivity. We use ultrafast optics, Raman spectroscopy and inelastic X-ray scattering measurements to examine the phonon bandstructure evolution of the optical and acoustic branches, as well as thermal conductivity under varied temperatures and pressures up to 32 gigapascals. Using atomistic theory, we attribute the anomalous high-pressure behaviour to competitive heat conduction channels from interactive high-order anharmonicity physics inherent to the unique phonon bandstructure. Our study verifies ab initio theory calculations and we show that the phonon dynamics—resulting from competing three-phonon and four-phonon scattering processes—are beyond those expected from classical models and seen in common materials. This work uses high-pressure spectroscopy combined with atomistic theory as a powerful approach to probe complex phonon physics and provide fundamental insights for understanding microscopic energy transport in materials of extreme properties. Main Understanding materials properties under high pressure is critical to many areas, from planetary science, geophysics and condensed-matter theory, to new chemical bonding and superconductivity 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 . Over 100 years of literature studies of high pressure thermal transport, from the first experiment 9 , to additional analysis 10 , 11 , 12 , 13 , the lattice thermal conductivity of crystals has been found to increase monotonically with hydrostatic pressure, unless a phase transition takes place. From a theoretical perspective 9 , 14 , the crystal lattice symmetry remains under hydrostatic pressure, and therefore such a universal increase of thermal conductivity can be well understood as a result of volume shrink under pressure that leads to increased atom density and atomic bonding strength. Classical theories 15 , 16 , 17 , 18 , 19 use parameterized models to link with the Debye temperature, bulk modulus and Grüneisen parameters to predict that thermal conductivity must increase with pressure 20 . Although a quantum mechanical picture for this governing rule is missing, it has shown consistency with all experimental reports in the literature so far. Here we measured high-pressure thermal transport in a recently discovered semiconductor material, cubic boron arsenide (BAs), and observed anomalous pressure dependence of the thermal conductivity that has not, to our knowledge, been measured in any other materials 9 , 10 , 11 , 12 , 13 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 (see summary in Fig. 1a ). On the basis of our experimental characterizations, and in combination with ab initio atomistic theory, we attribute this anomalous behaviour to competitive heat conduction channels that are inherent and arise from the unique bandstructure and high-order phonon physics. We verified ab initio calculations and the unique competition mechanisms from interactive high-order anharmonic scattering processes that are beyond understanding using classical theories. Fig. 1: Anomalous thermal conductivity of BAs under high pressure compared to literature studies. a , Summary of thermal conductivities of non-metal crystals as a function of hydrostatic pressure (CsCl 21 , CsBr 21 , NaCl 22 , NaI 22 , quartz 23 , mica 24 , ice 25 , MgSiO 3 26 , diamond 27 , MgO 28 , BN 29 , GaAs 30 ). Results from existing literature indicate a ubiquitous increase in lattice thermal conductivity under a single phase, whereas BAs is an exception. b , Zinc blende crystal structure of cubic BAs. c , High-resolution transmission electron microscopy image showing atomically resolved lattices of BAs. Scale bar, 2 nm. Full size image BAs with high thermal conductivity To experimentally measure the high-pressure transport behaviour, we synthesized high-quality, single-crystal BAs and performed ultrafast pump–probe measurements under high pressure and temperature dependence. Cubic BAs (Fig. 1b ) is a semiconductor that was recently discovered to have an ultrahigh thermal conductivity 31 , 32 , 33 , 34 beyond most common materials and demonstrates high promise for electronics thermal management 35 , 36 . Importantly, these recent theoretical studies indicate that BAs can be an exception and showcase material for higher-order phonon anharmonicity. Ab initio theory expects anomalous thermal transport at high pressure 37 ; however, this has yet to be experimentally explored. Here we synthesized BAs crystals through chemical vapour deposition in a customized three-zone furnace as described in our recent reports 32 , 38 . The high crystal quality of BAs was carefully verified with structural characterizations (Fig. 1c ) and measurement of a room-temperature (298 K) thermal conductivity of approximately 1,300 W m − 1 K −1 (ref. 32 ). Our experimental set-up uses a diamond anvil cell (DAC) to provide high pressure, which was installed in a cryostat chamber for temperature control; pump–probe and optical measurements are applied to measure the sample through the optical window (Fig. 2a ). The DAC can generate tens of GPa of pressure on the loaded BAs crystals, as shown in Fig. 2b . Importantly, we performed synchrotron X-ray diffraction measurements up to 32.6 GPa and verified that BAs crystal remains stable in the cubic phase and that there is no phase transition under all pressures. We use pump–probe measurements based on ultrafast optics (Fig. 2c ) to perform in situ characterizations of the phonon properties under varied pressures and temperatures. The ultrafast set-up is configured for varied measurements, as discussed in the following. Fig. 2: Experimental set-up for in situ ultrafast optical measurements under high pressure. a , Schematic of DAC loaded with the sample for pump–probe measurements. b , BAs crystal in the DAC sample chamber from<|im_end|> <|im_start|>assistant UCLA researchers and their colleagues have discovered a new physics principle governing how heat transfers through materials, and the finding contradicts the conventional wisdom that heat always moves faster as pressure increases. Up until now, the common belief has held true in recorded observations and scientific experiments involving different materials such as gases, liquids and solids. The researchers detailed their discovery in a study published last week by Nature. They have found that boron arsenide, which has already been viewed as a highly promising material for heat management and advanced electronics, also has a unique property. After reaching an extremely high pressure that is hundreds of times greater than the pressure found at the bottom of the ocean, boron arsenide's thermal conductivity actually begins to decrease. The results suggest that there might be other materials experiencing the same phenomenon under extreme conditions. The advance may also lead to novel materials that could be developed for smart energy systems with built-in "pressure windows" so that the system only switches on within a certain pressure range before shutting off automatically after reaching a maximum pressure point. "This fundamental research finding shows that the general rule of pressure dependence starts to fail under extreme conditions," said study leader Yongjie Hu, an associate professor of mechanical and aerospace engineering at the UCLA Samueli School of Engineering. "We expect that this study will not only provide a benchmark for potentially revising current understanding of heat movement, but it could also impact established modeling predictions for extreme conditions, such as those found in the Earth's interior, where direct measurements are not possible." According to Hu, the research breakthrough may also lead to retooling of standard techniques used in shock wave studies. Thermal conductivity measured from in-situ spectroscopy experiment showing the activity slowing down under high pressure. Credit: The H-Lab/UCLA Similar to how a sound wave travels through a rung bell, heat travels through most materials by way of atomic vibrations. As pressure squeezes closer together the atoms inside a material, it enables heat to move through the material faster, atom by atom, until its structure breaks down or transforms to another phase. That is not the case, however, with boron arsenide. The research team observed that heat started to move slower under extreme pressure, suggesting a possible interference caused by different ways the heat vibrates through the structure as pressure mounts, similar to overlapping waves canceling each other out. Such interference involves higher-order interactions that cannot be explained by textbook physics. The results also suggest that the thermal conductivity of minerals can reach a maximum after a certain pressure range. "If applicable to planetary interiors, this may suggest a mechanism for an internal 'thermal window'—an internal layer within the planet where the mechanisms of heat flow are different from those below and above it," says co-author Abby Kavner, a professor of earth, planetary and space sciences at UCLA. "A layer like this may generate interesting dynamic behavior in the interiors of large planets." To achieve the extremely high-pressure environment for their heat-transfer demonstrations, the researchers placed and compressed a boron arsenide crystal between two diamonds in a controlled chamber. They then utilized quantum theory and several advanced imaging techniques, including ultrafast optics and inelastic X-ray scattering measurements, to observe and validate the previously unknown phenomenon. Mechanical engineering graduate students Suixuan Li, Zihao Qin, Huan Wu and Man Li from Hu's research group are the study's co-lead authors. Other authors are Kavner, Martin Kunz of Lawrence Berkeley National Laboratory and Ahmet Alatas of Argonne National Laboratory. <|im_end|>

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2,076

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Amorphous silica-aluminas (ASAs) are widely used in acid-catalyzed C-H activation reactions and biomass conversions in large scale, which can be promoted by increasing the strength of surface Brønsted acid sites (BAS). Here, we demonstrate the first observation on a synergistic effect caused by two neighboring Al centers interacting with the same silanol group in flame-made ASAs with high Al content. The two close Al centers decrease the electron density on the silanol oxygen and thereby enhance its acidity, which is comparable to that of dealuminated zeolites, while ASAs with small or moderate Al contents provide mainly moderate acidity, much lower than that of zeolites. The ASAs with enhanced acidity exhibit outstanding performances in C–H bond activation of benzene and glucose dehydration to 5-hydroxymethylfurfural, simultaneously with an excellent calcination stability and resistance to leaching, and they offer an interesting potential for a wide range of acid and multifunctional catalysis. Introduction Silica-alumina materials, particularly crystalline zeolites and amorphous silica-aluminas (ASAs), are among the most popular solid acids that have been widely commercialized as efficient and environmentally friendly catalysts in the petrochemical industry 1 , and in bio-refinery 2 . These materials can provide Brønsted acid sites (BAS) with tunable density and strength, which facilitates the optimization of the surface acidity to promote a series of important industrial chemical reactions, through the formation of surface complexes or transition states by proton transfer from BAS to reactants 3 , 4 , 5 , 6 , such as to initialize C–H activation for hydrocarbon conversions 7 , 8 , 9 , 10 , 11 , 12 . Zeolites with strong Brønsted acidity, are of increasing importance in various sustainable processes, in the fields of biomass conversion, CO 2 capture and conversion, air-pollution remediation, and water purification 13 . For instance, zeolites can efficiently catalyze the redox disproportionative conversion of biomass-derived sugars into α-hydroxy acids 14 , and they are more active than ASA catalysts, albeit the latter facilitate improved molecular diffusion in the porous network 15 . The lower performance of ASA in many catalytic applications is widely attributed to their moderate Brønsted acidity 1 , which fostered recent works on the discovery of ASAs with increased Brønsted acidity 5 , aiming at expanding their applications in a broad range of fields. The formation of BAS in silica-aluminas is based on aluminum centers distributed in the silica framework or network 6 , 16 , 17 , 18 , 19 , 20 , as (i) a tetra-coordinated aluminum species (Al IV ), replacing a Si 4+ atom in the zeolite framework, can introduce a negatively charged framework oxygen to be balanced by a proton, resulting in bridging OH groups 6 , 17 , 18 , and (ii) the interaction between Al IV atoms and neighboring silanols in the silica network can provide acidic OH groups, acting as BAS in ASA 5 , 21 , 22 , 23 , 24 . In crystalline zeolites, it is well accepted that increasing the Si/Al ratio can enhance the BAS strength by increasing the overall electronegativity 25 . However, the amount of BAS (e.g. bridging SiOHAl groups) is then significantly reduced, owing to the fewer Al sites in the framework. Alternatively, the introduction of extra-framework cations, such as Al 3+ and La 3+ , via dealumination or ion exchange can significantly improve the BAS strength due to a synergistic effect between Lewis acid sites (LAS) and nearby BAS 4 , 17 . Those solid acids have been widely applied in gas-phase cracking, such as fluid catalytic cracking processes 26 . However, extra-framework cations can easily leach out from solid acids during the liquid-phase reactions 27 . Additionally, the synergy between two nearby Al sites in the zeolite framework is impossible due to the absence of Al-O-Al linkage based on Löwenstein’s rule 28 . Enhancing the BAS strength in ASAs still remains a significant challenge. Although a surface bridging SiOHAl model has been proposed for the formation of BAS on ASA 21 , 29 , the strength of the BAS on ASA is generally lower than that on crystalline zeolites 1 , since the amorphous structure of ASAs weakens the Al-O bonds (2.94–4.43 Å) 24 , compared to those in the crystalline zeolite framework (1.88–2.0 Å) 30 . Two models have been proposed to account for BAS generation in ASA: (i) a flexible coordination between the Al atom and the neighboring silanol oxygen atom 5 , 23 , and (ii) a pseudo-bridging silanol (PBS) with a nearby Al atom 24 , 31 , 32 . In both models, it was proposed that a Lewis acidic Al center interacts with a nearby silanol group, withdrawing electron density from the hydroxyl O atom to enhance the acid strength of the hydroxyl proton. Notably, these models mainly account for the formation of moderate BAS. Nevertheless, the presence of an additional Al species in the vicinity of the SiOH site may further enhance the acid strength of ASA via a synergistic effect, which has not yet been evidenced to the best of our knowledge. In this work, the synergy between Al species in the ASA network has been studied using solid-state NMR spectroscopy and atom probe tomography (APT). The 27 Al double-quantum single-quantum (DQ-SQ) through-space homonuclear correlation (D-HOMCOR) NMR experiments allow us to probe 27 Al- 27 Al proximities by applying recoupling sequences that restore the dipolar interaction between neighboring 27 Al spins 33 , 34 , 35 , 36 . Unlike for crystallized materials, the investigation of the location and distribution of Al atoms is impossible in ASAs by routine characterization methods, such as X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM), due to their amorphous structure. Atom probe tomography (APT) can provide quantitative three-dimensional (3D) information on elemental distributions in catalyst nanoparticles at the atomic scale 37 , 38 . It has recently been employed with sub-nanometer-scale resolution on zeolite-based catalysts to establish their structure–composition–property relationships 39 , 40 , 41 , 42 , 43 . Here, we apply APT for", "role": "user" }, { "content": "Researchers at the University of Sydney have created a new material that has the potential to reduce CO2 emissions released during the refinement process of crude oil by up to 28 percent. Silica-alumina materials are among the most common solid acids that have been widely commercialised as efﬁcient and environmentally-friendly catalysts in the petrochemical and bio-reﬁnery industries. In a world first, a team of researchers at the University of Sydney led by Associate Professor Jun Huang, have produced a new amorphous silica-alumina catalyst with stronger acidity than any other silica-alumina material created before. \"This new catalyst can significantly reduce the amount of CO2 emitted by oil refineries, which has the potential to make the fossil fuel industry much greener and cleaner,\" Associate Professor Huang from the Faculty of Engineering and Sydney Nano Institute said. A significant amount of carbon is emitted during the refinement of crude oil to produce products like petroleum, gasoline and diesel. Estimates suggest 20 to 30 percent of crude oil is transferred to waste and further burnt in the chemical process, making oil refineries the second largest source of greenhouse gases behind power plants. Credit: University of Sydney Silica-aluminas with strong Brønsted acidity—a substance that gives up or donates hydrogen ions (protons) in a chemical reaction—are becoming increasingly important to various sustainability processes, including the fields of biomass conversion, CO2 capture and conversion, air-pollution remediation, and water purification. \"Renewable energy is important to achieving a more sustainable energy supply, but the reality is that we will still be reliant on fossil fuels in the foreseeable future. Therefore, we should do all we can to make this industry more efficient and reduce its carbon footprint while we transition to renewable energy sources \"This new catalyst offers some exciting prospects, if it were to be adopted by the entire oil refinery industry, we could potentially see a reduction of over 20 percent in CO2 emissions during the oil refinement process. That's the equivalent of double Australia's crude oil consumption, over 2 million barrels of oil per day.\" \"The new catalyst also has the potential to develop the biomass industry. We can now look to biomass material like algae to be part of sustainable energy solutions.\" The next steps for the researchers are to work on manufacturing the new catalyst at a large, industrial scale. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Amorphous silica-aluminas (ASAs) are widely used in acid-catalyzed C-H activation reactions and biomass conversions in large scale, which can be promoted by increasing the strength of surface Brønsted acid sites (BAS). Here, we demonstrate the first observation on a synergistic effect caused by two neighboring Al centers interacting with the same silanol group in flame-made ASAs with high Al content. The two close Al centers decrease the electron density on the silanol oxygen and thereby enhance its acidity, which is comparable to that of dealuminated zeolites, while ASAs with small or moderate Al contents provide mainly moderate acidity, much lower than that of zeolites. The ASAs with enhanced acidity exhibit outstanding performances in C–H bond activation of benzene and glucose dehydration to 5-hydroxymethylfurfural, simultaneously with an excellent calcination stability and resistance to leaching, and they offer an interesting potential for a wide range of acid and multifunctional catalysis. Introduction Silica-alumina materials, particularly crystalline zeolites and amorphous silica-aluminas (ASAs), are among the most popular solid acids that have been widely commercialized as efficient and environmentally friendly catalysts in the petrochemical industry 1 , and in bio-refinery 2 . These materials can provide Brønsted acid sites (BAS) with tunable density and strength, which facilitates the optimization of the surface acidity to promote a series of important industrial chemical reactions, through the formation of surface complexes or transition states by proton transfer from BAS to reactants 3 , 4 , 5 , 6 , such as to initialize C–H activation for hydrocarbon conversions 7 , 8 , 9 , 10 , 11 , 12 . Zeolites with strong Brønsted acidity, are of increasing importance in various sustainable processes, in the fields of biomass conversion, CO 2 capture and conversion, air-pollution remediation, and water purification 13 . For instance, zeolites can efficiently catalyze the redox disproportionative conversion of biomass-derived sugars into α-hydroxy acids 14 , and they are more active than ASA catalysts, albeit the latter facilitate improved molecular diffusion in the porous network 15 . The lower performance of ASA in many catalytic applications is widely attributed to their moderate Brønsted acidity 1 , which fostered recent works on the discovery of ASAs with increased Brønsted acidity 5 , aiming at expanding their applications in a broad range of fields. The formation of BAS in silica-aluminas is based on aluminum centers distributed in the silica framework or network 6 , 16 , 17 , 18 , 19 , 20 , as (i) a tetra-coordinated aluminum species (Al IV ), replacing a Si 4+ atom in the zeolite framework, can introduce a negatively charged framework oxygen to be balanced by a proton, resulting in bridging OH groups 6 , 17 , 18 , and (ii) the interaction between Al IV atoms and neighboring silanols in the silica network can provide acidic OH groups, acting as BAS in ASA 5 , 21 , 22 , 23 , 24 . In crystalline zeolites, it is well accepted that increasing the Si/Al ratio can enhance the BAS strength by increasing the overall electronegativity 25 . However, the amount of BAS (e.g. bridging SiOHAl groups) is then significantly reduced, owing to the fewer Al sites in the framework. Alternatively, the introduction of extra-framework cations, such as Al 3+ and La 3+ , via dealumination or ion exchange can significantly improve the BAS strength due to a synergistic effect between Lewis acid sites (LAS) and nearby BAS 4 , 17 . Those solid acids have been widely applied in gas-phase cracking, such as fluid catalytic cracking processes 26 . However, extra-framework cations can easily leach out from solid acids during the liquid-phase reactions 27 . Additionally, the synergy between two nearby Al sites in the zeolite framework is impossible due to the absence of Al-O-Al linkage based on Löwenstein’s rule 28 . Enhancing the BAS strength in ASAs still remains a significant challenge. Although a surface bridging SiOHAl model has been proposed for the formation of BAS on ASA 21 , 29 , the strength of the BAS on ASA is generally lower than that on crystalline zeolites 1 , since the amorphous structure of ASAs weakens the Al-O bonds (2.94–4.43 Å) 24 , compared to those in the crystalline zeolite framework (1.88–2.0 Å) 30 . Two models have been proposed to account for BAS generation in ASA: (i) a flexible coordination between the Al atom and the neighboring silanol oxygen atom 5 , 23 , and (ii) a pseudo-bridging silanol (PBS) with a nearby Al atom 24 , 31 , 32 . In both models, it was proposed that a Lewis acidic Al center interacts with a nearby silanol group, withdrawing electron density from the hydroxyl O atom to enhance the acid strength of the hydroxyl proton. Notably, these models mainly account for the formation of moderate BAS. Nevertheless, the presence of an additional Al species in the vicinity of the SiOH site may further enhance the acid strength of ASA via a synergistic effect, which has not yet been evidenced to the best of our knowledge. In this work, the synergy between Al species in the ASA network has been studied using solid-state NMR spectroscopy and atom probe tomography (APT). The 27 Al double-quantum single-quantum (DQ-SQ) through-space homonuclear correlation (D-HOMCOR) NMR experiments allow us to probe 27 Al- 27 Al proximities by applying recoupling sequences that restore the dipolar interaction between neighboring 27 Al spins 33 , 34 , 35 , 36 . Unlike for crystallized materials, the investigation of the location and distribution of Al atoms is impossible in ASAs by routine characterization methods, such as X-ray diffraction (XRD) and high-resolution transmission electron microscopy (HRTEM), due to their amorphous structure. Atom probe tomography (APT) can provide quantitative three-dimensional (3D) information on elemental distributions in catalyst nanoparticles at the atomic scale 37 , 38 . It has recently been employed with sub-nanometer-scale resolution on zeolite-based catalysts to establish their structure–composition–property relationships 39 , 40 , 41 , 42 , 43 . Here, we apply APT for<|im_end|> <|im_start|>assistant Researchers at the University of Sydney have created a new material that has the potential to reduce CO2 emissions released during the refinement process of crude oil by up to 28 percent. Silica-alumina materials are among the most common solid acids that have been widely commercialised as efﬁcient and environmentally-friendly catalysts in the petrochemical and bio-reﬁnery industries. In a world first, a team of researchers at the University of Sydney led by Associate Professor Jun Huang, have produced a new amorphous silica-alumina catalyst with stronger acidity than any other silica-alumina material created before. "This new catalyst can significantly reduce the amount of CO2 emitted by oil refineries, which has the potential to make the fossil fuel industry much greener and cleaner," Associate Professor Huang from the Faculty of Engineering and Sydney Nano Institute said. A significant amount of carbon is emitted during the refinement of crude oil to produce products like petroleum, gasoline and diesel. Estimates suggest 20 to 30 percent of crude oil is transferred to waste and further burnt in the chemical process, making oil refineries the second largest source of greenhouse gases behind power plants. Credit: University of Sydney Silica-aluminas with strong Brønsted acidity—a substance that gives up or donates hydrogen ions (protons) in a chemical reaction—are becoming increasingly important to various sustainability processes, including the fields of biomass conversion, CO2 capture and conversion, air-pollution remediation, and water purification. "Renewable energy is important to achieving a more sustainable energy supply, but the reality is that we will still be reliant on fossil fuels in the foreseeable future. Therefore, we should do all we can to make this industry more efficient and reduce its carbon footprint while we transition to renewable energy sources "This new catalyst offers some exciting prospects, if it were to be adopted by the entire oil refinery industry, we could potentially see a reduction of over 20 percent in CO2 emissions during the oil refinement process. That's the equivalent of double Australia's crude oil consumption, over 2 million barrels of oil per day." "The new catalyst also has the potential to develop the biomass industry. We can now look to biomass material like algae to be part of sustainable energy solutions." The next steps for the researchers are to work on manufacturing the new catalyst at a large, industrial scale. <|im_end|>

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279, 93140, 1990, 1403, 14373, 1708, 6732, 304, 279, 14017, 337, 635, 12914, 374, 12266, 4245, 311, 279, 19821, 315, 1708, 24540, 65473, 72541, 3196, 389, 445, 3029, 17378, 12711, 753, 6037, 220, 1591, 662, 29757, 9151, 279, 10998, 8333, 304, 5871, 2170, 2103, 8625, 264, 5199, 8815, 13, 10541, 264, 7479, 77847, 3252, 12095, 47861, 2149, 1646, 706, 1027, 11223, 369, 279, 18488, 315, 10998, 389, 89700, 220, 1691, 1174, 220, 1682, 1174, 279, 8333, 315, 279, 10998, 389, 89700, 374, 8965, 4827, 1109, 430, 389, 64568, 483, 14017, 337, 3695, 220, 16, 1174, 2533, 279, 1097, 16751, 788, 6070, 315, 5871, 2170, 7621, 729, 279, 1708, 24540, 27460, 320, 17, 13, 6281, 4235, 19, 13, 3391, 80352, 8, 220, 1187, 1174, 7863, 311, 1884, 304, 279, 64568, 483, 14017, 337, 635, 12914, 320, 16, 13, 2421, 4235, 17, 13, 15, 80352, 8, 220, 966, 662, 9220, 4211, 617, 1027, 11223, 311, 2759, 369, 10998, 9659, 304, 89700, 25, 320, 72, 8, 264, 19303, 38793, 1990, 279, 1708, 19670, 323, 279, 42617, 5554, 39710, 24463, 19670, 220, 20, 1174, 220, 1419, 1174, 323, 320, 3893, 8, 264, 35850, 12, 16621, 3252, 5554, 39710, 320, 83609, 8, 449, 264, 14373, 1708, 19670, 220, 1187, 1174, 220, 2148, 1174, 220, 843, 662, 763, 2225, 4211, 11, 433, 574, 11223, 430, 264, 21256, 84903, 1708, 4219, 84261, 449, 264, 14373, 5554, 39710, 1912, 11, 84060, 17130, 17915, 505, 279, 17055, 87, 4010, 507, 19670, 311, 18885, 279, 13935, 8333, 315, 279, 17055, 87, 4010, 82586, 13, 2876, 2915, 11, 1521, 4211, 14918, 2759, 369, 279, 18488, 315, 24070, 10998, 13, 35053, 11, 279, 9546, 315, 459, 5217, 1708, 9606, 304, 279, 53851, 315, 279, 12095, 47861, 2816, 1253, 4726, 18885, 279, 13935, 8333, 315, 89700, 4669, 264, 80526, 4633, 2515, 11, 902, 706, 539, 3686, 1027, 69457, 311, 279, 1888, 315, 1057, 6677, 13, 763, 420, 990, 11, 279, 93140, 1990, 1708, 9606, 304, 279, 89700, 4009, 706, 1027, 20041, 1701, 6573, 21395, 452, 18953, 66425, 51856, 323, 19670, 22477, 10390, 5814, 320, 67062, 570, 578, 220, 1544, 1708, 2033, 12, 31548, 372, 3254, 12, 31548, 372, 320, 35, 48, 6354, 48, 8, 1555, 29047, 5105, 263, 9834, 26670, 320, 35, 11529, 1937, 53420, 8, 452, 18953, 21896, 2187, 603, 311, 22477, 220, 1544, 1708, 12, 220, 1544, 1708, 22267, 318, 1385, 555, 19486, 1421, 283, 12127, 24630, 430, 15301, 279, 24522, 7569, 16628, 1990, 42617, 220, 1544, 1708, 45858, 220, 1644, 1174, 220, 1958, 1174, 220, 1758, 1174, 220, 1927, 662, 27140, 369, 64568, 1534, 7384, 11, 279, 8990, 315, 279, 3813, 323, 8141, 315, 1708, 33299, 374, 12266, 304, 5871, 2170, 555, 14348, 60993, 5528, 11, 1778, 439, 1630, 30630, 3722, 16597, 320, 55, 37790, 8, 323, 1579, 64036, 18874, 17130, 92914, 320, 17526, 21695, 705, 4245, 311, 872, 1097, 16751, 788, 6070, 13, 40616, 22477, 10390, 5814, 320, 67062, 8, 649, 3493, 47616, 2380, 33520, 320, 18, 35, 8, 2038, 389, 62235, 43785, 304, 51483, 94753, 520, 279, 25524, 5569, 220, 1806, 1174, 220, 1987, 662, 1102, 706, 6051, 1027, 20011, 449, 1207, 5392, 276, 21037, 13230, 11175, 389, 14017, 337, 635, 6108, 51483, 82, 311, 5813, 872, 6070, 4235, 77907, 4235, 3784, 12135, 220, 2137, 1174, 220, 1272, 1174, 220, 3174, 1174, 220, 2983, 1174, 220, 3391, 662, 5810, 11, 584, 3881, 362, 2898, 369, 128257, 198, 128256, 78191, 198, 60210, 520, 279, 3907, 315, 21972, 617, 3549, 264, 502, 3769, 430, 706, 279, 4754, 311, 8108, 7432, 17, 20748, 6004, 2391, 279, 74013, 1920, 315, 35750, 5707, 555, 709, 311, 220, 1591, 3346, 13, 8211, 3074, 19308, 372, 2259, 7384, 527, 4315, 279, 1455, 4279, 6573, 33969, 430, 617, 1027, 13882, 8518, 4147, 439, 31469, 171, 71831, 12575, 323, 57340, 22658, 51483, 82, 304, 279, 6896, 299, 32056, 323, 17332, 5621, 171, 71831, 77, 727, 19647, 13, 763, 264, 1917, 1176, 11, 264, 2128, 315, 12074, 520, 279, 3907, 315, 21972, 6197, 555, 33468, 17054, 12044, 59509, 11, 617, 9124, 264, 502, 1097, 16751, 788, 77889, 19308, 372, 2259, 51483, 449, 16643, 98026, 1109, 904, 1023, 77889, 19308, 372, 2259, 3769, 3549, 1603, 13, 330, 2028, 502, 51483, 649, 12207, 8108, 279, 3392, 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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract When a physical system is governed by statistical or dynamical equations possessing certain symmetries, its stationary states can be classified into phases according to which of those symmetries are preserved, and which are broken 1 , 2 . Near equilibrium, the properties of the system’s collective excitations reflect the symmetries of the underlying phase and thereby provide means for detecting these phases 3 , 4 . Here, we show that, in driven systems, the collective modes may take on a separate life, exhibiting their own spontaneous symmetry-breaking phenomena independent of the underlying equilibrium phase. We illustrate this principle by demonstrating a mechanism through which a non-magnetic interacting metal subjected to a linearly polarized driving field can spontaneously magnetize. The strong internal a.c. fields of the metal driven close to its plasmonic resonance 5 , 6 enable Berryogenesis: the spontaneous generation of a self-induced Bloch band Berry flux. The self-induced Berry flux supports and is sustained by a chiral circulating plasmonic motion that breaks the mirror symmetry of the system. This non-equilibrium phase transition may be of either continuous or discontinuous type. Berryogenesis can occur in a wide variety of multiband metals with high-quality plasmons, as available in present-day graphene devices 7 , 8 , 9 . Main Interacting many-body systems may exhibit collective modes of excitation whose emergent properties are unlike those of the constituent particles of the system. Importantly, such modes may host strong internal fields associated with the restoring force underlying the system’s collective oscillations. For example, plasmons have recently gained wide attention for their ability to resonantly enhance applied electric fields by many orders of magnitude 5 , 6 . Here we propose that new collective mode phases may arise due to feedback in which a system’s internal fields modify its microscopic properties, in turn altering its response to the driving field. Time-dependent driving by laser or microwave fields has recently emerged as a powerful tool for dynamically controlling the non-equilibrium properties of quantum matter 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 . As we discuss here, such fields provide the means to access non-equilibrium spontaneous symmetry breaking associated with novel collective mode phase transitions. To demonstrate this principle, we show how feedback due to the internal fields of a metallic disk driven at a frequency close to its natural dipole resonance (Fig. 1a ) gives rise to multistability and spontaneous symmetry breaking. When excited, the resonance may produce rotating fields that modify the system’s Bloch band Berry curvature (Fig. 1b ). The resulting amplitude-dependent Berry flux splits the resonance for right- and left-handed polarizations. This feedback between field strength, field chirality and Berry flux ultimately leads to a phenomenon we call Berryogenesis: the spontaneous appearance of a chiral circulating plasmonic motion together with a non-vanishing Berry flux in a non-magnetic material driven by a linearly polarized field (Fig. 1c ). Fig. 1: Spontaneous generation of Berry flux via plasmonic internal fields. a , When excited, the dipole mode of a metallic disk hosts an internal electric field, E int ( t ), that oscillates at the drive angular frequency, ω d . The corresponding motion is decomposed into right- and left-circulating amplitudes, \${\\cal{Z}}_ +\$ and \${\\cal{Z}}_ -\$ , respectively. b , Electronic Bloch functions at the Fermi energy E F (represented by pseuodospinors for graphene, in valleys K and K′) are dressed by an off-resonant rotating electric field with ħω d < 2 E F ; the dressing gently cants the pseudospins out of the equatorial plane. In this way, a.c. internal fields dynamically alter the system’s electronic properties, giving rise to feedback. c , Stability diagram, with stable (unstable) solutions of equation ( 5 ) indicated by black solid (red dashed) lines. For small amplitudes of a linearly polarized drive, the response is linearly polarized ( \$\\overline {\\cal{F}} = 0\$ ). Above threshold, the linearly polarized solution becomes unstable and the system spontaneously develops a right- or left-handed circulation. Parameters: E F = 160 meV, ħω d = 100 meV, ħω 0 = 100.125 meV, Q = 75. Full size image The threshold driving amplitudes that are needed to induce Berryogenesis are modest, and can be achieved in current high-quality graphene devices 7 , 8 , 9 with readily available terahertz to mid-infrared drives. While we use graphene for illustration due to its simplicity and favourability for near-term experiments, the mechanism we discuss is general and may apply to a wide variety of materials (for example, transition metal dichalcogenides and multiband semimetals). The ease with which large plasmon-enhanced internal fields can be accessed in graphene 6 , 9 makes it a natural platform for plasmonic non-equilibrium spontaneous symmetry breaking. We now demonstrate how a non-vanishing Berry flux can be induced in a non-magnetic metal subjected to an off-resonant a.c. field. As a concrete example, we consider electrons in graphene at finite doping, with Fermi energy E F > 0. Taking E F as the natural energy scale, we express the Hamiltonian for electrons in the K valley of graphene as $${\\cal{H}}_{\\rm{K}}(t) = E_{\\rm{F}}[\\tilde{\\mathbf{k}} - \\tilde{\\mathbf{A}}(t)]\\cdot {\\boldsymbol{\\sigma }},\\quad \\tilde{\\mathbf{A}}(t) = \\frac{{ev}}{{cE_{\\rm{F}}}}{\\mathbf{A}}(t)$$ (1) where v is the Fermi velocity of graphene, c is the speed of light, − e < 0 is the electron charge, σ = ( σ x , σ y ) is a vector of Pauli matrices and \$\\tilde{\\mathbf{k}} = {\\mathbf{k}}/k_{\\rm{F}}\$ is the normalized 2D wavevector, with ħvk F = E F . The vector potential A ( t ) describes the (time-varying) electromagnetic field. Importantly, A ( t ) may arise both due to an externally applied driving field, and due to time-dependent internal fields of the system when it is driven out of equilibrium. The Hamiltonian \${\\cal{H}}_{{\\rm{K}}^\\prime}(t)\$ for electrons in the K′ valley is the same as that in equation ( 1 ), with σ x → − σ x in σ . For illustration, we focus on a monochromatic field, A (", "role": "user" }, { "content": "Pioneering physicists from the University of Copenhagen and Nanyang Technological University in Singapore have discovered a way to get non-magnetic materials to make themselves magnetic by way of laser light. The phenomenon may also be used to endow many other materials with new properties. The intrinsic properties of materials arise from their chemistry—from the types of atoms that are present and the way that they are arranged. These factors determine, for example, how well a material may conduct electricity or whether or not it is magnetic. Therefore, the traditional route for changing or achieving new material properties has been through chemistry. Now, a pair of researchers from the University of Copenhagen and Nanyang Technological University in Singapore have discovered a new physical route to the transformation of material properties: when stimulated by laser light, a metal can transform itself from within and suddenly acquire new properties. \"For several years, we have been looking into how to transform the properties of a matter by irradiating it with certain types of light. What's new is that not only can we change the properties using light, we can trigger the material to change itself, from the inside out, and emerge into a new phase with completely new properties. For instance, a non-magnetic metal can suddenly transform into a magnet,\" explains Associate Professor Mark Rudner, a researcher at the University of Copenhagen's Niels Bohr Institute. He and colleague Justin Song of Nanyang Technological University in Singapore made the discovery that is now published in Nature Physics. The idea of using light to transform the properties of a material is not novel in itself. But up to now, researchers have only been capable of manipulating the properties already found in a material. Giving a metal its own \"separate life,\" allowing it to generate its own new properties, has never been seen before. By way of theoretical analysis, the researchers have succeeded in proving that when a non-magnetic metallic disk is irradiated with linearly polarized light, circulating electric currents and hence magnetism can spontaneously emerge in the disk. Researchers use so-called plasmons (a type of electron wave) found in the material to change its intrinsic properties. When the material is irradiated with laser light, plasmons in the metal disk begin to rotate in either a clockwise or counterclockwise direction. However, these plasmons change the quantum electronic structure of a material, which simultaneously alters their own behavior, catalyzing a feedback loop. Feedback from the plasmons' internal electric fields eventually causes the plasmons to break the intrinsic symmetry of the material and trigger an instability toward self-rotation that causes the metal to become magnetic. Technique can produce properties 'on demand' According to Mark Rudner, the new theory pries open an entire new mindset and most likely, a wide range of applications: \"It is an example of how the interaction between light and material can be used to produce certain properties in a material 'on demand.' It also paves the way for a multitude of uses, because the principle is quite general and can work on many types of materials. We have demonstrated that we can transform a material into a magnet. We might also be able to change it into a superconductor or something entirely different,\" says Rudner. He adds: \"You could call it 21st century alchemy. In the Middle Ages, people were fascinated by the prospect of transforming lead into gold. Today, we aim to get one material to behave like another by stimulating it with a laser.\" Among the possibilities, Rudner suggests that the principle could be useful in situations where one needs a material to alternate between behaving magnetically and not. It could also prove useful in opto-electronics—where, for example, light and electronics are combined for fiber-internet and sensor development. The researchers' next steps are to expand the catalog of properties that can be altered in analogous ways, and to help stimulate their experimental investigation and utilization. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract When a physical system is governed by statistical or dynamical equations possessing certain symmetries, its stationary states can be classified into phases according to which of those symmetries are preserved, and which are broken 1 , 2 . Near equilibrium, the properties of the system’s collective excitations reflect the symmetries of the underlying phase and thereby provide means for detecting these phases 3 , 4 . Here, we show that, in driven systems, the collective modes may take on a separate life, exhibiting their own spontaneous symmetry-breaking phenomena independent of the underlying equilibrium phase. We illustrate this principle by demonstrating a mechanism through which a non-magnetic interacting metal subjected to a linearly polarized driving field can spontaneously magnetize. The strong internal a.c. fields of the metal driven close to its plasmonic resonance 5 , 6 enable Berryogenesis: the spontaneous generation of a self-induced Bloch band Berry flux. The self-induced Berry flux supports and is sustained by a chiral circulating plasmonic motion that breaks the mirror symmetry of the system. This non-equilibrium phase transition may be of either continuous or discontinuous type. Berryogenesis can occur in a wide variety of multiband metals with high-quality plasmons, as available in present-day graphene devices 7 , 8 , 9 . Main Interacting many-body systems may exhibit collective modes of excitation whose emergent properties are unlike those of the constituent particles of the system. Importantly, such modes may host strong internal fields associated with the restoring force underlying the system’s collective oscillations. For example, plasmons have recently gained wide attention for their ability to resonantly enhance applied electric fields by many orders of magnitude 5 , 6 . Here we propose that new collective mode phases may arise due to feedback in which a system’s internal fields modify its microscopic properties, in turn altering its response to the driving field. Time-dependent driving by laser or microwave fields has recently emerged as a powerful tool for dynamically controlling the non-equilibrium properties of quantum matter 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 . As we discuss here, such fields provide the means to access non-equilibrium spontaneous symmetry breaking associated with novel collective mode phase transitions. To demonstrate this principle, we show how feedback due to the internal fields of a metallic disk driven at a frequency close to its natural dipole resonance (Fig. 1a ) gives rise to multistability and spontaneous symmetry breaking. When excited, the resonance may produce rotating fields that modify the system’s Bloch band Berry curvature (Fig. 1b ). The resulting amplitude-dependent Berry flux splits the resonance for right- and left-handed polarizations. This feedback between field strength, field chirality and Berry flux ultimately leads to a phenomenon we call Berryogenesis: the spontaneous appearance of a chiral circulating plasmonic motion together with a non-vanishing Berry flux in a non-magnetic material driven by a linearly polarized field (Fig. 1c ). Fig. 1: Spontaneous generation of Berry flux via plasmonic internal fields. a , When excited, the dipole mode of a metallic disk hosts an internal electric field, E int ( t ), that oscillates at the drive angular frequency, ω d . The corresponding motion is decomposed into right- and left-circulating amplitudes, ${\cal{Z}}_ +$ and ${\cal{Z}}_ -$ , respectively. b , Electronic Bloch functions at the Fermi energy E F (represented by pseuodospinors for graphene, in valleys K and K′) are dressed by an off-resonant rotating electric field with ħω d < 2 E F ; the dressing gently cants the pseudospins out of the equatorial plane. In this way, a.c. internal fields dynamically alter the system’s electronic properties, giving rise to feedback. c , Stability diagram, with stable (unstable) solutions of equation ( 5 ) indicated by black solid (red dashed) lines. For small amplitudes of a linearly polarized drive, the response is linearly polarized ( $\overline {\cal{F}} = 0$ ). Above threshold, the linearly polarized solution becomes unstable and the system spontaneously develops a right- or left-handed circulation. Parameters: E F = 160 meV, ħω d = 100 meV, ħω 0 = 100.125 meV, Q = 75. Full size image The threshold driving amplitudes that are needed to induce Berryogenesis are modest, and can be achieved in current high-quality graphene devices 7 , 8 , 9 with readily available terahertz to mid-infrared drives. While we use graphene for illustration due to its simplicity and favourability for near-term experiments, the mechanism we discuss is general and may apply to a wide variety of materials (for example, transition metal dichalcogenides and multiband semimetals). The ease with which large plasmon-enhanced internal fields can be accessed in graphene 6 , 9 makes it a natural platform for plasmonic non-equilibrium spontaneous symmetry breaking. We now demonstrate how a non-vanishing Berry flux can be induced in a non-magnetic metal subjected to an off-resonant a.c. field. As a concrete example, we consider electrons in graphene at finite doping, with Fermi energy E F > 0. Taking E F as the natural energy scale, we express the Hamiltonian for electrons in the K valley of graphene as $${\cal{H}}_{\rm{K}}(t) = E_{\rm{F}}[\tilde{\mathbf{k}} - \tilde{\mathbf{A}}(t)]\cdot {\boldsymbol{\sigma }},\quad \tilde{\mathbf{A}}(t) = \frac{{ev}}{{cE_{\rm{F}}}}{\mathbf{A}}(t)$$ (1) where v is the Fermi velocity of graphene, c is the speed of light, − e < 0 is the electron charge, σ = ( σ x , σ y ) is a vector of Pauli matrices and $\tilde{\mathbf{k}} = {\mathbf{k}}/k_{\rm{F}}$ is the normalized 2D wavevector, with ħvk F = E F . The vector potential A ( t ) describes the (time-varying) electromagnetic field. Importantly, A ( t ) may arise both due to an externally applied driving field, and due to time-dependent internal fields of the system when it is driven out of equilibrium. The Hamiltonian ${\cal{H}}_{{\rm{K}}^\prime}(t)$ for electrons in the K′ valley is the same as that in equation ( 1 ), with σ x → − σ x in σ . For illustration, we focus on a monochromatic field, A (<|im_end|> <|im_start|>assistant Pioneering physicists from the University of Copenhagen and Nanyang Technological University in Singapore have discovered a way to get non-magnetic materials to make themselves magnetic by way of laser light. The phenomenon may also be used to endow many other materials with new properties. The intrinsic properties of materials arise from their chemistry—from the types of atoms that are present and the way that they are arranged. These factors determine, for example, how well a material may conduct electricity or whether or not it is magnetic. Therefore, the traditional route for changing or achieving new material properties has been through chemistry. Now, a pair of researchers from the University of Copenhagen and Nanyang Technological University in Singapore have discovered a new physical route to the transformation of material properties: when stimulated by laser light, a metal can transform itself from within and suddenly acquire new properties. "For several years, we have been looking into how to transform the properties of a matter by irradiating it with certain types of light. What's new is that not only can we change the properties using light, we can trigger the material to change itself, from the inside out, and emerge into a new phase with completely new properties. For instance, a non-magnetic metal can suddenly transform into a magnet," explains Associate Professor Mark Rudner, a researcher at the University of Copenhagen's Niels Bohr Institute. He and colleague Justin Song of Nanyang Technological University in Singapore made the discovery that is now published in Nature Physics. The idea of using light to transform the properties of a material is not novel in itself. But up to now, researchers have only been capable of manipulating the properties already found in a material. Giving a metal its own "separate life," allowing it to generate its own new properties, has never been seen before. By way of theoretical analysis, the researchers have succeeded in proving that when a non-magnetic metallic disk is irradiated with linearly polarized light, circulating electric currents and hence magnetism can spontaneously emerge in the disk. Researchers use so-called plasmons (a type of electron wave) found in the material to change its intrinsic properties. When the material is irradiated with laser light, plasmons in the metal disk begin to rotate in either a clockwise or counterclockwise direction. However, these plasmons change the quantum electronic structure of a material, which simultaneously alters their own behavior, catalyzing a feedback loop. Feedback from the plasmons' internal electric fields eventually causes the plasmons to break the intrinsic symmetry of the material and trigger an instability toward self-rotation that causes the metal to become magnetic. Technique can produce properties 'on demand' According to Mark Rudner, the new theory pries open an entire new mindset and most likely, a wide range of applications: "It is an example of how the interaction between light and material can be used to produce certain properties in a material 'on demand.' It also paves the way for a multitude of uses, because the principle is quite general and can work on many types of materials. We have demonstrated that we can transform a material into a magnet. We might also be able to change it into a superconductor or something entirely different," says Rudner. He adds: "You could call it 21st century alchemy. In the Middle Ages, people were fascinated by the prospect of transforming lead into gold. Today, we aim to get one material to behave like another by stimulating it with a laser." Among the possibilities, Rudner suggests that the principle could be useful in situations where one needs a material to alternate between behaving magnetically and not. It could also prove useful in opto-electronics—where, for example, light and electronics are combined for fiber-internet and sensor development. The researchers' next steps are to expand the catalog of properties that can be altered in analogous ways, and to help stimulate their experimental investigation and utilization. <|im_end|>

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2,294

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Malaria, caused by the protozoan Plasmodium , is a devastating mosquito-borne disease with the potential to affect nearly half the world's population 1 . Despite mounting substantial T and B cell responses, humans fail to efficiently control blood-stage malaria or develop sterilizing immunity to reinfections 2 . Although forkhead box P3 (FOXP3) + CD4 + regulatory T (T reg ) cells form a part of these responses 3 , 4 , 5 , their influence remains disputed and their mode of action is unknown. Here we show that T reg cells expand in both humans and mice in blood-stage malaria and interfere with conventional T helper cell responses and follicular T helper (T FH )–B cell interactions in germinal centers. Mechanistically, T reg cells function in a critical temporal window to impede protective immunity through cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4). Targeting T reg cells or CTLA-4 in this precise window accelerated parasite clearance and generated species-transcending immunity to blood-stage malaria in mice. Our study uncovers a critical mechanism of immunosuppression associated with blood-stage malaria that delays parasite clearance and prevents development of potent adaptive immunity to reinfection. These data also reveal a temporally discrete and potentially therapeutically amenable functional role for T reg cells and CTLA-4 in limiting antimalarial immunity. Main CD4 + T helper cells are essential for control of malaria in mouse models of the disease 6 . We show that the frequencies of activated T helper cells increased in mice with malaria and in a cohort of Malian children ( n = 15; Supplementary Table 1 ) diagnosed with febrile malaria ( Supplementary Figs. 1c and 2 ). T helper cell depletion after established infection with the normally nonlethal Plasmodium yoelii 17XNL ( P. yoelii ) resulted in uncontrolled parasitemia and death in infected mice ( Supplementary Fig. 1a,b ). Unlike CD4 + T cell responses to most other infections in mice (for example, Listeria monocytogenes ), expansion of pathogen-specific T helper cells (defined as CD49d + CD11a hi CD4 + ) 7 in response to P. yoelii infection is distinctly biphasic. Specifically, the frequencies and total numbers of pathogen-specific T helper cells increased after P. yoelii infection and then temporarily fell or plateaued before rising again prior to parasite clearance ( Supplementary Fig. 1d–f ). Although the mechanisms underlying this unique hiatus in T helper cell expansion were unknown, we speculated that it was due to the widely acknowledged immunosuppression that occurs in blood-stage malaria 5 . This notion was reinforced by our observation of increased numbers and frequencies of FOXP3 + CD4 + T reg cells, a key immunosuppressive cell population, during the blood stage of malaria in humans and mice ( Fig. 1a–d ). We observed that higher parasite densities were associated with higher frequencies of T reg cells in humans; also, chloroquine treatment to decrease parasitemia reduced T reg cell frequencies and increased T helper cell frequencies in mice ( Supplementary Fig. 3a–c ). The role of T reg cells in malaria remains controversial 5 , 8 , 9 : some independent studies suggest that T reg cells suppress protection 10 , 11 , 12 , while others imply that they enhance it 13 , 14 . Importantly, these studies manipulated T reg cells (most of which express CD25) before or shortly after Plasmodium infection using anti-CD25 antibody–mediated depletion 10 , 11 , 13 , 14 , 15 or the (more precise) Foxp3 –diptheria toxin receptor (DTR) system 16 , 17 . Although variations in approaches may underlie these inconsistencies, the timing of T reg cell targeting could be a critical consideration for understanding malaria. Here we observed that expansion of T reg cells in P. yoelii –infected mice preceded or coincided with the hiatus in T helper cell responses, suggesting a causal relationship beginning ∼ 10 days post infection (d.p.i.). To test this proposition, we depleted both circulating and lymphoid 18 , 19 , 20 T reg cells in P. yoelii –infected Foxp3 -DTR ( Supplementary Fig. 4a,b ) and C57BL/6 ( Supplementary Fig. 5a ) mice with diphtheria toxin 21 and anti-CD25 antibody 10 , respectively, beginning at 9 d.p.i. T reg depletion interrupted the hiatus in T helper cell responses, restored expansion of Plasmodium -specific T helper cells and substantially accelerated control of P. yoelii infection ( Fig. 1e,f and Supplementary Fig. 5b,c ). In contrast, T reg depletion at 0 and 2 d.p.i. in Foxp3 -DTR mice resulted in the death of P. yoelii –infected mice ( Supplementary Fig. 4c ). Figure 1: T reg cells expand and modulate T helper cell responses and immunity to malaria. ( a ) Longitudinal frequencies of FOXP3 + T reg cells among the total CD4 + T cell population in peripheral blood mononuclear cells (PBMCs) from a cohort of children in Mali ( Supplementary Table 1 ) before, during, and after infection with acute febrile malaria. Each connected line indicates a unique subject. ( b ) Kinetics of activated (CD49d + CD11a hi ) T helper or FOXP3 + T reg cell frequencies among the total CD4 + T cell population in circulation in P. yoelii –infected C57BL/6 mice. ( c , d ) Absolute numbers of FOXP3 + CD4 + T reg cells in spleen ( c ) and lymph nodes (LN) ( d ) at the indicated time points in P. yoelii –infected C57BL/6 mice. ( e , f ) Frequencies of activated CD4 + T helper cells among the total CD4 + T cell population in circulation ( e ) and parasitemia ( f ) at various time points following infection with P. yoelii in C57BL/6 or Foxp3 -DTR mice treated with diphtheria toxin (Rx DT) or PBS (Rx PBS) at 9 and 11 d.p.i., as indicated by the pink label below the x axis. All experimental data represent one of at least three separate experiments with five mice per group and are presented as mean ± s.e.m. Statistical analysis was performed by comparing the indicated groups using one-way ANOVA", "role": "user" }, { "content": "A molecule that prevents the immune system from attacking cancer may play a similar role with malaria. A new study by researchers at the University of Iowa Carver College of Medicine shows that targeting the molecule at the right time during infection allows mice to quickly clear malaria. Importantly the treated mice also develop lasting immunity to malaria. The molecule is a checkpoint protein called anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). In cancer, CTLA-4 is a target for new immunotherapy drugs that prevent cancer from supressing the immune system. In the new study, published in Nature Medicine, the UI researchers show that CTLA-4 is expressed and released by a subset of immune cells called regulatory T cells (Tregs) that are involved in immune suppression. \"People have long known that malaria is associated with a huge immunosupressive response, but no one knew the mechanism,\" say Samarchith (Sam) Kurup, PhD, a UI assistant research scientist and first author on the study. \"The CTLA-4 molecule interferes with appropriate immune activation,\" explains John Harty, PhD, UI professor of microbiology and immunology and senior study author. \"Specifically, it interferes with the function of several types of T helper cells whose job it is to drive immune responses against malaria.\" Malaria is a serious, life-threatening disease across most of the developing world. There are 200 million cases of malaria each year and almost 500,000 malaria-related deaths. The malaria parasite, which is transmitted by mosquito bites, persists in the blood for long periods. Critically, although there are drugs that can cure the infection, humans do not develop immunity to infection, which means a person can get reinfected with malaria year after year. Multiple infections eventually make a person resistant to the severity of the disease symptom, but when the person - usually a young child - experiences their first few infections, the disease can be deadly. Malaria meddles with immune responses In most infectious diseases, a group of immune cells called T helper cells increases in number, cooperates with B cells to make antibodies that clear the infection, then leaves behind memory T and B cells to defend against reinfection with the same pathogen. That doesn't happen in malaria. Instead, there is a period where the T helper cell expansion stalls. During that critical time period, the UI reseachers showed that the Treg population increases. \"Our observation that the Tregs went up when the T helper cells stopped going up showed a timing relationship that suggested the possibility of a functional relationship,\" says Harty, who also is a UI professor of pathology. When the UI team eliminated Treg cells in mice with blood-stage malaria infections, the expansion of the T helper cells did not plateau; they kept expanding and cleared the infection faster. Further experiments revealed that Tregs suppress the normal immune response by continuously expressing and shedding the CTLA-4 molecule, which interferes with the normal immune function of T helper cells. It also interferes with another set of T helper cells (follicular T helper cells) whose job it is to help make antibodies against malaria. Malaria prevents the host body (human or mouse) from developing lasting immunity. A new University of Iowa study, led by microbiology professor John Harty, has homed in on a potential culprit of this immunosuppression. The molecule, CTLA-4, is produced by a type of immune cell called a Treg cell. Blocking CTLA-4 at the right time during blood-stage infection allows mice to quickly clear malaria. Importantly the treated mice also develop lasting immunity to malaria.The video, captured with intravital confocal immunofluorescence microscopy, shows Treg cells (green) delivering CTLA-4 to B cell (blue/ magenta)-Helper T cell (red) clusters in the spleen of a mouse. The CTLA-4 molecule inhibits efficient production of antibodies against malaria.If this pathway works in humans as it does in mice, blocking CTLA-4 might be a way to improve malaria treatment and boost immunity to reinfection. The study was published Sept. 11 online in Nature Medicine. Credit: Samarchith Kurup/ Scott Anthony, dept. of Microbiology and Immunology, University of Iowa. \"Tregs meddle with these processes through the CTLA-4 molecule,\" Harty says. Blocking CTLA-4 at the right time during blood-stage infection cured mice of the infection and promoted immunity against reinfections. It even provided protection against challenge from another deadlier malaria parasite. Previous work in Harty's lab found that blocking a different checkpoint protein called PDL1 at a later point in malaria infection also improved the host immune response to malaria. The new work shows that the CTLA-4 pathway is in play at an earlier stage in malaria infection, and shows that the two pathways don't overlap. \"Both pathways impede the appropriate activation of the immune system, but in different ways, targeting different interactions, and at different time points,\" Harty says. \"The more we understand how and when these pathways are operating, the better chance we have to rescue them.\" Of mice and men Harty and Kurup are quick to point out that findings in mice often do not translate easily to human patients, but access to unique human data may help determine if the CTLA-4 findings are relevant in humans. For about a decade, Harty has collaborated with Peter Crompton, an National Institutes of Health (NIH) scientist who works with malaria patients in the African country of Mali. The clinic where Crompton's colleagues work tracks around 700 children year after year. During each wet season, when malaria is endemic, children are diagnosed and treated for malaria, and the team collects blood samples for immunological studies. \"This has been a very potent resource for us,\" Harty says. \"When we look at blood samples from the same infection timeframe that we investigated in the mouse, we see some of the same immune changes (expansion of Tregs and upregulation of CTLA-4) are also happening in humans. That does not prove that everything is the same, but at the level of resolution that we have, there is some reasonable similarity.\" \"Practically, we have shown there is a pathway that can be targeted, and although CTLA-4 blockers that are available as cancer immunotherapies are too costly and impractical to use for malaria, there may be other parts of this immunological pathway that could be targeted using other drugs or small molecules, to produce the same effect,\" Kurup says. The malaria parasite is adept at developing resistance to antimalarial medicines that target it directly, as has happened time and time again. The UI approach focuses on modulating or improving the immune response of the host. \"The parasite can't become resistant to that,\" Harty says. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Malaria, caused by the protozoan Plasmodium , is a devastating mosquito-borne disease with the potential to affect nearly half the world's population 1 . Despite mounting substantial T and B cell responses, humans fail to efficiently control blood-stage malaria or develop sterilizing immunity to reinfections 2 . Although forkhead box P3 (FOXP3) + CD4 + regulatory T (T reg ) cells form a part of these responses 3 , 4 , 5 , their influence remains disputed and their mode of action is unknown. Here we show that T reg cells expand in both humans and mice in blood-stage malaria and interfere with conventional T helper cell responses and follicular T helper (T FH )–B cell interactions in germinal centers. Mechanistically, T reg cells function in a critical temporal window to impede protective immunity through cytotoxic-T-lymphocyte-associated protein-4 (CTLA-4). Targeting T reg cells or CTLA-4 in this precise window accelerated parasite clearance and generated species-transcending immunity to blood-stage malaria in mice. Our study uncovers a critical mechanism of immunosuppression associated with blood-stage malaria that delays parasite clearance and prevents development of potent adaptive immunity to reinfection. These data also reveal a temporally discrete and potentially therapeutically amenable functional role for T reg cells and CTLA-4 in limiting antimalarial immunity. Main CD4 + T helper cells are essential for control of malaria in mouse models of the disease 6 . We show that the frequencies of activated T helper cells increased in mice with malaria and in a cohort of Malian children ( n = 15; Supplementary Table 1 ) diagnosed with febrile malaria ( Supplementary Figs. 1c and 2 ). T helper cell depletion after established infection with the normally nonlethal Plasmodium yoelii 17XNL ( P. yoelii ) resulted in uncontrolled parasitemia and death in infected mice ( Supplementary Fig. 1a,b ). Unlike CD4 + T cell responses to most other infections in mice (for example, Listeria monocytogenes ), expansion of pathogen-specific T helper cells (defined as CD49d + CD11a hi CD4 + ) 7 in response to P. yoelii infection is distinctly biphasic. Specifically, the frequencies and total numbers of pathogen-specific T helper cells increased after P. yoelii infection and then temporarily fell or plateaued before rising again prior to parasite clearance ( Supplementary Fig. 1d–f ). Although the mechanisms underlying this unique hiatus in T helper cell expansion were unknown, we speculated that it was due to the widely acknowledged immunosuppression that occurs in blood-stage malaria 5 . This notion was reinforced by our observation of increased numbers and frequencies of FOXP3 + CD4 + T reg cells, a key immunosuppressive cell population, during the blood stage of malaria in humans and mice ( Fig. 1a–d ). We observed that higher parasite densities were associated with higher frequencies of T reg cells in humans; also, chloroquine treatment to decrease parasitemia reduced T reg cell frequencies and increased T helper cell frequencies in mice ( Supplementary Fig. 3a–c ). The role of T reg cells in malaria remains controversial 5 , 8 , 9 : some independent studies suggest that T reg cells suppress protection 10 , 11 , 12 , while others imply that they enhance it 13 , 14 . Importantly, these studies manipulated T reg cells (most of which express CD25) before or shortly after Plasmodium infection using anti-CD25 antibody–mediated depletion 10 , 11 , 13 , 14 , 15 or the (more precise) Foxp3 –diptheria toxin receptor (DTR) system 16 , 17 . Although variations in approaches may underlie these inconsistencies, the timing of T reg cell targeting could be a critical consideration for understanding malaria. Here we observed that expansion of T reg cells in P. yoelii –infected mice preceded or coincided with the hiatus in T helper cell responses, suggesting a causal relationship beginning ∼ 10 days post infection (d.p.i.). To test this proposition, we depleted both circulating and lymphoid 18 , 19 , 20 T reg cells in P. yoelii –infected Foxp3 -DTR ( Supplementary Fig. 4a,b ) and C57BL/6 ( Supplementary Fig. 5a ) mice with diphtheria toxin 21 and anti-CD25 antibody 10 , respectively, beginning at 9 d.p.i. T reg depletion interrupted the hiatus in T helper cell responses, restored expansion of Plasmodium -specific T helper cells and substantially accelerated control of P. yoelii infection ( Fig. 1e,f and Supplementary Fig. 5b,c ). In contrast, T reg depletion at 0 and 2 d.p.i. in Foxp3 -DTR mice resulted in the death of P. yoelii –infected mice ( Supplementary Fig. 4c ). Figure 1: T reg cells expand and modulate T helper cell responses and immunity to malaria. ( a ) Longitudinal frequencies of FOXP3 + T reg cells among the total CD4 + T cell population in peripheral blood mononuclear cells (PBMCs) from a cohort of children in Mali ( Supplementary Table 1 ) before, during, and after infection with acute febrile malaria. Each connected line indicates a unique subject. ( b ) Kinetics of activated (CD49d + CD11a hi ) T helper or FOXP3 + T reg cell frequencies among the total CD4 + T cell population in circulation in P. yoelii –infected C57BL/6 mice. ( c , d ) Absolute numbers of FOXP3 + CD4 + T reg cells in spleen ( c ) and lymph nodes (LN) ( d ) at the indicated time points in P. yoelii –infected C57BL/6 mice. ( e , f ) Frequencies of activated CD4 + T helper cells among the total CD4 + T cell population in circulation ( e ) and parasitemia ( f ) at various time points following infection with P. yoelii in C57BL/6 or Foxp3 -DTR mice treated with diphtheria toxin (Rx DT) or PBS (Rx PBS) at 9 and 11 d.p.i., as indicated by the pink label below the x axis. All experimental data represent one of at least three separate experiments with five mice per group and are presented as mean ± s.e.m. Statistical analysis was performed by comparing the indicated groups using one-way ANOVA<|im_end|> <|im_start|>assistant A molecule that prevents the immune system from attacking cancer may play a similar role with malaria. A new study by researchers at the University of Iowa Carver College of Medicine shows that targeting the molecule at the right time during infection allows mice to quickly clear malaria. Importantly the treated mice also develop lasting immunity to malaria. The molecule is a checkpoint protein called anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). In cancer, CTLA-4 is a target for new immunotherapy drugs that prevent cancer from supressing the immune system. In the new study, published in Nature Medicine, the UI researchers show that CTLA-4 is expressed and released by a subset of immune cells called regulatory T cells (Tregs) that are involved in immune suppression. "People have long known that malaria is associated with a huge immunosupressive response, but no one knew the mechanism," say Samarchith (Sam) Kurup, PhD, a UI assistant research scientist and first author on the study. "The CTLA-4 molecule interferes with appropriate immune activation," explains John Harty, PhD, UI professor of microbiology and immunology and senior study author. "Specifically, it interferes with the function of several types of T helper cells whose job it is to drive immune responses against malaria." Malaria is a serious, life-threatening disease across most of the developing world. There are 200 million cases of malaria each year and almost 500,000 malaria-related deaths. The malaria parasite, which is transmitted by mosquito bites, persists in the blood for long periods. Critically, although there are drugs that can cure the infection, humans do not develop immunity to infection, which means a person can get reinfected with malaria year after year. Multiple infections eventually make a person resistant to the severity of the disease symptom, but when the person - usually a young child - experiences their first few infections, the disease can be deadly. Malaria meddles with immune responses In most infectious diseases, a group of immune cells called T helper cells increases in number, cooperates with B cells to make antibodies that clear the infection, then leaves behind memory T and B cells to defend against reinfection with the same pathogen. That doesn't happen in malaria. Instead, there is a period where the T helper cell expansion stalls. During that critical time period, the UI reseachers showed that the Treg population increases. "Our observation that the Tregs went up when the T helper cells stopped going up showed a timing relationship that suggested the possibility of a functional relationship," says Harty, who also is a UI professor of pathology. When the UI team eliminated Treg cells in mice with blood-stage malaria infections, the expansion of the T helper cells did not plateau; they kept expanding and cleared the infection faster. Further experiments revealed that Tregs suppress the normal immune response by continuously expressing and shedding the CTLA-4 molecule, which interferes with the normal immune function of T helper cells. It also interferes with another set of T helper cells (follicular T helper cells) whose job it is to help make antibodies against malaria. Malaria prevents the host body (human or mouse) from developing lasting immunity. A new University of Iowa study, led by microbiology professor John Harty, has homed in on a potential culprit of this immunosuppression. The molecule, CTLA-4, is produced by a type of immune cell called a Treg cell. Blocking CTLA-4 at the right time during blood-stage infection allows mice to quickly clear malaria. Importantly the treated mice also develop lasting immunity to malaria.The video, captured with intravital confocal immunofluorescence microscopy, shows Treg cells (green) delivering CTLA-4 to B cell (blue/ magenta)-Helper T cell (red) clusters in the spleen of a mouse. The CTLA-4 molecule inhibits efficient production of antibodies against malaria.If this pathway works in humans as it does in mice, blocking CTLA-4 might be a way to improve malaria treatment and boost immunity to reinfection. The study was published Sept. 11 online in Nature Medicine. Credit: Samarchith Kurup/ Scott Anthony, dept. of Microbiology and Immunology, University of Iowa. "Tregs meddle with these processes through the CTLA-4 molecule," Harty says. Blocking CTLA-4 at the right time during blood-stage infection cured mice of the infection and promoted immunity against reinfections. It even provided protection against challenge from another deadlier malaria parasite. Previous work in Harty's lab found that blocking a different checkpoint protein called PDL1 at a later point in malaria infection also improved the host immune response to malaria. The new work shows that the CTLA-4 pathway is in play at an earlier stage in malaria infection, and shows that the two pathways don't overlap. "Both pathways impede the appropriate activation of the immune system, but in different ways, targeting different interactions, and at different time points," Harty says. "The more we understand how and when these pathways are operating, the better chance we have to rescue them." Of mice and men Harty and Kurup are quick to point out that findings in mice often do not translate easily to human patients, but access to unique human data may help determine if the CTLA-4 findings are relevant in humans. For about a decade, Harty has collaborated with Peter Crompton, an National Institutes of Health (NIH) scientist who works with malaria patients in the African country of Mali. The clinic where Crompton's colleagues work tracks around 700 children year after year. During each wet season, when malaria is endemic, children are diagnosed and treated for malaria, and the team collects blood samples for immunological studies. "This has been a very potent resource for us," Harty says. "When we look at blood samples from the same infection timeframe that we investigated in the mouse, we see some of the same immune changes (expansion of Tregs and upregulation of CTLA-4) are also happening in humans. That does not prove that everything is the same, but at the level of resolution that we have, there is some reasonable similarity." "Practically, we have shown there is a pathway that can be targeted, and although CTLA-4 blockers that are available as cancer immunotherapies are too costly and impractical to use for malaria, there may be other parts of this immunological pathway that could be targeted using other drugs or small molecules, to produce the same effect," Kurup says. The malaria parasite is adept at developing resistance to antimalarial medicines that target it directly, as has happened time and time again. The UI approach focuses on modulating or improving the immune response of the host. "The parasite can't become resistant to that," Harty says. <|im_end|>

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315, 279, 3552, 13, 330, 791, 85573, 649, 956, 3719, 31785, 311, 430, 1359, 473, 6862, 2795, 13, 220, 128257, 198 ]

2,844

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract In aggressive interactions, game theory predicts that animals should assess an opponent’s condition relative to their own prior to escalation or retreat. Despite the benefits of such mutual assessment , few studies have been able to reject simpler assessment strategies. Here we report evidence for mutual assessment in a wild primate. Gelada ( Theropithecus gelada ) males have conspicuous loud calls that may function as a signal of male quality. “Leader” males with harems putatively use loud calls to deter challenges from non-reproductive “bachelor” males. By contrast, leader males pose no threat to each other and congregate in large groups for a dilution effect against bachelors. In playback experiments and natural observations, gelada males responded to loud calls according to both their own and their opponent’s attributes. Although primates routinely classify others relative to themselves using individual attributes, this represents some of the first direct evidence for mutual assessment in primate signaling contests. Introduction Limited resources lead animals into contests. Because aggressive contests are costly, game theory predicts that contestants will assess the costs and benefits of a particular contest before escalating 1 , 2 . Contestants with a high ability to compete (i.e., high resource holding potential – RHP) should escalate the contest, while those with a low ability to compete (low RHP) should withdraw. Despite the simplicity of this prediction, there is enormous debate about how animals make these decisions 3 . It stands to reason that a contestant should gather information about their opponent’s condition and compare that to their own ( mutual assessment 2 ). However, many empirical studies find it difficult to reject “simpler” assessment strategies 4 such as self-assessment (relying solely on one’s own condition 5 ), or opponent-only assessment (relying solely on a rival’s condition 6 ). For example, when an inferior contestant withdraws from an aggressive contest with an opponent, the contestant may indeed be using mutual assessment, or they may simply be withdrawing because the damage incurred was too high. Therefore, a “cumulative” self-assessment strategy is difficult to distinguish from a “sequential” mutual assessment one 4 . Non-contact displays – such as those involving animal signals – avoid this problem entirely 7 . Contestants do not accumulate sufficient costs during displays for a cumulative assessment strategy to operate. Therefore, measuring receiver responses based on the relative quality of the signaler and the receiver makes for a strong test of mutual assessment. However, within the vast literature documenting receiver responses to putative signals based on the quality of the signaler 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , only a handful of studies also examined receiver responses based on the relative quality of the signaler and the receiver 7 , 19 , 20 , 21 , 22 . Thus, the current evidence for many signals is only sufficient for identifying opponent-only assessment. In practice, however, it is likely that many of these taxa may be using mutual assessment. In non-human primates (hereafter, “primates”), there is very little evidence for mutual assessment based solely on the content encoded in a signal for two reasons. First, experimental manipulations are necessary. In one of the few captive experiments that sought to examine mutual assessment (e.g., manipulated scrotal color and staged contests in male vervet monkeys, Chlorocebus pygerythrus ), the results were inconclusive possibly because it is near impossible to recreate realistic scenarios that males typically encounter in the wild 22 . Second, primates tend to rely predominantly on social information that derives from individual recognition (not signals) to guide their interactions 23 . The use of this social information can be quite sophisticated (e.g., eavesdropping) 24 or quite simple (e.g., requiring nothing more than recognizing an individual) 23 . For example, in primate systems with linear dominance hierarchies, the dominance rank of an individual determines the outcome of most social interactions 25 , 26 , 27 . Typically, these interactions are not thought to be based on the relative Resource Holding Potential (RHP) of contestants at the time of the interaction, but rather based on social knowledge of contestants derived from a recent history of interactions with them 28 . However, results from previous research on mutual assessment have not been able to entirely distinguish whether primate subjects use individual identity or quality signals as the underlying basis for assessment, even in cases where playback experiments were able to manipulate the individual and/or the signal. For example, playback experiments in chacma baboons ( Papio ursinus ) have shown that subjects respond to loud call displays based on the relative RHP of contestants 19 , 25 , 26 . Specifically, based on simulated loud call contests, chacma males were more likely to enter vocal contests if the opponent’s rank was similar to their own 26 , they were able to discriminate between the relative ranks of “third party” contestants 25 , and they were more interested in calls that were manipulated to suggest a higher quality male 19 . Combined, these three studies suggest that mutual assessment may be occurring in chacma baboons. However, the first two studies 25 , 26 and half of the third study 19 were conducted entirely with familiar rivals. In a parallel study on chacma male grunts (soft vocalizations that are unlikely to carry information about the sender’s competitive ability), researchers also observed that the strongest responses occurred between similarly-ranked males 29 . Therefore, because known males were used, it is impossible to distinguish whether chacma male assessment hinged on individual recognition (knowing who is calling) or signal strength (knowing the quality of the caller). In the only experiment to use unknown callers, the subjects did not alter their responses according to their own rank – they all attended more strongly to the higher quality loud call 19 . Therefore, although these results are certainly suggestive, they fall just short of providing clear evidence of mutual assessment in the context of animal signals. Here", "role": "user" }, { "content": "Gelada males—a close relative to baboons—pay attention to the loud calls of a rival to gain information about his relative fighting ability compared to themselves, a new study indicated. Researchers at the University of Michigan, Georgia State University and Princeton University found evidence that gelada males decide to escalate contests with their opponents based on their own condition relative to the condition of their opponent. They appear to do this by using the acoustic quality of the loud calls of their rivals—long-distance vocalizations that carry honest information about the fighting ability of the caller. There has been much debate on specifically how animals make competitive decisions during contests. Game theoretical models predict that animals should assess an opponent's condition relative to their own condition prior to engaging in combat to avoid costly fights they are unlikely to win, a strategy known as mutual assessment. Despite the benefits of such mutual comparisons (\"I am stronger than him\"), remarkably few studies have been able to reject much simpler assessment strategies such as self-assessment (\"I am strong and should fight\") and opponent-only assessment (\"he is strong and so I should not fight\"). Researchers say one approach for distinguishing these strategies is to use animal displays (rather than aggressive contests) to examine how animals make informed decisions about rivals. \"Particularly for quality signals that contain honest information on the condition of its bearer, signals used in animal displays offer an ideal situation for examining mutual assessment because they are low cost and allow for experimental manipulation,\" said Marcela Benítez, a postdoctoral research associate at Georgia State University and the study's lead author. In geladas, harem-holding \"leader\" males engage in loud call displays to deter challenges from \"bachelor\" males, who must compete with leaders to gain reproductive access to females. Supporting a mutual assessment strategy, gelada males responded to loud calls of different quality (in both playback experiments as well as in natural observations) according to attributes of themselves and their opponent. \"Previous studies in wild primates have shown that they use mutual assessment, but this was between animals that knew one other,\" said Jacinta Beehner, U-M associate professor of psychology and anthropology. \"They see Kevin and they remember that they beat him in a previous fight. The novelty of our finding is that we have shown that primates can do this even for completely unfamiliar individuals—using signals.\" Although primates routinely classify others relative to themselves using individual attributes, this represents some of the first direct evidence for mutual assessment in primate signaling contests, Benítez said. The findings appear in Scientific Reports. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract In aggressive interactions, game theory predicts that animals should assess an opponent’s condition relative to their own prior to escalation or retreat. Despite the benefits of such mutual assessment , few studies have been able to reject simpler assessment strategies. Here we report evidence for mutual assessment in a wild primate. Gelada ( Theropithecus gelada ) males have conspicuous loud calls that may function as a signal of male quality. “Leader” males with harems putatively use loud calls to deter challenges from non-reproductive “bachelor” males. By contrast, leader males pose no threat to each other and congregate in large groups for a dilution effect against bachelors. In playback experiments and natural observations, gelada males responded to loud calls according to both their own and their opponent’s attributes. Although primates routinely classify others relative to themselves using individual attributes, this represents some of the first direct evidence for mutual assessment in primate signaling contests. Introduction Limited resources lead animals into contests. Because aggressive contests are costly, game theory predicts that contestants will assess the costs and benefits of a particular contest before escalating 1 , 2 . Contestants with a high ability to compete (i.e., high resource holding potential – RHP) should escalate the contest, while those with a low ability to compete (low RHP) should withdraw. Despite the simplicity of this prediction, there is enormous debate about how animals make these decisions 3 . It stands to reason that a contestant should gather information about their opponent’s condition and compare that to their own ( mutual assessment 2 ). However, many empirical studies find it difficult to reject “simpler” assessment strategies 4 such as self-assessment (relying solely on one’s own condition 5 ), or opponent-only assessment (relying solely on a rival’s condition 6 ). For example, when an inferior contestant withdraws from an aggressive contest with an opponent, the contestant may indeed be using mutual assessment, or they may simply be withdrawing because the damage incurred was too high. Therefore, a “cumulative” self-assessment strategy is difficult to distinguish from a “sequential” mutual assessment one 4 . Non-contact displays – such as those involving animal signals – avoid this problem entirely 7 . Contestants do not accumulate sufficient costs during displays for a cumulative assessment strategy to operate. Therefore, measuring receiver responses based on the relative quality of the signaler and the receiver makes for a strong test of mutual assessment. However, within the vast literature documenting receiver responses to putative signals based on the quality of the signaler 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , only a handful of studies also examined receiver responses based on the relative quality of the signaler and the receiver 7 , 19 , 20 , 21 , 22 . Thus, the current evidence for many signals is only sufficient for identifying opponent-only assessment. In practice, however, it is likely that many of these taxa may be using mutual assessment. In non-human primates (hereafter, “primates”), there is very little evidence for mutual assessment based solely on the content encoded in a signal for two reasons. First, experimental manipulations are necessary. In one of the few captive experiments that sought to examine mutual assessment (e.g., manipulated scrotal color and staged contests in male vervet monkeys, Chlorocebus pygerythrus ), the results were inconclusive possibly because it is near impossible to recreate realistic scenarios that males typically encounter in the wild 22 . Second, primates tend to rely predominantly on social information that derives from individual recognition (not signals) to guide their interactions 23 . The use of this social information can be quite sophisticated (e.g., eavesdropping) 24 or quite simple (e.g., requiring nothing more than recognizing an individual) 23 . For example, in primate systems with linear dominance hierarchies, the dominance rank of an individual determines the outcome of most social interactions 25 , 26 , 27 . Typically, these interactions are not thought to be based on the relative Resource Holding Potential (RHP) of contestants at the time of the interaction, but rather based on social knowledge of contestants derived from a recent history of interactions with them 28 . However, results from previous research on mutual assessment have not been able to entirely distinguish whether primate subjects use individual identity or quality signals as the underlying basis for assessment, even in cases where playback experiments were able to manipulate the individual and/or the signal. For example, playback experiments in chacma baboons ( Papio ursinus ) have shown that subjects respond to loud call displays based on the relative RHP of contestants 19 , 25 , 26 . Specifically, based on simulated loud call contests, chacma males were more likely to enter vocal contests if the opponent’s rank was similar to their own 26 , they were able to discriminate between the relative ranks of “third party” contestants 25 , and they were more interested in calls that were manipulated to suggest a higher quality male 19 . Combined, these three studies suggest that mutual assessment may be occurring in chacma baboons. However, the first two studies 25 , 26 and half of the third study 19 were conducted entirely with familiar rivals. In a parallel study on chacma male grunts (soft vocalizations that are unlikely to carry information about the sender’s competitive ability), researchers also observed that the strongest responses occurred between similarly-ranked males 29 . Therefore, because known males were used, it is impossible to distinguish whether chacma male assessment hinged on individual recognition (knowing who is calling) or signal strength (knowing the quality of the caller). In the only experiment to use unknown callers, the subjects did not alter their responses according to their own rank – they all attended more strongly to the higher quality loud call 19 . Therefore, although these results are certainly suggestive, they fall just short of providing clear evidence of mutual assessment in the context of animal signals. Here<|im_end|> <|im_start|>assistant Gelada males—a close relative to baboons—pay attention to the loud calls of a rival to gain information about his relative fighting ability compared to themselves, a new study indicated. Researchers at the University of Michigan, Georgia State University and Princeton University found evidence that gelada males decide to escalate contests with their opponents based on their own condition relative to the condition of their opponent. They appear to do this by using the acoustic quality of the loud calls of their rivals—long-distance vocalizations that carry honest information about the fighting ability of the caller. There has been much debate on specifically how animals make competitive decisions during contests. Game theoretical models predict that animals should assess an opponent's condition relative to their own condition prior to engaging in combat to avoid costly fights they are unlikely to win, a strategy known as mutual assessment. Despite the benefits of such mutual comparisons ("I am stronger than him"), remarkably few studies have been able to reject much simpler assessment strategies such as self-assessment ("I am strong and should fight") and opponent-only assessment ("he is strong and so I should not fight"). Researchers say one approach for distinguishing these strategies is to use animal displays (rather than aggressive contests) to examine how animals make informed decisions about rivals. "Particularly for quality signals that contain honest information on the condition of its bearer, signals used in animal displays offer an ideal situation for examining mutual assessment because they are low cost and allow for experimental manipulation," said Marcela Benítez, a postdoctoral research associate at Georgia State University and the study's lead author. In geladas, harem-holding "leader" males engage in loud call displays to deter challenges from "bachelor" males, who must compete with leaders to gain reproductive access to females. Supporting a mutual assessment strategy, gelada males responded to loud calls of different quality (in both playback experiments as well as in natural observations) according to attributes of themselves and their opponent. "Previous studies in wild primates have shown that they use mutual assessment, but this was between animals that knew one other," said Jacinta Beehner, U-M associate professor of psychology and anthropology. "They see Kevin and they remember that they beat him in a previous fight. The novelty of our finding is that we have shown that primates can do this even for completely unfamiliar individuals—using signals." Although primates routinely classify others relative to themselves using individual attributes, this represents some of the first direct evidence for mutual assessment in primate signaling contests, Benítez said. The findings appear in Scientific Reports. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Nematic order on curved surfaces is often disrupted by the presence of topological defects, which are singular regions in which the orientational order is undefined. In the presence of force-generating active materials, these defects are able to migrate through space like swimming microorganisms. We use toroidal surfaces to show that despite their highly chaotic and non-equilibrium dynamics, pairs of defects unbind and segregate in regions of opposite Gaussian curvature. Using numerical simulations, we find that the degree of defect unbinding can be controlled by tuning the system activity, and even suppressed in strongly active systems. Furthermore, by using the defects as active microrheological tracers and quantitatively comparing our experimental and theoretical results, we are able to determine material properties of the active nematic. Our results illustrate how topology and geometry can be used to control the behaviour of active materials, and introduce a new avenue for the quantitative mechanical characterization of active fluids. Main Defects are singular regions where the characteristic order in a material is undefined. The human hand, for example, is lined by parallel ridges and associated defects, which play a pivotal role in fingerprint identification. More broadly, defects play a significant role in physics and materials science; for example, defect proliferation is the mechanism behind the celebrated Kosterlitz–Thouless–Halperin–Nelson–Young (KTHNY) phase transition 1 , 2 , 3 , and defect entanglement can add orders of magnitude to the stiffness of normally soft liquid crystals 4 , 5 . Furthermore, since defects can serve as preferential sites for chemical linking, they can be used to help assemble hierarchical structures that hold promise for both photonic and biosensing applications 6 , 7 . Remarkably, when defects are combined with force-generating active materials, the structural complexity comes to life, giving rise to a spectacular variety of self-regulated behaviours, such as self-sustained oscillations and spontaneous formation of morphological features, including kinks, protrusions 8 and undirected motility 8 , 9 . These remarkable observations have acted as a stimulus for investigating how biological functionality emerges from the interplay between activity, the geometry of the system and the structure of the internal phase 10 , 11 , 12 . In this context, defects that could be present in active materials could be harnessed to achieve life-like functionality, since defects are extremely sensitive to the intrinsic geometry of the space they inhabit. This is clearly exemplified in a nematic liquid crystal composed of anisotropic mesogens aligned along a common direction, referred to as the nematic director n , on a sphere. As you ‘cannot comb a hairy ball’, there will necessarily be irreducible singularities on the surface; however, the type and number of singularities depends on the energetics of the system 13 . As it was theoretically predicted 6 , 14 and then experimentally observed 15 , such a system attains its lowest energy configuration when nematic order is disrupted at the location of four point defects arranged on the vertices of a tetrahedron. Around each defect the nematic director rotates by π. Each defect is then said to carry an s = +1/2 topological charge, which is defined as the winding number of n along a path encircling the defect. From this definition, it is evident that s is quantized and can take on only a discrete set of values; for a nematic, s must be an integer multiple of 1/2. A formal statement of the constraint on the total topological charge on a closed (compact and without boundary) surface is given by the Poincaré–Hopf theorem 16 , which forces the total topological charge to be equal to the surface Euler characteristic χ = 1/(2π)∫ K d A (ref. 16 ), where K = ( R 1 R 2 ) −1 is the Gaussian curvature, with R 1 and R 2 the principal radii of curvature at a point on the surface 16 . For a sphere of radius R , there are four +1/2 defects, consistent with having K = R −2 everywhere and χ = 2. The connection between defects and the space they inhabit is predicted to go beyond topology. The theory of defects on curved surfaces connects the topology of the confining surface to the free energy associated to a given defect configuration via the Gaussian curvature of the surface 13 . Thus, even though there have been new discoveries examining defective structures on spherical surfaces 15 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , the constant Gaussian curvature implies that only the size of the sphere will have any impact on the defect structure; this is confirmed by the size-dependent onset of grain-boundary scars in colloidal crystals on the surface of emulsion droplets 18 , 19 . Even when the nematic mesogens are active and the four +1/2 defects on the sphere become mobile, the defect dynamics can be explained without any mention of Gaussian curvature 8 . Despite theoretical interest in the interplay between varying Gaussian curvature and topological defects, with few exceptions 24 , 25 , 26 , there has been little experimental work with defects on surfaces where the Gaussian curvature is non-constant. More notably, there has been no experimental work where the defects have the option to explore regions with both positive (sphere-like) and negative (saddle-like) Gaussian curvature. In this case and for nematic order, the topological charge is expected to unbind into +1/2 and −1/2 defects (see Fig. 1a ), which in turn are attracted by regions of like-sign Gaussian curvature 27 , 28 , 29 . In this Article, we explore this experimentally for the first time using an active nematic liquid crystal comprised of microtubules and kinesin, constrained to lie on a toroidal surface (see Fig. 1b ), which has positive Gaussian curvature on the exterior, negative Gaussian curvature on the interior, and is such that χ = 0. This implies that a nematic liquid crystal on a torus can be either defect-free or populated by the same amount of positive and negative defects.", "role": "user" }, { "content": "Imagine a tiny donut-shaped droplet, covered with wriggling worms. The worms are packed so tightly together that they must locally line up with respect to each other. In this situation, we would say the worms form a nematic liquid crystal, an ordered phase similar to the materials used in many flat panel displays. However, the nematic phase formed by the worms is filled with tiny regions where the local alignment is lost - defects in the otherwise aligned material. In addition, because the worms are constantly moving and changing their configuration, this nematic phase is active and far from equilibrium. In research reported in the journal Nature Physics, scientists from the Georgia Institute of Technology and Leiden University in The Netherlands have described the results of a combined theoretical and experimental examination of such an active nematic on the surface of donut-shaped - toroidal - droplets. However, the researchers didn't use actual worms, but an active nematic composed of flexible filaments covered with microscopic engines that are constantly converting energy into motion. This particular active material, originally developed at Brandeis University, borrows elements of cellular machinery, with bundles of rod-like microtubules forming the filaments, kinesin motor proteins acting as the engines, and ATP as the fuel. When this activity is combined with defects, the defects \"come to life,\" moving around like swimming microorganisms and exploring space - in this case, exploring the surface of the toroidal droplets. By studying toroidal droplets covered by this active nematic, the researchers confirmed a longstanding theoretical prediction about liquid crystals at equilibrium, first discussed by Bowick, Nelson and Travesset [Phys.Rev. E 69, 041102 (2004)] that nematic defects on the curved surface of such droplets will be sensitive to the local curvature. However, since the active nematic used in this work is far from equilibrium, the researchers also found how the internal activity changed and enriched the expectations. \"There have been predictions that say defects are very sensitive to the space they inhabit, specifically to the curvature of the space,\" said Perry Ellis, a graduate student in the Georgia Tech School of Physics and the paper's first author. \"The torus is a great place to investigate this because the outside of the torus, the part that looks locally like a sphere, has positive curvature while the inner part of a torus, the part that looks like a saddle, has negative curvature.\" \"The quantity that characterizes a defect is what we call its topological charge or winding number,\" said Alberto Fernandez-Nieves, a professor in Georgia Tech's School of Physics and another of the paper's co-authors. \"It expresses how the alignment direction of the nematic liquid crystal changes as we go around the defect. This topological charge is quantized, meaning that it can only take values from a discrete set that are multiples of one-half. \" In these experiments, each defect has a topological charge of +1/2 or -1/2. To determine the charge and location of every defect, Ellis observed the toroidal droplets over time using a confocal microscope and then analyzed the resulting video using techniques borrowed from computer vision. The researchers found that even with the molecular motors driving the system out of equilibrium, the defects were still able to sense the curvature, with the +1/2 defects migrating towards the region of positive curvature and the -1/2 defects migrating towards the region of negative curvature. In this new work, the scientists took a step forward in understanding how to control and guide defects in an ordered material. \"We have learned that we can control and guide partially ordered active matter using the curvature of the underlying substrate,\" said Fernandez-Nieves. \"This work opens opportunities to study how the defects in these materials arrange on surfaces that do not have constant curvature. This opens the door for controlling active matter using curvature.\" An unexpected finding of the study was that the constant motion of the defects causes the average topological charge to become continuous, no longer taking only values that are multiples of one-half. \"In the active limit of our experiments, we found that the topological charge becomes a continuous variable that can now take on any value,\" said Fernandez-Nieves. \"This is reminiscent of what happens to many quantum systems at high temperature, where the quantum, discrete nature of the accessible states and associated variables is lost. Instead of being characterized by quantized properties, the system becomes characterized by continuum properties.\" Ellis' observations of the droplets compared well with those of numerical simulations done by Assistant Professor Luca Giomi and postdoctoral researcher Daniel Pearce at the Instituut-Lorentz for Theoretical Physics at the Universiteit Leiden in The Netherlands. \"Our theoretical model helped us decipher the experimental results and fully understand the physical mechanism governing defect motion,\" said Pearce, \"but also allowed us to go beyond the current experimental evidence.\" Added Giomi: \"Activity changes the nature of the interaction between defects and curvature. In weakly active systems, defects are attracted by regions of like-sign Gaussian curvature. But in strongly active systems, this effect becomes less relevant and defects behave as persistent random-walkers confined in a closed and inhomogeneous space\". There are many examples of active systems driven by internal activity, including swimming microorganisms, bird flocks, robot swarms and traffic flows. \"Active materials are everywhere, so our results aren't limited to just this system on a torus,\" Ellis added. \"You could see the same behavior in any active system with defects.\" The research sets the stage for future work in active fluids. \"Our results introduce a new framework to explore the mechanical properties of active fluids and suggest that partially ordered active matter can be guided and controlled via gradients in the intrinsic geometry of the underlying substrate,\" the authors wrote in a summary of their paper. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Nematic order on curved surfaces is often disrupted by the presence of topological defects, which are singular regions in which the orientational order is undefined. In the presence of force-generating active materials, these defects are able to migrate through space like swimming microorganisms. We use toroidal surfaces to show that despite their highly chaotic and non-equilibrium dynamics, pairs of defects unbind and segregate in regions of opposite Gaussian curvature. Using numerical simulations, we find that the degree of defect unbinding can be controlled by tuning the system activity, and even suppressed in strongly active systems. Furthermore, by using the defects as active microrheological tracers and quantitatively comparing our experimental and theoretical results, we are able to determine material properties of the active nematic. Our results illustrate how topology and geometry can be used to control the behaviour of active materials, and introduce a new avenue for the quantitative mechanical characterization of active fluids. Main Defects are singular regions where the characteristic order in a material is undefined. The human hand, for example, is lined by parallel ridges and associated defects, which play a pivotal role in fingerprint identification. More broadly, defects play a significant role in physics and materials science; for example, defect proliferation is the mechanism behind the celebrated Kosterlitz–Thouless–Halperin–Nelson–Young (KTHNY) phase transition 1 , 2 , 3 , and defect entanglement can add orders of magnitude to the stiffness of normally soft liquid crystals 4 , 5 . Furthermore, since defects can serve as preferential sites for chemical linking, they can be used to help assemble hierarchical structures that hold promise for both photonic and biosensing applications 6 , 7 . Remarkably, when defects are combined with force-generating active materials, the structural complexity comes to life, giving rise to a spectacular variety of self-regulated behaviours, such as self-sustained oscillations and spontaneous formation of morphological features, including kinks, protrusions 8 and undirected motility 8 , 9 . These remarkable observations have acted as a stimulus for investigating how biological functionality emerges from the interplay between activity, the geometry of the system and the structure of the internal phase 10 , 11 , 12 . In this context, defects that could be present in active materials could be harnessed to achieve life-like functionality, since defects are extremely sensitive to the intrinsic geometry of the space they inhabit. This is clearly exemplified in a nematic liquid crystal composed of anisotropic mesogens aligned along a common direction, referred to as the nematic director n , on a sphere. As you ‘cannot comb a hairy ball’, there will necessarily be irreducible singularities on the surface; however, the type and number of singularities depends on the energetics of the system 13 . As it was theoretically predicted 6 , 14 and then experimentally observed 15 , such a system attains its lowest energy configuration when nematic order is disrupted at the location of four point defects arranged on the vertices of a tetrahedron. Around each defect the nematic director rotates by π. Each defect is then said to carry an s = +1/2 topological charge, which is defined as the winding number of n along a path encircling the defect. From this definition, it is evident that s is quantized and can take on only a discrete set of values; for a nematic, s must be an integer multiple of 1/2. A formal statement of the constraint on the total topological charge on a closed (compact and without boundary) surface is given by the Poincaré–Hopf theorem 16 , which forces the total topological charge to be equal to the surface Euler characteristic χ = 1/(2π)∫ K d A (ref. 16 ), where K = ( R 1 R 2 ) −1 is the Gaussian curvature, with R 1 and R 2 the principal radii of curvature at a point on the surface 16 . For a sphere of radius R , there are four +1/2 defects, consistent with having K = R −2 everywhere and χ = 2. The connection between defects and the space they inhabit is predicted to go beyond topology. The theory of defects on curved surfaces connects the topology of the confining surface to the free energy associated to a given defect configuration via the Gaussian curvature of the surface 13 . Thus, even though there have been new discoveries examining defective structures on spherical surfaces 15 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , the constant Gaussian curvature implies that only the size of the sphere will have any impact on the defect structure; this is confirmed by the size-dependent onset of grain-boundary scars in colloidal crystals on the surface of emulsion droplets 18 , 19 . Even when the nematic mesogens are active and the four +1/2 defects on the sphere become mobile, the defect dynamics can be explained without any mention of Gaussian curvature 8 . Despite theoretical interest in the interplay between varying Gaussian curvature and topological defects, with few exceptions 24 , 25 , 26 , there has been little experimental work with defects on surfaces where the Gaussian curvature is non-constant. More notably, there has been no experimental work where the defects have the option to explore regions with both positive (sphere-like) and negative (saddle-like) Gaussian curvature. In this case and for nematic order, the topological charge is expected to unbind into +1/2 and −1/2 defects (see Fig. 1a ), which in turn are attracted by regions of like-sign Gaussian curvature 27 , 28 , 29 . In this Article, we explore this experimentally for the first time using an active nematic liquid crystal comprised of microtubules and kinesin, constrained to lie on a toroidal surface (see Fig. 1b ), which has positive Gaussian curvature on the exterior, negative Gaussian curvature on the interior, and is such that χ = 0. This implies that a nematic liquid crystal on a torus can be either defect-free or populated by the same amount of positive and negative defects.<|im_end|> <|im_start|>assistant Imagine a tiny donut-shaped droplet, covered with wriggling worms. The worms are packed so tightly together that they must locally line up with respect to each other. In this situation, we would say the worms form a nematic liquid crystal, an ordered phase similar to the materials used in many flat panel displays. However, the nematic phase formed by the worms is filled with tiny regions where the local alignment is lost - defects in the otherwise aligned material. In addition, because the worms are constantly moving and changing their configuration, this nematic phase is active and far from equilibrium. In research reported in the journal Nature Physics, scientists from the Georgia Institute of Technology and Leiden University in The Netherlands have described the results of a combined theoretical and experimental examination of such an active nematic on the surface of donut-shaped - toroidal - droplets. However, the researchers didn't use actual worms, but an active nematic composed of flexible filaments covered with microscopic engines that are constantly converting energy into motion. This particular active material, originally developed at Brandeis University, borrows elements of cellular machinery, with bundles of rod-like microtubules forming the filaments, kinesin motor proteins acting as the engines, and ATP as the fuel. When this activity is combined with defects, the defects "come to life," moving around like swimming microorganisms and exploring space - in this case, exploring the surface of the toroidal droplets. By studying toroidal droplets covered by this active nematic, the researchers confirmed a longstanding theoretical prediction about liquid crystals at equilibrium, first discussed by Bowick, Nelson and Travesset [Phys.Rev. E 69, 041102 (2004)] that nematic defects on the curved surface of such droplets will be sensitive to the local curvature. However, since the active nematic used in this work is far from equilibrium, the researchers also found how the internal activity changed and enriched the expectations. "There have been predictions that say defects are very sensitive to the space they inhabit, specifically to the curvature of the space," said Perry Ellis, a graduate student in the Georgia Tech School of Physics and the paper's first author. "The torus is a great place to investigate this because the outside of the torus, the part that looks locally like a sphere, has positive curvature while the inner part of a torus, the part that looks like a saddle, has negative curvature." "The quantity that characterizes a defect is what we call its topological charge or winding number," said Alberto Fernandez-Nieves, a professor in Georgia Tech's School of Physics and another of the paper's co-authors. "It expresses how the alignment direction of the nematic liquid crystal changes as we go around the defect. This topological charge is quantized, meaning that it can only take values from a discrete set that are multiples of one-half. " In these experiments, each defect has a topological charge of +1/2 or -1/2. To determine the charge and location of every defect, Ellis observed the toroidal droplets over time using a confocal microscope and then analyzed the resulting video using techniques borrowed from computer vision. The researchers found that even with the molecular motors driving the system out of equilibrium, the defects were still able to sense the curvature, with the +1/2 defects migrating towards the region of positive curvature and the -1/2 defects migrating towards the region of negative curvature. In this new work, the scientists took a step forward in understanding how to control and guide defects in an ordered material. "We have learned that we can control and guide partially ordered active matter using the curvature of the underlying substrate," said Fernandez-Nieves. "This work opens opportunities to study how the defects in these materials arrange on surfaces that do not have constant curvature. This opens the door for controlling active matter using curvature." An unexpected finding of the study was that the constant motion of the defects causes the average topological charge to become continuous, no longer taking only values that are multiples of one-half. "In the active limit of our experiments, we found that the topological charge becomes a continuous variable that can now take on any value," said Fernandez-Nieves. "This is reminiscent of what happens to many quantum systems at high temperature, where the quantum, discrete nature of the accessible states and associated variables is lost. Instead of being characterized by quantized properties, the system becomes characterized by continuum properties." Ellis' observations of the droplets compared well with those of numerical simulations done by Assistant Professor Luca Giomi and postdoctoral researcher Daniel Pearce at the Instituut-Lorentz for Theoretical Physics at the Universiteit Leiden in The Netherlands. "Our theoretical model helped us decipher the experimental results and fully understand the physical mechanism governing defect motion," said Pearce, "but also allowed us to go beyond the current experimental evidence." Added Giomi: "Activity changes the nature of the interaction between defects and curvature. In weakly active systems, defects are attracted by regions of like-sign Gaussian curvature. But in strongly active systems, this effect becomes less relevant and defects behave as persistent random-walkers confined in a closed and inhomogeneous space". There are many examples of active systems driven by internal activity, including swimming microorganisms, bird flocks, robot swarms and traffic flows. "Active materials are everywhere, so our results aren't limited to just this system on a torus," Ellis added. "You could see the same behavior in any active system with defects." The research sets the stage for future work in active fluids. "Our results introduce a new framework to explore the mechanical properties of active fluids and suggest that partially ordered active matter can be guided and controlled via gradients in the intrinsic geometry of the underlying substrate," the authors wrote in a summary of their paper. <|im_end|>

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2,501

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract This paper explores the relationship between specific household traits (region of residence, head of household occupation, financial diversity, female level of education, land and animal ownership, social capital, and climate perception) and choice of specific adaptation strategies used by households in two sites in Baja California Sur, Mexico, during a severe drought from 2006 to 2012 using survey data and key informant interviews. We analyzed the co-occurrence of household traits adopting different drought adaptation strategies, then applied Qualitative Comparative Analysis (QCA) to examine the relationship between traits and strategies and integrated interview data to understand how rancheros perceive associations. We found evidence of diversity among households within the larger cultural group, both in the types of resources they have available and in the adaptation strategies they select. However, the most robust finding across the analyses appeared to be urban access; that is, the more a household was able to access urban services including piped water, the less likely they were to have used one of the drought adaptation strategies under study. These findings suggest that social structure and public investments are stronger predictors of smallholder adaptation rather than individual household traits. We also found that rancheros seem to rely less on traditional environmental migration to adapt to drought and rather settle in key watershed zones. We call for targeted policies to address inequities to access fresh water, including urban water, during drought times for the benefit of overall watershed health and the sustainability of rural ranchero livelihoods as they evolve to respond to climatological and economic change. Access provided by Universität des es, -und Working on a manuscript? Avoid the common mistakes Introduction The increase in drought risk due to a progressively drier climate in the subtropical latitudes over parts of North America (Cook et al. 2010 ) translates to a growing need to understand how households will adapt to drought changes, and why households respond in certain ways. Furthermore, novel approaches are increasingly necessary to better understand complexity in household responses to these environmental changes (Kok et al. 2016 ; Okpara et al. 2016 ). This paper analyzes the relationship between specific household characteristics and their decisions to adopt drought adaptation strategies. It does so by combining multiple methods: analyzing the co-occurrence of household characteristics with adoption (or not) of drought adaptation strategy, and complementing this information with qualitative comparative analysis and the thematic analysis of qualitative interview data. Vulnerability research has highlighted specific household traits that enable the ability to adopt drought adaptation strategies, including financial diversity (de Janvry and Sadoulet 2001 ), the amount and type of land and livestock owned (Massey et al. 2010 ), membership in social organizations (a mechanism to draw on social capital and social networks for help) (Narayan and Pritchett 1999 ), female education (Blankespoor et al. 2010 ), and access to fresh water sources (Gray 2009 ). Previous research has also identified the main coping and adapting strategies that smallholder rural households take during drought: changing farm practices, finding off-farm work, and migrating. Changing farm practices and finding off-farm work have been shown to be important survival mechanisms among smallholder farmers (for example, Laube et al. 2012 ; Mardero et al. 2015 ). Others move the entire household or single household members away from the environmental threat (for example, Afifi et al. 2013 ; Alscher 2010 ; Gray and Mueller 2012 ; Leighton 2011 ; McLeman and Ploeger 2012 ), here defined as environmental migration. Footnote 1 Persistent environmental degradation might also undermine watershed health, reducing the economic benefit of staying for households who depend on immediate ecosystem services whether or not these households attribute their decision to the changing environmental conditions (IOM 2007 ). Climate model scenarios for Baja California Sur Mexico, predict that precipitation will decrease by as much as 30% by 2050 (Cavazos and Arriaga-Ramírez 2012 ). How households, and specifically rural households in this area, are likely to respond to extended droughts has not been well studied to date. Anecdotal evidence suggests that the rural households of Baja California Sur, known as rancheros sudcalifornianos, were more mobile in the past—they were able to move from one grazing area to another or switch to fishing on the coast to wait out the drought. The question of whether or not rancheros can maintain ranching as their main economic source and their lifestyles within a changing environmental and social context remains to be answered. In this paper, we assess whether and how specific household characteristics (traits) in Baja California Sur influence household adoption of four specific drought adaptation strategies: (1) environmental migration (direct), (2) household member migration (indirect), (3) changing farm practices, and (4) finding off-farm work. We assess these relationships by analyzing the co-occurrence of specific traits in cases of adoption versus not adoption of a drought adaptation strategy by analyzing how different trait configurations lead to adoption/not adoption of specific adaptation strategies, and by comparing these with an analysis of trait and adaptation strategy themes embedded in the in-depth interviews. Methods Study area The northern Mexican states registered significant drops in precipitation starting in 2006 and peaking in 2011–2012—the worst drought in Mexico in the previous 70 years (CONAGUA 2013 ). Baja California Sur recorded the most serious decrease in rainfall, by 70% ( ibid ). Mexico declared a federal drought emergency in three municipalities in Baja California Sur in 2011 where rural rancheros live ( ibid )—two of which are studied here (Figure 1 Site Map, Online Resources). The rural area adjacent to the state capital of La Paz runs along the corridors of the Novillo and Trincheras mountain ranges, which receive the most rain per year in this region and is considered the main recharge zone for the city’s only aquifer. Through discussions with local practitioners, it was estimated that the total population in 2010 in the Sierra catchments was approximately 750 persons in a 1417-km 2 area (Niparajá 2014 ). The other rural area, San Javier, is adjacent to the municipal capital of Loreto", "role": "user" }, { "content": "For farmers and ranchers in Mexico's southern Baja California peninsula during a six-year drought, the farther away they lived from urban areas, the more likely they were to have to make changes to cope with the dwindling supply of water, according to a Portland State University study. Melissa Haeffner, an assistant professor of environmental science and management at PSU's College of Liberal Arts and Sciences, said the findings highlight a rural-urban divide and show that ranchers' access to water was neither equal nor valued during the drought from 2006 to 2012. \"Where people live and how close they are to the city and how well the city can deliver those services to households was unequal across the population and it had devastating effects for households who were not able to access those resources,\" said Haeffner, the study's lead researcher. The study recommends government agencies focus efforts on enacting policies and programs to better protect rural households during a drought, such as supporting sustainable agriculture projects in the region, increasing transportation options to access city centers and providing access to insurance and credit schemes. The study, published online in February in the journal Regional Environmental Change, surveyed 163 households from two municipalities: a rural area adjacent to the state capital of La Paz and the village of San Javier, high in the Sierra la Giganta mountains. Haeffner looked at whether the ranchers migrated or stayed in place but had to change their farming practices or find different work because of the drought. She found that most people reported changing their practices—reducing their herds, trading cows for goats or corralling them, as some examples—or finding other work that could sustain them. But the biggest finding was that those who lived closer to the city center or the main highway had better access to water deliveries than those in more remote areas—because of distance and transportation issues—but still less than their urban counterparts. Haeffner said city dwellers were supplied with 250 liters per person per day, while the rural families had to rely on twice-weekly deliveries that only became less reliable as the drought dragged on. To make matters worse, the wells and streams that the ranchers and their ancestors had relied on for centuries were either contaminated or dried up. Haeffner said the narrow-minded view that ranchers are only drought-aid recipients needs to be challenged. \"If we think about their role in agriculture production and as people who are maintaining clean water for the city and the aquifer that serves the city, then we can think about how we support them and their livelihood in a completely different way,\" she said. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract This paper explores the relationship between specific household traits (region of residence, head of household occupation, financial diversity, female level of education, land and animal ownership, social capital, and climate perception) and choice of specific adaptation strategies used by households in two sites in Baja California Sur, Mexico, during a severe drought from 2006 to 2012 using survey data and key informant interviews. We analyzed the co-occurrence of household traits adopting different drought adaptation strategies, then applied Qualitative Comparative Analysis (QCA) to examine the relationship between traits and strategies and integrated interview data to understand how rancheros perceive associations. We found evidence of diversity among households within the larger cultural group, both in the types of resources they have available and in the adaptation strategies they select. However, the most robust finding across the analyses appeared to be urban access; that is, the more a household was able to access urban services including piped water, the less likely they were to have used one of the drought adaptation strategies under study. These findings suggest that social structure and public investments are stronger predictors of smallholder adaptation rather than individual household traits. We also found that rancheros seem to rely less on traditional environmental migration to adapt to drought and rather settle in key watershed zones. We call for targeted policies to address inequities to access fresh water, including urban water, during drought times for the benefit of overall watershed health and the sustainability of rural ranchero livelihoods as they evolve to respond to climatological and economic change. Access provided by Universität des es, -und Working on a manuscript? Avoid the common mistakes Introduction The increase in drought risk due to a progressively drier climate in the subtropical latitudes over parts of North America (Cook et al. 2010 ) translates to a growing need to understand how households will adapt to drought changes, and why households respond in certain ways. Furthermore, novel approaches are increasingly necessary to better understand complexity in household responses to these environmental changes (Kok et al. 2016 ; Okpara et al. 2016 ). This paper analyzes the relationship between specific household characteristics and their decisions to adopt drought adaptation strategies. It does so by combining multiple methods: analyzing the co-occurrence of household characteristics with adoption (or not) of drought adaptation strategy, and complementing this information with qualitative comparative analysis and the thematic analysis of qualitative interview data. Vulnerability research has highlighted specific household traits that enable the ability to adopt drought adaptation strategies, including financial diversity (de Janvry and Sadoulet 2001 ), the amount and type of land and livestock owned (Massey et al. 2010 ), membership in social organizations (a mechanism to draw on social capital and social networks for help) (Narayan and Pritchett 1999 ), female education (Blankespoor et al. 2010 ), and access to fresh water sources (Gray 2009 ). Previous research has also identified the main coping and adapting strategies that smallholder rural households take during drought: changing farm practices, finding off-farm work, and migrating. Changing farm practices and finding off-farm work have been shown to be important survival mechanisms among smallholder farmers (for example, Laube et al. 2012 ; Mardero et al. 2015 ). Others move the entire household or single household members away from the environmental threat (for example, Afifi et al. 2013 ; Alscher 2010 ; Gray and Mueller 2012 ; Leighton 2011 ; McLeman and Ploeger 2012 ), here defined as environmental migration. Footnote 1 Persistent environmental degradation might also undermine watershed health, reducing the economic benefit of staying for households who depend on immediate ecosystem services whether or not these households attribute their decision to the changing environmental conditions (IOM 2007 ). Climate model scenarios for Baja California Sur Mexico, predict that precipitation will decrease by as much as 30% by 2050 (Cavazos and Arriaga-Ramírez 2012 ). How households, and specifically rural households in this area, are likely to respond to extended droughts has not been well studied to date. Anecdotal evidence suggests that the rural households of Baja California Sur, known as rancheros sudcalifornianos, were more mobile in the past—they were able to move from one grazing area to another or switch to fishing on the coast to wait out the drought. The question of whether or not rancheros can maintain ranching as their main economic source and their lifestyles within a changing environmental and social context remains to be answered. In this paper, we assess whether and how specific household characteristics (traits) in Baja California Sur influence household adoption of four specific drought adaptation strategies: (1) environmental migration (direct), (2) household member migration (indirect), (3) changing farm practices, and (4) finding off-farm work. We assess these relationships by analyzing the co-occurrence of specific traits in cases of adoption versus not adoption of a drought adaptation strategy by analyzing how different trait configurations lead to adoption/not adoption of specific adaptation strategies, and by comparing these with an analysis of trait and adaptation strategy themes embedded in the in-depth interviews. Methods Study area The northern Mexican states registered significant drops in precipitation starting in 2006 and peaking in 2011–2012—the worst drought in Mexico in the previous 70 years (CONAGUA 2013 ). Baja California Sur recorded the most serious decrease in rainfall, by 70% ( ibid ). Mexico declared a federal drought emergency in three municipalities in Baja California Sur in 2011 where rural rancheros live ( ibid )—two of which are studied here (Figure 1 Site Map, Online Resources). The rural area adjacent to the state capital of La Paz runs along the corridors of the Novillo and Trincheras mountain ranges, which receive the most rain per year in this region and is considered the main recharge zone for the city’s only aquifer. Through discussions with local practitioners, it was estimated that the total population in 2010 in the Sierra catchments was approximately 750 persons in a 1417-km 2 area (Niparajá 2014 ). The other rural area, San Javier, is adjacent to the municipal capital of Loreto<|im_end|> <|im_start|>assistant For farmers and ranchers in Mexico's southern Baja California peninsula during a six-year drought, the farther away they lived from urban areas, the more likely they were to have to make changes to cope with the dwindling supply of water, according to a Portland State University study. Melissa Haeffner, an assistant professor of environmental science and management at PSU's College of Liberal Arts and Sciences, said the findings highlight a rural-urban divide and show that ranchers' access to water was neither equal nor valued during the drought from 2006 to 2012. "Where people live and how close they are to the city and how well the city can deliver those services to households was unequal across the population and it had devastating effects for households who were not able to access those resources," said Haeffner, the study's lead researcher. The study recommends government agencies focus efforts on enacting policies and programs to better protect rural households during a drought, such as supporting sustainable agriculture projects in the region, increasing transportation options to access city centers and providing access to insurance and credit schemes. The study, published online in February in the journal Regional Environmental Change, surveyed 163 households from two municipalities: a rural area adjacent to the state capital of La Paz and the village of San Javier, high in the Sierra la Giganta mountains. Haeffner looked at whether the ranchers migrated or stayed in place but had to change their farming practices or find different work because of the drought. She found that most people reported changing their practices—reducing their herds, trading cows for goats or corralling them, as some examples—or finding other work that could sustain them. But the biggest finding was that those who lived closer to the city center or the main highway had better access to water deliveries than those in more remote areas—because of distance and transportation issues—but still less than their urban counterparts. Haeffner said city dwellers were supplied with 250 liters per person per day, while the rural families had to rely on twice-weekly deliveries that only became less reliable as the drought dragged on. To make matters worse, the wells and streams that the ranchers and their ancestors had relied on for centuries were either contaminated or dried up. Haeffner said the narrow-minded view that ranchers are only drought-aid recipients needs to be challenged. "If we think about their role in agriculture production and as people who are maintaining clean water for the city and the aquifer that serves the city, then we can think about how we support them and their livelihood in a completely different way," she said. <|im_end|>

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1,852

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Memory is believed to occur in the human brain as a result of two types of synaptic plasticity: short-term plasticity (STP) and long-term potentiation (LTP; refs 1 , 2 , 3 , 4 ). In neuromorphic engineering 5 , 6 , emulation of known neural behaviour has proven to be difficult to implement in software because of the highly complex interconnected nature of thought processes. Here we report the discovery of a Ag 2 S inorganic synapse, which emulates the synaptic functions of both STP and LTP characteristics through the use of input pulse repetition time. The structure known as an atomic switch 7 , 8 , operating at critical voltages, stores information as STP with a spontaneous decay of conductance level in response to intermittent input stimuli, whereas frequent stimulation results in a transition to LTP. The Ag 2 S inorganic synapse has interesting characteristics with analogies to an individual biological synapse, and achieves dynamic memorization in a single device without the need of external preprogramming. A psychological model related to the process of memorizing and forgetting is also demonstrated using the inorganic synapses. Our Ag 2 S element indicates a breakthrough in mimicking synaptic behaviour essential for the further creation of artificial neural systems that emulate characteristics of human memory. Main Neuroplasticity, where changes in the strength of synaptic connections (or weights) are caused by memorization events, underlies the ability of the brain to memorize. STP is achieved through the temporal enhancement of a synaptic connection, which then quickly decays to its initial state. However, repeated stimulation causes a permanent change in the connection to achieve LTP; shorter repetition intervals enable efficient LTP formation from fewer stimuli. Although synaptic behaviour has been imitated by hardware-based neural networks such as hybrid complementary metal–oxide–semiconductor analogue circuits or other artificial neural devices 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , no inherent hardware-based memorizing ability has been implemented and is currently achieved through software programming. Recently, electrically induced switching phenomena have been shown in nanoscale ionic-based devices, which have been proposed as a basis for future non-volatile memories 21 , 22 , 23 . In non-stoichiometric materials with ionic and electronic conductivity, ion migration is coupled to reduction and oxidation processes that result in large electrical conductance changes. Artificial synaptic devices operated by ion migration have been reported 24 , and some of these devices 25 , 26 have shown evidence of spike-timing-dependent plasticity 27 characteristics. Spike-timing-dependent plasticity is an important memorization mechanism related to the synaptic strength of connections in biological circuits and synthetic devices that emulate the spike-timing-dependent plasticity model. They require precise control of the relative timing between the signals applied to the two electrodes, to mimic the pre- and post-synaptic potentials in biological systems. In previous work, we reported an atomic switch 7 , 8 , which is a two-terminal electroionics-based device, where formation and annihilation of a metallic atom bridge is controlled in a nanogap situated between two electrodes (typical current–voltage characteristics are presented in Supplementary Fig. S1 ). It uses a solid-state electrochemical reaction, which indicates the presence of some characteristics of memory formation related to a synaptic connection 28 , 29 . Namely, the switch showed two types of conductance state: one that rapidly fades away after weak signal inputs, analogous to STP, and a second long-lived stable state requiring a strong signal for erasure, conceptually analogous to LTP. Changes in conductance, including a transition between these two states, were observed on application of specific bias voltages, where conductance was determined by the history of previous input signals. As the adjustment of the timing of pre- and post-synaptic potential is not required, a new approach for emulating synaptic behaviour is available for exploration. However, a time dependence was not observed in that work, although it is an essential characteristic of neuroplasticity. Here, we report that the decay of conductance occurred in STP without any application of bias voltage, resulting in both time-dependent STP and LTP behaviour in a single device, which we find is dependent on stimulation rate. In a Ag 2 S inorganic synapse, we relate the temporal enhancement of conductance to STP, and find that it occurs before the complete formation of a metallic atomic-sized bridge, and that the decay in conductance is explainable by deformation of an incomplete bridge. Once a robust bridge is formed, the enhancement persists for a long period of time, that is, corresponding to LTP, as schematically illustrated in Fig. 1a . Moreover, we present a psychological model related to memorizing and forgetting, that was duplicated through a rehearsal process of the inorganic synapse by using the decay behaviour in measured electrical conductance. Figure 1: Inorganic synapse showing STP and LTP, depending on input-pulse repetition time. a , Schematics of a Ag 2 S inorganic synapse and the signal transmission of a biological synapse. Application of input pulses causes the precipitation of Ag atoms from the Ag 2 S electrode, resulting in the formation of a Ag atomic bridge between the Ag 2 S electrode and a counter metal electrode. When the precipitated Ag atoms do not form a bridge, the inorganic synapse works as STP. After an atomic bridge is formed, it works as LTP. In the case of a biological synapse, the release of neurotransmitters is caused by the arrival of action potentials generated by firing, and then a signal is transmitted as a synaptic potential. Frequent stimulation causes long-term enhancement in the strength of the synaptic connection. b , c , Change in the conductance of the inorganic synapse when the input pulses ( V =80 mV, W =0.5 s) were applied with intervals of T =20 s ( b ) and 2 s ( c ). The conductance of the inorganic synapse with a single atomic contact is 2 e 2 / h (=77.5 μS), where e is the elementary charge, and h is Planck’s constant.", "role": "user" }, { "content": "A joint research group of International Center for Materials Nanoarchitectonics, NIMS, and Department of Chemistry and Biochemistry, University of California, Los Angeles succeeded in developing a new inorganic device named \"synapse device\". National Institute of Materials Science (NIMS) and Japan Science and Technology Agency (JST) announced that a joint research group of International Center for Materials Nanoarchitectonics, NIMS, and Department of Chemistry and Biochemistry, University of California, Los Angeles succeeded in developing a new inorganic device named \"synapse device\", which automatically realizes two types of functions analogous to those of the human brain, i.e., memorizing and forgetting. Details are published online in Nature Materials. The device is made with the atomic switch which consists of an Ag2S-coated metal Ag electrode and a counter electrode of platinum Pt, having a nanometer gap between the two electrodes. The atomic switch works by the formation and annihilation of an Ag-atom bridge between the electrodes, which is realized by controlling the solid-state electrochemical reaction of a mixed ionic and electronic conductor Ag2S. The research group discovered that the device emulates two types of synaptic function, short-term plasticity and long-term potentiation by varying input pulse repetition time which controls the formation of the Ag-atom bridges. The published paper in Nature Materials remarks that the Ag2S device indicates a breakthrough in mimicking synaptic behavior essential for further creation of artificial neural systems that emulate human memories. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Memory is believed to occur in the human brain as a result of two types of synaptic plasticity: short-term plasticity (STP) and long-term potentiation (LTP; refs 1 , 2 , 3 , 4 ). In neuromorphic engineering 5 , 6 , emulation of known neural behaviour has proven to be difficult to implement in software because of the highly complex interconnected nature of thought processes. Here we report the discovery of a Ag 2 S inorganic synapse, which emulates the synaptic functions of both STP and LTP characteristics through the use of input pulse repetition time. The structure known as an atomic switch 7 , 8 , operating at critical voltages, stores information as STP with a spontaneous decay of conductance level in response to intermittent input stimuli, whereas frequent stimulation results in a transition to LTP. The Ag 2 S inorganic synapse has interesting characteristics with analogies to an individual biological synapse, and achieves dynamic memorization in a single device without the need of external preprogramming. A psychological model related to the process of memorizing and forgetting is also demonstrated using the inorganic synapses. Our Ag 2 S element indicates a breakthrough in mimicking synaptic behaviour essential for the further creation of artificial neural systems that emulate characteristics of human memory. Main Neuroplasticity, where changes in the strength of synaptic connections (or weights) are caused by memorization events, underlies the ability of the brain to memorize. STP is achieved through the temporal enhancement of a synaptic connection, which then quickly decays to its initial state. However, repeated stimulation causes a permanent change in the connection to achieve LTP; shorter repetition intervals enable efficient LTP formation from fewer stimuli. Although synaptic behaviour has been imitated by hardware-based neural networks such as hybrid complementary metal–oxide–semiconductor analogue circuits or other artificial neural devices 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , no inherent hardware-based memorizing ability has been implemented and is currently achieved through software programming. Recently, electrically induced switching phenomena have been shown in nanoscale ionic-based devices, which have been proposed as a basis for future non-volatile memories 21 , 22 , 23 . In non-stoichiometric materials with ionic and electronic conductivity, ion migration is coupled to reduction and oxidation processes that result in large electrical conductance changes. Artificial synaptic devices operated by ion migration have been reported 24 , and some of these devices 25 , 26 have shown evidence of spike-timing-dependent plasticity 27 characteristics. Spike-timing-dependent plasticity is an important memorization mechanism related to the synaptic strength of connections in biological circuits and synthetic devices that emulate the spike-timing-dependent plasticity model. They require precise control of the relative timing between the signals applied to the two electrodes, to mimic the pre- and post-synaptic potentials in biological systems. In previous work, we reported an atomic switch 7 , 8 , which is a two-terminal electroionics-based device, where formation and annihilation of a metallic atom bridge is controlled in a nanogap situated between two electrodes (typical current–voltage characteristics are presented in Supplementary Fig. S1 ). It uses a solid-state electrochemical reaction, which indicates the presence of some characteristics of memory formation related to a synaptic connection 28 , 29 . Namely, the switch showed two types of conductance state: one that rapidly fades away after weak signal inputs, analogous to STP, and a second long-lived stable state requiring a strong signal for erasure, conceptually analogous to LTP. Changes in conductance, including a transition between these two states, were observed on application of specific bias voltages, where conductance was determined by the history of previous input signals. As the adjustment of the timing of pre- and post-synaptic potential is not required, a new approach for emulating synaptic behaviour is available for exploration. However, a time dependence was not observed in that work, although it is an essential characteristic of neuroplasticity. Here, we report that the decay of conductance occurred in STP without any application of bias voltage, resulting in both time-dependent STP and LTP behaviour in a single device, which we find is dependent on stimulation rate. In a Ag 2 S inorganic synapse, we relate the temporal enhancement of conductance to STP, and find that it occurs before the complete formation of a metallic atomic-sized bridge, and that the decay in conductance is explainable by deformation of an incomplete bridge. Once a robust bridge is formed, the enhancement persists for a long period of time, that is, corresponding to LTP, as schematically illustrated in Fig. 1a . Moreover, we present a psychological model related to memorizing and forgetting, that was duplicated through a rehearsal process of the inorganic synapse by using the decay behaviour in measured electrical conductance. Figure 1: Inorganic synapse showing STP and LTP, depending on input-pulse repetition time. a , Schematics of a Ag 2 S inorganic synapse and the signal transmission of a biological synapse. Application of input pulses causes the precipitation of Ag atoms from the Ag 2 S electrode, resulting in the formation of a Ag atomic bridge between the Ag 2 S electrode and a counter metal electrode. When the precipitated Ag atoms do not form a bridge, the inorganic synapse works as STP. After an atomic bridge is formed, it works as LTP. In the case of a biological synapse, the release of neurotransmitters is caused by the arrival of action potentials generated by firing, and then a signal is transmitted as a synaptic potential. Frequent stimulation causes long-term enhancement in the strength of the synaptic connection. b , c , Change in the conductance of the inorganic synapse when the input pulses ( V =80 mV, W =0.5 s) were applied with intervals of T =20 s ( b ) and 2 s ( c ). The conductance of the inorganic synapse with a single atomic contact is 2 e 2 / h (=77.5 μS), where e is the elementary charge, and h is Planck’s constant.<|im_end|> <|im_start|>assistant A joint research group of International Center for Materials Nanoarchitectonics, NIMS, and Department of Chemistry and Biochemistry, University of California, Los Angeles succeeded in developing a new inorganic device named "synapse device". National Institute of Materials Science (NIMS) and Japan Science and Technology Agency (JST) announced that a joint research group of International Center for Materials Nanoarchitectonics, NIMS, and Department of Chemistry and Biochemistry, University of California, Los Angeles succeeded in developing a new inorganic device named "synapse device", which automatically realizes two types of functions analogous to those of the human brain, i.e., memorizing and forgetting. Details are published online in Nature Materials. The device is made with the atomic switch which consists of an Ag2S-coated metal Ag electrode and a counter electrode of platinum Pt, having a nanometer gap between the two electrodes. The atomic switch works by the formation and annihilation of an Ag-atom bridge between the electrodes, which is realized by controlling the solid-state electrochemical reaction of a mixed ionic and electronic conductor Ag2S. The research group discovered that the device emulates two types of synaptic function, short-term plasticity and long-term potentiation by varying input pulse repetition time which controls the formation of the Ag-atom bridges. The published paper in Nature Materials remarks that the Ag2S device indicates a breakthrough in mimicking synaptic behavior essential for further creation of artificial neural systems that emulate human memories. <|im_end|>

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11, 28772, 12172, 374, 34356, 311, 14278, 323, 71162, 11618, 430, 1121, 304, 3544, 20314, 6929, 685, 4442, 13, 59294, 99827, 7766, 24026, 555, 28772, 12172, 617, 1027, 5068, 220, 1187, 1174, 323, 1063, 315, 1521, 7766, 220, 914, 1174, 220, 1627, 617, 6982, 6029, 315, 37393, 2442, 60176, 43918, 12466, 488, 220, 1544, 17910, 13, 61352, 2442, 60176, 43918, 12466, 488, 374, 459, 3062, 16420, 2065, 17383, 5552, 311, 279, 99827, 8333, 315, 13537, 304, 24156, 46121, 323, 28367, 7766, 430, 66585, 279, 37393, 2442, 60176, 43918, 12466, 488, 1646, 13, 2435, 1397, 24473, 2585, 315, 279, 8844, 18912, 1990, 279, 17738, 9435, 311, 279, 1403, 80390, 11, 311, 56459, 279, 864, 12, 323, 1772, 1355, 1910, 53274, 95358, 304, 24156, 6067, 13, 763, 3766, 990, 11, 584, 5068, 459, 25524, 3480, 220, 22, 1174, 220, 23, 1174, 902, 374, 264, 1403, 91723, 25396, 290, 1233, 6108, 3756, 11, 1405, 18488, 323, 3008, 92341, 315, 264, 46258, 19670, 14497, 374, 14400, 304, 264, 20622, 540, 391, 31183, 1990, 1403, 80390, 320, 3737, 950, 1510, 4235, 85, 27587, 17910, 527, 10666, 304, 99371, 23966, 13, 328, 16, 7609, 1102, 5829, 264, 6573, 21395, 25396, 32056, 13010, 11, 902, 15151, 279, 9546, 315, 1063, 17910, 315, 5044, 18488, 5552, 311, 264, 99827, 3717, 220, 1591, 1174, 220, 1682, 662, 31074, 989, 11, 279, 3480, 8710, 1403, 4595, 315, 6929, 685, 1614, 25, 832, 430, 19019, 87509, 3201, 1306, 7621, 8450, 11374, 11, 79283, 311, 4015, 47, 11, 323, 264, 2132, 1317, 62954, 15528, 1614, 23537, 264, 3831, 8450, 369, 2781, 4058, 11, 7434, 1870, 79283, 311, 445, 4334, 13, 29240, 304, 6929, 685, 11, 2737, 264, 9320, 1990, 1521, 1403, 5415, 11, 1051, 13468, 389, 3851, 315, 3230, 15837, 16798, 1154, 11, 1405, 6929, 685, 574, 11075, 555, 279, 3925, 315, 3766, 1988, 17738, 13, 1666, 279, 28174, 315, 279, 18912, 315, 864, 12, 323, 1772, 1355, 1910, 53274, 4754, 374, 539, 2631, 11, 264, 502, 5603, 369, 991, 15853, 99827, 17432, 374, 2561, 369, 27501, 13, 4452, 11, 264, 892, 44393, 574, 539, 13468, 304, 430, 990, 11, 8051, 433, 374, 459, 7718, 29683, 315, 18247, 501, 5174, 488, 13, 5810, 11, 584, 1934, 430, 279, 31815, 315, 6929, 685, 10222, 304, 4015, 47, 2085, 904, 3851, 315, 15837, 22465, 11, 13239, 304, 2225, 892, 43918, 4015, 47, 323, 445, 4334, 17432, 304, 264, 3254, 3756, 11, 902, 584, 1505, 374, 18222, 389, 41959, 4478, 13, 763, 264, 4701, 220, 17, 328, 304, 61694, 6925, 7629, 11, 584, 29243, 279, 37015, 27886, 315, 6929, 685, 311, 4015, 47, 11, 323, 1505, 430, 433, 13980, 1603, 279, 4686, 18488, 315, 264, 46258, 25524, 28935, 14497, 11, 323, 430, 279, 31815, 304, 6929, 685, 374, 10552, 481, 555, 91621, 315, 459, 33243, 14497, 13, 9843, 264, 22514, 14497, 374, 14454, 11, 279, 27886, 67145, 369, 264, 1317, 4261, 315, 892, 11, 430, 374, 11, 12435, 311, 445, 4334, 11, 439, 20225, 7167, 36762, 304, 23966, 13, 220, 16, 64, 662, 23674, 11, 584, 3118, 264, 24064, 1646, 5552, 311, 16420, 4954, 323, 66127, 11, 430, 574, 56003, 1555, 264, 89955, 1920, 315, 279, 304, 61694, 6925, 7629, 555, 1701, 279, 31815, 17432, 304, 17303, 20314, 6929, 685, 13, 19575, 220, 16, 25, 763, 61694, 6925, 7629, 9204, 4015, 47, 323, 445, 4334, 11, 11911, 389, 1988, 2320, 17660, 54515, 892, 13, 264, 1174, 328, 2464, 29470, 315, 264, 4701, 220, 17, 328, 304, 61694, 6925, 7629, 323, 279, 8450, 18874, 315, 264, 24156, 6925, 7629, 13, 7473, 315, 1988, 66557, 11384, 279, 61050, 315, 4701, 33299, 505, 279, 4701, 220, 17, 328, 72048, 11, 13239, 304, 279, 18488, 315, 264, 4701, 25524, 14497, 1990, 279, 4701, 220, 17, 328, 72048, 323, 264, 5663, 9501, 72048, 13, 3277, 279, 36841, 33337, 4701, 33299, 656, 539, 1376, 264, 14497, 11, 279, 304, 61694, 6925, 7629, 4375, 439, 4015, 47, 13, 4740, 459, 25524, 14497, 374, 14454, 11, 433, 4375, 439, 445, 4334, 13, 763, 279, 1162, 315, 264, 24156, 6925, 7629, 11, 279, 4984, 315, 90351, 83189, 374, 9057, 555, 279, 19163, 315, 1957, 95358, 8066, 555, 23677, 11, 323, 1243, 264, 8450, 374, 34699, 439, 264, 99827, 4754, 13, 7730, 17187, 41959, 11384, 1317, 9860, 27886, 304, 279, 8333, 315, 279, 99827, 3717, 13, 293, 1174, 272, 1174, 10604, 304, 279, 6929, 685, 315, 279, 304, 61694, 6925, 7629, 994, 279, 1988, 66557, 320, 650, 284, 1490, 296, 53, 11, 468, 284, 15, 13, 20, 274, 8, 1051, 9435, 449, 28090, 315, 350, 284, 508, 274, 320, 293, 883, 323, 220, 17, 274, 320, 272, 7609, 578, 6929, 685, 315, 279, 304, 61694, 6925, 7629, 449, 264, 3254, 25524, 3729, 374, 220, 17, 384, 220, 17, 611, 305, 39838, 2813, 13, 20, 33983, 50, 705, 1405, 384, 374, 279, 36256, 6900, 11, 323, 305, 374, 9878, 377, 753, 6926, 13, 128257, 198, 128256, 78191, 198, 32, 10496, 3495, 1912, 315, 7327, 5955, 369, 32009, 64051, 1132, 8525, 263, 1233, 11, 452, 63564, 11, 323, 6011, 315, 42846, 323, 24432, 52755, 11, 3907, 315, 7188, 11, 9853, 12167, 26399, 304, 11469, 264, 502, 304, 61694, 3756, 7086, 330, 20960, 7629, 3756, 3343, 5165, 10181, 315, 32009, 10170, 320, 45, 63564, 8, 323, 6457, 10170, 323, 12053, 16784, 320, 41, 790, 8, 7376, 430, 264, 10496, 3495, 1912, 315, 7327, 5955, 369, 32009, 64051, 1132, 8525, 263, 1233, 11, 452, 63564, 11, 323, 6011, 315, 42846, 323, 24432, 52755, 11, 3907, 315, 7188, 11, 9853, 12167, 26399, 304, 11469, 264, 502, 304, 61694, 3756, 7086, 330, 20960, 7629, 3756, 498, 902, 9651, 52694, 1403, 4595, 315, 5865, 79283, 311, 1884, 315, 279, 3823, 8271, 11, 602, 1770, 2637, 16420, 4954, 323, 66127, 13, 12589, 527, 4756, 2930, 304, 22037, 32009, 13, 578, 3756, 374, 1903, 449, 279, 25524, 3480, 902, 17610, 315, 459, 4701, 17, 50, 23283, 660, 9501, 4701, 72048, 323, 264, 5663, 72048, 315, 63327, 52170, 11, 3515, 264, 20622, 21037, 13225, 1990, 279, 1403, 80390, 13, 578, 25524, 3480, 4375, 555, 279, 18488, 323, 3008, 92341, 315, 459, 4701, 12, 22612, 14497, 1990, 279, 80390, 11, 902, 374, 15393, 555, 26991, 279, 6573, 21395, 25396, 32056, 13010, 315, 264, 9709, 220, 21427, 323, 14683, 61856, 4701, 17, 50, 13, 578, 3495, 1912, 11352, 430, 279, 3756, 991, 24031, 1403, 4595, 315, 99827, 734, 11, 2875, 9860, 12466, 488, 323, 1317, 9860, 36875, 7246, 555, 29865, 1988, 28334, 54515, 892, 902, 11835, 279, 18488, 315, 279, 4701, 12, 22612, 40073, 13, 578, 4756, 5684, 304, 22037, 32009, 24208, 430, 279, 4701, 17, 50, 3756, 15151, 264, 42445, 304, 28003, 16671, 99827, 7865, 7718, 369, 4726, 9886, 315, 21075, 30828, 6067, 430, 66585, 3823, 19459, 13, 220, 128257, 198 ]

1,639

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The nanoscale mode volumes of surface plasmon polaritons have enabled plasmonic lasers and condensates with ultrafast operation 1 , 2 , 3 , 4 . Most plasmonic lasers are based on noble metals, rendering the optical mode structure inert to external fields. Here we demonstrate active magnetic-field control over lasing in a periodic array of Co/Pt multilayer nanodots immersed in an IR-140 dye solution. We exploit the magnetic nature of the nanoparticles combined with mode tailoring to control the lasing action. Under circularly polarized excitation, angle-resolved photoluminescence measurements reveal a transition between the lasing action and non-lasing emission as the nanodot magnetization is reversed. Our results introduce magnetization as a means of externally controlling plasmonic nanolasers, complementary to modulation by excitation 5 , gain medium 6 , 7 or substrate 8 . Further, the results show how the effects of magnetization on light that are inherently weak can be observed in the lasing regime, inspiring studies of topological photonics 9 , 10 , 11 . Main Plasmonic nanostructures feature electromagnetic modes that confine light into sub-wavelength volumes. Consequently, the Purcell effect is strong, and when such structures are paired with emitters, enhancement of both spontaneous and stimulated emission can be achieved. Plasmonic lasers have been realized with architectures ranging from single nanoparticles and metal–insulator thin films to random, aperiodic, periodic and superperiodic arrays of nanoparticles 1 , 2 , 3 , 12 , 13 , 14 , 15 . Although the effects of the nanoparticle shape and arrangement have been extensively studied 5 , 8 , 14 , the material choice has been mostly limited to noble metals, except for some recently proposed alternatives 16 , 17 . The selection of noble metals, and in particular dielectric alternatives, is motivated by the minimization of ohmic losses typical for plasmonic materials. Lower damping leads to a higher mode quality ( Q ) factor and a stronger Purcell effect, which benefits lasing. Due to inherently high ohmic losses, nanostructures made of magnetic materials have been largely overlooked as a platform for plasmonic lasers, even when they, in principle, would offer the powerful possibility of modifying the optical modes by a magnetic field during device operation 17 . Here we demonstrate that this unique advantage can be experimentally realized. Contrary to noble metals, the permittivity tensor of magnetic metals contains non-zero off-diagonal components that depend on the direction of magnetization. Consequently, magnetic switching alters the optical response of magnetic materials, giving rise to magneto-optical phenomena such as the Faraday effect, magneto-optical Kerr effect and magnetic circular dichroism (MCD). Although these effects have been successfully exploited in the field of plasmonics for biosensing applications utilizing phase-sensitive detection 18 , the absolute modulation of light intensity through magneto-optics is weak. For instance, the polarization of light reflected from or transmitted through arrays of magnetic nanodots rotates by up to 1° 19 , which corresponds to an intensity modulation of the order 1%. Here we show that, although small, magneto-optical effects lead to subtle changes in the mode structure of the array; these, in turn, become prominently visible due to nonlinearities inherent in a lasing process, enabling full on–off switching of the lasing action by an external magnetic field. To demonstrate the magnetic-field control of plasmonic lasing, we fabricated square and rectangular arrays of Co/Pt multilayer nanodots on a Au/SiO 2 bilayer and immersed the structures in a gain medium consisting of a 12 mM IR-140 dye solution (Methods). Figure 1a shows the full Ta(2)/Pt(4)/[Co(1)/Pt(1)] 30 /Pt(2) nanodot multilayer stack, where the [Co(1)/Pt(1)] bilayer repeats 30 times and the numbers in the parentheses indicate the layer thickness in nanometres. Hereafter, we refer to these structures as Co/Pt nanodots. Co/Pt multilayers were selected as the nanodot material because of their abrupt magnetic switching in a perpendicular magnetic field and full remanence (Supplementary Fig. 1 ), enabling the non-volatile magnetic-field control of plasmonic lasing. Nanodots of diameter D = 220 nm were arranged in periodic lattices (Fig. 1a ) with periods p x = p y = 590 nm for square arrays and p y ranging from 520 to 540 nm in steps of 5 nm for rectangular arrays. Arranging metallic nanostructures into periodic lattices enables the excitation of surface lattice resonances (SLRs), which are hybridized modes of the lattice diffraction orders and localized surface plasmons (LSPs) of the nanodots 20 . The experimental reflectivity spectrum of the square array ( p x = p y = 590 nm) displays a pronounced minimum at the SLR wavelength (Fig. 1b ), in agreement with finite-element method (FEM) simulations (Supplementary Fig. 2 ). The SLR of the nanodot array overlaps with the emission spectrum of the gain medium (Supplementary Fig. 3 ), which is essential for optical feedback. Moreover, the Q factor of the SLR mode compares with that of noble-metal systems 19 , providing high rates of stimulated emission. Fig. 1: Magnetic-field control of plasmonic lasing in a square array of Co/Pt nanodots. a , Co/Pt nanodots (top) with diameter D = 220 nm, height of 68 nm and perpendicular magnetization arranged in periodic lattices ( p x = p y = 590 nm) on top of a Au/SiO 2 bilayer (bottom). b , Experimental MCD and reflectivity spectra. Both spectra show prominent features at the SLR wavelength determined by the lattice period. The MCD spectrum is obtained by subtracting the reflectivity spectra of σ + light for up and down magnetization and signal normalization. The dashed line marks the wavelength of the pump pulses in the lasing experiments. c , PL intensity spectra recorded normal to the sample plane using σ − and σ + excitation for three pump fluences. For clarity, the PL intensity spectra corresponding to 48.9 μJ cm –2 have been multiplied by a factor of 10 and each fluence pair is vertically offset by 2,000 counts. d , e , PL intensity as a function of the pump laser fluence for σ − ( d ) and σ + ( e ) excitation.", "role": "user" }, { "content": "A magnetic field can be used to switch nanolasers on and off, shows new research from Aalto University. The physics underlying this discovery paves the way for the development of optical signals that cannot be disturbed by external disruptions, leading to unprecedented robustness in signal processing. Lasers concentrate light into extremely bright beams that are useful in a variety of domains, such as broadband communication and medical diagnostics devices. About ten years ago, extremely small and fast lasers known as plasmonic nanolasers were developed. These nanolasers are potentially more power-efficient than traditional lasers, and they have been of great advantage in many fields—for example, nanolasers have increased the sensitivity of biosensors used in medical diagnostics. So far, switching nanolasers on and off has required manipulating them directly, either mechanically or with the use of heat or light. Now, researchers have found a way to remotely control nanolasers. \"The novelty here is that we are able to control the lasing signal with an external magnetic field. By changing the magnetic field around our magnetic nanostructures, we can turn the lasing on and off,\" says Professor Sebastiaan van Dijken of Aalto University. The team accomplished this by making plasmonic nanolasers from different materials than normal. Instead of the usual noble metals, such as gold or silver, they used magnetic cobalt-platinum nanodots patterned on a continuous layer of gold and insulating silicon dioxide. Their analysis showed that both the material and the arrangement of the nanodots in periodic arrays were required for the effect. Photonics advances towards extremely robust signal processing The new control mechanism may prove useful in a range of devices that make use of optical signals, but its implications for the emerging field of topological photonics are even more exciting. Topological photonics aims to produce light signals that are not disturbed by external disruptions. This would have applications in many domains by providing very robust signal processing. \"The idea is that you can create specific optical modes that are topological, that have certain characteristics which allow them to be transported and protected against any disturbance,\" explains van Dijken. \"That means if there are defects in the device or because the material is rough, the light can just pass them by without being disturbed, because it is topologically protected.\" So far, creating topologically protected optical signals using magnetic materials has required strong magnetic fields. The new research shows that the effect of magnetism in this context can be unexpectedly amplified using a nanoparticle array of a particular symmetry. The researchers believe their findings could point the way to new, nanoscale, topologically protected signals. \"Normally, magnetic materials can cause a very minor change in the absorption and polarization of light. In these experiments, we produced very significant changes in the optical response—up to 20 percent. This has never been seen before,\" says van Dijken. Academy Professor Päivi Törmä adds that 'these results hold great potential for the realization of topological photonic structures wherein magnetization effects are amplified by a suitable choice of the nanoparticle array geometry.\" The results are published in Nature Photonics. These findings are the result of a long-lasting collaboration between the Nanomagnetism and Spintronics group led by Professor van Dijken and the Quantum Dynamics group led by Professor Törmä, both in the Department of Applied Physics at Aalto University. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The nanoscale mode volumes of surface plasmon polaritons have enabled plasmonic lasers and condensates with ultrafast operation 1 , 2 , 3 , 4 . Most plasmonic lasers are based on noble metals, rendering the optical mode structure inert to external fields. Here we demonstrate active magnetic-field control over lasing in a periodic array of Co/Pt multilayer nanodots immersed in an IR-140 dye solution. We exploit the magnetic nature of the nanoparticles combined with mode tailoring to control the lasing action. Under circularly polarized excitation, angle-resolved photoluminescence measurements reveal a transition between the lasing action and non-lasing emission as the nanodot magnetization is reversed. Our results introduce magnetization as a means of externally controlling plasmonic nanolasers, complementary to modulation by excitation 5 , gain medium 6 , 7 or substrate 8 . Further, the results show how the effects of magnetization on light that are inherently weak can be observed in the lasing regime, inspiring studies of topological photonics 9 , 10 , 11 . Main Plasmonic nanostructures feature electromagnetic modes that confine light into sub-wavelength volumes. Consequently, the Purcell effect is strong, and when such structures are paired with emitters, enhancement of both spontaneous and stimulated emission can be achieved. Plasmonic lasers have been realized with architectures ranging from single nanoparticles and metal–insulator thin films to random, aperiodic, periodic and superperiodic arrays of nanoparticles 1 , 2 , 3 , 12 , 13 , 14 , 15 . Although the effects of the nanoparticle shape and arrangement have been extensively studied 5 , 8 , 14 , the material choice has been mostly limited to noble metals, except for some recently proposed alternatives 16 , 17 . The selection of noble metals, and in particular dielectric alternatives, is motivated by the minimization of ohmic losses typical for plasmonic materials. Lower damping leads to a higher mode quality ( Q ) factor and a stronger Purcell effect, which benefits lasing. Due to inherently high ohmic losses, nanostructures made of magnetic materials have been largely overlooked as a platform for plasmonic lasers, even when they, in principle, would offer the powerful possibility of modifying the optical modes by a magnetic field during device operation 17 . Here we demonstrate that this unique advantage can be experimentally realized. Contrary to noble metals, the permittivity tensor of magnetic metals contains non-zero off-diagonal components that depend on the direction of magnetization. Consequently, magnetic switching alters the optical response of magnetic materials, giving rise to magneto-optical phenomena such as the Faraday effect, magneto-optical Kerr effect and magnetic circular dichroism (MCD). Although these effects have been successfully exploited in the field of plasmonics for biosensing applications utilizing phase-sensitive detection 18 , the absolute modulation of light intensity through magneto-optics is weak. For instance, the polarization of light reflected from or transmitted through arrays of magnetic nanodots rotates by up to 1° 19 , which corresponds to an intensity modulation of the order 1%. Here we show that, although small, magneto-optical effects lead to subtle changes in the mode structure of the array; these, in turn, become prominently visible due to nonlinearities inherent in a lasing process, enabling full on–off switching of the lasing action by an external magnetic field. To demonstrate the magnetic-field control of plasmonic lasing, we fabricated square and rectangular arrays of Co/Pt multilayer nanodots on a Au/SiO 2 bilayer and immersed the structures in a gain medium consisting of a 12 mM IR-140 dye solution (Methods). Figure 1a shows the full Ta(2)/Pt(4)/[Co(1)/Pt(1)] 30 /Pt(2) nanodot multilayer stack, where the [Co(1)/Pt(1)] bilayer repeats 30 times and the numbers in the parentheses indicate the layer thickness in nanometres. Hereafter, we refer to these structures as Co/Pt nanodots. Co/Pt multilayers were selected as the nanodot material because of their abrupt magnetic switching in a perpendicular magnetic field and full remanence (Supplementary Fig. 1 ), enabling the non-volatile magnetic-field control of plasmonic lasing. Nanodots of diameter D = 220 nm were arranged in periodic lattices (Fig. 1a ) with periods p x = p y = 590 nm for square arrays and p y ranging from 520 to 540 nm in steps of 5 nm for rectangular arrays. Arranging metallic nanostructures into periodic lattices enables the excitation of surface lattice resonances (SLRs), which are hybridized modes of the lattice diffraction orders and localized surface plasmons (LSPs) of the nanodots 20 . The experimental reflectivity spectrum of the square array ( p x = p y = 590 nm) displays a pronounced minimum at the SLR wavelength (Fig. 1b ), in agreement with finite-element method (FEM) simulations (Supplementary Fig. 2 ). The SLR of the nanodot array overlaps with the emission spectrum of the gain medium (Supplementary Fig. 3 ), which is essential for optical feedback. Moreover, the Q factor of the SLR mode compares with that of noble-metal systems 19 , providing high rates of stimulated emission. Fig. 1: Magnetic-field control of plasmonic lasing in a square array of Co/Pt nanodots. a , Co/Pt nanodots (top) with diameter D = 220 nm, height of 68 nm and perpendicular magnetization arranged in periodic lattices ( p x = p y = 590 nm) on top of a Au/SiO 2 bilayer (bottom). b , Experimental MCD and reflectivity spectra. Both spectra show prominent features at the SLR wavelength determined by the lattice period. The MCD spectrum is obtained by subtracting the reflectivity spectra of σ + light for up and down magnetization and signal normalization. The dashed line marks the wavelength of the pump pulses in the lasing experiments. c , PL intensity spectra recorded normal to the sample plane using σ − and σ + excitation for three pump fluences. For clarity, the PL intensity spectra corresponding to 48.9 μJ cm –2 have been multiplied by a factor of 10 and each fluence pair is vertically offset by 2,000 counts. d , e , PL intensity as a function of the pump laser fluence for σ − ( d ) and σ + ( e ) excitation.<|im_end|> <|im_start|>assistant A magnetic field can be used to switch nanolasers on and off, shows new research from Aalto University. The physics underlying this discovery paves the way for the development of optical signals that cannot be disturbed by external disruptions, leading to unprecedented robustness in signal processing. Lasers concentrate light into extremely bright beams that are useful in a variety of domains, such as broadband communication and medical diagnostics devices. About ten years ago, extremely small and fast lasers known as plasmonic nanolasers were developed. These nanolasers are potentially more power-efficient than traditional lasers, and they have been of great advantage in many fields—for example, nanolasers have increased the sensitivity of biosensors used in medical diagnostics. So far, switching nanolasers on and off has required manipulating them directly, either mechanically or with the use of heat or light. Now, researchers have found a way to remotely control nanolasers. "The novelty here is that we are able to control the lasing signal with an external magnetic field. By changing the magnetic field around our magnetic nanostructures, we can turn the lasing on and off," says Professor Sebastiaan van Dijken of Aalto University. The team accomplished this by making plasmonic nanolasers from different materials than normal. Instead of the usual noble metals, such as gold or silver, they used magnetic cobalt-platinum nanodots patterned on a continuous layer of gold and insulating silicon dioxide. Their analysis showed that both the material and the arrangement of the nanodots in periodic arrays were required for the effect. Photonics advances towards extremely robust signal processing The new control mechanism may prove useful in a range of devices that make use of optical signals, but its implications for the emerging field of topological photonics are even more exciting. Topological photonics aims to produce light signals that are not disturbed by external disruptions. This would have applications in many domains by providing very robust signal processing. "The idea is that you can create specific optical modes that are topological, that have certain characteristics which allow them to be transported and protected against any disturbance," explains van Dijken. "That means if there are defects in the device or because the material is rough, the light can just pass them by without being disturbed, because it is topologically protected." So far, creating topologically protected optical signals using magnetic materials has required strong magnetic fields. The new research shows that the effect of magnetism in this context can be unexpectedly amplified using a nanoparticle array of a particular symmetry. The researchers believe their findings could point the way to new, nanoscale, topologically protected signals. "Normally, magnetic materials can cause a very minor change in the absorption and polarization of light. In these experiments, we produced very significant changes in the optical response—up to 20 percent. This has never been seen before," says van Dijken. Academy Professor Päivi Törmä adds that 'these results hold great potential for the realization of topological photonic structures wherein magnetization effects are amplified by a suitable choice of the nanoparticle array geometry." The results are published in Nature Photonics. These findings are the result of a long-lasting collaboration between the Nanomagnetism and Spintronics group led by Professor van Dijken and the Quantum Dynamics group led by Professor Törmä, both in the Department of Applied Physics at Aalto University. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The initiating oncogenic event in almost half of human lung adenocarcinomas is still unknown, a fact that complicates the development of selective targeted therapies. Yet these tumours harbour a number of alterations without obvious oncogenic function including BRAF-inactivating mutations. Inactivating BRAF mutants in lung predominate over the activating V600E mutant that is frequently observed in other tumour types 1 . Here we demonstrate that the expression of an endogenous Braf(D631A) kinase-inactive isoform in mice (corresponding to the human BRAF(D594A) mutation) triggers lung adenocarcinoma in vivo , indicating that BRAF-inactivating mutations are initiating events in lung oncogenesis. Moreover, inactivating BRAF mutations have also been identified in a subset of KRAS-driven human lung tumours. Co-expression of Kras(G12V) and Braf(D631A) in mouse lung cells markedly enhances tumour initiation, a phenomenon mediated by Craf kinase activity 2 , 3 , and effectively accelerates tumour progression when activated in advanced lung adenocarcinomas. We also report a key role for the wild-type Braf kinase in sustaining Kras(G12V)/Braf(D631A)-driven tumours. Ablation of the wild-type Braf allele prevents the development of lung adenocarcinoma by inducing a further increase in MAPK signalling that results in oncogenic toxicity; this effect can be abolished by pharmacological inhibition of Mek to restore tumour growth. However, the loss of wild-type Braf also induces transdifferentiation of club cells, which leads to the rapid development of lethal intrabronchiolar lesions. These observations indicate that the signal intensity of the MAPK pathway is a critical determinant not only in tumour development, but also in dictating the nature of the cancer-initiating cell and ultimately the resulting tumour phenotype. Main The RAS–MAPK signalling cascade serves as a central node in transducing signals from membrane receptors to the nucleus. This pathway is aberrantly activated in a substantial fraction of human cancers 4 . Moreover, germline mutations resulting in limited activation of this signalling cascade cause developmental disorders known as RASopathies 5 . There is also abundant evidence that elevated RAS–MAPK signalling results in cellular toxicity that may serve as a natural barrier to cancer progression early in tumorigenesis 6 . Finally, genetic abrogation of this pathway in adult mice results in their rapid death 7 . These findings suggest that defined thresholds of RAS–MAPK activity are required for homeostasis as well as for malignant transformation, but compelling genetic evidence is missing. In order to augment MAPK signalling in controlled increments we have taken advantage of the expression of an endogenous Braf(D631A) kinase-dead isoform (corresponding to the human BRAF(D594A) mutant) that is known to induce Erk phosphorylation in a Craf-dependent manner 2 , 8 . This effect, known as the MAPK paradox, is due to enhanced heterodimerization and activation of the catalytically competent Craf protomer in Braf(D631A)–Craf complexes 2 , 3 . In agreement with these observations, lack of wild-type Braf expression in Kras G12V cell lines expressing Braf(D631A) increased the intensity and duration of MAPK signalling ( Extended Data Fig. 1 ), probably as a result of the exclusive formation of Braf(D631A)–Craf heterodimers. Thus, to generate controlled thresholds of MAPK intensity in vivo , we combined wild-type Braf , conditional knockout Braf lox and conditional knock-in Braf LSLD631A with an inducible Kras LSLG12Vgeo allele 9 (where LSL indicates a lox-STOP-lox motif). The resulting Kras +/ LSLG12Vgeo (hereto designated as K), Kras +/ LSLG12Vgeo ; Braf +/ LSLD631A (designated as KB) and Kras +/ LSLG12Vgeo ; Braf lox/LSLD631A (designated as KBL) strains were intratracheally infected with adenovirus expressing Cre recombinase (Ad-Cre). Cre-mediated recombination of these alleles results in the induction of distinct levels of Ras–MAPK signalling, with Braf +/+ driving lower activity, Braf +/ D631A intermediate intensity and Braf − /D631A maximal activation. This strategy allowed us to investigate the effect of various MAPK activity thresholds on cell transformation, adenocarcinoma development and cellular toxicity in vivo . Lung cells expressing these conditional alleles were identified by co-expression of the Kras(G12V) oncoprotein with β-geo, a chimaeric bacterial protein with β-galactosidase activity 9 ( Extended Data Fig. 2 ). As illustrated in Fig. 1a , small X-gal + hyperplasias could be readily detected in the lungs of K mice 1 month after Ad-Cre infection. By constrast, Ad-Cre-infected KB mice displayed abundant hyperplastic areas together with adenomas, a lesion that is extremely infrequent in K mice at this early stage 10 . Remarkably, X-gal + alveolar hyperplasias and adenomas were nearly absent in Ad-Cre-infected KBL animals. These mice, however, displayed hypertrophic bronchi as their most prominent feature ( Fig. 1a ). The lack of Kras G12V -driven alveolar lesions in KBL mice is unlikely to be a consequence of the absence of an active Braf, since this kinase is dispensable for the development of Kras G12V -driven lung adenocarcinoma 7 , 11 . Thus, we explored the possibility that the absence of alveolar lesions was due to some sort of cellular toxicity such as that caused by the induction of senescence or DNA damage, two phenomena known to act as barriers to tumour development 6 , 12 , 13 . Indeed, examination of lung lysates and sections from KBL mice detected p19 Arf and p53 tumour suppressors, active caspase-3 and γ-H2AX, a marker for DNA damage, as early as 1 week following Ad-Cre infection ( Fig. 1b, c ). We did not observe differences in senescence-associated β-gal staining (data not shown). The concomitant increase in the phosphorylation of Erk1/2 and p90Rsk suggested that elevated MAPK signalling triggered a stress response that impaired tumour cell proliferation. Yet it has been recently described that mutant Kras -driven lung adenocarcinomas display a tonic activation of the DNA damage response to prevent the induction of genotoxic stress 14 . We hypothesize that the exclusive formation of Braf(D631A)–Craf complexes in KBL mice exceeded such a toxic signalling threshold and induced a stress response incompatible with tumour development. Thus, our results indicate that Ras-oncogenic toxicity is quantitatively dictated by MAPK function. In support of this hypothesis, whereas Mek inhibition prevented tumour growth in Ad-Cre-infected KB mice, it rescued the toxic phenotype in KBL animals in a dose-dependent manner and restored", "role": "user" }, { "content": "The initiating oncogenic event in almost half of human lung adenocarcinomas is still unknown, complicating the development of selective targeted therapies. Yet these tumours harbour a number of alterations without obvious oncogenic function, including BRAF-inactivating mutations. Researchers at the Spanish National Cancer Research Centre (CNIO) have demonstrated that the expression of an endogenous Braf (D631A) kinase-inactive isoform in mice, corresponding to the human BRAF(D594A) mutation, triggers lung adenocarcinoma in vivo, indicating that BRAF-inactivating mutations are initiating events in lung oncogenesis. The paper, published in Nature, indicates that the signal intensity of the MAPK pathway is a critical determinant not only in tumour development, but also in dictating the nature of the cancer-initiating cell and ultimately the resulting tumour phenotype. The RAS-MAPK signalling cascade serves as a central node in transducing signals from membrane receptors to the nucleus. This pathway is aberrantly activated in a substantial fraction of human cancers. There is also abundant evidence that elevated RAS-MAPK signaling results in cellular toxicity that may serve as a natural barrier to cancer progression early in tumorigenesis. These findings suggest that defined thresholds of RAS-MAPK activity are required for homeostasis as well as for malignant transformation, but compelling genetic evidence is missing. Mutational analysis of different human cancers has recently uncovered that among the BRAF hot spots in lung adenocarcinoma, which comprise a component of the RAS-MAP kinase pathway, those resulting in inactivating mutations predominate over the V600E activating substitution, the main oncogenic form in other tumours such as melanoma. However, the contribution of BRAF-inactive mutants to lung cancer progression is unclear. Using public databases, researchers have identified inactivating BRAF mutations in a subset of KRAS-driven human lung tumours. Subsequently, using mouse models, researchers have replicated these observations showing that the co-expression of oncogenic Kras and inactive Braf markedly enhances the onset of lung adenocarcinoma. Also, this combination accelerates tumour progression when the inactivating Braf mutation is genetically induced in advanced tumors. Surprisingly, in this same study, the researchers showed that individually, the inactivating mutations of Braf are also oncogenic events that induce the appearance of lung adenocarcinoma. The paper provides the first genetic evidence demonstrating that a kinase-inactivating Braf mutation induces lung adenocarcinoma development. Moreover, results suggest that lung adenocarcinoma patients with hypoactive BRAF could benefit from therapies based on selective CRAF inhibitors. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The initiating oncogenic event in almost half of human lung adenocarcinomas is still unknown, a fact that complicates the development of selective targeted therapies. Yet these tumours harbour a number of alterations without obvious oncogenic function including BRAF-inactivating mutations. Inactivating BRAF mutants in lung predominate over the activating V600E mutant that is frequently observed in other tumour types 1 . Here we demonstrate that the expression of an endogenous Braf(D631A) kinase-inactive isoform in mice (corresponding to the human BRAF(D594A) mutation) triggers lung adenocarcinoma in vivo , indicating that BRAF-inactivating mutations are initiating events in lung oncogenesis. Moreover, inactivating BRAF mutations have also been identified in a subset of KRAS-driven human lung tumours. Co-expression of Kras(G12V) and Braf(D631A) in mouse lung cells markedly enhances tumour initiation, a phenomenon mediated by Craf kinase activity 2 , 3 , and effectively accelerates tumour progression when activated in advanced lung adenocarcinomas. We also report a key role for the wild-type Braf kinase in sustaining Kras(G12V)/Braf(D631A)-driven tumours. Ablation of the wild-type Braf allele prevents the development of lung adenocarcinoma by inducing a further increase in MAPK signalling that results in oncogenic toxicity; this effect can be abolished by pharmacological inhibition of Mek to restore tumour growth. However, the loss of wild-type Braf also induces transdifferentiation of club cells, which leads to the rapid development of lethal intrabronchiolar lesions. These observations indicate that the signal intensity of the MAPK pathway is a critical determinant not only in tumour development, but also in dictating the nature of the cancer-initiating cell and ultimately the resulting tumour phenotype. Main The RAS–MAPK signalling cascade serves as a central node in transducing signals from membrane receptors to the nucleus. This pathway is aberrantly activated in a substantial fraction of human cancers 4 . Moreover, germline mutations resulting in limited activation of this signalling cascade cause developmental disorders known as RASopathies 5 . There is also abundant evidence that elevated RAS–MAPK signalling results in cellular toxicity that may serve as a natural barrier to cancer progression early in tumorigenesis 6 . Finally, genetic abrogation of this pathway in adult mice results in their rapid death 7 . These findings suggest that defined thresholds of RAS–MAPK activity are required for homeostasis as well as for malignant transformation, but compelling genetic evidence is missing. In order to augment MAPK signalling in controlled increments we have taken advantage of the expression of an endogenous Braf(D631A) kinase-dead isoform (corresponding to the human BRAF(D594A) mutant) that is known to induce Erk phosphorylation in a Craf-dependent manner 2 , 8 . This effect, known as the MAPK paradox, is due to enhanced heterodimerization and activation of the catalytically competent Craf protomer in Braf(D631A)–Craf complexes 2 , 3 . In agreement with these observations, lack of wild-type Braf expression in Kras G12V cell lines expressing Braf(D631A) increased the intensity and duration of MAPK signalling ( Extended Data Fig. 1 ), probably as a result of the exclusive formation of Braf(D631A)–Craf heterodimers. Thus, to generate controlled thresholds of MAPK intensity in vivo , we combined wild-type Braf , conditional knockout Braf lox and conditional knock-in Braf LSLD631A with an inducible Kras LSLG12Vgeo allele 9 (where LSL indicates a lox-STOP-lox motif). The resulting Kras +/ LSLG12Vgeo (hereto designated as K), Kras +/ LSLG12Vgeo ; Braf +/ LSLD631A (designated as KB) and Kras +/ LSLG12Vgeo ; Braf lox/LSLD631A (designated as KBL) strains were intratracheally infected with adenovirus expressing Cre recombinase (Ad-Cre). Cre-mediated recombination of these alleles results in the induction of distinct levels of Ras–MAPK signalling, with Braf +/+ driving lower activity, Braf +/ D631A intermediate intensity and Braf − /D631A maximal activation. This strategy allowed us to investigate the effect of various MAPK activity thresholds on cell transformation, adenocarcinoma development and cellular toxicity in vivo . Lung cells expressing these conditional alleles were identified by co-expression of the Kras(G12V) oncoprotein with β-geo, a chimaeric bacterial protein with β-galactosidase activity 9 ( Extended Data Fig. 2 ). As illustrated in Fig. 1a , small X-gal + hyperplasias could be readily detected in the lungs of K mice 1 month after Ad-Cre infection. By constrast, Ad-Cre-infected KB mice displayed abundant hyperplastic areas together with adenomas, a lesion that is extremely infrequent in K mice at this early stage 10 . Remarkably, X-gal + alveolar hyperplasias and adenomas were nearly absent in Ad-Cre-infected KBL animals. These mice, however, displayed hypertrophic bronchi as their most prominent feature ( Fig. 1a ). The lack of Kras G12V -driven alveolar lesions in KBL mice is unlikely to be a consequence of the absence of an active Braf, since this kinase is dispensable for the development of Kras G12V -driven lung adenocarcinoma 7 , 11 . Thus, we explored the possibility that the absence of alveolar lesions was due to some sort of cellular toxicity such as that caused by the induction of senescence or DNA damage, two phenomena known to act as barriers to tumour development 6 , 12 , 13 . Indeed, examination of lung lysates and sections from KBL mice detected p19 Arf and p53 tumour suppressors, active caspase-3 and γ-H2AX, a marker for DNA damage, as early as 1 week following Ad-Cre infection ( Fig. 1b, c ). We did not observe differences in senescence-associated β-gal staining (data not shown). The concomitant increase in the phosphorylation of Erk1/2 and p90Rsk suggested that elevated MAPK signalling triggered a stress response that impaired tumour cell proliferation. Yet it has been recently described that mutant Kras -driven lung adenocarcinomas display a tonic activation of the DNA damage response to prevent the induction of genotoxic stress 14 . We hypothesize that the exclusive formation of Braf(D631A)–Craf complexes in KBL mice exceeded such a toxic signalling threshold and induced a stress response incompatible with tumour development. Thus, our results indicate that Ras-oncogenic toxicity is quantitatively dictated by MAPK function. In support of this hypothesis, whereas Mek inhibition prevented tumour growth in Ad-Cre-infected KB mice, it rescued the toxic phenotype in KBL animals in a dose-dependent manner and restored<|im_end|> <|im_start|>assistant The initiating oncogenic event in almost half of human lung adenocarcinomas is still unknown, complicating the development of selective targeted therapies. Yet these tumours harbour a number of alterations without obvious oncogenic function, including BRAF-inactivating mutations. Researchers at the Spanish National Cancer Research Centre (CNIO) have demonstrated that the expression of an endogenous Braf (D631A) kinase-inactive isoform in mice, corresponding to the human BRAF(D594A) mutation, triggers lung adenocarcinoma in vivo, indicating that BRAF-inactivating mutations are initiating events in lung oncogenesis. The paper, published in Nature, indicates that the signal intensity of the MAPK pathway is a critical determinant not only in tumour development, but also in dictating the nature of the cancer-initiating cell and ultimately the resulting tumour phenotype. The RAS-MAPK signalling cascade serves as a central node in transducing signals from membrane receptors to the nucleus. This pathway is aberrantly activated in a substantial fraction of human cancers. There is also abundant evidence that elevated RAS-MAPK signaling results in cellular toxicity that may serve as a natural barrier to cancer progression early in tumorigenesis. These findings suggest that defined thresholds of RAS-MAPK activity are required for homeostasis as well as for malignant transformation, but compelling genetic evidence is missing. Mutational analysis of different human cancers has recently uncovered that among the BRAF hot spots in lung adenocarcinoma, which comprise a component of the RAS-MAP kinase pathway, those resulting in inactivating mutations predominate over the V600E activating substitution, the main oncogenic form in other tumours such as melanoma. However, the contribution of BRAF-inactive mutants to lung cancer progression is unclear. Using public databases, researchers have identified inactivating BRAF mutations in a subset of KRAS-driven human lung tumours. Subsequently, using mouse models, researchers have replicated these observations showing that the co-expression of oncogenic Kras and inactive Braf markedly enhances the onset of lung adenocarcinoma. Also, this combination accelerates tumour progression when the inactivating Braf mutation is genetically induced in advanced tumors. Surprisingly, in this same study, the researchers showed that individually, the inactivating mutations of Braf are also oncogenic events that induce the appearance of lung adenocarcinoma. The paper provides the first genetic evidence demonstrating that a kinase-inactivating Braf mutation induces lung adenocarcinoma development. Moreover, results suggest that lung adenocarcinoma patients with hypoactive BRAF could benefit from therapies based on selective CRAF inhibitors. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The identity of the dominant root-associated microbial symbionts in a forest determines the ability of trees to access limiting nutrients from atmospheric or soil pools 1 , 2 , sequester carbon 3 , 4 and withstand the effects of climate change 5 , 6 . Characterizing the global distribution of these symbioses and identifying the factors that control this distribution are thus integral to understanding the present and future functioning of forest ecosystems. Here we generate a spatially explicit global map of the symbiotic status of forests, using a database of over 1.1 million forest inventory plots that collectively contain over 28,000 tree species. Our analyses indicate that climate variables—in particular, climatically controlled variation in the rate of decomposition—are the primary drivers of the global distribution of major symbioses. We estimate that ectomycorrhizal trees, which represent only 2% of all plant species 7 , constitute approximately 60% of tree stems on Earth. Ectomycorrhizal symbiosis dominates forests in which seasonally cold and dry climates inhibit decomposition, and is the predominant form of symbiosis at high latitudes and elevation. By contrast, arbuscular mycorrhizal trees dominate in aseasonal, warm tropical forests, and occur with ectomycorrhizal trees in temperate biomes in which seasonally warm-and-wet climates enhance decomposition. Continental transitions between forests dominated by ectomycorrhizal or arbuscular mycorrhizal trees occur relatively abruptly along climate-driven decomposition gradients; these transitions are probably caused by positive feedback effects between plants and microorganisms. Symbiotic nitrogen fixers—which are insensitive to climatic controls on decomposition (compared with mycorrhizal fungi)—are most abundant in arid biomes with alkaline soils and high maximum temperatures. The climatically driven global symbiosis gradient that we document provides a spatially explicit quantitative understanding of microbial symbioses at the global scale, and demonstrates the critical role of microbial mutualisms in shaping the distribution of plant species. Main Microbial symbionts strongly influence the functioning of forest ecosystems. Root-associated microorganisms exploit inorganic, organic 2 and/or atmospheric forms of nutrients that enable plant growth 1 , determine how trees respond to increased concentrations 6 of CO 2 , regulate the respiratory activity of soil microorganisms 3 , 8 and affect plant species diversity by altering the strength of conspecific negative density dependence 9 . Despite the growing recognition of the importance of root symbioses for forest functioning 1 , 6 , 10 and the potential to integrate symbiotic status into Earth system models that predict functional changes to the terrestrial biosphere 10 , we lack spatially explicit quantitative maps of root symbioses at the global scale. Quantitative maps of tree symbiotic states would link the biogeography of functional traits of belowground microbial symbionts with their 3.1 trillion host trees 11 , which are spread across Earth’s forests, woodlands and savannahs. The dominant guilds of tree root symbionts—arbuscular mycorrhizal fungi, ectomycorrhizal fungi, ericoid mycorrhizal fungi and nitrogen-fixing bacteria (N-fixers)—are all based on the exchange of plant photosynthate for limiting macronutrients. Arbuscular mycorrhizal symbiosis evolved nearly 500 million years ago, and ectomycorrhizal, ericoid mycorrhizal and N-fixer plant taxa have evolved multiple times from an arbuscular-mycorrhizal basal state. Plants that are involved in arbuscular mycorrhizal symbiosis comprise nearly 80% of all terrestrial plant species; these plants principally rely on arbuscular mycorrhizal fungi for enhancing mineral phosphorus uptake 12 . In contrast to arbuscular mycorrhizal fungi, ectomycorrhizal fungi evolved from multiple lineages of saprotrophic ancestors and, as a result, some ectomycorrhizal fungi are capable of directly mobilizing organic sources of soil nutrients (particularly nitrogen) 2 . Associations with ectomycorrhizal fungi—but not arbuscular mycorrhizal fungi—have previously been shown to enable trees to accelerate photosynthesis in response to increased concentrations of atmospheric CO 2 when soil nitrogen is limiting 6 , and to inhibit soil respiration by decomposer microorganisms 3 , 8 . Because increased plant photosynthesis and decreased soil respiration both reduce atmospheric CO 2 concentrations, the ectomycorrhizal symbiosis is associated with buffering the Earth’s climate against anthropogenic change. In contrast to mycorrhizal fungi, which extract nutrients from the soil, symbiotic N-fixers (Rhizobia and Actinobacteria) convert atmospheric N 2 to plant-usable forms. Symbiotic N-fixers are responsible for a large fraction of biological soil-nitrogen inputs, which can increase nitrogen availability in forests in which N-fixers are locally abundant 13 . Symbioses with either N-fixers or ectomycorrhizal fungi often demand more plant photosynthate than does arbuscular mycorrhizal symbiosis 12 , 14 , 15 . Because tree growth and reproduction are limited by access to inorganic, organic and atmospheric sources of nitrogen, the distribution of root symbioses is likely to reflect environmental conditions that maximize the cost:benefit ratio of symbiotic exchange as well as physiological constraints on the different symbionts. One of the earliest efforts 16 to understand the functional biogeography of plant root symbioses categorically classified biomes by their perceived dominant mycorrhizal type, and hypothesized that seasonal climates favour hosts that associate with ectomycorrhizal fungi (owing to the ability of these hosts to compete directly for organic nitrogen). By contrast, it has more recently been proposed that sensitivity to low temperatures has prevented N-fixers from dominating outside of the tropics, despite the potential for nitrogen fixation to alleviate nitrogen limitation in boreal forests 15 , 17 . However, global-scale tests of these proposed biogeographical patterns and their climate drivers are lacking. To address this, we compiled a global ground-sourced survey database to reveal the numerical abundances of each type of symbiosis across the globe. Such a database is essential for identifying the potential mechanisms that underlie transitions in forest symbiotic state along climatic gradients 18 , 19 . We determined the abundance of tree symbioses using an extension of the plot-based Global Forest Biodiversity (GFB) database that we term the GFBi; this extended database contains over 1.1 million forest inventory plots of individual-based measurement records, from which we derive abundance information for entire tree communities (Fig. 1 ). Using published literature on the evolutionary histories of mycorrhizal and N-fixer symbioses, we assigned plant species from the GFBi to one of five root-associated symbiotic guilds: arbuscular mycorrhizal, ectomycorrhizal, ericoid mycorrhizal, N-fixer and weakly arbuscular or non-mycorrhizal. We then used", "role": "user" }, { "content": "In and around the tangled roots of the forest floor, fungi and bacteria grow with trees, exchanging nutrients for carbon in a vast, global marketplace. A new effort to map the most abundant of these symbiotic relationships—involving more than 1.1 million forest sites and 28,000 tree species—has revealed factors that determine where different types of symbionts will flourish. The work could help scientists understand how symbiotic partnerships structure the world's forests and how they could be affected by a warming climate. Stanford University researchers worked alongside a team of over 200 scientists to generate these maps, published May 16 in Nature. From the work, they revealed a new biological rule, which the team named Read's Rule after pioneer in symbiosis research Sir David Read. In one example of how they could apply this research, the group used their map to predict how symbioses might change by 2070 if carbon emissions continue unabated. This scenario resulted in a 10 percent reduction in the biomass of tree species that associate with a type of fungi found primarily in cooler regions. The researchers cautioned that such a loss could lead to more carbon in the atmosphere because these fungi tend to increase the amount of carbon stored in soil. \"There's only so many different symbiotic types and we're showing that they obey clear rules,\" said Brian Steidinger, a postdoctoral researcher at Stanford and lead author of the paper. \"Our models predict massive changes to the symbiotic state of the world's forests—changes that could affect the kind of climate your grandchildren are going to live in.\" One of three maps showing the distribution of trees likely to associate with the three major types of symbiotic bacteria or fungi. Credit: Brian Steidinger Three symbioses Hidden to most observers, these inter-kingdom collaborations between microbes and trees are highly diverse. The researchers focused on mapping three of the most common types of symbioses: arbuscular mycorrhizal fungi, ectomycorrhizal fungi and nitrogen-fixing bacteria. Each of these types encompasses thousands of species of fungi or bacteria that form unique partnerships with different tree species. Thirty years ago, Read drew maps by hand of where he thought different symbiotic fungi might reside, based on the nutrients they provide. Ectomycorrhizal fungi feed trees nitrogen directly from organic matter—like decaying leaves—so, he proposed, they would be more successful in cooler places where decomposition is slow and leaf litter is abundant. In contrast, he thought arbuscular mycorrhizal fungi would dominate in the tropics where tree growth is limited by soil phosphorous. Research by others has added that nitrogen-fixing bacteria seem to grow poorly in cool temperatures. Testing Read's ideas had to wait, however, because proof required gathering data from large numbers of trees in diverse parts of the globe. That information became available with the Global Forest Biodiversity Initiative (GFBI), which surveyed forests, woodlands and savannas from every continent (except Antarctica) and ecosystem on Earth. The team fed the location of 31 million trees from that database along with information about what symbiotic fungi or bacteria most often associates with those species into a learning algorithm that determined how different variables such as climate, soil chemistry, vegetation and topography seem to influence the prevalence of each symbiosis. From this, they found that nitrogen-fixing bacteria are probably limited by temperature and soil acidity, whereas the two types of fungal symbioses are heavily influenced by variables that affect decomposition rates—the rate at which organic matter breaks down in the environment—such as temperature and moisture. One of three maps showing the distribution of trees likely to associate with the three major types of symbiotic bacteria or fungi. Credit: Brian Steidinger \"These are incredibly strong global patterns, as striking as other fundamental global biodiversity patterns out there,\" said Kabir Peay, assistant professor of biology in the School of Humanities and Sciences and senior author of the study. \"But before this hard data, knowledge of these patterns was limited to experts in mycorrhizal or nitrogen-fixer ecology, even though it is important to a wide range of ecologists, evolutionary biologists and earth scientists.\" Although the research supported Read's hypothesis—finding arbuscular mycorrhizal fungi in warmer forests and ectomycorrhizal fungi in colder forests—the transitions across biomes from one symbiotic type to another were much more abrupt than expected, based on the gradual changes in variables that affect decomposition. This supports another hypothesis, the researchers thought: that ectomycorrhizal fungi change their local environment to further reduce decomposition rates. This feedback loop may help explain why the researchers saw the 10 percent reduction in ectomycorrhizal fungi when they simulated what would happen if carbon emissions continued unabated to 2070. Warming temperatures could force ectomycorrhizal fungi over a climatic tipping point, beyond the range of environments they can alter to their liking. Mapping collaboration The data behind this map represents real trees from more than 70 countries and collaboration, led by Jingjing Liang of Purdue University and Tom Crowther of ETH Zürich, between hundreds of researchers who speak different languages, study different ecosystems and confront different challenges. \"There are more than 1.1 million forest plots in the dataset and every one of those was measured by a person on the ground. In many cases, as part of these measurements, they essentially gave the tree a hug,\" said Steidinger. \"So much effort—hikes, sweat, ticks, long days—is in that map.\" The maps from this study will be made freely available, in hopes of helping other scientists include tree symbionts in their work. In the future, the researchers intend to expand their work beyond forests and to continue trying to understand how climate change affects ecosystems. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The identity of the dominant root-associated microbial symbionts in a forest determines the ability of trees to access limiting nutrients from atmospheric or soil pools 1 , 2 , sequester carbon 3 , 4 and withstand the effects of climate change 5 , 6 . Characterizing the global distribution of these symbioses and identifying the factors that control this distribution are thus integral to understanding the present and future functioning of forest ecosystems. Here we generate a spatially explicit global map of the symbiotic status of forests, using a database of over 1.1 million forest inventory plots that collectively contain over 28,000 tree species. Our analyses indicate that climate variables—in particular, climatically controlled variation in the rate of decomposition—are the primary drivers of the global distribution of major symbioses. We estimate that ectomycorrhizal trees, which represent only 2% of all plant species 7 , constitute approximately 60% of tree stems on Earth. Ectomycorrhizal symbiosis dominates forests in which seasonally cold and dry climates inhibit decomposition, and is the predominant form of symbiosis at high latitudes and elevation. By contrast, arbuscular mycorrhizal trees dominate in aseasonal, warm tropical forests, and occur with ectomycorrhizal trees in temperate biomes in which seasonally warm-and-wet climates enhance decomposition. Continental transitions between forests dominated by ectomycorrhizal or arbuscular mycorrhizal trees occur relatively abruptly along climate-driven decomposition gradients; these transitions are probably caused by positive feedback effects between plants and microorganisms. Symbiotic nitrogen fixers—which are insensitive to climatic controls on decomposition (compared with mycorrhizal fungi)—are most abundant in arid biomes with alkaline soils and high maximum temperatures. The climatically driven global symbiosis gradient that we document provides a spatially explicit quantitative understanding of microbial symbioses at the global scale, and demonstrates the critical role of microbial mutualisms in shaping the distribution of plant species. Main Microbial symbionts strongly influence the functioning of forest ecosystems. Root-associated microorganisms exploit inorganic, organic 2 and/or atmospheric forms of nutrients that enable plant growth 1 , determine how trees respond to increased concentrations 6 of CO 2 , regulate the respiratory activity of soil microorganisms 3 , 8 and affect plant species diversity by altering the strength of conspecific negative density dependence 9 . Despite the growing recognition of the importance of root symbioses for forest functioning 1 , 6 , 10 and the potential to integrate symbiotic status into Earth system models that predict functional changes to the terrestrial biosphere 10 , we lack spatially explicit quantitative maps of root symbioses at the global scale. Quantitative maps of tree symbiotic states would link the biogeography of functional traits of belowground microbial symbionts with their 3.1 trillion host trees 11 , which are spread across Earth’s forests, woodlands and savannahs. The dominant guilds of tree root symbionts—arbuscular mycorrhizal fungi, ectomycorrhizal fungi, ericoid mycorrhizal fungi and nitrogen-fixing bacteria (N-fixers)—are all based on the exchange of plant photosynthate for limiting macronutrients. Arbuscular mycorrhizal symbiosis evolved nearly 500 million years ago, and ectomycorrhizal, ericoid mycorrhizal and N-fixer plant taxa have evolved multiple times from an arbuscular-mycorrhizal basal state. Plants that are involved in arbuscular mycorrhizal symbiosis comprise nearly 80% of all terrestrial plant species; these plants principally rely on arbuscular mycorrhizal fungi for enhancing mineral phosphorus uptake 12 . In contrast to arbuscular mycorrhizal fungi, ectomycorrhizal fungi evolved from multiple lineages of saprotrophic ancestors and, as a result, some ectomycorrhizal fungi are capable of directly mobilizing organic sources of soil nutrients (particularly nitrogen) 2 . Associations with ectomycorrhizal fungi—but not arbuscular mycorrhizal fungi—have previously been shown to enable trees to accelerate photosynthesis in response to increased concentrations of atmospheric CO 2 when soil nitrogen is limiting 6 , and to inhibit soil respiration by decomposer microorganisms 3 , 8 . Because increased plant photosynthesis and decreased soil respiration both reduce atmospheric CO 2 concentrations, the ectomycorrhizal symbiosis is associated with buffering the Earth’s climate against anthropogenic change. In contrast to mycorrhizal fungi, which extract nutrients from the soil, symbiotic N-fixers (Rhizobia and Actinobacteria) convert atmospheric N 2 to plant-usable forms. Symbiotic N-fixers are responsible for a large fraction of biological soil-nitrogen inputs, which can increase nitrogen availability in forests in which N-fixers are locally abundant 13 . Symbioses with either N-fixers or ectomycorrhizal fungi often demand more plant photosynthate than does arbuscular mycorrhizal symbiosis 12 , 14 , 15 . Because tree growth and reproduction are limited by access to inorganic, organic and atmospheric sources of nitrogen, the distribution of root symbioses is likely to reflect environmental conditions that maximize the cost:benefit ratio of symbiotic exchange as well as physiological constraints on the different symbionts. One of the earliest efforts 16 to understand the functional biogeography of plant root symbioses categorically classified biomes by their perceived dominant mycorrhizal type, and hypothesized that seasonal climates favour hosts that associate with ectomycorrhizal fungi (owing to the ability of these hosts to compete directly for organic nitrogen). By contrast, it has more recently been proposed that sensitivity to low temperatures has prevented N-fixers from dominating outside of the tropics, despite the potential for nitrogen fixation to alleviate nitrogen limitation in boreal forests 15 , 17 . However, global-scale tests of these proposed biogeographical patterns and their climate drivers are lacking. To address this, we compiled a global ground-sourced survey database to reveal the numerical abundances of each type of symbiosis across the globe. Such a database is essential for identifying the potential mechanisms that underlie transitions in forest symbiotic state along climatic gradients 18 , 19 . We determined the abundance of tree symbioses using an extension of the plot-based Global Forest Biodiversity (GFB) database that we term the GFBi; this extended database contains over 1.1 million forest inventory plots of individual-based measurement records, from which we derive abundance information for entire tree communities (Fig. 1 ). Using published literature on the evolutionary histories of mycorrhizal and N-fixer symbioses, we assigned plant species from the GFBi to one of five root-associated symbiotic guilds: arbuscular mycorrhizal, ectomycorrhizal, ericoid mycorrhizal, N-fixer and weakly arbuscular or non-mycorrhizal. We then used<|im_end|> <|im_start|>assistant In and around the tangled roots of the forest floor, fungi and bacteria grow with trees, exchanging nutrients for carbon in a vast, global marketplace. A new effort to map the most abundant of these symbiotic relationships—involving more than 1.1 million forest sites and 28,000 tree species—has revealed factors that determine where different types of symbionts will flourish. The work could help scientists understand how symbiotic partnerships structure the world's forests and how they could be affected by a warming climate. Stanford University researchers worked alongside a team of over 200 scientists to generate these maps, published May 16 in Nature. From the work, they revealed a new biological rule, which the team named Read's Rule after pioneer in symbiosis research Sir David Read. In one example of how they could apply this research, the group used their map to predict how symbioses might change by 2070 if carbon emissions continue unabated. This scenario resulted in a 10 percent reduction in the biomass of tree species that associate with a type of fungi found primarily in cooler regions. The researchers cautioned that such a loss could lead to more carbon in the atmosphere because these fungi tend to increase the amount of carbon stored in soil. "There's only so many different symbiotic types and we're showing that they obey clear rules," said Brian Steidinger, a postdoctoral researcher at Stanford and lead author of the paper. "Our models predict massive changes to the symbiotic state of the world's forests—changes that could affect the kind of climate your grandchildren are going to live in." One of three maps showing the distribution of trees likely to associate with the three major types of symbiotic bacteria or fungi. Credit: Brian Steidinger Three symbioses Hidden to most observers, these inter-kingdom collaborations between microbes and trees are highly diverse. The researchers focused on mapping three of the most common types of symbioses: arbuscular mycorrhizal fungi, ectomycorrhizal fungi and nitrogen-fixing bacteria. Each of these types encompasses thousands of species of fungi or bacteria that form unique partnerships with different tree species. Thirty years ago, Read drew maps by hand of where he thought different symbiotic fungi might reside, based on the nutrients they provide. Ectomycorrhizal fungi feed trees nitrogen directly from organic matter—like decaying leaves—so, he proposed, they would be more successful in cooler places where decomposition is slow and leaf litter is abundant. In contrast, he thought arbuscular mycorrhizal fungi would dominate in the tropics where tree growth is limited by soil phosphorous. Research by others has added that nitrogen-fixing bacteria seem to grow poorly in cool temperatures. Testing Read's ideas had to wait, however, because proof required gathering data from large numbers of trees in diverse parts of the globe. That information became available with the Global Forest Biodiversity Initiative (GFBI), which surveyed forests, woodlands and savannas from every continent (except Antarctica) and ecosystem on Earth. The team fed the location of 31 million trees from that database along with information about what symbiotic fungi or bacteria most often associates with those species into a learning algorithm that determined how different variables such as climate, soil chemistry, vegetation and topography seem to influence the prevalence of each symbiosis. From this, they found that nitrogen-fixing bacteria are probably limited by temperature and soil acidity, whereas the two types of fungal symbioses are heavily influenced by variables that affect decomposition rates—the rate at which organic matter breaks down in the environment—such as temperature and moisture. One of three maps showing the distribution of trees likely to associate with the three major types of symbiotic bacteria or fungi. Credit: Brian Steidinger "These are incredibly strong global patterns, as striking as other fundamental global biodiversity patterns out there," said Kabir Peay, assistant professor of biology in the School of Humanities and Sciences and senior author of the study. "But before this hard data, knowledge of these patterns was limited to experts in mycorrhizal or nitrogen-fixer ecology, even though it is important to a wide range of ecologists, evolutionary biologists and earth scientists." Although the research supported Read's hypothesis—finding arbuscular mycorrhizal fungi in warmer forests and ectomycorrhizal fungi in colder forests—the transitions across biomes from one symbiotic type to another were much more abrupt than expected, based on the gradual changes in variables that affect decomposition. This supports another hypothesis, the researchers thought: that ectomycorrhizal fungi change their local environment to further reduce decomposition rates. This feedback loop may help explain why the researchers saw the 10 percent reduction in ectomycorrhizal fungi when they simulated what would happen if carbon emissions continued unabated to 2070. Warming temperatures could force ectomycorrhizal fungi over a climatic tipping point, beyond the range of environments they can alter to their liking. Mapping collaboration The data behind this map represents real trees from more than 70 countries and collaboration, led by Jingjing Liang of Purdue University and Tom Crowther of ETH Zürich, between hundreds of researchers who speak different languages, study different ecosystems and confront different challenges. "There are more than 1.1 million forest plots in the dataset and every one of those was measured by a person on the ground. In many cases, as part of these measurements, they essentially gave the tree a hug," said Steidinger. "So much effort—hikes, sweat, ticks, long days—is in that map." The maps from this study will be made freely available, in hopes of helping other scientists include tree symbionts in their work. In the future, the researchers intend to expand their work beyond forests and to continue trying to understand how climate change affects ecosystems. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Synthesis of hindered amines using the atom-efficient hydroaminomethylation (HAM) route remains a challenge. Here, we report a general and accelerated HAM in segmented flow, achieved via a cooperative effect between rhodium (Rh)/N-Xantphos and a co-catalyst (2-Fluoro-4-methylbenzoic acid) to increase the reactivity by 70 fold when compared to Rh/Xantphos in batch reactors. The cooperation between Rh and the co-catalyst facilitates the cleavage of the H–H bond and drives the equilibrium-limited condensation step forward. Online reaction optimization expands the scope to include alkyl, aryl, and primary amines. In-flow solvent tuning enables selectivity switching from amine to enamine without the need for changing the ligand. Furthermore, leveraging the ionic nature of the catalyst, we present a robust Rh recovery strategy up to 4 recycles without loss of activity. Introduction Amines are essential building blocks in agrochemicals, detergents, and fine chemicals 1 , 2 , 3 . For example, alkylated anilines and carbazoles are used as chromophores in synthesis of organic light emitting diodes (OLEDs) 4 , 5 , alkylated phenylenediamines are applied as antioxidants in rubber, and long chain fatty amines are components in personal care and lubrication formulations. Moreover, the amine moiety is common in several drugs, including Ibutilide, Melperone, Terfenadine, Aripiprazole, Fluspirilene, and Difenidol 1 . Carbon–nitrogen (C–N) bonds are widely common in bioactive molecules and thus, rapid C–N bond formation reactions are essential tools for the generation of large molecular libraries for structure-activity-relationship mapping (SAR), and the on-demand synthesis of isotopically labeled tracers with relatively short half-life such as the 11 C labeled PET tracers 6 , 7 , 8 . The emerging trend towards decentralized manufacturing of pharmaceuticals and fine chemicals promotes continuous flow production as the preferred method of choice 9 , 10 , 11 . Four conventional processes are typically used in the large scale synthesis of aliphatic amines: (1) amination of alcohols, (2) amination of alkyl halides, (3) reduction of nitrile compounds, and (4) reductive amination of carbonyl compounds 3 , which all require multistep processing and purification. HydroAminoMethylation (HAM) is an alternative one-pot synthetic route for sustainable manufacturing of amines from economic starting materials (olefins) without the need for the multistep rection-separation as needed in routes (1), (3), and (4) or the generation of metal halide solid waste that requires disposal as in route (2). HAM is an atom-efficient route as it produces no waste other than water as the sole byproduct. Substitution on the amine α carbon is often introduced in active pharmaceutical ingredients to control their lipophilicity and rate of metabolism 12 . However, hindered amines are usually synthesized by less economic routes such as the amination of alkyl halides. The HAM reaction proceeds through three main steps in an auto-tandem fashion (Fig. 1a ): (i) hydroformylation, (ii) condensation, and (iii) enamine hydrogenation. Steps (ii) and (iii) are often referred to as the reductive amination of aldehydes. Steps (i) and (iii) are gas–liquid reactions and thus provide an exciting opportunity for intensification through flow chemistry (segmented gas–liquid flow format). Step (ii) is a liquid phase condensation reaction that can be equilibrium-limited with sterically hindered amines and thus the undesired aldehyde self-condensation becomes the major reaction. This is a significant drawback that has limited the scope of HAM reactions to non-hindered amines 13 , 14 . Recent studies have demonstrated advances in the rate acceleration and substrate scope expansion of HAM reactions 15 , 16 . However, examples of HAM with sterically hindered amines are rare, and alternative complex routes are developed specifically for their alkylation 17 . The cost associated with catalyst is another drawback that limits the use of HAM in large scale production. In addition to the increasing demand for expanding the substrate scope of HAM reactions to sterically hindered amines, there is a need for continuous operation of HAM with recycling the expensive rhodium (Rh) catalyst to enhance the process sustainability and promote decentralized manufacturing of pharmaceuticals and fine chemicals. Fig. 1: HAM reaction scheme and a summary of prior HAM work vs. this work. a Amine formation by tandem hydroformylation-condensation-hydrogenation reactions. M: metal, L: ligand. b – e Different approaches to amine syntheses via HAM reaction. Full size image The application of the bidentate, commercially available phosphine ligand, Xantphos, in the Rh-catalyzed HAM reactions to maintain high selectivity towards the linear amine was pioneered by Beller and co-workers 18 . However, the HAM reaction is still plagued by the use of expensive cationic Rh(cod) + BF 4 − catalyst and the slow kinetics (batch reaction time > 24 h at 115 °C, TOF < 200 mol/mol Rh/h) which makes it unsuitable for continuous synthesis (Fig. 1b ). The reaction kinetics were enhanced by Hartwig and co-workers. through the addition of the iridium (Ir)-based Xiao’s hydrogenation catalyst and sodium formate to accelerate the enamine hydrogenation step (Fig. 1a , step iii), resulting in a complete conversion in 20 h at 80 °C (Fig. 1c ) 19 . Despite the addition of 1 mol% of Xiao’s Ir catalyst, the hydroformylation step (Fig. 1a , step i) remained slow. To overcome the slow rate of the hydroformylation step, the Rh catalyst loading was increased by 5 times relative to the Rh loading in the study by Beller and co-workers, which resulted in TOF values below 50 mol/mol Rh/h. A more economic Rh source, Rh(acac)(CO) 2 , was used by Hartwig and co-workers. and the bidentate phosphene ligand, BISBI, showed better yields when compared to Xantphos under similar reaction conditions. Despite the significant advancements of the HAM synthetic route in batch reactions, no α-branched amines have been demonstrated. This major limitation arises from the equilibrium-limited condensation and slow hydrogenation of the branched enamine in batch reactors. Wasserscheid and co-workers demonstrated that Rh/Xantphos catalyst for continuous gas phase HAM reaction (TOF values up to 500 mol/mol Rh/h) could be recycled by immobilizing the catalyst in supported ionic liquid phase on activated carbon 20 . Recently, continuous HAM of 1-decene with the non-hindered diethylamine was demonstrated by Seidensticker and co-workers with catalyst recycling (0.1", "role": "user" }, { "content": "Researchers at North Carolina State University have developed a faster, less expensive technique for producing hindered amines—a class of chemicals used as building blocks in products ranging from pharmaceuticals and agrochemicals to detergents and organic light emitting diodes. \"Hindered amines are used in a tremendous variety of products, but all of the existing techniques for producing these amines are complicated and expensive,\" says Milad Abolhasani, corresponding author of a paper on the new technique and an associate professor of chemical and biomolecular engineering at NC State. \"We set out to develop a better method for synthesizing these hindered amines, and we were successful.\" One of the less expensive techniques for producing hindered amines is hydroaminomethylation, or HAM. However, the chemical industry has largely avoided using HAM, because there are too many ways things can go wrong—leaving producers with undesirable chemicals instead of the functionalized amines they were trying to make. Researchers have improved the HAM process over the years. But all of the techniques for avoiding undesirable byproducts have meant extending the timeframe of the HAM process, so that it takes hours to perform all of the necessary reactions. Until now. \"We've developed a HAM technique that makes use of continuous flow reactor technologies to produce hindered amines more efficiently,\" Abolhasani says. \"Our HAM process takes less than 30 minutes in most cases. The only products are hindered amines and water. And we are able to recycle the primary catalyst, rhodium/N-Xantphos, which further drives down costs.\" The success of the new technique is made possible by two things. First, by using a continuous flow reactor that allows for continuous flow of both gases and liquids in a segmented flow format, the researchers were able to make the kinetics of the reaction far more efficient. Second, the new technique makes use of a co-catalyst—fluorinated benzoic acid—which reduces the amount of energy needed to perform some of the necessary reactions in the HAM process. Ultimately, this technique drives down the cost of producing hindered amines using inexpensive feedstock, allowing users to produce them more quickly and with no toxic byproducts. \"By designing a cooperative catalyst system, we've demonstrated that the rate of the HAM reactions in our system can be 70 times higher than the existing state-of-the-art processes,\" says Malek Ibrahim, first author of the paper and a former postdoctoral researcher at NC State. \"This process is also a good example for how flow chemistry platforms can improve catalyst turnover frequency, which is increasingly important as the price of rhodium catalysts goes up.\" The new technique is particularly attractive for decentralized manufacturing operations, since the small footprint of the necessary equipment and its scalability allows users to efficiently produce hindered amines on site and on demand. \"What's more, the same technique can also be used to produce enamines—which are other chemical building blocks—on demand, simply by tuning the solvents we use in the flow reactor,\" Ibrahim says. \"You can literally switch back and forth between producing amines and enamines without having to stop the production process, since the only thing you're changing is the solvent mixture.\" The researchers have filed a provisional patent on the new technique and are now looking for industrial partners to put the technique into widespread use. The paper, \"Recyclable Cooperative Catalyst for Accelerated Hydroaminomethylation of Hindered Amines in a Continuous Segmented Flow Reactor,\" will be published May 4 in the journal Nature Communications. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Synthesis of hindered amines using the atom-efficient hydroaminomethylation (HAM) route remains a challenge. Here, we report a general and accelerated HAM in segmented flow, achieved via a cooperative effect between rhodium (Rh)/N-Xantphos and a co-catalyst (2-Fluoro-4-methylbenzoic acid) to increase the reactivity by 70 fold when compared to Rh/Xantphos in batch reactors. The cooperation between Rh and the co-catalyst facilitates the cleavage of the H–H bond and drives the equilibrium-limited condensation step forward. Online reaction optimization expands the scope to include alkyl, aryl, and primary amines. In-flow solvent tuning enables selectivity switching from amine to enamine without the need for changing the ligand. Furthermore, leveraging the ionic nature of the catalyst, we present a robust Rh recovery strategy up to 4 recycles without loss of activity. Introduction Amines are essential building blocks in agrochemicals, detergents, and fine chemicals 1 , 2 , 3 . For example, alkylated anilines and carbazoles are used as chromophores in synthesis of organic light emitting diodes (OLEDs) 4 , 5 , alkylated phenylenediamines are applied as antioxidants in rubber, and long chain fatty amines are components in personal care and lubrication formulations. Moreover, the amine moiety is common in several drugs, including Ibutilide, Melperone, Terfenadine, Aripiprazole, Fluspirilene, and Difenidol 1 . Carbon–nitrogen (C–N) bonds are widely common in bioactive molecules and thus, rapid C–N bond formation reactions are essential tools for the generation of large molecular libraries for structure-activity-relationship mapping (SAR), and the on-demand synthesis of isotopically labeled tracers with relatively short half-life such as the 11 C labeled PET tracers 6 , 7 , 8 . The emerging trend towards decentralized manufacturing of pharmaceuticals and fine chemicals promotes continuous flow production as the preferred method of choice 9 , 10 , 11 . Four conventional processes are typically used in the large scale synthesis of aliphatic amines: (1) amination of alcohols, (2) amination of alkyl halides, (3) reduction of nitrile compounds, and (4) reductive amination of carbonyl compounds 3 , which all require multistep processing and purification. HydroAminoMethylation (HAM) is an alternative one-pot synthetic route for sustainable manufacturing of amines from economic starting materials (olefins) without the need for the multistep rection-separation as needed in routes (1), (3), and (4) or the generation of metal halide solid waste that requires disposal as in route (2). HAM is an atom-efficient route as it produces no waste other than water as the sole byproduct. Substitution on the amine α carbon is often introduced in active pharmaceutical ingredients to control their lipophilicity and rate of metabolism 12 . However, hindered amines are usually synthesized by less economic routes such as the amination of alkyl halides. The HAM reaction proceeds through three main steps in an auto-tandem fashion (Fig. 1a ): (i) hydroformylation, (ii) condensation, and (iii) enamine hydrogenation. Steps (ii) and (iii) are often referred to as the reductive amination of aldehydes. Steps (i) and (iii) are gas–liquid reactions and thus provide an exciting opportunity for intensification through flow chemistry (segmented gas–liquid flow format). Step (ii) is a liquid phase condensation reaction that can be equilibrium-limited with sterically hindered amines and thus the undesired aldehyde self-condensation becomes the major reaction. This is a significant drawback that has limited the scope of HAM reactions to non-hindered amines 13 , 14 . Recent studies have demonstrated advances in the rate acceleration and substrate scope expansion of HAM reactions 15 , 16 . However, examples of HAM with sterically hindered amines are rare, and alternative complex routes are developed specifically for their alkylation 17 . The cost associated with catalyst is another drawback that limits the use of HAM in large scale production. In addition to the increasing demand for expanding the substrate scope of HAM reactions to sterically hindered amines, there is a need for continuous operation of HAM with recycling the expensive rhodium (Rh) catalyst to enhance the process sustainability and promote decentralized manufacturing of pharmaceuticals and fine chemicals. Fig. 1: HAM reaction scheme and a summary of prior HAM work vs. this work. a Amine formation by tandem hydroformylation-condensation-hydrogenation reactions. M: metal, L: ligand. b – e Different approaches to amine syntheses via HAM reaction. Full size image The application of the bidentate, commercially available phosphine ligand, Xantphos, in the Rh-catalyzed HAM reactions to maintain high selectivity towards the linear amine was pioneered by Beller and co-workers 18 . However, the HAM reaction is still plagued by the use of expensive cationic Rh(cod) + BF 4 − catalyst and the slow kinetics (batch reaction time > 24 h at 115 °C, TOF < 200 mol/mol Rh/h) which makes it unsuitable for continuous synthesis (Fig. 1b ). The reaction kinetics were enhanced by Hartwig and co-workers. through the addition of the iridium (Ir)-based Xiao’s hydrogenation catalyst and sodium formate to accelerate the enamine hydrogenation step (Fig. 1a , step iii), resulting in a complete conversion in 20 h at 80 °C (Fig. 1c ) 19 . Despite the addition of 1 mol% of Xiao’s Ir catalyst, the hydroformylation step (Fig. 1a , step i) remained slow. To overcome the slow rate of the hydroformylation step, the Rh catalyst loading was increased by 5 times relative to the Rh loading in the study by Beller and co-workers, which resulted in TOF values below 50 mol/mol Rh/h. A more economic Rh source, Rh(acac)(CO) 2 , was used by Hartwig and co-workers. and the bidentate phosphene ligand, BISBI, showed better yields when compared to Xantphos under similar reaction conditions. Despite the significant advancements of the HAM synthetic route in batch reactions, no α-branched amines have been demonstrated. This major limitation arises from the equilibrium-limited condensation and slow hydrogenation of the branched enamine in batch reactors. Wasserscheid and co-workers demonstrated that Rh/Xantphos catalyst for continuous gas phase HAM reaction (TOF values up to 500 mol/mol Rh/h) could be recycled by immobilizing the catalyst in supported ionic liquid phase on activated carbon 20 . Recently, continuous HAM of 1-decene with the non-hindered diethylamine was demonstrated by Seidensticker and co-workers with catalyst recycling (0.1<|im_end|> <|im_start|>assistant Researchers at North Carolina State University have developed a faster, less expensive technique for producing hindered amines—a class of chemicals used as building blocks in products ranging from pharmaceuticals and agrochemicals to detergents and organic light emitting diodes. "Hindered amines are used in a tremendous variety of products, but all of the existing techniques for producing these amines are complicated and expensive," says Milad Abolhasani, corresponding author of a paper on the new technique and an associate professor of chemical and biomolecular engineering at NC State. "We set out to develop a better method for synthesizing these hindered amines, and we were successful." One of the less expensive techniques for producing hindered amines is hydroaminomethylation, or HAM. However, the chemical industry has largely avoided using HAM, because there are too many ways things can go wrong—leaving producers with undesirable chemicals instead of the functionalized amines they were trying to make. Researchers have improved the HAM process over the years. But all of the techniques for avoiding undesirable byproducts have meant extending the timeframe of the HAM process, so that it takes hours to perform all of the necessary reactions. Until now. "We've developed a HAM technique that makes use of continuous flow reactor technologies to produce hindered amines more efficiently," Abolhasani says. "Our HAM process takes less than 30 minutes in most cases. The only products are hindered amines and water. And we are able to recycle the primary catalyst, rhodium/N-Xantphos, which further drives down costs." The success of the new technique is made possible by two things. First, by using a continuous flow reactor that allows for continuous flow of both gases and liquids in a segmented flow format, the researchers were able to make the kinetics of the reaction far more efficient. Second, the new technique makes use of a co-catalyst—fluorinated benzoic acid—which reduces the amount of energy needed to perform some of the necessary reactions in the HAM process. Ultimately, this technique drives down the cost of producing hindered amines using inexpensive feedstock, allowing users to produce them more quickly and with no toxic byproducts. "By designing a cooperative catalyst system, we've demonstrated that the rate of the HAM reactions in our system can be 70 times higher than the existing state-of-the-art processes," says Malek Ibrahim, first author of the paper and a former postdoctoral researcher at NC State. "This process is also a good example for how flow chemistry platforms can improve catalyst turnover frequency, which is increasingly important as the price of rhodium catalysts goes up." The new technique is particularly attractive for decentralized manufacturing operations, since the small footprint of the necessary equipment and its scalability allows users to efficiently produce hindered amines on site and on demand. "What's more, the same technique can also be used to produce enamines—which are other chemical building blocks—on demand, simply by tuning the solvents we use in the flow reactor," Ibrahim says. "You can literally switch back and forth between producing amines and enamines without having to stop the production process, since the only thing you're changing is the solvent mixture." The researchers have filed a provisional patent on the new technique and are now looking for industrial partners to put the technique into widespread use. The paper, "Recyclable Cooperative Catalyst for Accelerated Hydroaminomethylation of Hindered Amines in a Continuous Segmented Flow Reactor," will be published May 4 in the journal Nature Communications. <|im_end|>

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2,314

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Living cells and the extracellular matrix (ECM) can exhibit complex interactions that define key developmental, physiological and pathological processes. Here, we report a new type of directed migration—which we term ‘topotaxis’—guided by the gradient of the nanoscale topographic features in the cells’ ECM environment. We show that the direction of topotaxis is reflective of the effective cell stiffness, and that it depends on the balance of the ECM-triggered signalling pathways PI(3)K–Akt and ROCK–MLCK. In melanoma cancer cells, this balance can be altered by different ECM inputs, pharmacological perturbations or genetic alterations, particularly a loss of PTEN in aggressive melanoma cells. We conclude that topotaxis is a product of the material properties of cells and the surrounding ECM, and propose that the invasive capacity of many cancers may depend broadly on topotactic responses, providing a potentially attractive mechanism for controlling invasive and metastatic behaviour. Main Living cells have evolved a range of mechanisms to recognize a diverse set of environmental cues, including those present in spatially graded doses. For instance, in addition to being sensitive to spatial gradients of various dissolved chemical factors (chemotaxis) 1 , many eukaryotic cell types can detect gradients in the chemical or physical properties of the cell adhesion substratum, such as the graded density of the surface-bound ECM proteins (haptotaxis) 2 , 3 or graded substratum rigidity (durotaxis) 4 , 5 . Within these gradients, individual cells can migrate towards higher ECM densities or stiffer areas of the substratum. Our understanding of the mechano-chemical guidance cues associated with adhesion substrata comes mostly from studies in which the cell substratum is defined to be flat and featureless. However, the more native, in vivo cell adhesion surfaces are topographically more complex, primarily owing to a large diversity of ECM features spanning multiple scales of size and organization. For example, collagen fibrils and fibres interlinked within complex matrices are exemplary of this three-dimensional (3D) topographic complexity 6 . A convenient way to mimic and study the effects of complex ECM topographies, while retaining the advantages of essentially 2D experimentation, is to use quasi-3D, nanopatterned surfaces, capturing the in vivo geometry and size ranges of large ECM fibres. In our previous analysis, we found that many types of mammalian cell have the ability not only to anisotropically orient their migration and polarization in contact with ridged nano-topographic structures 7 , 8 , 9 , 10 , but also to detect and respond to gradients of these nanoscale features by biasing their directional migration 11 , 12 . This phenomenon of single-cell sensitivity to the topography gradient, also reported on the microscale 13 , which we will term here ‘topotaxis’, is still poorly understood. In particular, it is not clear whether it is a version of the more accepted haptotaxis and durotaxis processes, or if it is distinct from them in some essential way. Furthermore, the molecular basis of topotaxis is still not explored. Finally, it has not been addressed whether there is a potential for topotaxis to affect the invasive behaviour of cancer cells interacting with the surrounding ECM. We thus set out to examine topotaxis in the context of one of the most invasive cancers, melanoma. Melanoma, an aggressive cancer mostly affecting the skin, results in the highest percentage of skin-cancer-related deaths 14 . Melanoma tumours can transition from more benign radial growth patterns to more invasive, vertical growth 14 . In the latter case, cell invasion takes place through the dermis, a collagen-rich and cell-poor layer of connective tissue. Within dermis, collagen fibres are highly organized and frequently aligned, presenting an organized ECM-based adhesion substratum. As cancer cells migrate through the collagen matrix, they frequently express proteins, such as matrix metalloproteinases (MMPs), that can break down collagen fibres, which can cause the inhomogeneous density in the matrix and generate arrays of severed fibre bundles 15 , 16 . Melanoma cells and resident fibroblasts can also deposit matrix components, for example, fibronectin (FN), which is essential for invasive cell migration 17 , 18 . Increasing melanoma invasiveness is frequently associated with a range of genetic changes, one of which is a loss of functional PTEN, which can lead to over-activation of the PI(3)K–Akt signalling pathway 14 . Although this pathway has been associated with controlling cell migration, how it can influence melanoma invasiveness is unknown. Here, we provide evidence for topotaxis of melanoma cells, and show that it depends on the material properties of both the model matrix environment (density and structure) and the cell itself (stiffness). Genetic changes, such as loss of PTEN, and the local density of ECM can determine the directionality of topotaxis-driven cell migration. In particular, we show that there exist conditions under which more aggressive melanoma cells can shift in the direction of sparser ECM-mimicking quasi-3D matrix, whereas, strikingly, non-invasive melanoma cells shift in the opposite direction. We suggest a model accounting for this behaviour and show that, in agreement with model predictions, the manipulation of the PI(3)K–Akt- or ROCK–MLCK-dependent signalling pathways can determine the direction of the topotactic movement. The results have important implications for understanding the interplay between genetic mutations associated with cancer aggressiveness and the invasive properties of the cells. The results can also account for basic mechanisms underlying topotaxis in different cell types, and underscore the importance of accounting for materials properties of cells and their microenvironment in understanding physiological and pathological processes. Melanoma cells undergo topotaxis To examine topotactic properties of melanoma cells, we used capillary force lithography to fabricate arrays of nanoscale posts with graded post density. We refer to these arrays as graded post density arrays (GPDAs). The GPDAs had the gradient of post spacing in one of the orthogonal directions ( x direction in Fig. 1a ), with the density varying between 0.3 and 4.2 μm, and constant spacing (600 nm) in the other direction ( y direction in Fig. 1a ). Each post was 600 nm in diameter, within the range of natural collagen fibre (from 50 nm to 20 μm; refs 6 ,", "role": "user" }, { "content": "A new study sheds light on how melanoma cells change from benign to malignant, and how the complex interaction between the cells and their surrounding environment affects outcomes of the cancer. The transition from the radial growth patterns of benign melanoma cells to the vertical patterns of malignant cells has long been a mystery to researchers. But a study from the lab of Andre Levchenko, the John C. Malone Professor of Biomedical Engineering and director of the Yale Systems Biology Institute, has found that the cells' stiffness—determined by the specific balance of two signaling pathways—plays a major role in directing cell migration through the complex environment. Cells essentially sense and follow the nanoscale topography, a phenomenon the researchers have coined \"topotaxis.\" The findings, published in the online edition of the journal Nature Materials on March 14, could lead to new treatments and diagnostic tests, the researchers said. Levchenko and his colleagues found that melanoma cells in the extracellular matrix (ECM)—the body's living tissue—migrate toward either dense or sparse areas of the matrix. Benign cells veer toward the dense area, where they have little room to move and stay on the surface. Malignant cells move toward sparse areas that allow them to grab onto the fibers of the matrix and more effectively spread out. This directed migration of the cells is partly dependent on the cells' material properties: Because they can negotiate the topography better, soft invasive cells are more capable of spreading out than stiff cells. How aggressively the cells move is determined by the chemical cues they receive. Contained in the matrix itself, these cues are processed by a network of pathways that breaks off into two branches. The direction of the cells' migration depends on which branch is dominant. The balance of these pathways is determined by the genetic state of the cells. A mutation that causes the loss of the gene PTEN—a common genetic mutation in aggressive forms of melanoma—will alter the balance. \"We know now that we can interpret genetic changes in the context of this signaling network, which enables us to understand better why genetic changes may lead to metastatic spread,\" said Levchenko, who is a member of the Yale Cancer Center. These findings also suggest avenues for reversing that invasive transition in cell behavior. It doesn't necessarily require restoring the PTEN gene, but restoring the balance of the pathways to their original state through genetic manipulations or using a set of drugs. \"In our experiments, we can take a cell that's aggressive and make it revert to a benign form and vice versa,\" he said. \"As soon as you change the balance, the cells start moving in the opposition direction.\" To study the cell behavior, Levchenko's lab is using models of the matrix made from precisely nanofabricated quasi-3D environments. More complex than the 2D environments of Petri dishes, these environments feature the complex topography and textures of ECM, but are more readily analyzed than the actual tissue. \"Here it's more controlled—we can measure cell stiffness, we can measure activity of these pathways and networks, we can very precisely control the activity of the cells.\" Levchenko also sees a potential in the findings for a less invasive diagnostic test. \"We can take cells and drop them on these nanofabricated surfaces to mimic the matrix, and depending on where they move, we can actually tell whether they're benign or malignant,\" he said. \"That gives us an interesting possibility that didn't exist before—to characterize the degree of invasiveness based on how the cells behave.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Living cells and the extracellular matrix (ECM) can exhibit complex interactions that define key developmental, physiological and pathological processes. Here, we report a new type of directed migration—which we term ‘topotaxis’—guided by the gradient of the nanoscale topographic features in the cells’ ECM environment. We show that the direction of topotaxis is reflective of the effective cell stiffness, and that it depends on the balance of the ECM-triggered signalling pathways PI(3)K–Akt and ROCK–MLCK. In melanoma cancer cells, this balance can be altered by different ECM inputs, pharmacological perturbations or genetic alterations, particularly a loss of PTEN in aggressive melanoma cells. We conclude that topotaxis is a product of the material properties of cells and the surrounding ECM, and propose that the invasive capacity of many cancers may depend broadly on topotactic responses, providing a potentially attractive mechanism for controlling invasive and metastatic behaviour. Main Living cells have evolved a range of mechanisms to recognize a diverse set of environmental cues, including those present in spatially graded doses. For instance, in addition to being sensitive to spatial gradients of various dissolved chemical factors (chemotaxis) 1 , many eukaryotic cell types can detect gradients in the chemical or physical properties of the cell adhesion substratum, such as the graded density of the surface-bound ECM proteins (haptotaxis) 2 , 3 or graded substratum rigidity (durotaxis) 4 , 5 . Within these gradients, individual cells can migrate towards higher ECM densities or stiffer areas of the substratum. Our understanding of the mechano-chemical guidance cues associated with adhesion substrata comes mostly from studies in which the cell substratum is defined to be flat and featureless. However, the more native, in vivo cell adhesion surfaces are topographically more complex, primarily owing to a large diversity of ECM features spanning multiple scales of size and organization. For example, collagen fibrils and fibres interlinked within complex matrices are exemplary of this three-dimensional (3D) topographic complexity 6 . A convenient way to mimic and study the effects of complex ECM topographies, while retaining the advantages of essentially 2D experimentation, is to use quasi-3D, nanopatterned surfaces, capturing the in vivo geometry and size ranges of large ECM fibres. In our previous analysis, we found that many types of mammalian cell have the ability not only to anisotropically orient their migration and polarization in contact with ridged nano-topographic structures 7 , 8 , 9 , 10 , but also to detect and respond to gradients of these nanoscale features by biasing their directional migration 11 , 12 . This phenomenon of single-cell sensitivity to the topography gradient, also reported on the microscale 13 , which we will term here ‘topotaxis’, is still poorly understood. In particular, it is not clear whether it is a version of the more accepted haptotaxis and durotaxis processes, or if it is distinct from them in some essential way. Furthermore, the molecular basis of topotaxis is still not explored. Finally, it has not been addressed whether there is a potential for topotaxis to affect the invasive behaviour of cancer cells interacting with the surrounding ECM. We thus set out to examine topotaxis in the context of one of the most invasive cancers, melanoma. Melanoma, an aggressive cancer mostly affecting the skin, results in the highest percentage of skin-cancer-related deaths 14 . Melanoma tumours can transition from more benign radial growth patterns to more invasive, vertical growth 14 . In the latter case, cell invasion takes place through the dermis, a collagen-rich and cell-poor layer of connective tissue. Within dermis, collagen fibres are highly organized and frequently aligned, presenting an organized ECM-based adhesion substratum. As cancer cells migrate through the collagen matrix, they frequently express proteins, such as matrix metalloproteinases (MMPs), that can break down collagen fibres, which can cause the inhomogeneous density in the matrix and generate arrays of severed fibre bundles 15 , 16 . Melanoma cells and resident fibroblasts can also deposit matrix components, for example, fibronectin (FN), which is essential for invasive cell migration 17 , 18 . Increasing melanoma invasiveness is frequently associated with a range of genetic changes, one of which is a loss of functional PTEN, which can lead to over-activation of the PI(3)K–Akt signalling pathway 14 . Although this pathway has been associated with controlling cell migration, how it can influence melanoma invasiveness is unknown. Here, we provide evidence for topotaxis of melanoma cells, and show that it depends on the material properties of both the model matrix environment (density and structure) and the cell itself (stiffness). Genetic changes, such as loss of PTEN, and the local density of ECM can determine the directionality of topotaxis-driven cell migration. In particular, we show that there exist conditions under which more aggressive melanoma cells can shift in the direction of sparser ECM-mimicking quasi-3D matrix, whereas, strikingly, non-invasive melanoma cells shift in the opposite direction. We suggest a model accounting for this behaviour and show that, in agreement with model predictions, the manipulation of the PI(3)K–Akt- or ROCK–MLCK-dependent signalling pathways can determine the direction of the topotactic movement. The results have important implications for understanding the interplay between genetic mutations associated with cancer aggressiveness and the invasive properties of the cells. The results can also account for basic mechanisms underlying topotaxis in different cell types, and underscore the importance of accounting for materials properties of cells and their microenvironment in understanding physiological and pathological processes. Melanoma cells undergo topotaxis To examine topotactic properties of melanoma cells, we used capillary force lithography to fabricate arrays of nanoscale posts with graded post density. We refer to these arrays as graded post density arrays (GPDAs). The GPDAs had the gradient of post spacing in one of the orthogonal directions ( x direction in Fig. 1a ), with the density varying between 0.3 and 4.2 μm, and constant spacing (600 nm) in the other direction ( y direction in Fig. 1a ). Each post was 600 nm in diameter, within the range of natural collagen fibre (from 50 nm to 20 μm; refs 6 ,<|im_end|> <|im_start|>assistant A new study sheds light on how melanoma cells change from benign to malignant, and how the complex interaction between the cells and their surrounding environment affects outcomes of the cancer. The transition from the radial growth patterns of benign melanoma cells to the vertical patterns of malignant cells has long been a mystery to researchers. But a study from the lab of Andre Levchenko, the John C. Malone Professor of Biomedical Engineering and director of the Yale Systems Biology Institute, has found that the cells' stiffness—determined by the specific balance of two signaling pathways—plays a major role in directing cell migration through the complex environment. Cells essentially sense and follow the nanoscale topography, a phenomenon the researchers have coined "topotaxis." The findings, published in the online edition of the journal Nature Materials on March 14, could lead to new treatments and diagnostic tests, the researchers said. Levchenko and his colleagues found that melanoma cells in the extracellular matrix (ECM)—the body's living tissue—migrate toward either dense or sparse areas of the matrix. Benign cells veer toward the dense area, where they have little room to move and stay on the surface. Malignant cells move toward sparse areas that allow them to grab onto the fibers of the matrix and more effectively spread out. This directed migration of the cells is partly dependent on the cells' material properties: Because they can negotiate the topography better, soft invasive cells are more capable of spreading out than stiff cells. How aggressively the cells move is determined by the chemical cues they receive. Contained in the matrix itself, these cues are processed by a network of pathways that breaks off into two branches. The direction of the cells' migration depends on which branch is dominant. The balance of these pathways is determined by the genetic state of the cells. A mutation that causes the loss of the gene PTEN—a common genetic mutation in aggressive forms of melanoma—will alter the balance. "We know now that we can interpret genetic changes in the context of this signaling network, which enables us to understand better why genetic changes may lead to metastatic spread," said Levchenko, who is a member of the Yale Cancer Center. These findings also suggest avenues for reversing that invasive transition in cell behavior. It doesn't necessarily require restoring the PTEN gene, but restoring the balance of the pathways to their original state through genetic manipulations or using a set of drugs. "In our experiments, we can take a cell that's aggressive and make it revert to a benign form and vice versa," he said. "As soon as you change the balance, the cells start moving in the opposition direction." To study the cell behavior, Levchenko's lab is using models of the matrix made from precisely nanofabricated quasi-3D environments. More complex than the 2D environments of Petri dishes, these environments feature the complex topography and textures of ECM, but are more readily analyzed than the actual tissue. "Here it's more controlled—we can measure cell stiffness, we can measure activity of these pathways and networks, we can very precisely control the activity of the cells." Levchenko also sees a potential in the findings for a less invasive diagnostic test. "We can take cells and drop them on these nanofabricated surfaces to mimic the matrix, and depending on where they move, we can actually tell whether they're benign or malignant," he said. "That gives us an interesting possibility that didn't exist before—to characterize the degree of invasiveness based on how the cells behave." <|im_end|>

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35940, 49122, 17915, 304, 279, 6303, 323, 7068, 18893, 315, 84450, 57525, 49707, 220, 868, 1174, 220, 845, 662, 11220, 276, 7942, 7917, 323, 19504, 16178, 299, 2067, 12019, 649, 1101, 16946, 6303, 6956, 11, 369, 3187, 11, 16178, 2298, 440, 258, 320, 42704, 705, 902, 374, 7718, 369, 53354, 2849, 12172, 220, 1114, 1174, 220, 972, 662, 74540, 68012, 7942, 1558, 300, 13071, 374, 14134, 5938, 449, 264, 2134, 315, 19465, 4442, 11, 832, 315, 902, 374, 264, 4814, 315, 16003, 19932, 965, 11, 902, 649, 3063, 311, 927, 12, 23863, 315, 279, 23396, 7, 18, 8, 42, 4235, 92040, 91977, 38970, 220, 975, 662, 10541, 420, 38970, 706, 1027, 5938, 449, 26991, 2849, 12172, 11, 1268, 433, 649, 10383, 68012, 7942, 1558, 300, 13071, 374, 9987, 13, 5810, 11, 584, 3493, 6029, 369, 1948, 354, 7332, 315, 68012, 7942, 7917, 11, 323, 1501, 430, 433, 14117, 389, 279, 3769, 6012, 315, 2225, 279, 1646, 6303, 4676, 320, 70918, 323, 6070, 8, 323, 279, 2849, 5196, 320, 267, 3168, 2136, 570, 75226, 4442, 11, 1778, 439, 4814, 315, 19932, 965, 11, 323, 279, 2254, 17915, 315, 80700, 649, 8417, 279, 5216, 2786, 315, 1948, 354, 7332, 32505, 2849, 12172, 13, 763, 4040, 11, 584, 1501, 430, 1070, 3073, 4787, 1234, 902, 810, 19738, 68012, 7942, 7917, 649, 6541, 304, 279, 5216, 315, 993, 10642, 80700, 1474, 318, 16671, 48844, 12, 18, 35, 6303, 11, 20444, 11, 21933, 398, 11, 2536, 3502, 78134, 68012, 7942, 7917, 6541, 304, 279, 14329, 5216, 13, 1226, 4284, 264, 1646, 24043, 369, 420, 17432, 323, 1501, 430, 11, 304, 9306, 449, 1646, 20492, 11, 279, 34786, 315, 279, 23396, 7, 18, 8, 42, 4235, 92040, 12, 477, 79620, 4235, 2735, 3096, 43918, 91977, 44014, 649, 8417, 279, 5216, 315, 279, 1948, 354, 24045, 7351, 13, 578, 3135, 617, 3062, 25127, 369, 8830, 279, 958, 1387, 1990, 19465, 34684, 5938, 449, 9572, 13632, 13071, 323, 279, 53354, 6012, 315, 279, 7917, 13, 578, 3135, 649, 1101, 2759, 369, 6913, 24717, 16940, 1948, 354, 7332, 304, 2204, 2849, 4595, 11, 323, 53209, 279, 12939, 315, 24043, 369, 7384, 6012, 315, 7917, 323, 872, 8162, 24175, 304, 8830, 53194, 323, 89961, 11618, 13, 11220, 276, 7942, 7917, 37771, 1948, 354, 7332, 2057, 21635, 1948, 354, 24045, 6012, 315, 68012, 7942, 7917, 11, 584, 1511, 2107, 35605, 5457, 46282, 5814, 311, 13354, 349, 18893, 315, 20622, 437, 2296, 8158, 449, 80273, 1772, 17915, 13, 1226, 8464, 311, 1521, 18893, 439, 80273, 1772, 17915, 18893, 320, 38, 23891, 2170, 570, 578, 480, 23891, 2170, 1047, 279, 20779, 315, 1772, 27032, 304, 832, 315, 279, 95680, 18445, 320, 865, 5216, 304, 23966, 13, 220, 16, 64, 7026, 449, 279, 17915, 29865, 1990, 220, 15, 13, 18, 323, 220, 19, 13, 17, 33983, 76, 11, 323, 6926, 27032, 320, 5067, 26807, 8, 304, 279, 1023, 5216, 320, 379, 5216, 304, 23966, 13, 220, 16, 64, 7609, 9062, 1772, 574, 220, 5067, 26807, 304, 23899, 11, 2949, 279, 2134, 315, 5933, 71313, 57525, 320, 1527, 220, 1135, 26807, 311, 220, 508, 33983, 76, 26, 44243, 220, 21, 1174, 128257, 198, 128256, 78191, 198, 32, 502, 4007, 77039, 3177, 389, 1268, 68012, 7942, 7917, 2349, 505, 65309, 311, 94329, 11, 323, 1268, 279, 6485, 16628, 1990, 279, 7917, 323, 872, 14932, 4676, 22223, 20124, 315, 279, 9572, 13, 578, 9320, 505, 279, 57936, 6650, 12912, 315, 65309, 68012, 7942, 7917, 311, 279, 12414, 12912, 315, 94329, 7917, 706, 1317, 1027, 264, 23347, 311, 12074, 13, 2030, 264, 4007, 505, 279, 10278, 315, 27525, 28120, 7674, 9509, 11, 279, 3842, 356, 13, 84171, 17054, 315, 12371, 61860, 17005, 323, 7690, 315, 279, 44552, 15264, 40023, 10181, 11, 706, 1766, 430, 279, 7917, 6, 70334, 2345, 67, 47737, 555, 279, 3230, 8335, 315, 1403, 43080, 44014, 2345, 28897, 264, 3682, 3560, 304, 46090, 2849, 12172, 1555, 279, 6485, 4676, 13, 59190, 16168, 5647, 323, 1833, 279, 20622, 437, 2296, 1948, 5814, 11, 264, 25885, 279, 12074, 617, 78718, 330, 3565, 354, 7332, 1210, 578, 14955, 11, 4756, 304, 279, 2930, 14002, 315, 279, 8486, 22037, 32009, 389, 5587, 220, 975, 11, 1436, 3063, 311, 502, 22972, 323, 15439, 7177, 11, 279, 12074, 1071, 13, 28120, 7674, 9509, 323, 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279, 8547, 315, 1558, 300, 13071, 3196, 389, 1268, 279, 7917, 36792, 1210, 220, 128257, 198 ]

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Skeletal muscle is an archetypal organ whose structure is tuned to match function. The magnitude of order in muscle fibers and myofibrils containing motor protein polymers determines the directed force output of the summed force vectors and, therefore, the muscle’s power performance on the structural level. Structure and function can change dramatically during disease states involving chronic remodeling. Cellular remodeling of the cytoarchitecture has been pursued using noninvasive and label-free multiphoton second harmonic generation (SHG) microscopy. Hereby, structure parameters can be extracted as a measure of myofibrillar order and thus are suggestive of the force output that a remodeled structure can still achieve. However, to date, the parameters have only been an indirect measure, and a precise calibration of optical SHG assessment for an exerted force has been elusive as no technology in existence correlates these factors. We engineered a novel, automated, high-precision biomechatronics system into a multiphoton microscope allows simultaneous isometric Ca 2+ -graded force or passive viscoelasticity measurements and SHG recordings. Using this MechaMorph system, we studied force and SHG in single EDL muscle fibers from wt and mdx mice; the latter serves as a model for compromised force and abnormal myofibrillar structure. We present Ca 2+ -graded isometric force, pCa-force curves, passive viscoelastic parameters and 3D structure in the same fiber for the first time. Furthermore, we provide a direct calibration of isometric force to morphology, which allows noninvasive prediction of the force output of single fibers from only multiphoton images, suggesting a potential application in the diagnosis of myopathies. Introduction Structure and function are inevitably related to each other. A desired function requires a tailored structure, while from a given structure, deductions regarding its function may be derived. This particularly applies to the concept of organ and tissue structures and functions. Skeletal muscle, for instance, is highly ordered and hierarchically structured by parallel and serial polymeric motor proteins, i.e., actomyosin filaments, and series elastic elements, to perform as a linear bioactuator to enable movement and to give in passively to external forces 1 . Within each muscle fiber, the concept of highly ordered elements, i.e., myofibrils aligned in parallel by sarcomeric and extrasarcomeric proteins at the z-disks 2 , ensures the well-known striation-pattern 3 and directs force production along the main fiber axis 4 . Thus, apart from fast signaling-related activation processes that determine muscle performance, e.g., excitation contraction coupling and Ca 2+ homeostasis 5 , a long-term predictor of muscle function is found in structural changes. This is particularly important as skeletal muscle has a high plasticity to respond to exercise with hypertrophy, to disuse with atrophy 6 , and to injury with complete regeneration and repair 7 . Similarly, muscle structure and cytoarchitecture are also major targets in muscle diseases, such as chronic inflammatory or degenerative diseases associated with ongoing degeneration-regeneration cycles, imperfect repair, and tissue and cellular remodeling. Examples include (poly/dermato-)myositis 8 , cancer cachexia 9 , muscular dystrophies 10 , and even aging 11 . Muscle structure remodeling involves not only the extracellular matrix (e.g., fibrosis) but also the remodeling of the sarcomere and the myofibrillar cytoarchitecture. For instance, a hallmark of structural cellular changes as a result of regeneration has been found in single fiber branching and splitting, for example, in Duchenne muscular dystrophy 12 , 13 , 14 , following weight-lift exercise 15 or toxin-induced myonecrosis 16 . Thus, it is not surprising that chronic conditions with ongoing remodeling are associated with progressive muscle weakness 12 , 17 . Therefore, the three-dimensional sterical arrangement of myofibrillar and cytoarchitecture may be considered an anatomical correlate to predict muscle force outcomes. It is tempting to speculate that imaging of the 3D muscle fiber architecture can be a modality for extrapolating mechanical performance instead of executing strenuous force recordings using force transducer technologies, in particular in cases involving single fibers. However, the assessment of skeletal muscle fiber architecture is not straightforward. Clinically, the diagnosis of myopathy in patients presenting muscle weakness is usually based on histology section analysis from muscle biopsies. Although cross-cut sections allow visualization of multiple cells at once, this approach is limited to one plane without any 3D aspect. Alternatively, confocal laser scanning microscopy has frequently been used to determine muscle fiber structure 13 , 18 , 19 . However, it always requires external labels, which may be harmful and prone to bleaching. More importantly, single muscle fibers with diameters exceeding 50 µm must already be considered thick samples where photon scattering and absorption can become substantial within the illuminated z-cone. An elegant alternative is multiphoton microscopy where infrared light ensures deeper penetration depths and less scattering while laser pulse excitation ensures excitation only within a focal volume of ∼ 1 µm 3 . Using a special nonlinear mode of multiphoton excitation through second harmonic generation (SHG), intrinsic signals can be visualized label-free. Biomolecules susceptible for SHG comprise collagen-I and myosin-II, enabling label-free, detailed structural analysis of subcellular cytoarchitecture and myofibrillar geometry in 3D 3 , 20 , 21 . Furthermore, several mathematical analysis strategies have been developed to describe the degree of myofibrillar disarray using quantitative morphometry in 2D images 14 , 20 , 22 and in 3D volumes of muscle or single fiber SHG stacks 23 , 24 , 25 . Our group introduced boundary tensor orientation analysis of myofibrillar striation patterns to extract two very sensitive parameters of ‘myofibrillar disorder,’ namely, cosine angle sums (CAS) and vernier densities (VDs). This approach has successfully been employed to describe alterations in 3D cytoarchitecture associated with various disease models 14 , 24 , 26 , 27 . In particular, such studies enabled the identification of the correlation between structure and morphology for the chronic progression of muscle weakness due to age or inherited myopathies. However, despite all the progress made in SHG imaging and pattern recognition analysis defining ultrastructural alterations, to date there is still no direct proof of how an altered sterical myofibrillar cytoarchitecture is correlated to an impaired muscle force. To obtain such a calibration, simultaneous measurements", "role": "user" }, { "content": "Biotechnologists at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have developed a system to accurately measure muscle weakness caused by structural changes in muscle tissue. The new method allows muscle function to be assessed using imaging without the need for sophisticated biomechanical recordings, and could in future even make taking tissue samples for diagnosing myopathy superfluous. The results have been published in the renowned journal Light: Science & Applications. The muscle is a highly ordered and hierarchically structured organ. This is reflected not only in the parallel bundling of muscle fibres, but also in the structure of individual cells. The myofibrils responsible for contraction consist of hundreds of identically structured units connected one after another. This orderly structure determines the force which is exerted and the strength of the muscle. Inflammatory or degenerative diseases or cancer can lead to a chronic restructuring of this architecture, causing scarring, stiffening or branching of muscle fibres and resulting in a dramatic reduction in muscular function. Although such changes in muscular morphology can already be tracked using non-invasive multiphoton microscopy, it has not yet been possible to assess muscle strength accurately on the basis of imaging alone. New system correlates structure and strength Researchers from the Chair of Medical Biotechnology have now developed a system that allows muscular weakness caused by structural changes to be measured at the same time as optically assessing muscular architecture. \"We engineered a miniaturized biomechatronics system and integrated it into a multiphoton microscope, allowing us to directly assess the strength and elasticity of individual muscle fibres at the same time as recording structural anomalies,\" explains Prof. Dr. Oliver Friedrich. In order to prove the muscle's ability to contract, the researchers dipped the muscle cells into solutions with increasing concentrations of free calcium ions. Calcium is also responsible for triggering muscle contractions in humans and animals. The viscoelasticity of the fibres was also measured, by stretching them little by little. A highly-sensitive detector recorded mechanical resistance exercised by the muscle fibres clamped on the device. Data pool for simplified diagnosis The technology developed by researchers at FAU is, however, merely the first step towards being able to diagnose muscle disorders much more easily in future: \"Being able to measure isometric strength and passive viscoelasticity at the same time as visually showing the morphometry of muscle cells has enabled us, for the first time, to obtain direct structure-function data pairs,\" Oliver Friedrich says. \"This allows us to establish significant linear correlations between the structure and function of muscles at the single fibre level.\" The data pool will be used in future to reliably predict forces and biomechanical performances in skeletal muscle exclusively using optical assessments based on SHG images (the initials stand for Second Harmonic Generation and refer to images created using lasers at second harmonic frequency), without the need for complex strength measurements. At present, muscle cells still have to be removed from the body before they can be examined using a multiphoton microscope. However, it is plausible that this may become superfluous in future if the necessary technology can continue to be miniaturized, making it possible for muscle function to be examined, for example, using a micro-endoscope. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Skeletal muscle is an archetypal organ whose structure is tuned to match function. The magnitude of order in muscle fibers and myofibrils containing motor protein polymers determines the directed force output of the summed force vectors and, therefore, the muscle’s power performance on the structural level. Structure and function can change dramatically during disease states involving chronic remodeling. Cellular remodeling of the cytoarchitecture has been pursued using noninvasive and label-free multiphoton second harmonic generation (SHG) microscopy. Hereby, structure parameters can be extracted as a measure of myofibrillar order and thus are suggestive of the force output that a remodeled structure can still achieve. However, to date, the parameters have only been an indirect measure, and a precise calibration of optical SHG assessment for an exerted force has been elusive as no technology in existence correlates these factors. We engineered a novel, automated, high-precision biomechatronics system into a multiphoton microscope allows simultaneous isometric Ca 2+ -graded force or passive viscoelasticity measurements and SHG recordings. Using this MechaMorph system, we studied force and SHG in single EDL muscle fibers from wt and mdx mice; the latter serves as a model for compromised force and abnormal myofibrillar structure. We present Ca 2+ -graded isometric force, pCa-force curves, passive viscoelastic parameters and 3D structure in the same fiber for the first time. Furthermore, we provide a direct calibration of isometric force to morphology, which allows noninvasive prediction of the force output of single fibers from only multiphoton images, suggesting a potential application in the diagnosis of myopathies. Introduction Structure and function are inevitably related to each other. A desired function requires a tailored structure, while from a given structure, deductions regarding its function may be derived. This particularly applies to the concept of organ and tissue structures and functions. Skeletal muscle, for instance, is highly ordered and hierarchically structured by parallel and serial polymeric motor proteins, i.e., actomyosin filaments, and series elastic elements, to perform as a linear bioactuator to enable movement and to give in passively to external forces 1 . Within each muscle fiber, the concept of highly ordered elements, i.e., myofibrils aligned in parallel by sarcomeric and extrasarcomeric proteins at the z-disks 2 , ensures the well-known striation-pattern 3 and directs force production along the main fiber axis 4 . Thus, apart from fast signaling-related activation processes that determine muscle performance, e.g., excitation contraction coupling and Ca 2+ homeostasis 5 , a long-term predictor of muscle function is found in structural changes. This is particularly important as skeletal muscle has a high plasticity to respond to exercise with hypertrophy, to disuse with atrophy 6 , and to injury with complete regeneration and repair 7 . Similarly, muscle structure and cytoarchitecture are also major targets in muscle diseases, such as chronic inflammatory or degenerative diseases associated with ongoing degeneration-regeneration cycles, imperfect repair, and tissue and cellular remodeling. Examples include (poly/dermato-)myositis 8 , cancer cachexia 9 , muscular dystrophies 10 , and even aging 11 . Muscle structure remodeling involves not only the extracellular matrix (e.g., fibrosis) but also the remodeling of the sarcomere and the myofibrillar cytoarchitecture. For instance, a hallmark of structural cellular changes as a result of regeneration has been found in single fiber branching and splitting, for example, in Duchenne muscular dystrophy 12 , 13 , 14 , following weight-lift exercise 15 or toxin-induced myonecrosis 16 . Thus, it is not surprising that chronic conditions with ongoing remodeling are associated with progressive muscle weakness 12 , 17 . Therefore, the three-dimensional sterical arrangement of myofibrillar and cytoarchitecture may be considered an anatomical correlate to predict muscle force outcomes. It is tempting to speculate that imaging of the 3D muscle fiber architecture can be a modality for extrapolating mechanical performance instead of executing strenuous force recordings using force transducer technologies, in particular in cases involving single fibers. However, the assessment of skeletal muscle fiber architecture is not straightforward. Clinically, the diagnosis of myopathy in patients presenting muscle weakness is usually based on histology section analysis from muscle biopsies. Although cross-cut sections allow visualization of multiple cells at once, this approach is limited to one plane without any 3D aspect. Alternatively, confocal laser scanning microscopy has frequently been used to determine muscle fiber structure 13 , 18 , 19 . However, it always requires external labels, which may be harmful and prone to bleaching. More importantly, single muscle fibers with diameters exceeding 50 µm must already be considered thick samples where photon scattering and absorption can become substantial within the illuminated z-cone. An elegant alternative is multiphoton microscopy where infrared light ensures deeper penetration depths and less scattering while laser pulse excitation ensures excitation only within a focal volume of ∼ 1 µm 3 . Using a special nonlinear mode of multiphoton excitation through second harmonic generation (SHG), intrinsic signals can be visualized label-free. Biomolecules susceptible for SHG comprise collagen-I and myosin-II, enabling label-free, detailed structural analysis of subcellular cytoarchitecture and myofibrillar geometry in 3D 3 , 20 , 21 . Furthermore, several mathematical analysis strategies have been developed to describe the degree of myofibrillar disarray using quantitative morphometry in 2D images 14 , 20 , 22 and in 3D volumes of muscle or single fiber SHG stacks 23 , 24 , 25 . Our group introduced boundary tensor orientation analysis of myofibrillar striation patterns to extract two very sensitive parameters of ‘myofibrillar disorder,’ namely, cosine angle sums (CAS) and vernier densities (VDs). This approach has successfully been employed to describe alterations in 3D cytoarchitecture associated with various disease models 14 , 24 , 26 , 27 . In particular, such studies enabled the identification of the correlation between structure and morphology for the chronic progression of muscle weakness due to age or inherited myopathies. However, despite all the progress made in SHG imaging and pattern recognition analysis defining ultrastructural alterations, to date there is still no direct proof of how an altered sterical myofibrillar cytoarchitecture is correlated to an impaired muscle force. To obtain such a calibration, simultaneous measurements<|im_end|> <|im_start|>assistant Biotechnologists at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have developed a system to accurately measure muscle weakness caused by structural changes in muscle tissue. The new method allows muscle function to be assessed using imaging without the need for sophisticated biomechanical recordings, and could in future even make taking tissue samples for diagnosing myopathy superfluous. The results have been published in the renowned journal Light: Science & Applications. The muscle is a highly ordered and hierarchically structured organ. This is reflected not only in the parallel bundling of muscle fibres, but also in the structure of individual cells. The myofibrils responsible for contraction consist of hundreds of identically structured units connected one after another. This orderly structure determines the force which is exerted and the strength of the muscle. Inflammatory or degenerative diseases or cancer can lead to a chronic restructuring of this architecture, causing scarring, stiffening or branching of muscle fibres and resulting in a dramatic reduction in muscular function. Although such changes in muscular morphology can already be tracked using non-invasive multiphoton microscopy, it has not yet been possible to assess muscle strength accurately on the basis of imaging alone. New system correlates structure and strength Researchers from the Chair of Medical Biotechnology have now developed a system that allows muscular weakness caused by structural changes to be measured at the same time as optically assessing muscular architecture. "We engineered a miniaturized biomechatronics system and integrated it into a multiphoton microscope, allowing us to directly assess the strength and elasticity of individual muscle fibres at the same time as recording structural anomalies," explains Prof. Dr. Oliver Friedrich. In order to prove the muscle's ability to contract, the researchers dipped the muscle cells into solutions with increasing concentrations of free calcium ions. Calcium is also responsible for triggering muscle contractions in humans and animals. The viscoelasticity of the fibres was also measured, by stretching them little by little. A highly-sensitive detector recorded mechanical resistance exercised by the muscle fibres clamped on the device. Data pool for simplified diagnosis The technology developed by researchers at FAU is, however, merely the first step towards being able to diagnose muscle disorders much more easily in future: "Being able to measure isometric strength and passive viscoelasticity at the same time as visually showing the morphometry of muscle cells has enabled us, for the first time, to obtain direct structure-function data pairs," Oliver Friedrich says. "This allows us to establish significant linear correlations between the structure and function of muscles at the single fibre level." The data pool will be used in future to reliably predict forces and biomechanical performances in skeletal muscle exclusively using optical assessments based on SHG images (the initials stand for Second Harmonic Generation and refer to images created using lasers at second harmonic frequency), without the need for complex strength measurements. At present, muscle cells still have to be removed from the body before they can be examined using a multiphoton microscope. However, it is plausible that this may become superfluous in future if the necessary technology can continue to be miniaturized, making it possible for muscle function to be examined, for example, using a micro-endoscope. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Traditionally, cultures have been treated as though they reside exclusively within, or perfectly overlap with countries. Indeed, the terms “country” and “culture” are often used interchangeably. As evidence mounts for substantial within-country cultural variation, and often between-country similarities, the problem with equating country and culture becomes more apparent. To help resolve the country-culture conundrum, we evaluate the extent to which political boundaries are suitable for clustering cultures based on a meta-analysis of 558 studies that used Hofstede’s (Culture’s consequences: international differences in work-related values. Sage Publications, Beverly Hills, 1980 ) cultural values framework. The results reveal that approximately 80 % of variation in cultural values resides within countries, confirming that country is often a poor proxy for culture. We also evaluate the relative suitability of other demographic and environmental characteristics, such as occupation, socio-economic status, wealth, freedom, globalization, and instability. Our results suggest that it may be more appropriate to talk about cultures of professions, socio-economic classes, and free versus oppressed societies, than about cultures of countries. Access provided by Universität des es, -und Working on a manuscript? Avoid the common mistakes 1 Introduction Traditionally, cultures have been assumed to reside within countries. From the earliest studies of cultural differences dating back over two centuries (Darton 1790 , see Fig. 1 ) to more recent research by Hofstede ( 1980 ) and the GLOBE team (House et al. 2004 ), the unit of analysis in cross-cultural studies has typically been country. The focus on national cultures has appropriate applications, but its dominance in research has led to a lack of attention to other plausible organizing units of culture. Equating cultures with countries and using country of origin and individual culture interchangeably became a common practice (Brewer and Venaik 2012 ). However, the appropriateness of this trend depends on answers to two questions, including: (1) are countries good proxies for cultures, and (2) could other factors be superior for describing boundaries of cultural regions or groups of people who display similar cultural values? Fig. 1 Page from one of the earliest studies into cultural differences by William Darton ( 1790 ) Full size image Culture is a multi-faceted construct. First, the word culture has many meanings, from a collective of people who share a common history, language and traditions, to characteristics of such a collective in terms of its artifacts, practices, and value systems. Illustrating the pervasiveness and possibly ambiguity of the term “culture,” a Google search for “culture” and its derivatives returns 1.5 billion hits, making it one of the most popular words on the Web. More than 60 years ago, Kroeber and Kluckhohn ( 1952 ) found 164 distinct definitions of culture. Despite the variety of definitions, several elements are common across most of them, principally that culture is: (1) a relatively stable, (2) multi-level construct comprised of values, beliefs, norms, traditions, and artifacts that (3) are shared in a given population (cf. Taras et al. 2009 ). Early empirical research on cross-cultural differences has been largely qualitative and focused on describing artifacts, rituals, and social institutions. However, following the publication of Hofstede’s ( 1980 ) seminal book, Culture’s Consequences, the focus shifted to cultural values. As noted by Taras et al. ( 2009 ), “culture is values” has become one of the commandments of cross-cultural management research. The almost exclusive focus on cultural values is often justified, but also problematic and limiting in many ways, particularly if measured using Hofstede’s ( 1980 ) framework, one that was developed based on a survey not actually originally intended for cultural analysis (cf. Baskerville 2003 ; McSweeney 2002 ; Taras and Steel 2009 for reviews of problems with Hofstede’s framework in general and for studying “culture” in particular). For the purpose of the present study, however, the question of whether or not the Hofstede’s framework is suitable for studying culture due to its limitations is secondary because most empirical research on culture over the past 35 years has relied on Hofstede’s framework. As Taras and Steel ( 2009 ) concluded, since the publication of Culture’s Consequences (Hofstede 1980 ), research on culture effectively became research on values. Indeed, reviews of cross-cultural research published in management, psychology and related disciplines confirm that empirical measurement of what is called “culture” has almost exclusively focused on assessing cultural values, usually by the means of self-response questionnaires (Caprar et al. 2015 ). Subsequent models following Hofstede’s work primarily refined his framework (e.g., House et al. 2004 (GLOBE); Schwartz 1994 ) rather than substantively altering it. Even though this work changed the wording of items and the list of the dimensions, the underlying practices remained the same and are subject to the same limitations (McSweeney 2013 ). Accordingly, the outcome of just about every major cross-cultural comparative study has been a set of national cultural means and country rankings along dimensions of cultural values (Taras et al. 2009 ). Thus, to settle the culture-versus-country debate, we rely on the approach to culture that is at the foundation of most of the empirical literature on the topic. Interpreting culture as inherently inseparable from country has become popular enough that the two terms often are used synonymously. For example, the word “culture” has been routinely included in titles of publications that provided cross-country (but not culture) comparisons, as in “ The Perception of Distributive Justice in Two Cultures ” (Marin 1982 ), “ Rules for Social Relationships in Four Cultures ” (Argyle 1986 ), “ The Effect of Culture on the Curvilinear Relationship between Performance and Turnover ” (Sturman et al. 2012 ), “A Cross - Cultural Examination of Self - Leadership” (Houghton et al. 2014 ), and many others (e.g., Bagozzi et al. 2003 ; Cialdini et al. 1999 ; Goodwin and Plaza 2000 ). Similarly, there are numerous examples when nationality or country of residence are used as proxies for cultural values, as illustrated by such quotes as “ cultural background was measured by the current citizenship (passport status) of each of the managers ”", "role": "user" }, { "content": "Researchers and businesses have often operated under the idea that work-related cultural values are defined by country - just think of stereotypes about countries that are known to have hard workers or are team-oriented. A new study finds that nationality is actually a bad proxy for work-related cultural values, and points to other groupings - such as occupation - as more reliable indicators. \"I study work-related values - how culture informs our beliefs and behaviors related to work,\" says Bradley Kirkman, co-author of a paper on the work. \"This field has long defined and measured culture based on national borders. We wanted to know if nationality is really the best way to delineate cultural values and boundaries. And we learned that it's not a very good marker.\" Kirkman is the General (Ret.) H. Hugh Shelton Distinguished Professor of Leadership and head of the Department of Management, Innovation and Entrepreneurship at North Carolina State University. The paper was co-authored by researchers at the University of North Carolina at Greensboro and the University of Calgary. To examine the issue, the researchers looked at data from 558 studies on work-related values. The studies covered 32 countries from around the world, including the United States, Brazil, France, South Africa and China. Specifically, the researchers evaluated variation, both within each country and between countries, on four work-related cultural values: Individualism, which measures the extent to which a society places emphasis on individuals as opposed to groups;Power distance, which measures the importance of status and hierarchy in work settings;Uncertainty avoidance, which measures the extent to which cultures are willing to accept ambiguity or the unknown; andQuantity versus quality of life, which measures emphasis on competition and material wealth versus emphasis on societal welfare and well-being. The researchers found that approximately 80 percent of variation in these values was within countries. For example, at the low end, only 16.6 percent of the variation on individualism was between countries - 83.4 percent of the variability was within countries. At the high end, 20.8 percent of variation on power distance was between countries - which still left 79.2 percent of the variability within countries. \"This told us that country does not equal culture on work-related values,\" Kirkman says. Researchers then evaluated other demographic and economic indicators to see if they could find a better proxy for work-related values - and they did. For example, occupation and socioeconomic status both significantly outperformed country as indicators on power distance. For example, only 20.8 percent of variation was between countries. But differences between occupations accounted for 50.1 percent, while differences between socioeconomic status accounted for 32.2 percent. Occupation and socioeconomic status also significantly outperformed country on individualism, but fared worse than nationality as indicators on uncertainty avoidance and quantity versus quality of life. \"This work highlights the illusion of national homogeneity and shows that there is a real danger in equating country and culture in a work context,\" Kirkman says. \"Making generalizations based on country can lead people to draw very inaccurate conclusions that may influence both individual and organizational business and management relationships. \"For example, if a U.S. manager is transferred to a foreign office and makes decisions based on national stereotypes about workplace culture, it could blow up in his or her face,\" Kirkman says. The paper, \"Does Country Equate with Culture? Beyond Geography in the Search for Cultural Boundaries,\" is published online in the journal Management International Review. Lead author of the paper is Vas Taras of UNC-Greensboro. The paper was co-authored by Piers Steel of the University of Calgary. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Traditionally, cultures have been treated as though they reside exclusively within, or perfectly overlap with countries. Indeed, the terms “country” and “culture” are often used interchangeably. As evidence mounts for substantial within-country cultural variation, and often between-country similarities, the problem with equating country and culture becomes more apparent. To help resolve the country-culture conundrum, we evaluate the extent to which political boundaries are suitable for clustering cultures based on a meta-analysis of 558 studies that used Hofstede’s (Culture’s consequences: international differences in work-related values. Sage Publications, Beverly Hills, 1980 ) cultural values framework. The results reveal that approximately 80 % of variation in cultural values resides within countries, confirming that country is often a poor proxy for culture. We also evaluate the relative suitability of other demographic and environmental characteristics, such as occupation, socio-economic status, wealth, freedom, globalization, and instability. Our results suggest that it may be more appropriate to talk about cultures of professions, socio-economic classes, and free versus oppressed societies, than about cultures of countries. Access provided by Universität des es, -und Working on a manuscript? Avoid the common mistakes 1 Introduction Traditionally, cultures have been assumed to reside within countries. From the earliest studies of cultural differences dating back over two centuries (Darton 1790 , see Fig. 1 ) to more recent research by Hofstede ( 1980 ) and the GLOBE team (House et al. 2004 ), the unit of analysis in cross-cultural studies has typically been country. The focus on national cultures has appropriate applications, but its dominance in research has led to a lack of attention to other plausible organizing units of culture. Equating cultures with countries and using country of origin and individual culture interchangeably became a common practice (Brewer and Venaik 2012 ). However, the appropriateness of this trend depends on answers to two questions, including: (1) are countries good proxies for cultures, and (2) could other factors be superior for describing boundaries of cultural regions or groups of people who display similar cultural values? Fig. 1 Page from one of the earliest studies into cultural differences by William Darton ( 1790 ) Full size image Culture is a multi-faceted construct. First, the word culture has many meanings, from a collective of people who share a common history, language and traditions, to characteristics of such a collective in terms of its artifacts, practices, and value systems. Illustrating the pervasiveness and possibly ambiguity of the term “culture,” a Google search for “culture” and its derivatives returns 1.5 billion hits, making it one of the most popular words on the Web. More than 60 years ago, Kroeber and Kluckhohn ( 1952 ) found 164 distinct definitions of culture. Despite the variety of definitions, several elements are common across most of them, principally that culture is: (1) a relatively stable, (2) multi-level construct comprised of values, beliefs, norms, traditions, and artifacts that (3) are shared in a given population (cf. Taras et al. 2009 ). Early empirical research on cross-cultural differences has been largely qualitative and focused on describing artifacts, rituals, and social institutions. However, following the publication of Hofstede’s ( 1980 ) seminal book, Culture’s Consequences, the focus shifted to cultural values. As noted by Taras et al. ( 2009 ), “culture is values” has become one of the commandments of cross-cultural management research. The almost exclusive focus on cultural values is often justified, but also problematic and limiting in many ways, particularly if measured using Hofstede’s ( 1980 ) framework, one that was developed based on a survey not actually originally intended for cultural analysis (cf. Baskerville 2003 ; McSweeney 2002 ; Taras and Steel 2009 for reviews of problems with Hofstede’s framework in general and for studying “culture” in particular). For the purpose of the present study, however, the question of whether or not the Hofstede’s framework is suitable for studying culture due to its limitations is secondary because most empirical research on culture over the past 35 years has relied on Hofstede’s framework. As Taras and Steel ( 2009 ) concluded, since the publication of Culture’s Consequences (Hofstede 1980 ), research on culture effectively became research on values. Indeed, reviews of cross-cultural research published in management, psychology and related disciplines confirm that empirical measurement of what is called “culture” has almost exclusively focused on assessing cultural values, usually by the means of self-response questionnaires (Caprar et al. 2015 ). Subsequent models following Hofstede’s work primarily refined his framework (e.g., House et al. 2004 (GLOBE); Schwartz 1994 ) rather than substantively altering it. Even though this work changed the wording of items and the list of the dimensions, the underlying practices remained the same and are subject to the same limitations (McSweeney 2013 ). Accordingly, the outcome of just about every major cross-cultural comparative study has been a set of national cultural means and country rankings along dimensions of cultural values (Taras et al. 2009 ). Thus, to settle the culture-versus-country debate, we rely on the approach to culture that is at the foundation of most of the empirical literature on the topic. Interpreting culture as inherently inseparable from country has become popular enough that the two terms often are used synonymously. For example, the word “culture” has been routinely included in titles of publications that provided cross-country (but not culture) comparisons, as in “ The Perception of Distributive Justice in Two Cultures ” (Marin 1982 ), “ Rules for Social Relationships in Four Cultures ” (Argyle 1986 ), “ The Effect of Culture on the Curvilinear Relationship between Performance and Turnover ” (Sturman et al. 2012 ), “A Cross - Cultural Examination of Self - Leadership” (Houghton et al. 2014 ), and many others (e.g., Bagozzi et al. 2003 ; Cialdini et al. 1999 ; Goodwin and Plaza 2000 ). Similarly, there are numerous examples when nationality or country of residence are used as proxies for cultural values, as illustrated by such quotes as “ cultural background was measured by the current citizenship (passport status) of each of the managers ”<|im_end|> <|im_start|>assistant Researchers and businesses have often operated under the idea that work-related cultural values are defined by country - just think of stereotypes about countries that are known to have hard workers or are team-oriented. A new study finds that nationality is actually a bad proxy for work-related cultural values, and points to other groupings - such as occupation - as more reliable indicators. "I study work-related values - how culture informs our beliefs and behaviors related to work," says Bradley Kirkman, co-author of a paper on the work. "This field has long defined and measured culture based on national borders. We wanted to know if nationality is really the best way to delineate cultural values and boundaries. And we learned that it's not a very good marker." Kirkman is the General (Ret.) H. Hugh Shelton Distinguished Professor of Leadership and head of the Department of Management, Innovation and Entrepreneurship at North Carolina State University. The paper was co-authored by researchers at the University of North Carolina at Greensboro and the University of Calgary. To examine the issue, the researchers looked at data from 558 studies on work-related values. The studies covered 32 countries from around the world, including the United States, Brazil, France, South Africa and China. Specifically, the researchers evaluated variation, both within each country and between countries, on four work-related cultural values: Individualism, which measures the extent to which a society places emphasis on individuals as opposed to groups;Power distance, which measures the importance of status and hierarchy in work settings;Uncertainty avoidance, which measures the extent to which cultures are willing to accept ambiguity or the unknown; andQuantity versus quality of life, which measures emphasis on competition and material wealth versus emphasis on societal welfare and well-being. The researchers found that approximately 80 percent of variation in these values was within countries. For example, at the low end, only 16.6 percent of the variation on individualism was between countries - 83.4 percent of the variability was within countries. At the high end, 20.8 percent of variation on power distance was between countries - which still left 79.2 percent of the variability within countries. "This told us that country does not equal culture on work-related values," Kirkman says. Researchers then evaluated other demographic and economic indicators to see if they could find a better proxy for work-related values - and they did. For example, occupation and socioeconomic status both significantly outperformed country as indicators on power distance. For example, only 20.8 percent of variation was between countries. But differences between occupations accounted for 50.1 percent, while differences between socioeconomic status accounted for 32.2 percent. Occupation and socioeconomic status also significantly outperformed country on individualism, but fared worse than nationality as indicators on uncertainty avoidance and quantity versus quality of life. "This work highlights the illusion of national homogeneity and shows that there is a real danger in equating country and culture in a work context," Kirkman says. "Making generalizations based on country can lead people to draw very inaccurate conclusions that may influence both individual and organizational business and management relationships. "For example, if a U.S. manager is transferred to a foreign office and makes decisions based on national stereotypes about workplace culture, it could blow up in his or her face," Kirkman says. The paper, "Does Country Equate with Culture? Beyond Geography in the Search for Cultural Boundaries," is published online in the journal Management International Review. Lead author of the paper is Vas Taras of UNC-Greensboro. The paper was co-authored by Piers Steel of the University of Calgary. <|im_end|>

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2,123

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract New satellite remote sensing and machine learning techniques offer untapped possibilities to monitor global biodiversity with unprecedented speed and precision. These efficiencies promise to reveal novel ecological insights at spatial scales which are germane to the management of populations and entire ecosystems. Here, we present a robust transferable deep learning pipeline to automatically locate and count large herds of migratory ungulates (wildebeest and zebra) in the Serengeti-Mara ecosystem using fine-resolution (38-50 cm) satellite imagery. The results achieve accurate detection of nearly 500,000 individuals across thousands of square kilometers and multiple habitat types, with an overall F1-score of 84.75% (Precision: 87.85%, Recall: 81.86%). This research demonstrates the capability of satellite remote sensing and machine learning techniques to automatically and accurately count very large populations of terrestrial mammals across a highly heterogeneous landscape. We also discuss the potential for satellite-derived species detections to advance basic understanding of animal behavior and ecology. Introduction The African continent has the greatest diversity and abundance of mammals in the world 1 . This status, however, is threatened by intensive land use changes driven by increasing natural resource extraction and infrastructure development 2 , 3 . Even in protected areas, Africa’s large mammal populations have declined by 59% in three decades 4 , and many are now categorized as endangered or threatened by the International Union for Conservation of Nature. Climate change promises to only accelerate these losses, underscoring the need for advanced monitoring techniques that can provide managers with information at a rate that keeps pace with local environmental changes 5 , 6 . Conventional methods for surveying large wildlife, especially in Africa, have relied on crewed aerial surveys for decades 7 , 8 , 9 , 10 , 11 . This approach has generated some of the longest-running ecological datasets in the world and formed the foundation of leading conservation strategies across the continent. However, crewed surveys introduce risks to human and wildlife and in many cases can only provide animal counts with coarse location precision. Moreover, all crewed aerial survey techniques are subject to biases arising from detection probability, observer experience and double counting 8 , 12 . Uncrewed aerial vehicles (UAVs) with imaging sensors offer a promising alternative to crewed surveys in some cases 13 , 14 , 15 , 16 , 17 , 18 . However, like crewed flights, UAVs are generally limited by fuel or battery life and, thus, are limited in scale and can be difficult to maintain in remote locations 19 . Moreover, UAVs can disturb wildlife when flown at low altitudes 20 , 21 , 22 , which has led to flight restrictions in some protected areas 23 . Recent advances in satellite technology have dramatically increased the feasibility of conducting uncrewed surveys in remote landscapes and at greater scales than UAVs are currently capable of. Many of the first applications of this technology focused on visualizing and analyzing easier-to-view environmental markers that, in certain contexts, provide insights to estimate population size (e.g., guano stains 24 , nests 25 , mounds and burrows 26 ). It took less than a few years, however, for the technology to accommodate manual counts at the scale of individual animals for species in unobscured contexts (e.g., polar bears 27 , albatrosses 28 , and Weddell seals 29 , 30 ). However, reliance on labor-intensive manual detection has restricted uptake by the conservation community, highlighting the need for automated techniques for processing fine-resolution satellite images. Machine learning and the associated sub-field of deep learning, have offered promising solutions to the challenge of conducting wildlife surveys from space. Over the past decade, deep learning has been a key driver of progress in science and engineering 31 . Such advancements have had a transformative impact on the field of computer vision, where the performance of some deep learning algorithms has achieved or surpassed human-level performance in many tasks 32 , 33 , 34 , 35 , 36 . At the same time, new collaborations between ecologists and computer scientists have provided several key advancements in automated animal detection from satellite imagery, including detection of the world’s largest marine and terrestrial vertebrates, such as whales 37 and elephants 38 , using object detection algorithms. However, the performance of current object detectors suffers from the small size of the objects in imagery 39 , 40 , 41 . The feasibility of successfully using object detection methods is dependent on the body size of the animal: mature whales have a body length of more than 20 m 42 , and African elephants are generally 3–5 m long 43 , both of which have more than eight pixels along the body length axis in submeter-resolution (e.g., 0.3–0.5 m) satellite imagery. A few studies have conducted automated surveys for smaller species with satellite images, such as for seals 44 and albatrosses 45 using pixel-based semantic segmentation algorithms. Image segmentation deep learning architectures such as U-Net 46 predict the class probability for every pixel, showing the potential to detect animals with a smaller size in satellite imagery. However, these early successes were limited to high-contrast species in homogeneous environments. The capability to reliably distinguish smaller animals (e.g., ≤9 pixels in size in satellite imagery, such as wildebeest, one of the African ungulate species) from complex backgrounds (e.g., mixed forest and savanna ecosystems) remains uninvestigated and continues to be a major question in satellite-based techniques for wildlife surveys 47 . Here, we address this shortcoming by presenting a robust framework for efficiently locating and counting wildebeest-sized animals with a body length of 1.5–2.5 m from submeter-resolution satellite imagery across a large, highly heterogeneous landscape. We do this by integrating a post-processing clustering module with a U-Net-based deep learning model, which uses high-precision pixel-based image segmentation to locate animals at the object level. We demonstrate the power of this framework by deploying it to locate and count the largest terrestrial mammal migration on the planet—the migration of white bearded wildebeest ( Connochaetes taurinus ) and plains zebra ( Equus quagga ) across", "role": "user" }, { "content": "In their research, associate professor from the NRS Department Tiejun Wang and his master's student Zijing Wu developed an AI-model to automatically locate and count large herds of migratory ungulates (wildebeest and zebra). They used their method in the Serengeti-Mara ecosystem using fine-resolution (38–50 cm) satellite imagery. They achieved accurate detection of nearly 500,000 individuals across thousands of square kilometers and multiple habitat types. The scientists at the Department of Natural Resources (ITC Faculty—University of Twente) recently published their results in the journal Nature Communications. The Great Wildebeest Migration is the largest terrestrial mammal migration on our planet. It drives multiple ecological processes that support the health of humans and wildlife across the region. However, due to climate and land cover/use change, this natural process is becoming compromised. Developing accurate, cost-effective monitoring methods has quickly become a vital necessity to protect wildebeests and the ecosystem. To address this issue, Tiejun Wang demonstrates, for the first time, the capability of satellite remote sensing and machine learning techniques to automatically and accurately count very large populations of wildebeest and zebras. Even across the highly heterogeneous landscape of their migration journey. Approximately 120.000 individual wildebeests are accurately detected by the algorithm in this large area. Each purple dot is one wildebeest. Credit: University of Twente \"We are currently in the first year of implementing the post-2020 global biodiversity framework, which the UN adopted at the 15th Conference of Parties to the UN Convention on Biological Diversity. The UN also recently established the Global Sustainability Development Goals as well as the first round of risk assessments on biodiversity and ecosystem services through the Intergovernmental Platform on Biodiversity and Ecosystem Services,\" explains Wang. \"The unprecedented biodiversity loss as well as the gaps in knowledge on key aspects of biodiversity (e.g., species populations) clarify the need to integrate biodiversity measurements on Earth from the ground and from space. Hence, the effort to combine bottom-up and top-down approaches for biodiversity monitoring has never been so critical,\" said Wang. New satellite remote sensing and machine learning techniques make it possible to monitor global biodiversity with speed and precision. These efficiencies promise to reveal novel ecological insights at spatial scales which are germane to the management of populations and entire ecosystems. Wang's research demonstrates, for the first time, the capability of satellite remote sensing and machine learning techniques to automatically and accurately count very large populations of terrestrial mammals across a highly heterogeneous landscape. This study yielded highly accurate results and the largest training dataset ever published from a satellite-based wildlife survey (53,906 annotations). Beyond providing a truly open-source and transferable method for satellite-based wildlife surveys, the approach is spatially scalable for the first-ever total counts of migratory ungulates in open landscapes. Observing expansive herds of migratory ungulates from space presents an entirely novel perspective for the study of the ecology of animal aggregations. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract New satellite remote sensing and machine learning techniques offer untapped possibilities to monitor global biodiversity with unprecedented speed and precision. These efficiencies promise to reveal novel ecological insights at spatial scales which are germane to the management of populations and entire ecosystems. Here, we present a robust transferable deep learning pipeline to automatically locate and count large herds of migratory ungulates (wildebeest and zebra) in the Serengeti-Mara ecosystem using fine-resolution (38-50 cm) satellite imagery. The results achieve accurate detection of nearly 500,000 individuals across thousands of square kilometers and multiple habitat types, with an overall F1-score of 84.75% (Precision: 87.85%, Recall: 81.86%). This research demonstrates the capability of satellite remote sensing and machine learning techniques to automatically and accurately count very large populations of terrestrial mammals across a highly heterogeneous landscape. We also discuss the potential for satellite-derived species detections to advance basic understanding of animal behavior and ecology. Introduction The African continent has the greatest diversity and abundance of mammals in the world 1 . This status, however, is threatened by intensive land use changes driven by increasing natural resource extraction and infrastructure development 2 , 3 . Even in protected areas, Africa’s large mammal populations have declined by 59% in three decades 4 , and many are now categorized as endangered or threatened by the International Union for Conservation of Nature. Climate change promises to only accelerate these losses, underscoring the need for advanced monitoring techniques that can provide managers with information at a rate that keeps pace with local environmental changes 5 , 6 . Conventional methods for surveying large wildlife, especially in Africa, have relied on crewed aerial surveys for decades 7 , 8 , 9 , 10 , 11 . This approach has generated some of the longest-running ecological datasets in the world and formed the foundation of leading conservation strategies across the continent. However, crewed surveys introduce risks to human and wildlife and in many cases can only provide animal counts with coarse location precision. Moreover, all crewed aerial survey techniques are subject to biases arising from detection probability, observer experience and double counting 8 , 12 . Uncrewed aerial vehicles (UAVs) with imaging sensors offer a promising alternative to crewed surveys in some cases 13 , 14 , 15 , 16 , 17 , 18 . However, like crewed flights, UAVs are generally limited by fuel or battery life and, thus, are limited in scale and can be difficult to maintain in remote locations 19 . Moreover, UAVs can disturb wildlife when flown at low altitudes 20 , 21 , 22 , which has led to flight restrictions in some protected areas 23 . Recent advances in satellite technology have dramatically increased the feasibility of conducting uncrewed surveys in remote landscapes and at greater scales than UAVs are currently capable of. Many of the first applications of this technology focused on visualizing and analyzing easier-to-view environmental markers that, in certain contexts, provide insights to estimate population size (e.g., guano stains 24 , nests 25 , mounds and burrows 26 ). It took less than a few years, however, for the technology to accommodate manual counts at the scale of individual animals for species in unobscured contexts (e.g., polar bears 27 , albatrosses 28 , and Weddell seals 29 , 30 ). However, reliance on labor-intensive manual detection has restricted uptake by the conservation community, highlighting the need for automated techniques for processing fine-resolution satellite images. Machine learning and the associated sub-field of deep learning, have offered promising solutions to the challenge of conducting wildlife surveys from space. Over the past decade, deep learning has been a key driver of progress in science and engineering 31 . Such advancements have had a transformative impact on the field of computer vision, where the performance of some deep learning algorithms has achieved or surpassed human-level performance in many tasks 32 , 33 , 34 , 35 , 36 . At the same time, new collaborations between ecologists and computer scientists have provided several key advancements in automated animal detection from satellite imagery, including detection of the world’s largest marine and terrestrial vertebrates, such as whales 37 and elephants 38 , using object detection algorithms. However, the performance of current object detectors suffers from the small size of the objects in imagery 39 , 40 , 41 . The feasibility of successfully using object detection methods is dependent on the body size of the animal: mature whales have a body length of more than 20 m 42 , and African elephants are generally 3–5 m long 43 , both of which have more than eight pixels along the body length axis in submeter-resolution (e.g., 0.3–0.5 m) satellite imagery. A few studies have conducted automated surveys for smaller species with satellite images, such as for seals 44 and albatrosses 45 using pixel-based semantic segmentation algorithms. Image segmentation deep learning architectures such as U-Net 46 predict the class probability for every pixel, showing the potential to detect animals with a smaller size in satellite imagery. However, these early successes were limited to high-contrast species in homogeneous environments. The capability to reliably distinguish smaller animals (e.g., ≤9 pixels in size in satellite imagery, such as wildebeest, one of the African ungulate species) from complex backgrounds (e.g., mixed forest and savanna ecosystems) remains uninvestigated and continues to be a major question in satellite-based techniques for wildlife surveys 47 . Here, we address this shortcoming by presenting a robust framework for efficiently locating and counting wildebeest-sized animals with a body length of 1.5–2.5 m from submeter-resolution satellite imagery across a large, highly heterogeneous landscape. We do this by integrating a post-processing clustering module with a U-Net-based deep learning model, which uses high-precision pixel-based image segmentation to locate animals at the object level. We demonstrate the power of this framework by deploying it to locate and count the largest terrestrial mammal migration on the planet—the migration of white bearded wildebeest ( Connochaetes taurinus ) and plains zebra ( Equus quagga ) across<|im_end|> <|im_start|>assistant In their research, associate professor from the NRS Department Tiejun Wang and his master's student Zijing Wu developed an AI-model to automatically locate and count large herds of migratory ungulates (wildebeest and zebra). They used their method in the Serengeti-Mara ecosystem using fine-resolution (38–50 cm) satellite imagery. They achieved accurate detection of nearly 500,000 individuals across thousands of square kilometers and multiple habitat types. The scientists at the Department of Natural Resources (ITC Faculty—University of Twente) recently published their results in the journal Nature Communications. The Great Wildebeest Migration is the largest terrestrial mammal migration on our planet. It drives multiple ecological processes that support the health of humans and wildlife across the region. However, due to climate and land cover/use change, this natural process is becoming compromised. Developing accurate, cost-effective monitoring methods has quickly become a vital necessity to protect wildebeests and the ecosystem. To address this issue, Tiejun Wang demonstrates, for the first time, the capability of satellite remote sensing and machine learning techniques to automatically and accurately count very large populations of wildebeest and zebras. Even across the highly heterogeneous landscape of their migration journey. Approximately 120.000 individual wildebeests are accurately detected by the algorithm in this large area. Each purple dot is one wildebeest. Credit: University of Twente "We are currently in the first year of implementing the post-2020 global biodiversity framework, which the UN adopted at the 15th Conference of Parties to the UN Convention on Biological Diversity. The UN also recently established the Global Sustainability Development Goals as well as the first round of risk assessments on biodiversity and ecosystem services through the Intergovernmental Platform on Biodiversity and Ecosystem Services," explains Wang. "The unprecedented biodiversity loss as well as the gaps in knowledge on key aspects of biodiversity (e.g., species populations) clarify the need to integrate biodiversity measurements on Earth from the ground and from space. Hence, the effort to combine bottom-up and top-down approaches for biodiversity monitoring has never been so critical," said Wang. New satellite remote sensing and machine learning techniques make it possible to monitor global biodiversity with speed and precision. These efficiencies promise to reveal novel ecological insights at spatial scales which are germane to the management of populations and entire ecosystems. Wang's research demonstrates, for the first time, the capability of satellite remote sensing and machine learning techniques to automatically and accurately count very large populations of terrestrial mammals across a highly heterogeneous landscape. This study yielded highly accurate results and the largest training dataset ever published from a satellite-based wildlife survey (53,906 annotations). Beyond providing a truly open-source and transferable method for satellite-based wildlife surveys, the approach is spatially scalable for the first-ever total counts of migratory ungulates in open landscapes. Observing expansive herds of migratory ungulates from space presents an entirely novel perspective for the study of the ecology of animal aggregations. <|im_end|>

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1,925

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Stomatal closure is one of the main physiological responses to increasing CO 2 concentration, which leads to a reduction in plant water loss. This response has the potential to trigger changes in the climate system by regulating surface energy budgets—a phenomenon known as CO 2 physiological forcing. However, its remote impacts on the Arctic climate system are unclear. Here we show that vegetation at high latitudes enhances the Arctic amplification via remote and time-delayed physiological forcing processes. Surface warming occurs at mid-to-high latitudes due to the physiological acclimation-induced reduction in evaporative cooling and resultant increase in sensible heat flux. This excessive surface heat energy is transported to the Arctic ocean and contributes to the sea ice loss, thereby enhancing Arctic warming. The surface warming in the Arctic is further amplified by local feedbacks, and consequently the contribution of physiological effects to Arctic warming represents about 10% of radiative forcing effects. Introduction The increase in atmospheric CO 2 concentration has an influence on plant physiology. Physiological responses to increasing CO 2 include changes in leaf area index (LAI) and stomatal conductance, and those affect the plant transpiration in opposite ways. First, one of the main physiological responses is the CO 2 fertilization effect—that is, an increase in the rate of photosynthesis 1 , 2 , 3 . This effect accounts for the largest contribution to the positive trends in the LAI detected by satellite data sets 4 and can also lead to an increase in plant transpiration, resulting in cooling effects 5 . Second, another plant response is a reduction in stomatal conductance. In other words, stomatal apertures open less widely under elevated CO 2 concentrations. These CO 2 -induced reductions in the stomatal conductance have been confirmed through experiments and from reconstruction data 2 , 3 , 6 , 7 . The stomatal closure resulting from elevated CO 2 levels can decrease the rate of transpiration by diminishing the amount of water loss from plants. This reduction in plant transpiration can lead to an increase of near-surface air temperature by decreasing the evaporative cooling effect and simultaneously increasing the sensible heat flux above the land surface 8 , 9 , 10 . This nonradiative effect from physiological acclimation is known as CO 2 physiological forcing 11 . Previous studies using model experiments have investigated how the physiological forcing will affect the future climate in vegetation-covered regions, through influences such as amplified heat extremes 12 , intensified zonal asymmetry of rainfall over tropical land 13 , drying over the Eastern Amazon 14 and Sahel greening 15 . This physiological effect has a potential to remotely alter the entire climate system through the redistribution of the surface energy and disturbance of hydrological cycle, but still, the remote impacts of physiological effect on the climate system are unclear especially in the Arctic region (north of 70°N). The Arctic is the region most sensitive to greenhouse warming and has experienced warming faster than the global average, a phenomenon known as Arctic amplification 16 . Many mechanisms have been suggested to explain the Arctic amplification including a role of diminishing sea ice 17 , 18 , seasonal storage and release of the absorbed shortwave (SW) radiation coupling with sea-ice loss 19 , 20 , 21 , enhanced downward longwave (LW) radiation due to an increase in water vapor and cloud fraction 22 , 23 , ocean biogeochemical feedback 24 , 25 , increased poleward energy transport 26 , 27 and other processes 28 , 29 . However, their relative contributions are still under debate and also many alternative mechanisms are under investigation. Here, we suggest that the CO 2 physiological forcing has a remote forcing on the Arctic climate and can intensify the Arctic amplification through the enhanced atmospheric poleward heat transport and the physical processes coupling with the Arctic sea-ice change. To examine the impacts of physiological acclimation under elevated CO 2 on the future climate system, we analyzed eight Earth system models (ESMs), which can simulate interactions between the physical climate system and the biogeochemical processes, from the Coupled Model Intercomparison Project Phase 5 (CMIP5) 30 (Supplementary Tables 1 and 2 ). In line with previous studies 12 , 13 , 31 , 32 , 33 , 34 , we respectively quantified the physiological forcing (Phy), which includes the CO 2 fertilization effect and the dependency of stomatal conductance on CO 2 , and CO 2 radiative forcing (Rad) (average CO 2 concentrations ~823 ppm) using carbon–climate feedback experiments (see the Methods section and Supplementary Table 3 ). Results Land surface warming by plant physiological effects Figure 1 shows changes in the annual mean evapotranspiration (ET), Bowen ratio (the ratio of sensible to latent heat fluxes), and near-surface air temperature resulting from the CO 2 physiological forcing. In contrast with the radiative effect inducing the increase in ET due to enhanced water-demand from the temperature rise (Supplementary Fig. 1 ), physiological effects cause a conspicuous and significant reduction in the annual mean ET in densely vegetated areas of the tropics and mid-to-high latitudes (Fig. 1a ) in line with previous studies 12 , 31 , 32 , 34 , 35 , 36 , 37 . In this idealized experiment for evaluating the CO 2 physiological forcing, the fertilization effect plays a role in increasing ET due to the resulting increased LAI, but the effect of stomatal closure works in the opposite way at the same time 5 , 10 , 37 . Therefore, this overall drop in ET suggests that the stomatal closure have a greater influence in controlling the total ET than the CO 2 fertilization, when only the physiological effects is considered under elevated CO 2 levels, in consistency with the argument in previous studies 12 , 31 , 34 , 37 . Fig. 1: Change in evapotranspiration, Bowen ratio and temperature resulting from CO 2 physiological forcing. Multimodel mean change of the annual mean evapotranspiration ( a ), Bowen ratio (sensible heat flux/latent heat flux) ( b ), and", "role": "user" }, { "content": "The vapor that plants emit when they breathe serves to lower land surface temperature, much like watering the yard on a hot day. Until now, the greenhouse effect has been blamed for the rise in global temperature. But an interesting study has shown that the Artic temperature rises when the moisture released by plants is reduced due to the increase of carbon dioxide (CO2 ) in the atmosphere. The joint research team led by Professor Jong-Seong Kug and doctoral candidate So Won Park of POSTECH's Division of Environmental Science and Engineering, and Researcher Jin-Soo Kim of the University of Zurich has confirmed that the increase in atmospheric CO2 concentration closes the pores (stomata) of plants in high-latitude areas and reduces their transpiration, which ultimately accelerates Arctic warming. The findings, which were studied through the Earth system models (ESM) simulations, were recently published in Nature Communications, an authoritative journal in science. Plants take in CO2 and emit oxygen through photosynthesis. During this process, the stomata of leaves open to absorb CO2 in the air and release moisture at the same time. However, when the CO2 concentration rises, plants can absorb enough CO2 without opening their stomata widely. If the stomata open narrowly, the amount of water vapor released also decreases. When this transpiration of plants declines, the land temperature rapidly rises under greenhouse warming. Recently, such a decrease in transpiration has been cited as one of the reasons for the surge in heat waves in the northern hemisphere. This response from the vegetation leads to the global climate change by controlling the exchange of energy between the surface and atmosphere, referred to as 'physiological forcing.' But so far, no study has confirmed the effects of physiological forcing on the Arctic climate system. The joint research team analyzed the EMS simulation and confirmed that the increase in CO2 leads to stomatal closure in land vegetation causing land warming, which in turn remotely speeds up Artic warming through atmospheric circulation and positive feedback in Earth systems process. In addition, a quantitative estimate of the stomatal closure's effect on Arctic warming due to increased CO2 showed that about 10% of the greenhouse effect is caused by this physiological forcing. Professor Jong-Seong Kug, who has studied Arctic warming in a variety of perspectives, commented, \"The stomatal closure effect due to the increased CO2 levels is not fully counted in the future climate projection.\" He pointed out, \"This means that Arctic warming can proceed much faster than currently forecast.\" He also warned that \"the increase in CO2 is accelerating global warming not only through the greenhouse effect that we all knew of, but also by changing the physiological function of plants.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Stomatal closure is one of the main physiological responses to increasing CO 2 concentration, which leads to a reduction in plant water loss. This response has the potential to trigger changes in the climate system by regulating surface energy budgets—a phenomenon known as CO 2 physiological forcing. However, its remote impacts on the Arctic climate system are unclear. Here we show that vegetation at high latitudes enhances the Arctic amplification via remote and time-delayed physiological forcing processes. Surface warming occurs at mid-to-high latitudes due to the physiological acclimation-induced reduction in evaporative cooling and resultant increase in sensible heat flux. This excessive surface heat energy is transported to the Arctic ocean and contributes to the sea ice loss, thereby enhancing Arctic warming. The surface warming in the Arctic is further amplified by local feedbacks, and consequently the contribution of physiological effects to Arctic warming represents about 10% of radiative forcing effects. Introduction The increase in atmospheric CO 2 concentration has an influence on plant physiology. Physiological responses to increasing CO 2 include changes in leaf area index (LAI) and stomatal conductance, and those affect the plant transpiration in opposite ways. First, one of the main physiological responses is the CO 2 fertilization effect—that is, an increase in the rate of photosynthesis 1 , 2 , 3 . This effect accounts for the largest contribution to the positive trends in the LAI detected by satellite data sets 4 and can also lead to an increase in plant transpiration, resulting in cooling effects 5 . Second, another plant response is a reduction in stomatal conductance. In other words, stomatal apertures open less widely under elevated CO 2 concentrations. These CO 2 -induced reductions in the stomatal conductance have been confirmed through experiments and from reconstruction data 2 , 3 , 6 , 7 . The stomatal closure resulting from elevated CO 2 levels can decrease the rate of transpiration by diminishing the amount of water loss from plants. This reduction in plant transpiration can lead to an increase of near-surface air temperature by decreasing the evaporative cooling effect and simultaneously increasing the sensible heat flux above the land surface 8 , 9 , 10 . This nonradiative effect from physiological acclimation is known as CO 2 physiological forcing 11 . Previous studies using model experiments have investigated how the physiological forcing will affect the future climate in vegetation-covered regions, through influences such as amplified heat extremes 12 , intensified zonal asymmetry of rainfall over tropical land 13 , drying over the Eastern Amazon 14 and Sahel greening 15 . This physiological effect has a potential to remotely alter the entire climate system through the redistribution of the surface energy and disturbance of hydrological cycle, but still, the remote impacts of physiological effect on the climate system are unclear especially in the Arctic region (north of 70°N). The Arctic is the region most sensitive to greenhouse warming and has experienced warming faster than the global average, a phenomenon known as Arctic amplification 16 . Many mechanisms have been suggested to explain the Arctic amplification including a role of diminishing sea ice 17 , 18 , seasonal storage and release of the absorbed shortwave (SW) radiation coupling with sea-ice loss 19 , 20 , 21 , enhanced downward longwave (LW) radiation due to an increase in water vapor and cloud fraction 22 , 23 , ocean biogeochemical feedback 24 , 25 , increased poleward energy transport 26 , 27 and other processes 28 , 29 . However, their relative contributions are still under debate and also many alternative mechanisms are under investigation. Here, we suggest that the CO 2 physiological forcing has a remote forcing on the Arctic climate and can intensify the Arctic amplification through the enhanced atmospheric poleward heat transport and the physical processes coupling with the Arctic sea-ice change. To examine the impacts of physiological acclimation under elevated CO 2 on the future climate system, we analyzed eight Earth system models (ESMs), which can simulate interactions between the physical climate system and the biogeochemical processes, from the Coupled Model Intercomparison Project Phase 5 (CMIP5) 30 (Supplementary Tables 1 and 2 ). In line with previous studies 12 , 13 , 31 , 32 , 33 , 34 , we respectively quantified the physiological forcing (Phy), which includes the CO 2 fertilization effect and the dependency of stomatal conductance on CO 2 , and CO 2 radiative forcing (Rad) (average CO 2 concentrations ~823 ppm) using carbon–climate feedback experiments (see the Methods section and Supplementary Table 3 ). Results Land surface warming by plant physiological effects Figure 1 shows changes in the annual mean evapotranspiration (ET), Bowen ratio (the ratio of sensible to latent heat fluxes), and near-surface air temperature resulting from the CO 2 physiological forcing. In contrast with the radiative effect inducing the increase in ET due to enhanced water-demand from the temperature rise (Supplementary Fig. 1 ), physiological effects cause a conspicuous and significant reduction in the annual mean ET in densely vegetated areas of the tropics and mid-to-high latitudes (Fig. 1a ) in line with previous studies 12 , 31 , 32 , 34 , 35 , 36 , 37 . In this idealized experiment for evaluating the CO 2 physiological forcing, the fertilization effect plays a role in increasing ET due to the resulting increased LAI, but the effect of stomatal closure works in the opposite way at the same time 5 , 10 , 37 . Therefore, this overall drop in ET suggests that the stomatal closure have a greater influence in controlling the total ET than the CO 2 fertilization, when only the physiological effects is considered under elevated CO 2 levels, in consistency with the argument in previous studies 12 , 31 , 34 , 37 . Fig. 1: Change in evapotranspiration, Bowen ratio and temperature resulting from CO 2 physiological forcing. Multimodel mean change of the annual mean evapotranspiration ( a ), Bowen ratio (sensible heat flux/latent heat flux) ( b ), and<|im_end|> <|im_start|>assistant The vapor that plants emit when they breathe serves to lower land surface temperature, much like watering the yard on a hot day. Until now, the greenhouse effect has been blamed for the rise in global temperature. But an interesting study has shown that the Artic temperature rises when the moisture released by plants is reduced due to the increase of carbon dioxide (CO2 ) in the atmosphere. The joint research team led by Professor Jong-Seong Kug and doctoral candidate So Won Park of POSTECH's Division of Environmental Science and Engineering, and Researcher Jin-Soo Kim of the University of Zurich has confirmed that the increase in atmospheric CO2 concentration closes the pores (stomata) of plants in high-latitude areas and reduces their transpiration, which ultimately accelerates Arctic warming. The findings, which were studied through the Earth system models (ESM) simulations, were recently published in Nature Communications, an authoritative journal in science. Plants take in CO2 and emit oxygen through photosynthesis. During this process, the stomata of leaves open to absorb CO2 in the air and release moisture at the same time. However, when the CO2 concentration rises, plants can absorb enough CO2 without opening their stomata widely. If the stomata open narrowly, the amount of water vapor released also decreases. When this transpiration of plants declines, the land temperature rapidly rises under greenhouse warming. Recently, such a decrease in transpiration has been cited as one of the reasons for the surge in heat waves in the northern hemisphere. This response from the vegetation leads to the global climate change by controlling the exchange of energy between the surface and atmosphere, referred to as 'physiological forcing.' But so far, no study has confirmed the effects of physiological forcing on the Arctic climate system. The joint research team analyzed the EMS simulation and confirmed that the increase in CO2 leads to stomatal closure in land vegetation causing land warming, which in turn remotely speeds up Artic warming through atmospheric circulation and positive feedback in Earth systems process. In addition, a quantitative estimate of the stomatal closure's effect on Arctic warming due to increased CO2 showed that about 10% of the greenhouse effect is caused by this physiological forcing. Professor Jong-Seong Kug, who has studied Arctic warming in a variety of perspectives, commented, "The stomatal closure effect due to the increased CO2 levels is not fully counted in the future climate projection." He pointed out, "This means that Arctic warming can proceed much faster than currently forecast." He also warned that "the increase in CO2 is accelerating global warming not only through the greenhouse effect that we all knew of, but also by changing the physiological function of plants." <|im_end|>

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32056, 11618, 11, 505, 279, 18733, 50185, 5008, 5783, 55805, 5907, 28673, 220, 20, 320, 10190, 3378, 20, 8, 220, 966, 320, 10254, 67082, 43252, 220, 16, 323, 220, 17, 7609, 763, 1584, 449, 3766, 7978, 220, 717, 1174, 220, 1032, 1174, 220, 2148, 1174, 220, 843, 1174, 220, 1644, 1174, 220, 1958, 1174, 584, 15947, 10484, 1908, 279, 53194, 25957, 320, 3438, 88, 705, 902, 5764, 279, 7432, 220, 17, 36214, 2065, 2515, 323, 279, 24999, 315, 20703, 4306, 6929, 685, 389, 7432, 220, 17, 1174, 323, 7432, 220, 17, 12164, 1413, 25957, 320, 43031, 8, 320, 17645, 7432, 220, 17, 32466, 4056, 23848, 64697, 8, 1701, 12782, 4235, 94874, 11302, 21896, 320, 4151, 279, 19331, 3857, 323, 99371, 6771, 220, 18, 7609, 18591, 11680, 7479, 24808, 555, 6136, 53194, 6372, 19575, 220, 16, 5039, 4442, 304, 279, 9974, 3152, 3721, 91001, 34489, 29579, 320, 1372, 705, 96620, 11595, 320, 1820, 11595, 315, 38761, 311, 42767, 8798, 31405, 288, 705, 323, 3221, 1355, 10730, 3805, 9499, 13239, 505, 279, 7432, 220, 17, 53194, 25957, 13, 763, 13168, 449, 279, 12164, 1413, 2515, 96811, 279, 5376, 304, 18241, 4245, 311, 24872, 3090, 57364, 505, 279, 9499, 10205, 320, 10254, 67082, 23966, 13, 220, 16, 7026, 53194, 6372, 5353, 264, 97985, 323, 5199, 14278, 304, 279, 9974, 3152, 18241, 304, 97617, 13294, 660, 5789, 315, 279, 21965, 1233, 323, 5209, 4791, 28661, 6987, 21237, 320, 30035, 13, 220, 16, 64, 883, 304, 1584, 449, 3766, 7978, 220, 717, 1174, 220, 2148, 1174, 220, 843, 1174, 220, 1958, 1174, 220, 1758, 1174, 220, 1927, 1174, 220, 1806, 662, 763, 420, 10728, 1534, 9526, 369, 38663, 279, 7432, 220, 17, 53194, 25957, 11, 279, 36214, 2065, 2515, 11335, 264, 3560, 304, 7859, 18241, 4245, 311, 279, 13239, 7319, 13256, 40, 11, 719, 279, 2515, 315, 20703, 4306, 22722, 4375, 304, 279, 14329, 1648, 520, 279, 1890, 892, 220, 20, 1174, 220, 605, 1174, 220, 1806, 662, 15636, 11, 420, 8244, 6068, 304, 18241, 13533, 430, 279, 20703, 4306, 22722, 617, 264, 7191, 10383, 304, 26991, 279, 2860, 18241, 1109, 279, 7432, 220, 17, 36214, 2065, 11, 994, 1193, 279, 53194, 6372, 374, 6646, 1234, 32389, 7432, 220, 17, 5990, 11, 304, 29237, 449, 279, 5811, 304, 3766, 7978, 220, 717, 1174, 220, 2148, 1174, 220, 1958, 1174, 220, 1806, 662, 23966, 13, 220, 16, 25, 10604, 304, 3721, 91001, 34489, 29579, 11, 96620, 11595, 323, 9499, 13239, 505, 7432, 220, 17, 53194, 25957, 13, 22950, 318, 725, 3152, 2349, 315, 279, 9974, 3152, 3721, 91001, 34489, 29579, 320, 264, 7026, 96620, 11595, 320, 82, 37864, 8798, 31405, 14, 51123, 8798, 31405, 8, 320, 293, 7026, 323, 128257, 198, 128256, 78191, 198, 791, 38752, 430, 11012, 17105, 994, 814, 37397, 17482, 311, 4827, 4363, 7479, 9499, 11, 1790, 1093, 73841, 279, 20085, 389, 264, 4106, 1938, 13, 30070, 1457, 11, 279, 37647, 2515, 706, 1027, 36197, 369, 279, 10205, 304, 3728, 9499, 13, 2030, 459, 7185, 4007, 706, 6982, 430, 279, 5277, 292, 9499, 38268, 994, 279, 32257, 6004, 555, 11012, 374, 11293, 4245, 311, 279, 5376, 315, 12782, 40589, 320, 8445, 17, 883, 304, 279, 16975, 13, 578, 10496, 3495, 2128, 6197, 555, 17054, 40648, 98628, 647, 735, 773, 323, 74657, 9322, 2100, 43549, 5657, 315, 13165, 93133, 596, 14829, 315, 25027, 10170, 323, 17005, 11, 323, 8483, 261, 39611, 6354, 2689, 13818, 315, 279, 3907, 315, 72826, 706, 11007, 430, 279, 5376, 304, 45475, 7432, 17, 20545, 34350, 279, 72028, 320, 267, 316, 460, 8, 315, 11012, 304, 1579, 2922, 17584, 5789, 323, 26338, 872, 1380, 29579, 11, 902, 13967, 14511, 988, 37518, 24808, 13, 578, 14955, 11, 902, 1051, 20041, 1555, 279, 9420, 1887, 4211, 320, 1600, 44, 8, 47590, 11, 1051, 6051, 4756, 304, 22037, 26545, 11, 459, 65693, 8486, 304, 8198, 13, 50298, 1935, 304, 7432, 17, 323, 17105, 24463, 1555, 7397, 74767, 13, 12220, 420, 1920, 11, 279, 20703, 460, 315, 11141, 1825, 311, 35406, 7432, 17, 304, 279, 3805, 323, 4984, 32257, 520, 279, 1890, 892, 13, 4452, 11, 994, 279, 7432, 17, 20545, 38268, 11, 11012, 649, 35406, 3403, 7432, 17, 2085, 8736, 872, 20703, 460, 13882, 13, 1442, 279, 20703, 460, 1825, 65047, 11, 279, 3392, 315, 3090, 38752, 6004, 1101, 43154, 13, 3277, 420, 1380, 29579, 315, 11012, 58054, 11, 279, 4363, 9499, 19019, 38268, 1234, 37647, 24808, 13, 42096, 11, 1778, 264, 18979, 304, 1380, 29579, 706, 1027, 22628, 439, 832, 315, 279, 8125, 369, 279, 22531, 304, 8798, 17301, 304, 279, 18671, 69766, 13, 1115, 2077, 505, 279, 54832, 11767, 311, 279, 3728, 10182, 2349, 555, 26991, 279, 9473, 315, 4907, 1990, 279, 7479, 323, 16975, 11, 14183, 311, 439, 364, 42305, 41314, 25957, 3238, 2030, 779, 3117, 11, 912, 4007, 706, 11007, 279, 6372, 315, 53194, 25957, 389, 279, 37518, 10182, 1887, 13, 578, 10496, 3495, 2128, 30239, 279, 71165, 19576, 323, 11007, 430, 279, 5376, 304, 7432, 17, 11767, 311, 20703, 4306, 22722, 304, 4363, 54832, 14718, 4363, 24808, 11, 902, 304, 2543, 39529, 25753, 709, 5277, 292, 24808, 1555, 45475, 35855, 323, 6928, 11302, 304, 9420, 6067, 1920, 13, 763, 5369, 11, 264, 47616, 16430, 315, 279, 20703, 4306, 22722, 596, 2515, 389, 37518, 24808, 4245, 311, 7319, 7432, 17, 8710, 430, 922, 220, 605, 4, 315, 279, 37647, 2515, 374, 9057, 555, 420, 53194, 25957, 13, 17054, 40648, 98628, 647, 735, 773, 11, 889, 706, 20041, 37518, 24808, 304, 264, 8205, 315, 39555, 11, 29786, 11, 330, 791, 20703, 4306, 22722, 2515, 4245, 311, 279, 7319, 7432, 17, 5990, 374, 539, 7373, 31094, 304, 279, 3938, 10182, 22343, 1210, 1283, 14618, 704, 11, 330, 2028, 3445, 430, 37518, 24808, 649, 10570, 1790, 10819, 1109, 5131, 18057, 1210, 1283, 1101, 19201, 430, 330, 1820, 5376, 304, 7432, 17, 374, 69741, 3728, 24808, 539, 1193, 1555, 279, 37647, 2515, 430, 584, 682, 7020, 315, 11, 719, 1101, 555, 10223, 279, 53194, 734, 315, 11012, 1210, 220, 128257, 198 ]

1,853

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Biochars produced from cotton gin waste (CG) and guayule bagasse (GB) were characterized and explored as potential adsorbents for the removal of pharmaceuticals (sulfapyridine-SPY, docusate-DCT and erythromycin-ETM) from aqueous solution. An increase in biochar pyrolysis temperature from 350 ο C to 700 ο C led to an increase in pH, specific surface area, and surface hydrophobicity. The electronegative surface of all tested biochars indicated that non-Coulombic mechanisms were involved in adsorption of the anionic or uncharged pharmaceuticals under experimental conditions. The adsorption capacities of Sulfapyridine (SPY), Docusate (DCT) and Erythromycin (ETM) on biochar were influenced by the contact time and solution pH, as well as biochar specific surface area and functional groups. Adsorption of these pharmaceutical compounds was dominated by a complex interplay of three mechanisms: hydrophobic partitioning, hydrogen bonding and π–π electron donor–acceptor (EDA) interactions. Despite weaker π–π EDA interactions, reduced hydrophobicity of SPY − and increased electrostatic repulsion between anionic SPY − and the electronegative CG biochar surface at higher pH, the adsorption of SPY unexpectedly increased from 40% to 70% with an increase in pH from 7 to 10. Under alkaline conditions, adsorption was dominated by the formation of strong negative charge-assisted H-bonding between the sulfonamide moiety of SPY and surface carboxylic groups. There seemed to be no appreciable and consistent differences in the extent of DCT and ETM adsorption as the pH changed. Results suggest the CG and GB biochars could act as effective adsorbents for the removal of pharmaceuticals from reclaimed water prior to irrigation. High surface area biochars with physico-chemical properties (e.g., presence of functional groups, high cation and anion exchange capacities) conducive to strong interactions with polar-nonpolar functionality of pharmaceuticals could be used to achieve significant contaminant removal from water. Graphic Abstract Working on a manuscript? Avoid the common mistakes FormalPara Highlights Biochar was obtained from the carbonization of cotton gin waste and guayule bagasse at three temperatures Biochar shows considerable potential for the adsorption of SPY, DCT and ETM and can be used as a cheap, environmentally friendly adsorbent Hydrophobic partitioning, electrostatic interactions, hydrogen bonding and π-π electron donor–acceptor (EDA) interactions can simultaneously influence adsorption and determine the sorptive affinity of biochars for pharmaceuticals 1 Introduction Anthropogenic activities, including increasing urbanization, population growth and intensive agricultural activities have introduced a broad range of emerging contaminants (ECs) into the environment (Houtman 2010 ; Pal et al. 2010 ; Fenet 2012). ECs are defined as chemicals and microorganisms that have been detected in the environment and can potentially cause toxic effects in aquatic and human life at trace-level concentrations (ng- μg/L levels), but for which no water quality regulations exist (Ahmed et al. 2017a ; USGS, 2015). There are several classes of ECs including pesticides, industrial additives, flame retardants, endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care products (PPCPSs). Among all classes of ECs, PPCPs are the most abundant in the environment and are often detected at elevated concentrations in surface and groundwaters (Daughton 2004 ) due to continuous human use. Additionally, wastewater treatment plants (WWTPs) are not effective at removing many of these chemicals, leading to the presence of various PPCPs in wastewater effluents (Gros et al. 2010 ; Sui et al. 2011 ). The World Health Organization (WHO) estimated that in 2025, two-third of the world’s population could be living in regions with limited access to water. Agriculture is the sector which requires the most water and is expected to be impacted by the shortage. To mitigate these impacts, treated wastewater or reclaimed water has become an important source of water for agricultural irrigation especially in arid regions of the world. Reclaimed water is wastewater from homes, offices, hospitals and industries that has undergone treatment to remove impurities such as nutrients and pathogens (DSWS 2011). Reclaimed water can be successfully used for irrigation because even after treatment, it still contains nitrogen and phosphorus that are essential to plant growth (Kinney et al. 2006 ). When treated wastewater is used for irrigation, contaminants such as pharmaceuticals may be introduced into crops from the soil through root uptake and translocation, leading to accumulation of these contaminants not only in the roots, but also in edible above-ground plant parts (Bartha et al. 2010 ). Erythromycin, a commonly used antibiotic, was found to accumulate over 5 months in soil irrigated with reclaimed water (Kinney et al. 2006 ). A study by Gibson et al. ( 2010 ) demonstrated that wastewater reused for irrigation contains pharmaceuticals such as ibuprofen (0.7–1.4 μg L −1 ), naproxen (7.2–13.5 μg L −1 ) and diclofenac (2.0–4.8 μg L −1 ). In addition, runoff from irrigated farmlands has been shown to impact surface water bodies and leach into groundwater. A study by Kolpin et al. ( 2002 ) showed that organic contaminants, including PPCPs, were detected in 80% of a network of 139 streams located downstream of urban networks and livestock production. Another study in New York on streams receiving wastewater discharge showed the presence of sulfamethoxazole and clindamycin at concentrations varying between 0.043 and 0.076 μg L −1 (Batt et al. 2006 ). Continuous accumulation and persistence of these chemicals in the environment can lead to ecotoxicological risks such as interference with endocrine systems of higher organisms, intersex characteristics in organisms such as fish, and microbiological resistance among bacterial populations (Belhaj et al. 2015 ). Continuing concerns regarding possible population-level impacts of pharmaceuticals from wastewater effluents has contributed to a search for sustainable and cheap technologies which will result in the effective removal of pharmaceuticals from reclaimed water. Recently, biochar has been explored as a potential material for the adsorption of pharmaceuticals from aqueous solutions (Ahmed et al. 2017 a; Mondal et al. 2016 ; Mostafapour et al. 2019 ; Sumalinog et al. 2018 ; Taheran et al. 2016 ; Yanyan et al. 2018 ). Biochar is a stable carbon (C)-rich, energy dense by-product synthesized through the pyrolysis of waste biomass in the absence of oxygen (Lehmann and Joseph 2009 ). Biochar has been employed as an adsorbent", "role": "user" }, { "content": "Biochar—a charcoal-like substance made primarily from agricultural waste products—holds promise for removing emerging contaminants such as pharmaceuticals from treated wastewater. That's the conclusion of a team of researchers that conducted a novel study that evaluated and compared the ability of biochar derived from two common leftover agricultural materials—cotton gin waste and guayule bagasse—to adsorb three common pharmaceutical compounds from an aqueous solution. In adsorption, one material, like a pharmaceutical compound, sticks to the surface of another, like the solid biochar particle. Conversely, in absorption, one material is taken internally into another; for example, a sponge absorbs water. Guayule, a shrub that grows in the arid Southwest, provided the waste for one of the biochars tested in the research. More properly called Parthenium argentatum, it has been cultivated as a source of rubber and latex. The plant is chopped to the ground and its branches mashed up to extract the latex. The dry, pulpy, fibrous residue that remains after stalks are crushed to extract the latex is called bagasse. The results are important, according to researcher Herschel Elliott, Penn State professor of agricultural and biological engineering, College of Agricultural Sciences, because they demonstrate the potential for biochar made from plentiful agricultural wastes—that otherwise must be disposed of—to serve as a low-cost additional treatment for reducing contaminants in treated wastewater used for irrigation. \"Most sewage treatment plants are currently not equipped to remove emerging contaminants such as pharmaceuticals, and if those toxic compounds can be removed by biochars, then wastewater can be recycled in irrigation systems,\" he said. \"That beneficial reuse is critical in regions such as the U.S. Southwest, where a lack of water hinders crop production.\" The pharmaceutical compounds used in the study to test whether the biochars would adsorb them from aqueous solution were: sulfapyridine, an antibacterial medication no longer prescribed for treatment of infections in humans but commonly used in veterinary medicine; docusate, widely used in medicines as a laxative and stool softener; and erythromycin, an antibiotic used to treat infections and acne. The results, published today (Nov. 16) in Biochar, suggest biochars made from agricultural waste materials could act as effective adsorbents to remove pharmaceuticals from reclaimed water prior to irrigation. However, the biochar derived from cotton gin waste was much more efficient. In the research, it adsorbed 98% of the docusate, 74% of the erythromycin and 70% of the sulfapyridine in aqueous solution. By comparison, the biochar derived from guayule bagasse adsorbed 50% of the docusate, 50% of the erythromycin and just 5% of the sulfapyridine. The research revealed that a temperature increase, from about 650 to about 1,300 degrees F in the oxygen-free pyrolysis process used to convert the agricultural waste materials to biochars, resulted in a greatly enhanced capacity to adsorb the pharmaceutical compounds. \"The most innovative part about the research was the use of the guayule bagasse because there have been no previous studies on using that material to produce biochar for the removal of emerging contaminants,\" said lead researcher Marlene Ndoun, a doctoral student in Penn State's Department of Agricultural and Biological Engineering. \"Same for cotton gin waste—research has been done on potential ways to remove other contaminants, but this is the first study to use cotton gin waste specifically to remove pharmaceuticals from water.\" For Ndoun, the research is more than theoretical. She said she wants to scale up the technology and make a difference in the world. Because cotton gin waste is widely available, even in the poorest regions, she believes it holds promise as a source of biochar to decontaminate water. \"I am originally from Cameroon, and the reason I'm even here is because I'm looking for ways to filter water in resource-limited communities, such as where I grew up,\" she said. \"We think if this could be scaled up, it would be ideal for use in countries in sub-Saharan Africa, where people don't have access to sophisticated equipment to purify their water.\" The next step, Ndoun explained, would be to develop a mixture of biochar material capable of adsorbing a wide range of contaminants from water. \"Beyond removing emerging contaminants such as pharmaceuticals, I am interested in blending biochar materials so that we have low-cost filters able to remove the typical contaminants we find in water, such as bacteria and organic matter,\" said Ndoun. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Biochars produced from cotton gin waste (CG) and guayule bagasse (GB) were characterized and explored as potential adsorbents for the removal of pharmaceuticals (sulfapyridine-SPY, docusate-DCT and erythromycin-ETM) from aqueous solution. An increase in biochar pyrolysis temperature from 350 ο C to 700 ο C led to an increase in pH, specific surface area, and surface hydrophobicity. The electronegative surface of all tested biochars indicated that non-Coulombic mechanisms were involved in adsorption of the anionic or uncharged pharmaceuticals under experimental conditions. The adsorption capacities of Sulfapyridine (SPY), Docusate (DCT) and Erythromycin (ETM) on biochar were influenced by the contact time and solution pH, as well as biochar specific surface area and functional groups. Adsorption of these pharmaceutical compounds was dominated by a complex interplay of three mechanisms: hydrophobic partitioning, hydrogen bonding and π–π electron donor–acceptor (EDA) interactions. Despite weaker π–π EDA interactions, reduced hydrophobicity of SPY − and increased electrostatic repulsion between anionic SPY − and the electronegative CG biochar surface at higher pH, the adsorption of SPY unexpectedly increased from 40% to 70% with an increase in pH from 7 to 10. Under alkaline conditions, adsorption was dominated by the formation of strong negative charge-assisted H-bonding between the sulfonamide moiety of SPY and surface carboxylic groups. There seemed to be no appreciable and consistent differences in the extent of DCT and ETM adsorption as the pH changed. Results suggest the CG and GB biochars could act as effective adsorbents for the removal of pharmaceuticals from reclaimed water prior to irrigation. High surface area biochars with physico-chemical properties (e.g., presence of functional groups, high cation and anion exchange capacities) conducive to strong interactions with polar-nonpolar functionality of pharmaceuticals could be used to achieve significant contaminant removal from water. Graphic Abstract Working on a manuscript? Avoid the common mistakes FormalPara Highlights Biochar was obtained from the carbonization of cotton gin waste and guayule bagasse at three temperatures Biochar shows considerable potential for the adsorption of SPY, DCT and ETM and can be used as a cheap, environmentally friendly adsorbent Hydrophobic partitioning, electrostatic interactions, hydrogen bonding and π-π electron donor–acceptor (EDA) interactions can simultaneously influence adsorption and determine the sorptive affinity of biochars for pharmaceuticals 1 Introduction Anthropogenic activities, including increasing urbanization, population growth and intensive agricultural activities have introduced a broad range of emerging contaminants (ECs) into the environment (Houtman 2010 ; Pal et al. 2010 ; Fenet 2012). ECs are defined as chemicals and microorganisms that have been detected in the environment and can potentially cause toxic effects in aquatic and human life at trace-level concentrations (ng- μg/L levels), but for which no water quality regulations exist (Ahmed et al. 2017a ; USGS, 2015). There are several classes of ECs including pesticides, industrial additives, flame retardants, endocrine disrupting compounds (EDCs) and pharmaceuticals and personal care products (PPCPSs). Among all classes of ECs, PPCPs are the most abundant in the environment and are often detected at elevated concentrations in surface and groundwaters (Daughton 2004 ) due to continuous human use. Additionally, wastewater treatment plants (WWTPs) are not effective at removing many of these chemicals, leading to the presence of various PPCPs in wastewater effluents (Gros et al. 2010 ; Sui et al. 2011 ). The World Health Organization (WHO) estimated that in 2025, two-third of the world’s population could be living in regions with limited access to water. Agriculture is the sector which requires the most water and is expected to be impacted by the shortage. To mitigate these impacts, treated wastewater or reclaimed water has become an important source of water for agricultural irrigation especially in arid regions of the world. Reclaimed water is wastewater from homes, offices, hospitals and industries that has undergone treatment to remove impurities such as nutrients and pathogens (DSWS 2011). Reclaimed water can be successfully used for irrigation because even after treatment, it still contains nitrogen and phosphorus that are essential to plant growth (Kinney et al. 2006 ). When treated wastewater is used for irrigation, contaminants such as pharmaceuticals may be introduced into crops from the soil through root uptake and translocation, leading to accumulation of these contaminants not only in the roots, but also in edible above-ground plant parts (Bartha et al. 2010 ). Erythromycin, a commonly used antibiotic, was found to accumulate over 5 months in soil irrigated with reclaimed water (Kinney et al. 2006 ). A study by Gibson et al. ( 2010 ) demonstrated that wastewater reused for irrigation contains pharmaceuticals such as ibuprofen (0.7–1.4 μg L −1 ), naproxen (7.2–13.5 μg L −1 ) and diclofenac (2.0–4.8 μg L −1 ). In addition, runoff from irrigated farmlands has been shown to impact surface water bodies and leach into groundwater. A study by Kolpin et al. ( 2002 ) showed that organic contaminants, including PPCPs, were detected in 80% of a network of 139 streams located downstream of urban networks and livestock production. Another study in New York on streams receiving wastewater discharge showed the presence of sulfamethoxazole and clindamycin at concentrations varying between 0.043 and 0.076 μg L −1 (Batt et al. 2006 ). Continuous accumulation and persistence of these chemicals in the environment can lead to ecotoxicological risks such as interference with endocrine systems of higher organisms, intersex characteristics in organisms such as fish, and microbiological resistance among bacterial populations (Belhaj et al. 2015 ). Continuing concerns regarding possible population-level impacts of pharmaceuticals from wastewater effluents has contributed to a search for sustainable and cheap technologies which will result in the effective removal of pharmaceuticals from reclaimed water. Recently, biochar has been explored as a potential material for the adsorption of pharmaceuticals from aqueous solutions (Ahmed et al. 2017 a; Mondal et al. 2016 ; Mostafapour et al. 2019 ; Sumalinog et al. 2018 ; Taheran et al. 2016 ; Yanyan et al. 2018 ). Biochar is a stable carbon (C)-rich, energy dense by-product synthesized through the pyrolysis of waste biomass in the absence of oxygen (Lehmann and Joseph 2009 ). Biochar has been employed as an adsorbent<|im_end|> <|im_start|>assistant Biochar—a charcoal-like substance made primarily from agricultural waste products—holds promise for removing emerging contaminants such as pharmaceuticals from treated wastewater. That's the conclusion of a team of researchers that conducted a novel study that evaluated and compared the ability of biochar derived from two common leftover agricultural materials—cotton gin waste and guayule bagasse—to adsorb three common pharmaceutical compounds from an aqueous solution. In adsorption, one material, like a pharmaceutical compound, sticks to the surface of another, like the solid biochar particle. Conversely, in absorption, one material is taken internally into another; for example, a sponge absorbs water. Guayule, a shrub that grows in the arid Southwest, provided the waste for one of the biochars tested in the research. More properly called Parthenium argentatum, it has been cultivated as a source of rubber and latex. The plant is chopped to the ground and its branches mashed up to extract the latex. The dry, pulpy, fibrous residue that remains after stalks are crushed to extract the latex is called bagasse. The results are important, according to researcher Herschel Elliott, Penn State professor of agricultural and biological engineering, College of Agricultural Sciences, because they demonstrate the potential for biochar made from plentiful agricultural wastes—that otherwise must be disposed of—to serve as a low-cost additional treatment for reducing contaminants in treated wastewater used for irrigation. "Most sewage treatment plants are currently not equipped to remove emerging contaminants such as pharmaceuticals, and if those toxic compounds can be removed by biochars, then wastewater can be recycled in irrigation systems," he said. "That beneficial reuse is critical in regions such as the U.S. Southwest, where a lack of water hinders crop production." The pharmaceutical compounds used in the study to test whether the biochars would adsorb them from aqueous solution were: sulfapyridine, an antibacterial medication no longer prescribed for treatment of infections in humans but commonly used in veterinary medicine; docusate, widely used in medicines as a laxative and stool softener; and erythromycin, an antibiotic used to treat infections and acne. The results, published today (Nov. 16) in Biochar, suggest biochars made from agricultural waste materials could act as effective adsorbents to remove pharmaceuticals from reclaimed water prior to irrigation. However, the biochar derived from cotton gin waste was much more efficient. In the research, it adsorbed 98% of the docusate, 74% of the erythromycin and 70% of the sulfapyridine in aqueous solution. By comparison, the biochar derived from guayule bagasse adsorbed 50% of the docusate, 50% of the erythromycin and just 5% of the sulfapyridine. The research revealed that a temperature increase, from about 650 to about 1,300 degrees F in the oxygen-free pyrolysis process used to convert the agricultural waste materials to biochars, resulted in a greatly enhanced capacity to adsorb the pharmaceutical compounds. "The most innovative part about the research was the use of the guayule bagasse because there have been no previous studies on using that material to produce biochar for the removal of emerging contaminants," said lead researcher Marlene Ndoun, a doctoral student in Penn State's Department of Agricultural and Biological Engineering. "Same for cotton gin waste—research has been done on potential ways to remove other contaminants, but this is the first study to use cotton gin waste specifically to remove pharmaceuticals from water." For Ndoun, the research is more than theoretical. She said she wants to scale up the technology and make a difference in the world. Because cotton gin waste is widely available, even in the poorest regions, she believes it holds promise as a source of biochar to decontaminate water. "I am originally from Cameroon, and the reason I'm even here is because I'm looking for ways to filter water in resource-limited communities, such as where I grew up," she said. "We think if this could be scaled up, it would be ideal for use in countries in sub-Saharan Africa, where people don't have access to sophisticated equipment to purify their water." The next step, Ndoun explained, would be to develop a mixture of biochar material capable of adsorbing a wide range of contaminants from water. "Beyond removing emerging contaminants such as pharmaceuticals, I am interested in blending biochar materials so that we have low-cost filters able to remove the typical contaminants we find in water, such as bacteria and organic matter," said Ndoun. <|im_end|>

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2,466

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood, and is often characterized by altered executive functioning. Executive function has been found to be supported by flexibility in dynamic brain reconfiguration. Thus, we applied multilayer community detection to resting-state fMRI data in 180 children with ADHD and 180 typically developing children (TDC) to identify alterations in dynamic brain reconfiguration in children with ADHD. We specifically evaluated MR derived neural flexibility, which is thought to underlie cognitive flexibility, or the ability to selectively switch between mental processes. Significantly decreased neural flexibility was observed in the ADHD group at both the whole brain (raw p = 0.0005) and sub-network levels ( p < 0.05, FDR corrected), particularly for the default mode network, attention-related networks, executive function-related networks, and primary networks. Furthermore, the subjects with ADHD who received medication exhibited significantly increased neural flexibility ( p = 0.025, FDR corrected) when compared to subjects with ADHD who were medication naïve, and their neural flexibility was not statistically different from the TDC group ( p = 0.74, FDR corrected). Finally, regional neural flexibility was capable of differentiating ADHD from TDC (Accuracy: 77% for tenfold cross-validation, 74.46% for independent test) and of predicting ADHD severity using clinical measures of symptom severity ( R 2 : 0.2794 for tenfold cross-validation, 0.156 for independent test). In conclusion, the present study found that neural flexibility is altered in children with ADHD and demonstrated the potential clinical utility of neural flexibility to identify children with ADHD, as well as to monitor treatment responses and disease severity. Introduction Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children, affecting 3–5% of children worldwide [ 1 , 2 ]. ADHD is characterized by developmentally inappropriate symptoms of inattention, impulsivity, and hyperactivity. Children with ADHD exhibit difficulties controlling their behaviors and attention, which affects their academic performance and social functioning [ 3 ]. Importantly, these symptoms often persist into adulthood [ 4 ]. Current ADHD diagnosis relies largely on behavioral assessments after symptoms onset. In addition, clinical diagnostic approaches could be subjective and thus may influence diagnostic accuracy. Thus, approaches capable of early and objective diagnosis of ADHD may provide an opportunity of early intervention to potentially minimize its long-term sequelae [ 5 , 6 , 7 ]. The development of machine learning methods has provided the opportunity to solve these concerns. By integrating neuroimaging data and machine learning methods, it is possible to differentiate subjects with ADHD from typically developing children (TDC) and, critically, to predict clinical outcomes [ 8 ]. A large number of neuroimaging studies have observed that symptoms of ADHD are driven by atypical brain network organization and impaired functional connectivity (FC) [ 9 , 10 , 11 , 12 ]. Disrupted whole brain and sub-network FC [ 9 , 13 ], altered small-world topology, higher local and lower global efficiency [ 14 ], and, finally, reduced segregation between default mode network (DMN) and task-relevant networks [ 15 , 16 ] have been reported in ADHD. However, one of the common assumptions of the aforementioned studies was that the brain is temporally stable during the entire imaging acquisition period (5–8 min). Recent evidence indicates that subjects are likely to engage in several types of mental activities during a resting period of imaging acquisition [ 17 , 18 ], which could result in altered functional brain network organization throughout the course of the scan [ 19 , 20 ]. More importantly, several lines of evidence have reported that brain dynamics are relevant for complex cognitive processes [ 21 , 22 , 23 ] and are related to psychiatric and neurologic disease [ 24 , 25 ]. Thus, measuring “dynamic” brain features through estimation of time-related variations across multiple short time windows has gained substantial interest [ 24 ]. Notably, altered dynamic brain states, distorted quasi-periodic patterns of brain activity, and changes in temporal variability of FC have been observed in ADHD [ 26 , 27 , 28 , 29 , 30 ]. Cognitive flexibility is a critical aspect of human cognition [ 31 ] and has been reported to be a biomarker for brain disorders [ 32 , 33 , 34 , 35 ]. Children with ADHD have reduced cognitive flexibility as compared to TDC (higher switch costs and slower reaction time) [ 36 , 37 , 38 ]. Recent studies have suggested that brain dynamics are important features underlying cognitive flexibility [ 21 , 23 , 39 , 40 , 41 ]. Specifically, neural flexibility, calculated as the frequency at which brain regions change their allegiance from one functional module to another during fMRI acquisition, has recently been proposed [ 42 , 43 ]. Neural flexibility not only potentially links to cognitive flexibility, but also has been reported to predict learning outcomes and executive functions in healthy subjects [ 42 , 44 ]. Therefore, neural flexibility might be a useful metric to reflect impaired cognitive flexibility in ADHD subjects. In this study, we aimed to determine whether neural flexibility can serve as a biomarker to differentiate children with ADHD from TDC and whether it is associated with ADHD severity. Specifically, we implemented machine learning methods on neural flexibility estimates to: (1) distinguish children with ADHD from TDC; and (2) to assess symptom severity in children with ADHD. We hypothesized that children with ADHD would exhibit lower neural flexibility than that of TDC and that it would successfully differentiate groups and predict symptom severity. Furthermore, although pharmacological treatments can ameliorate the core symptoms of ADHD and improve subjects’ future functional outcomes [ 45 ], only a few studies have investigated how medication use impacts functional network organization in ADHD [ 46 ]. Therefore, we additionally hypothesized that children with ADHD who were on medication would show a “recovery” of neural flexibility toward that observed in TDC. Methods We used two sites from a publicly available, multi-site ADHD dataset, the ADHD-200 study [ 47 ]: Peking University (PKU) and New York University", "role": "user" }, { "content": "Multitasking is not just an office skill. It's key to functioning as a human, and it involves something called cognitive flexibility—the ability to smoothly switch between mental processes. UNC scientists conducted a study to image the neural activity analogues to cognitive flexibility and discover differences in the brain activity of children with ADHD and those without. Their findings, in the journal Molecular Psychiatry, could help doctors diagnose children with ADHD and monitor the severity of the condition and treatment effectiveness. Some people are more cognitively flexible than others. It's just the luck of the genetic draw in some ways, though we can improve our cognitive flexibility once we realize we're being inflexible. Think of it like this: we're cognitively flexible when we can start dinner, let the onions simmer, text a friend, return to making dinner without scorching the onions, and then finish dinner while also carrying on a conversation with your spouse. We're also cognitively flexible when we switch communication styles while talking to a friend and then a daughter and then a coworker, or when we solve problems creatively, say, when you realize you don't have onions to make the dinner you want, so you need a new plan. It's part of our executive function, which includes accessing memories and exhibiting self control. Poor executive function is a hallmark of ADHD in children and adults. When we're cognitively inflexible, we can't focus on some of the tasks, we pick up the phone and scroll social media without thinking, forgetting what we're doing while making dinner. In adults but especially in children, such cognitive inflexibility can wreak havoc with an individual's ability to learn and accomplish tasks. UNC scientists led by senior author Weili Lin, Ph.D., director of the UNC Biomedical Research Imaging Center (BRIC), wanted to find out what's happening throughout the brain when executive function, particularly cognitive flexibility, is off line. Lin and colleagues used functional magnetic resonance imaging (fMRI) to study the neural flexibility of 180 children diagnosed with ADHD and 180 typically developing children. \"We observed significantly decreased neural flexibility in the ADHD group at both the whole brain and sub-network levels,\" said Lin, the Dixie Boney Soo Distinguished Professor of Neurological Medicine in the UNC Department of Radiology, \"particularly for the default mode network, attention-related networks, executive function-related networks, and primary networks of the brain involved in sensory, motor and visual processing.\" The researchers also found that children with ADHD who received medication exhibited significantly increased neural flexibility compared to children with ADHD who were not taking medication. Children on medication displayed neural flexibility that was not statistically different from the group of traditionally developing children. Lastly, the researchers found that they could use fMRI to discover neural flexibility differences across entire brain regions between children with ADHA and the traditionally developing children. \"And we were able to predict ADHD severity using clinical measures of symptom severity,\" Lin said. \"We think our study demonstrate the potential clinical utility of neural flexibility to identify children with ADHD, as well as to monitor treatment responses and the severity of the condition in individual children.\" Other authors of the paper are first author Weiyan Yin, Tengfei Li, Jessica Cohen, Hongtu Zhu, Ziliang Zhu—all of UNC-Chapel Hill—and Peter Mucha, formerly of UNC and now at Dartmouth University. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood, and is often characterized by altered executive functioning. Executive function has been found to be supported by flexibility in dynamic brain reconfiguration. Thus, we applied multilayer community detection to resting-state fMRI data in 180 children with ADHD and 180 typically developing children (TDC) to identify alterations in dynamic brain reconfiguration in children with ADHD. We specifically evaluated MR derived neural flexibility, which is thought to underlie cognitive flexibility, or the ability to selectively switch between mental processes. Significantly decreased neural flexibility was observed in the ADHD group at both the whole brain (raw p = 0.0005) and sub-network levels ( p < 0.05, FDR corrected), particularly for the default mode network, attention-related networks, executive function-related networks, and primary networks. Furthermore, the subjects with ADHD who received medication exhibited significantly increased neural flexibility ( p = 0.025, FDR corrected) when compared to subjects with ADHD who were medication naïve, and their neural flexibility was not statistically different from the TDC group ( p = 0.74, FDR corrected). Finally, regional neural flexibility was capable of differentiating ADHD from TDC (Accuracy: 77% for tenfold cross-validation, 74.46% for independent test) and of predicting ADHD severity using clinical measures of symptom severity ( R 2 : 0.2794 for tenfold cross-validation, 0.156 for independent test). In conclusion, the present study found that neural flexibility is altered in children with ADHD and demonstrated the potential clinical utility of neural flexibility to identify children with ADHD, as well as to monitor treatment responses and disease severity. Introduction Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders in children, affecting 3–5% of children worldwide [ 1 , 2 ]. ADHD is characterized by developmentally inappropriate symptoms of inattention, impulsivity, and hyperactivity. Children with ADHD exhibit difficulties controlling their behaviors and attention, which affects their academic performance and social functioning [ 3 ]. Importantly, these symptoms often persist into adulthood [ 4 ]. Current ADHD diagnosis relies largely on behavioral assessments after symptoms onset. In addition, clinical diagnostic approaches could be subjective and thus may influence diagnostic accuracy. Thus, approaches capable of early and objective diagnosis of ADHD may provide an opportunity of early intervention to potentially minimize its long-term sequelae [ 5 , 6 , 7 ]. The development of machine learning methods has provided the opportunity to solve these concerns. By integrating neuroimaging data and machine learning methods, it is possible to differentiate subjects with ADHD from typically developing children (TDC) and, critically, to predict clinical outcomes [ 8 ]. A large number of neuroimaging studies have observed that symptoms of ADHD are driven by atypical brain network organization and impaired functional connectivity (FC) [ 9 , 10 , 11 , 12 ]. Disrupted whole brain and sub-network FC [ 9 , 13 ], altered small-world topology, higher local and lower global efficiency [ 14 ], and, finally, reduced segregation between default mode network (DMN) and task-relevant networks [ 15 , 16 ] have been reported in ADHD. However, one of the common assumptions of the aforementioned studies was that the brain is temporally stable during the entire imaging acquisition period (5–8 min). Recent evidence indicates that subjects are likely to engage in several types of mental activities during a resting period of imaging acquisition [ 17 , 18 ], which could result in altered functional brain network organization throughout the course of the scan [ 19 , 20 ]. More importantly, several lines of evidence have reported that brain dynamics are relevant for complex cognitive processes [ 21 , 22 , 23 ] and are related to psychiatric and neurologic disease [ 24 , 25 ]. Thus, measuring “dynamic” brain features through estimation of time-related variations across multiple short time windows has gained substantial interest [ 24 ]. Notably, altered dynamic brain states, distorted quasi-periodic patterns of brain activity, and changes in temporal variability of FC have been observed in ADHD [ 26 , 27 , 28 , 29 , 30 ]. Cognitive flexibility is a critical aspect of human cognition [ 31 ] and has been reported to be a biomarker for brain disorders [ 32 , 33 , 34 , 35 ]. Children with ADHD have reduced cognitive flexibility as compared to TDC (higher switch costs and slower reaction time) [ 36 , 37 , 38 ]. Recent studies have suggested that brain dynamics are important features underlying cognitive flexibility [ 21 , 23 , 39 , 40 , 41 ]. Specifically, neural flexibility, calculated as the frequency at which brain regions change their allegiance from one functional module to another during fMRI acquisition, has recently been proposed [ 42 , 43 ]. Neural flexibility not only potentially links to cognitive flexibility, but also has been reported to predict learning outcomes and executive functions in healthy subjects [ 42 , 44 ]. Therefore, neural flexibility might be a useful metric to reflect impaired cognitive flexibility in ADHD subjects. In this study, we aimed to determine whether neural flexibility can serve as a biomarker to differentiate children with ADHD from TDC and whether it is associated with ADHD severity. Specifically, we implemented machine learning methods on neural flexibility estimates to: (1) distinguish children with ADHD from TDC; and (2) to assess symptom severity in children with ADHD. We hypothesized that children with ADHD would exhibit lower neural flexibility than that of TDC and that it would successfully differentiate groups and predict symptom severity. Furthermore, although pharmacological treatments can ameliorate the core symptoms of ADHD and improve subjects’ future functional outcomes [ 45 ], only a few studies have investigated how medication use impacts functional network organization in ADHD [ 46 ]. Therefore, we additionally hypothesized that children with ADHD who were on medication would show a “recovery” of neural flexibility toward that observed in TDC. Methods We used two sites from a publicly available, multi-site ADHD dataset, the ADHD-200 study [ 47 ]: Peking University (PKU) and New York University<|im_end|> <|im_start|>assistant Multitasking is not just an office skill. It's key to functioning as a human, and it involves something called cognitive flexibility—the ability to smoothly switch between mental processes. UNC scientists conducted a study to image the neural activity analogues to cognitive flexibility and discover differences in the brain activity of children with ADHD and those without. Their findings, in the journal Molecular Psychiatry, could help doctors diagnose children with ADHD and monitor the severity of the condition and treatment effectiveness. Some people are more cognitively flexible than others. It's just the luck of the genetic draw in some ways, though we can improve our cognitive flexibility once we realize we're being inflexible. Think of it like this: we're cognitively flexible when we can start dinner, let the onions simmer, text a friend, return to making dinner without scorching the onions, and then finish dinner while also carrying on a conversation with your spouse. We're also cognitively flexible when we switch communication styles while talking to a friend and then a daughter and then a coworker, or when we solve problems creatively, say, when you realize you don't have onions to make the dinner you want, so you need a new plan. It's part of our executive function, which includes accessing memories and exhibiting self control. Poor executive function is a hallmark of ADHD in children and adults. When we're cognitively inflexible, we can't focus on some of the tasks, we pick up the phone and scroll social media without thinking, forgetting what we're doing while making dinner. In adults but especially in children, such cognitive inflexibility can wreak havoc with an individual's ability to learn and accomplish tasks. UNC scientists led by senior author Weili Lin, Ph.D., director of the UNC Biomedical Research Imaging Center (BRIC), wanted to find out what's happening throughout the brain when executive function, particularly cognitive flexibility, is off line. Lin and colleagues used functional magnetic resonance imaging (fMRI) to study the neural flexibility of 180 children diagnosed with ADHD and 180 typically developing children. "We observed significantly decreased neural flexibility in the ADHD group at both the whole brain and sub-network levels," said Lin, the Dixie Boney Soo Distinguished Professor of Neurological Medicine in the UNC Department of Radiology, "particularly for the default mode network, attention-related networks, executive function-related networks, and primary networks of the brain involved in sensory, motor and visual processing." The researchers also found that children with ADHD who received medication exhibited significantly increased neural flexibility compared to children with ADHD who were not taking medication. Children on medication displayed neural flexibility that was not statistically different from the group of traditionally developing children. Lastly, the researchers found that they could use fMRI to discover neural flexibility differences across entire brain regions between children with ADHA and the traditionally developing children. "And we were able to predict ADHD severity using clinical measures of symptom severity," Lin said. "We think our study demonstrate the potential clinical utility of neural flexibility to identify children with ADHD, as well as to monitor treatment responses and the severity of the condition in individual children." Other authors of the paper are first author Weiyan Yin, Tengfei Li, Jessica Cohen, Hongtu Zhu, Ziliang Zhu—all of UNC-Chapel Hill—and Peter Mucha, formerly of UNC and now at Dartmouth University. <|im_end|>

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1,988

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract High Arctic ecosystems and Indigenous livelihoods are tightly linked and exposed to climate change, yet assessing their sensitivity requires a long-term perspective. Here, we assess the vulnerability of the North Water polynya, a unique seaice ecosystem that sustains the world’s northernmost Inuit communities and several keystone Arctic species. We reconstruct mid-to-late Holocene changes in sea ice, marine primary production, and little auk colony dynamics through multi-proxy analysis of marine and lake sediment cores. Our results suggest a productive ecosystem by 4400–4200 cal yrs b2k coincident with the arrival of the first humans in Greenland. Climate forcing during the late Holocene, leading to periods of polynya instability and marine productivity decline, is strikingly coeval with the human abandonment of Greenland from c. 2200–1200 cal yrs b2k. Our long-term perspective highlights the future decline of the North Water ecosystem, due to climate warming and changing sea-ice conditions, as an important climate change risk. Introduction The impact of changing sea-ice conditions on the productivity of resources that sustain Indigenous livelihoods in the Arctic has been identified by the IPCC as an emerging climate change risk, stemming from the triangular-intersection of an exposure, a hazard and a vulnerability 1 In this context, the well-documented millennial-scale dependence of local communities on the North Water (NOW) represents an exposure 2 , 3 , defined by the IPCC as the presence of e.g. people, livelihoods or ecosystems in settings that could be adversely affected 1 The NOW or Pikialasorsuaq (‘the great upwelling’ in Greenlandic) is the largest and most productive polynya in the northern hemisphere, an annually recurring ice-free area in northern Baffin Bay (Fig. 1 ). The ice-free waters of the NOW allow for an enhanced and unusually early phytoplankton bloom lasting for two-four months 4 The polynya ecosystem sustains keystone Arctic species, including Arctic cod, seabirds, and marine mammals such as narwhal, beluga, walrus, and polar bear 5 , which all serve to underpin the hunting and fishing economies of Inuit communities in the region 3 , 6 The World Conservation Union (IUCN) has identified the NOW as one of the most ecologically significant marine areas in the Arctic and proposed it as a UNESCO Natural Marine World Heritage Site due to its Outstanding Universal Value 7 . Fig. 1: Location and configuration of the North Water polynya. a Marine and lacustrine core sites, main ocean currents, prehistoric human migration routes, and present-day distribution of little auk colonies. The extent of the polynya is defined as in ref. 17 . b Example of late-June polynya configuration with a stable ice arch c . Example of late-June configuration in the absence of the Kane Basin ice arch. Satellite images from NASA EOSDIS. Several Inuit communities rely directly on the polynya resources today, including Qaanaaq, Siorapaluk, Qeqertat and Savissivik in Northwest Greenland, and Grise Fiord in Nunavut. Background map figures were created using Ocean Data View 73 . Full size image The seasonal formation and physical conditions of the NOW rely primarily on the consolidation of an ice arch or bridge across the southern Kane Basin during winter, which blocks the inflow of multiyear sea ice from the Arctic Ocean (Fig. 1 ). When the ice arch is stable, newly formed sea ice south of the arch is continuously removed by northerly winds and ocean currents, which also promotes a deep mixed layer during winter and high nutrient availability for the spring phytoplankton bloom 4 Entrainment of deeper and warmer Atlantic-derived water masses further limits sea ice growth and provides nutrients that sustain high primary productivity rates 4 . Diatoms, including open-water, marginal ice zone, and sea-ice (sympagic) taxa, are the main primary producers in the NOW (e.g. ref. 8 ) and although grazing pressure may vary, a significant fraction of the diatom production in the euphotic zone reaches the seafloor sediments either as intact cells and spores or empty frustules (after grazing or lysis) 9 . Following nutrient exhaustion, species belonging to the diatom genus Chaetoceros can produce large amounts of highly silicified, fast-sinking resting spores 10 that generally preserve well in the sediments and reflect changes in productivity levels over time. The NOW supports >80% of the global breeding population of little auk, which is the most abundant seabird in the North Atlantic 11 . The little auk is tightly linked to the copepod Calanus hyperboreus , on which the chicks are raised, and >60 million birds depend on the unique availability of this prey item in the NOW 12 . By transporting vast quantities of marine-derived nutrients (MDN) from sea to land in the form of guano, little auks have transformed extensive parts of the NOW coastal landscapes into green oases 13 , 14 . At little auk colonies, temporal changes in the MDN flux in sediments can be used as a proxy for changes in bird numbers and, by inference, NOW productivity over time 15 . Due to its resource richness in one of Earth’s most inhospitable environments, and its strategic location at the southern edge of the narrowest point between Canada and Greenland, the NOW region represents the gateway of prehistoric migrations into Greenland and has been the stage for cultural transitions since the first humans crossed the Nares Strait c. 4400 yrs b2k 2 , 16 . The NOW is of critical significance to Inuit communities today 6 , 17 , and transformative shifts in the ecosystem, due to changing sea-ice conditions, represent an emerging hazard, in this context referring to a climate-related trend with negative impacts 1 . Ice-arch dynamics in Nares Strait have shown a tendency towards instability and earlier spring collapses, linked to changes in sea-ice regime and wind forcing 18 , 19 , 20 . This raises concerns as to whether the NOW ecosystem will persevere in a warming climate. Evaluating risks and defining climate adaptation measures for this unique ecosystem requires an understanding of past ecological and societal responses, but this knowledge is lacking due to a paucity of long-term records. Here, we explore the", "role": "user" }, { "content": "The University of Helsinki's Environmental Change Research Unit (ECRU) took part in an international study investigating the millennia-long history of the most important oasis in the Arctic and the potential effects of climate change on its future. The North Water Polynya is an area of year-round open water located between northwest Greenland and Ellesmere Island, Canada, in northern Baffin Bay, which is otherwise covered by sea ice roughly eight months of the year. The area is known as an Arctic oasis, and one of the main migration routes of Greenland's original population runs just north of the area. In the study, microfossils and chemical biomarkers preserved in marine and lake sediments were analyzed as keys to the past, exposing historical variation in the North Water Polynya in the past 6,000 years. The polynya's high rate of primary production, for which, in marine environments, diatoms and other microalgae are responsible, maintains a diverse and unique ecosystem that serves as a safe haven for a range of species in Arctic conditions, which are otherwise harsh. Keystone Arctic species, such as the polar bear, the walrus and the narwhal, also thrive there. For the indigenous populations reliant on hunting and fishing, this area, the largest polynya in the northern hemisphere, has been a lifeline. According to the study, the polynya was stable and its primary production was high roughly 4,400–4,200 years ago, at the time when people arrived in Greenland from Canada over the frozen Nares Strait. A millennium of instability and new heat records However, the polynya's stability has varied over the last millennia: during the warmer climate periods 2,200–1,200 years ago, the area was unstable and its productivity fell drastically. When primary production rates are low, significant reductions are seen in the populations of organisms in the upper levels of the food web, such as zooplankton, fish and marine mammals. \"According to archaeological finds, there were no inhabitants in the area during this period. It's a mystery that can potentially be explained, in light of the research findings, by conditions that were unfavorable to people reliant on hunting and fishing,\" says researcher Kaarina Weckström from the Environmental Change Research Unit, University of Helsinki. The researchers point out that air temperatures have never reached the current level in northwest Greenland in the 6,000-year-long period of the polynya's history studied. Global warming and reduction in sea ice caused by human activity have led to the polynya's instability. The area is maintained by favorable ocean currents and winds, and particularly by an ice bridge located north of the polynya, which prevents drift ice in the Arctic Ocean traveling further south. It is the annual formation of this natural block that the warming of the climate is now threatening. \"This area, the Arctic's most important oasis, is likely to disappear if temperatures continue to rise as forecast. It would be important to at least slow climate change down, in order for Arctic indigenous peoples to have some kind of a chance to adapt to their future living conditions. Then again, as the history of the polynya suggests, if we can reduce greenhouse gas emissions and mitigate the rising air temperature, both Arctic sea ice and the polynya can be restored,\" Weckström sums up. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract High Arctic ecosystems and Indigenous livelihoods are tightly linked and exposed to climate change, yet assessing their sensitivity requires a long-term perspective. Here, we assess the vulnerability of the North Water polynya, a unique seaice ecosystem that sustains the world’s northernmost Inuit communities and several keystone Arctic species. We reconstruct mid-to-late Holocene changes in sea ice, marine primary production, and little auk colony dynamics through multi-proxy analysis of marine and lake sediment cores. Our results suggest a productive ecosystem by 4400–4200 cal yrs b2k coincident with the arrival of the first humans in Greenland. Climate forcing during the late Holocene, leading to periods of polynya instability and marine productivity decline, is strikingly coeval with the human abandonment of Greenland from c. 2200–1200 cal yrs b2k. Our long-term perspective highlights the future decline of the North Water ecosystem, due to climate warming and changing sea-ice conditions, as an important climate change risk. Introduction The impact of changing sea-ice conditions on the productivity of resources that sustain Indigenous livelihoods in the Arctic has been identified by the IPCC as an emerging climate change risk, stemming from the triangular-intersection of an exposure, a hazard and a vulnerability 1 In this context, the well-documented millennial-scale dependence of local communities on the North Water (NOW) represents an exposure 2 , 3 , defined by the IPCC as the presence of e.g. people, livelihoods or ecosystems in settings that could be adversely affected 1 The NOW or Pikialasorsuaq (‘the great upwelling’ in Greenlandic) is the largest and most productive polynya in the northern hemisphere, an annually recurring ice-free area in northern Baffin Bay (Fig. 1 ). The ice-free waters of the NOW allow for an enhanced and unusually early phytoplankton bloom lasting for two-four months 4 The polynya ecosystem sustains keystone Arctic species, including Arctic cod, seabirds, and marine mammals such as narwhal, beluga, walrus, and polar bear 5 , which all serve to underpin the hunting and fishing economies of Inuit communities in the region 3 , 6 The World Conservation Union (IUCN) has identified the NOW as one of the most ecologically significant marine areas in the Arctic and proposed it as a UNESCO Natural Marine World Heritage Site due to its Outstanding Universal Value 7 . Fig. 1: Location and configuration of the North Water polynya. a Marine and lacustrine core sites, main ocean currents, prehistoric human migration routes, and present-day distribution of little auk colonies. The extent of the polynya is defined as in ref. 17 . b Example of late-June polynya configuration with a stable ice arch c . Example of late-June configuration in the absence of the Kane Basin ice arch. Satellite images from NASA EOSDIS. Several Inuit communities rely directly on the polynya resources today, including Qaanaaq, Siorapaluk, Qeqertat and Savissivik in Northwest Greenland, and Grise Fiord in Nunavut. Background map figures were created using Ocean Data View 73 . Full size image The seasonal formation and physical conditions of the NOW rely primarily on the consolidation of an ice arch or bridge across the southern Kane Basin during winter, which blocks the inflow of multiyear sea ice from the Arctic Ocean (Fig. 1 ). When the ice arch is stable, newly formed sea ice south of the arch is continuously removed by northerly winds and ocean currents, which also promotes a deep mixed layer during winter and high nutrient availability for the spring phytoplankton bloom 4 Entrainment of deeper and warmer Atlantic-derived water masses further limits sea ice growth and provides nutrients that sustain high primary productivity rates 4 . Diatoms, including open-water, marginal ice zone, and sea-ice (sympagic) taxa, are the main primary producers in the NOW (e.g. ref. 8 ) and although grazing pressure may vary, a significant fraction of the diatom production in the euphotic zone reaches the seafloor sediments either as intact cells and spores or empty frustules (after grazing or lysis) 9 . Following nutrient exhaustion, species belonging to the diatom genus Chaetoceros can produce large amounts of highly silicified, fast-sinking resting spores 10 that generally preserve well in the sediments and reflect changes in productivity levels over time. The NOW supports >80% of the global breeding population of little auk, which is the most abundant seabird in the North Atlantic 11 . The little auk is tightly linked to the copepod Calanus hyperboreus , on which the chicks are raised, and >60 million birds depend on the unique availability of this prey item in the NOW 12 . By transporting vast quantities of marine-derived nutrients (MDN) from sea to land in the form of guano, little auks have transformed extensive parts of the NOW coastal landscapes into green oases 13 , 14 . At little auk colonies, temporal changes in the MDN flux in sediments can be used as a proxy for changes in bird numbers and, by inference, NOW productivity over time 15 . Due to its resource richness in one of Earth’s most inhospitable environments, and its strategic location at the southern edge of the narrowest point between Canada and Greenland, the NOW region represents the gateway of prehistoric migrations into Greenland and has been the stage for cultural transitions since the first humans crossed the Nares Strait c. 4400 yrs b2k 2 , 16 . The NOW is of critical significance to Inuit communities today 6 , 17 , and transformative shifts in the ecosystem, due to changing sea-ice conditions, represent an emerging hazard, in this context referring to a climate-related trend with negative impacts 1 . Ice-arch dynamics in Nares Strait have shown a tendency towards instability and earlier spring collapses, linked to changes in sea-ice regime and wind forcing 18 , 19 , 20 . This raises concerns as to whether the NOW ecosystem will persevere in a warming climate. Evaluating risks and defining climate adaptation measures for this unique ecosystem requires an understanding of past ecological and societal responses, but this knowledge is lacking due to a paucity of long-term records. Here, we explore the<|im_end|> <|im_start|>assistant The University of Helsinki's Environmental Change Research Unit (ECRU) took part in an international study investigating the millennia-long history of the most important oasis in the Arctic and the potential effects of climate change on its future. The North Water Polynya is an area of year-round open water located between northwest Greenland and Ellesmere Island, Canada, in northern Baffin Bay, which is otherwise covered by sea ice roughly eight months of the year. The area is known as an Arctic oasis, and one of the main migration routes of Greenland's original population runs just north of the area. In the study, microfossils and chemical biomarkers preserved in marine and lake sediments were analyzed as keys to the past, exposing historical variation in the North Water Polynya in the past 6,000 years. The polynya's high rate of primary production, for which, in marine environments, diatoms and other microalgae are responsible, maintains a diverse and unique ecosystem that serves as a safe haven for a range of species in Arctic conditions, which are otherwise harsh. Keystone Arctic species, such as the polar bear, the walrus and the narwhal, also thrive there. For the indigenous populations reliant on hunting and fishing, this area, the largest polynya in the northern hemisphere, has been a lifeline. According to the study, the polynya was stable and its primary production was high roughly 4,400–4,200 years ago, at the time when people arrived in Greenland from Canada over the frozen Nares Strait. A millennium of instability and new heat records However, the polynya's stability has varied over the last millennia: during the warmer climate periods 2,200–1,200 years ago, the area was unstable and its productivity fell drastically. When primary production rates are low, significant reductions are seen in the populations of organisms in the upper levels of the food web, such as zooplankton, fish and marine mammals. "According to archaeological finds, there were no inhabitants in the area during this period. It's a mystery that can potentially be explained, in light of the research findings, by conditions that were unfavorable to people reliant on hunting and fishing," says researcher Kaarina Weckström from the Environmental Change Research Unit, University of Helsinki. The researchers point out that air temperatures have never reached the current level in northwest Greenland in the 6,000-year-long period of the polynya's history studied. Global warming and reduction in sea ice caused by human activity have led to the polynya's instability. The area is maintained by favorable ocean currents and winds, and particularly by an ice bridge located north of the polynya, which prevents drift ice in the Arctic Ocean traveling further south. It is the annual formation of this natural block that the warming of the climate is now threatening. "This area, the Arctic's most important oasis, is likely to disappear if temperatures continue to rise as forecast. It would be important to at least slow climate change down, in order for Arctic indigenous peoples to have some kind of a chance to adapt to their future living conditions. Then again, as the history of the polynya suggests, if we can reduce greenhouse gas emissions and mitigate the rising air temperature, both Arctic sea ice and the polynya can be restored," Weckström sums up. <|im_end|>

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2,047

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract While behavior of equilibrium systems is well understood, evolution of nonequilibrium ones is much less clear. Yet, many researches have suggested that the principle of the maximum entropy production is of key importance in complex systems away from equilibrium. Here, we present a quantitative study of large ensembles of carbon nanotubes suspended in a non-conducting non-polar fluid subject to a strong electric field. Being driven out of equilibrium, the suspension spontaneously organizes into an electrically conducting state under a wide range of parameters. Such self-assembly allows the Joule heating and, therefore, the entropy production in the fluid, to be maximized. Curiously, we find that emerging self-assembled structures can start to wiggle. The wiggling takes place only until the entropy production in the suspension reaches its maximum, at which time the wiggling stops and the structure becomes quasi-stable. Thus, we provide strong evidence that maximum entropy production principle plays an essential role in the evolution of self-organizing systems far from equilibrium. Introduction Classical thermodynamics offers elaborated theoretical instruments to study behavior of systems that are in or near equilibrium. But often objects and processes which we deal with in everyday life, such as living biological organisms or weather events, are far from equilibrium. Therefore, the search for principia governing nonequilibrium systems is of great interest. The notion of entropy in equilibrium states and its production in nonequilibrium processes not only form the basis of modern thermodynamics and statistical physics, but have also been at the core of various philosophical discussions concerned with the evolution of the world, the course of time, etc. There is a general agreement on how the entropy of a nonequilibrium system should evolve, postulated by the second law of thermodynamics. At the same time, the question how entropy production changes with time is still extensively discussed. So-called the maximum entropy production principle (MEPP) 1 , 2 , 3 was proposed in the middle of 20 th century 4 , 5 , 6 , 7 and may be viewed as the natural generalization of the Clausius-Boltzmann-Gibbs formulation of the second law. According to MEPP, a nonequilibrium system evolves such as to maximize its entropy production under present constraints. Proponents of this principle demonstrated that it can be used as a powerful tool to solve various environmental 8 , 9 , 10 , biological 11 , 12 and physical problems 13 , 14 , 15 , 16 . It is interesting to notice that there are publications attempting to disprove MEPP 17 , 18 , 19 , 20 , 21 , 22 . However, the most recent review 23 argues that all these claims seemingly disproving MEPP are based on experiments, which do not belong to the sphere of applicability of the principle. Frequently, thermodynamic systems driven out of equilibrium have a tendency for symmetry breaking. This includes pattern formation 24 , spontaneous self-assembly of particles either dispersed in colloids 25 , 26 , 27 , suspended at the air-fluid 28 , 29 or fluid-fluid interfaces 30 . One of the best-known examples of symmetry breaking is the emergence of Rayleigh–Bénard (RB) convection cells 31 in a layer of oil placed on a hot plate. Ordering that is present in the RB cells reduces the oil entropy. At the same time, convective flows associated with the RB structures increase the heat transfer rate, leading to a greater entropy production of the entire system, which includes the hot plate and the environment. It is unclear under which conditions nonequilibrium systems develop a new order. Yet, it is plausible to hypothesize that MEPP might be one of the main guiding principles for not only the evolution of biological species, but their appearance on Earth due to the strongly nonequilibrium energy distribution created by the Sun 32 , 33 . Nonequilibrium conditions occur because the Sun supplies photons with energies of many thousands of Kelvins, which is much larger than the temperature of the surface of the Earth. Taking into account these facts, we believe that investigations of the MEPP applicability for self-organizing systems is a very promising direction of research, from the viewpoint of both the substantiation of the MEPP and for better understanding and predicting behavioral and evolutionary trends in nonequilibrium systems. In this work, we investigate possible evolution paths of an electrorheological (ER) fluid 34 exposed to a strong electric field (E-field) towards an attractor state. Our setup provides means to study nonequilibrium processes quantitatively . In particular, it enables precise measurements of generated Joule heating (the precision is limited by a very small and uncertain fraction of internal work done by the voltage source that is used to create order in the system of nanotubes). As a result, entropy production in the fluid, which is directly proportional to the Joule heating, can be correlated with the process of self-assembly of carbon nanotube (CNT) chains occurring under the effect of the applied E-field 35 , 36 , 37 , 38 , 39 . We demonstrate that in such complex systems as ER fluids the state with maximum entropy production acts as an attractor. Results When the ER fluid is driven far from equilibrium by a strong E-field, it may exhibit a spontaneous collective behavior, such as emergence of avalanches and chain formation. Previous studies were suggestive that these processes lead to maximization of the entropy production rate 40 . Here we use a different suspension of conducting particles and observe that the ER fluid evolves towards quasi-stable states characterized by the maximum (or near-maximum) rate of entropy increase in a wide range of excitation parameters. The evolution usually proceeds in two phases: an “avalanche” phase followed by a “stable” phase, which onsets when the entropy generation reaches its pre-determined maximum. We discovered that close to the end of the avalanche phase self-assembled dissipative structures can start to wiggle, i.e. exhibit quasi-periodic motion and deformation (for the video containing details see the supplementary online material ). Due to a visual resemblance to a living organism, we term such states", "role": "user" }, { "content": "The second law of thermodynamics tells us that all systems evolve toward a state of maximum entropy, wherein all energy is dissipated as heat, and no available energy remains to do work. Since the mid-20th century, research has pointed to an extension of the second law for nonequilibrium systems: the Maximum Entropy Production Principle (MEPP) states that a system away from equilibrium evolves in such a way as to maximize entropy production, given present constraints. Now, physicists Alexey Bezryadin, Alfred Hubler, and Andrey Belkin from the University of Illinois at Urbana-Champaign, have demonstrated the emergence of self-organized structures that drive the evolution of a non-equilibrium system to a state of maximum entropy production. The authors suggest MEPP underlies the evolution of the artificial system's self-organization, in the same way that it underlies the evolution of ordered systems (biological life) on Earth. The team's results are published in Nature Publishing Group's online journal Scientific Reports. MEPP may have profound implications for our understanding of the evolution of biological life on Earth and of the underlying rules that govern the behavior and evolution of all nonequilibrium systems. Life emerged on Earth from the strongly nonequilibrium energy distribution created by the Sun's hot photons striking a cooler planet. Plants evolved to capture high energy photons and produce heat, generating entropy. Then animals evolved to eat plants increasing the dissipation of heat energy and maximizing entropy production. In their experiment, the researchers suspended a large number of carbon nanotubes in a non-conducting non-polar fluid and drove the system out of equilibrium by applying a strong electric field. Once electrically charged, the system evolved toward maximum entropy through two distinct intermediate states, with the spontaneous emergence of self-assembled conducting nanotube chains. In the first state, the \"avalanche\" regime, the conductive chains aligned themselves according to the polarity of the applied voltage, allowing the system to carry current and thus to dissipate heat and produce entropy. The chains appeared to sprout appendages as nanotubes aligned themselves so as to adjoin adjacent parallel chains, effectively increasing entropy production. But frequently, this self-organization was destroyed through avalanches triggered by the heating and charging that emanates from the emerging electric current streams. Carbon nanotube cloud becomes \"alive\" in strong electric field. This experiment was done by A. Belkin and A. Bezryadin in collaboration with A. Hubler. Credit: University of Illinois at Urbana-Champaign \"The avalanches were apparent in the changes of the electric current over time,\" said Bezryadin. Following avalanches, the chains with their appendages \"wiggled,\" resembling a living thing, similar to an insect. \"Toward the final stages of this regime, the appendages were not destroyed during the avalanches, but rather retracted until the avalanche ended, then reformed their connection. So it was obvious that the avalanches correspond to the 'feeding cycle' of the 'nanotube inset',\" comments Bezryadin. In the second relatively stable stage of evolution, the entropy production rate reached maximum or near maximum. This state is quasi-stable in that there were no destructive avalanches. The study points to a possible classification scheme for evolutionary stages and a criterium for the point at which evolution of the system is irreversible—wherein entropy production in the self-organizing subsystem reaches its maximum possible value. Further experimentation on a larger scale is necessary to affirm these underlying principals, but if they hold true, they will prove a great advantage in predicting behavioral and evolutionary trends in nonequilibrium systems. The authors draw an analogy between the evolution of intelligent life forms on Earth and the emergence of the wiggling bugs in their experiment. The researchers note that further quantitative studies are needed to round out this comparison. In particular, they would need to demonstrate that their \"wiggling bugs\" can multiply, which would require the experiment be reproduced on a significantly larger scale. Such a study, if successful, would have implications for the eventual development of technologies that feature self-organized artificial intelligence, an idea explored elsewhere by co-author Alfred Hubler, funded by the Defense Advanced Research Projects Agency. \"The general trend of the evolution of biological systems seems to be this: more advanced life forms tend to dissipate more energy by broadening their access to various forms of stored energy,\" Bezryadin proposes. \"Thus a common underlying principle can be suggested between our self-organized clouds of nanotubes, which generate more and more heat by reducing their electrical resistance and thus allow more current to flow, and the biological systems which look for new means to find food, either through biological adaptation or by inventing more technologies. \"Extended sources of food allow biological forms to further grow, multiply, consume more food and thus produce more heat and generate entropy. It seems reasonable to say that real life organisms are still far from the absolute maximum of the entropy production rate. In both cases, there are 'avalanches' or 'extinction events', which set back this evolution. Only if all free energy given by the Sun is consumed, by building a Dyson sphere for example, and converted into heat then a definitely stable phase of the evolution can be expected.\" \"Intelligence, as far as we know, is inseparable from life,\" he adds. \"Thus, to achieve artificial life or artificial intelligence, our recommendation would be to study systems which are far from equilibrium, with many degrees of freedom—many building blocks—so that they can self-organize and participate in some evolution. The entropy production criterium appears to be the guiding principle of the evolution efficiency.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract While behavior of equilibrium systems is well understood, evolution of nonequilibrium ones is much less clear. Yet, many researches have suggested that the principle of the maximum entropy production is of key importance in complex systems away from equilibrium. Here, we present a quantitative study of large ensembles of carbon nanotubes suspended in a non-conducting non-polar fluid subject to a strong electric field. Being driven out of equilibrium, the suspension spontaneously organizes into an electrically conducting state under a wide range of parameters. Such self-assembly allows the Joule heating and, therefore, the entropy production in the fluid, to be maximized. Curiously, we find that emerging self-assembled structures can start to wiggle. The wiggling takes place only until the entropy production in the suspension reaches its maximum, at which time the wiggling stops and the structure becomes quasi-stable. Thus, we provide strong evidence that maximum entropy production principle plays an essential role in the evolution of self-organizing systems far from equilibrium. Introduction Classical thermodynamics offers elaborated theoretical instruments to study behavior of systems that are in or near equilibrium. But often objects and processes which we deal with in everyday life, such as living biological organisms or weather events, are far from equilibrium. Therefore, the search for principia governing nonequilibrium systems is of great interest. The notion of entropy in equilibrium states and its production in nonequilibrium processes not only form the basis of modern thermodynamics and statistical physics, but have also been at the core of various philosophical discussions concerned with the evolution of the world, the course of time, etc. There is a general agreement on how the entropy of a nonequilibrium system should evolve, postulated by the second law of thermodynamics. At the same time, the question how entropy production changes with time is still extensively discussed. So-called the maximum entropy production principle (MEPP) 1 , 2 , 3 was proposed in the middle of 20 th century 4 , 5 , 6 , 7 and may be viewed as the natural generalization of the Clausius-Boltzmann-Gibbs formulation of the second law. According to MEPP, a nonequilibrium system evolves such as to maximize its entropy production under present constraints. Proponents of this principle demonstrated that it can be used as a powerful tool to solve various environmental 8 , 9 , 10 , biological 11 , 12 and physical problems 13 , 14 , 15 , 16 . It is interesting to notice that there are publications attempting to disprove MEPP 17 , 18 , 19 , 20 , 21 , 22 . However, the most recent review 23 argues that all these claims seemingly disproving MEPP are based on experiments, which do not belong to the sphere of applicability of the principle. Frequently, thermodynamic systems driven out of equilibrium have a tendency for symmetry breaking. This includes pattern formation 24 , spontaneous self-assembly of particles either dispersed in colloids 25 , 26 , 27 , suspended at the air-fluid 28 , 29 or fluid-fluid interfaces 30 . One of the best-known examples of symmetry breaking is the emergence of Rayleigh–Bénard (RB) convection cells 31 in a layer of oil placed on a hot plate. Ordering that is present in the RB cells reduces the oil entropy. At the same time, convective flows associated with the RB structures increase the heat transfer rate, leading to a greater entropy production of the entire system, which includes the hot plate and the environment. It is unclear under which conditions nonequilibrium systems develop a new order. Yet, it is plausible to hypothesize that MEPP might be one of the main guiding principles for not only the evolution of biological species, but their appearance on Earth due to the strongly nonequilibrium energy distribution created by the Sun 32 , 33 . Nonequilibrium conditions occur because the Sun supplies photons with energies of many thousands of Kelvins, which is much larger than the temperature of the surface of the Earth. Taking into account these facts, we believe that investigations of the MEPP applicability for self-organizing systems is a very promising direction of research, from the viewpoint of both the substantiation of the MEPP and for better understanding and predicting behavioral and evolutionary trends in nonequilibrium systems. In this work, we investigate possible evolution paths of an electrorheological (ER) fluid 34 exposed to a strong electric field (E-field) towards an attractor state. Our setup provides means to study nonequilibrium processes quantitatively . In particular, it enables precise measurements of generated Joule heating (the precision is limited by a very small and uncertain fraction of internal work done by the voltage source that is used to create order in the system of nanotubes). As a result, entropy production in the fluid, which is directly proportional to the Joule heating, can be correlated with the process of self-assembly of carbon nanotube (CNT) chains occurring under the effect of the applied E-field 35 , 36 , 37 , 38 , 39 . We demonstrate that in such complex systems as ER fluids the state with maximum entropy production acts as an attractor. Results When the ER fluid is driven far from equilibrium by a strong E-field, it may exhibit a spontaneous collective behavior, such as emergence of avalanches and chain formation. Previous studies were suggestive that these processes lead to maximization of the entropy production rate 40 . Here we use a different suspension of conducting particles and observe that the ER fluid evolves towards quasi-stable states characterized by the maximum (or near-maximum) rate of entropy increase in a wide range of excitation parameters. The evolution usually proceeds in two phases: an “avalanche” phase followed by a “stable” phase, which onsets when the entropy generation reaches its pre-determined maximum. We discovered that close to the end of the avalanche phase self-assembled dissipative structures can start to wiggle, i.e. exhibit quasi-periodic motion and deformation (for the video containing details see the supplementary online material ). Due to a visual resemblance to a living organism, we term such states<|im_end|> <|im_start|>assistant The second law of thermodynamics tells us that all systems evolve toward a state of maximum entropy, wherein all energy is dissipated as heat, and no available energy remains to do work. Since the mid-20th century, research has pointed to an extension of the second law for nonequilibrium systems: the Maximum Entropy Production Principle (MEPP) states that a system away from equilibrium evolves in such a way as to maximize entropy production, given present constraints. Now, physicists Alexey Bezryadin, Alfred Hubler, and Andrey Belkin from the University of Illinois at Urbana-Champaign, have demonstrated the emergence of self-organized structures that drive the evolution of a non-equilibrium system to a state of maximum entropy production. The authors suggest MEPP underlies the evolution of the artificial system's self-organization, in the same way that it underlies the evolution of ordered systems (biological life) on Earth. The team's results are published in Nature Publishing Group's online journal Scientific Reports. MEPP may have profound implications for our understanding of the evolution of biological life on Earth and of the underlying rules that govern the behavior and evolution of all nonequilibrium systems. Life emerged on Earth from the strongly nonequilibrium energy distribution created by the Sun's hot photons striking a cooler planet. Plants evolved to capture high energy photons and produce heat, generating entropy. Then animals evolved to eat plants increasing the dissipation of heat energy and maximizing entropy production. In their experiment, the researchers suspended a large number of carbon nanotubes in a non-conducting non-polar fluid and drove the system out of equilibrium by applying a strong electric field. Once electrically charged, the system evolved toward maximum entropy through two distinct intermediate states, with the spontaneous emergence of self-assembled conducting nanotube chains. In the first state, the "avalanche" regime, the conductive chains aligned themselves according to the polarity of the applied voltage, allowing the system to carry current and thus to dissipate heat and produce entropy. The chains appeared to sprout appendages as nanotubes aligned themselves so as to adjoin adjacent parallel chains, effectively increasing entropy production. But frequently, this self-organization was destroyed through avalanches triggered by the heating and charging that emanates from the emerging electric current streams. Carbon nanotube cloud becomes "alive" in strong electric field. This experiment was done by A. Belkin and A. Bezryadin in collaboration with A. Hubler. Credit: University of Illinois at Urbana-Champaign "The avalanches were apparent in the changes of the electric current over time," said Bezryadin. Following avalanches, the chains with their appendages "wiggled," resembling a living thing, similar to an insect. "Toward the final stages of this regime, the appendages were not destroyed during the avalanches, but rather retracted until the avalanche ended, then reformed their connection. So it was obvious that the avalanches correspond to the 'feeding cycle' of the 'nanotube inset'," comments Bezryadin. In the second relatively stable stage of evolution, the entropy production rate reached maximum or near maximum. This state is quasi-stable in that there were no destructive avalanches. The study points to a possible classification scheme for evolutionary stages and a criterium for the point at which evolution of the system is irreversible—wherein entropy production in the self-organizing subsystem reaches its maximum possible value. Further experimentation on a larger scale is necessary to affirm these underlying principals, but if they hold true, they will prove a great advantage in predicting behavioral and evolutionary trends in nonequilibrium systems. The authors draw an analogy between the evolution of intelligent life forms on Earth and the emergence of the wiggling bugs in their experiment. The researchers note that further quantitative studies are needed to round out this comparison. In particular, they would need to demonstrate that their "wiggling bugs" can multiply, which would require the experiment be reproduced on a significantly larger scale. Such a study, if successful, would have implications for the eventual development of technologies that feature self-organized artificial intelligence, an idea explored elsewhere by co-author Alfred Hubler, funded by the Defense Advanced Research Projects Agency. "The general trend of the evolution of biological systems seems to be this: more advanced life forms tend to dissipate more energy by broadening their access to various forms of stored energy," Bezryadin proposes. "Thus a common underlying principle can be suggested between our self-organized clouds of nanotubes, which generate more and more heat by reducing their electrical resistance and thus allow more current to flow, and the biological systems which look for new means to find food, either through biological adaptation or by inventing more technologies. "Extended sources of food allow biological forms to further grow, multiply, consume more food and thus produce more heat and generate entropy. It seems reasonable to say that real life organisms are still far from the absolute maximum of the entropy production rate. In both cases, there are 'avalanches' or 'extinction events', which set back this evolution. Only if all free energy given by the Sun is consumed, by building a Dyson sphere for example, and converted into heat then a definitely stable phase of the evolution can be expected." "Intelligence, as far as we know, is inseparable from life," he adds. "Thus, to achieve artificial life or artificial intelligence, our recommendation would be to study systems which are far from equilibrium, with many degrees of freedom—many building blocks—so that they can self-organize and participate in some evolution. The entropy production criterium appears to be the guiding principle of the evolution efficiency." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Laser diodes are efficient light sources. However, state-of-the-art laser diode-based lighting systems rely on light-converting inorganic phosphor materials, which strongly limit the efficiency and lifetime, as well as achievable light output due to energy losses, saturation, thermal degradation, and low irradiance levels. Here, we demonstrate a macroscopically expanded, three-dimensional diffuser composed of interconnected hollow hexagonal boron nitride microtubes with nanoscopic wall-thickness, acting as an artificial solid fog, capable of withstanding ~10 times the irradiance level of remote phosphors. In contrast to phosphors, no light conversion is required as the diffuser relies solely on strong broadband (full visible range) lossless multiple light scattering events, enabled by a highly porous (>99.99%) non-absorbing nanoarchitecture, resulting in efficiencies of ~98%. This can unleash the potential of lasers for high-brightness lighting applications, such as automotive headlights, projection technology or lighting for large spaces. Introduction Solid-state lighting (SSL) is defined as light emitted by solid-state electroluminescence 1 . Its current power efficiency, i.e., the optical output power of the SSL device per unit input electrical power 2 , is ~70% and there is no fundamental physical reason why efficiencies well beyond 70% could not be reached 2 , 3 , 4 . SSL is thus expected to replace all conventional light sources by 2035 5 , including halogen, xenon, incandescent, and fluorescent lamps 4 , 6 , 7 , 8 . At present, light emitting diodes (LEDs) are the most efficient devices for white-light generation 2 , 3 , 6 . Their adoption is predicted to achieve a 75% reduction of energy consumption for lighting by 2035 5 in the US alone, which would result in a total energy saving of 6.75 × 10 16 TJ (equivalent to nearly $630 billion in avoided energy costs) and thus drastically reduce greenhouse emission worldwide 5 . However, the so-called “efficiency droop” still limits the operation of LEDs to very low input power densities, with current densities ~0.01 kA cm −2 2 , 9 . Consequently, for a higher light output the physical size of a LED has to be increased. In contrast to LEDs, laser diodes (LDs) can be operated at much higher current densities (>10 kA cm −2 ), with peak efficiencies close to that of LEDs 2 . This results in a higher light output per unit area, e.g., a 0.1 mm 2 LD source can produce the same amount of light as a 1 cm 2 LED. Hence, the target to generate more photons at high-power densities (kW cm −2 ) and decrease the cost per lumen can only be satisfied by using LDs 2 , 4 , 8 . State-of-the-art LD-based lighting devices exploit a blue LD pumping, e.g., a yellow-light emitting phosphor, resulting in white light (Fig. 1a ) 2 , 4 . However, the performance of such systems is strongly limited by the properties of the phosphor. The efficiency of state-of-the-art light emitting phosphors, such as doped yttrium-aluminum-garnet, is mainly determined by two types of energy losses, the stokes shift (~80% efficiency) and the photoluminescence quantum yield (~90%) 10 . Both these loss mechanisms scale with temperature 10 (e.g., as a result of illumination) and therefore phosphor luminescence suffers from saturation 10 , aging 11 , and thermal quenching 10 , limiting the irradiance to ~5 kW cm −2 and thus the overall light output. Even though new concepts such as glass encapsulation 12 , 13 , phosphor monoliths 14 , or composite ceramic phosphors 15 , 16 , 17 can increase the irradiance level up to ~10–20 kW cm −2 , the true potential of lasers for high-brightness lighting applications, with possible light outputs of several MW cm −2 , still remains unemployed. Fig. 1: Schematics of laser-based lighting concepts. a White-light generation by employing a remote phosphor that converts a part of the blue laser light into yellow light resulting in white light. b White-light generation based on an artificial solid fog in combination with an R+G+B laser system. A macroscopically expanded porous (>99.99%) network of interconnected and hollow hBN microtubes with nanoscopic wall thickness is used to convert directed laser light into an isotropic high-brightness white light source, exploiting multiple light scattering. c Schematic comparison of efficiencies of both systems. In the case of remote phosphor, light conversion results in a strong efficiency reduction, whereas the negligible absorption and conversionless light-scattering properties of the hBN foam allow for almost zero losses in light intensity. Full size image Here, we demonstrate a tunable, disordered, cubic centimetre-sized ceramic nanoarchitecture as an efficient (> 98%) broadband (> 450–640 nm) diffuser, that in combination with a RGB (red-green-blue) laser system (Fig. 1b ), is an alternative to the conventional used phosphors with a single laser (Fig. 1a ). The diffuser withstands ~10 times the irradiance level achievable by state-of-the-art phosphors, enabling a lighting system whose efficiency is mainly determined by that of the LDs used, due to the lack of any conversion effects (Fig. 1c ). The concept is based on a highly porous (> 99.99), macroscopic, and translucent network of randomly arranged and interconnected hexagonal boron nitride (hBN) hollow microtubes, that we call Aero-BN. The material acts like an artificial solid fog, but with a defined hierarchical internal structure - a combination of well separated feature sizes greater than, equal to, as well as below the magnitude of the impinging wavelength. The Aero-BN diffuser enables an isotropic light distribution from a multitude of coherent laser light sources at the same time, while simultaneously reducing speckle contrast to values well below the detection limit of the human eye (< 4%) 18 . Especially the latter is a strict requirement for LD-based lighting, that is not met by today’s commercially available diffuser systems (Supplementary Note 1 and Supplementary Table 1 ). Even though the current state of LD technology - with laser efficiencies < 20% for green 19 and < 40% for blue 2 , 19 - is still limiting the application of LD-based lighting systems, fast progress in the development of more", "role": "user" }, { "content": "With a porosity of 99.99 %, it consists practically only of air, making it one of the lightest materials in the world: Aerobornitride is the name of the material developed by an international research team led by Kiel University. The scientists assume that they have thereby created a central basis for bringing laser light into a broad application range. Based on a boron-nitrogen compound, they developed a special three-dimensional nanostructure that scatters light very strongly and hardly absorbs it. Irradiated with a laser, the material emits uniform lighting, which, depending on the type of laser, is much more efficient and powerful than LED light. Thus, lamps for car headlights, projectors or room lighting with laser light could become smaller and brighter in the future. The research team presents their results in the current issue of the renowned journal Nature Communications, which was published today. More light in the smallest space In research and industry, laser light has long been considered the \"next generation\" of light sources that could even exceed the efficiency of LEDs (light-emitting diode). \"For very bright or a lot of light, you need a large number of LEDs and thus space. But the same amount of light could also be obtained with a single laser diode that is one-thousandth smaller,\" Dr. Fabian Schütt emphasizes the potential. The materials scientist from the working group \"Functional Nanomaterials\" at Kiel University is the first author of the study, which involves other researchers from Germany, England, Italy, Denmark and South Korea. Powerful small light sources allow numerous applications. The first test applications, such as in car headlights, are already available, but laser lamps have not yet become widely accepted. On the one hand, this is due to the intense, directed light of the laser diodes. On the other hand, the light consists of only one wavelength, so it is monochromatic. This leads to an unpleasant flickering when a laser beam hits a surface and is reflected there. Bornitride, on which the new light material is based, is also called \"white graphene\" because of its similar atomic structure. Credit: Julia Siekmann, CAU Porous structure scatters the light extremely strongly \"Previous developments to laser light normally work with phosphors. However, they produce a relatively cold light, are not stable in the long term and are not very efficient,\" says Professor Rainer Adelung, head of the working group. The research team in Kiel is taking a different approach: They developed a highly scattering nanostructure of hexagonal boron nitride, also known as \"white graphene,\" which absorbs almost no light. The structure consists of a filigree network of countless fine hollow microtubes. When a laser beam hits these, it is extremely scattered inside the network structure, creating a homogeneous light source. \"Our material acts more or less like an artificial fog that produces a uniform, pleasant light output,\" explains Schütt. The strong scattering also contributes to the fact that the disturbing flickering is no longer visible to the human eye. The nanostructure not only ensures that the material withstands the intense laser light, but can also scatter different wavelengths. Red, green and blue laser light can be mixed in order to create specific color effects in addition to normal white—for example, for use in innovative room lighting. Here, extremely lightweight laser diodes could lead to completely new design concepts in the future. \"However, in order to compete with LEDs in the future, the efficiency of laser diodes must be improved as well,\" says Schütt. The research team is now looking for industrial partners to take the step from the laboratory to application. Within the fine network of hollow tubes measuring only a few micrometers in size incident laser beams are so strongly scattered that a homogeneous white light is produced. Credit: Kiel University Due to its inner structure, the material can scatter different wavelengths, i.e. green, red and blue laser light. Credit: Fabian Schütt Wide range of applications for aeromaterials Meanwhile the researchers from Kiel can use their method to develop highly porous nanostructures for different materials, besides boron nitride also graphene or graphite. In this way, more and more new, lightweight materials, so-called \"aeromaterials,\" are created, which allow particularly innovative applications. For example, the scientists are currently doing research in collaboration with companies and other universities to develop self-cleaning air filters for aircraft. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Laser diodes are efficient light sources. However, state-of-the-art laser diode-based lighting systems rely on light-converting inorganic phosphor materials, which strongly limit the efficiency and lifetime, as well as achievable light output due to energy losses, saturation, thermal degradation, and low irradiance levels. Here, we demonstrate a macroscopically expanded, three-dimensional diffuser composed of interconnected hollow hexagonal boron nitride microtubes with nanoscopic wall-thickness, acting as an artificial solid fog, capable of withstanding ~10 times the irradiance level of remote phosphors. In contrast to phosphors, no light conversion is required as the diffuser relies solely on strong broadband (full visible range) lossless multiple light scattering events, enabled by a highly porous (>99.99%) non-absorbing nanoarchitecture, resulting in efficiencies of ~98%. This can unleash the potential of lasers for high-brightness lighting applications, such as automotive headlights, projection technology or lighting for large spaces. Introduction Solid-state lighting (SSL) is defined as light emitted by solid-state electroluminescence 1 . Its current power efficiency, i.e., the optical output power of the SSL device per unit input electrical power 2 , is ~70% and there is no fundamental physical reason why efficiencies well beyond 70% could not be reached 2 , 3 , 4 . SSL is thus expected to replace all conventional light sources by 2035 5 , including halogen, xenon, incandescent, and fluorescent lamps 4 , 6 , 7 , 8 . At present, light emitting diodes (LEDs) are the most efficient devices for white-light generation 2 , 3 , 6 . Their adoption is predicted to achieve a 75% reduction of energy consumption for lighting by 2035 5 in the US alone, which would result in a total energy saving of 6.75 × 10 16 TJ (equivalent to nearly $630 billion in avoided energy costs) and thus drastically reduce greenhouse emission worldwide 5 . However, the so-called “efficiency droop” still limits the operation of LEDs to very low input power densities, with current densities ~0.01 kA cm −2 2 , 9 . Consequently, for a higher light output the physical size of a LED has to be increased. In contrast to LEDs, laser diodes (LDs) can be operated at much higher current densities (>10 kA cm −2 ), with peak efficiencies close to that of LEDs 2 . This results in a higher light output per unit area, e.g., a 0.1 mm 2 LD source can produce the same amount of light as a 1 cm 2 LED. Hence, the target to generate more photons at high-power densities (kW cm −2 ) and decrease the cost per lumen can only be satisfied by using LDs 2 , 4 , 8 . State-of-the-art LD-based lighting devices exploit a blue LD pumping, e.g., a yellow-light emitting phosphor, resulting in white light (Fig. 1a ) 2 , 4 . However, the performance of such systems is strongly limited by the properties of the phosphor. The efficiency of state-of-the-art light emitting phosphors, such as doped yttrium-aluminum-garnet, is mainly determined by two types of energy losses, the stokes shift (~80% efficiency) and the photoluminescence quantum yield (~90%) 10 . Both these loss mechanisms scale with temperature 10 (e.g., as a result of illumination) and therefore phosphor luminescence suffers from saturation 10 , aging 11 , and thermal quenching 10 , limiting the irradiance to ~5 kW cm −2 and thus the overall light output. Even though new concepts such as glass encapsulation 12 , 13 , phosphor monoliths 14 , or composite ceramic phosphors 15 , 16 , 17 can increase the irradiance level up to ~10–20 kW cm −2 , the true potential of lasers for high-brightness lighting applications, with possible light outputs of several MW cm −2 , still remains unemployed. Fig. 1: Schematics of laser-based lighting concepts. a White-light generation by employing a remote phosphor that converts a part of the blue laser light into yellow light resulting in white light. b White-light generation based on an artificial solid fog in combination with an R+G+B laser system. A macroscopically expanded porous (>99.99%) network of interconnected and hollow hBN microtubes with nanoscopic wall thickness is used to convert directed laser light into an isotropic high-brightness white light source, exploiting multiple light scattering. c Schematic comparison of efficiencies of both systems. In the case of remote phosphor, light conversion results in a strong efficiency reduction, whereas the negligible absorption and conversionless light-scattering properties of the hBN foam allow for almost zero losses in light intensity. Full size image Here, we demonstrate a tunable, disordered, cubic centimetre-sized ceramic nanoarchitecture as an efficient (> 98%) broadband (> 450–640 nm) diffuser, that in combination with a RGB (red-green-blue) laser system (Fig. 1b ), is an alternative to the conventional used phosphors with a single laser (Fig. 1a ). The diffuser withstands ~10 times the irradiance level achievable by state-of-the-art phosphors, enabling a lighting system whose efficiency is mainly determined by that of the LDs used, due to the lack of any conversion effects (Fig. 1c ). The concept is based on a highly porous (> 99.99), macroscopic, and translucent network of randomly arranged and interconnected hexagonal boron nitride (hBN) hollow microtubes, that we call Aero-BN. The material acts like an artificial solid fog, but with a defined hierarchical internal structure - a combination of well separated feature sizes greater than, equal to, as well as below the magnitude of the impinging wavelength. The Aero-BN diffuser enables an isotropic light distribution from a multitude of coherent laser light sources at the same time, while simultaneously reducing speckle contrast to values well below the detection limit of the human eye (< 4%) 18 . Especially the latter is a strict requirement for LD-based lighting, that is not met by today’s commercially available diffuser systems (Supplementary Note 1 and Supplementary Table 1 ). Even though the current state of LD technology - with laser efficiencies < 20% for green 19 and < 40% for blue 2 , 19 - is still limiting the application of LD-based lighting systems, fast progress in the development of more<|im_end|> <|im_start|>assistant With a porosity of 99.99 %, it consists practically only of air, making it one of the lightest materials in the world: Aerobornitride is the name of the material developed by an international research team led by Kiel University. The scientists assume that they have thereby created a central basis for bringing laser light into a broad application range. Based on a boron-nitrogen compound, they developed a special three-dimensional nanostructure that scatters light very strongly and hardly absorbs it. Irradiated with a laser, the material emits uniform lighting, which, depending on the type of laser, is much more efficient and powerful than LED light. Thus, lamps for car headlights, projectors or room lighting with laser light could become smaller and brighter in the future. The research team presents their results in the current issue of the renowned journal Nature Communications, which was published today. More light in the smallest space In research and industry, laser light has long been considered the "next generation" of light sources that could even exceed the efficiency of LEDs (light-emitting diode). "For very bright or a lot of light, you need a large number of LEDs and thus space. But the same amount of light could also be obtained with a single laser diode that is one-thousandth smaller," Dr. Fabian Schütt emphasizes the potential. The materials scientist from the working group "Functional Nanomaterials" at Kiel University is the first author of the study, which involves other researchers from Germany, England, Italy, Denmark and South Korea. Powerful small light sources allow numerous applications. The first test applications, such as in car headlights, are already available, but laser lamps have not yet become widely accepted. On the one hand, this is due to the intense, directed light of the laser diodes. On the other hand, the light consists of only one wavelength, so it is monochromatic. This leads to an unpleasant flickering when a laser beam hits a surface and is reflected there. Bornitride, on which the new light material is based, is also called "white graphene" because of its similar atomic structure. Credit: Julia Siekmann, CAU Porous structure scatters the light extremely strongly "Previous developments to laser light normally work with phosphors. However, they produce a relatively cold light, are not stable in the long term and are not very efficient," says Professor Rainer Adelung, head of the working group. The research team in Kiel is taking a different approach: They developed a highly scattering nanostructure of hexagonal boron nitride, also known as "white graphene," which absorbs almost no light. The structure consists of a filigree network of countless fine hollow microtubes. When a laser beam hits these, it is extremely scattered inside the network structure, creating a homogeneous light source. "Our material acts more or less like an artificial fog that produces a uniform, pleasant light output," explains Schütt. The strong scattering also contributes to the fact that the disturbing flickering is no longer visible to the human eye. The nanostructure not only ensures that the material withstands the intense laser light, but can also scatter different wavelengths. Red, green and blue laser light can be mixed in order to create specific color effects in addition to normal white—for example, for use in innovative room lighting. Here, extremely lightweight laser diodes could lead to completely new design concepts in the future. "However, in order to compete with LEDs in the future, the efficiency of laser diodes must be improved as well," says Schütt. The research team is now looking for industrial partners to take the step from the laboratory to application. Within the fine network of hollow tubes measuring only a few micrometers in size incident laser beams are so strongly scattered that a homogeneous white light is produced. Credit: Kiel University Due to its inner structure, the material can scatter different wavelengths, i.e. green, red and blue laser light. Credit: Fabian Schütt Wide range of applications for aeromaterials Meanwhile the researchers from Kiel can use their method to develop highly porous nanostructures for different materials, besides boron nitride also graphene or graphite. In this way, more and more new, lightweight materials, so-called "aeromaterials," are created, which allow particularly innovative applications. For example, the scientists are currently doing research in collaboration with companies and other universities to develop self-cleaning air filters for aircraft. <|im_end|>

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71, 15967, 8, 42902, 8162, 83, 51725, 11, 430, 584, 1650, 89523, 7826, 45, 13, 578, 3769, 14385, 1093, 459, 21075, 6573, 31349, 11, 719, 449, 264, 4613, 70994, 5419, 6070, 482, 264, 10824, 315, 1664, 19180, 4668, 12562, 7191, 1109, 11, 6273, 311, 11, 439, 1664, 439, 3770, 279, 26703, 315, 279, 3242, 24992, 46406, 13, 578, 89523, 7826, 45, 3722, 882, 20682, 459, 69551, 45036, 3177, 8141, 505, 264, 49068, 315, 56887, 21120, 3177, 8336, 520, 279, 1890, 892, 11, 1418, 25291, 18189, 2395, 377, 273, 13168, 311, 2819, 1664, 3770, 279, 18468, 4017, 315, 279, 3823, 8071, 23246, 220, 19, 11587, 220, 972, 662, 36625, 279, 15629, 374, 264, 7452, 16686, 369, 29977, 6108, 18186, 11, 430, 374, 539, 2322, 555, 3432, 753, 54453, 2561, 3722, 882, 6067, 320, 10254, 67082, 7181, 220, 16, 323, 99371, 6771, 220, 16, 7609, 7570, 3582, 279, 1510, 1614, 315, 29977, 5557, 482, 449, 21120, 92126, 366, 220, 508, 4, 369, 6307, 220, 777, 323, 366, 220, 1272, 4, 369, 6437, 220, 17, 1174, 220, 777, 482, 374, 2103, 33994, 279, 3851, 315, 29977, 6108, 18186, 6067, 11, 5043, 5208, 304, 279, 4500, 315, 810, 128257, 198, 128256, 78191, 198, 2409, 264, 4247, 22828, 315, 220, 1484, 13, 1484, 127036, 433, 17610, 32367, 1193, 315, 3805, 11, 3339, 433, 832, 315, 279, 3177, 478, 7384, 304, 279, 1917, 25, 64150, 677, 1540, 275, 1425, 374, 279, 836, 315, 279, 3769, 8040, 555, 459, 6625, 3495, 2128, 6197, 555, 735, 13327, 3907, 13, 578, 14248, 9855, 430, 814, 617, 28592, 3549, 264, 8792, 8197, 369, 12967, 21120, 3177, 1139, 264, 7353, 3851, 2134, 13, 20817, 389, 264, 32732, 263, 5392, 275, 26252, 24549, 11, 814, 8040, 264, 3361, 2380, 33520, 51593, 7993, 430, 1156, 10385, 3177, 1633, 16917, 323, 20781, 91111, 433, 13, 79141, 2836, 660, 449, 264, 21120, 11, 279, 3769, 73880, 14113, 18186, 11, 902, 11, 11911, 389, 279, 955, 315, 21120, 11, 374, 1790, 810, 11297, 323, 8147, 1109, 13414, 3177, 13, 14636, 11, 50552, 369, 1841, 88720, 11, 2447, 1105, 477, 3130, 18186, 449, 21120, 3177, 1436, 3719, 9333, 323, 53657, 304, 279, 3938, 13, 578, 3495, 2128, 18911, 872, 3135, 304, 279, 1510, 4360, 315, 279, 37048, 8486, 22037, 26545, 11, 902, 574, 4756, 3432, 13, 4497, 3177, 304, 279, 25655, 3634, 763, 3495, 323, 5064, 11, 21120, 3177, 706, 1317, 1027, 6646, 279, 330, 3684, 9659, 1, 315, 3177, 8336, 430, 1436, 1524, 12771, 279, 15374, 315, 56672, 320, 4238, 37612, 15154, 1891, 536, 570, 330, 2520, 1633, 10107, 477, 264, 2763, 315, 3177, 11, 499, 1205, 264, 3544, 1396, 315, 56672, 323, 8617, 3634, 13, 2030, 279, 1890, 3392, 315, 3177, 1436, 1101, 387, 12457, 449, 264, 3254, 21120, 1891, 536, 430, 374, 832, 7716, 52949, 339, 9333, 1359, 2999, 13, 19797, 1122, 5124, 2448, 5683, 66159, 279, 4754, 13, 578, 7384, 28568, 505, 279, 3318, 1912, 330, 72371, 33242, 316, 2229, 82, 1, 520, 735, 13327, 3907, 374, 279, 1176, 3229, 315, 279, 4007, 11, 902, 18065, 1023, 12074, 505, 10057, 11, 9635, 11, 15704, 11, 35440, 323, 4987, 12126, 13, 75458, 2678, 3177, 8336, 2187, 12387, 8522, 13, 578, 1176, 1296, 8522, 11, 1778, 439, 304, 1841, 88720, 11, 527, 2736, 2561, 11, 719, 21120, 50552, 617, 539, 3686, 3719, 13882, 11928, 13, 1952, 279, 832, 1450, 11, 420, 374, 4245, 311, 279, 19428, 11, 15910, 3177, 315, 279, 21120, 1891, 2601, 13, 1952, 279, 1023, 1450, 11, 279, 3177, 17610, 315, 1193, 832, 46406, 11, 779, 433, 374, 1647, 5059, 99866, 13, 1115, 11767, 311, 459, 47989, 29447, 4776, 994, 264, 21120, 24310, 13280, 264, 7479, 323, 374, 27000, 1070, 13, 38916, 275, 1425, 11, 389, 902, 279, 502, 3177, 3769, 374, 3196, 11, 374, 1101, 2663, 330, 5902, 66192, 1, 1606, 315, 1202, 4528, 25524, 6070, 13, 16666, 25, 40394, 8663, 16400, 1036, 11, 9362, 52, 20388, 788, 6070, 1156, 10385, 279, 3177, 9193, 16917, 330, 21994, 26006, 311, 21120, 3177, 14614, 990, 449, 33088, 1105, 13, 4452, 11, 814, 8356, 264, 12309, 9439, 3177, 11, 527, 539, 15528, 304, 279, 1317, 4751, 323, 527, 539, 1633, 11297, 1359, 2795, 17054, 432, 1780, 2467, 301, 2234, 11, 2010, 315, 279, 3318, 1912, 13, 578, 3495, 2128, 304, 735, 13327, 374, 4737, 264, 2204, 5603, 25, 2435, 8040, 264, 7701, 72916, 51593, 7993, 315, 12651, 24346, 32732, 263, 25719, 1425, 11, 1101, 3967, 439, 330, 5902, 66192, 1359, 902, 91111, 4661, 912, 3177, 13, 578, 6070, 17610, 315, 264, 1488, 343, 770, 4009, 315, 28701, 7060, 42902, 8162, 83, 51725, 13, 3277, 264, 21120, 24310, 13280, 1521, 11, 433, 374, 9193, 38067, 4871, 279, 4009, 6070, 11, 6968, 264, 87282, 3177, 2592, 13, 330, 8140, 3769, 14385, 810, 477, 2753, 1093, 459, 21075, 31349, 430, 19159, 264, 14113, 11, 24729, 3177, 2612, 1359, 15100, 5124, 2448, 5683, 13, 578, 3831, 72916, 1101, 44072, 311, 279, 2144, 430, 279, 34973, 29447, 4776, 374, 912, 5129, 9621, 311, 279, 3823, 8071, 13, 578, 51593, 7993, 539, 1193, 26420, 430, 279, 3769, 51571, 82, 279, 19428, 21120, 3177, 11, 719, 649, 1101, 45577, 2204, 93959, 13, 3816, 11, 6307, 323, 6437, 21120, 3177, 649, 387, 9709, 304, 2015, 311, 1893, 3230, 1933, 6372, 304, 5369, 311, 4725, 4251, 72318, 3187, 11, 369, 1005, 304, 18699, 3130, 18186, 13, 5810, 11, 9193, 30244, 21120, 1891, 2601, 1436, 3063, 311, 6724, 502, 2955, 19476, 304, 279, 3938, 13, 330, 11458, 11, 304, 2015, 311, 20874, 449, 56672, 304, 279, 3938, 11, 279, 15374, 315, 21120, 1891, 2601, 2011, 387, 13241, 439, 1664, 1359, 2795, 5124, 2448, 5683, 13, 578, 3495, 2128, 374, 1457, 3411, 369, 13076, 8717, 311, 1935, 279, 3094, 505, 279, 27692, 311, 3851, 13, 25218, 279, 7060, 4009, 315, 42902, 34083, 30090, 1193, 264, 2478, 19748, 442, 2481, 304, 1404, 10672, 21120, 51045, 527, 779, 16917, 38067, 430, 264, 87282, 4251, 3177, 374, 9124, 13, 16666, 25, 735, 13327, 3907, 24586, 311, 1202, 9358, 6070, 11, 279, 3769, 649, 45577, 2204, 93959, 11, 602, 1770, 13, 6307, 11, 2579, 323, 6437, 21120, 3177, 13, 16666, 25, 19797, 1122, 5124, 2448, 5683, 33845, 2134, 315, 8522, 369, 34548, 316, 2229, 82, 26982, 279, 12074, 505, 735, 13327, 649, 1005, 872, 1749, 311, 2274, 7701, 94761, 51593, 47194, 369, 2204, 7384, 11, 28858, 32732, 263, 25719, 1425, 1101, 66192, 477, 95273, 13, 763, 420, 1648, 11, 810, 323, 810, 502, 11, 30244, 7384, 11, 779, 19434, 330, 64, 261, 316, 2229, 82, 1359, 527, 3549, 11, 902, 2187, 8104, 18699, 8522, 13, 1789, 3187, 11, 279, 14248, 527, 5131, 3815, 3495, 304, 20632, 449, 5220, 323, 1023, 23978, 311, 2274, 659, 1824, 60051, 3805, 13711, 369, 14467, 13, 220, 128257, 198 ]

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract A new synthesis approach for aluminum particles enables an aluminum core to be passivated by an oxidizing salt: aluminum iodate hexahydrate (AIH). Transmission electron microscopy (TEM) images show that AIH replaces the Al 2 O 3 passivation layer on Al particles that limits Al oxidation. The new core-shell particle reactivity was characterized using laser-induced air shock from energetic materials (LASEM) and results for two different Al-AIH core-shell samples that vary in the AIH concentration demonstrate their potential use for explosive enhancement on both fast (detonation velocity) and slow (blast effects) timescales. Estimates of the detonation velocity for TNT-AIH composites suggest an enhancement of up to 30% may be achievable over pure TNT detonation velocities. Replacement of Al 2 O 3 with AIH allows Al to react on similar timescales as detonation waves. The AIH mixtures tested here have relatively low concentrations of AIH (15 wt. % and 6 wt. %) compared to previously reported samples (57.8 wt. %) and still increase TNT performance by up to 30%. Further optimization of AIH synthesis could result in additional increases in explosive performance. Introduction The effect of aluminum (Al) additives on the laser-induced plasma chemistry of the military explosive cyclotrimethylenetrinitramine (RDX) was previously demonstrated using time-resolved emission spectroscopy 1 ; increasing the Al content resulted in an increase in plasma temperature (due to the exothermic formation of AlO and Al 2 O 3 ) and an increase in C 2 /soot formation because of the oxygen-scavenging Al reactions. Exothermic reactions were subsequently shown to increase the laser-induced shock wave velocity and/or the laser-induced deflagration reaction following pulsed laser excitation of energetic materials 2 . The strong correlation between the measured laser-induced shock velocities produced by laser ablation of energetic materials and the reported detonation velocities from large-scale detonation tests provides a laboratory-scale method for estimating the fast (i.e., microsecond-timescale) energy release from milligram quantities of energetic materials 3 . The laser-induced air shock from energetic materials (LASEM) technique has recently been used to estimate the detonation velocities of novel energetic materials 4 , 5 and conventional military explosives doped with Al or boron (B) additives 6 . Slower energy release such as that from combustion reactions in air results in strong laser-induced deflagration reactions on the millisecond timescale 7 ; typically, energetic materials such as trinitrotoluene (TNT) that make good propellants have significantly higher deflagration intensities than more powerful military explosives such as RDX that produce faster detonation waves (and thus, faster laser-induced shock velocities). Therefore, TNT is a good baseline explosive to evaluate the performance of metal particle additives that typically enhance late-time blast effects but inhibit detonation velocities. Because of its high heat of oxidation, Al powder (typically 20% by weight) is commonly added to TNT to enhance the late-time blast effects of the explosion; tritonal is a typical Al-TNT formulation 8 . Since only a fraction of the available chemical energy is released from conventional metal particle formulations on the microsecond-timescale (resulting in lower detonation velocities), significant research efforts have been devoted to decreasing the reaction time of the metal additive in order to enhance the explosive performance 8 . One approach recently introduced involves chemically altering the oxidation shell of an Al particle that is initially composed of an amorphous Al 2 O 3 outer shell and crystalline Al core. When Al particles are exposed to oxygen during synthesis, an amorphous Al 2 O 3 passivation layer forms around Al particles. The Al 2 O 3 passivation layer can act as a heat sink and oxygen diffusion barrier that slows Al oxidation reactions. Capellos et al . 9 and Baker et al . 10 developed an eigenvalue detonation model to determine the effects of the Al 2 O 3 passivation layer on Al oxidation when Al powders are used as additives in explosive mixtures. Their results show that the Al 2 O 3 passivation layer surrounding Al particles delays the onset of Al oxidation such that Al oxidation does not occur in the detonation wave 9 , 10 . Reducing the limiting effects of the Al 2 O 3 passivation layer could significantly decrease the ignition delay of Al particles and significantly enhance explosive performance. The motivation for this work is to explore chemical synthesis routes that alter the Al 2 O 3 shell toward greater reactivity at microsecond timescales and are aligned with the chemical reactions behind the detonation wave. When exposed to highly acidic solutions (i.e., pH < 4), Al 2 O 3 becomes soluble and dissolves in solution 11 . The solubility of Al 2 O 3 in acidic solutions has been utilized in the synthesis of Al energetic materials to remove the Al 2 O 3 passivation layer surrounding Al particles and replace Al 2 O 3 with a reactive salt 12 , 13 . In Smith et al . 12 , 13 , it was shown that aluminum iodate hexahydrate (AIH) replaces the Al 2 O 3 passivation layer when Al particles are added to concentrated solutions of iodic acid. The Al 0 -AIH core-shell particles significantly increased reactivity with flame speeds measured as high as 3200 m/s 14 . These high flame speeds suggest the Al-AIH particles have great potential to exceed the reactive timescale limitations of Al particles when combined with explosives such as TNT. The objective of this study is to examine the energy release from novel Al 0 -AIH samples that vary slightly in AIH concentration from ~6% AIH to 15% AIH (i.e., AIH6 and AIH15) then compare to the reactions of conventional micron-sized Al particles, alumina (Al 2 O 3 ), and a physical mixture of Al/I 2 O 5 . This analysis is further extended to composites of TNT with each of these additives: micron-sized Al, Al 2 O 3 , Al/I 2 O 5 , AIH6 and AIH15. The goal is to understand AIH contribution to detonation and/or deflagration reactions using the laboratory-scale LASEM technique. Experimental Aluminum iodate hexahydrate synthesis and characterization The mixing procedure used", "role": "user" }, { "content": "Army scientists proved a decades-old prediction that mixing TNT and novel aluminum nanoparticles can significantly enhance energetic performance. This explosive discovery is expected to extend the reach of U.S. Army firepower in battle. Researchers from the U.S. Army Research Laboratory and Texas Tech University demonstrated up to 30-percent enhancement in the detonation velocity of the explosive TNT by adding novel aluminum nanoparticles in which the native alumina shell has been replaced with an oxidizing salt called AIH, or aluminum iodate hexahydrate. The structure of the AIH-coated aluminum nanoparticles was revealed for the very first time through high resolution transmission electron (TEM) microscopy performed by ARL's Dr. Chi-Chin Wu, a materials researcher who leads the plasma research for the lab's Energetic Materials Science Branch in the Lethality Division of Weapons and Materials Research Directorate. Wu said this revolutionary research offers the potential for the exploitation of aluminum and potentially other metallic nanoparticles in explosive formulations to extend the range and destructive power of Army weapons systems, a key objective of the Army's \"Long Range Precision Fires\" modernization priority. \"We believe these results show tremendous promise for enhancing the detonation performance of conventional military explosives with aluminum nanoparticles for the first time,\" said ARL's Dr. Jennifer Gottfried, a physical chemist who collaborated on the research. Single nanoparticle extracted out from a view of native aluminum particles at 150,000 magnification. The image highlights the amorphous oxide shell surrounding the crystalline core. Credit: ARL \"It is very exciting to advance science to a point where we can harness more chemical energy from metal particles at faster timescales. This is an exciting time for transforming energy generation technology,\" said Dr. Michelle L. Pantoya, the J. W. Wright Regents Chair in Mechanical Engineering and Professor at Texas Tech University. Details of this breakthrough work are described in the team's May 28 published paper \"Improving the Explosive Performance of Aluminum Nanoparticles with Aluminum Iodate Hexahydrate (AIH)\" by Jennifer L. Gottfried, Dylan K. Smith, Chi-Chin Wu, and Michelle L. Pantoya in the high-impact journal Scientific Reports. The team found that the crystalline aluminum core was effectively protected against unwanted oxidation by the AIH shell, which appears as protruding nodules on the aluminum surface. The enhanced reactivity due to this unique morphological feature and novel core-shell structure was demonstrated by laser-induced air shock from energetic materials experiments, an innovative laboratory-scale energetic testing method developed by Gottfried. This technique involves impacting the sample with a high-energy, focused laser pulse to violently break apart the explosive molecules. The interaction of the laser with the material forms a laser-induced plasma and produces a shock wave that expands into the surrounding air. The energy released from an explosive sample can then be experimentally determined by measuring the laser-induced shock velocity with a high-speed camera. It was predicted decades ago that aluminum nanoparticles have the potential to enhance the energetic performance of explosives and propellants because of their high energy content and potential for rapid burning. This is because they have exceptionally large surface areas compared to their total volume and a very large heat of reaction. However, the surface of the aluminum nanoparticles is naturally oxidized in air to form a thick alumina shell, typically 20% by weight, which not only lowers the energy content of the nanoparticles by reducing the amount of active aluminum, it also slows the rate of energy release because it acts as a barrier to the reaction of the aluminum with the explosive. Therefore, replacing the oxide shell, as successfully achieved by TTU, can significantly improve the explosive performance. An AIH-salt crystal found at 400,000 magnification. The background is the carbon support film on the specimen grid. Credit: U.S. Army These preliminary joint efforts have also led to a formal research collaboration under an ARL Director's Research Award, the fiscal 2018 External Collaboration Initiative between Wu and TTU. After publishing two papers in high-impact scientific journals in the past year, the team is poised to pursue additional energetics research with aluminum nanoparticles by working with the U.S. Army Research, Development and Engineering Command at Picatinny Arsenal, New Jersey, and the Air Force Research Laboratory. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract A new synthesis approach for aluminum particles enables an aluminum core to be passivated by an oxidizing salt: aluminum iodate hexahydrate (AIH). Transmission electron microscopy (TEM) images show that AIH replaces the Al 2 O 3 passivation layer on Al particles that limits Al oxidation. The new core-shell particle reactivity was characterized using laser-induced air shock from energetic materials (LASEM) and results for two different Al-AIH core-shell samples that vary in the AIH concentration demonstrate their potential use for explosive enhancement on both fast (detonation velocity) and slow (blast effects) timescales. Estimates of the detonation velocity for TNT-AIH composites suggest an enhancement of up to 30% may be achievable over pure TNT detonation velocities. Replacement of Al 2 O 3 with AIH allows Al to react on similar timescales as detonation waves. The AIH mixtures tested here have relatively low concentrations of AIH (15 wt. % and 6 wt. %) compared to previously reported samples (57.8 wt. %) and still increase TNT performance by up to 30%. Further optimization of AIH synthesis could result in additional increases in explosive performance. Introduction The effect of aluminum (Al) additives on the laser-induced plasma chemistry of the military explosive cyclotrimethylenetrinitramine (RDX) was previously demonstrated using time-resolved emission spectroscopy 1 ; increasing the Al content resulted in an increase in plasma temperature (due to the exothermic formation of AlO and Al 2 O 3 ) and an increase in C 2 /soot formation because of the oxygen-scavenging Al reactions. Exothermic reactions were subsequently shown to increase the laser-induced shock wave velocity and/or the laser-induced deflagration reaction following pulsed laser excitation of energetic materials 2 . The strong correlation between the measured laser-induced shock velocities produced by laser ablation of energetic materials and the reported detonation velocities from large-scale detonation tests provides a laboratory-scale method for estimating the fast (i.e., microsecond-timescale) energy release from milligram quantities of energetic materials 3 . The laser-induced air shock from energetic materials (LASEM) technique has recently been used to estimate the detonation velocities of novel energetic materials 4 , 5 and conventional military explosives doped with Al or boron (B) additives 6 . Slower energy release such as that from combustion reactions in air results in strong laser-induced deflagration reactions on the millisecond timescale 7 ; typically, energetic materials such as trinitrotoluene (TNT) that make good propellants have significantly higher deflagration intensities than more powerful military explosives such as RDX that produce faster detonation waves (and thus, faster laser-induced shock velocities). Therefore, TNT is a good baseline explosive to evaluate the performance of metal particle additives that typically enhance late-time blast effects but inhibit detonation velocities. Because of its high heat of oxidation, Al powder (typically 20% by weight) is commonly added to TNT to enhance the late-time blast effects of the explosion; tritonal is a typical Al-TNT formulation 8 . Since only a fraction of the available chemical energy is released from conventional metal particle formulations on the microsecond-timescale (resulting in lower detonation velocities), significant research efforts have been devoted to decreasing the reaction time of the metal additive in order to enhance the explosive performance 8 . One approach recently introduced involves chemically altering the oxidation shell of an Al particle that is initially composed of an amorphous Al 2 O 3 outer shell and crystalline Al core. When Al particles are exposed to oxygen during synthesis, an amorphous Al 2 O 3 passivation layer forms around Al particles. The Al 2 O 3 passivation layer can act as a heat sink and oxygen diffusion barrier that slows Al oxidation reactions. Capellos et al . 9 and Baker et al . 10 developed an eigenvalue detonation model to determine the effects of the Al 2 O 3 passivation layer on Al oxidation when Al powders are used as additives in explosive mixtures. Their results show that the Al 2 O 3 passivation layer surrounding Al particles delays the onset of Al oxidation such that Al oxidation does not occur in the detonation wave 9 , 10 . Reducing the limiting effects of the Al 2 O 3 passivation layer could significantly decrease the ignition delay of Al particles and significantly enhance explosive performance. The motivation for this work is to explore chemical synthesis routes that alter the Al 2 O 3 shell toward greater reactivity at microsecond timescales and are aligned with the chemical reactions behind the detonation wave. When exposed to highly acidic solutions (i.e., pH < 4), Al 2 O 3 becomes soluble and dissolves in solution 11 . The solubility of Al 2 O 3 in acidic solutions has been utilized in the synthesis of Al energetic materials to remove the Al 2 O 3 passivation layer surrounding Al particles and replace Al 2 O 3 with a reactive salt 12 , 13 . In Smith et al . 12 , 13 , it was shown that aluminum iodate hexahydrate (AIH) replaces the Al 2 O 3 passivation layer when Al particles are added to concentrated solutions of iodic acid. The Al 0 -AIH core-shell particles significantly increased reactivity with flame speeds measured as high as 3200 m/s 14 . These high flame speeds suggest the Al-AIH particles have great potential to exceed the reactive timescale limitations of Al particles when combined with explosives such as TNT. The objective of this study is to examine the energy release from novel Al 0 -AIH samples that vary slightly in AIH concentration from ~6% AIH to 15% AIH (i.e., AIH6 and AIH15) then compare to the reactions of conventional micron-sized Al particles, alumina (Al 2 O 3 ), and a physical mixture of Al/I 2 O 5 . This analysis is further extended to composites of TNT with each of these additives: micron-sized Al, Al 2 O 3 , Al/I 2 O 5 , AIH6 and AIH15. The goal is to understand AIH contribution to detonation and/or deflagration reactions using the laboratory-scale LASEM technique. Experimental Aluminum iodate hexahydrate synthesis and characterization The mixing procedure used<|im_end|> <|im_start|>assistant Army scientists proved a decades-old prediction that mixing TNT and novel aluminum nanoparticles can significantly enhance energetic performance. This explosive discovery is expected to extend the reach of U.S. Army firepower in battle. Researchers from the U.S. Army Research Laboratory and Texas Tech University demonstrated up to 30-percent enhancement in the detonation velocity of the explosive TNT by adding novel aluminum nanoparticles in which the native alumina shell has been replaced with an oxidizing salt called AIH, or aluminum iodate hexahydrate. The structure of the AIH-coated aluminum nanoparticles was revealed for the very first time through high resolution transmission electron (TEM) microscopy performed by ARL's Dr. Chi-Chin Wu, a materials researcher who leads the plasma research for the lab's Energetic Materials Science Branch in the Lethality Division of Weapons and Materials Research Directorate. Wu said this revolutionary research offers the potential for the exploitation of aluminum and potentially other metallic nanoparticles in explosive formulations to extend the range and destructive power of Army weapons systems, a key objective of the Army's "Long Range Precision Fires" modernization priority. "We believe these results show tremendous promise for enhancing the detonation performance of conventional military explosives with aluminum nanoparticles for the first time," said ARL's Dr. Jennifer Gottfried, a physical chemist who collaborated on the research. Single nanoparticle extracted out from a view of native aluminum particles at 150,000 magnification. The image highlights the amorphous oxide shell surrounding the crystalline core. Credit: ARL "It is very exciting to advance science to a point where we can harness more chemical energy from metal particles at faster timescales. This is an exciting time for transforming energy generation technology," said Dr. Michelle L. Pantoya, the J. W. Wright Regents Chair in Mechanical Engineering and Professor at Texas Tech University. Details of this breakthrough work are described in the team's May 28 published paper "Improving the Explosive Performance of Aluminum Nanoparticles with Aluminum Iodate Hexahydrate (AIH)" by Jennifer L. Gottfried, Dylan K. Smith, Chi-Chin Wu, and Michelle L. Pantoya in the high-impact journal Scientific Reports. The team found that the crystalline aluminum core was effectively protected against unwanted oxidation by the AIH shell, which appears as protruding nodules on the aluminum surface. The enhanced reactivity due to this unique morphological feature and novel core-shell structure was demonstrated by laser-induced air shock from energetic materials experiments, an innovative laboratory-scale energetic testing method developed by Gottfried. This technique involves impacting the sample with a high-energy, focused laser pulse to violently break apart the explosive molecules. The interaction of the laser with the material forms a laser-induced plasma and produces a shock wave that expands into the surrounding air. The energy released from an explosive sample can then be experimentally determined by measuring the laser-induced shock velocity with a high-speed camera. It was predicted decades ago that aluminum nanoparticles have the potential to enhance the energetic performance of explosives and propellants because of their high energy content and potential for rapid burning. This is because they have exceptionally large surface areas compared to their total volume and a very large heat of reaction. However, the surface of the aluminum nanoparticles is naturally oxidized in air to form a thick alumina shell, typically 20% by weight, which not only lowers the energy content of the nanoparticles by reducing the amount of active aluminum, it also slows the rate of energy release because it acts as a barrier to the reaction of the aluminum with the explosive. Therefore, replacing the oxide shell, as successfully achieved by TTU, can significantly improve the explosive performance. An AIH-salt crystal found at 400,000 magnification. The background is the carbon support film on the specimen grid. Credit: U.S. Army These preliminary joint efforts have also led to a formal research collaboration under an ARL Director's Research Award, the fiscal 2018 External Collaboration Initiative between Wu and TTU. After publishing two papers in high-impact scientific journals in the past year, the team is poised to pursue additional energetics research with aluminum nanoparticles by working with the U.S. Army Research, Development and Engineering Command at Picatinny Arsenal, New Jersey, and the Air Force Research Laboratory. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Recent experiments have shown that optogenetic activation of serotonin neurons in the dorsal raphe nucleus (DRN) in mice enhances patience in waiting for future rewards. Here, we show that serotonin effect in promoting waiting is maximized by both high probability and high timing uncertainty of reward. Optogenetic activation of serotonergic neurons prolongs waiting time in no-reward trials in a task with 75% food reward probability, but not with 50 or 25% reward probabilities. Serotonin effect in promoting waiting increases when the timing of reward presentation becomes unpredictable. To coherently explain the experimental data, we propose a Bayesian decision model of waiting that assumes that serotonin neuron activation increases the prior probability or subjective confidence of reward delivery. The present data and modeling point to the possibility of a generalized role of serotonin in resolving trade-offs, not only between immediate and delayed rewards, but also between sensory evidence and subjective confidence. Introduction The neuromodulator, serotonin, is extensively involved in behavioral, affective, and cognitive functions of the brain. Chemical and electrode recordings from the dorsal raphe nucleus (DRN) have shown that the activity of serotonin neurons increases when animals perform tasks requiring them to wait for delayed rewards 1 , 2 , 3 . Local pharmacological inhibition of DRN serotonin neural activity in rats impairs their patience in waiting for delayed rewards 4 . We recently used transgenic mice that express the channelrhodopsin-2 (ChR2) variant C128S in serotonin neurons 5 , 6 and showed that their selective activation in the DRN enhances the patience of mice waiting for both a conditioned reinforcer tone and a food reward 7 . A recent study also confirmed that optogenetic activation of DRN serotonin neurons enhances patience in waiting 8 . These results established a causal relationship between serotonin neural activation and patience in waiting for future rewards. We therefore questioned whether activation of serotonin neurons always promotes waiting for delayed reward or whether its effect depends on the subject’s reward prediction. In our previous optogenetic study, serotonergic activation prolonged waiting time by ~30% before the mice eventually gave up waiting 7 . Serotonin neuron activation was most effective at the time when mice decided whether to continue waiting 7 . These results suggest that cognitive status, such as the anticipation of future rewards, modulates the promotion of patience by serotonin. In the current study, we tested whether the probability, amount, and timing uncertainty of future rewards affects promotion of patience by serotonin neuron activation. We find that serotonin effect in promoting waiting is maximized by both high-reward probability (RP) and high-reward timing uncertainty. We further propose a Bayesian decision model of waiting, which assumes serotonin neuron activation increases the prior RP to reproduce the major features of the experimental results. The model reproduces the more prominent effect of serotonin with reward timing uncertainty because the likelihood function for reward delivery has a longer tail in time. The present data and modeling suggest that serotonin neuron activation enhance patience in waiting for future rewards by increasing subjective confidence of future goals. Results Serotonin effect on waiting depends on reward probability Mice (seven transgenic mice and five wild-type (WT) mice) were trained to perform a sequential tone-food waiting task that required them to wait for a delayed tone (conditioned reinforcer) at a tone site and then to wait for delayed food (primary reward) at a reward site (Fig. 1a, b ). In experiment 1, to examine whether the predicted probability and amount of reward affect the promotion of patience by serotonin neuron activation, we prepared six combinations of RP (75, 50, and 25%) and reward amount (1, 2, and 3 food pellets) (Supplementary Fig. 1 ). Fig. 1 Schematic of the sequential tone-food waiting task. a Diagram of the test in which optogenetic stimulation was applied during the reward-delay period (experiments 1 and 2). b Time sequence of serotonin activation trials and serotonin no-activation trials. In serotonin activation trials, 0.8 s of blue light was delivered at the onset of the reward delay. In serotonin no-activation trials, 0.8 s of yellow light was applied at the onset of the reward delay. In each trial, 1 s of yellow light was used at the onset of food presentation or at the reward wait error. Blue and yellow bars denote blue and yellow light stimulation, respectively. Brown- and red-shaded regions denote tone- and reward-delay periods, respectively. Orange-shaded regions denote duration of tone presentation. c Locations of optical fibers in the DRN. Light blue bars in the DRN represent tracks of implanted optical fibers. Coronal drawings were adapted from ref. 48 with permission Full size image In the experiment, during which 75% of the nose pokes for 3 s were rewarded with one food pellet (Supplementary Fig. 1a ), waiting time in the 25% of trials with no reward (i.e., omission) was significantly longer with serotonin neuron activation (7.89 ± 0.08 s, mean ± s.e.m.) than without activation (6.95 ± 0.09 s; t (5) = 24.05, P = 2.32 × 10 −6 , n = 6 mice, paired t -test) (Figs. 2 a and 3a ; Supplementary Fig. 2 ). The effect was significantly seen in each of the six mice tested ( P < 0.022, Mann–Whitney U- test) (Supplementary Fig. 3 ). We confirmed, in five WT mice, that waiting time in the blue light trials (7.36 ± 0.31 s) was not significantly different from that in the yellow light trials (7.35 ± 0.32 s; t (4) = 0.33, P = 0.76, n = 5 mice, paired t -test). In the 75% one-pellet test, we analyzed control group (WT) data with ChR2-expressing group (ChR2) in a two-way analysis of variance (ANOVA). There was a significant main effect of light (two levels within-subject factors; yellow and blue, F (1,9) = 366.83, P < 10 −6 ) but no significant main effect of group (two levels between-subject factors; ChR2 and WT, F (1,9) = 0.062, P = 0.81). There was a significant main effect of interaction (light × group, F", "role": "user" }, { "content": "People usually have the ability to put aside the desire for immediate gratification in anticipation of something good. But this isn't just a human trait—a new study shows that mice can be patient, too, revealing a link between the brain's chemical system and the mice's belief about how waiting will pay off. The effect of the neuromodulator serotonin on mice's ability to stay patient when waiting for a reward is at the core of a new study published in Nature Communications. The authors, Dr. Katsuhiko Miyazaki and Dr. Kayoko Miyazaki, analyzed how the rodents behaved under the influence of serotonin, as part of a study conducted in the Neural Computation Unit at the Okinawa Institute of Science and Technology Graduate University (OIST). Serotonin is a chemical messenger that influences neuron functions. It has been linked to a wide array of behaviors encompassing mood, sleep, cravings and spontaneity. The power of the chemical over human behavior has made it a key focus in the treatment of mental conditions such as depression by selective serotonin receptor inhibitors (SSRIs), which slow down the reabsorption of serotonin and keep it active in the brain. \"Serotonin has had a lot of study in pharmacology, and serotonergic drugs are commonly prescribed,\" said Katsuhiko Miyazaki, \"but the role that serotonin has over behavior isn't clear.\" The team investigated for a causal relationship between serotonin levels and behavior in mice. The mice were trained to perform a task to obtain a food reward, placing their noses into a small hole and waiting—a behavior called a \"nose poke.\" After a pre-set duration, the reward was delivered. In a previous study, the team used a method called optogenetics, a method allowing scientist to use light to stimulate specific neurons with precise timing. These neurons are genetically modified to a produce a light-sensitive protein and are then stimulated by shining light along a fiber optic implanted in the brain. In the study, serotonin-producing neurons were optogenetically stimulated in a part of the brain called the dorsal raphe nucleus (DRN). These neurons then fired widely into the forebrain. The result was that increasing the activity of serotonin neurons in the DRN drastically increased the amount of time mice were willing to wait for a food reward. In a test where food rewards were always delivered after 6 seconds, serotonin's effect of extending nose-poke time was small (left). But in tests where food goes was delivered after two, six, or ten seconds later, serotonin boosted nose poke times significantly (right). Credit: OIST While the study showed that serotonin increased patience, the latest study tested whether mice respond similarly in circumstances when getting a reward was uncertain. Would mice wait for food regardless of the probability and timing of its presentation, or would they give up if they predicted a low chance of return on their time investment? The new trials showed there are limits to serotonin's ability to enhance patience. Mice were given a nose-poke trial with a 75 percent chance of a reward, with a three second waiting period before the reward was delivered. When these mice were subject to a no-reward outcome, their waiting time was prolonged, as expected from the previous paper. However, in tests where the chance of reward delivery following a nose-poke was 50 percent or 25 percent, increasing serotonin had no effect on the mice's waiting time. \"The patience effect only works when the mouse thinks there is a high probability of reward,\" said Dr. Miyazaki. They also found that serotonin stimulation made the mice to wait longer when the timing of a reward was harder to predict. In some sessions with a 75 percent chance of getting a reward, mice were rewarded after precise periods, while in other sessions, they were rewarded after randomized timing. The extended waiting times by serotonin neuron stimulation were more prominent when the reward timing was randomized. (Fig. 2). To explain the results of their experiment, the team constructed a computational model to explain the experimental data. In the model, the mice were able to expect when a food reward would be delivered, and to judge when they were subject to a no-reward trial. The model could reproduce the experimental results by assuming that serotonin affects confidence of receiving a reward when subjective confidence is high. In a 75 percent reward probability trial, for example, serotonin made the mice behave as if there was a 95 percent chance of reward. The model also reproduced the result of timing uncertainty. When the mice were uncertain of the timing of reward delivery, it became difficult for them to judge whether they were waiting in a reward trial or no-reward trial. Serotonin stimulation increased the mice's belief that they were in a reward trial, delaying their judgment further as reward timing was less clear. The findings show that the relationship between the activation of serotonin and subsequent behavior is highly dependent on the animals' belief about the circumstances. These results may have implications for our understanding of how humans taking serotonin boosting drugs can also be affected. \"This could help explain why combined treatment of depression with SSRIs and Cognitive Behavior Therapy (CBT) is more effective than just SSRIs alone,\" said Dr. Miyazaki. \"The psychological boost of the therapy is enhanced by raised serotonin levels.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Recent experiments have shown that optogenetic activation of serotonin neurons in the dorsal raphe nucleus (DRN) in mice enhances patience in waiting for future rewards. Here, we show that serotonin effect in promoting waiting is maximized by both high probability and high timing uncertainty of reward. Optogenetic activation of serotonergic neurons prolongs waiting time in no-reward trials in a task with 75% food reward probability, but not with 50 or 25% reward probabilities. Serotonin effect in promoting waiting increases when the timing of reward presentation becomes unpredictable. To coherently explain the experimental data, we propose a Bayesian decision model of waiting that assumes that serotonin neuron activation increases the prior probability or subjective confidence of reward delivery. The present data and modeling point to the possibility of a generalized role of serotonin in resolving trade-offs, not only between immediate and delayed rewards, but also between sensory evidence and subjective confidence. Introduction The neuromodulator, serotonin, is extensively involved in behavioral, affective, and cognitive functions of the brain. Chemical and electrode recordings from the dorsal raphe nucleus (DRN) have shown that the activity of serotonin neurons increases when animals perform tasks requiring them to wait for delayed rewards 1 , 2 , 3 . Local pharmacological inhibition of DRN serotonin neural activity in rats impairs their patience in waiting for delayed rewards 4 . We recently used transgenic mice that express the channelrhodopsin-2 (ChR2) variant C128S in serotonin neurons 5 , 6 and showed that their selective activation in the DRN enhances the patience of mice waiting for both a conditioned reinforcer tone and a food reward 7 . A recent study also confirmed that optogenetic activation of DRN serotonin neurons enhances patience in waiting 8 . These results established a causal relationship between serotonin neural activation and patience in waiting for future rewards. We therefore questioned whether activation of serotonin neurons always promotes waiting for delayed reward or whether its effect depends on the subject’s reward prediction. In our previous optogenetic study, serotonergic activation prolonged waiting time by ~30% before the mice eventually gave up waiting 7 . Serotonin neuron activation was most effective at the time when mice decided whether to continue waiting 7 . These results suggest that cognitive status, such as the anticipation of future rewards, modulates the promotion of patience by serotonin. In the current study, we tested whether the probability, amount, and timing uncertainty of future rewards affects promotion of patience by serotonin neuron activation. We find that serotonin effect in promoting waiting is maximized by both high-reward probability (RP) and high-reward timing uncertainty. We further propose a Bayesian decision model of waiting, which assumes serotonin neuron activation increases the prior RP to reproduce the major features of the experimental results. The model reproduces the more prominent effect of serotonin with reward timing uncertainty because the likelihood function for reward delivery has a longer tail in time. The present data and modeling suggest that serotonin neuron activation enhance patience in waiting for future rewards by increasing subjective confidence of future goals. Results Serotonin effect on waiting depends on reward probability Mice (seven transgenic mice and five wild-type (WT) mice) were trained to perform a sequential tone-food waiting task that required them to wait for a delayed tone (conditioned reinforcer) at a tone site and then to wait for delayed food (primary reward) at a reward site (Fig. 1a, b ). In experiment 1, to examine whether the predicted probability and amount of reward affect the promotion of patience by serotonin neuron activation, we prepared six combinations of RP (75, 50, and 25%) and reward amount (1, 2, and 3 food pellets) (Supplementary Fig. 1 ). Fig. 1 Schematic of the sequential tone-food waiting task. a Diagram of the test in which optogenetic stimulation was applied during the reward-delay period (experiments 1 and 2). b Time sequence of serotonin activation trials and serotonin no-activation trials. In serotonin activation trials, 0.8 s of blue light was delivered at the onset of the reward delay. In serotonin no-activation trials, 0.8 s of yellow light was applied at the onset of the reward delay. In each trial, 1 s of yellow light was used at the onset of food presentation or at the reward wait error. Blue and yellow bars denote blue and yellow light stimulation, respectively. Brown- and red-shaded regions denote tone- and reward-delay periods, respectively. Orange-shaded regions denote duration of tone presentation. c Locations of optical fibers in the DRN. Light blue bars in the DRN represent tracks of implanted optical fibers. Coronal drawings were adapted from ref. 48 with permission Full size image In the experiment, during which 75% of the nose pokes for 3 s were rewarded with one food pellet (Supplementary Fig. 1a ), waiting time in the 25% of trials with no reward (i.e., omission) was significantly longer with serotonin neuron activation (7.89 ± 0.08 s, mean ± s.e.m.) than without activation (6.95 ± 0.09 s; t (5) = 24.05, P = 2.32 × 10 −6 , n = 6 mice, paired t -test) (Figs. 2 a and 3a ; Supplementary Fig. 2 ). The effect was significantly seen in each of the six mice tested ( P < 0.022, Mann–Whitney U- test) (Supplementary Fig. 3 ). We confirmed, in five WT mice, that waiting time in the blue light trials (7.36 ± 0.31 s) was not significantly different from that in the yellow light trials (7.35 ± 0.32 s; t (4) = 0.33, P = 0.76, n = 5 mice, paired t -test). In the 75% one-pellet test, we analyzed control group (WT) data with ChR2-expressing group (ChR2) in a two-way analysis of variance (ANOVA). There was a significant main effect of light (two levels within-subject factors; yellow and blue, F (1,9) = 366.83, P < 10 −6 ) but no significant main effect of group (two levels between-subject factors; ChR2 and WT, F (1,9) = 0.062, P = 0.81). There was a significant main effect of interaction (light × group, F<|im_end|> <|im_start|>assistant People usually have the ability to put aside the desire for immediate gratification in anticipation of something good. But this isn't just a human trait—a new study shows that mice can be patient, too, revealing a link between the brain's chemical system and the mice's belief about how waiting will pay off. The effect of the neuromodulator serotonin on mice's ability to stay patient when waiting for a reward is at the core of a new study published in Nature Communications. The authors, Dr. Katsuhiko Miyazaki and Dr. Kayoko Miyazaki, analyzed how the rodents behaved under the influence of serotonin, as part of a study conducted in the Neural Computation Unit at the Okinawa Institute of Science and Technology Graduate University (OIST). Serotonin is a chemical messenger that influences neuron functions. It has been linked to a wide array of behaviors encompassing mood, sleep, cravings and spontaneity. The power of the chemical over human behavior has made it a key focus in the treatment of mental conditions such as depression by selective serotonin receptor inhibitors (SSRIs), which slow down the reabsorption of serotonin and keep it active in the brain. "Serotonin has had a lot of study in pharmacology, and serotonergic drugs are commonly prescribed," said Katsuhiko Miyazaki, "but the role that serotonin has over behavior isn't clear." The team investigated for a causal relationship between serotonin levels and behavior in mice. The mice were trained to perform a task to obtain a food reward, placing their noses into a small hole and waiting—a behavior called a "nose poke." After a pre-set duration, the reward was delivered. In a previous study, the team used a method called optogenetics, a method allowing scientist to use light to stimulate specific neurons with precise timing. These neurons are genetically modified to a produce a light-sensitive protein and are then stimulated by shining light along a fiber optic implanted in the brain. In the study, serotonin-producing neurons were optogenetically stimulated in a part of the brain called the dorsal raphe nucleus (DRN). These neurons then fired widely into the forebrain. The result was that increasing the activity of serotonin neurons in the DRN drastically increased the amount of time mice were willing to wait for a food reward. In a test where food rewards were always delivered after 6 seconds, serotonin's effect of extending nose-poke time was small (left). But in tests where food goes was delivered after two, six, or ten seconds later, serotonin boosted nose poke times significantly (right). Credit: OIST While the study showed that serotonin increased patience, the latest study tested whether mice respond similarly in circumstances when getting a reward was uncertain. Would mice wait for food regardless of the probability and timing of its presentation, or would they give up if they predicted a low chance of return on their time investment? The new trials showed there are limits to serotonin's ability to enhance patience. Mice were given a nose-poke trial with a 75 percent chance of a reward, with a three second waiting period before the reward was delivered. When these mice were subject to a no-reward outcome, their waiting time was prolonged, as expected from the previous paper. However, in tests where the chance of reward delivery following a nose-poke was 50 percent or 25 percent, increasing serotonin had no effect on the mice's waiting time. "The patience effect only works when the mouse thinks there is a high probability of reward," said Dr. Miyazaki. They also found that serotonin stimulation made the mice to wait longer when the timing of a reward was harder to predict. In some sessions with a 75 percent chance of getting a reward, mice were rewarded after precise periods, while in other sessions, they were rewarded after randomized timing. The extended waiting times by serotonin neuron stimulation were more prominent when the reward timing was randomized. (Fig. 2). To explain the results of their experiment, the team constructed a computational model to explain the experimental data. In the model, the mice were able to expect when a food reward would be delivered, and to judge when they were subject to a no-reward trial. The model could reproduce the experimental results by assuming that serotonin affects confidence of receiving a reward when subjective confidence is high. In a 75 percent reward probability trial, for example, serotonin made the mice behave as if there was a 95 percent chance of reward. The model also reproduced the result of timing uncertainty. When the mice were uncertain of the timing of reward delivery, it became difficult for them to judge whether they were waiting in a reward trial or no-reward trial. Serotonin stimulation increased the mice's belief that they were in a reward trial, delaying their judgment further as reward timing was less clear. The findings show that the relationship between the activation of serotonin and subsequent behavior is highly dependent on the animals' belief about the circumstances. These results may have implications for our understanding of how humans taking serotonin boosting drugs can also be affected. "This could help explain why combined treatment of depression with SSRIs and Cognitive Behavior Therapy (CBT) is more effective than just SSRIs alone," said Dr. Miyazaki. "The psychological boost of the therapy is enhanced by raised serotonin levels." <|im_end|>

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]

2,464

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Guidelines Hypothesis Interesting Images Letter New Book Received Obituary Opinion Perspective Proceeding Paper Project Report Protocol Registered Report Reply Retraction Short Note Study Protocol Systematic Review Technical Note Tutorial Viewpoint All Article Types Advanced Search Section All Sections Cancer Biomarkers Cancer Causes, Screening and Diagnosis Cancer Drug Development Cancer Epidemiology and Prevention Cancer Immunology and Immunotherapy Cancer Informatics and Big Data Cancer Metastasis Cancer Pathophysiology Cancer Therapy Clinical Trials of Cancer Infectious Agents and Cancer Methods and Technologies Development Molecular Cancer Biology Pediatric Oncology Systematic Review or Meta-Analysis in Cancer Research Transplant Oncology and Cancer Nursing Care Tumor Microenvironment All Sections Special Issue All Special Issues \"The 10th International MDM2 Workshop\"—Opening Up New Avenues for MDM2 and p53 Research T Cells and Myeloid Cells in Cancer Immunotherapy Helicobacter pylori Associated Cancer TP53 in Solid Tumors and Hematological Malignancies How Does Obesity Cause Cancer? Methylation Changes in Early Stage Non-small Cell Lung Cancer: New Evidences, Methodological Approaches and Applications Cancer and Liposomes 10th Anniversary of Cancers—Targeted Therapies for Ovarian Cancer Treatment from Bench to Bedside 2nd Edition: Adolescent and Young Adult Oncology 2nd Edition: Advances in the Management of Thyroid Cancer 2nd Edition: Colorectal Cancers 2nd Edition: Combination and Innovative Therapies for Pancreatic Cancer 2nd Edition: Estrogen Receptor-Positive (ER+) Breast Cancers 2nd Edition: New Perspectives of Ocular Oncology 2nd Edition: Resistance Mechanisms in Malignant Brain Tumors 3rd Etnean Occupational Medicine Workshop—Breast Cancer and Work 3D Cell Culture Cancer Models: Development and Applications A Deeper Dive into Signaling Pathways in Cancers A Selection of Papers from the Cancer Therapy 2021 Virtual Scientific Meeting A Selection of Papers from the Meeting on Cancer Science and Targeted Therapy Conference A Special Issue on Tumor Stroma Actionable Mutations in Lung Cancer Acute Myeloid Leukemia Acute Myeloid Leukemia (AML) Acute Myeloid Leukemia: From Diagnosis to Treatment Acute Myeloid Leukemia: The Future Is Bright Acute Promyelocytic Leukemia Acute Promyelocytic Leukemia (APML) Adaptation Strategies of Circulating Tumor Cells Adhesion and Integrins Adjuvant Chemotherapy for Colorectal Cancer Adrenocortical Carcinoma Advance and New Insights in Bladder Cancer Advance in Colorectal Cancer: A Themed Issue in Honor of Prof. Bengt Glimelius Advance in Computational Methods in Cancer Research Advance in Morbidity and Survivorship of Breast Cancer Advance in Supportive and Palliative Care in Cancer Advance Research in Thrombosis and Hematologic Malignancies Advanced Cancer Nanotheranostics Advanced Neuroendocrine Tumors Advanced NSCLC with Oncogene Addiction: An Ongoing Revolution Advanced Ovarian Cancer Advanced Pancreatic Cancer Advanced Prostate Cancer: From Bench to Bedside Advanced Research in Cancer Initiation and Early Detection Advanced Research in Glycoproteins and Cancer Advanced Research in Oncology in 2022 Advanced Research in Oncology in 2023 Advanced Research in Organs-on-a-Chip and Cancer Advanced Research in Pancreatic Ductal Adenocarcinoma Advanced Therapies for Hematological Cancers Advances and Research Progress in Hepatocellular Carcinoma Advances in Adrenocortical Carcinoma Research: Diagnosis, Treatment and Prognosis Advances in Antitumor Molecular-Targeted Agents of Urological Cancers Advances in Bone Metastatic Cancer Research Advances in Breast Cancer Brain Metastases Advances in Breast Cancer: A Themed Issue in Honor of Prof. Fernando Schmitt Advances in Breast Cancer: From Pathogenesis to Therapy Advances in Cancer Chemoprevention Advances in Cancer Cachexia Advances in Cancer Data and Statistics Advances in Cancer Disparities Advances in Cancer Epigenetics Advances in Cancer Radiotherapy Advances in Cancer Stem Cell Research Advances in Chordoma Advances in Chronic Lymphocytic Leukaemia (CLL) Research Advances in Diagnosis and Treatment for Bone and Soft Tissue Sarcoma Advances in Diagnosis, Treatment and Management of Endocrine Neoplasms Advances in Diagnostics and Treatment of Head and Neck Cancer Advances in Endometrial Cancer: From Pathogenesis, Pathology Diagnosis and Molecular Classification to Targeted Therapy Advances in Experimental Radiotherapy Advances in Follicular Lymphoma Advances in Genetic and Molecular Approaches to Skin Cancer Advances in Genetics and Epigenetics of Bladder Cancer Advances in Gynecological Oncology: From Pathogenesis to Therapy Advances in Head and Neck Cancer Research Advances in Head and Neck Squamous Cell Carcinoma Advances in Hematological Neoplasms: A Wide Perspective on the 2022 WHO and International Consensus Classifications Advances in HPB/GI Imaging Advances in Human-Papillomavirus-Related Squamous Cell Carcinoma: From Pathogenesis to Treatment Advances in Integrins in Cancer Advances in Locally Advanced and Metastatic Kidney Cancer Advances in Lymphoma, Plasma Cell Myeloma, and Leukemia Diagnostics Advances in Modern Radiation Oncology Advances in Neuroendocrine Neoplasms Advances in NK/T-cell Lymphoma, Epidemiology, Biology and Therapy Advances in Oral Cancers and Precancers Advances in Our Understanding of ALK-Related Cancers: A Selection of Papers from the Joint Annual Meeting of the European Research Initiative for ALK-Related Malignancies (ERIA) and the European Union Marie Curie European Training Network ALKATRAS Advances in Pancreatic Cancer Research Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment Advances in Papillary Thyroid Cancer Research Advances in Parathyroid Carcinoma: From Bench to Bedside Advances in Plasma Cell Dyscrasias Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer Advances in Research, Diagnosis and Treatment of Brain Metastases Advances in Salivary Gland Carcinoma Advances in Soft Tissue and Bone Sarcoma Advances in Stimuli-Responsive Nanostructures for Cancer Therapy and Diagnosis Advances in Surgical Management of Colorectal Liver Metastases: Toward a Better Patient Selection, Lower Surgical Stress, and Multidisciplinary Approach Advances in the biological responses to radiation-induced DNA damage: A selection of papers from the Joint 43rd European Radiation Research Society (ERRS) and 20th German Society for Biological Radiation Research (GBS) Annual Meetings Advances in the Diagnosis, Prognosis and Treatment of Diffuse Large B-cell Lymphoma Advances in the Management of Hepatocellular Carcinoma Advances in the Management of Oligometastatic Disease in Non-colorectal Non-neuroendocrine Tumors Advances in the Management of Thyroid Cancer Advances in Thoracic Carcinoma and Translational Research Advances in Thoracic Oncology Advances in Thymic Tumors Advances in Translational Ovarian Cancer Research Advances in Translational Research for Soft Tissue Sarcomas Advances in Treatment for Hepatobiliary and Pancreatic Cancers: Multi-Disciplinary Strategies and Outcome Evaluation Advances in Treatment of Rare Tumors Advances in Triple-Negative Breast Cancer Advances in Tumor Angiogenesis Advances of Brain Mapping in Cancer Research Advances in Head and Neck Cancer Biology and Clinical Management Advances in In Vivo Quantitative and Qualitative Imaging Characterization of Gliomas", "role": "user" }, { "content": "Apoptosis is the mechanism by which defective cells promote their own death to protect the body. It is a complex process, with many stages, in which the different parts of the cell gradually degrade. In glioblastoma cells, even when apoptosis begins, the process stops at one of the stages and allows the cell to survive. In previous studies, researchers had already demonstrated that glioblastoma cells have insufficient levels of DFF40/CAD, a protein that, during apoptosis, orchestrates the breakdown of the cell nucleus. This shortage means that the fragmentation step is not completed and the cell can recover. In the article, published in Cancers and coordinated by Dr. Víctor J. Yuste, professor at the Department of Biochemistry and Molecular Biology at the UAB Faculty of Medicine and researcher at the Institut de Neurociències of the UAB (INc-UAB), the researchers administered to the tumor cells a substance derived from the cotton plant, gossypol. This molecule enhances the activity of DFF40/CAD. The result is that, in the treated cells, the nuclear fragmentation process is completed and the cell dies. Dr. Laura Martinez-Escardó, researcher at the Department of Biochemistry and Molecular Biology of the UAB and first author of the work explains the finding, says, \"We have seen that, contrary to other drugs, gossypol allows DFF40/CAD to stay in the nucleus for longer to promote its fragmentation. With our study, we demonstrated that compounds such as gossypol can push these cells to a point of no return after starting the cell death process without modifying them genetically.\" Dr. Yuste says, \"Promoting apoptosis to end properly in tumor cells could be a good therapeutic strategy to treat glioblastoma. The findings presented are promising and encourage us to carry out further research. The new results help us better understand the biology of this aggressive tumor and may provide us with new tools for the development of more effective strategies. This is especially interesting because there is currently no cure for this disease.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Guidelines Hypothesis Interesting Images Letter New Book Received Obituary Opinion Perspective Proceeding Paper Project Report Protocol Registered Report Reply Retraction Short Note Study Protocol Systematic Review Technical Note Tutorial Viewpoint All Article Types Advanced Search Section All Sections Cancer Biomarkers Cancer Causes, Screening and Diagnosis Cancer Drug Development Cancer Epidemiology and Prevention Cancer Immunology and Immunotherapy Cancer Informatics and Big Data Cancer Metastasis Cancer Pathophysiology Cancer Therapy Clinical Trials of Cancer Infectious Agents and Cancer Methods and Technologies Development Molecular Cancer Biology Pediatric Oncology Systematic Review or Meta-Analysis in Cancer Research Transplant Oncology and Cancer Nursing Care Tumor Microenvironment All Sections Special Issue All Special Issues "The 10th International MDM2 Workshop"—Opening Up New Avenues for MDM2 and p53 Research T Cells and Myeloid Cells in Cancer Immunotherapy Helicobacter pylori Associated Cancer TP53 in Solid Tumors and Hematological Malignancies How Does Obesity Cause Cancer? Methylation Changes in Early Stage Non-small Cell Lung Cancer: New Evidences, Methodological Approaches and Applications Cancer and Liposomes 10th Anniversary of Cancers—Targeted Therapies for Ovarian Cancer Treatment from Bench to Bedside 2nd Edition: Adolescent and Young Adult Oncology 2nd Edition: Advances in the Management of Thyroid Cancer 2nd Edition: Colorectal Cancers 2nd Edition: Combination and Innovative Therapies for Pancreatic Cancer 2nd Edition: Estrogen Receptor-Positive (ER+) Breast Cancers 2nd Edition: New Perspectives of Ocular Oncology 2nd Edition: Resistance Mechanisms in Malignant Brain Tumors 3rd Etnean Occupational Medicine Workshop—Breast Cancer and Work 3D Cell Culture Cancer Models: Development and Applications A Deeper Dive into Signaling Pathways in Cancers A Selection of Papers from the Cancer Therapy 2021 Virtual Scientific Meeting A Selection of Papers from the Meeting on Cancer Science and Targeted Therapy Conference A Special Issue on Tumor Stroma Actionable Mutations in Lung Cancer Acute Myeloid Leukemia Acute Myeloid Leukemia (AML) Acute Myeloid Leukemia: From Diagnosis to Treatment Acute Myeloid Leukemia: The Future Is Bright Acute Promyelocytic Leukemia Acute Promyelocytic Leukemia (APML) Adaptation Strategies of Circulating Tumor Cells Adhesion and Integrins Adjuvant Chemotherapy for Colorectal Cancer Adrenocortical Carcinoma Advance and New Insights in Bladder Cancer Advance in Colorectal Cancer: A Themed Issue in Honor of Prof. Bengt Glimelius Advance in Computational Methods in Cancer Research Advance in Morbidity and Survivorship of Breast Cancer Advance in Supportive and Palliative Care in Cancer Advance Research in Thrombosis and Hematologic Malignancies Advanced Cancer Nanotheranostics Advanced Neuroendocrine Tumors Advanced NSCLC with Oncogene Addiction: An Ongoing Revolution Advanced Ovarian Cancer Advanced Pancreatic Cancer Advanced Prostate Cancer: From Bench to Bedside Advanced Research in Cancer Initiation and Early Detection Advanced Research in Glycoproteins and Cancer Advanced Research in Oncology in 2022 Advanced Research in Oncology in 2023 Advanced Research in Organs-on-a-Chip and Cancer Advanced Research in Pancreatic Ductal Adenocarcinoma Advanced Therapies for Hematological Cancers Advances and Research Progress in Hepatocellular Carcinoma Advances in Adrenocortical Carcinoma Research: Diagnosis, Treatment and Prognosis Advances in Antitumor Molecular-Targeted Agents of Urological Cancers Advances in Bone Metastatic Cancer Research Advances in Breast Cancer Brain Metastases Advances in Breast Cancer: A Themed Issue in Honor of Prof. Fernando Schmitt Advances in Breast Cancer: From Pathogenesis to Therapy Advances in Cancer Chemoprevention Advances in Cancer Cachexia Advances in Cancer Data and Statistics Advances in Cancer Disparities Advances in Cancer Epigenetics Advances in Cancer Radiotherapy Advances in Cancer Stem Cell Research Advances in Chordoma Advances in Chronic Lymphocytic Leukaemia (CLL) Research Advances in Diagnosis and Treatment for Bone and Soft Tissue Sarcoma Advances in Diagnosis, Treatment and Management of Endocrine Neoplasms Advances in Diagnostics and Treatment of Head and Neck Cancer Advances in Endometrial Cancer: From Pathogenesis, Pathology Diagnosis and Molecular Classification to Targeted Therapy Advances in Experimental Radiotherapy Advances in Follicular Lymphoma Advances in Genetic and Molecular Approaches to Skin Cancer Advances in Genetics and Epigenetics of Bladder Cancer Advances in Gynecological Oncology: From Pathogenesis to Therapy Advances in Head and Neck Cancer Research Advances in Head and Neck Squamous Cell Carcinoma Advances in Hematological Neoplasms: A Wide Perspective on the 2022 WHO and International Consensus Classifications Advances in HPB/GI Imaging Advances in Human-Papillomavirus-Related Squamous Cell Carcinoma: From Pathogenesis to Treatment Advances in Integrins in Cancer Advances in Locally Advanced and Metastatic Kidney Cancer Advances in Lymphoma, Plasma Cell Myeloma, and Leukemia Diagnostics Advances in Modern Radiation Oncology Advances in Neuroendocrine Neoplasms Advances in NK/T-cell Lymphoma, Epidemiology, Biology and Therapy Advances in Oral Cancers and Precancers Advances in Our Understanding of ALK-Related Cancers: A Selection of Papers from the Joint Annual Meeting of the European Research Initiative for ALK-Related Malignancies (ERIA) and the European Union Marie Curie European Training Network ALKATRAS Advances in Pancreatic Cancer Research Advances in Pancreatic Ductal Adenocarcinoma Diagnosis and Treatment Advances in Papillary Thyroid Cancer Research Advances in Parathyroid Carcinoma: From Bench to Bedside Advances in Plasma Cell Dyscrasias Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer Advances in Research, Diagnosis and Treatment of Brain Metastases Advances in Salivary Gland Carcinoma Advances in Soft Tissue and Bone Sarcoma Advances in Stimuli-Responsive Nanostructures for Cancer Therapy and Diagnosis Advances in Surgical Management of Colorectal Liver Metastases: Toward a Better Patient Selection, Lower Surgical Stress, and Multidisciplinary Approach Advances in the biological responses to radiation-induced DNA damage: A selection of papers from the Joint 43rd European Radiation Research Society (ERRS) and 20th German Society for Biological Radiation Research (GBS) Annual Meetings Advances in the Diagnosis, Prognosis and Treatment of Diffuse Large B-cell Lymphoma Advances in the Management of Hepatocellular Carcinoma Advances in the Management of Oligometastatic Disease in Non-colorectal Non-neuroendocrine Tumors Advances in the Management of Thyroid Cancer Advances in Thoracic Carcinoma and Translational Research Advances in Thoracic Oncology Advances in Thymic Tumors Advances in Translational Ovarian Cancer Research Advances in Translational Research for Soft Tissue Sarcomas Advances in Treatment for Hepatobiliary and Pancreatic Cancers: Multi-Disciplinary Strategies and Outcome Evaluation Advances in Treatment of Rare Tumors Advances in Triple-Negative Breast Cancer Advances in Tumor Angiogenesis Advances of Brain Mapping in Cancer Research Advances in Head and Neck Cancer Biology and Clinical Management Advances in In Vivo Quantitative and Qualitative Imaging Characterization of Gliomas<|im_end|> <|im_start|>assistant Apoptosis is the mechanism by which defective cells promote their own death to protect the body. It is a complex process, with many stages, in which the different parts of the cell gradually degrade. In glioblastoma cells, even when apoptosis begins, the process stops at one of the stages and allows the cell to survive. In previous studies, researchers had already demonstrated that glioblastoma cells have insufficient levels of DFF40/CAD, a protein that, during apoptosis, orchestrates the breakdown of the cell nucleus. This shortage means that the fragmentation step is not completed and the cell can recover. In the article, published in Cancers and coordinated by Dr. Víctor J. Yuste, professor at the Department of Biochemistry and Molecular Biology at the UAB Faculty of Medicine and researcher at the Institut de Neurociències of the UAB (INc-UAB), the researchers administered to the tumor cells a substance derived from the cotton plant, gossypol. This molecule enhances the activity of DFF40/CAD. The result is that, in the treated cells, the nuclear fragmentation process is completed and the cell dies. Dr. Laura Martinez-Escardó, researcher at the Department of Biochemistry and Molecular Biology of the UAB and first author of the work explains the finding, says, "We have seen that, contrary to other drugs, gossypol allows DFF40/CAD to stay in the nucleus for longer to promote its fragmentation. With our study, we demonstrated that compounds such as gossypol can push these cells to a point of no return after starting the cell death process without modifying them genetically." Dr. Yuste says, "Promoting apoptosis to end properly in tumor cells could be a good therapeutic strategy to treat glioblastoma. The findings presented are promising and encourage us to carry out further research. The new results help us better understand the biology of this aggressive tumor and may provide us with new tools for the development of more effective strategies. This is especially interesting because there is currently no cure for this disease." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract China’s Mars rover, Zhurong, touched down on Utopia Planitia in the northern lowlands of Mars (109.925° E, 25.066° N) in May 2021, and has been conducting in situ investigations of the landing area in conjunction with the Tianwen-1 orbiter. Here we present surface properties derived from the Zhurong rover’s traverse during the first 60 sols of rover operations. Our analysis of the rover’s position from locomotion data and camera imagery over that time shows that the rover traversed 450.9 m southwards over a flat surface with mild wheel slippage. Soil parameters determined by terramechanics, which observes wheel–terrain interactions, indicate that the topsoil has high bearing strength and cohesion. The soil’s equivalent stiffness is estimated to range from 1,390 to 5,872 kPa per m N , and the internal friction angle ranges from 21° to 34° under a cohesion of 1.5 to 6 kPa. Aeolian bedforms in the area are primarily transverse aeolian ridges, indicating northeastern local wind directions. Surface rocks imaged by the rover cameras show evidence of physical weathering processes, such as wind erosion, and potential chemical weathering processes. Joint investigations utilizing the scientific payloads of the rover and the orbiter can provide insights into local aeolian and aqueous history, and the habitability evolution of the northern lowlands on Mars. Main The Mars Exploration Probe Tianwen-1 lander, including the Zhurong rover, landed on Utopia Planitia of Mars on 15 May 2021 1 and successfully fulfilled the goals of orbiting, landing and roving on Mars. The Zhurong rover (Extended Data Fig. 1 ), a six-wheeled solar-powered robot with rocker-bogie suspension, is the first rover to land on the Northern Plain of Mars. Zhurong, working in high-mobility performance (Extended Data Table 1 ) and carrying six scientific payloads 2 , 3 , 4 , 5 , 6 , 7 , has been roving and conducting in situ investigations for more than the designed 90-sol primary mission at the time of this writing, and collected complementary scientific data at different scales and precisions for five primary scientific objectives 7 . Seven gigabits of scientific data have been relayed via the Tianwen-1 orbiter by the end of the first 60 sols, and some of them are currently under study. Here we present preliminary surface characterization results of the landing site based on the first 60 sols of cooperative observations from the Zhurong rover and the Tianwen-1 orbiter. Landing site description The landing site is localized to 109.925° E, 25.066° N in the planetocentric frame tied to the IAU/IAG 2000 Mars coordinate system using orbital, descent and rover images 8 , and mapped to the Tianwen-1’s high-resolution imaging camera (HiRIC)-derived digital elevation map at an elevation of −4,099.8 m (Fig. 1a ). The landing site has been further confirmed by the high-resolution imaging science experiment (HiRISE) onboard the Mars reconnaissance orbiter (MRO; Fig. 1b–e ), in which the lander and the rover can be identified. The landing site lies in the Late Hesperian lowland unit, dated to ~3.32–3.36 billion years ago 9 . The region contains hundreds of superposed pedestal-crater forms, thumbprint terrain, topographically subdued wrinkle ridges and narrow grabens northeast of Alba Mons 10 . We highlight the local area in a circular shape that might be within reach of the rover (centred on 109.925° E, 24.980° N; diameter, 20 km; Extended Data Fig. 2a ). The elevation of the landing area gradually increases heading south from −4,219 to −3,989 m, with an average elevation of −4,095 m and a standard deviation of 42.11 m (based on the Mars orbiter laser altimeter (MOLA) 11 digital elevation map 128PPD; 463 m pixel −1 ). Approximately 99% of the area consists of slopes less than 5°, and relatively high slopes are primarily distributed at impact crater rims (Extended Data Fig. 2b ). Therefore, the area is flat and may facilitate long-distance traversal and exploration of the Zhurong rover. Fig. 1: Regional geomorphological features of the Tianwen-1 landing site. a , Major physiographic features of the Tianwen-1 touchdown spot (in southern Utopia Planitia) on a base map of MOLA. Also shown are previous landings or roving missions (Viking 2, InSight, Mars Science Laboratory (MSL) Curiosity 39 , Mars Exploration Rover (MER) Spirit). The base map is a portion of the MOLA shaded-relief topographic map of Mars with geoid elevations (available at ). b – e , Orbital view ( b ) and enlarged images of the Tianwen-1 lander and Zhurong rover ( c ), parachute and backshell ( d ) and heatshield ( e ). The HiRISE image is ESP_069665_2055 at 29.2 cm pixel −1 (with 1 × 1 binning) acquired by NASA’s Mars reconnaissance orbiter on 6 June 2021. c , The Tianwen-1 lander (large bright green spot) and Zhurong rover (small bright green spot). d , The parachute (long bright white spot) and backshell (round bright green spot) located 109.923° N, 25.059° E at ~350 m to the southwest of the lander. e , The heatshield (109.901° N, 25.048° E) is ~1,617 m southwest of the lander in the panchromatic image. f , A 360° panorama of the Tianwen-1 landing site taken by the NaTeCam on sol 6 while the Zhurong rover was sitting on the lander platform. The panorama is composed of 12 images taken by the NaTeCam at a beginning azimuth of 164° at 30° intervals. The surface is smooth and flat without large boulders. Two plume-impinged traces reveal dark materials when removing the bright-toned dust and topsoil. On the southeast of the lander, there are several bright transverse aeolian ridges and small craters surrounded by several dark-toned rocks, probably ejected from the crater. Image credit: CNSA/BACC. Full size image The 360° panorama composed of 12 images taken by the navigation and terrain camera (NaTeCam) (Fig. 1f ) shows an overview of gentle topography at the landing site, with major surface geological features including aeolian bedforms, small craters and rocks. The surface is smooth and flat, without boulders. A bedrock is semi-buried in the reddish soil close to the plume-impinged traces.", "role": "user" }, { "content": "A team of researchers affiliated with multiple institutions in China and one each from Canada and Germany, has found data from the Chinese Mars rover Zhurong over its first 60 sols, showing evidence of wind erosion and possibly impacts from water erosion, as well. In their paper published in the journal Nature Geoscience, they discuss what they have found thus far. China's Mars rover Zhurong has been on the surface of Mars since May of last year. During that time, it has rolled approximately 450 meters over the course of 60 Martian days (sols). Recently, the team working with Zhurong made the data from the rover public. In this new effort, the researchers have been studying the data sent back to learn more about what it has found. Zhurong was deployed on the planet's Utopia Planitia—a volcanic plain situated in the northern hemisphere. It is a site that some have suggested was likely once covered with water. Data from the rover's cameras showed that the part of the plain where Zhurong has been rolling along is generally quite flat, with very few boulders. And data from the wheels showed that the surface beneath the rover is covered with small, non-round rocks. Zhurong has also been collecting soil samples as it wanders—thus far, the composition of the soil in the area is similar to that collected by rovers on other parts of the planet. Image data has also shown that the small rocks have etched grooves on them that appear to be due to wind erosion. They also found some evidence of flakiness in some of the rocks, possible evidence of water erosion. The researchers also found evidence of mega-ripples on the surface—features formed by wind—similar to sand dunes on Earth. They found the ripples appeared as bright streaks when viewed from an orbiting craft. They theorize the reason the ripples appear so bright is because they have been covered by a very thin layer of dust. If that turns out to the be case, they note, it would suggest that the wind that had formed the ripples was no longer present. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract China’s Mars rover, Zhurong, touched down on Utopia Planitia in the northern lowlands of Mars (109.925° E, 25.066° N) in May 2021, and has been conducting in situ investigations of the landing area in conjunction with the Tianwen-1 orbiter. Here we present surface properties derived from the Zhurong rover’s traverse during the first 60 sols of rover operations. Our analysis of the rover’s position from locomotion data and camera imagery over that time shows that the rover traversed 450.9 m southwards over a flat surface with mild wheel slippage. Soil parameters determined by terramechanics, which observes wheel–terrain interactions, indicate that the topsoil has high bearing strength and cohesion. The soil’s equivalent stiffness is estimated to range from 1,390 to 5,872 kPa per m N , and the internal friction angle ranges from 21° to 34° under a cohesion of 1.5 to 6 kPa. Aeolian bedforms in the area are primarily transverse aeolian ridges, indicating northeastern local wind directions. Surface rocks imaged by the rover cameras show evidence of physical weathering processes, such as wind erosion, and potential chemical weathering processes. Joint investigations utilizing the scientific payloads of the rover and the orbiter can provide insights into local aeolian and aqueous history, and the habitability evolution of the northern lowlands on Mars. Main The Mars Exploration Probe Tianwen-1 lander, including the Zhurong rover, landed on Utopia Planitia of Mars on 15 May 2021 1 and successfully fulfilled the goals of orbiting, landing and roving on Mars. The Zhurong rover (Extended Data Fig. 1 ), a six-wheeled solar-powered robot with rocker-bogie suspension, is the first rover to land on the Northern Plain of Mars. Zhurong, working in high-mobility performance (Extended Data Table 1 ) and carrying six scientific payloads 2 , 3 , 4 , 5 , 6 , 7 , has been roving and conducting in situ investigations for more than the designed 90-sol primary mission at the time of this writing, and collected complementary scientific data at different scales and precisions for five primary scientific objectives 7 . Seven gigabits of scientific data have been relayed via the Tianwen-1 orbiter by the end of the first 60 sols, and some of them are currently under study. Here we present preliminary surface characterization results of the landing site based on the first 60 sols of cooperative observations from the Zhurong rover and the Tianwen-1 orbiter. Landing site description The landing site is localized to 109.925° E, 25.066° N in the planetocentric frame tied to the IAU/IAG 2000 Mars coordinate system using orbital, descent and rover images 8 , and mapped to the Tianwen-1’s high-resolution imaging camera (HiRIC)-derived digital elevation map at an elevation of −4,099.8 m (Fig. 1a ). The landing site has been further confirmed by the high-resolution imaging science experiment (HiRISE) onboard the Mars reconnaissance orbiter (MRO; Fig. 1b–e ), in which the lander and the rover can be identified. The landing site lies in the Late Hesperian lowland unit, dated to ~3.32–3.36 billion years ago 9 . The region contains hundreds of superposed pedestal-crater forms, thumbprint terrain, topographically subdued wrinkle ridges and narrow grabens northeast of Alba Mons 10 . We highlight the local area in a circular shape that might be within reach of the rover (centred on 109.925° E, 24.980° N; diameter, 20 km; Extended Data Fig. 2a ). The elevation of the landing area gradually increases heading south from −4,219 to −3,989 m, with an average elevation of −4,095 m and a standard deviation of 42.11 m (based on the Mars orbiter laser altimeter (MOLA) 11 digital elevation map 128PPD; 463 m pixel −1 ). Approximately 99% of the area consists of slopes less than 5°, and relatively high slopes are primarily distributed at impact crater rims (Extended Data Fig. 2b ). Therefore, the area is flat and may facilitate long-distance traversal and exploration of the Zhurong rover. Fig. 1: Regional geomorphological features of the Tianwen-1 landing site. a , Major physiographic features of the Tianwen-1 touchdown spot (in southern Utopia Planitia) on a base map of MOLA. Also shown are previous landings or roving missions (Viking 2, InSight, Mars Science Laboratory (MSL) Curiosity 39 , Mars Exploration Rover (MER) Spirit). The base map is a portion of the MOLA shaded-relief topographic map of Mars with geoid elevations (available at ). b – e , Orbital view ( b ) and enlarged images of the Tianwen-1 lander and Zhurong rover ( c ), parachute and backshell ( d ) and heatshield ( e ). The HiRISE image is ESP_069665_2055 at 29.2 cm pixel −1 (with 1 × 1 binning) acquired by NASA’s Mars reconnaissance orbiter on 6 June 2021. c , The Tianwen-1 lander (large bright green spot) and Zhurong rover (small bright green spot). d , The parachute (long bright white spot) and backshell (round bright green spot) located 109.923° N, 25.059° E at ~350 m to the southwest of the lander. e , The heatshield (109.901° N, 25.048° E) is ~1,617 m southwest of the lander in the panchromatic image. f , A 360° panorama of the Tianwen-1 landing site taken by the NaTeCam on sol 6 while the Zhurong rover was sitting on the lander platform. The panorama is composed of 12 images taken by the NaTeCam at a beginning azimuth of 164° at 30° intervals. The surface is smooth and flat without large boulders. Two plume-impinged traces reveal dark materials when removing the bright-toned dust and topsoil. On the southeast of the lander, there are several bright transverse aeolian ridges and small craters surrounded by several dark-toned rocks, probably ejected from the crater. Image credit: CNSA/BACC. Full size image The 360° panorama composed of 12 images taken by the navigation and terrain camera (NaTeCam) (Fig. 1f ) shows an overview of gentle topography at the landing site, with major surface geological features including aeolian bedforms, small craters and rocks. The surface is smooth and flat, without boulders. A bedrock is semi-buried in the reddish soil close to the plume-impinged traces.<|im_end|> <|im_start|>assistant A team of researchers affiliated with multiple institutions in China and one each from Canada and Germany, has found data from the Chinese Mars rover Zhurong over its first 60 sols, showing evidence of wind erosion and possibly impacts from water erosion, as well. In their paper published in the journal Nature Geoscience, they discuss what they have found thus far. China's Mars rover Zhurong has been on the surface of Mars since May of last year. During that time, it has rolled approximately 450 meters over the course of 60 Martian days (sols). Recently, the team working with Zhurong made the data from the rover public. In this new effort, the researchers have been studying the data sent back to learn more about what it has found. Zhurong was deployed on the planet's Utopia Planitia—a volcanic plain situated in the northern hemisphere. It is a site that some have suggested was likely once covered with water. Data from the rover's cameras showed that the part of the plain where Zhurong has been rolling along is generally quite flat, with very few boulders. And data from the wheels showed that the surface beneath the rover is covered with small, non-round rocks. Zhurong has also been collecting soil samples as it wanders—thus far, the composition of the soil in the area is similar to that collected by rovers on other parts of the planet. Image data has also shown that the small rocks have etched grooves on them that appear to be due to wind erosion. They also found some evidence of flakiness in some of the rocks, possible evidence of water erosion. The researchers also found evidence of mega-ripples on the surface—features formed by wind—similar to sand dunes on Earth. They found the ripples appeared as bright streaks when viewed from an orbiting craft. They theorize the reason the ripples appear so bright is because they have been covered by a very thin layer of dust. If that turns out to the be case, they note, it would suggest that the wind that had formed the ripples was no longer present. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Leptomeningeal disease (LMD) is a devastating complication of solid tumor malignancies, with dire prognosis and no effective systemic treatment options. Over the past decade, the incidence of LMD has steadily increased due to therapeutics that have extended the survival of cancer patients, highlighting the need for new interventions. To examine the efficacy of immune checkpoint inhibitors (ICI) in patients with LMD, we completed two phase II clinical trials. Here, we investigate the cellular and molecular features underpinning observed patient trajectories in these trials by applying single-cell RNA and cell-free DNA profiling to longitudinal cerebrospinal fluid (CSF) draws from enrolled patients. We recover immune and malignant cell types in the CSF, characterize cell behavior changes following ICI, and identify genomic features associated with relevant clinical phenomena. Overall, our study describes the liquid LMD tumor microenvironment prior to and following ICI treatment and demonstrates clinical utility of cell-free and single-cell genomic measurements for LMD research. Introduction LMD—the infiltration of tumor cells into the leptomeninges and CSF—is an especially devastating complication of solid tumor malignancies, as it is usually rapidly fatal, with a median survival of about 4–6 weeks 1 . Approximately 5–8% of all cancer patients develop LMD 1 , 2 , 3 , with common histologies including breast cancer, lung cancer, and melanoma 2 , 3 . Furthermore, over the past decade, the incidence of LMD has risen due to increased patient survival through better tolerated and more effective treatment strategies. An effective systemic therapy for LMD is thus urgently needed, as current measures (e.g., craniospinal radiation and intrathecal therapies) have uncertain benefit and significant adverse effects 4 . Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, and demonstrated remarkable response rates in a variety of metastatic, chemotherapy-refractory solid tumors 5 , 6 , 7 . More recently, ICI has emerged as a promising option for central nervous system (CNS) metastases. Preclinical data have demonstrated infiltration of T cells and programmed death-ligand 1 (PD-L1) expression in brain metastases (BM) of various histologies 8 , 9 , suggesting the potential for ICI to be efficacious in the CNS. Relatedly, ICI for metastatic melanoma and non-small cell lung cancer parenchymal brain metastases has demonstrated objective intracranial responses at a rate similar to systemic disease 10 , 11 . To our knowledge, however, ICI as treatment for LMD has not been evaluated in prospective clinical trials. To address this unmet need, we initiated two phase II clinical trials of ICI in patients with LMD of any histology (NCT02886585, NCT02939300; see Methods). One trial (NCT02886585) evaluated the efficacy of an antibody targeting programmed cell death protein 1 (PD-1, drug name pembrolizumab) and the other (NCT02939300) evaluated targeting of PD-1 (drug name nivolumab) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, drug name ipilimumab). Both of these treatments were administered intravenously (IV), with blood and CSF drawn prior to each dose when clinically indicated (see Methods) and sent for genomic analysis. Notably, both trials achieved primary endpoint (60% and 44% of patients were alive at 3 months after enrollment in the pembrolizumab and ipilimumab/nivolumab trials, respectively) and showed improved overall median survival (3.6 and 2.9 months in the pembrolizumab and ipilimumab/nivolumab trials, respectively) compared to historical controls 12 , 13 . Despite the promise shown in NCT02886585 and NCT02939300, questions remain regarding the utility and long-term efficacy of ICI to treat LMD. For example, it is not known whether the clinical benefit observed in these patients is strictly a result of the systemic effects of ICI administration, or whether these extend to the CNS. Additionally, the cellular and molecular features that underlie patient response have yet to be elucidated. Here, we applied single-cell RNA-sequencing (scRNA-Seq) and cell-free DNA-sequencing (cfDNA-Seq) in conjunction with conventional clinical assays to serial CSF and peripheral blood leukocyte (PBL) samples from patients on these two ICI trials to: (1) describe the cellular composition of the LMD tumor microenvironment (TME); (2) assess inflammatory immune responses within the CSF; and, (3) identify potential factors informing the clinical courses observed in individual patients. Results scRNA-Seq of the LMD TME We performed longitudinal high-throughput scRNA-Seq (Fig. 1a ) on 12 pre-treatment and 25 post-treatment low-input CSF samples from 19 total patients enrolled in NCT02886585 and NCT02939300, including 9 patients sampled at multiple time points. After filtering for low quality cells, we retained 34,742 single cells from available clinical trial samples (Supplementary Fig. 1 ), which we further classified and visualized using dimensionality reduction by principal component analysis (PCA) 14 and uniform manifold approximation and projection (UMAP; Methods) 14 , 15 . Our analyses reveal 17 distinct clusters, which we identified through differential gene expression (Supplementary Data 2 ) as adaptive immune cells (including T cells, immunoglobulin-expressing B cells), innate immune cells (including dendritic cells, monocytes, and macrophages), and non-immune cells (Fig. 1b, c ). The non-immune cell clusters ( n = 11) exhibited strong patient-specific representation while the immune clusters ( n = 5) grouped by phenotype rather than patient (Supplementary Fig. 2 ), consistent with previous observations derived through scRNA-Seq of human tumors 16 , 17 . Fig. 1: Development of a pipeline for scRNA/cfDNA from longitudinally sampled CSF samples before and after ICI therapy. a Schematic representation of the longitudinal sampling performed on patients in this study. b Longitudinal sampling overview from patients in each study, including trial primary endpoint (dashed line), and date of patient mortality, when known. c UMAP of single-cell transcriptomes from all captured CSF cells in both trials, colored by patient, with cell type of origin indicated. Full size image After initially identifying non-immune clusters via unsupervised clustering, we confirmed their malignancy status for samples from NCT02886585 by inferring copy number variation (CNV) profiles for each cell and matching to DNA-based profiling results 17 , 18 , 19 . DNA-derived CNV profiles were obtained via whole exome sequencing (WES) of cell-free DNA (cfDNA) extracted from the CSF. Using these data, we confirmed that patient-specific non-immune clusters shared the inferred CNV profiles (as previously described) of their time-point matched cfDNA", "role": "user" }, { "content": "Two new studies indicate that immunotherapy may benefit people with leptomeningeal carcinomatosis (LMD), a rare but serious complication of cancer that has spread to the brain and/or spinal cord. The research, which was led by investigators at Massachusetts General Hospital (MGH), Dana-Farber Cancer Institute and the Broad Institute, is published in Nature Communications. Although advances in cancer treatment have extended patient survival, some cancers come back, often in a different location in the body. This may in part help explain recent increases in the incidence of LMD—when tumor cells infiltrate the leptomeninges (layers of tissue that cover the brain and spinal cord) and cerebrospinal fluid. Approximately 5–8% of all patients with cancer develop LMD after first being diagnosed with breast cancer, lung cancer, melanoma or other malignancies. Current treatment options rarely benefit patients with LMD, and there is an urgent need for new therapies. Immune checkpoint inhibitors are important medications that boost the immune system's response against various cancers, but their effects against LMD are unclear. To investigate, researchers conducted two phase II clinical trials. When they collected and analyzed immune cells and cancer cells from the cerebrospinal fluid of patients in the trials both before and after treatment with immune checkpoint inhibitors, the scientists found signs that the therapy was having an effect. For example, the number of certain cancer-killing immune cells and the expression of particular genes within cells were higher following treatment. The second article in Nature Communications presents the results of one of the phase II studies, which included 18 patients with LMD who received combined ipilimumab and nivolumab (two types of immune checkpoint inhibitors) until the cancer progressed or the patient experienced unacceptable toxicity. The primary endpoint was overall survival at 3 months, and 8 of the 18 patients were alive at that time. (Historically, patients survive for a median of 3–7 weeks after being diagnosed with LMD.) One-third of patients experienced one or more serious adverse events. Two patients discontinued treatment due to unacceptable toxicity. The most frequent adverse events include fatigue, nausea, fever, anorexia and rash. The authors noted that larger, multicenter clinical trials are needed to validate their results. \"In these two published studies, we demonstrated—in patients through a clinical trial and microscopically in the laboratory—that immune checkpoint blockade has promising activity for patients with LMD. More data is needed, but this is an exciting first step towards showing that immune checkpoint blockade may have a role in treating this devastating disease,\" says co-author Priscilla K. Brastianos, MD, who is the director of the Central Nervous System Metastasis Center at MGH and an associate professor of medicine at Harvard Medical School. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Leptomeningeal disease (LMD) is a devastating complication of solid tumor malignancies, with dire prognosis and no effective systemic treatment options. Over the past decade, the incidence of LMD has steadily increased due to therapeutics that have extended the survival of cancer patients, highlighting the need for new interventions. To examine the efficacy of immune checkpoint inhibitors (ICI) in patients with LMD, we completed two phase II clinical trials. Here, we investigate the cellular and molecular features underpinning observed patient trajectories in these trials by applying single-cell RNA and cell-free DNA profiling to longitudinal cerebrospinal fluid (CSF) draws from enrolled patients. We recover immune and malignant cell types in the CSF, characterize cell behavior changes following ICI, and identify genomic features associated with relevant clinical phenomena. Overall, our study describes the liquid LMD tumor microenvironment prior to and following ICI treatment and demonstrates clinical utility of cell-free and single-cell genomic measurements for LMD research. Introduction LMD—the infiltration of tumor cells into the leptomeninges and CSF—is an especially devastating complication of solid tumor malignancies, as it is usually rapidly fatal, with a median survival of about 4–6 weeks 1 . Approximately 5–8% of all cancer patients develop LMD 1 , 2 , 3 , with common histologies including breast cancer, lung cancer, and melanoma 2 , 3 . Furthermore, over the past decade, the incidence of LMD has risen due to increased patient survival through better tolerated and more effective treatment strategies. An effective systemic therapy for LMD is thus urgently needed, as current measures (e.g., craniospinal radiation and intrathecal therapies) have uncertain benefit and significant adverse effects 4 . Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, and demonstrated remarkable response rates in a variety of metastatic, chemotherapy-refractory solid tumors 5 , 6 , 7 . More recently, ICI has emerged as a promising option for central nervous system (CNS) metastases. Preclinical data have demonstrated infiltration of T cells and programmed death-ligand 1 (PD-L1) expression in brain metastases (BM) of various histologies 8 , 9 , suggesting the potential for ICI to be efficacious in the CNS. Relatedly, ICI for metastatic melanoma and non-small cell lung cancer parenchymal brain metastases has demonstrated objective intracranial responses at a rate similar to systemic disease 10 , 11 . To our knowledge, however, ICI as treatment for LMD has not been evaluated in prospective clinical trials. To address this unmet need, we initiated two phase II clinical trials of ICI in patients with LMD of any histology (NCT02886585, NCT02939300; see Methods). One trial (NCT02886585) evaluated the efficacy of an antibody targeting programmed cell death protein 1 (PD-1, drug name pembrolizumab) and the other (NCT02939300) evaluated targeting of PD-1 (drug name nivolumab) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4, drug name ipilimumab). Both of these treatments were administered intravenously (IV), with blood and CSF drawn prior to each dose when clinically indicated (see Methods) and sent for genomic analysis. Notably, both trials achieved primary endpoint (60% and 44% of patients were alive at 3 months after enrollment in the pembrolizumab and ipilimumab/nivolumab trials, respectively) and showed improved overall median survival (3.6 and 2.9 months in the pembrolizumab and ipilimumab/nivolumab trials, respectively) compared to historical controls 12 , 13 . Despite the promise shown in NCT02886585 and NCT02939300, questions remain regarding the utility and long-term efficacy of ICI to treat LMD. For example, it is not known whether the clinical benefit observed in these patients is strictly a result of the systemic effects of ICI administration, or whether these extend to the CNS. Additionally, the cellular and molecular features that underlie patient response have yet to be elucidated. Here, we applied single-cell RNA-sequencing (scRNA-Seq) and cell-free DNA-sequencing (cfDNA-Seq) in conjunction with conventional clinical assays to serial CSF and peripheral blood leukocyte (PBL) samples from patients on these two ICI trials to: (1) describe the cellular composition of the LMD tumor microenvironment (TME); (2) assess inflammatory immune responses within the CSF; and, (3) identify potential factors informing the clinical courses observed in individual patients. Results scRNA-Seq of the LMD TME We performed longitudinal high-throughput scRNA-Seq (Fig. 1a ) on 12 pre-treatment and 25 post-treatment low-input CSF samples from 19 total patients enrolled in NCT02886585 and NCT02939300, including 9 patients sampled at multiple time points. After filtering for low quality cells, we retained 34,742 single cells from available clinical trial samples (Supplementary Fig. 1 ), which we further classified and visualized using dimensionality reduction by principal component analysis (PCA) 14 and uniform manifold approximation and projection (UMAP; Methods) 14 , 15 . Our analyses reveal 17 distinct clusters, which we identified through differential gene expression (Supplementary Data 2 ) as adaptive immune cells (including T cells, immunoglobulin-expressing B cells), innate immune cells (including dendritic cells, monocytes, and macrophages), and non-immune cells (Fig. 1b, c ). The non-immune cell clusters ( n = 11) exhibited strong patient-specific representation while the immune clusters ( n = 5) grouped by phenotype rather than patient (Supplementary Fig. 2 ), consistent with previous observations derived through scRNA-Seq of human tumors 16 , 17 . Fig. 1: Development of a pipeline for scRNA/cfDNA from longitudinally sampled CSF samples before and after ICI therapy. a Schematic representation of the longitudinal sampling performed on patients in this study. b Longitudinal sampling overview from patients in each study, including trial primary endpoint (dashed line), and date of patient mortality, when known. c UMAP of single-cell transcriptomes from all captured CSF cells in both trials, colored by patient, with cell type of origin indicated. Full size image After initially identifying non-immune clusters via unsupervised clustering, we confirmed their malignancy status for samples from NCT02886585 by inferring copy number variation (CNV) profiles for each cell and matching to DNA-based profiling results 17 , 18 , 19 . DNA-derived CNV profiles were obtained via whole exome sequencing (WES) of cell-free DNA (cfDNA) extracted from the CSF. Using these data, we confirmed that patient-specific non-immune clusters shared the inferred CNV profiles (as previously described) of their time-point matched cfDNA<|im_end|> <|im_start|>assistant Two new studies indicate that immunotherapy may benefit people with leptomeningeal carcinomatosis (LMD), a rare but serious complication of cancer that has spread to the brain and/or spinal cord. The research, which was led by investigators at Massachusetts General Hospital (MGH), Dana-Farber Cancer Institute and the Broad Institute, is published in Nature Communications. Although advances in cancer treatment have extended patient survival, some cancers come back, often in a different location in the body. This may in part help explain recent increases in the incidence of LMD—when tumor cells infiltrate the leptomeninges (layers of tissue that cover the brain and spinal cord) and cerebrospinal fluid. Approximately 5–8% of all patients with cancer develop LMD after first being diagnosed with breast cancer, lung cancer, melanoma or other malignancies. Current treatment options rarely benefit patients with LMD, and there is an urgent need for new therapies. Immune checkpoint inhibitors are important medications that boost the immune system's response against various cancers, but their effects against LMD are unclear. To investigate, researchers conducted two phase II clinical trials. When they collected and analyzed immune cells and cancer cells from the cerebrospinal fluid of patients in the trials both before and after treatment with immune checkpoint inhibitors, the scientists found signs that the therapy was having an effect. For example, the number of certain cancer-killing immune cells and the expression of particular genes within cells were higher following treatment. The second article in Nature Communications presents the results of one of the phase II studies, which included 18 patients with LMD who received combined ipilimumab and nivolumab (two types of immune checkpoint inhibitors) until the cancer progressed or the patient experienced unacceptable toxicity. The primary endpoint was overall survival at 3 months, and 8 of the 18 patients were alive at that time. (Historically, patients survive for a median of 3–7 weeks after being diagnosed with LMD.) One-third of patients experienced one or more serious adverse events. Two patients discontinued treatment due to unacceptable toxicity. The most frequent adverse events include fatigue, nausea, fever, anorexia and rash. The authors noted that larger, multicenter clinical trials are needed to validate their results. "In these two published studies, we demonstrated—in patients through a clinical trial and microscopically in the laboratory—that immune checkpoint blockade has promising activity for patients with LMD. More data is needed, but this is an exciting first step towards showing that immune checkpoint blockade may have a role in treating this devastating disease," says co-author Priscilla K. Brastianos, MD, who is the director of the Central Nervous System Metastasis Center at MGH and an associate professor of medicine at Harvard Medical School. <|im_end|>

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2,094

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Emergence of new viral agents is driven by evolution of interactions between viral proteins and host targets. For instance, increased infectivity of SARS-CoV-2 compared to SARS-CoV-1 arose in part through rapid evolution along the interface between the spike protein and its human receptor ACE2, leading to increased binding affinity. To facilitate broader exploration of how pathogen–host interactions might impact transmission and virulence in the ongoing COVID-19 pandemic, we performed state-of-the-art interface prediction followed by molecular docking to construct a three-dimensional structural interactome between SARS-CoV-2 and human. We additionally carried out downstream meta-analyses to investigate enrichment of sequence divergence between SARS-CoV-1 and SARS-CoV-2 or human population variants along viral–human protein-interaction interfaces, predict changes in binding affinity by these mutations/variants and further prioritize drug repurposing candidates predicted to competitively bind human targets. We believe this resource ( ) will aid in development and testing of informed hypotheses for SARS-CoV-2 etiology and treatments. Main The ongoing global COVID-19 pandemic has resulted in over 210 million SARS-CoV-2 infections and over 4.4 million deaths worldwide 1 . The coronavirus family of enveloped viruses causes respiratory and enteric tract infections in avian and mammalian hosts 2 . Seven well characterized human coronaviruses 3 , 4 , 5 exhibit symptoms ranging from mild respiratory illness to severe pneumonia and acute respiratory distress syndrome. These coronaviruses are either highly transmissible yet generally not highly pathogenic (for example HCoV-229E and HCoV-OC43) or highly pathogenic but poorly transmissible (SARS-CoV-1 and MERS-CoV). Unique from these, SARS-CoV-2 is both highly transmissible and capable of causing severe disease with infectivity and pathogenesis differing between individuals 6 , 7 . While ~25–35% of infected individuals experience only mild or minimal symptoms, ~1–2% of infected patients die primarily from severe respiratory failure and acute respiratory distress syndrome 8 , 9 . Differences in morbidity, hospitalization and mortality among different ethnic groups 10 , 11 , 12 , 13 , 14 , 15 are not fully explained by cardiometabolic, socioeconomic or behavioral factors, suggesting a role for human genetic variation in SARS-CoV-2 pathogenicity. Insights into the evolution of SARS-CoV-2, its elevated transmission relative to SARS-CoV-1 and dynamic range of symptoms have been key areas of interest. These traits are likely driven by molecular mechanisms of pathology, including interactions between the virus and its host, but specific causes are yet to be fully characterized. Networks of protein–protein interactions between pathogens and their hosts provide one avenue to understand mechanisms of infection and pathology. Viral–human interactome maps have been compiled for SARS-CoV-1 (ref. 16 ), HIV 17 , Ebola virus 18 and Dengue and Zika viruses 19 among others. Recent, affinity-purification mass spectrometry experiments on 29 SARS-CoV-2 proteins identified 332 viral–human interactions 20 . Interspecies interactions contribute to disease progression by facilitating pathogen entry into host cells 21 , 22 , 23 , 24 , 25 , 26 , inhibiting host response proteins and pathways 27 , 28 , 29 and hijacking cell signaling or metabolism to accelerate cellular (and consequentially viral) replication 30 , 31 , 32 . Structures and dynamics of these interactions can provide insights into their roles. For instance, the viral–human binding interface between poxvirus chemokine inhibitor vCCI and human MIP-1β is shown to occlude domains vital to chemokine homodimerization, receptor binding and interactions with GAG, thus explaining the inhibitory effect of poxvirus on chemokine signaling 29 . Additionally, the dynamics of a herpesvirus cyclin and human CDK2 interaction induce a conformational change on CDK2 that matches its interaction with human cyclin A, leading to dysregulated cell cycle progression 31 . Because protein–protein interactions mediate the majority of protein function 33 , 34 , 35 , targeted disruption by small-molecule inhibitors that compete for the same binding site provide a precise toolkit to modulate cellular function 33 , 35 , 36 , 37 , 38 . For instance, BCL-2 inhibitors that displace bound anti-apoptotic BCL-X interactors can treat chronic lymphocytic leukemia pathogenesis 39 . This approach can be particularly effective in viral networks and several potent inhibitors of key interactions have been developed. Disruption of viral complexes involved in viral replication has been successful in vaccinia virus 40 and human papilloma virus therapies 41 , 42 . Specifically, disruption of viral–host protein–protein interactions involved in early viral infection is an important therapeutic strategy. Discovery that a population variant in the membrane protein CCR5 conferred resistance to HIV-1 by disrupting its interaction with the viral envelope glycoprotein led to the development of Maraviroc as a US Food and Drug Administration-approved treatment for HIV-1 that functions by blocking the interface for this interaction 23 , 43 . Here we apply a full-interactome modeling framework to construct a three-dimensional (3D) structural interactome between SARS-CoV-2 and human proteins. Our framework first applies our previous ECLAIR framework 44 to identify interface residues for the whole SARS-CoV-2–human interactome and leverages these predictions to guide atomic-resolution interface modeling and docking in HADDOCK 45 , 46 . We additionally carried out in silico scanning mutagenesis in PyRosetta 47 to predict the impact of mutations on interaction binding affinity and explored the overlap between protein–protein and protein–drug binding sites. All results from our 3D structural interactome are provided as a user-friendly web server allowing exploration of individual interactions or bulk download and analysis of the whole dataset. We further explore the utility of our 3D interactome modeling approach in identifying key interactions undergoing evolution along viral-protein interfaces, highlighting population variants on human interfaces that could modulate the strength of viral–host interactions to confer protection from or susceptibility to COVID-19 and prioritizing drug candidates predicted to bind competitively at viral–human interaction interfaces, some of which could potentially be used for therapeutic purposes. Cumulatively these predictions and analyses are intended as a resource to facilitate investigation and further characterization of SARS-CoV-2–human interactions. Results Enrichment of variation on the spike–ACE2-binding interface We highlight the utility of computational and structural approaches to model the SARS-CoV-2–human interactome, from the interaction between the SARS-CoV-2 spike protein (S) and human angiotensin-converting enzyme 2 (ACE2) (Fig. 1a ). This interaction", "role": "user" }, { "content": "A computational tool allows researchers to precisely predict locations on the surfaces of human and COVID-19 viral proteins that bind with each other, a breakthrough that will greatly benefit our understanding of the virus and the development of drugs that block binding sites. The tool's developers have provided a user-friendly interactive web server that displays all of the protein structures, such that virologists and clinicians without computational skills can make use of the protein models to see if existing drugs, or those in development, fit into the proper binding sites. The study, published Nov. 29 in Nature Methods, describes the tool and uses it to predict how the SARS-COV-2 diverged structurally from SARS-COV-1 (which caused a SARS outbreak in 2002-04); how genetic variation of proteins in human populations may contribute to virus-human binding and higher risk of infection; and which existing drugs show promise for binding to targets on surfaces of human proteins. \"Our computational tool allows you to see with unprecedented resolution where the viral proteins are binding on the human protein, and therefore, we can really understand what part of these proteins are key for these interactions,\" said Hiayuan Yu, the study's senior author and a professor in the Department of Biological Statistics and Computational Biology and the Weill Institute for Cell and Molecular Biology. Shayne Wierbowski, a graduate student in Yu's lab, is the paper's first author. A previous study by other scientists described interactions between COVID-19 and human proteins, for the purpose of repurposing human drugs to block the virus from binding. But binding interfaces are small compared to the overall protein's surface, and previous research has lacked the detailed resolution to understand exactly where drugs might block a binding site. \"The tool we developed to predict protein-to-protein interfaces is the most accurate,\" Yu said, \"and we can use it to make the most informed predictions for any interactions.\" The pandemic spurred a surge of research worldwide to understand the structure of SARS-COV-2, with scientists using advanced imaging technologies to reveal proteins that make the virus infectious. As a result, Yu and colleagues were able to validate their computationally predicted structures against those described by others using imaging technologies. The tool also allows researchers to predict how genetic variations in human proteins affect viral-protein interactions, as two people of similar health and age can have diverging responses to catching COVID-19, with some being asymptomatic and others showing dramatic negative reactions. \"Because of our structural models, we can predict how mutations to proteins in individuals potentially affect viral interactions,\" Yu said. The results could one day shed light on whether some individuals may be at higher risk due to their genetics, which could prioritize them for monitoring, vaccines and treatments. Additionally, the tool will not only help clinicians develop drugs that precisely target human protein binding sites, it can also help reduce toxic or negative effects that could result when drugs bind to the wrong sites. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Emergence of new viral agents is driven by evolution of interactions between viral proteins and host targets. For instance, increased infectivity of SARS-CoV-2 compared to SARS-CoV-1 arose in part through rapid evolution along the interface between the spike protein and its human receptor ACE2, leading to increased binding affinity. To facilitate broader exploration of how pathogen–host interactions might impact transmission and virulence in the ongoing COVID-19 pandemic, we performed state-of-the-art interface prediction followed by molecular docking to construct a three-dimensional structural interactome between SARS-CoV-2 and human. We additionally carried out downstream meta-analyses to investigate enrichment of sequence divergence between SARS-CoV-1 and SARS-CoV-2 or human population variants along viral–human protein-interaction interfaces, predict changes in binding affinity by these mutations/variants and further prioritize drug repurposing candidates predicted to competitively bind human targets. We believe this resource ( ) will aid in development and testing of informed hypotheses for SARS-CoV-2 etiology and treatments. Main The ongoing global COVID-19 pandemic has resulted in over 210 million SARS-CoV-2 infections and over 4.4 million deaths worldwide 1 . The coronavirus family of enveloped viruses causes respiratory and enteric tract infections in avian and mammalian hosts 2 . Seven well characterized human coronaviruses 3 , 4 , 5 exhibit symptoms ranging from mild respiratory illness to severe pneumonia and acute respiratory distress syndrome. These coronaviruses are either highly transmissible yet generally not highly pathogenic (for example HCoV-229E and HCoV-OC43) or highly pathogenic but poorly transmissible (SARS-CoV-1 and MERS-CoV). Unique from these, SARS-CoV-2 is both highly transmissible and capable of causing severe disease with infectivity and pathogenesis differing between individuals 6 , 7 . While ~25–35% of infected individuals experience only mild or minimal symptoms, ~1–2% of infected patients die primarily from severe respiratory failure and acute respiratory distress syndrome 8 , 9 . Differences in morbidity, hospitalization and mortality among different ethnic groups 10 , 11 , 12 , 13 , 14 , 15 are not fully explained by cardiometabolic, socioeconomic or behavioral factors, suggesting a role for human genetic variation in SARS-CoV-2 pathogenicity. Insights into the evolution of SARS-CoV-2, its elevated transmission relative to SARS-CoV-1 and dynamic range of symptoms have been key areas of interest. These traits are likely driven by molecular mechanisms of pathology, including interactions between the virus and its host, but specific causes are yet to be fully characterized. Networks of protein–protein interactions between pathogens and their hosts provide one avenue to understand mechanisms of infection and pathology. Viral–human interactome maps have been compiled for SARS-CoV-1 (ref. 16 ), HIV 17 , Ebola virus 18 and Dengue and Zika viruses 19 among others. Recent, affinity-purification mass spectrometry experiments on 29 SARS-CoV-2 proteins identified 332 viral–human interactions 20 . Interspecies interactions contribute to disease progression by facilitating pathogen entry into host cells 21 , 22 , 23 , 24 , 25 , 26 , inhibiting host response proteins and pathways 27 , 28 , 29 and hijacking cell signaling or metabolism to accelerate cellular (and consequentially viral) replication 30 , 31 , 32 . Structures and dynamics of these interactions can provide insights into their roles. For instance, the viral–human binding interface between poxvirus chemokine inhibitor vCCI and human MIP-1β is shown to occlude domains vital to chemokine homodimerization, receptor binding and interactions with GAG, thus explaining the inhibitory effect of poxvirus on chemokine signaling 29 . Additionally, the dynamics of a herpesvirus cyclin and human CDK2 interaction induce a conformational change on CDK2 that matches its interaction with human cyclin A, leading to dysregulated cell cycle progression 31 . Because protein–protein interactions mediate the majority of protein function 33 , 34 , 35 , targeted disruption by small-molecule inhibitors that compete for the same binding site provide a precise toolkit to modulate cellular function 33 , 35 , 36 , 37 , 38 . For instance, BCL-2 inhibitors that displace bound anti-apoptotic BCL-X interactors can treat chronic lymphocytic leukemia pathogenesis 39 . This approach can be particularly effective in viral networks and several potent inhibitors of key interactions have been developed. Disruption of viral complexes involved in viral replication has been successful in vaccinia virus 40 and human papilloma virus therapies 41 , 42 . Specifically, disruption of viral–host protein–protein interactions involved in early viral infection is an important therapeutic strategy. Discovery that a population variant in the membrane protein CCR5 conferred resistance to HIV-1 by disrupting its interaction with the viral envelope glycoprotein led to the development of Maraviroc as a US Food and Drug Administration-approved treatment for HIV-1 that functions by blocking the interface for this interaction 23 , 43 . Here we apply a full-interactome modeling framework to construct a three-dimensional (3D) structural interactome between SARS-CoV-2 and human proteins. Our framework first applies our previous ECLAIR framework 44 to identify interface residues for the whole SARS-CoV-2–human interactome and leverages these predictions to guide atomic-resolution interface modeling and docking in HADDOCK 45 , 46 . We additionally carried out in silico scanning mutagenesis in PyRosetta 47 to predict the impact of mutations on interaction binding affinity and explored the overlap between protein–protein and protein–drug binding sites. All results from our 3D structural interactome are provided as a user-friendly web server allowing exploration of individual interactions or bulk download and analysis of the whole dataset. We further explore the utility of our 3D interactome modeling approach in identifying key interactions undergoing evolution along viral-protein interfaces, highlighting population variants on human interfaces that could modulate the strength of viral–host interactions to confer protection from or susceptibility to COVID-19 and prioritizing drug candidates predicted to bind competitively at viral–human interaction interfaces, some of which could potentially be used for therapeutic purposes. Cumulatively these predictions and analyses are intended as a resource to facilitate investigation and further characterization of SARS-CoV-2–human interactions. Results Enrichment of variation on the spike–ACE2-binding interface We highlight the utility of computational and structural approaches to model the SARS-CoV-2–human interactome, from the interaction between the SARS-CoV-2 spike protein (S) and human angiotensin-converting enzyme 2 (ACE2) (Fig. 1a ). This interaction<|im_end|> <|im_start|>assistant A computational tool allows researchers to precisely predict locations on the surfaces of human and COVID-19 viral proteins that bind with each other, a breakthrough that will greatly benefit our understanding of the virus and the development of drugs that block binding sites. The tool's developers have provided a user-friendly interactive web server that displays all of the protein structures, such that virologists and clinicians without computational skills can make use of the protein models to see if existing drugs, or those in development, fit into the proper binding sites. The study, published Nov. 29 in Nature Methods, describes the tool and uses it to predict how the SARS-COV-2 diverged structurally from SARS-COV-1 (which caused a SARS outbreak in 2002-04); how genetic variation of proteins in human populations may contribute to virus-human binding and higher risk of infection; and which existing drugs show promise for binding to targets on surfaces of human proteins. "Our computational tool allows you to see with unprecedented resolution where the viral proteins are binding on the human protein, and therefore, we can really understand what part of these proteins are key for these interactions," said Hiayuan Yu, the study's senior author and a professor in the Department of Biological Statistics and Computational Biology and the Weill Institute for Cell and Molecular Biology. Shayne Wierbowski, a graduate student in Yu's lab, is the paper's first author. A previous study by other scientists described interactions between COVID-19 and human proteins, for the purpose of repurposing human drugs to block the virus from binding. But binding interfaces are small compared to the overall protein's surface, and previous research has lacked the detailed resolution to understand exactly where drugs might block a binding site. "The tool we developed to predict protein-to-protein interfaces is the most accurate," Yu said, "and we can use it to make the most informed predictions for any interactions." The pandemic spurred a surge of research worldwide to understand the structure of SARS-COV-2, with scientists using advanced imaging technologies to reveal proteins that make the virus infectious. As a result, Yu and colleagues were able to validate their computationally predicted structures against those described by others using imaging technologies. The tool also allows researchers to predict how genetic variations in human proteins affect viral-protein interactions, as two people of similar health and age can have diverging responses to catching COVID-19, with some being asymptomatic and others showing dramatic negative reactions. "Because of our structural models, we can predict how mutations to proteins in individuals potentially affect viral interactions," Yu said. The results could one day shed light on whether some individuals may be at higher risk due to their genetics, which could prioritize them for monitoring, vaccines and treatments. Additionally, the tool will not only help clinicians develop drugs that precisely target human protein binding sites, it can also help reduce toxic or negative effects that could result when drugs bind to the wrong sites. <|im_end|>

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16628, 49853, 264, 390, 1659, 278, 2349, 389, 11325, 42, 17, 430, 9248, 1202, 16628, 449, 3823, 32343, 258, 362, 11, 6522, 311, 22709, 81722, 2849, 11008, 33824, 220, 2148, 662, 9393, 13128, 4235, 79565, 22639, 1812, 6629, 279, 8857, 315, 13128, 734, 220, 1644, 1174, 220, 1958, 1174, 220, 1758, 1174, 17550, 44219, 555, 2678, 1474, 55269, 68642, 430, 20874, 369, 279, 1890, 11212, 2816, 3493, 264, 24473, 66994, 311, 1491, 6468, 35693, 734, 220, 1644, 1174, 220, 1758, 1174, 220, 1927, 1174, 220, 1806, 1174, 220, 1987, 662, 1789, 2937, 11, 426, 3218, 12, 17, 68642, 430, 834, 2050, 6965, 7294, 46256, 2985, 14546, 426, 3218, 31650, 16681, 1105, 649, 4322, 21249, 43745, 511, 70504, 96306, 1853, 52379, 220, 2137, 662, 1115, 5603, 649, 387, 8104, 7524, 304, 29962, 14488, 323, 3892, 36875, 68642, 315, 1401, 22639, 617, 1027, 8040, 13, 4185, 14455, 315, 29962, 69125, 6532, 304, 29962, 48891, 706, 1027, 6992, 304, 14027, 91550, 17188, 220, 1272, 323, 3823, 26365, 484, 7942, 17188, 52312, 220, 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220, 1774, 1174, 220, 2790, 662, 1226, 37938, 11953, 704, 304, 5554, 4042, 36201, 5318, 8703, 14093, 304, 5468, 75120, 27625, 220, 2618, 311, 7168, 279, 5536, 315, 34684, 389, 16628, 11212, 51552, 323, 36131, 279, 28347, 1990, 13128, 4235, 79565, 323, 13128, 4235, 73821, 11212, 6732, 13, 2052, 3135, 505, 1057, 220, 18, 35, 24693, 16681, 638, 527, 3984, 439, 264, 1217, 22658, 3566, 3622, 10923, 27501, 315, 3927, 22639, 477, 20155, 4232, 323, 6492, 315, 279, 4459, 10550, 13, 1226, 4726, 13488, 279, 15919, 315, 1057, 220, 18, 35, 16681, 638, 34579, 5603, 304, 25607, 1401, 22639, 47397, 15740, 3235, 29962, 10039, 39340, 25066, 11, 39686, 7187, 27103, 389, 3823, 25066, 430, 1436, 1491, 6468, 279, 8333, 315, 29962, 4235, 3875, 22639, 311, 49843, 9313, 505, 477, 88636, 311, 20562, 12, 777, 323, 45777, 4954, 5623, 11426, 19698, 311, 10950, 52304, 3210, 520, 29962, 4235, 26380, 16628, 25066, 11, 1063, 315, 902, 1436, 13893, 387, 1511, 369, 37471, 10096, 13, 32678, 360, 8046, 1521, 20492, 323, 29060, 527, 10825, 439, 264, 5211, 311, 28696, 8990, 323, 4726, 60993, 315, 328, 17485, 87271, 53, 12, 17, 4235, 26380, 22639, 13, 18591, 2998, 14172, 479, 315, 23851, 389, 279, 37393, 4235, 5693, 17, 65500, 3834, 1226, 11415, 279, 15919, 315, 55580, 323, 24693, 20414, 311, 1646, 279, 328, 17485, 87271, 53, 12, 17, 4235, 26380, 16681, 638, 11, 505, 279, 16628, 1990, 279, 328, 17485, 87271, 53, 12, 17, 37393, 13128, 320, 50, 8, 323, 3823, 6590, 11345, 729, 258, 15204, 50517, 49242, 220, 17, 320, 5693, 17, 8, 320, 30035, 13, 220, 16, 64, 7609, 1115, 16628, 128257, 198, 128256, 78191, 198, 32, 55580, 5507, 6276, 12074, 311, 24559, 7168, 10687, 389, 279, 27529, 315, 3823, 323, 20562, 12, 777, 29962, 28896, 430, 10950, 449, 1855, 1023, 11, 264, 42445, 430, 690, 19407, 8935, 1057, 8830, 315, 279, 17188, 323, 279, 4500, 315, 11217, 430, 2565, 11212, 6732, 13, 578, 5507, 596, 13707, 617, 3984, 264, 1217, 22658, 21416, 3566, 3622, 430, 19207, 682, 315, 279, 13128, 14726, 11, 1778, 430, 3355, 299, 848, 1705, 323, 78545, 2085, 55580, 7512, 649, 1304, 1005, 315, 279, 13128, 4211, 311, 1518, 422, 6484, 11217, 11, 477, 1884, 304, 4500, 11, 5052, 1139, 279, 6300, 11212, 6732, 13, 578, 4007, 11, 4756, 4723, 13, 220, 1682, 304, 22037, 19331, 11, 16964, 279, 5507, 323, 5829, 433, 311, 7168, 1268, 279, 328, 17485, 7813, 40057, 12, 17, 37441, 3640, 2080, 43024, 505, 328, 17485, 7813, 40057, 12, 16, 320, 8370, 9057, 264, 328, 17485, 31188, 304, 220, 1049, 17, 12, 2371, 1237, 1268, 19465, 23851, 315, 28896, 304, 3823, 22673, 1253, 17210, 311, 17188, 70095, 11212, 323, 5190, 5326, 315, 19405, 26, 323, 902, 6484, 11217, 1501, 11471, 369, 11212, 311, 11811, 389, 27529, 315, 3823, 28896, 13, 330, 8140, 55580, 5507, 6276, 499, 311, 1518, 449, 31069, 11175, 1405, 279, 29962, 28896, 527, 11212, 389, 279, 3823, 13128, 11, 323, 9093, 11, 584, 649, 2216, 3619, 1148, 961, 315, 1521, 28896, 527, 1401, 369, 1521, 22639, 1359, 1071, 21694, 352, 10602, 28372, 11, 279, 4007, 596, 10195, 3229, 323, 264, 14561, 304, 279, 6011, 315, 63711, 25647, 323, 93028, 40023, 323, 279, 1226, 484, 10181, 369, 14299, 323, 60825, 40023, 13, 74984, 818, 468, 1291, 65, 29384, 11, 264, 19560, 5575, 304, 28372, 596, 10278, 11, 374, 279, 5684, 596, 1176, 3229, 13, 362, 3766, 4007, 555, 1023, 14248, 7633, 22639, 1990, 20562, 12, 777, 323, 3823, 28896, 11, 369, 279, 7580, 315, 2109, 324, 8478, 3823, 11217, 311, 2565, 279, 17188, 505, 11212, 13, 2030, 11212, 25066, 527, 2678, 7863, 311, 279, 8244, 13128, 596, 7479, 11, 323, 3766, 3495, 706, 49101, 279, 11944, 11175, 311, 3619, 7041, 1405, 11217, 2643, 2565, 264, 11212, 2816, 13, 330, 791, 5507, 584, 8040, 311, 7168, 13128, 4791, 10039, 39340, 25066, 374, 279, 1455, 13687, 1359, 28372, 1071, 11, 330, 438, 584, 649, 1005, 433, 311, 1304, 279, 1455, 16369, 20492, 369, 904, 22639, 1210, 578, 28522, 85747, 264, 22531, 315, 3495, 15603, 311, 3619, 279, 6070, 315, 328, 17485, 7813, 40057, 12, 17, 11, 449, 14248, 1701, 11084, 32758, 14645, 311, 16805, 28896, 430, 1304, 279, 17188, 50600, 13, 1666, 264, 1121, 11, 28372, 323, 18105, 1051, 3025, 311, 9788, 872, 3801, 30154, 19698, 14726, 2403, 1884, 7633, 555, 3885, 1701, 32758, 14645, 13, 578, 5507, 1101, 6276, 12074, 311, 7168, 1268, 19465, 27339, 304, 3823, 28896, 7958, 29962, 10039, 39340, 22639, 11, 439, 1403, 1274, 315, 4528, 2890, 323, 4325, 649, 617, 37441, 3252, 14847, 311, 34168, 20562, 12, 777, 11, 449, 1063, 1694, 97354, 13795, 323, 3885, 9204, 22520, 8389, 25481, 13, 330, 18433, 315, 1057, 24693, 4211, 11, 584, 649, 7168, 1268, 34684, 311, 28896, 304, 7931, 13893, 7958, 29962, 22639, 1359, 28372, 1071, 13, 578, 3135, 1436, 832, 1938, 25351, 3177, 389, 3508, 1063, 7931, 1253, 387, 520, 5190, 5326, 4245, 311, 872, 56104, 11, 902, 1436, 63652, 1124, 369, 16967, 11, 40300, 323, 22972, 13, 23212, 11, 279, 5507, 690, 539, 1193, 1520, 78545, 2274, 11217, 430, 24559, 2218, 3823, 13128, 11212, 6732, 11, 433, 649, 1101, 1520, 8108, 21503, 477, 8389, 6372, 430, 1436, 1121, 994, 11217, 10950, 311, 279, 5076, 6732, 13, 220, 128257, 198 ]

2,075

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Background The gut microbiome changes in response to a range of environmental conditions, life events and disease states. Pregnancy is a natural life event that involves major physiological adaptation yet studies of the microbiome in pregnancy are limited and their findings inconsistent. Pregnancy with type 1 diabetes (T1D) is associated with increased maternal and fetal risks but the gut microbiome in this context has not been characterized. By whole metagenome sequencing (WMS), we defined the taxonomic composition and function of the gut bacterial microbiome across 70 pregnancies, 36 in women with T1D. Results Women with and without T1D exhibited compositional and functional changes in the gut microbiome across pregnancy. Profiles in women with T1D were distinct, with an increase in bacteria that produce lipopolysaccharides and a decrease in those that produce short-chain fatty acids, especially in the third trimester. In addition, women with T1D had elevated concentrations of fecal calprotectin, a marker of intestinal inflammation, and serum intestinal fatty acid-binding protein (I-FABP), a marker of intestinal epithelial damage. Conclusions Women with T1D exhibit a shift towards a more pro-inflammatory gut microbiome during pregnancy, associated with evidence of intestinal inflammation. These changes could contribute to the increased risk of pregnancy complications in women with T1D and are potentially modifiable by dietary means. Video abstract Background The gut microbiome provides essential metabolites, vitamins, co-factors and hormones, protects against pathogenic microorganisms and has a key role in the development of the immune and other systems [ 1 , 2 ]. Changes in the composition of the gut microbiome are associated with ageing, environmental conditions, life events and disease states [ 2 , 3 , 4 ]. In pregnancy, women undergo significant physiological changes, but only recently has the gut microbiome been studied in this context [ 5 , 6 ]. Koren et al. [ 5 ] sampled the gut microbiome in the first and third trimesters and found that the taxonomic composition in the first trimester was similar to that of non-pregnant women but in the third trimester the abundance of Actinobacteria and Proteobacteria phyla increased along with an overall decrease in bacterial richness (alpha diversity). In studies in germ-free mice, they observed that inoculation with third compared to first trimester feces led to greater weight gain, insulin resistance and gut inflammation and suggested this was an adaptive proinflammatory response to defend the fetus from pathogens and provide it with nutrients. In contrast, after analysing fecal samples weekly across pregnancy, DiGiulio et al. [ 6 ] found no significant temporal differences in diversity or composition of the gut microbiome. These contrary findings and the dearth of studies warrant further investigation of the gut microbiome in pregnancy. Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing β cells in the islets of the pancreas are destroyed by T lymphocytes leading to insulin deficiency [ 7 ]. In pregnancy, T1D is associated with systemic and intra-uterine markers of sub-clinical inflammation and higher risks of complications for mother and fetus [ 8 , 9 , 10 ]. Alterations in the bacterial gut microbiome have been reported in T1D, mainly in children at high risk and at diagnosis (reviewed in [ 11 ], [ 12 , 13 , 14 , 15 , 16 , 17 ]). They include a decrease in alpha diversity (richness) [ 12 , 13 , 14 ] and in the abundance of lactate- and butyrate-producing and mucin-degrading bacteria [ 13 , 14 , 15 , 16 , 17 ], and an increase in the abundance of the Bacteroides genus [ 13 , 14 ]. Functionally, these compositional changes are reflected by a decreased abundance of genes encoding related metabolic pathways and enzymes, e.g. butyryl-coenzyme A (CoA)-CoA transferase [ 15 ] and butyryl-CoA dehydrogenase for butyrate synthesis [ 16 ]. These changes are not necessarily specific for T1D but nevertheless, they may have clinical consequences, including in pregnancy. Gut butyrate is a key determinant of gut health and regulator of gene expression and homeostatic immunity [ 18 , 19 , 20 ]. It is the major energy source for the colonic mucosa, induces the synthesis of mucin and it promotes gut epithelial integrity, preventing ‘gut leakiness’. In the non-obese diabetic (NOD) mouse model of T1D, dietary butyrate supplementation promoted an increase in regulatory T cells and a decrease in the incidence of spontaneous diabetes [ 20 ]. Increased gut leakiness has been described in established T1D [ 21 ] and recently by ourselves in association with gut microbiome changes in children with islet autoimmunity who progressed to T1D [ 22 ]. Gut leakiness with translocation of toxins and dietary antigens into the blood may result in systemic inflammation, reported with T1D in pregnancy complicated by pre-eclampsia [ 10 ]. Because a consensus about the gut microbiome in pregnancy is lacking, even in the absence of T1D, we applied shotgun whole metagenomic sequencing (WMS) to analyse the gut microbiome across pregnancy in women with and without T1D participating in the Australia-wide Environmental Determinants of Islet Autoimmunity (ENDIA) study. Results Study population Fecal samples were collected between February 2013 and October 2017 from women enrolled in the ENDIA study, a prospective, pregnancy-birth cohort study that follows 1500 Australian children who have a first-degree relative with T1D [ 23 ]. Thirty-five women (36 pregnancies) with T1D and 31 women (34 pregnancies) without T1D had each provided from one to three fecal samples across pregnancy (total 134 samples) for analysis by shotgun WMS (Fig. 1 ). Table 1 summarizes and compares characteristics of the T1D and non-T1D pregnancies. Fig. 1 Fecal samples obtained in pregnancy. n: number of samples; T1: trimester 1; T2: trimester 2; T3: trimester 3; T1D: women with type 1 diabetes; Non-T1D: women without T1D Full size image Table 1 Summary of characteristics of non-T1D and T1D pregnancies Full size table Whole metagenomic sequencing The WMS dataset, 47,766,763 ± 10,956,057 (mean ± SD) paired-end reads per sample, was obtained using an Illumina NovaSeq 6000. Raw reads (SRA accession: PRJNA604850) were pre-processed using", "role": "user" }, { "content": "A recent study by WEHI and ENDIA has found type 1 diabetes is associated with changes in the gut microbiome during pregnancy and could contribute to complications in both the mother and baby. The research found a link between type 1 diabetes and changes in the gut microbiome that are associated with intestinal inflammation, which could account for the increase in pregnancy complications in women with the condition. The study revealed pregnant women with type 1 diabetes had a decrease in \"good\" gut bacteria that normally protect against inflammation and an increase in 'bad' gut bacteria that promote intestinal inflammation and damage to the intestinal lining. These changes could contribute to the increased risk of pregnancy complications seen in women with type 1 diabetes and could potentially be modified by dietary changes. Gut health linked to pregnancy complications The research was part of the ENDIA (Environmental Determinants of Islet Autoimmunity) study, investigating genetic and environmental factors that may contribute to the development of islet autoimmunity and type 1 diabetes in children. The observational study has recruited 1500 babies from pregnancy who have an immediate relative with type 1 diabetes and is following them through childhood. WEHI clinician-scientist Professor Len Harrison, who led the research, said women with type 1 diabetes have a higher frequency of complications in pregnancy. \"We decided to study the gut microbiome because there was evidence of systemic and intra-uterine inflammation in pregnancy for women with type 1 diabetes that could conceivably be related,\" he said. Together with colleagues in bioinformatics at WEHI, as well as ENDIA partners, the study team undertook whole genome sequence analysis of samples from pregnant women. The samples were taken from groups of women at different stages of pregnancy. \"In women with type 1 diabetes, we observed changes in their gut microbiome, including a decrease in 'good' gut bacteria and an increase in 'bad' gut bacteria,\" he said. \"The 'good' bacteria make substances that prevent inflammation and the 'bad' bacteria release substances that activate the immune system to trigger inflammation.\" \"We are now investigating if these changes are linked to the higher rate of complications during pregnancy in women with type 1 diabetes.\" Professor Harrison said changes in the gut microbiome of the mother could have implications for the pregnancy and for the health of the baby. \"It is also possible that the changes we observed in the mothers with type 1 diabetes might have a lasting influence on the baby which continues after birth,\" he said. Changing diet Professor Harrison said the next stage of the project was to identify markers that would determine which women with type 1 diabetes might benefit from safe interventions during pregnancy, including dietary changes. \"We believe that if these women made some safe dietary modifications it could help to restore the health of their microbiome and lower their risk of complications during pregnancy. This is what we are investigating now,\" he said. \"We will also look into the immune system of their babies at birth to see what impacts that impaired maternal gut health has on the baby after birth.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Background The gut microbiome changes in response to a range of environmental conditions, life events and disease states. Pregnancy is a natural life event that involves major physiological adaptation yet studies of the microbiome in pregnancy are limited and their findings inconsistent. Pregnancy with type 1 diabetes (T1D) is associated with increased maternal and fetal risks but the gut microbiome in this context has not been characterized. By whole metagenome sequencing (WMS), we defined the taxonomic composition and function of the gut bacterial microbiome across 70 pregnancies, 36 in women with T1D. Results Women with and without T1D exhibited compositional and functional changes in the gut microbiome across pregnancy. Profiles in women with T1D were distinct, with an increase in bacteria that produce lipopolysaccharides and a decrease in those that produce short-chain fatty acids, especially in the third trimester. In addition, women with T1D had elevated concentrations of fecal calprotectin, a marker of intestinal inflammation, and serum intestinal fatty acid-binding protein (I-FABP), a marker of intestinal epithelial damage. Conclusions Women with T1D exhibit a shift towards a more pro-inflammatory gut microbiome during pregnancy, associated with evidence of intestinal inflammation. These changes could contribute to the increased risk of pregnancy complications in women with T1D and are potentially modifiable by dietary means. Video abstract Background The gut microbiome provides essential metabolites, vitamins, co-factors and hormones, protects against pathogenic microorganisms and has a key role in the development of the immune and other systems [ 1 , 2 ]. Changes in the composition of the gut microbiome are associated with ageing, environmental conditions, life events and disease states [ 2 , 3 , 4 ]. In pregnancy, women undergo significant physiological changes, but only recently has the gut microbiome been studied in this context [ 5 , 6 ]. Koren et al. [ 5 ] sampled the gut microbiome in the first and third trimesters and found that the taxonomic composition in the first trimester was similar to that of non-pregnant women but in the third trimester the abundance of Actinobacteria and Proteobacteria phyla increased along with an overall decrease in bacterial richness (alpha diversity). In studies in germ-free mice, they observed that inoculation with third compared to first trimester feces led to greater weight gain, insulin resistance and gut inflammation and suggested this was an adaptive proinflammatory response to defend the fetus from pathogens and provide it with nutrients. In contrast, after analysing fecal samples weekly across pregnancy, DiGiulio et al. [ 6 ] found no significant temporal differences in diversity or composition of the gut microbiome. These contrary findings and the dearth of studies warrant further investigation of the gut microbiome in pregnancy. Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing β cells in the islets of the pancreas are destroyed by T lymphocytes leading to insulin deficiency [ 7 ]. In pregnancy, T1D is associated with systemic and intra-uterine markers of sub-clinical inflammation and higher risks of complications for mother and fetus [ 8 , 9 , 10 ]. Alterations in the bacterial gut microbiome have been reported in T1D, mainly in children at high risk and at diagnosis (reviewed in [ 11 ], [ 12 , 13 , 14 , 15 , 16 , 17 ]). They include a decrease in alpha diversity (richness) [ 12 , 13 , 14 ] and in the abundance of lactate- and butyrate-producing and mucin-degrading bacteria [ 13 , 14 , 15 , 16 , 17 ], and an increase in the abundance of the Bacteroides genus [ 13 , 14 ]. Functionally, these compositional changes are reflected by a decreased abundance of genes encoding related metabolic pathways and enzymes, e.g. butyryl-coenzyme A (CoA)-CoA transferase [ 15 ] and butyryl-CoA dehydrogenase for butyrate synthesis [ 16 ]. These changes are not necessarily specific for T1D but nevertheless, they may have clinical consequences, including in pregnancy. Gut butyrate is a key determinant of gut health and regulator of gene expression and homeostatic immunity [ 18 , 19 , 20 ]. It is the major energy source for the colonic mucosa, induces the synthesis of mucin and it promotes gut epithelial integrity, preventing ‘gut leakiness’. In the non-obese diabetic (NOD) mouse model of T1D, dietary butyrate supplementation promoted an increase in regulatory T cells and a decrease in the incidence of spontaneous diabetes [ 20 ]. Increased gut leakiness has been described in established T1D [ 21 ] and recently by ourselves in association with gut microbiome changes in children with islet autoimmunity who progressed to T1D [ 22 ]. Gut leakiness with translocation of toxins and dietary antigens into the blood may result in systemic inflammation, reported with T1D in pregnancy complicated by pre-eclampsia [ 10 ]. Because a consensus about the gut microbiome in pregnancy is lacking, even in the absence of T1D, we applied shotgun whole metagenomic sequencing (WMS) to analyse the gut microbiome across pregnancy in women with and without T1D participating in the Australia-wide Environmental Determinants of Islet Autoimmunity (ENDIA) study. Results Study population Fecal samples were collected between February 2013 and October 2017 from women enrolled in the ENDIA study, a prospective, pregnancy-birth cohort study that follows 1500 Australian children who have a first-degree relative with T1D [ 23 ]. Thirty-five women (36 pregnancies) with T1D and 31 women (34 pregnancies) without T1D had each provided from one to three fecal samples across pregnancy (total 134 samples) for analysis by shotgun WMS (Fig. 1 ). Table 1 summarizes and compares characteristics of the T1D and non-T1D pregnancies. Fig. 1 Fecal samples obtained in pregnancy. n: number of samples; T1: trimester 1; T2: trimester 2; T3: trimester 3; T1D: women with type 1 diabetes; Non-T1D: women without T1D Full size image Table 1 Summary of characteristics of non-T1D and T1D pregnancies Full size table Whole metagenomic sequencing The WMS dataset, 47,766,763 ± 10,956,057 (mean ± SD) paired-end reads per sample, was obtained using an Illumina NovaSeq 6000. Raw reads (SRA accession: PRJNA604850) were pre-processed using<|im_end|> <|im_start|>assistant A recent study by WEHI and ENDIA has found type 1 diabetes is associated with changes in the gut microbiome during pregnancy and could contribute to complications in both the mother and baby. The research found a link between type 1 diabetes and changes in the gut microbiome that are associated with intestinal inflammation, which could account for the increase in pregnancy complications in women with the condition. The study revealed pregnant women with type 1 diabetes had a decrease in "good" gut bacteria that normally protect against inflammation and an increase in 'bad' gut bacteria that promote intestinal inflammation and damage to the intestinal lining. These changes could contribute to the increased risk of pregnancy complications seen in women with type 1 diabetes and could potentially be modified by dietary changes. Gut health linked to pregnancy complications The research was part of the ENDIA (Environmental Determinants of Islet Autoimmunity) study, investigating genetic and environmental factors that may contribute to the development of islet autoimmunity and type 1 diabetes in children. The observational study has recruited 1500 babies from pregnancy who have an immediate relative with type 1 diabetes and is following them through childhood. WEHI clinician-scientist Professor Len Harrison, who led the research, said women with type 1 diabetes have a higher frequency of complications in pregnancy. "We decided to study the gut microbiome because there was evidence of systemic and intra-uterine inflammation in pregnancy for women with type 1 diabetes that could conceivably be related," he said. Together with colleagues in bioinformatics at WEHI, as well as ENDIA partners, the study team undertook whole genome sequence analysis of samples from pregnant women. The samples were taken from groups of women at different stages of pregnancy. "In women with type 1 diabetes, we observed changes in their gut microbiome, including a decrease in 'good' gut bacteria and an increase in 'bad' gut bacteria," he said. "The 'good' bacteria make substances that prevent inflammation and the 'bad' bacteria release substances that activate the immune system to trigger inflammation." "We are now investigating if these changes are linked to the higher rate of complications during pregnancy in women with type 1 diabetes." Professor Harrison said changes in the gut microbiome of the mother could have implications for the pregnancy and for the health of the baby. "It is also possible that the changes we observed in the mothers with type 1 diabetes might have a lasting influence on the baby which continues after birth," he said. Changing diet Professor Harrison said the next stage of the project was to identify markers that would determine which women with type 1 diabetes might benefit from safe interventions during pregnancy, including dietary changes. "We believe that if these women made some safe dietary modifications it could help to restore the health of their microbiome and lower their risk of complications during pregnancy. This is what we are investigating now," he said. "We will also look into the immune system of their babies at birth to see what impacts that impaired maternal gut health has on the baby after birth." <|im_end|>

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2,064

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Ethologists predicted that parental care evolves by modifying behavioural precursors in the asocial ancestor. As a corollary, we predict that the evolved mechanistic changes reside in genetic pathways underlying these traits. Here we test our hypothesis in female burying beetles, Nicrophorus vespilloides , an insect where caring adults regurgitate food to begging, dependent offspring. We quantify neuropeptide abundance in brains collected from three behavioural states: solitary virgins, individuals actively parenting or post-parenting solitary adults and quantify 133 peptides belonging to 18 neuropeptides. Eight neuropeptides differ in abundance in one or more states, with increased abundance during parenting in seven. None of these eight neuropeptides have been associated with parental care previously, but all have roles in predicted behavioural precursors for parenting. Our study supports the hypothesis that predictable traits and pathways are targets of selection during the evolution of parenting and suggests additional candidate neuropeptides to study in the context of parenting. Introduction The selective pressures that lead to the evolution of parental care are well documented 1 . Parental care typically evolves to minimize unusually stressful or hazardous environments for offspring 2 , 3 , 4 . Although this hypothesis is widely supported 4 , parental care is not the only evolutionary solution to adverse conditions. Moreover, it may not be the most likely response as the evolution of parenting reflects changes in multiple behavioural inputs, involving many pathways 5 . At a minimum, the evolutionary transition from asociality (social interactions limited to mating) to subsociality (extensive social interactions between parents and offspring involving parental care) is predicted to require modification of several contributing behaviours including tendencies for dispersal, feeding, mating, aggression and tolerance of social interactions 1 , 2 , 3 . Caring parents no longer disperse from a mating site, they provision food rather than feed themselves, they pause reproduction and mating, they show aggression to protect offspring and shared resources rather than their own resources, and they tolerate the presence of others and increased social interactions 1 , 2 , 3 , 4 , 6 . The early ethological literature therefore predicts that parental care evolves only when there are suitable behavioural and ecological precursors present within the evolutionary ancestor, such as nest building, defensive postures and aggression, and potentially shared resources 2 , 3 . The early predictions of the specific constituent behaviours were made without reference to the mechanistic changes that would be required. Implied, however, is that repurposing existing traits involves changes in the timing and direction of interactions. This suggests a potential mechanism: that changes in timing of gene expression are involved in the evolution of derived behaviour 1 . If true, we can use the predicted behaviours to be modified from non-parenting to parenting to infer the underlying mechanisms. We specifically hypothesize that modifying behaviours affecting parenting will result from altered gene expression rather than the evolution of novel genes. This hypothesis is a natural extension of Wright’s theory of nearly universal pleiotropy 7 , suggesting that genes gain functions when used in novel contexts, and the ubiquity of changes of gene regulation that are seen during evolutionary transisitions 8 , 9 , 10 . Moreover, this is consistent with previous work that uses the nature of selection to predict the genetic changes underlying the evolution of social behaviour 1 , 6 , 11 , 12 . For example, when parenting, animals are typically selected to be unreceptive to mating. We therefore predict that mechanisms that influence mating will be altered. Following this logic, overall we predict that parenting will involve changes in expression of genes that influence mating, feeding, aggression, and increased tolerance for social interactions as these are the behaviours modified as lineages evolve from asocial to subsocial 1 , 2 , 3 . However, following Wright 7 , we also predict polygenic changes rather than one or few genes. Thus, we need to use techniques that can detect multiple changes. Studies of changes in gene expression have been revolutionized by an ability to assay overall transcriptional changes in many genes simultaneously. However, transcriptomics is not a particularly powerful method for identifying changes in expression of many genes that code for proteins that influence behaviour, such as neuropeptides, that have low gene expression 13 , highly restricted sites of release 14 , and can be hard to detect with transcriptomic studies that are not highly tissue specific 15 . Proteomics provides a complementary approach that overcomes some of these limitations and provides a method to target protein categories of interest. Adopting a complementary approach is necessary because neuropeptides strongly influence the social behaviour of animals 16 and many neuropeptides are likely to be associated with parenting. One of the most studied neuropeptides, oxytocin, is necessary for parenting across the animal kingdom 17 . There is a causal relationship between the neuropeptide galinin and parental care in mice 18 . In the burying beetle Nicrophorus vespilloides , neuropeptide F receptor is differentially expressed between parenting and non-parenting states 19 . The importance of neuropeptides is expected, as parenting individuals must undergo many rapid shifts in behaviour. Neuropeptides can exhibit their influence within minutes, have highly localized effects targeting very select neural circuits, or have highly widespread effects targeting many and diffuse neural circuits 14 . Here we test the hypothesis that a transition from a non-parenting state to a parenting state will reflect differences in neuropeptides known to be generally associated with mating, feeding, aggression and increased social tolerance and that neuropeptides influencing other traits will not change during parenting. To test this, we estimated the abundances of neuropeptides of the burying beetles N. vespilloides sampled from a solitary and parenting states. N. vespilloides adults are normally solitary but switch to parenting in the presence of appropriate resources. Parenting in this species is extensive and elaborate. Adult beetles are stimulated to parent after they locate a vertebrate carcass and bury it. Parents remain on this carcass and provide indirect care by removing the fur or feathers and forming a", "role": "user" }, { "content": "University of Georgia researchers have confirmed that becoming a parent brings about more than just the obvious offspring—it also rewires the parents' brain. The study, published this month in Nature Communications, finds that the transition from a non-parenting state to a parenting state reflects differences in neuropeptides generally associated with mating, feeding, aggression and increased social tolerance. Neuropeptides are small proteins that allow neurons in the brain to communicate with each other; they also influence behavior. The team's research-tested on an insect, the burying beetle Nicrophorus vespilloides-provides a predictive framework for studying the genetics of parenting and social interactions. The burying beetle is intimately involved in raising its children, including regurgitating food to its begging offspring. \"We tested the idea that we could predict the genetic pathways involved in parenting based on old predictions from ethologists in the 1960s and 1970s,\" said the study's lead author Allen Moore, Distinguished Research Professor and head of the department of genetics. \"When [burying beetle] parents feed their babies, they are feeding others rather than themselves and so genes that influence food-seeking behavior are likely to be involved.\" Behavioral scientists predicted that genetic changes occur over time to develop parenting in a species. Based on this hypothesis, Moore's team sequenced and assembled the genome of the burying beetle and measured the abundance of neuropeptides. They theorized that behaviors related to parenting stemmed from alterations in existing genes rather than the evolution of new ones. By looking at parenting and non-parenting beetles, their tests indicated that neuropeptides changed in abundance during parenting. \"When new traits evolve, evolution tends to modify existing genetic pathways rather than create new genes,\" Moore said. The research, Moore said, suggests that many of the genes influencing parenting will be the same across many species. The commonality among organisms will help researchers identify genetic pathways important to parenting. \"It is exciting science when you take a step toward predicting the genetic changes involved in a behavior as complicated as parental care,\" he said. \"And it was pleasing to collaborate with colleagues in genetics and Complex Carbohydrate Research Center, which allowed us to apply techniques that wouldn't otherwise be available to test our ideas.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Ethologists predicted that parental care evolves by modifying behavioural precursors in the asocial ancestor. As a corollary, we predict that the evolved mechanistic changes reside in genetic pathways underlying these traits. Here we test our hypothesis in female burying beetles, Nicrophorus vespilloides , an insect where caring adults regurgitate food to begging, dependent offspring. We quantify neuropeptide abundance in brains collected from three behavioural states: solitary virgins, individuals actively parenting or post-parenting solitary adults and quantify 133 peptides belonging to 18 neuropeptides. Eight neuropeptides differ in abundance in one or more states, with increased abundance during parenting in seven. None of these eight neuropeptides have been associated with parental care previously, but all have roles in predicted behavioural precursors for parenting. Our study supports the hypothesis that predictable traits and pathways are targets of selection during the evolution of parenting and suggests additional candidate neuropeptides to study in the context of parenting. Introduction The selective pressures that lead to the evolution of parental care are well documented 1 . Parental care typically evolves to minimize unusually stressful or hazardous environments for offspring 2 , 3 , 4 . Although this hypothesis is widely supported 4 , parental care is not the only evolutionary solution to adverse conditions. Moreover, it may not be the most likely response as the evolution of parenting reflects changes in multiple behavioural inputs, involving many pathways 5 . At a minimum, the evolutionary transition from asociality (social interactions limited to mating) to subsociality (extensive social interactions between parents and offspring involving parental care) is predicted to require modification of several contributing behaviours including tendencies for dispersal, feeding, mating, aggression and tolerance of social interactions 1 , 2 , 3 . Caring parents no longer disperse from a mating site, they provision food rather than feed themselves, they pause reproduction and mating, they show aggression to protect offspring and shared resources rather than their own resources, and they tolerate the presence of others and increased social interactions 1 , 2 , 3 , 4 , 6 . The early ethological literature therefore predicts that parental care evolves only when there are suitable behavioural and ecological precursors present within the evolutionary ancestor, such as nest building, defensive postures and aggression, and potentially shared resources 2 , 3 . The early predictions of the specific constituent behaviours were made without reference to the mechanistic changes that would be required. Implied, however, is that repurposing existing traits involves changes in the timing and direction of interactions. This suggests a potential mechanism: that changes in timing of gene expression are involved in the evolution of derived behaviour 1 . If true, we can use the predicted behaviours to be modified from non-parenting to parenting to infer the underlying mechanisms. We specifically hypothesize that modifying behaviours affecting parenting will result from altered gene expression rather than the evolution of novel genes. This hypothesis is a natural extension of Wright’s theory of nearly universal pleiotropy 7 , suggesting that genes gain functions when used in novel contexts, and the ubiquity of changes of gene regulation that are seen during evolutionary transisitions 8 , 9 , 10 . Moreover, this is consistent with previous work that uses the nature of selection to predict the genetic changes underlying the evolution of social behaviour 1 , 6 , 11 , 12 . For example, when parenting, animals are typically selected to be unreceptive to mating. We therefore predict that mechanisms that influence mating will be altered. Following this logic, overall we predict that parenting will involve changes in expression of genes that influence mating, feeding, aggression, and increased tolerance for social interactions as these are the behaviours modified as lineages evolve from asocial to subsocial 1 , 2 , 3 . However, following Wright 7 , we also predict polygenic changes rather than one or few genes. Thus, we need to use techniques that can detect multiple changes. Studies of changes in gene expression have been revolutionized by an ability to assay overall transcriptional changes in many genes simultaneously. However, transcriptomics is not a particularly powerful method for identifying changes in expression of many genes that code for proteins that influence behaviour, such as neuropeptides, that have low gene expression 13 , highly restricted sites of release 14 , and can be hard to detect with transcriptomic studies that are not highly tissue specific 15 . Proteomics provides a complementary approach that overcomes some of these limitations and provides a method to target protein categories of interest. Adopting a complementary approach is necessary because neuropeptides strongly influence the social behaviour of animals 16 and many neuropeptides are likely to be associated with parenting. One of the most studied neuropeptides, oxytocin, is necessary for parenting across the animal kingdom 17 . There is a causal relationship between the neuropeptide galinin and parental care in mice 18 . In the burying beetle Nicrophorus vespilloides , neuropeptide F receptor is differentially expressed between parenting and non-parenting states 19 . The importance of neuropeptides is expected, as parenting individuals must undergo many rapid shifts in behaviour. Neuropeptides can exhibit their influence within minutes, have highly localized effects targeting very select neural circuits, or have highly widespread effects targeting many and diffuse neural circuits 14 . Here we test the hypothesis that a transition from a non-parenting state to a parenting state will reflect differences in neuropeptides known to be generally associated with mating, feeding, aggression and increased social tolerance and that neuropeptides influencing other traits will not change during parenting. To test this, we estimated the abundances of neuropeptides of the burying beetles N. vespilloides sampled from a solitary and parenting states. N. vespilloides adults are normally solitary but switch to parenting in the presence of appropriate resources. Parenting in this species is extensive and elaborate. Adult beetles are stimulated to parent after they locate a vertebrate carcass and bury it. Parents remain on this carcass and provide indirect care by removing the fur or feathers and forming a<|im_end|> <|im_start|>assistant University of Georgia researchers have confirmed that becoming a parent brings about more than just the obvious offspring—it also rewires the parents' brain. The study, published this month in Nature Communications, finds that the transition from a non-parenting state to a parenting state reflects differences in neuropeptides generally associated with mating, feeding, aggression and increased social tolerance. Neuropeptides are small proteins that allow neurons in the brain to communicate with each other; they also influence behavior. The team's research-tested on an insect, the burying beetle Nicrophorus vespilloides-provides a predictive framework for studying the genetics of parenting and social interactions. The burying beetle is intimately involved in raising its children, including regurgitating food to its begging offspring. "We tested the idea that we could predict the genetic pathways involved in parenting based on old predictions from ethologists in the 1960s and 1970s," said the study's lead author Allen Moore, Distinguished Research Professor and head of the department of genetics. "When [burying beetle] parents feed their babies, they are feeding others rather than themselves and so genes that influence food-seeking behavior are likely to be involved." Behavioral scientists predicted that genetic changes occur over time to develop parenting in a species. Based on this hypothesis, Moore's team sequenced and assembled the genome of the burying beetle and measured the abundance of neuropeptides. They theorized that behaviors related to parenting stemmed from alterations in existing genes rather than the evolution of new ones. By looking at parenting and non-parenting beetles, their tests indicated that neuropeptides changed in abundance during parenting. "When new traits evolve, evolution tends to modify existing genetic pathways rather than create new genes," Moore said. The research, Moore said, suggests that many of the genes influencing parenting will be the same across many species. The commonality among organisms will help researchers identify genetic pathways important to parenting. "It is exciting science when you take a step toward predicting the genetic changes involved in a behavior as complicated as parental care," he said. "And it was pleasing to collaborate with colleagues in genetics and Complex Carbohydrate Research Center, which allowed us to apply techniques that wouldn't otherwise be available to test our ideas." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Birth asphyxia constitutes a major global public health burden for millions of infants, despite hypothermia therapy. There is a critical need for real time surrogate markers of therapeutic success, to aid in patient selection and/or modification of interventions in neonatal encephalopathy (NE). This is a proof of concept study aiming to quantify neurovascular coupling (NVC) using wavelet analysis of the dynamic coherence between amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in NE. NVC coupling is assessed by a wavelet metric estimation of percent time of coherence between NIRS S ct O 2 and aEEG for 78 hours after birth. An abnormal outcome was predefined by a Bayley III score <85 by 18–24 m. We observed high coherence, intact NVC, between the oscillations of S ct O 2 and aEEG in the frequency range of 0.00025–0.001 Hz in the non-encephalopathic newborns. NVC coherence was significantly decreased in encephalopathic newborns who were cooled vs. non-encephalopathic controls (median IQR 3[2–9] vs.36 [33–39]; p < 0.01), and was significantly lower in those with abnormal 24 months outcomes relative to those with normal outcomes (median IQR 2[1–3] vs 28[19–26], p = 0.04). Wavelet coherence analysis of neurovascular coupling in NE may identify infants at risk for abnormal outcomes. Introduction Despite hypothermia therapy for hypoxic neonatal encephalopathy (NE), 50% of treated newborns have disabilities at 12–18 months of age 1 , 2 . The asphyxia insult impairs fetal cerebral blood flow (CBF) and is manifested postnatally by a distinctive neonatal encephalopathy (NE), which is usually classified after birth using the clinical modified Sarnat stages as mild, moderate and severe NE 3 . Recent reports suggest new evidence of cognitive impairment in a subset of 30–50% of “mild NE” cases, who are currently not recognized or offered any therapies 4 , 5 . While adjuvant therapies are being sought, an important focus of research is to recognize which neonates are in need of therapies to improve outcome 6 , 7 . The challenge in the field of neonatal brain injury has been the difficulty to clinically discern the mild-moderate NE severity within the short therapeutic window after birth. A sensitive and specific physiological marker that directly assesses neurovascular function in real-time, and is a marker of clinical outcomes, is critically needed to guide therapies 8 , 9 , 10 . The neurovascular unit consists of neurons, astrocytes, endothelial cells of blood–brain barrier (BBB), myocytes, pericytes and extracellular matrix components which play an important role in the delivery of oxygen and nutrients to the brain and the maintenance of cerebral circulation homeostasis 9 , 11 , 12 . Individual metrics of electroencephalography 6 , 13 , 14 , 15 and near-infrared spectroscopy (NIRS) 16 , 17 have been used independently to assess the function of neurovascular unit, but the ability to study coupling in real time of NIRS and EEG in HIE has received little attention 11 , 17 , 18 , 19 These methods demonstrated that a severe asphyxia insult leads to impaired function, but the extent of dysfunctional neurovascular coupling (NVC), and its impact on clinical outcome of newborns with encephalopathy cannot be currently assessed in real time due to limited methodology 20 , 21 . Intrinsic oscillating activities at multiple time scales have been described in cortical neurons across mammalian species 22 . These oscillations span from the very low to ultra-fast frequencies and although difficult to measure, are functionally relevant, phylogenetically conserved across species, and play important roles in facilitating synaptic plasticity and brain functional connectivity 22 . Cerebral blood flow (CBF) and brain tissue oxygenation also manifest oscillations at multiple time scales which occur simultaneously with changes in neuronal activities suggesting NVC 23 . Our previous work demonstrated a new time-frequency domain wavelet analysis of the dynamic relationship between spontaneous oscillations in mean arterial pressure and NIRS-measured cerebral tissue oxygen saturation (S ct O 2 ) allowed quantification of cerebral autoregulation at the bedside in newborns with encephalopathy 24 , 25 . We use the novel wavelet analysis to quantify NVC at the bedside, as defined in a global context to reflect the relationship between each of 1) NIRS S ct O 2 , a surrogate of CBF under steady state conditions, and 2) the amplitude integrated EEG (aEEG), which measures ensemble neuronal activity. The aims in this proof of concept study are to assess the feasibility of using the wavelet analysis to quantify NVC at the bedside, and its potential to stratify NE severity and identify newborns at high risks for abnormal outcomes following neuroprotective therapies. Results Patient characteristics Twenty inborn newborns with fetal metabolic acidosis were evaluated and screened during the one year study period. Of those, ten newborns had simultaneous aEEG and NIRS recordings which were suitable for wavelet analysis. The study was approved by UT Southwestern IRB and parental consent was obtained. These ten newborns comprised eight with moderate to severe encephalopathy who received hypothermia and two with no encephalopathy who did not meet criteria for cooling and served as references. Patient characteristics are summarized in Table 1 . Neuromonitoring was initiated at 12 ± 2 hours for duration of 60 ± 6 hours with no artifacts during recording. No scalp edema or any other complications were noted and no leads were replaced during the duration of the recording. No infant had seizures during the recording period. Only one infant had clinical seizures within 6 hours of life prior to enrollment. All cooled infants were categorized to have moderate encephalopathy, except one who was severe. All infants with a normal outcome had continuous patterns on aEEG. Sleep wake cycles (SWCs) were identified by aEEG in eight infants, occurring every 60–90 minute as summarized in Table 1 , two infants showed no SWC. MRI was available on all patients and was performed at a median age of 7 days. The MRI was abnormal in 4 neonates with white matter injury and watershed infarcts, one had added basal ganglia involvement. Abnormal outcome with Bayley III scores <85 at 18–24 months occurred", "role": "user" }, { "content": "UT Southwestern Medical Center pediatric researchers have harnessed an analytical tool used to predict the weather to evaluate the effectiveness of therapies to reduce brain injury in newborns who suffer oxygen deprivation during birth. The analytical tool, called wavelet analysis technology, is best known for predicting long-term weather patterns, such as El Nino. UT Southwestern researchers say this same analytical tool can help improve assessment and treatment of newborns with asphyxia, which is when the baby's brain is deprived of oxygen due to complications during birth. The non-invasive method produces real-time heat maps of the infant's brain that doctors can use to determine whether therapies to prevent brain damage are effective. \"These are babies to whom something catastrophic happened at birth. What this technology does is measure physiologic parameters of the brain - blood flow and nerve cell activity - to produce a real-time image of what we are calling 'neurovascular coupling.' If there is high coherence between these two variables, you know that things are going well,\" said Dr. Lina Chalak, Associate Professor of Pediatrics at UT Southwestern and lead author of the study. The wavelet analysis correlates information from two non-invasive technologies that are currently used on a day-to-day basis in neonatal intensive care: amplitude EEG and near infrared spectroscopy. The approach combines the results from these commonly done tests in a sophisticated way and creates a new proxy measure of brain health called neurovascular coupling. When neuronal activity and brain perfusion are synchronized - as indicated by large areas of red on heat maps created by this method - treatment is working well. About 12,000 newborns experience oxygen deprivation (asphyxia) during birth in the U.S. each year, according to a 2010 article in Lancet. This can occur for a number of reasons, such as the cord being wrapped around the baby's neck, a difficult breech birth, or the separation of the placenta from the uterus too soon, Dr. Chalak explained. These infants are at high risk of developing serious consequences such as cerebral palsy, epilepsy, and cognitive deficits. No treatments were available until about 10 years ago when a national study in which UT Southwestern participated, showed that reducing the baby's core temperature could counteract the impact of birth asphyxia for some infants. The cooling blankets are now standard treatment, but only about half of babies treated with a cooling blanket benefit. Until the adaptation of the wavelet technology, doctors couldn't determine which infants were benefitting from cooling treatment and which babies may need additional therapies, which are being developed. Dr. Lina Chalak, Associate Professor of Pediatrics at UT Southwestern Medical Center and a specialist in treating birth asphyxia, uses wavelet analysis of amplitude EEG and near infrared spectroscopy to create a proxy measure of brain health she calls 'neurovascular coupling.' Credit: UT Southwestern Wavelet analysis information also can help in evaluation of new therapies. Dr. Chalak plans to use wavelet analysis as part of the HEAL study, a large clinical trial to determine the effectiveness of erythropoietin, a hormone that promotes the formation of red blood cells, to treat newborns with asphyxia. Wavelet analysis will be used to evaluate infants who are part of the HEAL study at the Neonatal Intensive Care Unit at William P. Clements Jr. University Hospital, Parkland Hospital, and Children's Medical Center. Wavelet technology also may help determine which children should be treated. \"Of the babies who are oxygen-deprived, some don't qualify for cooling because their brain damage or encephalopathy is judged to be mild. Yet some of these children have adverse outcomes. This technology may help us identify who needs cooling,\" said Dr. Rashmin Savani, Chief of Neonatal-Perinatal Medicine and Professor of Pediatrics and of Integrative Biology, who holds The William Buchanan Chair in Pediatrics. It could also lead to other discoveries. \"Understanding of brain blood flow regulation and its impact on brain function in newborns with asphyxia using this novel technology has great potential for developing new sensitive biomarkers for clinical diagnosis, treatment, and prognosis for these sick babies, which is desperately needed in the field,\" said co-author Dr. Rong Zhang, Associate Professor of Neurology and Neurotherapeutics, and of Internal Medicine, and a member of the Peter O'Donnell Jr. Brain Institute at UT Southwestern. The research appears in Scientific Reports. Other UT Southwestern researchers who contributed to this paper are Dr. Beverley Adams-Huet, Assistant Professor of Clinical Sciences and of Internal Medicine; Diana Vasil, research nurse; and Dr. Takashi Tarumi, Instructor in Neurology and Neurotherapeutics, along with Dr. Fenghua Tian, Assistant Professor of Biomedical Engineering at UT Arlington. The research was funded by grants from the National Institutes of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health. Dr. Chalak said the new tools represent a paradigm shift for physicians who treat oxygen-deprived newborns. \"Hopefully, the future will be bright for babies who suffered asphyxia, differing from the bleak prognoses of the past.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Birth asphyxia constitutes a major global public health burden for millions of infants, despite hypothermia therapy. There is a critical need for real time surrogate markers of therapeutic success, to aid in patient selection and/or modification of interventions in neonatal encephalopathy (NE). This is a proof of concept study aiming to quantify neurovascular coupling (NVC) using wavelet analysis of the dynamic coherence between amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in NE. NVC coupling is assessed by a wavelet metric estimation of percent time of coherence between NIRS S ct O 2 and aEEG for 78 hours after birth. An abnormal outcome was predefined by a Bayley III score <85 by 18–24 m. We observed high coherence, intact NVC, between the oscillations of S ct O 2 and aEEG in the frequency range of 0.00025–0.001 Hz in the non-encephalopathic newborns. NVC coherence was significantly decreased in encephalopathic newborns who were cooled vs. non-encephalopathic controls (median IQR 3[2–9] vs.36 [33–39]; p < 0.01), and was significantly lower in those with abnormal 24 months outcomes relative to those with normal outcomes (median IQR 2[1–3] vs 28[19–26], p = 0.04). Wavelet coherence analysis of neurovascular coupling in NE may identify infants at risk for abnormal outcomes. Introduction Despite hypothermia therapy for hypoxic neonatal encephalopathy (NE), 50% of treated newborns have disabilities at 12–18 months of age 1 , 2 . The asphyxia insult impairs fetal cerebral blood flow (CBF) and is manifested postnatally by a distinctive neonatal encephalopathy (NE), which is usually classified after birth using the clinical modified Sarnat stages as mild, moderate and severe NE 3 . Recent reports suggest new evidence of cognitive impairment in a subset of 30–50% of “mild NE” cases, who are currently not recognized or offered any therapies 4 , 5 . While adjuvant therapies are being sought, an important focus of research is to recognize which neonates are in need of therapies to improve outcome 6 , 7 . The challenge in the field of neonatal brain injury has been the difficulty to clinically discern the mild-moderate NE severity within the short therapeutic window after birth. A sensitive and specific physiological marker that directly assesses neurovascular function in real-time, and is a marker of clinical outcomes, is critically needed to guide therapies 8 , 9 , 10 . The neurovascular unit consists of neurons, astrocytes, endothelial cells of blood–brain barrier (BBB), myocytes, pericytes and extracellular matrix components which play an important role in the delivery of oxygen and nutrients to the brain and the maintenance of cerebral circulation homeostasis 9 , 11 , 12 . Individual metrics of electroencephalography 6 , 13 , 14 , 15 and near-infrared spectroscopy (NIRS) 16 , 17 have been used independently to assess the function of neurovascular unit, but the ability to study coupling in real time of NIRS and EEG in HIE has received little attention 11 , 17 , 18 , 19 These methods demonstrated that a severe asphyxia insult leads to impaired function, but the extent of dysfunctional neurovascular coupling (NVC), and its impact on clinical outcome of newborns with encephalopathy cannot be currently assessed in real time due to limited methodology 20 , 21 . Intrinsic oscillating activities at multiple time scales have been described in cortical neurons across mammalian species 22 . These oscillations span from the very low to ultra-fast frequencies and although difficult to measure, are functionally relevant, phylogenetically conserved across species, and play important roles in facilitating synaptic plasticity and brain functional connectivity 22 . Cerebral blood flow (CBF) and brain tissue oxygenation also manifest oscillations at multiple time scales which occur simultaneously with changes in neuronal activities suggesting NVC 23 . Our previous work demonstrated a new time-frequency domain wavelet analysis of the dynamic relationship between spontaneous oscillations in mean arterial pressure and NIRS-measured cerebral tissue oxygen saturation (S ct O 2 ) allowed quantification of cerebral autoregulation at the bedside in newborns with encephalopathy 24 , 25 . We use the novel wavelet analysis to quantify NVC at the bedside, as defined in a global context to reflect the relationship between each of 1) NIRS S ct O 2 , a surrogate of CBF under steady state conditions, and 2) the amplitude integrated EEG (aEEG), which measures ensemble neuronal activity. The aims in this proof of concept study are to assess the feasibility of using the wavelet analysis to quantify NVC at the bedside, and its potential to stratify NE severity and identify newborns at high risks for abnormal outcomes following neuroprotective therapies. Results Patient characteristics Twenty inborn newborns with fetal metabolic acidosis were evaluated and screened during the one year study period. Of those, ten newborns had simultaneous aEEG and NIRS recordings which were suitable for wavelet analysis. The study was approved by UT Southwestern IRB and parental consent was obtained. These ten newborns comprised eight with moderate to severe encephalopathy who received hypothermia and two with no encephalopathy who did not meet criteria for cooling and served as references. Patient characteristics are summarized in Table 1 . Neuromonitoring was initiated at 12 ± 2 hours for duration of 60 ± 6 hours with no artifacts during recording. No scalp edema or any other complications were noted and no leads were replaced during the duration of the recording. No infant had seizures during the recording period. Only one infant had clinical seizures within 6 hours of life prior to enrollment. All cooled infants were categorized to have moderate encephalopathy, except one who was severe. All infants with a normal outcome had continuous patterns on aEEG. Sleep wake cycles (SWCs) were identified by aEEG in eight infants, occurring every 60–90 minute as summarized in Table 1 , two infants showed no SWC. MRI was available on all patients and was performed at a median age of 7 days. The MRI was abnormal in 4 neonates with white matter injury and watershed infarcts, one had added basal ganglia involvement. Abnormal outcome with Bayley III scores <85 at 18–24 months occurred<|im_end|> <|im_start|>assistant UT Southwestern Medical Center pediatric researchers have harnessed an analytical tool used to predict the weather to evaluate the effectiveness of therapies to reduce brain injury in newborns who suffer oxygen deprivation during birth. The analytical tool, called wavelet analysis technology, is best known for predicting long-term weather patterns, such as El Nino. UT Southwestern researchers say this same analytical tool can help improve assessment and treatment of newborns with asphyxia, which is when the baby's brain is deprived of oxygen due to complications during birth. The non-invasive method produces real-time heat maps of the infant's brain that doctors can use to determine whether therapies to prevent brain damage are effective. "These are babies to whom something catastrophic happened at birth. What this technology does is measure physiologic parameters of the brain - blood flow and nerve cell activity - to produce a real-time image of what we are calling 'neurovascular coupling.' If there is high coherence between these two variables, you know that things are going well," said Dr. Lina Chalak, Associate Professor of Pediatrics at UT Southwestern and lead author of the study. The wavelet analysis correlates information from two non-invasive technologies that are currently used on a day-to-day basis in neonatal intensive care: amplitude EEG and near infrared spectroscopy. The approach combines the results from these commonly done tests in a sophisticated way and creates a new proxy measure of brain health called neurovascular coupling. When neuronal activity and brain perfusion are synchronized - as indicated by large areas of red on heat maps created by this method - treatment is working well. About 12,000 newborns experience oxygen deprivation (asphyxia) during birth in the U.S. each year, according to a 2010 article in Lancet. This can occur for a number of reasons, such as the cord being wrapped around the baby's neck, a difficult breech birth, or the separation of the placenta from the uterus too soon, Dr. Chalak explained. These infants are at high risk of developing serious consequences such as cerebral palsy, epilepsy, and cognitive deficits. No treatments were available until about 10 years ago when a national study in which UT Southwestern participated, showed that reducing the baby's core temperature could counteract the impact of birth asphyxia for some infants. The cooling blankets are now standard treatment, but only about half of babies treated with a cooling blanket benefit. Until the adaptation of the wavelet technology, doctors couldn't determine which infants were benefitting from cooling treatment and which babies may need additional therapies, which are being developed. Dr. Lina Chalak, Associate Professor of Pediatrics at UT Southwestern Medical Center and a specialist in treating birth asphyxia, uses wavelet analysis of amplitude EEG and near infrared spectroscopy to create a proxy measure of brain health she calls 'neurovascular coupling.' Credit: UT Southwestern Wavelet analysis information also can help in evaluation of new therapies. Dr. Chalak plans to use wavelet analysis as part of the HEAL study, a large clinical trial to determine the effectiveness of erythropoietin, a hormone that promotes the formation of red blood cells, to treat newborns with asphyxia. Wavelet analysis will be used to evaluate infants who are part of the HEAL study at the Neonatal Intensive Care Unit at William P. Clements Jr. University Hospital, Parkland Hospital, and Children's Medical Center. Wavelet technology also may help determine which children should be treated. "Of the babies who are oxygen-deprived, some don't qualify for cooling because their brain damage or encephalopathy is judged to be mild. Yet some of these children have adverse outcomes. This technology may help us identify who needs cooling," said Dr. Rashmin Savani, Chief of Neonatal-Perinatal Medicine and Professor of Pediatrics and of Integrative Biology, who holds The William Buchanan Chair in Pediatrics. It could also lead to other discoveries. "Understanding of brain blood flow regulation and its impact on brain function in newborns with asphyxia using this novel technology has great potential for developing new sensitive biomarkers for clinical diagnosis, treatment, and prognosis for these sick babies, which is desperately needed in the field," said co-author Dr. Rong Zhang, Associate Professor of Neurology and Neurotherapeutics, and of Internal Medicine, and a member of the Peter O'Donnell Jr. Brain Institute at UT Southwestern. The research appears in Scientific Reports. Other UT Southwestern researchers who contributed to this paper are Dr. Beverley Adams-Huet, Assistant Professor of Clinical Sciences and of Internal Medicine; Diana Vasil, research nurse; and Dr. Takashi Tarumi, Instructor in Neurology and Neurotherapeutics, along with Dr. Fenghua Tian, Assistant Professor of Biomedical Engineering at UT Arlington. The research was funded by grants from the National Institutes of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health. Dr. Chalak said the new tools represent a paradigm shift for physicians who treat oxygen-deprived newborns. "Hopefully, the future will be bright for babies who suffered asphyxia, differing from the bleak prognoses of the past." <|im_end|>

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2,482

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The main feedstock for the value-added phosphorus chemicals used in industry and research is white phosphorus (P 4 ), from which the key intermediate for forming P(III) compounds is PCl 3 . Owing to its high reactivity, syntheses based on PCl 3 are often accompanied by product mixtures and laborious work-up procedures, so an alternative process to form a viable P(III) transfer reagent is desirable. Our concept of oxidative onioation, where white phosphorus is selectively converted into triflate salts of versatile P 1 transfer reagents such as [P(L N ) 3 ][OTf] 3 (L N is a cationic, N-based substituent; that is, 4-dimethylaminopyridinio), provides a convenient alternative for the implementation of P–O, P–N and P–C bonds while circumventing the use of PCl 3 . We use p-block element compounds of type R n E (for example, Ph 3 As or PhI) to access weak adducts between nitrogen Lewis bases L N and the corresponding dications [R n EL N ] 2+ . The proposed equilibrium between [R n EL N ] 2+ + L N and [R n E(L N ) 2 ] 2+ allows for the complete oxidative onioation of all six P–P bonds in P 4 to yield highly reactive and versatile trications [P(L N ) 3 ] 3+ . Main Phosphorus is an essential building block of all biological life. It not only fuels the global food economy but has also found a plethora of additional applications in industry 1 . Phosphate rock is the natural but non-renewable resource of this highly important element. The majority of phosphate rock is used for the production of phosphoric acid (H 3 PO 4 ) via the wet process using concentrated sulfuric acid (Fig. 1 ) 2 , 3 , 4 , 5 , 6 . This process provides a product that is mainly used for fertilizers (~90%) 2 , 3 , 4 , 5 , 6 . The industrial reduction of phosphate rock is termed the electrothermal process and yields white phosphorus (P 4 ), which is the major phosphorus source for industrial and academic applications, for example, pharmaceuticals, flame retardants, battery ingredients, fertilizers, herbicides, metals and electronics etchants, as well as additional phosphorus fine chemicals 2 , 3 , 4 , 5 , 6 . Fig. 1: Routes into value-added phosphorus chemicals from phosphate rock. Transformation of phosphate rock via the wet process to phosphoric acid (H 3 PO 4 ) and via the thermal process to white phosphorus (P 4 ) with subsequent (oxy)chlorination to PCl 3 , OPCl 3 or P 4 O 10 . The green box outlines the present work: oxidative onioation of P 4 to give [P(L N ) 3 ][OTf] 3 , a viable alternative to PCl 3 . An element compound R n E is oxidized to an element oxide R n EO. In the onio-ligand assisted deoxygenation, the R n EO is deoxygenated using an oxygen scavenger in the presence of an N-based ligand (L N ) to give [R n E(L N ) 2 ][OTf] 2 , a weak adduct that undergoes an equilibrium dissociation into cation [R n EL N ][OTf] 2 and uncoordinated ligand L N . This weak adduct is regarded as an oxidative onio-reagent for the desired P 4 oxidation. The element compound R n E is retrieved to close the cycle. L N is a suitable nitrogen-based Lewis base (dimethylaminopyridine, pyridine and quinoline) and R n E is a p-block-element compound (triphenylarsane and phenyl iodide); Tf 2 O = trifluoromethanesulfonic anhydride; Me 3 SiOTf = trimethylsilyl triflate. Equations are not balanced. Full size image Among the range of key phosphorus intermediates, PCl 3 is still the most important P(III) source. The production of this very important bulk chemical includes the use of chlorine gas (Cl 2 ), which is widely considered to be problematic; however, as yet, there is no alternative 2 , 3 , 4 , 5 , 6 for industrial and laboratory applications. PCl 3 is used in subsequent transformation reactions such as hydrolysis, alcoholysis, salt metathesis and Grignard reactions to obtain value-added phosphorus chemicals. These reactions often suffer from low selectivity and/or require an additional base in some cases (for example, to capture HCl). In this regard, the functionalization of white phosphorus into chemically useful products without the use of chlorine gas 7 , 8 , 9 , 10 , 11 , 12 , 13 has received much interest from the research community, including efforts to develop ecologically friendlier chemistry routes 5 , 6 , 14 . Recent contributions in this field include the light-induced catalytic functionalization of P 4 or its transformation using tributyltin hydride 15 , 16 . However, such reactions are extremely challenging and still very rare due to the selective and complete cleavage of all six P–P bonds of the reactive P 4 tetrahedron and, in turn, the selective formation of new phosphorus-element bonds. A selective transformation of white phosphorus to a single P(III) compound that is a viable alternative to PCl 3 is thus highly desirable. The issues accompanying white phosphorus processing guided our research in the direction of developing an alternative route towards an easy-to-handle P(III) precursor from which a variety of value-added phosphorus compounds might be synthesized. During our research on N-heterocyclic phosphanes, such as pyrazolylphosphanes, we realized the substantial advantage of utilizing pyrazolyl substituents (or related N-based substituents) as extremely amenable leaving groups on phosphorus, rendering these pyrazolylphosphanes as synthetic equivalents of a P 1 synthon 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 . We have previously demonstrated that certain N-heterocyclic phosphorus compounds are highly reactive, but allow for controlled reactions in which these compounds serve as P 1 building blocks and where the side product can either be recycled or is of synthetic importance 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 . The results discussed in this work converge on the concept of oxidative onioation,", "role": "user" }, { "content": "Chemists at the Technische Universität Dresden have developed a new, more sustainable process for synthesizing numerous important everyday chemicals from white phosphorus. The new process has the potential to establish innovative, more resource-efficient processes in the chemical industry. The groundbreaking results, which are the product of more than a decade of intensive research, have now been published in the journal Nature Chemistry. The chemical element phosphorus (P) is one of the essential building blocks of all biological life and, based on it, a function-giving component of many products: in medicines, food products or fertilizers. In nature, phosphorus occurs exclusively in bound form as phosphate in the earth's crust. However, continental deposits are finite and are estimated to last for only a few more decades. For industrial use, phosphates are converted into the so-called white phosphorus by laborious chemical processes. Alongside red, black and violet phosphorus, white phosphorus is the most important modification of the element in industrial terms and, to date, is still an irreplaceable starting point for the production of many pharmaceuticals, flame retardants, battery electrolytes, herbicides and other phosphorus fine chemicals. For the production of phosphorus-containing everyday chemicals, the white phosphorus is mostly converted by chlorination with chlorine gas to phosphorus trichloride (PCl3); a corrosive and toxic liquid, which is of central importance for the chemical industry as a large-scale industrial intermediate. However, the production and use of PCl3, which has so far been without alternative, is highly problematic. The chemist Prof. Jan J. Weigand of the TU Dresden and his team have now succeeded in specifically converting white phosphorus (P4) into an alternative and much less problematic phosphorus intermediate reagent. In this process, the use of chlorine gas can be completely omitted. Instead, the process chemicals needed to convert the white phosphorus are recyclable. \"Economic factors still stand in the way of industrial application of the process, however a rethink is currently taking place here due to necessary, more sustainable aspects in the chemical industry. The more resource-conserving and efficient use of finite raw materials and the development of sustainable processes in many areas of chemistry are of the utmost importance. This work is a decisive breakthrough in phosphorus chemistry and of great importance for the further development of more sustainable and environmentally friendly processes,\" affirms Dr. Kai Schwedtmann, one of the two first authors of the publication. Prof. Weigand and his group are currently developing further concepts with the aim of completely eliminating the need to use white phosphorus or PCl3 for the synthesis of pharmaceuticals, flame retardants, battery electrolytes, herbicides and other phosphorus fine chemicals: \"In order to meet the greatest challenges of our time, a rethink must also take place in the chemical industry. We want to make a small contribution to this with our research by developing a 'blueprint' for a more modern and more sustainable phosphorus chemistry.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The main feedstock for the value-added phosphorus chemicals used in industry and research is white phosphorus (P 4 ), from which the key intermediate for forming P(III) compounds is PCl 3 . Owing to its high reactivity, syntheses based on PCl 3 are often accompanied by product mixtures and laborious work-up procedures, so an alternative process to form a viable P(III) transfer reagent is desirable. Our concept of oxidative onioation, where white phosphorus is selectively converted into triflate salts of versatile P 1 transfer reagents such as [P(L N ) 3 ][OTf] 3 (L N is a cationic, N-based substituent; that is, 4-dimethylaminopyridinio), provides a convenient alternative for the implementation of P–O, P–N and P–C bonds while circumventing the use of PCl 3 . We use p-block element compounds of type R n E (for example, Ph 3 As or PhI) to access weak adducts between nitrogen Lewis bases L N and the corresponding dications [R n EL N ] 2+ . The proposed equilibrium between [R n EL N ] 2+ + L N and [R n E(L N ) 2 ] 2+ allows for the complete oxidative onioation of all six P–P bonds in P 4 to yield highly reactive and versatile trications [P(L N ) 3 ] 3+ . Main Phosphorus is an essential building block of all biological life. It not only fuels the global food economy but has also found a plethora of additional applications in industry 1 . Phosphate rock is the natural but non-renewable resource of this highly important element. The majority of phosphate rock is used for the production of phosphoric acid (H 3 PO 4 ) via the wet process using concentrated sulfuric acid (Fig. 1 ) 2 , 3 , 4 , 5 , 6 . This process provides a product that is mainly used for fertilizers (~90%) 2 , 3 , 4 , 5 , 6 . The industrial reduction of phosphate rock is termed the electrothermal process and yields white phosphorus (P 4 ), which is the major phosphorus source for industrial and academic applications, for example, pharmaceuticals, flame retardants, battery ingredients, fertilizers, herbicides, metals and electronics etchants, as well as additional phosphorus fine chemicals 2 , 3 , 4 , 5 , 6 . Fig. 1: Routes into value-added phosphorus chemicals from phosphate rock. Transformation of phosphate rock via the wet process to phosphoric acid (H 3 PO 4 ) and via the thermal process to white phosphorus (P 4 ) with subsequent (oxy)chlorination to PCl 3 , OPCl 3 or P 4 O 10 . The green box outlines the present work: oxidative onioation of P 4 to give [P(L N ) 3 ][OTf] 3 , a viable alternative to PCl 3 . An element compound R n E is oxidized to an element oxide R n EO. In the onio-ligand assisted deoxygenation, the R n EO is deoxygenated using an oxygen scavenger in the presence of an N-based ligand (L N ) to give [R n E(L N ) 2 ][OTf] 2 , a weak adduct that undergoes an equilibrium dissociation into cation [R n EL N ][OTf] 2 and uncoordinated ligand L N . This weak adduct is regarded as an oxidative onio-reagent for the desired P 4 oxidation. The element compound R n E is retrieved to close the cycle. L N is a suitable nitrogen-based Lewis base (dimethylaminopyridine, pyridine and quinoline) and R n E is a p-block-element compound (triphenylarsane and phenyl iodide); Tf 2 O = trifluoromethanesulfonic anhydride; Me 3 SiOTf = trimethylsilyl triflate. Equations are not balanced. Full size image Among the range of key phosphorus intermediates, PCl 3 is still the most important P(III) source. The production of this very important bulk chemical includes the use of chlorine gas (Cl 2 ), which is widely considered to be problematic; however, as yet, there is no alternative 2 , 3 , 4 , 5 , 6 for industrial and laboratory applications. PCl 3 is used in subsequent transformation reactions such as hydrolysis, alcoholysis, salt metathesis and Grignard reactions to obtain value-added phosphorus chemicals. These reactions often suffer from low selectivity and/or require an additional base in some cases (for example, to capture HCl). In this regard, the functionalization of white phosphorus into chemically useful products without the use of chlorine gas 7 , 8 , 9 , 10 , 11 , 12 , 13 has received much interest from the research community, including efforts to develop ecologically friendlier chemistry routes 5 , 6 , 14 . Recent contributions in this field include the light-induced catalytic functionalization of P 4 or its transformation using tributyltin hydride 15 , 16 . However, such reactions are extremely challenging and still very rare due to the selective and complete cleavage of all six P–P bonds of the reactive P 4 tetrahedron and, in turn, the selective formation of new phosphorus-element bonds. A selective transformation of white phosphorus to a single P(III) compound that is a viable alternative to PCl 3 is thus highly desirable. The issues accompanying white phosphorus processing guided our research in the direction of developing an alternative route towards an easy-to-handle P(III) precursor from which a variety of value-added phosphorus compounds might be synthesized. During our research on N-heterocyclic phosphanes, such as pyrazolylphosphanes, we realized the substantial advantage of utilizing pyrazolyl substituents (or related N-based substituents) as extremely amenable leaving groups on phosphorus, rendering these pyrazolylphosphanes as synthetic equivalents of a P 1 synthon 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 . We have previously demonstrated that certain N-heterocyclic phosphorus compounds are highly reactive, but allow for controlled reactions in which these compounds serve as P 1 building blocks and where the side product can either be recycled or is of synthetic importance 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 . The results discussed in this work converge on the concept of oxidative onioation,<|im_end|> <|im_start|>assistant Chemists at the Technische Universität Dresden have developed a new, more sustainable process for synthesizing numerous important everyday chemicals from white phosphorus. The new process has the potential to establish innovative, more resource-efficient processes in the chemical industry. The groundbreaking results, which are the product of more than a decade of intensive research, have now been published in the journal Nature Chemistry. The chemical element phosphorus (P) is one of the essential building blocks of all biological life and, based on it, a function-giving component of many products: in medicines, food products or fertilizers. In nature, phosphorus occurs exclusively in bound form as phosphate in the earth's crust. However, continental deposits are finite and are estimated to last for only a few more decades. For industrial use, phosphates are converted into the so-called white phosphorus by laborious chemical processes. Alongside red, black and violet phosphorus, white phosphorus is the most important modification of the element in industrial terms and, to date, is still an irreplaceable starting point for the production of many pharmaceuticals, flame retardants, battery electrolytes, herbicides and other phosphorus fine chemicals. For the production of phosphorus-containing everyday chemicals, the white phosphorus is mostly converted by chlorination with chlorine gas to phosphorus trichloride (PCl3); a corrosive and toxic liquid, which is of central importance for the chemical industry as a large-scale industrial intermediate. However, the production and use of PCl3, which has so far been without alternative, is highly problematic. The chemist Prof. Jan J. Weigand of the TU Dresden and his team have now succeeded in specifically converting white phosphorus (P4) into an alternative and much less problematic phosphorus intermediate reagent. In this process, the use of chlorine gas can be completely omitted. Instead, the process chemicals needed to convert the white phosphorus are recyclable. "Economic factors still stand in the way of industrial application of the process, however a rethink is currently taking place here due to necessary, more sustainable aspects in the chemical industry. The more resource-conserving and efficient use of finite raw materials and the development of sustainable processes in many areas of chemistry are of the utmost importance. This work is a decisive breakthrough in phosphorus chemistry and of great importance for the further development of more sustainable and environmentally friendly processes," affirms Dr. Kai Schwedtmann, one of the two first authors of the publication. Prof. Weigand and his group are currently developing further concepts with the aim of completely eliminating the need to use white phosphorus or PCl3 for the synthesis of pharmaceuticals, flame retardants, battery electrolytes, herbicides and other phosphorus fine chemicals: "In order to meet the greatest challenges of our time, a rethink must also take place in the chemical industry. We want to make a small contribution to this with our research by developing a 'blueprint' for a more modern and more sustainable phosphorus chemistry." <|im_end|>

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2,090

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Asymmetric transition-metal catalysis has had a far-reaching impact on chemical synthesis. However, non-precious metal-catalysed strategies that provide direct entry to compounds with enantioenriched trisubstituted and fully substituted stereogenic centres are scarce. Here we show that a sterically encumbered chiral N -heterocyclic carbene-Ni(0) catalyst, in conjunction with an organotriflate and a metal alkoxide as hydride donor, promotes 1,2-hydroarylation and hydroalkenylation of diverse alkenes and 1,3-dienes. Replacing the metal alkoxide with an organometallic reagent allows installation of two different carbogenic motifs. These multicomponent reactions proceed through regio- and enantioselective carbonickelation followed by carbon–nickel bond transformation, providing a streamlined pathway towards enantioenriched carbon- or heteroatom-substituted tertiary or quaternary stereogenic centres. Through selective carbofunctionalizations, enantiodivergent access to opposite enantiomers may be achieved using the same catalyst antipode. The method enables practical access to complex bioactive molecules and other medicinally valuable but synthetically challenging building blocks, such as those that contain deuterated methyl groups. Main Enantioenriched tri- and tetrasubstituted stereogenic centres, particularly those linked to aromatic or olefinic moieties, feature widely among natural products and synthetic drug candidates 1 , 2 (Fig. 1a ). The spatial arrangement of atoms around such centres often dictates the overall shape of a molecule and influences its biological function or toxicity. Because opposite enantiomers may possess vastly different activities 3 , 4 , the ability to exert exquisite control over the absolute configuration to access enantiomerically pure compounds through asymmetric catalysis 5 , 6 is of the utmost importance in pharmaceutical 7 and agrochemical 8 research. In addition, catalytic enantioselective synthesis helps to avoid the necessity for cumbersome resolutions of racemic mixtures. Fig. 1: The importance of developing enantioselective olefin cross-coupling reactions using non-precious metal catalysis. a , Tri- and tetrasubstituted stereocentres are commonly embedded within natural products and drugs. b , Established base-metal-catalysed carbofunctionalization strategies for introducing stereocentres and their associated challenges. c , Our report on regio- and enantioselective olefin cross-coupling reactions catalysed by a bulky chiral NHC–nickel(0) complex. R, G, functional group; Ar, aryl group; L, ligand; M, metal; X, halide or pseudohalide; Tf, triflyl. Full size image Transition-metal-catalysed enantioselective multicomponent coupling of carbogenic functionalities with prochiral carbon–carbon π -frameworks is an attractive avenue for generating molecular complexity and stereogenicity 9 . In particular, the process of Markovnikov-selective 1,2-hydrocarbofunctionalization 10 , 11 , in which adjacent C−C and C−H bonds can be installed with precision, offers the opportunity to control the stereochemical outcome when a chiral organometallic catalytic species is involved to promote enantiofacial discrimination of the substrate. To this end, seminal advances in Pd-catalysed reductive Heck-type reactions that forge C( sp 2 )−C( sp 3 ) bonds have been reported 12 . In recent years, the surge in demand for non-precious metal catalysis as a more sustainable alternative 13 has led to a number of related developments in enantioselective olefin coupling transformations 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 (Fig. 1b ). A significant proportion of these olefin hydrocarbofunctionalizations proceed through sequential hydrometallation/carbofunctionalization regimes via a chiral metal–hydride intermediate I derived from a hydride donor such as an alcohol 18 , 19 , 20 , 21 , 22 or hydrosilane 23 , 24 , 25 , 26 , 27 . Enantioselectivity is typically dictated during the regioselective hydrometallation event from I to II (electronic stabilization by the α-substituent R), before reaction with a carbon electrophile or organometallic nucleophile to give the final product. On the other hand, transformations that incorporate two carbogenic moieties via III and IV have been documented, although the scope is restricted to styrene homo-diarylation using aryl halides to deliver enantioenriched triarylethanes 28 . Despite these efforts, established base-metal-catalysed regimes are often plagued by critical problems that preclude their widespread adoption across chemical research (Fig. 1b , grey inset). For example, the scope of most reported methods has centred on constructing enantioenriched tertiary stereocentres 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 . Analogous reactions that lead to crowded tetrasubstituted carbon centres 31 remain underdeveloped. This is not surprising, because access to these products is often thwarted by the increased steric congestion within the putative tertiary alkylmetal intermediate 32 obtained after metal–hydride addition to 1,1-disubstituted alkenes, which inadvertently raises the energy barriers for hydrometallation and the subsequent C−C bond formation. Added to this complication is the inability of a chiral catalytic entity to appreciably differentiate the enantiotopic faces of a 1,1-disubstituted olefin (versus a monosubstituted variant) for high selectivity 33 . Although the enantioselective generation of all-carbon quaternary stereocentres is a primal objective in organic synthesis 7 , 31 , 34 , 35 , 36 , 37 , methodologies that achieve this by direct carbofunctionalization of readily available olefin feedstocks, without relying on intramolecularity or activating/directing auxiliaries using non-precious metal catalysis, are unexpectedly scarce. Furthermore, most of these hydroarylation and hydroalkenylation protocols employed either styrenes 18 , 19 , 20 , 21 , 23 , 24 , 25 , 28 , N -acyl enamines 26 , 27 or aryl-1,3-dienes 18 , 20 , 22 as substrates, which give rise to a limited range of enantioenriched products. In addition, poor regio- and enantioselectivities were observed with alkyl-substituted 1,3-dienes 22 , which are prone to allylic rearrangement and thus show difficulty in undergoing selective carbo-additions 38 . The corresponding transformations with the less reactive enol ethers, N -vinylheteroarenes or vinylsilanes affording heteroatom-substituted stereocentres that are prevalent in pharmaceuticals 39 , 40 are also exceedingly rare. For dicarbofunctionalization, efficient addition of two distinct carbon units is challenging owing to undesired side reactions arising from competitive coupling between the reagents 41 , as well as adventitious β-H elimination 42 of the alkylmetal intermediate analogous to IV . In light of the aforementioned challenges, a unified enantioselective olefin cross-coupling manifold that enables access to various categories of enantioenriched tri- and tetrasubstituted", "role": "user" }, { "content": "NUS chemists have developed an effective method to access enantioenriched drug-like compounds through multicomponent olefin cross-coupling using chiral nickel-based catalysts. Chiral molecules containing enantioenriched tri- and tetrasubstituted stereogenic centers are found among many natural products and drugs. The spatial arrangement of atoms around such centers often dictates the overall shape of a molecule and influences its biological function or toxicity. Thus, the ability to generate enantiomerically pure compounds through asymmetric catalysis is vital in pharmaceutical and agrochemical research. However, related strategies that employ non-precious metal-derived catalyst systems to promote enantioselective synthesis using cheap and abundant olefin starting materials often have limited scope. This constrains their widespread adoption. A research team led by Assistant Professor Koh Ming Joo, from the Department of Chemistry, National University of Singapore has designed a new strategy that leverages widely available nickel catalysts containing hindered N-heterocyclic carbene (NHC) ligands, to merge olefins with an organotriflate and a metal alkoxide as hydride donor. Replacing the metal alkoxide with an organometallic reagent enables installation of two different carbogenic groups. These multicomponent reactions provide a streamlined pathway towards chiral molecules bearing enantioenriched carbon- or heteroatom-substituted tertiary or quaternary stereogenic centers. This is a collaboration with Professor Shi-Liang Shi, from the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences. The findings were published in Nature Catalysis. Prof. Koh said, \"Through selective carbofunctionalizations, we can even access opposite enantiomers of a chiral molecule by using a single chiral catalyst antipode. This is difficult to achieve using alternative systems, demonstrating a unique advantage of our catalytic regime. We can now utilize this new protocol as a general platform to produce valuable chiral molecules with high stereochemical purity.\" \"We believe this methodology will significantly enrich the toolbox of asymmetric catalysis to facilitate countless applications in stereoselective natural product synthesis and drug discovery,\" added Prof. Koh. The research team is developing new chiral NHC-nickel catalysts to promote olefin cross-coupling transformations that can potentially address other unresolved challenges in organic synthesis. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Asymmetric transition-metal catalysis has had a far-reaching impact on chemical synthesis. However, non-precious metal-catalysed strategies that provide direct entry to compounds with enantioenriched trisubstituted and fully substituted stereogenic centres are scarce. Here we show that a sterically encumbered chiral N -heterocyclic carbene-Ni(0) catalyst, in conjunction with an organotriflate and a metal alkoxide as hydride donor, promotes 1,2-hydroarylation and hydroalkenylation of diverse alkenes and 1,3-dienes. Replacing the metal alkoxide with an organometallic reagent allows installation of two different carbogenic motifs. These multicomponent reactions proceed through regio- and enantioselective carbonickelation followed by carbon–nickel bond transformation, providing a streamlined pathway towards enantioenriched carbon- or heteroatom-substituted tertiary or quaternary stereogenic centres. Through selective carbofunctionalizations, enantiodivergent access to opposite enantiomers may be achieved using the same catalyst antipode. The method enables practical access to complex bioactive molecules and other medicinally valuable but synthetically challenging building blocks, such as those that contain deuterated methyl groups. Main Enantioenriched tri- and tetrasubstituted stereogenic centres, particularly those linked to aromatic or olefinic moieties, feature widely among natural products and synthetic drug candidates 1 , 2 (Fig. 1a ). The spatial arrangement of atoms around such centres often dictates the overall shape of a molecule and influences its biological function or toxicity. Because opposite enantiomers may possess vastly different activities 3 , 4 , the ability to exert exquisite control over the absolute configuration to access enantiomerically pure compounds through asymmetric catalysis 5 , 6 is of the utmost importance in pharmaceutical 7 and agrochemical 8 research. In addition, catalytic enantioselective synthesis helps to avoid the necessity for cumbersome resolutions of racemic mixtures. Fig. 1: The importance of developing enantioselective olefin cross-coupling reactions using non-precious metal catalysis. a , Tri- and tetrasubstituted stereocentres are commonly embedded within natural products and drugs. b , Established base-metal-catalysed carbofunctionalization strategies for introducing stereocentres and their associated challenges. c , Our report on regio- and enantioselective olefin cross-coupling reactions catalysed by a bulky chiral NHC–nickel(0) complex. R, G, functional group; Ar, aryl group; L, ligand; M, metal; X, halide or pseudohalide; Tf, triflyl. Full size image Transition-metal-catalysed enantioselective multicomponent coupling of carbogenic functionalities with prochiral carbon–carbon π -frameworks is an attractive avenue for generating molecular complexity and stereogenicity 9 . In particular, the process of Markovnikov-selective 1,2-hydrocarbofunctionalization 10 , 11 , in which adjacent C−C and C−H bonds can be installed with precision, offers the opportunity to control the stereochemical outcome when a chiral organometallic catalytic species is involved to promote enantiofacial discrimination of the substrate. To this end, seminal advances in Pd-catalysed reductive Heck-type reactions that forge C( sp 2 )−C( sp 3 ) bonds have been reported 12 . In recent years, the surge in demand for non-precious metal catalysis as a more sustainable alternative 13 has led to a number of related developments in enantioselective olefin coupling transformations 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 (Fig. 1b ). A significant proportion of these olefin hydrocarbofunctionalizations proceed through sequential hydrometallation/carbofunctionalization regimes via a chiral metal–hydride intermediate I derived from a hydride donor such as an alcohol 18 , 19 , 20 , 21 , 22 or hydrosilane 23 , 24 , 25 , 26 , 27 . Enantioselectivity is typically dictated during the regioselective hydrometallation event from I to II (electronic stabilization by the α-substituent R), before reaction with a carbon electrophile or organometallic nucleophile to give the final product. On the other hand, transformations that incorporate two carbogenic moieties via III and IV have been documented, although the scope is restricted to styrene homo-diarylation using aryl halides to deliver enantioenriched triarylethanes 28 . Despite these efforts, established base-metal-catalysed regimes are often plagued by critical problems that preclude their widespread adoption across chemical research (Fig. 1b , grey inset). For example, the scope of most reported methods has centred on constructing enantioenriched tertiary stereocentres 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 . Analogous reactions that lead to crowded tetrasubstituted carbon centres 31 remain underdeveloped. This is not surprising, because access to these products is often thwarted by the increased steric congestion within the putative tertiary alkylmetal intermediate 32 obtained after metal–hydride addition to 1,1-disubstituted alkenes, which inadvertently raises the energy barriers for hydrometallation and the subsequent C−C bond formation. Added to this complication is the inability of a chiral catalytic entity to appreciably differentiate the enantiotopic faces of a 1,1-disubstituted olefin (versus a monosubstituted variant) for high selectivity 33 . Although the enantioselective generation of all-carbon quaternary stereocentres is a primal objective in organic synthesis 7 , 31 , 34 , 35 , 36 , 37 , methodologies that achieve this by direct carbofunctionalization of readily available olefin feedstocks, without relying on intramolecularity or activating/directing auxiliaries using non-precious metal catalysis, are unexpectedly scarce. Furthermore, most of these hydroarylation and hydroalkenylation protocols employed either styrenes 18 , 19 , 20 , 21 , 23 , 24 , 25 , 28 , N -acyl enamines 26 , 27 or aryl-1,3-dienes 18 , 20 , 22 as substrates, which give rise to a limited range of enantioenriched products. In addition, poor regio- and enantioselectivities were observed with alkyl-substituted 1,3-dienes 22 , which are prone to allylic rearrangement and thus show difficulty in undergoing selective carbo-additions 38 . The corresponding transformations with the less reactive enol ethers, N -vinylheteroarenes or vinylsilanes affording heteroatom-substituted stereocentres that are prevalent in pharmaceuticals 39 , 40 are also exceedingly rare. For dicarbofunctionalization, efficient addition of two distinct carbon units is challenging owing to undesired side reactions arising from competitive coupling between the reagents 41 , as well as adventitious β-H elimination 42 of the alkylmetal intermediate analogous to IV . In light of the aforementioned challenges, a unified enantioselective olefin cross-coupling manifold that enables access to various categories of enantioenriched tri- and tetrasubstituted<|im_end|> <|im_start|>assistant NUS chemists have developed an effective method to access enantioenriched drug-like compounds through multicomponent olefin cross-coupling using chiral nickel-based catalysts. Chiral molecules containing enantioenriched tri- and tetrasubstituted stereogenic centers are found among many natural products and drugs. The spatial arrangement of atoms around such centers often dictates the overall shape of a molecule and influences its biological function or toxicity. Thus, the ability to generate enantiomerically pure compounds through asymmetric catalysis is vital in pharmaceutical and agrochemical research. However, related strategies that employ non-precious metal-derived catalyst systems to promote enantioselective synthesis using cheap and abundant olefin starting materials often have limited scope. This constrains their widespread adoption. A research team led by Assistant Professor Koh Ming Joo, from the Department of Chemistry, National University of Singapore has designed a new strategy that leverages widely available nickel catalysts containing hindered N-heterocyclic carbene (NHC) ligands, to merge olefins with an organotriflate and a metal alkoxide as hydride donor. Replacing the metal alkoxide with an organometallic reagent enables installation of two different carbogenic groups. These multicomponent reactions provide a streamlined pathway towards chiral molecules bearing enantioenriched carbon- or heteroatom-substituted tertiary or quaternary stereogenic centers. This is a collaboration with Professor Shi-Liang Shi, from the Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences. The findings were published in Nature Catalysis. Prof. Koh said, "Through selective carbofunctionalizations, we can even access opposite enantiomers of a chiral molecule by using a single chiral catalyst antipode. This is difficult to achieve using alternative systems, demonstrating a unique advantage of our catalytic regime. We can now utilize this new protocol as a general platform to produce valuable chiral molecules with high stereochemical purity." "We believe this methodology will significantly enrich the toolbox of asymmetric catalysis to facilitate countless applications in stereoselective natural product synthesis and drug discovery," added Prof. Koh. The research team is developing new chiral NHC-nickel catalysts to promote olefin cross-coupling transformations that can potentially address other unresolved challenges in organic synthesis. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Detecting rare cells within blood has numerous applications in disease diagnostics. Existing rare cell detection techniques are typically hindered by their high cost and low throughput. Here, we present a computational cytometer based on magnetically modulated lensless speckle imaging, which introduces oscillatory motion to the magnetic-bead-conjugated rare cells of interest through a periodic magnetic force and uses lensless time-resolved holographic speckle imaging to rapidly detect the target cells in three dimensions (3D). In addition to using cell-specific antibodies to magnetically label target cells, detection specificity is further enhanced through a deep-learning-based classifier that is based on a densely connected pseudo-3D convolutional neural network (P3D CNN), which automatically detects rare cells of interest based on their spatio-temporal features under a controlled magnetic force. To demonstrate the performance of this technique, we built a high-throughput, compact and cost-effective prototype for detecting MCF7 cancer cells spiked in whole blood samples. Through serial dilution experiments, we quantified the limit of detection (LoD) as 10 cells per millilitre of whole blood, which could be further improved through multiplexing parallel imaging channels within the same instrument. This compact, cost-effective and high-throughput computational cytometer can potentially be used for rare cell detection and quantification in bodily fluids for a variety of biomedical applications. Introduction Rare cell detection aims to identify a sufficient number of low-abundance cells within a vast majority of background cells, which typically requires the processing of large volumes of biological sample. The detection and enumeration of these rare cells are vital for disease diagnostics, the evaluation of disease progression and the characterization of immune response 1 , 2 , 3 . For instance, circulating foetal cells present in maternal blood are recognized as a source of foetal genomic DNA, and their isolation is crucial for the implementation of routine prenatal diagnostic testing 4 . As another example, antigen-specific T cells in peripheral blood play a central role in mediating immune response and the formation of immunological memory, which could lead to the prediction of immune protection and diagnosis of immune-related diseases 5 . Circulating endothelial cells with a mature phenotype are increased in patients with certain types of cancer and several pathological conditions, indicating their potential as disease markers 6 . Circulating tumour cells (CTCs) are implicated in various stages of cancer, and have therefore been collected to study their role in the metastatic cascade and to predict patient outcomes from both the disease and treatments received 7 . To highlight yet another example, haematopoietic stem and progenitor cells, which reside predominantly in bone marrow with low numbers, also found in peripheral blood, possess the unique capacity for self-renewal and multilineage differentiation, and their trafficking in blood may be connected to disease processes 8 . The specific and sensitive detection of these rare cells in human blood and other bodily fluids is therefore of great interest. However, millions of events need to be acquired to obtain a sufficient number of these low-abundance cells (e.g., typically <1000 target cells per millilitre of blood 9 ). The direct detection of rare cells from whole blood requires the processing of large amounts of patient sample (e.g., up to a few hundred millilitres 10 ), which is both unrealistic and time consuming. To alleviate this issue, highly specific labelling methods are often used before detection for sample purification/enrichment to facilitate rapid detection and processing 5 , 10 . Among these labelling techniques, the use of colloidal magnetic particles as labelling reagents offers benefits in forming stable suspensions, fast reaction kinetics 10 and minimum damage to the target cells, with high viability retained 11 . Motivated by these important needs and the associated challenges, various technologies have been developed and employed for detecting rare cells in blood. Most of these existing detection methods involve three steps: capture, enrichment and detection 12 . The capture and enrichment steps use a number of methods, such as barcoded particles 13 , magnetic beads 14 , micro-machines 15 , microfluidic chips 16 and density gradient centrifugation 12 , 17 . Following the enrichment step, these rare cells can be detected via commonly used techniques, such as immunofluorescence 18 , 19 , electrical impedance 20 and Raman scattering 21 measurements, among others. Notably, commercial products for rare cell detection, such as the CellSearch system 22 , which automates magnetic labelling, isolation, fluorescence labelling and automated counting, are generally high cost, limiting their adoption worldwide 12 . Therefore, cost-effective, reliable and high-throughput rare cell detection techniques are urgently needed to improve the early diagnosis of diseases, including cancer, so that earlier treatments can be carried out, helping us to improve patient outcomes while also reducing healthcare costs 23 , 24 . The recent advances in machine learning and, specifically, deep learning have pushed the frontiers of biomedical imaging and image analysis 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , enabling rapid and accurate pathogen detection 39 , 40 , 41 , 42 and computer-assisted diagnostic methods 43 , 44 , 45 , 46 , 47 . Powered by deep learning, we demonstrate here that speckle imaging using lensless chip-scale microscopy can be employed for the specific and sensitive detection of rare cells in blood with low cost and high throughput. This novel cell detection and cytometry technique are based on magnetically modulated lensless speckle imaging, which specifically labels rare cells of interest using magnetic particles attached to surface markers of interest and generates periodic and well-controlled motion on target cells by alternating the external magnetic field applied to a large sample volume. The holographic diffraction and the resulting speckle patterns of the moving cells are then captured using a compact and cost-effective on-chip lensless imager (Fig. 1 ), and are computationally analysed by a deep-learning-based algorithm to rapidly detect and accurately identify the rare cells of interest in a high-throughput manner based on their unique spatio-temporal features. Although previous work has employed the idea", "role": "user" }, { "content": "Detection of rare cells in blood and other bodily fluids has numerous important applications including diagnostics, monitoring disease progression and evaluating immune response. For example, detecting and collecting circulating tumour cells (CTCs) in blood can help cancer diagnostics, study their role in the metastatic cascade and predict patient outcomes. However, because each millilitre of whole blood contains billions of blood cells, the rare cells (such as CTCs) that occur at extremely low concentrations (typically lower than 100-1000 cells per millilitre) are very difficult to detect. Although various solutions have been developed to address this challenge, existing techniques in general are limited by high cost and low throughput. Researchers at UCLA Henry Samueli School of Engineering have developed a new cytometry platform to detect rare cells in blood with high throughput and low cost. Published in Light: Science and Applications, this novel cytometry technique, termed magnetically modulated lensless speckle imaging, first uses magnetic bead labelling to enrich the target cells. Then the enriched liquid sample containing magnetic bead-labelled target cells is placed under an alternating magnetic field, which causes the target cells to oscillate laterally at a fixed frequency. At the same time, a laser diode illuminates the sample from above and an image sensor positioned below the sample captures a high-frame-rate lensless video of the time-varying optical pattern generated by the sample. The recorded spatiotemporal pattern contains the information needed to detect the oscillating target cells. The researchers built a compact and low-cost prototype of this computational lensless cytometer using off-the-shelf image sensors, laser diodes and electromagnets, and used a custom-built translation stage to allow the imager unit to scan liquid sample loaded in a glass tube. The prototype can screen the equivalent of ~1.2 mL of whole blood sample in ~7 min, while costing only ~$750 and weighing ~2.1 kg. Multiple parallel imaging channels can also be easily added to the system to further increase sample throughput. To ensure optimal sensitivity and specificity of rare cell detection, a two-step computational procedure was developed, which involved a computational motion analysis algorithm to detect micro-objects oscillating at the specified alternating frequency, and then a deep learning-based classification algorithm based on a densely connected pseudo-3-D convolutional neural network (P3D CNN) structure. The deep neural network greatly improved the accuracy of the technique, resulting in a limit of detection of 10 cells per millilitre of whole blood. This AI-driven cytometry technique relies on the magnetic particles for both cell enrichment and detection, which reduces the time and cost for detecting rare cells while maintaining a high sensitivity. This compact, low-cost yet powerful cytometry system may find numerous applications especially in resource-limited settings. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Detecting rare cells within blood has numerous applications in disease diagnostics. Existing rare cell detection techniques are typically hindered by their high cost and low throughput. Here, we present a computational cytometer based on magnetically modulated lensless speckle imaging, which introduces oscillatory motion to the magnetic-bead-conjugated rare cells of interest through a periodic magnetic force and uses lensless time-resolved holographic speckle imaging to rapidly detect the target cells in three dimensions (3D). In addition to using cell-specific antibodies to magnetically label target cells, detection specificity is further enhanced through a deep-learning-based classifier that is based on a densely connected pseudo-3D convolutional neural network (P3D CNN), which automatically detects rare cells of interest based on their spatio-temporal features under a controlled magnetic force. To demonstrate the performance of this technique, we built a high-throughput, compact and cost-effective prototype for detecting MCF7 cancer cells spiked in whole blood samples. Through serial dilution experiments, we quantified the limit of detection (LoD) as 10 cells per millilitre of whole blood, which could be further improved through multiplexing parallel imaging channels within the same instrument. This compact, cost-effective and high-throughput computational cytometer can potentially be used for rare cell detection and quantification in bodily fluids for a variety of biomedical applications. Introduction Rare cell detection aims to identify a sufficient number of low-abundance cells within a vast majority of background cells, which typically requires the processing of large volumes of biological sample. The detection and enumeration of these rare cells are vital for disease diagnostics, the evaluation of disease progression and the characterization of immune response 1 , 2 , 3 . For instance, circulating foetal cells present in maternal blood are recognized as a source of foetal genomic DNA, and their isolation is crucial for the implementation of routine prenatal diagnostic testing 4 . As another example, antigen-specific T cells in peripheral blood play a central role in mediating immune response and the formation of immunological memory, which could lead to the prediction of immune protection and diagnosis of immune-related diseases 5 . Circulating endothelial cells with a mature phenotype are increased in patients with certain types of cancer and several pathological conditions, indicating their potential as disease markers 6 . Circulating tumour cells (CTCs) are implicated in various stages of cancer, and have therefore been collected to study their role in the metastatic cascade and to predict patient outcomes from both the disease and treatments received 7 . To highlight yet another example, haematopoietic stem and progenitor cells, which reside predominantly in bone marrow with low numbers, also found in peripheral blood, possess the unique capacity for self-renewal and multilineage differentiation, and their trafficking in blood may be connected to disease processes 8 . The specific and sensitive detection of these rare cells in human blood and other bodily fluids is therefore of great interest. However, millions of events need to be acquired to obtain a sufficient number of these low-abundance cells (e.g., typically <1000 target cells per millilitre of blood 9 ). The direct detection of rare cells from whole blood requires the processing of large amounts of patient sample (e.g., up to a few hundred millilitres 10 ), which is both unrealistic and time consuming. To alleviate this issue, highly specific labelling methods are often used before detection for sample purification/enrichment to facilitate rapid detection and processing 5 , 10 . Among these labelling techniques, the use of colloidal magnetic particles as labelling reagents offers benefits in forming stable suspensions, fast reaction kinetics 10 and minimum damage to the target cells, with high viability retained 11 . Motivated by these important needs and the associated challenges, various technologies have been developed and employed for detecting rare cells in blood. Most of these existing detection methods involve three steps: capture, enrichment and detection 12 . The capture and enrichment steps use a number of methods, such as barcoded particles 13 , magnetic beads 14 , micro-machines 15 , microfluidic chips 16 and density gradient centrifugation 12 , 17 . Following the enrichment step, these rare cells can be detected via commonly used techniques, such as immunofluorescence 18 , 19 , electrical impedance 20 and Raman scattering 21 measurements, among others. Notably, commercial products for rare cell detection, such as the CellSearch system 22 , which automates magnetic labelling, isolation, fluorescence labelling and automated counting, are generally high cost, limiting their adoption worldwide 12 . Therefore, cost-effective, reliable and high-throughput rare cell detection techniques are urgently needed to improve the early diagnosis of diseases, including cancer, so that earlier treatments can be carried out, helping us to improve patient outcomes while also reducing healthcare costs 23 , 24 . The recent advances in machine learning and, specifically, deep learning have pushed the frontiers of biomedical imaging and image analysis 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , enabling rapid and accurate pathogen detection 39 , 40 , 41 , 42 and computer-assisted diagnostic methods 43 , 44 , 45 , 46 , 47 . Powered by deep learning, we demonstrate here that speckle imaging using lensless chip-scale microscopy can be employed for the specific and sensitive detection of rare cells in blood with low cost and high throughput. This novel cell detection and cytometry technique are based on magnetically modulated lensless speckle imaging, which specifically labels rare cells of interest using magnetic particles attached to surface markers of interest and generates periodic and well-controlled motion on target cells by alternating the external magnetic field applied to a large sample volume. The holographic diffraction and the resulting speckle patterns of the moving cells are then captured using a compact and cost-effective on-chip lensless imager (Fig. 1 ), and are computationally analysed by a deep-learning-based algorithm to rapidly detect and accurately identify the rare cells of interest in a high-throughput manner based on their unique spatio-temporal features. Although previous work has employed the idea<|im_end|> <|im_start|>assistant Detection of rare cells in blood and other bodily fluids has numerous important applications including diagnostics, monitoring disease progression and evaluating immune response. For example, detecting and collecting circulating tumour cells (CTCs) in blood can help cancer diagnostics, study their role in the metastatic cascade and predict patient outcomes. However, because each millilitre of whole blood contains billions of blood cells, the rare cells (such as CTCs) that occur at extremely low concentrations (typically lower than 100-1000 cells per millilitre) are very difficult to detect. Although various solutions have been developed to address this challenge, existing techniques in general are limited by high cost and low throughput. Researchers at UCLA Henry Samueli School of Engineering have developed a new cytometry platform to detect rare cells in blood with high throughput and low cost. Published in Light: Science and Applications, this novel cytometry technique, termed magnetically modulated lensless speckle imaging, first uses magnetic bead labelling to enrich the target cells. Then the enriched liquid sample containing magnetic bead-labelled target cells is placed under an alternating magnetic field, which causes the target cells to oscillate laterally at a fixed frequency. At the same time, a laser diode illuminates the sample from above and an image sensor positioned below the sample captures a high-frame-rate lensless video of the time-varying optical pattern generated by the sample. The recorded spatiotemporal pattern contains the information needed to detect the oscillating target cells. The researchers built a compact and low-cost prototype of this computational lensless cytometer using off-the-shelf image sensors, laser diodes and electromagnets, and used a custom-built translation stage to allow the imager unit to scan liquid sample loaded in a glass tube. The prototype can screen the equivalent of ~1.2 mL of whole blood sample in ~7 min, while costing only ~$750 and weighing ~2.1 kg. Multiple parallel imaging channels can also be easily added to the system to further increase sample throughput. To ensure optimal sensitivity and specificity of rare cell detection, a two-step computational procedure was developed, which involved a computational motion analysis algorithm to detect micro-objects oscillating at the specified alternating frequency, and then a deep learning-based classification algorithm based on a densely connected pseudo-3-D convolutional neural network (P3D CNN) structure. The deep neural network greatly improved the accuracy of the technique, resulting in a limit of detection of 10 cells per millilitre of whole blood. This AI-driven cytometry technique relies on the magnetic particles for both cell enrichment and detection, which reduces the time and cost for detecting rare cells while maintaining a high sensitivity. This compact, low-cost yet powerful cytometry system may find numerous applications especially in resource-limited settings. <|im_end|>

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1,879

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract A flaring X-ray source was found near the galaxy NGC 4697 (ref. 1 ). Two brief flares were seen, separated by four years. During each flare, the flux increased by a factor of 90 on a timescale of about one minute. There is no associated optical source at the position of the flares 1 , but if the source was at the distance of NGC 4697, then the luminosities of the flares were greater than 10 39 erg per second. Here we report the results of a search of archival X-ray data for 70 nearby galaxies looking for similar flares. We found two ultraluminous flaring sources in globular clusters or ultracompact dwarf companions of parent elliptical galaxies. One source flared once to a peak luminosity of 9 × 10 40 erg per second; the other flared five times to 10 40 erg per second. The rise times of all of the flares were less than one minute, and the flares then decayed over about an hour. When not flaring, the sources appear to be normal accreting neutron-star or black-hole X-ray binaries, but they are located in old stellar populations, unlike the magnetars, anomalous X-ray pulsars or soft γ repeaters that have repetitive flares of similar luminosities. Main One flaring source (hereafter Source 1) is located at right ascension RA = 12 h 42 min 51.4 s and declination dec. = +02° 38′ 35″ (J2000) near the Virgo elliptical galaxy NGC 4636 (distance from Milky Way d = 14.3 Mpc) 2 , 3 . A plot of the cumulative X-ray photon arrival time and a crude background-subtracted light curve for this source derived from an approximately 76,000-s Chandra observation taken on 2003 February 14 are shown in Fig. 1 . Prior to and after the flare, the X-ray count rate of the source was (2.1 ± 0.2) × 10 −3 counts per second (errors given here and elsewhere, unless otherwise stated, are 1 σ ). This count rate corresponds to a 0.3–10-keV luminosity of (7.9 ± 0.8) × 10 38 erg s −1 for a power-law spectral model with a best-fit photon index of Γ = 1.6 ± 0.3 (see Methods), assuming the source is at the distance of NGC 4636. About 12,000 s into the observation, the source flared dramatically, with six photons detected in a 22-s span, leading to a conservative peak flare count rate of counts per second—an increase in emission by a factor of 70–200 over its persistent (non-flare) state. Assuming the same spectral model as in the persistent state, the flare peaks at . Following the initial 22-s burst, the source emitted at a less intense, but still elevated, rate for the next 1,400 s. In total, 25 photons were emitted during the flare, for an average X-ray luminosity of (7 ± 2) × 10 39 erg s −1 and a total flare energy of (9 ± 2) × 10 42 erg. We assess that the probability of this burst being due to a random Poisson fluctuation of the persistent count rate is about 6 × 10 −6 (see Methods). Although the photon statistics during the 25-photon burst were limited, there was no evidence that the spectrum of the source differed during the flare. There are no apparent flares in the combined 370,000 s of the other Chandra and XMM-Newton observations of NGC 4636, either before or after 2003 February 14 (see Extended Data Table 1 ). Figure 1: Chandra cumulative X-ray photon arrival time and light curve for Source 1 in the NGC 4636 globular cluster. a , In total, 162 photons were detected over the approximately 76,000-s observation. The flare began after 12,000 s of observation and lasted for 1,400 s. The beginning and end of the flare are indicated by up and down arrows, respectively. b , Within the grey shaded region in a we derive the background-subtracted X-ray light curve. Each time bin contains five photons, with error bars representing the 1 σ uncertainty expected from Poisson statistics. PowerPoint slide Full size image A previous study 4 spatially associated Source 1 with a purported globular cluster of NGC 4636 that was identified through Washington C-band and Kron–Cousins R-band system CTIO Blanco Telescope imaging 5 . Although faint ( R = 23.02), the optical source identified as CTIO ID 6444 had a C − R = 1.94 colour that is consistent with a globular cluster of near-solar metallicity 5 . Follow-up spectroscopic observations 6 of a sub-sample of the globular cluster candidates in the vicinity of the globular cluster that hosts Source 1 found that 52 out of 54 (96%) of the objects with a C − R colour and magnitude similar to CTIO ID 6444 were confirmed to be globular clusters of NGC 4636, with the two remaining objects identified as foreground Galactic stars. The hard X-ray spectrum of Source 1 during its persistent phase (see Methods) evidences against it being a late-type Galactic dwarf star, for which the X-ray emission tends to be quite soft. Galactic RS CVn stars exhibit hard X-ray emission in quiescence and are known to undergo X-ray flares, but these stars have much higher optical-to-X-ray flux ratios 7 compared to Source 1. Therefore, it is highly likely that the optical counterpart of Source 1 is a globular cluster within NGC 4636. On the basis of its absolute R-band magnitude and ratio of mass to light ( M / L = 4.1, with M in units of solar masses M ⊙ and L in solar R-band luminosities), we estimate the globular cluster to have a mass of 3 × 10 5 M ⊙ (see Methods). A second X-ray source located near the elliptical galaxy NGC 5128 showed similar flaring behaviour. In the 2007 March 30 Chandra observation of NGC 5128, a source at RA = 13 h 25 min 52.7 s, dec. = −43° 05′ 46″ (J2000; hereafter Source 2) began the observation emitting at a count rate of (9.5 ± 1.5) × 10 −4 counts per", "role": "user" }, { "content": "This image shows the location of a remarkable source that dramatically flares in X-rays unlike any ever seen. Along with another similar source found in a different galaxy, these objects may represent an entirely new phenomenon, as reported in our latest press release. These two objects were both found in elliptical galaxies, NGC 5128 (also known as Centaurus A) shown here and NGC 4636. In this Chandra X-ray Observatory image of NGC 5128, low, medium, and high-energy X-rays are colored red, green, and blue, and the location of the flaring source is outlined in the box to the lower left. Both of these mysterious sources flare dramatically - becoming a hundred times brighter in X-rays in about a minute before steadily returning to their original X-ray levels about an hour later. At their X-ray peak, these objects qualify as ultraluminous X-ray sources (ULXs) that give off hundreds to thousands of times more X-rays than typical X-ray binary systems where a star is orbiting a black hole or neutron star. Five flares were detected from the source located near NGC 5128, which is at a distance of about 12 million light years from Earth. A movie showing the average change in X-rays for the three flares with the most complete Chandra data, covering both the rise and fall, is shown in the inset. The source associated with the elliptical galaxy NGC 4636, which is located about 47 million light years away, was observed to flare once. This Chandra X-ray Observatory image shows the galaxy NGC5128 with its hot gas and many X-ray point sources. The circled source flared by a factor of 200 in less than a minute on multiple occasions. Credit: NASA/CXC/U.Birmingham/M.Burke et al. The only other objects known to have such rapid, bright, repeated flares involve young neutron stars such as magnetars, which have extremely powerful magnetic fields. However, these newly flaring sources are found in populations of much older stars. Unlike magnetars, the new flaring sources are likely located in dense stellar environments, one in a globular cluster and the other in a small, compact galaxy. When they are not flaring, these newly discovered sources appear to be normal binary systems where a black hole or neutron star is pulling material from a companion star similar to the Sun. This indicates that the flares do not significantly disrupt the binary system. While the nature of these flares is unknown, the team has begun to search for answers. One idea is that the flares represent episodes when matter pulled away from a companion star falls rapidly onto a black hole or neutron star. This could happen when the companion makes its closest approach to the compact object in an eccentric orbit. Another explanation could involve matter falling onto an intermediate-mass black hole, with a mass of about 800 times that of the Sun for one source and 80 times that of the Sun for the other. This result is describing in a paper appearing in the journal Nature on October 20, 2016. The authors are Jimmy Irwin (University of Alabama), Peter Maksym (Harvard-Smithsonian Center for Astrophysics), Gregory Sivakoff (University of Alberta), Aaron Romanowsky (San Jose State University), Dacheng Lin (University of New Hampshire), Tyler Speegle, Ian Prado, David Mildebrath (University of Alabama), Jay Strader (Michigan State University), Jifeng Lui (Chinese Academy of Sciences), and Jon Miller (University of Michigan). ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract A flaring X-ray source was found near the galaxy NGC 4697 (ref. 1 ). Two brief flares were seen, separated by four years. During each flare, the flux increased by a factor of 90 on a timescale of about one minute. There is no associated optical source at the position of the flares 1 , but if the source was at the distance of NGC 4697, then the luminosities of the flares were greater than 10 39 erg per second. Here we report the results of a search of archival X-ray data for 70 nearby galaxies looking for similar flares. We found two ultraluminous flaring sources in globular clusters or ultracompact dwarf companions of parent elliptical galaxies. One source flared once to a peak luminosity of 9 × 10 40 erg per second; the other flared five times to 10 40 erg per second. The rise times of all of the flares were less than one minute, and the flares then decayed over about an hour. When not flaring, the sources appear to be normal accreting neutron-star or black-hole X-ray binaries, but they are located in old stellar populations, unlike the magnetars, anomalous X-ray pulsars or soft γ repeaters that have repetitive flares of similar luminosities. Main One flaring source (hereafter Source 1) is located at right ascension RA = 12 h 42 min 51.4 s and declination dec. = +02° 38′ 35″ (J2000) near the Virgo elliptical galaxy NGC 4636 (distance from Milky Way d = 14.3 Mpc) 2 , 3 . A plot of the cumulative X-ray photon arrival time and a crude background-subtracted light curve for this source derived from an approximately 76,000-s Chandra observation taken on 2003 February 14 are shown in Fig. 1 . Prior to and after the flare, the X-ray count rate of the source was (2.1 ± 0.2) × 10 −3 counts per second (errors given here and elsewhere, unless otherwise stated, are 1 σ ). This count rate corresponds to a 0.3–10-keV luminosity of (7.9 ± 0.8) × 10 38 erg s −1 for a power-law spectral model with a best-fit photon index of Γ = 1.6 ± 0.3 (see Methods), assuming the source is at the distance of NGC 4636. About 12,000 s into the observation, the source flared dramatically, with six photons detected in a 22-s span, leading to a conservative peak flare count rate of counts per second—an increase in emission by a factor of 70–200 over its persistent (non-flare) state. Assuming the same spectral model as in the persistent state, the flare peaks at . Following the initial 22-s burst, the source emitted at a less intense, but still elevated, rate for the next 1,400 s. In total, 25 photons were emitted during the flare, for an average X-ray luminosity of (7 ± 2) × 10 39 erg s −1 and a total flare energy of (9 ± 2) × 10 42 erg. We assess that the probability of this burst being due to a random Poisson fluctuation of the persistent count rate is about 6 × 10 −6 (see Methods). Although the photon statistics during the 25-photon burst were limited, there was no evidence that the spectrum of the source differed during the flare. There are no apparent flares in the combined 370,000 s of the other Chandra and XMM-Newton observations of NGC 4636, either before or after 2003 February 14 (see Extended Data Table 1 ). Figure 1: Chandra cumulative X-ray photon arrival time and light curve for Source 1 in the NGC 4636 globular cluster. a , In total, 162 photons were detected over the approximately 76,000-s observation. The flare began after 12,000 s of observation and lasted for 1,400 s. The beginning and end of the flare are indicated by up and down arrows, respectively. b , Within the grey shaded region in a we derive the background-subtracted X-ray light curve. Each time bin contains five photons, with error bars representing the 1 σ uncertainty expected from Poisson statistics. PowerPoint slide Full size image A previous study 4 spatially associated Source 1 with a purported globular cluster of NGC 4636 that was identified through Washington C-band and Kron–Cousins R-band system CTIO Blanco Telescope imaging 5 . Although faint ( R = 23.02), the optical source identified as CTIO ID 6444 had a C − R = 1.94 colour that is consistent with a globular cluster of near-solar metallicity 5 . Follow-up spectroscopic observations 6 of a sub-sample of the globular cluster candidates in the vicinity of the globular cluster that hosts Source 1 found that 52 out of 54 (96%) of the objects with a C − R colour and magnitude similar to CTIO ID 6444 were confirmed to be globular clusters of NGC 4636, with the two remaining objects identified as foreground Galactic stars. The hard X-ray spectrum of Source 1 during its persistent phase (see Methods) evidences against it being a late-type Galactic dwarf star, for which the X-ray emission tends to be quite soft. Galactic RS CVn stars exhibit hard X-ray emission in quiescence and are known to undergo X-ray flares, but these stars have much higher optical-to-X-ray flux ratios 7 compared to Source 1. Therefore, it is highly likely that the optical counterpart of Source 1 is a globular cluster within NGC 4636. On the basis of its absolute R-band magnitude and ratio of mass to light ( M / L = 4.1, with M in units of solar masses M ⊙ and L in solar R-band luminosities), we estimate the globular cluster to have a mass of 3 × 10 5 M ⊙ (see Methods). A second X-ray source located near the elliptical galaxy NGC 5128 showed similar flaring behaviour. In the 2007 March 30 Chandra observation of NGC 5128, a source at RA = 13 h 25 min 52.7 s, dec. = −43° 05′ 46″ (J2000; hereafter Source 2) began the observation emitting at a count rate of (9.5 ± 1.5) × 10 −4 counts per<|im_end|> <|im_start|>assistant This image shows the location of a remarkable source that dramatically flares in X-rays unlike any ever seen. Along with another similar source found in a different galaxy, these objects may represent an entirely new phenomenon, as reported in our latest press release. These two objects were both found in elliptical galaxies, NGC 5128 (also known as Centaurus A) shown here and NGC 4636. In this Chandra X-ray Observatory image of NGC 5128, low, medium, and high-energy X-rays are colored red, green, and blue, and the location of the flaring source is outlined in the box to the lower left. Both of these mysterious sources flare dramatically - becoming a hundred times brighter in X-rays in about a minute before steadily returning to their original X-ray levels about an hour later. At their X-ray peak, these objects qualify as ultraluminous X-ray sources (ULXs) that give off hundreds to thousands of times more X-rays than typical X-ray binary systems where a star is orbiting a black hole or neutron star. Five flares were detected from the source located near NGC 5128, which is at a distance of about 12 million light years from Earth. A movie showing the average change in X-rays for the three flares with the most complete Chandra data, covering both the rise and fall, is shown in the inset. The source associated with the elliptical galaxy NGC 4636, which is located about 47 million light years away, was observed to flare once. This Chandra X-ray Observatory image shows the galaxy NGC5128 with its hot gas and many X-ray point sources. The circled source flared by a factor of 200 in less than a minute on multiple occasions. Credit: NASA/CXC/U.Birmingham/M.Burke et al. The only other objects known to have such rapid, bright, repeated flares involve young neutron stars such as magnetars, which have extremely powerful magnetic fields. However, these newly flaring sources are found in populations of much older stars. Unlike magnetars, the new flaring sources are likely located in dense stellar environments, one in a globular cluster and the other in a small, compact galaxy. When they are not flaring, these newly discovered sources appear to be normal binary systems where a black hole or neutron star is pulling material from a companion star similar to the Sun. This indicates that the flares do not significantly disrupt the binary system. While the nature of these flares is unknown, the team has begun to search for answers. One idea is that the flares represent episodes when matter pulled away from a companion star falls rapidly onto a black hole or neutron star. This could happen when the companion makes its closest approach to the compact object in an eccentric orbit. Another explanation could involve matter falling onto an intermediate-mass black hole, with a mass of about 800 times that of the Sun for one source and 80 times that of the Sun for the other. This result is describing in a paper appearing in the journal Nature on October 20, 2016. The authors are Jimmy Irwin (University of Alabama), Peter Maksym (Harvard-Smithsonian Center for Astrophysics), Gregory Sivakoff (University of Alberta), Aaron Romanowsky (San Jose State University), Dacheng Lin (University of New Hampshire), Tyler Speegle, Ian Prado, David Mildebrath (University of Alabama), Jay Strader (Michigan State University), Jifeng Lui (Chinese Academy of Sciences), and Jon Miller (University of Michigan). <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract We examined the usefulness of dried spot blood and saliva samples in SARS-CoV-2 antibody analyses. We analyzed 1231 self-collected dried spot blood and saliva samples from healthcare workers. Participants filled in a questionnaire on their COVID-19 exposures, infections, and vaccinations. Anti-SARS-CoV-2 IgG, IgA, and IgM levels were determined from both samples using the GSP/DELFIA method. The level of exposure was the strongest determinant of all blood antibody classes and saliva IgG, increasing as follows: (1) no exposure (healthy, non-vaccinated), (2) exposed, (3) former COVID-19 infection, (4) one vaccination, (5) two vaccinations, and (6) vaccination and former infection. While the blood IgG assay had a 99.5% sensitivity and 75.3% specificity to distinguish participants with two vaccinations from all other types of exposure, the corresponding percentages for saliva IgG were 85.3% and 65.7%. Both blood and saliva IgG-seropositivity proportions followed similar trends to the exposures reported in the questionnaires. Self-collected dry blood and saliva spot samples combined with the GSP/DELFIA technique comprise a valuable tool to investigate an individual’s immune response to SARS-CoV-2 exposure or vaccination. Saliva IgG has high potential to monitor vaccination response wane, since the sample is non-invasive and easy to collect. Working on a manuscript? Avoid the common mistakes Introduction Serological assays are useful in investigating an individual’s immune status and response to vaccinations as well as in perceiving epidemiological information on the spread of the infection. Especially after the implementation of vaccination programs, serological surveys of large populations are essential in evaluating the level and duration of antibody responses [ 1 ]. Most serological tests are based on the detection of the IgG and IgM antibodies that recognize SARS-CoV-2 nucleoprotein (N), viral spike glycoprotein S1 subunit, or its receptor-binding domain (RBD), but some applications have also been developed to detect IgA antibodies against these antigens [ 2 , 3 , 4 , 5 ]. Most SARS-CoV-2 vaccines are designed to use the viral spike glycoprotein or part of it as the immunogen. Over 90% of subjects start to develop IgG antibodies to SARS-CoV-2 antigens 10–11 days after the onset of symptoms [ 4 , 6 , 7 ]. Serum IgM and IgA levels elevate synchronously to or slightly earlier than IgG, and their seroconversion occurs between days 6 and 15 [ 8 , 9 ]. A stronger exposure and the severity of the COVID-19 infection are associated with higher antibody levels and a longer durability of antibodies [ 9 , 10 ]. Mucosal immunity is crucial in limiting respiratory infections. In the oral cavity, class IgG and IgM antibodies mainly diffuse from blood circulation into gingival crevicular fluid and further into the saliva. IgA antibodies are produced in mucosa, and they are responsible for the early humoral immunity against SARS-CoV-2, neutralizing the virus [ 11 , 12 ]. Serum and saliva anti-SARS-CoV-2 display similar temporal kinetics [ 8 ]. Both serum and saliva IgG antibodies are detected up to 9 months after COVID-19 infection, whereas IgA and IgM antibodies decline more rapidly [ 8 , 13 ]. Significant decrease in serum IgG levels was observed 6 months after second dose of vaccination reflecting the superior long-term humoral response after natural infection compared to vaccine-induced response [ 14 ]. Easily performed collection of samples that do not require a laboratory setting is essential for large-scale population screening. Dried blood spot (DBS) samples have been reported to be a valid alternative to plasma/serum collection for anti-SARS-CoV-2 IgG detection as the antibody levels measured from DBS samples correlate with the levels detected from traditional serum/plasma samples [ 15 , 16 , 17 , 18 ]. Saliva is an easily collectable, non-invasive sample material suitable for anti-SARS-CoV-2 IgG, IgA, and IgM detection [ 8 ]. However, dried saliva spot samples have not been utilized in SARS-CoV-2 diagnostics. The aim of our study was to explore the usefulness of self-collected DBS and dried saliva spot (DSS) samples in the analysis of the immune response against SARS-CoV-2. IgG, IgM, and IgA-class antibodies were detected from the dry spot samples collected from 1200 healthcare professionals to find out if DBS and DSS samples can be used to detect an antibody response caused by either natural infection or vaccines. In particular, we were interested to investigate whether saliva is applicable in the antibody analyses. Materials and methods The study population comprised healthcare and social workers, who were recruited between January and March 2021 in the Uusimaa region of Southern Finland. During the COVID-19 epidemic in Finland 78,565 laboratory confirmed cases (1.4% of population) were registered from January 3, 2020 to March 31, 2021 [ 19 ]. The worst epidemic situation has been in the southern part of Finland, which has the largest population and highest population density in the country. SARS-CoV-2 vaccinations started in Finland at the beginning of 2021, with critical healthcare workers and risk groups. The participants worked either in specialized care at the Helsinki University Hospital (HUS) or in primary and social care for the City of Helsinki (HEL). The inclusion criterion for participation was age of at least 18 years. Consent for participation was given using Suomi.fi e-services with a strong identification . The participants were recruited through work mailing lists and intranet. In the case of HUS, the participants of the present study were restricted only to those who had participated in the previous questionnaire study concerning COVID-19 exposure among HUS personnel ( n = 866), presenting a random sample [ 20 ]. The list of different occupations among the participants is presented in Supplementary Table 1. The study was conducted according to the guidelines of the Declaration of Helsinki and the study design was approved by the local ethical committees of the Helsinki University Hospital and the City of Helsinki (HUS/1450/2020, HUS/157/2020, HUS/182/2021, HEL 2020-007596T 13 02 01). Sampling sets for self-collection of blood and saliva samples were delivered to the participants either at their home address or at their workplace. Each sampling set included a PerkinElmer 226 Sample Collection Card designed for dried blood spot (DBS) collection,", "role": "user" }, { "content": "In a study by the University of Helsinki and HUS Helsinki University Hospital, the levels of antibodies associated with the SARS-CoV-2 virus were analyzed in more than 1,200 employees in the social welfare and health care sector to determine whether there were differences in different antibody classes according to viral exposure. Dried saliva and blood samples collected between January and March 2021 were utilized in the study. The exposure and background data were collected using a questionnaire. Based on the results, immunoglobulin G (IgG) has a 99.5% sensitivity and 75.3% specificity to distinguish people with two vaccinations from non-exposed and exposed individuals, individuals with previous COVID-19 infection, and those with one vaccination. IgG measured from saliva also had an 85.3% sensitivity and 65.7% specificity in distinguishing people with two vaccinations from the other groups. The results of the study have been published in the Medical Microbiology and Immunology journal. Dentists had the lowest amount of antibodies against the virus The study attested to the exposure of social welfare and health care employees to coronavirus, visible in the results as elevated antibody levels. A total of 47.5% of nurses and 47.7% of doctors were seropositive due to either a previous infection, vaccination or exposure, whereas only 8.7% of dentists had been exposed to the virus. In addition to dentists, the lowest antibody levels were observed in administrative staff and social workers. The highest antibody levels in both the blood and saliva were found in those who had both had COVID-19 and had been vaccinated. The lowest antibody levels were seen in individuals who had not been exposed to the virus, who had not had a previous infection and who had not received a vaccination. \"Against our expectations, there have been fewer coronavirus infections and instances of exposure among dental care staff compared to, for example, hospital doctors, even though a lot of aerosol-producing procedures are carried out close to the patient in dental care,\" researcher Laura Lahdentausta says. At the time of sample collection, the dental care staff had also received the lowest number of coronavirus vaccines, which was reflected in their antibody levels. New information on using saliva in antibody studies Another goal of the study was to develop research methods. In fact, the study provides important information on the use of saliva in the determination of antibody levels. \"Based on the results, dried samples reliably reveal antibodies associated with the virus,\" says Professor Pirkko Pussinen. The benefit of dried saliva and fingertip blood samples is that they are easy to collect. Samples can be taken at home outside laboratory conditions. Their collection is inexpensive and, in the case of saliva samples, non-invasive. \"In the future, this assay technique based on dried spot samples could be effectively utilized to monitor both the immune response produced by vaccination and the need for vaccines in large patient populations,\" Pussinen adds. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract We examined the usefulness of dried spot blood and saliva samples in SARS-CoV-2 antibody analyses. We analyzed 1231 self-collected dried spot blood and saliva samples from healthcare workers. Participants filled in a questionnaire on their COVID-19 exposures, infections, and vaccinations. Anti-SARS-CoV-2 IgG, IgA, and IgM levels were determined from both samples using the GSP/DELFIA method. The level of exposure was the strongest determinant of all blood antibody classes and saliva IgG, increasing as follows: (1) no exposure (healthy, non-vaccinated), (2) exposed, (3) former COVID-19 infection, (4) one vaccination, (5) two vaccinations, and (6) vaccination and former infection. While the blood IgG assay had a 99.5% sensitivity and 75.3% specificity to distinguish participants with two vaccinations from all other types of exposure, the corresponding percentages for saliva IgG were 85.3% and 65.7%. Both blood and saliva IgG-seropositivity proportions followed similar trends to the exposures reported in the questionnaires. Self-collected dry blood and saliva spot samples combined with the GSP/DELFIA technique comprise a valuable tool to investigate an individual’s immune response to SARS-CoV-2 exposure or vaccination. Saliva IgG has high potential to monitor vaccination response wane, since the sample is non-invasive and easy to collect. Working on a manuscript? Avoid the common mistakes Introduction Serological assays are useful in investigating an individual’s immune status and response to vaccinations as well as in perceiving epidemiological information on the spread of the infection. Especially after the implementation of vaccination programs, serological surveys of large populations are essential in evaluating the level and duration of antibody responses [ 1 ]. Most serological tests are based on the detection of the IgG and IgM antibodies that recognize SARS-CoV-2 nucleoprotein (N), viral spike glycoprotein S1 subunit, or its receptor-binding domain (RBD), but some applications have also been developed to detect IgA antibodies against these antigens [ 2 , 3 , 4 , 5 ]. Most SARS-CoV-2 vaccines are designed to use the viral spike glycoprotein or part of it as the immunogen. Over 90% of subjects start to develop IgG antibodies to SARS-CoV-2 antigens 10–11 days after the onset of symptoms [ 4 , 6 , 7 ]. Serum IgM and IgA levels elevate synchronously to or slightly earlier than IgG, and their seroconversion occurs between days 6 and 15 [ 8 , 9 ]. A stronger exposure and the severity of the COVID-19 infection are associated with higher antibody levels and a longer durability of antibodies [ 9 , 10 ]. Mucosal immunity is crucial in limiting respiratory infections. In the oral cavity, class IgG and IgM antibodies mainly diffuse from blood circulation into gingival crevicular fluid and further into the saliva. IgA antibodies are produced in mucosa, and they are responsible for the early humoral immunity against SARS-CoV-2, neutralizing the virus [ 11 , 12 ]. Serum and saliva anti-SARS-CoV-2 display similar temporal kinetics [ 8 ]. Both serum and saliva IgG antibodies are detected up to 9 months after COVID-19 infection, whereas IgA and IgM antibodies decline more rapidly [ 8 , 13 ]. Significant decrease in serum IgG levels was observed 6 months after second dose of vaccination reflecting the superior long-term humoral response after natural infection compared to vaccine-induced response [ 14 ]. Easily performed collection of samples that do not require a laboratory setting is essential for large-scale population screening. Dried blood spot (DBS) samples have been reported to be a valid alternative to plasma/serum collection for anti-SARS-CoV-2 IgG detection as the antibody levels measured from DBS samples correlate with the levels detected from traditional serum/plasma samples [ 15 , 16 , 17 , 18 ]. Saliva is an easily collectable, non-invasive sample material suitable for anti-SARS-CoV-2 IgG, IgA, and IgM detection [ 8 ]. However, dried saliva spot samples have not been utilized in SARS-CoV-2 diagnostics. The aim of our study was to explore the usefulness of self-collected DBS and dried saliva spot (DSS) samples in the analysis of the immune response against SARS-CoV-2. IgG, IgM, and IgA-class antibodies were detected from the dry spot samples collected from 1200 healthcare professionals to find out if DBS and DSS samples can be used to detect an antibody response caused by either natural infection or vaccines. In particular, we were interested to investigate whether saliva is applicable in the antibody analyses. Materials and methods The study population comprised healthcare and social workers, who were recruited between January and March 2021 in the Uusimaa region of Southern Finland. During the COVID-19 epidemic in Finland 78,565 laboratory confirmed cases (1.4% of population) were registered from January 3, 2020 to March 31, 2021 [ 19 ]. The worst epidemic situation has been in the southern part of Finland, which has the largest population and highest population density in the country. SARS-CoV-2 vaccinations started in Finland at the beginning of 2021, with critical healthcare workers and risk groups. The participants worked either in specialized care at the Helsinki University Hospital (HUS) or in primary and social care for the City of Helsinki (HEL). The inclusion criterion for participation was age of at least 18 years. Consent for participation was given using Suomi.fi e-services with a strong identification . The participants were recruited through work mailing lists and intranet. In the case of HUS, the participants of the present study were restricted only to those who had participated in the previous questionnaire study concerning COVID-19 exposure among HUS personnel ( n = 866), presenting a random sample [ 20 ]. The list of different occupations among the participants is presented in Supplementary Table 1. The study was conducted according to the guidelines of the Declaration of Helsinki and the study design was approved by the local ethical committees of the Helsinki University Hospital and the City of Helsinki (HUS/1450/2020, HUS/157/2020, HUS/182/2021, HEL 2020-007596T 13 02 01). Sampling sets for self-collection of blood and saliva samples were delivered to the participants either at their home address or at their workplace. Each sampling set included a PerkinElmer 226 Sample Collection Card designed for dried blood spot (DBS) collection,<|im_end|> <|im_start|>assistant In a study by the University of Helsinki and HUS Helsinki University Hospital, the levels of antibodies associated with the SARS-CoV-2 virus were analyzed in more than 1,200 employees in the social welfare and health care sector to determine whether there were differences in different antibody classes according to viral exposure. Dried saliva and blood samples collected between January and March 2021 were utilized in the study. The exposure and background data were collected using a questionnaire. Based on the results, immunoglobulin G (IgG) has a 99.5% sensitivity and 75.3% specificity to distinguish people with two vaccinations from non-exposed and exposed individuals, individuals with previous COVID-19 infection, and those with one vaccination. IgG measured from saliva also had an 85.3% sensitivity and 65.7% specificity in distinguishing people with two vaccinations from the other groups. The results of the study have been published in the Medical Microbiology and Immunology journal. Dentists had the lowest amount of antibodies against the virus The study attested to the exposure of social welfare and health care employees to coronavirus, visible in the results as elevated antibody levels. A total of 47.5% of nurses and 47.7% of doctors were seropositive due to either a previous infection, vaccination or exposure, whereas only 8.7% of dentists had been exposed to the virus. In addition to dentists, the lowest antibody levels were observed in administrative staff and social workers. The highest antibody levels in both the blood and saliva were found in those who had both had COVID-19 and had been vaccinated. The lowest antibody levels were seen in individuals who had not been exposed to the virus, who had not had a previous infection and who had not received a vaccination. "Against our expectations, there have been fewer coronavirus infections and instances of exposure among dental care staff compared to, for example, hospital doctors, even though a lot of aerosol-producing procedures are carried out close to the patient in dental care," researcher Laura Lahdentausta says. At the time of sample collection, the dental care staff had also received the lowest number of coronavirus vaccines, which was reflected in their antibody levels. New information on using saliva in antibody studies Another goal of the study was to develop research methods. In fact, the study provides important information on the use of saliva in the determination of antibody levels. "Based on the results, dried samples reliably reveal antibodies associated with the virus," says Professor Pirkko Pussinen. The benefit of dried saliva and fingertip blood samples is that they are easy to collect. Samples can be taken at home outside laboratory conditions. Their collection is inexpensive and, in the case of saliva samples, non-invasive. "In the future, this assay technique based on dried spot samples could be effectively utilized to monitor both the immune response produced by vaccination and the need for vaccines in large patient populations," Pussinen adds. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract The common bed bug ( Cimex lectularius ) has been a persistent pest of humans for thousands of years, yet the genetic basis of the bed bug’s basic biology and adaptation to dense human environments is largely unknown. Here we report the assembly, annotation and phylogenetic mapping of the 697.9-Mb Cimex lectularius genome, with an N50 of 971 kb, using both long and short read technologies. A RNA-seq time course across all five developmental stages and male and female adults generated 36,985 coding and noncoding gene models. The most pronounced change in gene expression during the life cycle occurs after feeding on human blood and included genes from the Wolbachia endosymbiont, which shows a simultaneous and coordinated host/commensal response to haematophagous activity. These data provide a rich genetic resource for mapping activity and density of C. lectularius across human hosts and cities, which can help track, manage and control bed bug infestations. Introduction The common bed bug, Cimex lectularius , has been associated with humans for thousands of years 1 . There are over 90 described species classified in the family Cimicidae (Order Hemiptera) 2 , 3 , of which three cimicid species are known to be intimate associates of humans: the common bed bug of the temperate regions ( C. lectularius Linnaeus, 1758), the tropical bed bug ( C. hemipterus Fabricius, 1803) and the West African species that feeds on humans and bats ( Leptocimex boueti Brumpt, 1910) 4 . The temperate species analysed in this study, C. lectularius , is the most predominant cimicid in densely inhabited human environments such as indoor dwellings and cities. Several theories exist with respect to how these species made the transition to humans as their primary host 5 . A leading hypothesis posits that the transition occurred when humans lived in caves, where they were exposed to bugs that fed on bats and on other cave-dwelling mammals 1 , 6 . On the establishment of human settlements and dwellings outside caves, human-adapted cimicids accompanied their new host. Given the time that elapsed since this transition, present-day bed bug populations feeding on humans and bats have undergone genetic differentiation in sympatry 7 . Early hunter–gatherer and herder populations migrated over long distances; however, as small towns and villages (and later cities) became established, bed bug infestations grew 8 . Commerce and human travel then contributed to expanded distributions of bed bugs throughout Europe, Asia and the Americas. European bed bug infestations were recorded in Germany and France by the eleventh and thirteenth centuries, respectively 9 . Bed bugs were also reported in England in 1583 carboxylesterase (CE); however, infestations were uncommon until the seventeenth and eighteenth centuries 1 , 10 . The emergence of heated homes and air travel since the late 1900s has accelerated bed bug infestations in cities globally 11 , as bed bugs could then thrive throughout the year in indoor environments with constant access to blood meals as well as migrate opportunistically and rapidly. Finally, public and commercial locales have been reported to be potentially infested 12 , 13 , as bed bugs are easily transported between their homes and these places by unsuspecting citizens 1 , 5 . A lull in bed bug infestations began with the introduction of insecticides in the mid-1900s (refs 9 , 14 ); however, a resurgence since the late 1990s and the evolution of insecticide resistance have prompted research to understand the basis of this resistance 15 , 16 , 17 . There is a limited molecular understanding of the biology of the bed bug before, during and after feeding on human blood 18 , which is essential to their life cycle since bed bugs are temporary ectoparasites, whereby they access their hosts for blood feeding and then seek the refuge of the indoor environment for digestion, waste production and mating 9 . To address these questions, we produced the first genome sequence draft of the bed bug, an RNA-sequencing (RNA-seq) functional annotation profile of gene expression across all life stages, and then a full gene annotation and phylogenetic analysis of this important urban pest. In combination with a parallel effort on environmental metagenomics of the highly urbanized and populated landscape of New York City (NYC), we also show that such a draft genome sequence can be used to map and characterize citywide phylogeographic relationships of bed bugs as they interact with their human hosts. Results Sample collection To build the genome and transcriptome profiles, we extracted DNA and RNA from the standard laboratory Har-73 insecticide-susceptible strain of C. lectularius . The bed bug has typical developmental stages of an insect that exhibits hemimetabolous metamorphosis ( Fig. 1 ). Each of the immature stages are nymphal, and there is no pupal stage between the final immature stage and the adult. Blood feeding begins in the first instar nymph stage after hatching from the egg and continues through the next four nymphal instars, followed by the adult male and female. We collected RNA from animals at each of these stages and then sequenced RNA from each collection at each time point in triplicate ( Supplementary Table 1 ). Notably, we collected RNA from unfed bed bugs and recently fed bed bugs to examine the functional genomic profile of the bed bug in relation to blood meals. To avoid human or haemophilic bacterial contamination of the DNA used in genome sequencing and assembly, we used first instar nymphs that recently hatched but had not taken any blood meals. Figure 1: The bed bug life cycle and developmental gene expression profile. The seven stages of the life cycle for C. lectularius are shown, starting from an egg and proceeding through five nymphal instar stages, with final differentiation into adult male and female. We used the annotation and RNA-seq data (five individuals per time point in triplicate) to calculate the number of DEGs between all developmental stages and sexes. The DEGs from both adult male and female comprise the arrow from eggs to first instar. The", "role": "user" }, { "content": "Scientists have assembled the first complete genome of one of humanity's oldest and least-loved companions: the bedbug. The new work, led by researchers at the American Museum of Natural History and Weill Cornell Medicine, and published Feb. 2 in Nature Communications, could help combat pesticide resistance in the unwelcome parasite. The data also provides a rich genetic resource for mapping bedbug activity in human hosts and in cities, including subways. \"Bedbugs are one of New York City's most iconic living fossils, along with cockroaches, meaning that their outward appearance has hardly changed throughout their long lineage,\" said corresponding author George Amato, director of the museum's Sackler Institute for Comparative Genomics. \"But despite their static look, we know that they continue to evolve, mostly in ways that make it harder for humans to dissociate with them. This work gives us the genetic basis to explore the bedbug's basic biology and its adaptation to dense human environments.\" The common bedbug (Cimex lectularius) has been coupled with humans for thousands of years. This species is found in temperate regions and prefers to feed on human blood. In recent decades, the prevalence of heated homes and global air travel has accelerated infestations in urban areas, where bedbugs have constant access to blood meals and opportunities to migrate to new hosts. A resurgence in bedbug infestations since the late 1990s is largely associated with the evolution of the insects' resistance to known pesticides, many of which are not suitable for indoor application. \"Bedbugs all but vanished from human lives in the 1940s because of the widespread use of DDT, but unfortunately, overuse contributed to resistance issues quite soon after that in bedbugs and other insect pests,\" said Louis Sorkin, an author on the paper and a senior scientific assistant in the museum's Division of Invertebrate Zoology. \"Today, a very high percentage of bedbugs have genetic mutations that make them resistant to the insecticides that were commonly used to battle these urban pests. This makes the control of bedbugs extremely labor-intensive.\" The researchers extracted DNA and RNA from preserved and living collections, including samples from a population that was first collected in 1973 and has been maintained by museum staff members since then. RNA was sampled from males and females representing each of the bug's six life stages, before and after blood meals, to paint a full picture of the bedbug genome. \"It's not enough to just sequence a genome, because by itself it does not tell the full story,\" said corresponding author Mark Siddall, a curator in the museum's Division of Invertebrate Zoology and Sackler Institute for Comparative Genomics. \"In addition to the DNA, you want to get the RNA, or the expressed genes, and you want that not just from a single bedbug, but from both males and females at each part of the life cycle. Then you can really start asking questions about how certain genes relate to blood-feeding, insecticide resistance and other vital functions.\" The researchers found that the number of genes was fairly consistent throughout the bedbug life cycle, but they observed notable changes in gene expression, especially after the first blood meal. Some genes, expressed only after the bedbug first drinks blood, are linked to insecticide resistance, including mechanisms that result in better detoxification and thicker chitin, or skin. This suggests that bedbugs are likely most vulnerable during the first nymph stage, potentially making it a good target for future insecticides. The scientists also identified three types of anticoagulant genes and their related proteins – characteristics consistent with a highly specialized blood feeder. When compared with 20 other arthropod genomes, the genome of the common bedbug shows close relationships to the kissing bug (Rhodnius prolixus), one of several vectors for Chagas disease, and the body louse (Pediculus humanus), which both have tight associations with humans. The bedbug microbiome also contains more than 1,500 genes that map to more than 400 different species of bacteria, indicating that bedbugs harbor a rich suite of endosymbionts that are likely essential for their growth and reproduction. This indicates that antibiotics that attack bacteria beneficial to bed bugs (but that are non-essential to humans) could complement control of the insects via pesticides. In addition, the study incorporated DNA data collected concurrently from more than 1,400 locations across New York City, including every subway station, to look at microbial diversity. For this work, the researchers used the new genomic data to focus exclusively on the diversity of bedbugs. They found differences in the genetic makeup of bedbugs that reside in different parts of the city, as measured by traces of DNA on east-west versus north-south subway lines, as well as between borough locations and among surfaces (e.g., benches vs. turnstiles). The findings suggest that areas of the city in close proximity to each other have bedbug populations that are related, and that bedbugs from one borough can be distinct from those in another borough. This kind of information can be used to map the pathways of migration of bedbug infestations in established and new urban environments. \"A great feature of metagenomics and microbiome data is its power to reveal new biology, since you can map previously unknown sequences to a new genome as soon as it is finished,\" said Christopher Mason, an associate professor of computational genomics in the Department of Physiology and Biophysics and the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicine at Weill Cornell Medicine and a senior author. \"With every genome that is sequenced and annotated, the genetic understanding of the world around us becomes more in focus.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract The common bed bug ( Cimex lectularius ) has been a persistent pest of humans for thousands of years, yet the genetic basis of the bed bug’s basic biology and adaptation to dense human environments is largely unknown. Here we report the assembly, annotation and phylogenetic mapping of the 697.9-Mb Cimex lectularius genome, with an N50 of 971 kb, using both long and short read technologies. A RNA-seq time course across all five developmental stages and male and female adults generated 36,985 coding and noncoding gene models. The most pronounced change in gene expression during the life cycle occurs after feeding on human blood and included genes from the Wolbachia endosymbiont, which shows a simultaneous and coordinated host/commensal response to haematophagous activity. These data provide a rich genetic resource for mapping activity and density of C. lectularius across human hosts and cities, which can help track, manage and control bed bug infestations. Introduction The common bed bug, Cimex lectularius , has been associated with humans for thousands of years 1 . There are over 90 described species classified in the family Cimicidae (Order Hemiptera) 2 , 3 , of which three cimicid species are known to be intimate associates of humans: the common bed bug of the temperate regions ( C. lectularius Linnaeus, 1758), the tropical bed bug ( C. hemipterus Fabricius, 1803) and the West African species that feeds on humans and bats ( Leptocimex boueti Brumpt, 1910) 4 . The temperate species analysed in this study, C. lectularius , is the most predominant cimicid in densely inhabited human environments such as indoor dwellings and cities. Several theories exist with respect to how these species made the transition to humans as their primary host 5 . A leading hypothesis posits that the transition occurred when humans lived in caves, where they were exposed to bugs that fed on bats and on other cave-dwelling mammals 1 , 6 . On the establishment of human settlements and dwellings outside caves, human-adapted cimicids accompanied their new host. Given the time that elapsed since this transition, present-day bed bug populations feeding on humans and bats have undergone genetic differentiation in sympatry 7 . Early hunter–gatherer and herder populations migrated over long distances; however, as small towns and villages (and later cities) became established, bed bug infestations grew 8 . Commerce and human travel then contributed to expanded distributions of bed bugs throughout Europe, Asia and the Americas. European bed bug infestations were recorded in Germany and France by the eleventh and thirteenth centuries, respectively 9 . Bed bugs were also reported in England in 1583 carboxylesterase (CE); however, infestations were uncommon until the seventeenth and eighteenth centuries 1 , 10 . The emergence of heated homes and air travel since the late 1900s has accelerated bed bug infestations in cities globally 11 , as bed bugs could then thrive throughout the year in indoor environments with constant access to blood meals as well as migrate opportunistically and rapidly. Finally, public and commercial locales have been reported to be potentially infested 12 , 13 , as bed bugs are easily transported between their homes and these places by unsuspecting citizens 1 , 5 . A lull in bed bug infestations began with the introduction of insecticides in the mid-1900s (refs 9 , 14 ); however, a resurgence since the late 1990s and the evolution of insecticide resistance have prompted research to understand the basis of this resistance 15 , 16 , 17 . There is a limited molecular understanding of the biology of the bed bug before, during and after feeding on human blood 18 , which is essential to their life cycle since bed bugs are temporary ectoparasites, whereby they access their hosts for blood feeding and then seek the refuge of the indoor environment for digestion, waste production and mating 9 . To address these questions, we produced the first genome sequence draft of the bed bug, an RNA-sequencing (RNA-seq) functional annotation profile of gene expression across all life stages, and then a full gene annotation and phylogenetic analysis of this important urban pest. In combination with a parallel effort on environmental metagenomics of the highly urbanized and populated landscape of New York City (NYC), we also show that such a draft genome sequence can be used to map and characterize citywide phylogeographic relationships of bed bugs as they interact with their human hosts. Results Sample collection To build the genome and transcriptome profiles, we extracted DNA and RNA from the standard laboratory Har-73 insecticide-susceptible strain of C. lectularius . The bed bug has typical developmental stages of an insect that exhibits hemimetabolous metamorphosis ( Fig. 1 ). Each of the immature stages are nymphal, and there is no pupal stage between the final immature stage and the adult. Blood feeding begins in the first instar nymph stage after hatching from the egg and continues through the next four nymphal instars, followed by the adult male and female. We collected RNA from animals at each of these stages and then sequenced RNA from each collection at each time point in triplicate ( Supplementary Table 1 ). Notably, we collected RNA from unfed bed bugs and recently fed bed bugs to examine the functional genomic profile of the bed bug in relation to blood meals. To avoid human or haemophilic bacterial contamination of the DNA used in genome sequencing and assembly, we used first instar nymphs that recently hatched but had not taken any blood meals. Figure 1: The bed bug life cycle and developmental gene expression profile. The seven stages of the life cycle for C. lectularius are shown, starting from an egg and proceeding through five nymphal instar stages, with final differentiation into adult male and female. We used the annotation and RNA-seq data (five individuals per time point in triplicate) to calculate the number of DEGs between all developmental stages and sexes. The DEGs from both adult male and female comprise the arrow from eggs to first instar. The<|im_end|> <|im_start|>assistant Scientists have assembled the first complete genome of one of humanity's oldest and least-loved companions: the bedbug. The new work, led by researchers at the American Museum of Natural History and Weill Cornell Medicine, and published Feb. 2 in Nature Communications, could help combat pesticide resistance in the unwelcome parasite. The data also provides a rich genetic resource for mapping bedbug activity in human hosts and in cities, including subways. "Bedbugs are one of New York City's most iconic living fossils, along with cockroaches, meaning that their outward appearance has hardly changed throughout their long lineage," said corresponding author George Amato, director of the museum's Sackler Institute for Comparative Genomics. "But despite their static look, we know that they continue to evolve, mostly in ways that make it harder for humans to dissociate with them. This work gives us the genetic basis to explore the bedbug's basic biology and its adaptation to dense human environments." The common bedbug (Cimex lectularius) has been coupled with humans for thousands of years. This species is found in temperate regions and prefers to feed on human blood. In recent decades, the prevalence of heated homes and global air travel has accelerated infestations in urban areas, where bedbugs have constant access to blood meals and opportunities to migrate to new hosts. A resurgence in bedbug infestations since the late 1990s is largely associated with the evolution of the insects' resistance to known pesticides, many of which are not suitable for indoor application. "Bedbugs all but vanished from human lives in the 1940s because of the widespread use of DDT, but unfortunately, overuse contributed to resistance issues quite soon after that in bedbugs and other insect pests," said Louis Sorkin, an author on the paper and a senior scientific assistant in the museum's Division of Invertebrate Zoology. "Today, a very high percentage of bedbugs have genetic mutations that make them resistant to the insecticides that were commonly used to battle these urban pests. This makes the control of bedbugs extremely labor-intensive." The researchers extracted DNA and RNA from preserved and living collections, including samples from a population that was first collected in 1973 and has been maintained by museum staff members since then. RNA was sampled from males and females representing each of the bug's six life stages, before and after blood meals, to paint a full picture of the bedbug genome. "It's not enough to just sequence a genome, because by itself it does not tell the full story," said corresponding author Mark Siddall, a curator in the museum's Division of Invertebrate Zoology and Sackler Institute for Comparative Genomics. "In addition to the DNA, you want to get the RNA, or the expressed genes, and you want that not just from a single bedbug, but from both males and females at each part of the life cycle. Then you can really start asking questions about how certain genes relate to blood-feeding, insecticide resistance and other vital functions." The researchers found that the number of genes was fairly consistent throughout the bedbug life cycle, but they observed notable changes in gene expression, especially after the first blood meal. Some genes, expressed only after the bedbug first drinks blood, are linked to insecticide resistance, including mechanisms that result in better detoxification and thicker chitin, or skin. This suggests that bedbugs are likely most vulnerable during the first nymph stage, potentially making it a good target for future insecticides. The scientists also identified three types of anticoagulant genes and their related proteins – characteristics consistent with a highly specialized blood feeder. When compared with 20 other arthropod genomes, the genome of the common bedbug shows close relationships to the kissing bug (Rhodnius prolixus), one of several vectors for Chagas disease, and the body louse (Pediculus humanus), which both have tight associations with humans. The bedbug microbiome also contains more than 1,500 genes that map to more than 400 different species of bacteria, indicating that bedbugs harbor a rich suite of endosymbionts that are likely essential for their growth and reproduction. This indicates that antibiotics that attack bacteria beneficial to bed bugs (but that are non-essential to humans) could complement control of the insects via pesticides. In addition, the study incorporated DNA data collected concurrently from more than 1,400 locations across New York City, including every subway station, to look at microbial diversity. For this work, the researchers used the new genomic data to focus exclusively on the diversity of bedbugs. They found differences in the genetic makeup of bedbugs that reside in different parts of the city, as measured by traces of DNA on east-west versus north-south subway lines, as well as between borough locations and among surfaces (e.g., benches vs. turnstiles). The findings suggest that areas of the city in close proximity to each other have bedbug populations that are related, and that bedbugs from one borough can be distinct from those in another borough. This kind of information can be used to map the pathways of migration of bedbug infestations in established and new urban environments. "A great feature of metagenomics and microbiome data is its power to reveal new biology, since you can map previously unknown sequences to a new genome as soon as it is finished," said Christopher Mason, an associate professor of computational genomics in the Department of Physiology and Biophysics and the HRH Prince Alwaleed Bin Talal Bin Abdulaziz Al-Saud Institute for Computational Biomedicine at Weill Cornell Medicine and a senior author. "With every genome that is sequenced and annotated, the genetic understanding of the world around us becomes more in focus." <|im_end|>

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2,521

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Twisted van der Waals heterostructures have latterly received prominent attention for their many remarkable experimental properties and the promise that they hold for realizing elusive states of matter in the laboratory. We propose that these systems can, in fact, be used as a robust quantum simulation platform that enables the study of strongly correlated physics and topology in quantum materials. Among the features that make these materials a versatile toolbox are the tunability of their properties through readily accessible external parameters such as gating, straining, packing and twist angle; the feasibility to realize and control a large number of fundamental many-body quantum models relevant in the field of condensed-matter physics; and finally, the availability of experimental readout protocols that directly map their rich phase diagrams in and out of equilibrium. This general framework makes it possible to robustly realize and functionalize new phases of matter in a modular fashion, thus broadening the landscape of accessible physics and holding promise for future technological applications. Main The inseparability of groups of particles into products of their individual states underpins the most counterintuitive predictions of quantum mechanics. In condensed-matter physics, recent focus has been placed on finding and understanding quantum materials — systems in which a delicate balance between the crystal lattice and strong electronic interactions lead to new inseparable, collective behaviours with exotic properties. Encompassing rich phenomenologies ranging from superconductivity at high temperatures to topologically ordered states of matter with fractionalized excitations, numerous materials have recently come under intense scrutiny for the realization of quantum phases on demand 1 . A major impediment to the systematic study of correlated electron physics is the comparative lack of tunability of conventional chemical compounds. The main means of control are pressure, strain and doping. This limited range of control knobs severely limits experimental exploration of the wider phase diagram, essential to guide the discovery of novel quantum phases and to controlled studies of quantum criticality, unconventional phase transitions, or realizations of exotic topological states of matter that are both of fundamental interest and could have applications in emerging quantum technologies such as quantum computing and simulation. Another impediment lies in the difficulty of solving these paradigmatic quantum Hamiltonians via present computational approaches. As an alternative, in the early 80s, Feynman proposed quantum simulation as a paradigm to turn the problem upside down 2 : implementing clean models using real physical systems, to ‘simulate’ the ground state, thermodynamic behaviour or non-equilibrium dynamics of such models. If the implementation is well controlled, the results can be used to disentangle the more complex material’s phenomena for which the original model was set up, as well as to guide the way towards stabilizing and controlling new and exotic phases of matter in real quantum materials. Much progress has been achieved via studying ultracold gases of bosonic and fermionic atoms, which can be confined in optical lattices to realize lattice models of condensed-matter physics in a controlled manner 3 . While these systems are highly controllable and can faithfully realize certain quantum Hamiltonians, it remains an experimental challenge to engineer Hamiltonians with tunable long-range interactions and especially to access low-temperature emergent long-range ordered phases, such as the intriguing d -wave state of the t – t ′ repulsive Hubbard model 4 . This Review identifies moiré heterostructures of van der Waals materials as an alternative and complementary condensed-matter approach to realize a large set of highly controllable quantum Hamiltonians. While such systems do not typically afford the high level of isolation and precise tunability that cold atomic systems do, the large degree of tunability control available through readily accessible experimental knobs allows for the exploration of phase diagrams of vast and novel sets of many-body Hamiltonians in and out of equilibrium and at very low temperatures. In particular, we review how different choices of two-dimensional (2D) heterostructure compositions at different twist angles realize a wide range of effective low-energy electronic tight-binding Hamiltonians with various geometries, dimensionality, frustration, spin–orbit coupling as well as interactions beyond the Hubbard limit, including partially screened and unscreened Coulomb interactions. This allows for flexible interaction engineering as well as control of band structure and topology. Realizing model quantum Hamiltonians in van der Waals heterostructures Moiré heterostructures of van der Waals materials exploit quantum interference to quench the effective kinetic energy scales, which permits both driving the system at low energies to an interaction-dominated regime, and drastically enhancing anisotropies or reducing symmetries of the monolayer. Conceptually, the physical mechanism can be understood straightforwardly in analogy to classical moiré interference patterns (Fig. 1 , centre): if two identical patterns with a discrete translation symmetry in two dimensions are superimposed at an angle, the combined motif retains a periodicity at much longer wavelengths for an infinite set of small rational angles. Fig. 1: Moiré quantum simulator. Stacking sheets of van der Waals heterostructures with a twist gives rise to a plethora of effective low-energy Hamiltonians. Some of these realizations that were studied in the literature are given in the inner circle of the figure with the corresponding lattice, band structure and potential phases of matter that can be realized. For the red band structure, the dashed lines indicate the flat bands additionally present in the case of twisted bilayer MoS 2 compared with TBG. In the outer circle, we outline a perspective on possible future directions of moiré quantum simulators with many intriguing developments to be expected. k , k x , k y and k z denote momentum and momentum in the x , y and z directions, respectively. E and E k refer to band energy. Full size image Similarly, a heterostructure of two or more monolayers with commensurate lattice constants stacked at a twist retains spatial periodicity for small commensurate angles, albeit with a much larger moiré unit cell. This moiré superlattice can span many unit cells and defines a new crystal structure with a mini Brillouin zone. Within this moiré Brillouin zone, the folded bands lead to a multitude of crossings, which are subsequently", "role": "user" }, { "content": "Researchers from the MPSD, the RWTH Aachen University and the Flatiron Institute, Columbia University (both in the U.S.) and part of the Max Planck—New York City Center for Non-equilibrium Quantum Phenomena have provided a fresh perspective on the potential of twisted van der Waals materials for realizing novel and elusive states of matter and providing a unique materials-based quantum simulation platform. The team has laid out an exciting road map for the vibrant field of twisted van der Waals materials, reviewing the rapid progress made recently and adding their unique vision of intriguing avenues of future research to be completed. In their work, now published in Nature Physics, the team demonstrates that the future of twisted van der Waals materials is bright—both in terms of fundamental science as well as their potential applications in materials science and quantum information technologies. Twisted van der Waals materials consist of stacked layers of two-dimensional systems at a relative rotation angle. They are shown to provide a versatile toolbox to realize many highly sought-after quantum model systems, which exhibit exotic and—so far—elusive phases of mater of potential relevance to material science and quantum technologies. Hence those twisted van der Waals materials define a materials-based quantum simulator. This is particularly exciting as twisted van der Waals materials offer tantalizing opportunities to provide clean systems which are extremely well controlled by the twist angle, stacking sequence, substrate or gating techniques. However, this article demonstrates that the potential of twisted van der Waals materials even multiplies when brought together with other blossoming fields of condensed matter and quantum technology research. The potential for extensions is vast, with even more rich physics to be uncovered by, for example, by investigating the interaction of non-equilibrium states or cavities with the already promising van der Waals materials \"One of the strengths of these novel materials is that they provide an unprecedented level of tunability,\" says lead author Dante Kennes. \"This allows us to effectively realize many of the different lattice quantum models, which have taken center stage in the last few decades in the field of condensed matter research.\" Thus, exotic phases of matter, such as the elusive spin-liquid phase or systems with topological properties favorable to quantum technologies might be on the horizon. \"We are really at the beginning of an intriguing journey to explore the vast amount of chemical and physical combinations in the field,\" co-author Lede Xian reports about his recent work. \" Many more exciting discoveries, some of which we outline in our work, will follow,\" adds fellow author Martin Claassen. Twisted van der Waals materials offer a wonderful and formidable experimental challenge due to their complexity. They also open up completely new routes of manipulating and controlling quantum materials, according to Ángel Rubio, the director of the MPSD's Theory Department: \"These materials let us unravel new phases of matter and promise a wide range of exciting applications in quantum technologies. We have just touched the surface of those possibilities in this perspective article and we can expect many more surprises in this exciting research journey.\" As this work illustrates, the ratio between questions answered and interesting questions to be addressed in the future makes this a particularly promising and vibrant research field, adds Ángel Rubio: \"This plethora of exciting new phenomena can be enlarged further when considering driving those systems out of equilibrium or embedding them in optical cavities. Many interesting phenomena are waiting to be unraveled ahead of us!\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Twisted van der Waals heterostructures have latterly received prominent attention for their many remarkable experimental properties and the promise that they hold for realizing elusive states of matter in the laboratory. We propose that these systems can, in fact, be used as a robust quantum simulation platform that enables the study of strongly correlated physics and topology in quantum materials. Among the features that make these materials a versatile toolbox are the tunability of their properties through readily accessible external parameters such as gating, straining, packing and twist angle; the feasibility to realize and control a large number of fundamental many-body quantum models relevant in the field of condensed-matter physics; and finally, the availability of experimental readout protocols that directly map their rich phase diagrams in and out of equilibrium. This general framework makes it possible to robustly realize and functionalize new phases of matter in a modular fashion, thus broadening the landscape of accessible physics and holding promise for future technological applications. Main The inseparability of groups of particles into products of their individual states underpins the most counterintuitive predictions of quantum mechanics. In condensed-matter physics, recent focus has been placed on finding and understanding quantum materials — systems in which a delicate balance between the crystal lattice and strong electronic interactions lead to new inseparable, collective behaviours with exotic properties. Encompassing rich phenomenologies ranging from superconductivity at high temperatures to topologically ordered states of matter with fractionalized excitations, numerous materials have recently come under intense scrutiny for the realization of quantum phases on demand 1 . A major impediment to the systematic study of correlated electron physics is the comparative lack of tunability of conventional chemical compounds. The main means of control are pressure, strain and doping. This limited range of control knobs severely limits experimental exploration of the wider phase diagram, essential to guide the discovery of novel quantum phases and to controlled studies of quantum criticality, unconventional phase transitions, or realizations of exotic topological states of matter that are both of fundamental interest and could have applications in emerging quantum technologies such as quantum computing and simulation. Another impediment lies in the difficulty of solving these paradigmatic quantum Hamiltonians via present computational approaches. As an alternative, in the early 80s, Feynman proposed quantum simulation as a paradigm to turn the problem upside down 2 : implementing clean models using real physical systems, to ‘simulate’ the ground state, thermodynamic behaviour or non-equilibrium dynamics of such models. If the implementation is well controlled, the results can be used to disentangle the more complex material’s phenomena for which the original model was set up, as well as to guide the way towards stabilizing and controlling new and exotic phases of matter in real quantum materials. Much progress has been achieved via studying ultracold gases of bosonic and fermionic atoms, which can be confined in optical lattices to realize lattice models of condensed-matter physics in a controlled manner 3 . While these systems are highly controllable and can faithfully realize certain quantum Hamiltonians, it remains an experimental challenge to engineer Hamiltonians with tunable long-range interactions and especially to access low-temperature emergent long-range ordered phases, such as the intriguing d -wave state of the t – t ′ repulsive Hubbard model 4 . This Review identifies moiré heterostructures of van der Waals materials as an alternative and complementary condensed-matter approach to realize a large set of highly controllable quantum Hamiltonians. While such systems do not typically afford the high level of isolation and precise tunability that cold atomic systems do, the large degree of tunability control available through readily accessible experimental knobs allows for the exploration of phase diagrams of vast and novel sets of many-body Hamiltonians in and out of equilibrium and at very low temperatures. In particular, we review how different choices of two-dimensional (2D) heterostructure compositions at different twist angles realize a wide range of effective low-energy electronic tight-binding Hamiltonians with various geometries, dimensionality, frustration, spin–orbit coupling as well as interactions beyond the Hubbard limit, including partially screened and unscreened Coulomb interactions. This allows for flexible interaction engineering as well as control of band structure and topology. Realizing model quantum Hamiltonians in van der Waals heterostructures Moiré heterostructures of van der Waals materials exploit quantum interference to quench the effective kinetic energy scales, which permits both driving the system at low energies to an interaction-dominated regime, and drastically enhancing anisotropies or reducing symmetries of the monolayer. Conceptually, the physical mechanism can be understood straightforwardly in analogy to classical moiré interference patterns (Fig. 1 , centre): if two identical patterns with a discrete translation symmetry in two dimensions are superimposed at an angle, the combined motif retains a periodicity at much longer wavelengths for an infinite set of small rational angles. Fig. 1: Moiré quantum simulator. Stacking sheets of van der Waals heterostructures with a twist gives rise to a plethora of effective low-energy Hamiltonians. Some of these realizations that were studied in the literature are given in the inner circle of the figure with the corresponding lattice, band structure and potential phases of matter that can be realized. For the red band structure, the dashed lines indicate the flat bands additionally present in the case of twisted bilayer MoS 2 compared with TBG. In the outer circle, we outline a perspective on possible future directions of moiré quantum simulators with many intriguing developments to be expected. k , k x , k y and k z denote momentum and momentum in the x , y and z directions, respectively. E and E k refer to band energy. Full size image Similarly, a heterostructure of two or more monolayers with commensurate lattice constants stacked at a twist retains spatial periodicity for small commensurate angles, albeit with a much larger moiré unit cell. This moiré superlattice can span many unit cells and defines a new crystal structure with a mini Brillouin zone. Within this moiré Brillouin zone, the folded bands lead to a multitude of crossings, which are subsequently<|im_end|> <|im_start|>assistant Researchers from the MPSD, the RWTH Aachen University and the Flatiron Institute, Columbia University (both in the U.S.) and part of the Max Planck—New York City Center for Non-equilibrium Quantum Phenomena have provided a fresh perspective on the potential of twisted van der Waals materials for realizing novel and elusive states of matter and providing a unique materials-based quantum simulation platform. The team has laid out an exciting road map for the vibrant field of twisted van der Waals materials, reviewing the rapid progress made recently and adding their unique vision of intriguing avenues of future research to be completed. In their work, now published in Nature Physics, the team demonstrates that the future of twisted van der Waals materials is bright—both in terms of fundamental science as well as their potential applications in materials science and quantum information technologies. Twisted van der Waals materials consist of stacked layers of two-dimensional systems at a relative rotation angle. They are shown to provide a versatile toolbox to realize many highly sought-after quantum model systems, which exhibit exotic and—so far—elusive phases of mater of potential relevance to material science and quantum technologies. Hence those twisted van der Waals materials define a materials-based quantum simulator. This is particularly exciting as twisted van der Waals materials offer tantalizing opportunities to provide clean systems which are extremely well controlled by the twist angle, stacking sequence, substrate or gating techniques. However, this article demonstrates that the potential of twisted van der Waals materials even multiplies when brought together with other blossoming fields of condensed matter and quantum technology research. The potential for extensions is vast, with even more rich physics to be uncovered by, for example, by investigating the interaction of non-equilibrium states or cavities with the already promising van der Waals materials "One of the strengths of these novel materials is that they provide an unprecedented level of tunability," says lead author Dante Kennes. "This allows us to effectively realize many of the different lattice quantum models, which have taken center stage in the last few decades in the field of condensed matter research." Thus, exotic phases of matter, such as the elusive spin-liquid phase or systems with topological properties favorable to quantum technologies might be on the horizon. "We are really at the beginning of an intriguing journey to explore the vast amount of chemical and physical combinations in the field," co-author Lede Xian reports about his recent work. " Many more exciting discoveries, some of which we outline in our work, will follow," adds fellow author Martin Claassen. Twisted van der Waals materials offer a wonderful and formidable experimental challenge due to their complexity. They also open up completely new routes of manipulating and controlling quantum materials, according to Ángel Rubio, the director of the MPSD's Theory Department: "These materials let us unravel new phases of matter and promise a wide range of exciting applications in quantum technologies. We have just touched the surface of those possibilities in this perspective article and we can expect many more surprises in this exciting research journey." As this work illustrates, the ratio between questions answered and interesting questions to be addressed in the future makes this a particularly promising and vibrant research field, adds Ángel Rubio: "This plethora of exciting new phenomena can be enlarged further when considering driving those systems out of equilibrium or embedding them in optical cavities. Many interesting phenomena are waiting to be unraveled ahead of us!" <|im_end|>

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61002, 17432, 477, 2536, 63359, 46780, 30295, 315, 1778, 4211, 13, 1442, 279, 8292, 374, 1664, 14400, 11, 279, 3135, 649, 387, 1511, 311, 834, 306, 4134, 279, 810, 6485, 3769, 753, 44247, 369, 902, 279, 4113, 1646, 574, 743, 709, 11, 439, 1664, 439, 311, 8641, 279, 1648, 7119, 27276, 4954, 323, 26991, 502, 323, 39418, 35530, 315, 5030, 304, 1972, 31228, 7384, 13, 24191, 5208, 706, 1027, 17427, 4669, 21630, 37232, 582, 820, 45612, 315, 43746, 14338, 323, 81682, 21427, 33299, 11, 902, 649, 387, 45408, 304, 29393, 326, 1617, 1238, 311, 13383, 55372, 4211, 315, 75826, 1474, 1683, 22027, 304, 264, 14400, 11827, 220, 18, 662, 6104, 1521, 6067, 527, 7701, 687, 69855, 323, 649, 94176, 13383, 3738, 31228, 24051, 5493, 11, 433, 8625, 459, 22772, 8815, 311, 24490, 24051, 5493, 449, 11716, 481, 1317, 31608, 22639, 323, 5423, 311, 2680, 3428, 12, 35658, 7425, 306, 1317, 31608, 11713, 35530, 11, 1778, 439, 279, 41765, 294, 482, 31498, 1614, 315, 279, 259, 1389, 259, 117162, 2109, 58921, 81000, 1646, 220, 19, 662, 1115, 10506, 36611, 4647, 404, 978, 30548, 78, 47194, 315, 5355, 2761, 29614, 1147, 7384, 439, 459, 10778, 323, 58535, 75826, 1474, 1683, 5603, 311, 13383, 264, 3544, 743, 315, 7701, 687, 69855, 31228, 24051, 5493, 13, 6104, 1778, 6067, 656, 539, 11383, 10150, 279, 1579, 2237, 315, 31398, 323, 24473, 11716, 2968, 430, 9439, 25524, 6067, 656, 11, 279, 3544, 8547, 315, 11716, 2968, 2585, 2561, 1555, 31368, 15987, 22772, 90185, 6276, 369, 279, 27501, 315, 10474, 47287, 315, 13057, 323, 11775, 7437, 315, 1690, 9534, 24051, 5493, 304, 323, 704, 315, 56411, 323, 520, 1633, 3428, 20472, 13, 763, 4040, 11, 584, 3477, 1268, 2204, 11709, 315, 1403, 33520, 320, 17, 35, 8, 30548, 78, 7993, 62644, 520, 2204, 27744, 27030, 13383, 264, 7029, 2134, 315, 7524, 3428, 65487, 14683, 10508, 65500, 24051, 5493, 449, 5370, 69086, 4108, 11, 13167, 2786, 11, 33086, 11, 12903, 4235, 75441, 59086, 439, 1664, 439, 22639, 7953, 279, 81000, 4017, 11, 2737, 26310, 58677, 323, 7120, 2240, 291, 67948, 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25112, 315, 5355, 2761, 29614, 1147, 30548, 78, 47194, 449, 264, 27744, 6835, 10205, 311, 264, 68706, 315, 7524, 3428, 65487, 24051, 5493, 13, 4427, 315, 1521, 1972, 8200, 430, 1051, 20041, 304, 279, 17649, 527, 2728, 304, 279, 9358, 12960, 315, 279, 7216, 449, 279, 12435, 55372, 11, 7200, 6070, 323, 4754, 35530, 315, 5030, 430, 649, 387, 15393, 13, 1789, 279, 2579, 7200, 6070, 11, 279, 67822, 5238, 13519, 279, 10269, 21562, 37938, 3118, 304, 279, 1162, 315, 38817, 20934, 1155, 6178, 50, 220, 17, 7863, 449, 31180, 38, 13, 763, 279, 16335, 12960, 11, 584, 21782, 264, 13356, 389, 3284, 3938, 18445, 315, 4647, 404, 978, 31228, 1675, 42391, 449, 1690, 41765, 26006, 311, 387, 3685, 13, 597, 1174, 597, 865, 1174, 597, 379, 323, 597, 1167, 79164, 24151, 323, 24151, 304, 279, 865, 1174, 379, 323, 1167, 18445, 11, 15947, 13, 469, 323, 469, 597, 8464, 311, 7200, 4907, 13, 8797, 1404, 2217, 35339, 11, 264, 30548, 78, 7993, 315, 1403, 477, 810, 1647, 337, 5184, 449, 1081, 729, 62259, 55372, 18508, 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2115, 315, 38817, 5355, 2761, 29614, 1147, 7384, 11, 34988, 279, 11295, 5208, 1903, 6051, 323, 7999, 872, 5016, 11376, 315, 41765, 73234, 315, 3938, 3495, 311, 387, 8308, 13, 763, 872, 990, 11, 1457, 4756, 304, 22037, 28415, 11, 279, 2128, 32216, 430, 279, 3938, 315, 38817, 5355, 2761, 29614, 1147, 7384, 374, 10107, 2345, 21704, 304, 3878, 315, 16188, 8198, 439, 1664, 439, 872, 4754, 8522, 304, 7384, 8198, 323, 31228, 2038, 14645, 13, 12015, 13539, 5355, 2761, 29614, 1147, 7384, 6824, 315, 42415, 13931, 315, 1403, 33520, 6067, 520, 264, 8844, 12984, 9392, 13, 2435, 527, 6982, 311, 3493, 264, 33045, 68970, 311, 13383, 1690, 7701, 16495, 45673, 31228, 1646, 6067, 11, 902, 31324, 39418, 323, 2345, 708, 3117, 2345, 301, 22784, 35530, 315, 53251, 315, 4754, 41961, 311, 3769, 8198, 323, 31228, 14645, 13, 32140, 1884, 38817, 5355, 2761, 29614, 1147, 7384, 7124, 264, 7384, 6108, 31228, 42991, 13, 1115, 374, 8104, 13548, 439, 38817, 5355, 2761, 29614, 1147, 7384, 3085, 95685, 4954, 10708, 311, 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449, 1948, 5848, 6012, 37849, 311, 31228, 14645, 2643, 387, 389, 279, 35174, 13, 330, 1687, 527, 2216, 520, 279, 7314, 315, 459, 41765, 11879, 311, 13488, 279, 13057, 3392, 315, 11742, 323, 7106, 28559, 304, 279, 2115, 1359, 1080, 43802, 445, 15686, 1630, 1122, 6821, 922, 813, 3293, 990, 13, 330, 9176, 810, 13548, 54098, 11, 1063, 315, 902, 584, 21782, 304, 1057, 990, 11, 690, 1833, 1359, 11621, 12637, 3229, 11826, 57438, 28376, 13, 12015, 13539, 5355, 2761, 29614, 1147, 7384, 3085, 264, 11364, 323, 54829, 22772, 8815, 4245, 311, 872, 23965, 13, 2435, 1101, 1825, 709, 6724, 502, 11543, 315, 63614, 323, 26991, 31228, 7384, 11, 4184, 311, 43912, 983, 301, 45014, 11, 279, 7690, 315, 279, 94043, 35, 596, 31535, 6011, 25, 330, 9673, 7384, 1095, 603, 75073, 502, 35530, 315, 5030, 323, 11471, 264, 7029, 2134, 315, 13548, 8522, 304, 31228, 14645, 13, 1226, 617, 1120, 24891, 279, 7479, 315, 1884, 24525, 304, 420, 13356, 4652, 323, 584, 649, 1755, 1690, 810, 46540, 304, 420, 13548, 3495, 11879, 1210, 1666, 420, 990, 46480, 11, 279, 11595, 1990, 4860, 19089, 323, 7185, 4860, 311, 387, 20669, 304, 279, 3938, 3727, 420, 264, 8104, 26455, 323, 34076, 3495, 2115, 11, 11621, 43912, 983, 301, 45014, 25, 330, 2028, 68706, 315, 13548, 502, 44247, 649, 387, 74117, 4726, 994, 13126, 10043, 1884, 6067, 704, 315, 56411, 477, 40188, 1124, 304, 29393, 57709, 1385, 13, 9176, 7185, 44247, 527, 8748, 311, 387, 41480, 29285, 8469, 315, 603, 9135, 220, 128257, 198 ]

1,967

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Our Moon periodically moves through the magnetic tail of the Earth that contains terrestrial ions of hydrogen and oxygen. A possible density contrast might have been discovered that could be consistent with the presence of water phase of potential terrestrial origin. Using novel gravity aspects (descriptors) derived from harmonic potential coefficients of gravity field of the Moon, we discovered gravity strike angle anomalies that point to water phase locations in the polar regions of the Moon. Our analysis suggests that impact cratering processes were responsible for specific pore space network that were subsequently filled with the water phase filling volumes of permafrost in the lunar subsurface. In this work, we suggest the accumulation of up to ~ 3000 km 3 of terrestrial water phase (Earth’s atmospheric escape) now filling the pore spaced regolith, portion of which is distributed along impact zones of the polar regions of the Moon. These unique locations serve as potential resource utilization sites for future landing exploration and habitats (e.g., NASA Artemis Plan objectives). Introduction NASA’s return to the lunar surface (i.e. Artemis Plan) requires mission planning for near surface water phase resources 1 . The lunar surface regolith is coupled with ion-magnetohydrodynamical processes that may have contributed to the deposition of water phase on its surface. This is because the lunar environment is exposed for five days of each Earth orbit period to a magnetic field tail extending all the way from the Earth’s geomagnetic field 2 . Recent measurements from the Kaguya lunar orbiter (JAXA) have revealed significant numbers of oxygen ions during the time when the lunar orbit was inside the geomagnetic field 2 . This provided the necessary evidence that oxygen ions were not coming from the intrinsic solar winds. This is because the high temperature of the solar corona allows for only multi-charged oxygen ions (O5+, O6+, O7+ and O8+) as observed by Advanced Composition Explorer (ACE) space satellite with O+ in negligible amounts 3 . However, 1–10 keV O+ ions were observed to populate the Moon’s environment during the transition through the plasma sheet that originated from the Earth’s ionosphere 2 , 4 . The terrestrial ion’s flux density during the Moon’s passage through the magnetotail was estimated between 2.1 × 10 4 cm 2 s −1 and 2.6 × 10 4 cm −2 s −1 2 , 5 . This process of Earth-lunar geoionic O+ accumulation fluctuated over the history of the earth for several reasons: Initially (1), when the geomagnetic field may have not been well developed or even absent in ancient times 6 the O+ accumulation was more intense. When applying this possibility from the Earth to Mars, where the global magnetic field is absent 7 , 8 , there, an ionospheric plasma sheet develops in absence of the global magnetic field and transfers ion, mostly oxygen, down the plasma sheet as observed by Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft 9 . The second source (2) of ion enhancement has to do with the increasing distance between the Earth and the Moon in their history 10 . The third source (3) of ion variability is an episodical increase of the solar activity observed by MAVEN mission 11 . Evidence of such ion transfer mechanisms 9 supports a hypothesis that a part of the terrestrial atmosphere that was lost in the past is now likely preserved within the surface of lunar polar regolith. For this hypothesis there is a support from observation of nitrogen and noble gases isotopes 12 . The recent advancements in Earth's atmospheric escape warrants new analysis of water phase deposits on the Moon. We apply our novel gravity aspects (descriptors) derived from harmonic potential coefficients of gravity field of the Moon by considering these novel ionic transfer mechanisms on depositional history of water phase formation, from which gravity strike anomalies appear. While the loss of the ions from the atmospheres of terrestrial planets depends on processes at the atmosphere-surface interface, there are a significant loss mechanisms occurring in the upper atmosphere. For example, the ionosphere’s loss of ions due to space plasma acceleration can dynamically control the evolution of the atmosphere 5 . The geomagnetic field creates an obstacle to the solar wind preventing a direct abrasion of terrestrial neutral ions (oxygens, hydrogens) via thermal and non-thermal activities 13 . Four main pathways of terrestrial ions constitute of (i) magnetopause escape, (ii) magnetopause ring current dayside escape, (iii) anti-sunward flow escape, and (iv) lobe/mantle escape (Fig. 1 ). When ions are escaping via these pathways 5 , 14 , 15 , they can be returned towards the Earth and be added back to the atmosphere 5 . This occurs when the collision-less path distance becomes small enough that plasma on this length scale dissipates and the geomagnetic field lines and plasma field lines become reconnected 16 . Independently, ion outflow (including mostly H+, O+) from the uppermost terrestrial polar ionosphere has a time dependent typical thermal energies of 0.3 eV 16 . This terrestrial polar wind outflow is on the order of 10 25 ions s −1 during the solar maximum activity, having average flow rates across the solar minimum and maximum of ~ 5 × 10 24 ions s −1 , caused by electric field disturbance due to charge difference between the ions and faster moving electrons 16 . Prior work has shown, during the dark sky conditions of lunar eclipses, that the differential effects of these energetic H+/O+ ionic species strike the Moon’s surface when engulfed by magnetotail transit. This observation suggested that omnipresent exospheric sources are augmented by these variable plasma impact sources in the solar wind reconnection with Earth’s magnetotail 17 . There is one order of magnitude difference between the estimates of the polar outflow and the four ion escape routes 5 . Here we consider this unknown loss of ions may account for volume of ions deposited on the Moon. Figure 1 Sketch showing three-dimensional cutaway of Earth’s magnetosphere. The blue and white arrows are motion", "role": "user" }, { "content": "Hydrogen and oxygen ions escaping from Earth's upper atmosphere and combining on the moon could be one of the sources of the known lunar water and ice, according to new research by University of Alaska Fairbanks Geophysical Institute scientists. The work led by UAF Geophysical Institute associate research professor Gunther Kletetschka adds to a growing body of research about water at the moon's north and south poles. Finding water is key to NASA's Artemis project, the planned long-term human presence on the moon. NASA plans to send humans back to the moon this decade. \"As NASA's Artemis team plans to build a base camp on the moon's south pole, the water ions that originated many eons ago on Earth can be used in the astronauts' life support system,\" Kletetschka said. The new research estimates the moon's polar regions could hold up to 3,500 cubic kilometers—840 cubic miles—or more of surface permafrost or subsurface liquid water created from ions that escaped Earth's atmosphere. That's a volume comparable to North America's Lake Huron, the world's eighth-largest lake. Researchers based that total on the lowest volume model calculation—1% of Earth's atmospheric escape reaching the moon. A majority of the lunar water is generally believed to have been deposited by asteroids and comets that collided with the moon. Most was during a period known as the Late Heavy Bombardment. In that period, about 3.5 billion years ago when the solar system was about 1 billion years old, it is argued that the early inner planets and Earth's moon sustained unusually heavy impact from asteroids. Scientists also hypothesize that the solar wind is a source. The solar wind carries oxygen and hydrogen ions, which may have combined and been deposited on the moon as water molecules. Now there's an additional way to explain how water accumulates on the moon. The research was published March 16 in the journal Scientific Reports in a paper authored by Kletetschka and co-authored by Ph.D. student Nicholas Hasson of the Geophysical Institute and UAF Water and Environmental Research Center at the Institute for Northern Engineering. Several colleagues from the Czech Republic are also among the co-authors. This diagram from the research paper authored by Gunther Kletetschka shows the moon approaching Earth's magnetotail. Credit: Gunther Kletetschka Kletetschka and his colleagues suggest hydrogen and oxygen ions are driven into the moon when it passes through the tail of the Earth's magnetosphere, which it does on five days of the moon's monthly trip around the planet. The magnetosphere is the teardrop-shaped bubble created by Earth's magnetic field that shields the planet from much of the continual stream of charged solar particles. Recent measurements from multiple space agencies—NASA, European Space Agency, Japan Aerospace Exploration Agency and Indian Space Research Organization—revealed significant numbers of water-forming ions present during the moon's transit through this part of the magnetosphere. These ions have slowly accumulated since the Late Heavy Bombardment. The presence of the moon in the magnetosphere's tail, called the magnetotail, temporarily affects some of Earth's magnetic field lines—those that are broken and which simply trail off into space for many thousands of miles. Not all of Earth's field lines are attached to the planet at both ends; some have only one attachment point. Think of each of these as a thread tethered to a pole on a windy day. The moon's presence in the magnetotail causes some of these broken field lines to reconnect with their opposing broken counterpart. When that happens, hydrogen and oxygen ions that had escaped Earth rush to those reconnected field lines and are accelerated back toward Earth. The paper's authors suggest many of those returning ions hit the passing moon, which has no magnetosphere of its own to repel them. \"It is like the moon is in the shower—a shower of water ions coming back to Earth, falling on the moon's surface,\" Kletetschka said. The ions then combine to form the lunar permafrost. Some of that, through geologic and other processes such as asteroid impacts, is driven below the surface, where it can become liquid water. The research team used gravitational data from NASA's Lunar Reconnaissance Orbiter to study polar regions along with several major lunar craters. Anomalies in underground measurements at impact craters indicate locations of fractured rock conducive to containing liquid water or ice. Gravity measurements at those subsurface locations suggest the presence of ice or liquid water, the research paper reads. The latest research builds on work published in December 2020 by four of the new paper's authors, including Kletetschka. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Our Moon periodically moves through the magnetic tail of the Earth that contains terrestrial ions of hydrogen and oxygen. A possible density contrast might have been discovered that could be consistent with the presence of water phase of potential terrestrial origin. Using novel gravity aspects (descriptors) derived from harmonic potential coefficients of gravity field of the Moon, we discovered gravity strike angle anomalies that point to water phase locations in the polar regions of the Moon. Our analysis suggests that impact cratering processes were responsible for specific pore space network that were subsequently filled with the water phase filling volumes of permafrost in the lunar subsurface. In this work, we suggest the accumulation of up to ~ 3000 km 3 of terrestrial water phase (Earth’s atmospheric escape) now filling the pore spaced regolith, portion of which is distributed along impact zones of the polar regions of the Moon. These unique locations serve as potential resource utilization sites for future landing exploration and habitats (e.g., NASA Artemis Plan objectives). Introduction NASA’s return to the lunar surface (i.e. Artemis Plan) requires mission planning for near surface water phase resources 1 . The lunar surface regolith is coupled with ion-magnetohydrodynamical processes that may have contributed to the deposition of water phase on its surface. This is because the lunar environment is exposed for five days of each Earth orbit period to a magnetic field tail extending all the way from the Earth’s geomagnetic field 2 . Recent measurements from the Kaguya lunar orbiter (JAXA) have revealed significant numbers of oxygen ions during the time when the lunar orbit was inside the geomagnetic field 2 . This provided the necessary evidence that oxygen ions were not coming from the intrinsic solar winds. This is because the high temperature of the solar corona allows for only multi-charged oxygen ions (O5+, O6+, O7+ and O8+) as observed by Advanced Composition Explorer (ACE) space satellite with O+ in negligible amounts 3 . However, 1–10 keV O+ ions were observed to populate the Moon’s environment during the transition through the plasma sheet that originated from the Earth’s ionosphere 2 , 4 . The terrestrial ion’s flux density during the Moon’s passage through the magnetotail was estimated between 2.1 × 10 4 cm 2 s −1 and 2.6 × 10 4 cm −2 s −1 2 , 5 . This process of Earth-lunar geoionic O+ accumulation fluctuated over the history of the earth for several reasons: Initially (1), when the geomagnetic field may have not been well developed or even absent in ancient times 6 the O+ accumulation was more intense. When applying this possibility from the Earth to Mars, where the global magnetic field is absent 7 , 8 , there, an ionospheric plasma sheet develops in absence of the global magnetic field and transfers ion, mostly oxygen, down the plasma sheet as observed by Mars Atmosphere and Volatile Evolution (MAVEN) spacecraft 9 . The second source (2) of ion enhancement has to do with the increasing distance between the Earth and the Moon in their history 10 . The third source (3) of ion variability is an episodical increase of the solar activity observed by MAVEN mission 11 . Evidence of such ion transfer mechanisms 9 supports a hypothesis that a part of the terrestrial atmosphere that was lost in the past is now likely preserved within the surface of lunar polar regolith. For this hypothesis there is a support from observation of nitrogen and noble gases isotopes 12 . The recent advancements in Earth's atmospheric escape warrants new analysis of water phase deposits on the Moon. We apply our novel gravity aspects (descriptors) derived from harmonic potential coefficients of gravity field of the Moon by considering these novel ionic transfer mechanisms on depositional history of water phase formation, from which gravity strike anomalies appear. While the loss of the ions from the atmospheres of terrestrial planets depends on processes at the atmosphere-surface interface, there are a significant loss mechanisms occurring in the upper atmosphere. For example, the ionosphere’s loss of ions due to space plasma acceleration can dynamically control the evolution of the atmosphere 5 . The geomagnetic field creates an obstacle to the solar wind preventing a direct abrasion of terrestrial neutral ions (oxygens, hydrogens) via thermal and non-thermal activities 13 . Four main pathways of terrestrial ions constitute of (i) magnetopause escape, (ii) magnetopause ring current dayside escape, (iii) anti-sunward flow escape, and (iv) lobe/mantle escape (Fig. 1 ). When ions are escaping via these pathways 5 , 14 , 15 , they can be returned towards the Earth and be added back to the atmosphere 5 . This occurs when the collision-less path distance becomes small enough that plasma on this length scale dissipates and the geomagnetic field lines and plasma field lines become reconnected 16 . Independently, ion outflow (including mostly H+, O+) from the uppermost terrestrial polar ionosphere has a time dependent typical thermal energies of 0.3 eV 16 . This terrestrial polar wind outflow is on the order of 10 25 ions s −1 during the solar maximum activity, having average flow rates across the solar minimum and maximum of ~ 5 × 10 24 ions s −1 , caused by electric field disturbance due to charge difference between the ions and faster moving electrons 16 . Prior work has shown, during the dark sky conditions of lunar eclipses, that the differential effects of these energetic H+/O+ ionic species strike the Moon’s surface when engulfed by magnetotail transit. This observation suggested that omnipresent exospheric sources are augmented by these variable plasma impact sources in the solar wind reconnection with Earth’s magnetotail 17 . There is one order of magnitude difference between the estimates of the polar outflow and the four ion escape routes 5 . Here we consider this unknown loss of ions may account for volume of ions deposited on the Moon. Figure 1 Sketch showing three-dimensional cutaway of Earth’s magnetosphere. The blue and white arrows are motion<|im_end|> <|im_start|>assistant Hydrogen and oxygen ions escaping from Earth's upper atmosphere and combining on the moon could be one of the sources of the known lunar water and ice, according to new research by University of Alaska Fairbanks Geophysical Institute scientists. The work led by UAF Geophysical Institute associate research professor Gunther Kletetschka adds to a growing body of research about water at the moon's north and south poles. Finding water is key to NASA's Artemis project, the planned long-term human presence on the moon. NASA plans to send humans back to the moon this decade. "As NASA's Artemis team plans to build a base camp on the moon's south pole, the water ions that originated many eons ago on Earth can be used in the astronauts' life support system," Kletetschka said. The new research estimates the moon's polar regions could hold up to 3,500 cubic kilometers—840 cubic miles—or more of surface permafrost or subsurface liquid water created from ions that escaped Earth's atmosphere. That's a volume comparable to North America's Lake Huron, the world's eighth-largest lake. Researchers based that total on the lowest volume model calculation—1% of Earth's atmospheric escape reaching the moon. A majority of the lunar water is generally believed to have been deposited by asteroids and comets that collided with the moon. Most was during a period known as the Late Heavy Bombardment. In that period, about 3.5 billion years ago when the solar system was about 1 billion years old, it is argued that the early inner planets and Earth's moon sustained unusually heavy impact from asteroids. Scientists also hypothesize that the solar wind is a source. The solar wind carries oxygen and hydrogen ions, which may have combined and been deposited on the moon as water molecules. Now there's an additional way to explain how water accumulates on the moon. The research was published March 16 in the journal Scientific Reports in a paper authored by Kletetschka and co-authored by Ph.D. student Nicholas Hasson of the Geophysical Institute and UAF Water and Environmental Research Center at the Institute for Northern Engineering. Several colleagues from the Czech Republic are also among the co-authors. This diagram from the research paper authored by Gunther Kletetschka shows the moon approaching Earth's magnetotail. Credit: Gunther Kletetschka Kletetschka and his colleagues suggest hydrogen and oxygen ions are driven into the moon when it passes through the tail of the Earth's magnetosphere, which it does on five days of the moon's monthly trip around the planet. The magnetosphere is the teardrop-shaped bubble created by Earth's magnetic field that shields the planet from much of the continual stream of charged solar particles. Recent measurements from multiple space agencies—NASA, European Space Agency, Japan Aerospace Exploration Agency and Indian Space Research Organization—revealed significant numbers of water-forming ions present during the moon's transit through this part of the magnetosphere. These ions have slowly accumulated since the Late Heavy Bombardment. The presence of the moon in the magnetosphere's tail, called the magnetotail, temporarily affects some of Earth's magnetic field lines—those that are broken and which simply trail off into space for many thousands of miles. Not all of Earth's field lines are attached to the planet at both ends; some have only one attachment point. Think of each of these as a thread tethered to a pole on a windy day. The moon's presence in the magnetotail causes some of these broken field lines to reconnect with their opposing broken counterpart. When that happens, hydrogen and oxygen ions that had escaped Earth rush to those reconnected field lines and are accelerated back toward Earth. The paper's authors suggest many of those returning ions hit the passing moon, which has no magnetosphere of its own to repel them. "It is like the moon is in the shower—a shower of water ions coming back to Earth, falling on the moon's surface," Kletetschka said. The ions then combine to form the lunar permafrost. Some of that, through geologic and other processes such as asteroid impacts, is driven below the surface, where it can become liquid water. The research team used gravitational data from NASA's Lunar Reconnaissance Orbiter to study polar regions along with several major lunar craters. Anomalies in underground measurements at impact craters indicate locations of fractured rock conducive to containing liquid water or ice. Gravity measurements at those subsurface locations suggest the presence of ice or liquid water, the research paper reads. The latest research builds on work published in December 2020 by four of the new paper's authors, including Kletetschka. <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Genetic liability to substance use disorders can be parsed into loci that confer general or substance-specific addiction risk. We report a multivariate genome-wide association meta-analysis that disaggregates general and substance-specific loci from published summary statistics of problematic alcohol use, problematic tobacco use, cannabis use disorder and opioid use disorder in a sample of 1,025,550 individuals of European descent and 92,630 individuals of African descent. Nineteen independent single-nucleotide polymorphisms were genome-wide significant ( P < 5 × 10 –8 ) for the general addiction risk factor (addiction-rf), which showed high polygenicity. Across ancestries, PDE4B was significant (among other genes), suggesting dopamine regulation as a cross-substance vulnerability. An addiction-rf polygenic risk score was associated with substance use disorders, psychopathologies, somatic conditions and environments associated with the onset of addictions. Substance-specific loci (9 for alcohol, 32 for tobacco, 5 for cannabis and 1 for opioids) included metabolic and receptor genes. These findings provide insight into genetic risk loci for substance use disorders that could be leveraged as treatment targets. Main The lives lost, impacts on individuals and families, and socioeconomic costs attributable to substance use reflect a growing public health crisis 1 . For example, in the United States, 13.5% of deaths among young adults 2 are attributable to alcohol, smoking is the leading risk factor for mortality in males 3 , and the odds of dying by opioid overdose are greater than those of dying in a motor vehicle crash 4 . Despite the large impact of substance use and substance use disorders 5 , there is limited knowledge of the molecular genetic underpinnings of addiction broadly. Individual substance use disorders (SUDs) are heritable ( h 2 , ~50–60%) and highly polygenic 6 , 7 . Recent large-scale genome-wide association studies (GWASs) have identified loci associated with problematic drinking 8 , 9 , alcohol use disorder (AUD) 10 , 11 , cigarettes smoked per day 12 , nicotine dependence 13 , 14 , cannabis use disorder (CUD) 15 and opioid use disorder (OUD) 16 . Echoing evidence from twin and family studies 17 , these GWASs show that the genetic architecture of SUDs is characterized by a high degree of commonality 18 , that is, a general addiction genetic factor likely conveys vulnerability to multiple SUDs. Even after accounting for genetic correlations with non-problematic substance use and with other psychiatrically relevant traits and disorders, there is considerable variance that is unique to this general risk for addiction, indicating that a liability to addiction reflects more than just the combined genetic liability to substance use and psychopathology 18 , 19 , 20 , 21 . We conducted a multivariate GWAS of the largest available discovery GWASs of SUDs, including problematic alcohol use (PAU: N = 435,563; continuous) 8 , problematic tobacco use (PTU: N = 270,120; continuous) 12 , 13 , 18 , CUD ( N = 384,032, cases = 14,080) 15 and OUD ( N = 79,729, cases = 10,544 cases) 16 . First, we partitioned single-nucleotide polymorphism (SNP) effects into five sources of variation: (1) a general addiction risk factor (referred to as the addiction-rf), and risks specific to (2) alcohol, (3) nicotine, (4) cannabis and (5) opioids. Second, we identified biological pathways underlying risk for these five SUD phenotypes using gene, expression quantitative trait locus (eQTL) and pathway enrichment analyses. Third, we examined whether currently available medications could potentially be repurposed to treat SUDs 22 . Fourth, we assessed the association of a polygenic risk score (PRS) derived from the addiction-rf with general SUD phenotypes in an independent case/control sample. Fifth, we examined the extent to which genetic liability to the addiction-rf is shared with other phenotypes (for example, physical and mental health outcomes). Sixth, we tested whether the addiction-rf PRS was associated with medical diagnoses derived from electronic health records (EHRs) and with behavioural phenotypes in largely substance-naive 9–10-year-old children. Results Addiction risk factor in European ancestry GWAS As in our prior study 18 , we estimated a single factor model, scaled the variance of the addiction-rf to 1 and allowed loadings to be estimated freely. The single factor model that loaded on OUD ( N effective = 30,443), PAU ( N effective = 300,789), PTU ( N effective = 270,120) and CUD ( N effective = 46,351) fit the data well ( χ 2 (1) = 0.017, P = 0.896, comparative fit index (CFI) = 1, standardized root mean square residual (SRMR) = 0.002). The latent factor loaded significantly on all indicators (standardized loadings on OUD = 0.83, PAU = 0.58, PTU = 0.36, CUD = 0.93; see Supplementary Fig. 1 for full model). The addiction-rf was associated with 19 independent ( r 2 < 0.1) genome-wide significant (GWS) SNPs that mapped to 17 genomic risk loci (Fig. 1 ; Table 1 ; Supplementary Table 1 for lead SNPs and Supplementary Table 2 for genomic risk loci). The most significant SNP ( rs6589386 , P = 2.9 × 10 –12 ) was intergenic, but closest to DRD2 , which was GWS in gene-based analyses ( P = 7.9 × 10 –12 ; Supplementary Table 3 ). Further, rs6589386 was an eQTL for DRD2 in the cerebellum, and Hi-C analyses (in FUMA) 23 revealed that the variant made chromatin contact with the promoter of the gene (Supplementary Fig. 2 ). Fig. 1: Manhattan plot of the addiction-rf GWAS results. The dotted line represents genome-wide significance at 5 × 10 –8 . Each SNP peak is annotated with the closest mapped gene from FUMA (Table 1 ) . We have not included all SNPs in the credible set in Table 1 , but they are shown in Supplementary Table 4 . Significance is set at genome-wide significance Bonferroni correction is a two-sided test ( P < 5 × 10 –8 ). Full size image Table 1 Lead GWAS significant variants Full size table Gene-based analyses identified 42 significantly associated genes (Supplementary Table 3 ); the most significant signals were FTO ( P = 1.86 × 10 –13 ), DRD2", "role": "user" }, { "content": "By combing through genomic data of over 1 million people, scientists have identified genes commonly inherited across addiction disorders, regardless of the substance being used. This dataset—one of the largest of its kind—may help reveal new treatment targets across multiple substance use disorders, including for people diagnosed with more than one. The findings also reinforce the role of the dopamine system in addiction, by showing that the combination of genes underlying addiction disorders was also associated with regulation of dopamine signaling. Published today in Nature Mental Health, the study was led by researchers at the Washington University in St. Louis, along with more than 150 co-authors from around the world. There has been limited knowledge of the molecular genetic underpinnings of addiction until now. Further, most clinical trials and behavioral studies have focused on individual substances, rather than addiction more broadly. \"Genetics play a key role in determining health throughout our lives, but they are not destiny. Our hope with genomic studies is to further illuminate factors that may protect or predispose a person to substance use disorders—knowledge that can be used to expand preventative services and empower individuals to make informed decisions about drug use,\" said NIDA Director, Nora Volkow, M.D. \"A better understanding of genetics also brings us one step closer to developing personalized interventions that are tailored to an individual's unique biology, environment, and lived experience in order to provide the most benefits.\" In 2021, more than 46 million people in the United States aged 12 or older had at least one substance use disorder, and only 6.3% had received treatment. Moreover, people who use drugs are facing an increasingly dangerous drug supply, now often tainted with fentanyl. Approximately 107,000 people died of drug overdoses in 2021, and 37% of these deaths involved simultaneous exposure to both opioids and stimulant drugs. Drug use and addiction represent a public health crisis, characterized by high social, emotional, and financial costs to families, communities, and society. Substance use disorders are heritable and influenced by complex interactions among multiple genes and environmental factors. In recent decades, a data-rich method, called genome-wide association, has emerged to try to identify specific genes involved in certain disorders. This method involves searching entire genomes for regions of genetic variation, called single-nucleotide polymorphisms (SNPs), that associate with the same disease, disorder, condition, or behavior among multiple people. In this study, researchers used this method to pinpoint areas in the genome associated with general addiction risk, as well as the risk of specific substance use disorders—namely, alcohol, nicotine, cannabis, and opioid use disorders—in a sample of 1,025,550 individuals with genes indicating European ancestry and 92,630 individuals with genes indicating African ancestry. \"Using genomics, we can create a data-driven pipeline to prioritize existing medications for further study and improve chances of discovering new treatments. To do this accurately, it's critical that the genetic evidence we gather includes globally representative populations and that we have members of communities historically underrepresented in biomedical research leading and contributing to these kinds of studies,\" said Alexander Hatoum, Ph.D., a research assistant professor at Washington University in St. Louis and lead author of the study. Hatoum and the research team discovered various molecular patterns underlying addiction, including 19 independent SNPs significantly associated with general addiction risk and 47 SNPs for specific substance disorders among the European ancestry sample. The strongest gene signals consistent across the various disorders mapped to areas in the genome known to control regulation of dopamine signaling, suggesting that genetic variation in dopamine signaling regulation, rather than in dopamine signaling itself, is central to addiction risk. Compared to other genetic predictors, the genomic pattern identified here was also a more sensitive predictor of having two or more substance use disorders at once. The genomic pattern also predicted higher risk of mental and physical illness, including psychiatric disorders, suicidal behavior, respiratory disease, heart disease, and chronic pain conditions. In children aged 9 or 10 years without any experience of substance use, these genes correlated with parental substance use and externalizing behavior. \"Substance use disorders and mental disorders often co-occur, and we know that the most effective treatments help people address both issues at the same time. The shared genetic mechanisms between substance use and mental disorders revealed in this study underscore the importance of thinking about these disorders in tandem,\" said NIMH Director Joshua A. Gordon, M.D., Ph.D. Genomic analysis in the African ancestry sample revealed one SNP associated with general addiction risk and one substance-specific SNP for risk of alcohol use disorder. The dearth of findings here underscores ongoing disparities in data inclusion of globally representative populations that must be addressed to ensure data robustness and accuracy, Hatoum and co-authors note. The inclusion of data from different ancestral groups in this study cannot and should not be used to assign or categorize variable genetic risk for substance use disorder to specific populations. As genetic information is used to better understand human health and health inequities, expansive and inclusive data collection is essential. NIDA and other Institutes at NIH supported a recently released report on responsible use and interpretation of population-level genomic data by the National Academies of Sciences, Engineering, and Medicine. See also a corresponding statement from the NIH. While Hatoum and colleagues have identified a genetic pattern indicating broad addiction risk, they note that substance use-specific diagnoses still have meaning. \"The current study validates previous findings of alcohol-specific risk variants, and, importantly, makes this finding in a very large and more diverse study population,\" said NIAAA Director George F. Koob, Ph.D. \"The finding of shared genetic risk variants across different substance use disorders provides insight into some of the mechanisms that underlie these disorders and the relationships with other mental health conditions. Together the findings of alcohol-specific risk variants and common addiction-related variants provide powerful support for individualized prevention and treatment.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Genetic liability to substance use disorders can be parsed into loci that confer general or substance-specific addiction risk. We report a multivariate genome-wide association meta-analysis that disaggregates general and substance-specific loci from published summary statistics of problematic alcohol use, problematic tobacco use, cannabis use disorder and opioid use disorder in a sample of 1,025,550 individuals of European descent and 92,630 individuals of African descent. Nineteen independent single-nucleotide polymorphisms were genome-wide significant ( P < 5 × 10 –8 ) for the general addiction risk factor (addiction-rf), which showed high polygenicity. Across ancestries, PDE4B was significant (among other genes), suggesting dopamine regulation as a cross-substance vulnerability. An addiction-rf polygenic risk score was associated with substance use disorders, psychopathologies, somatic conditions and environments associated with the onset of addictions. Substance-specific loci (9 for alcohol, 32 for tobacco, 5 for cannabis and 1 for opioids) included metabolic and receptor genes. These findings provide insight into genetic risk loci for substance use disorders that could be leveraged as treatment targets. Main The lives lost, impacts on individuals and families, and socioeconomic costs attributable to substance use reflect a growing public health crisis 1 . For example, in the United States, 13.5% of deaths among young adults 2 are attributable to alcohol, smoking is the leading risk factor for mortality in males 3 , and the odds of dying by opioid overdose are greater than those of dying in a motor vehicle crash 4 . Despite the large impact of substance use and substance use disorders 5 , there is limited knowledge of the molecular genetic underpinnings of addiction broadly. Individual substance use disorders (SUDs) are heritable ( h 2 , ~50–60%) and highly polygenic 6 , 7 . Recent large-scale genome-wide association studies (GWASs) have identified loci associated with problematic drinking 8 , 9 , alcohol use disorder (AUD) 10 , 11 , cigarettes smoked per day 12 , nicotine dependence 13 , 14 , cannabis use disorder (CUD) 15 and opioid use disorder (OUD) 16 . Echoing evidence from twin and family studies 17 , these GWASs show that the genetic architecture of SUDs is characterized by a high degree of commonality 18 , that is, a general addiction genetic factor likely conveys vulnerability to multiple SUDs. Even after accounting for genetic correlations with non-problematic substance use and with other psychiatrically relevant traits and disorders, there is considerable variance that is unique to this general risk for addiction, indicating that a liability to addiction reflects more than just the combined genetic liability to substance use and psychopathology 18 , 19 , 20 , 21 . We conducted a multivariate GWAS of the largest available discovery GWASs of SUDs, including problematic alcohol use (PAU: N = 435,563; continuous) 8 , problematic tobacco use (PTU: N = 270,120; continuous) 12 , 13 , 18 , CUD ( N = 384,032, cases = 14,080) 15 and OUD ( N = 79,729, cases = 10,544 cases) 16 . First, we partitioned single-nucleotide polymorphism (SNP) effects into five sources of variation: (1) a general addiction risk factor (referred to as the addiction-rf), and risks specific to (2) alcohol, (3) nicotine, (4) cannabis and (5) opioids. Second, we identified biological pathways underlying risk for these five SUD phenotypes using gene, expression quantitative trait locus (eQTL) and pathway enrichment analyses. Third, we examined whether currently available medications could potentially be repurposed to treat SUDs 22 . Fourth, we assessed the association of a polygenic risk score (PRS) derived from the addiction-rf with general SUD phenotypes in an independent case/control sample. Fifth, we examined the extent to which genetic liability to the addiction-rf is shared with other phenotypes (for example, physical and mental health outcomes). Sixth, we tested whether the addiction-rf PRS was associated with medical diagnoses derived from electronic health records (EHRs) and with behavioural phenotypes in largely substance-naive 9–10-year-old children. Results Addiction risk factor in European ancestry GWAS As in our prior study 18 , we estimated a single factor model, scaled the variance of the addiction-rf to 1 and allowed loadings to be estimated freely. The single factor model that loaded on OUD ( N effective = 30,443), PAU ( N effective = 300,789), PTU ( N effective = 270,120) and CUD ( N effective = 46,351) fit the data well ( χ 2 (1) = 0.017, P = 0.896, comparative fit index (CFI) = 1, standardized root mean square residual (SRMR) = 0.002). The latent factor loaded significantly on all indicators (standardized loadings on OUD = 0.83, PAU = 0.58, PTU = 0.36, CUD = 0.93; see Supplementary Fig. 1 for full model). The addiction-rf was associated with 19 independent ( r 2 < 0.1) genome-wide significant (GWS) SNPs that mapped to 17 genomic risk loci (Fig. 1 ; Table 1 ; Supplementary Table 1 for lead SNPs and Supplementary Table 2 for genomic risk loci). The most significant SNP ( rs6589386 , P = 2.9 × 10 –12 ) was intergenic, but closest to DRD2 , which was GWS in gene-based analyses ( P = 7.9 × 10 –12 ; Supplementary Table 3 ). Further, rs6589386 was an eQTL for DRD2 in the cerebellum, and Hi-C analyses (in FUMA) 23 revealed that the variant made chromatin contact with the promoter of the gene (Supplementary Fig. 2 ). Fig. 1: Manhattan plot of the addiction-rf GWAS results. The dotted line represents genome-wide significance at 5 × 10 –8 . Each SNP peak is annotated with the closest mapped gene from FUMA (Table 1 ) . We have not included all SNPs in the credible set in Table 1 , but they are shown in Supplementary Table 4 . Significance is set at genome-wide significance Bonferroni correction is a two-sided test ( P < 5 × 10 –8 ). Full size image Table 1 Lead GWAS significant variants Full size table Gene-based analyses identified 42 significantly associated genes (Supplementary Table 3 ); the most significant signals were FTO ( P = 1.86 × 10 –13 ), DRD2<|im_end|> <|im_start|>assistant By combing through genomic data of over 1 million people, scientists have identified genes commonly inherited across addiction disorders, regardless of the substance being used. This dataset—one of the largest of its kind—may help reveal new treatment targets across multiple substance use disorders, including for people diagnosed with more than one. The findings also reinforce the role of the dopamine system in addiction, by showing that the combination of genes underlying addiction disorders was also associated with regulation of dopamine signaling. Published today in Nature Mental Health, the study was led by researchers at the Washington University in St. Louis, along with more than 150 co-authors from around the world. There has been limited knowledge of the molecular genetic underpinnings of addiction until now. Further, most clinical trials and behavioral studies have focused on individual substances, rather than addiction more broadly. "Genetics play a key role in determining health throughout our lives, but they are not destiny. Our hope with genomic studies is to further illuminate factors that may protect or predispose a person to substance use disorders—knowledge that can be used to expand preventative services and empower individuals to make informed decisions about drug use," said NIDA Director, Nora Volkow, M.D. "A better understanding of genetics also brings us one step closer to developing personalized interventions that are tailored to an individual's unique biology, environment, and lived experience in order to provide the most benefits." In 2021, more than 46 million people in the United States aged 12 or older had at least one substance use disorder, and only 6.3% had received treatment. Moreover, people who use drugs are facing an increasingly dangerous drug supply, now often tainted with fentanyl. Approximately 107,000 people died of drug overdoses in 2021, and 37% of these deaths involved simultaneous exposure to both opioids and stimulant drugs. Drug use and addiction represent a public health crisis, characterized by high social, emotional, and financial costs to families, communities, and society. Substance use disorders are heritable and influenced by complex interactions among multiple genes and environmental factors. In recent decades, a data-rich method, called genome-wide association, has emerged to try to identify specific genes involved in certain disorders. This method involves searching entire genomes for regions of genetic variation, called single-nucleotide polymorphisms (SNPs), that associate with the same disease, disorder, condition, or behavior among multiple people. In this study, researchers used this method to pinpoint areas in the genome associated with general addiction risk, as well as the risk of specific substance use disorders—namely, alcohol, nicotine, cannabis, and opioid use disorders—in a sample of 1,025,550 individuals with genes indicating European ancestry and 92,630 individuals with genes indicating African ancestry. "Using genomics, we can create a data-driven pipeline to prioritize existing medications for further study and improve chances of discovering new treatments. To do this accurately, it's critical that the genetic evidence we gather includes globally representative populations and that we have members of communities historically underrepresented in biomedical research leading and contributing to these kinds of studies," said Alexander Hatoum, Ph.D., a research assistant professor at Washington University in St. Louis and lead author of the study. Hatoum and the research team discovered various molecular patterns underlying addiction, including 19 independent SNPs significantly associated with general addiction risk and 47 SNPs for specific substance disorders among the European ancestry sample. The strongest gene signals consistent across the various disorders mapped to areas in the genome known to control regulation of dopamine signaling, suggesting that genetic variation in dopamine signaling regulation, rather than in dopamine signaling itself, is central to addiction risk. Compared to other genetic predictors, the genomic pattern identified here was also a more sensitive predictor of having two or more substance use disorders at once. The genomic pattern also predicted higher risk of mental and physical illness, including psychiatric disorders, suicidal behavior, respiratory disease, heart disease, and chronic pain conditions. In children aged 9 or 10 years without any experience of substance use, these genes correlated with parental substance use and externalizing behavior. "Substance use disorders and mental disorders often co-occur, and we know that the most effective treatments help people address both issues at the same time. The shared genetic mechanisms between substance use and mental disorders revealed in this study underscore the importance of thinking about these disorders in tandem," said NIMH Director Joshua A. Gordon, M.D., Ph.D. Genomic analysis in the African ancestry sample revealed one SNP associated with general addiction risk and one substance-specific SNP for risk of alcohol use disorder. The dearth of findings here underscores ongoing disparities in data inclusion of globally representative populations that must be addressed to ensure data robustness and accuracy, Hatoum and co-authors note. The inclusion of data from different ancestral groups in this study cannot and should not be used to assign or categorize variable genetic risk for substance use disorder to specific populations. As genetic information is used to better understand human health and health inequities, expansive and inclusive data collection is essential. NIDA and other Institutes at NIH supported a recently released report on responsible use and interpretation of population-level genomic data by the National Academies of Sciences, Engineering, and Medicine. See also a corresponding statement from the NIH. While Hatoum and colleagues have identified a genetic pattern indicating broad addiction risk, they note that substance use-specific diagnoses still have meaning. "The current study validates previous findings of alcohol-specific risk variants, and, importantly, makes this finding in a very large and more diverse study population," said NIAAA Director George F. Koob, Ph.D. "The finding of shared genetic risk variants across different substance use disorders provides insight into some of the mechanisms that underlie these disorders and the relationships with other mental health conditions. Together the findings of alcohol-specific risk variants and common addiction-related variants provide powerful support for individualized prevention and treatment." <|im_end|>

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[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract More than three billion people rely on seafood for nutrition. However, fish are the predominant source of human exposure to methylmercury (MeHg), a potent neurotoxic substance. In the United States, 82% of population-wide exposure to MeHg is from the consumption of marine seafood and almost 40% is from fresh and canned tuna alone 1 . Around 80% of the inorganic mercury (Hg) that is emitted to the atmosphere from natural and human sources is deposited in the ocean 2 , where some is converted by microorganisms to MeHg. In predatory fish, environmental MeHg concentrations are amplified by a million times or more. Human exposure to MeHg has been associated with long-term neurocognitive deficits in children that persist into adulthood, with global costs to society that exceed US$20 billion 3 . The first global treaty on reductions in anthropogenic Hg emissions (the Minamata Convention on Mercury) entered into force in 2017. However, effects of ongoing changes in marine ecosystems on bioaccumulation of MeHg in marine predators that are frequently consumed by humans (for example, tuna, cod and swordfish) have not been considered when setting global policy targets. Here we use more than 30 years of data and ecosystem modelling to show that MeHg concentrations in Atlantic cod ( Gadus morhua ) increased by up to 23% between the 1970s and 2000s as a result of dietary shifts initiated by overfishing. Our model also predicts an estimated 56% increase in tissue MeHg concentrations in Atlantic bluefin tuna ( Thunnus thynnus ) due to increases in seawater temperature between a low point in 1969 and recent peak levels—which is consistent with 2017 observations. This estimated increase in tissue MeHg exceeds the modelled 22% reduction that was achieved in the late 1990s and 2000s as a result of decreased seawater MeHg concentrations. The recently reported plateau in global anthropogenic Hg emissions 4 suggests that ocean warming and fisheries management programmes will be major drivers of future MeHg concentrations in marine predators. Main The exploitation of fisheries in the northwestern Atlantic Ocean for hundreds of years has led to large fluctuations in herring, lobster and cod stocks, which has altered the structure of food webs and the availability of prey for remaining species 5 . We synthesized more than three decades of ecosystem data and MeHg concentrations in seawater, sediment and biological species that represent five trophic levels from the Gulf of Maine, a marginal sea in the northwestern Atlantic Ocean that has been exploited for commercial fisheries for more than 200 years. These data were used to develop and evaluate a mechanistic model for MeHg bioaccumulation that is based on bioenergetics and predator–prey interactions (see Methods ), to better understand the effects of ecosystem changes and overfishing 6 . A comparison of simulated MeHg concentrations based on extensive analysis of the stomach contents of two marine predators (Atlantic cod and spiny dogfish, Squalus acanthias ) in the 1970s and 2000s reveals that the effects of shifts in trophic structures caused by overfishing differed between these two species (Fig. 1a, b ). In the 1970s, cod consumed 8% more small clupeids than in the 2000s as a consequence of the overharvesting and reduced abundance of herring 7 . Simulated tissue MeHg concentrations in cod (larger than 10 kg) in the 1970s were 6–20% lower than for cod consuming a diet typical of the 2000s that relied more heavily on larger herring, lobster and other macroinvertebrates 7 . The 1970s diet for spiny dogfish when herring were limited included a higher proportion (around 20%) of squid and other cephalopods, which exhibit higher MeHg concentrations than many other prey fish. In contrast to cod, simulated MeHg concentrations in spiny dogfish were 33–61% higher in the 1970s than in the 2000s, when they consumed more herring and other clupeids 7 . These results illustrate that perturbations to the trophic structure of marine organisms from overfishing can have contrasting effects on MeHg concentrations across species. Such changes must therefore be assessed before concluding that temporal trends in biological MeHg concentrations reflect shifts in environmental Hg contamination. Fig. 1: Modelled effects of ecosystem change on MeHg concentrations in Atlantic cod and spiny dogfish. a , b , Differences in modelled MeHg concentrations in Atlantic cod ( a ) and spiny dogfish ( b ) based on a diet typical of the 1970s (dotted line) and the 2000s (solid line). Prey preferences for each time period were derived from the stomach contents of more than 2,000 fish 7 . c , d , Modelled changes in fish MeHg concentrations (relative to a diet typical of the 2000s) that result from a temperature increase of 1 °C; a shift in diet composition driven by overfishing of herring (represented by 1970s prey preferences when this last occurred); an assumed 20% decline in seawater MeHg concentration; the combination of both an increase in temperature and a decrease in seawater MeHg; and the simultaneous combination of all three factors. Source data Full size image Northward migration of the Gulf Stream and decadal oscillations in ocean circulation have led to unprecedented seawater warming in the Gulf of Maine between a low point in 1969 and 2015, which places this region in the top 1% of documented seawater temperature anomalies 8 . Both laboratory and field mesocosm data have demonstrated that rising temperatures lead to increases in MeHg concentrations in estuarine and freshwater fish 9 , 10 , but the magnitudes of potential changes in wild species are poorly understood. The effects of seawater warming are complicated by the narrow temperature niches of many marine fish species, which we account for in our food web model (see Methods ). Seawater warming of greater than 1–2 °C can lead to shifts in preferred foraging territory to higher latitudes or deeper in the water column, which alters the availability of prey for remaining species 11 . The effects of ecosystem changes on MeHg bioaccumulation vary across species and are not additive for predatory fish because of feeding relationships", "role": "user" }, { "content": "Add another item to the ever-growing list of the dangerous impacts of global climate change: Warming oceans are leading to an increase in the harmful neurotoxicant methylmercury in popular seafood, including cod, Atlantic bluefin tuna and swordfish, according to research led by the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Harvard T. H. Chan School of Public Health (HSPH). Researchers developed a first-of-its-kind, comprehensive model that simulates how environmental factors, including increasing sea temperatures and overfishing, impact levels of methylmercury in fish. The researchers found that while the regulation of mercury emissions have successfully reduced methylmercury levels in fish, spiking temperatures are driving those levels back up and will play a major role in the methylmercury levels of marine life in the future. The research is published in Nature. \"This research is a major advance in understanding how and why ocean predators, such as tuna and swordfish, are accumulating mercury,\" said Elsie Sunderland, the Gordon McKay Professor of Environmental Chemistry at SEAS and HSPH, and senior author of the paper. \"Being able to predict the future of mercury levels in fish is the holy grail of mercury research,\" said Amina Schartup, former research associate at SEAS and HSPH and first author of the paper. \"That question has been so difficult to answer because, until now, we didn't have a good understanding of why methylmercury levels were so high in big fish.\" It's been long understood that methylmercury, a type of organic mercury, bioaccumulates in food webs, meaning organisms at the top of the food chain have higher levels of methylmercury than those at the bottom. But to understand all the factors that influence the process, you have to understand how fish live. If you've ever owned a goldfish, you know that fish do pretty much two things: eat and swim. What they eat, how much they eat, and how much they swim all affect how much methylmercury fish will accumulate in the wild. Let's start with what fish eat. The researchers collected and analyzed 30 years of ecosystem data from the Gulf of Maine, including an extensive analysis of the stomach contents of two marine predators, Atlantic cod and spiny dogfish from the 1970s to 2000s. The researchers found that methylmercury levels in cod were 6 to 20 percent lower in 1970 than they were in 2000. Spiny dogfish, however, had levels 33 to 61 percent higher in 1970 compared to 2000 despite living in the same ecosystem and occupying a similar place in the food web. What accounts for these differences? A 1-degree increase in seawater temperature and a collapse in the herring population result in a 10-percent decrease in methylmercury levels in cod and a 70-percent increase in spiny dogfish. Credit: Harvard SEAS In the 1970s, the Gulf of Maine was experiencing a dramatic loss in herring population due to overfishing. Both cod and spiny dogfish eat herring. Without it, each turned to a different substitute. Cod ate other small fish such as shads and sardines, which are low in methylmercury. Spiny dogfish however, substituted herring with higher in methylmercury food such as squid and other cephalopods. When the herring population bounced back in 2000, cod reverted to a diet higher in methylmercury while spiny dogfish reverted to a diet lower in methylmercury. There's another factor that impacts what fish eat: mouth size. Unlike humans, fish can't chew—so most fish can only eat what fits in their mouth whole. However, there are a few exceptions. Swordfish, for example, use their titular bills to knock down large prey so they can eat it without resistance. Cephalopods catch prey with their tentacles and use their sharp beaks to rip off mouthfuls. \"There's always been a problem modeling methylmercury levels in organisms like cephalopods and swordfish because they don't follow typical bioaccumulation patterns based on their size,\" said Sunderland. \"Their unique feeding patterns means they can eat bigger prey, which means they're eating things that have bioaccumulated more methylmercury. We were able to represent that in our model.\" But what fish eat isn't the only thing that impacts their methylmercury levels. When Schartup was developing the model, she was having trouble accounting for the methylmercury levels in tuna, which are among the highest of all marine fish. Its place on the top of the food web accounts for part of this but doesn't fully explain just how high its levels are. Schartup solved that mystery with inspiration from an unlikely source: swimmer Michael Phelps. \"I was watching the Olympics and the TV commentators were talking about how Michael Phelps consumes 12,000 calories a day during the competition,\" Schartup remembered. \"I thought, that's six times more calories than I consume. If we were fish, he would be exposed to six times more methylmercury than me.\" As it turns out, high-speed hunters and migratory fish use a lot more energy than scavengers and other fish, which requires they consume more calories. \"These Michael Phelps-style fish eat a lot more for their size but, because they swim so much, they don't have compensatory growth that dilutes their body burden. So, you can model that as a function,\" said Schartup. A 20-percent decrease in emissions, with no change in seawater temps, decreases methylmercury levels in both cod and spiny dogfish by 20 percent. Credit: Harvard SEAS Another factor that comes into play is water temperature; as waters get warmer, fish use more energy to swim, which requires more calories. The Gulf of Maine is one of the fastest warming bodies of water in the world. The researchers found that between 2012 and 2017, methylmercury levels in Atlantic bluefin tuna increased by 3.5 percent per year despite decreasing emissions of mercury. Based on their model, the researchers predict that an increase of 1 degree Celsius in seawater temperature relative to the year 2000 would lead to a 32 percent increase in methylmercury levels in cod and a 70-percent increase in spiny dogfish. The model allows the researchers to simulate different scenarios at once. For example: A 1-degree increase in seawater temperature and a 20-percent decrease in mercury emissions result in increases in methylmercury levels of 10 percent in cod and 20 percent levels in spiny dogfish. A 1-degree increase in seawater temperature and a collapse in the herring population result in a 10-percent decrease in methylmercury levels in cod and a 70-percent increase in spiny dogfish. A 20-percent decrease in emissions, with no change in seawater temps, decreases methylmercury levels in both cod and spiny dogfish by 20 percent. \"This model allows us to look at all these different parameters at the same time, just as it happens in the real world,\" said Schartup. \"We have shown that the benefits of reducing mercury emissions holds, irrespective of what else is happening in the ecosystem. But if we want to continue the trend of reducing methylmercury exposure in the future, we need a two-pronged approach,\" said Sunderland. \"Climate change is going to exacerbate human exposure to methylmercury through seafood, so to protect ecosystems and human health, we need to regulate both mercury emissions and greenhouse gases.\" ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract More than three billion people rely on seafood for nutrition. However, fish are the predominant source of human exposure to methylmercury (MeHg), a potent neurotoxic substance. In the United States, 82% of population-wide exposure to MeHg is from the consumption of marine seafood and almost 40% is from fresh and canned tuna alone 1 . Around 80% of the inorganic mercury (Hg) that is emitted to the atmosphere from natural and human sources is deposited in the ocean 2 , where some is converted by microorganisms to MeHg. In predatory fish, environmental MeHg concentrations are amplified by a million times or more. Human exposure to MeHg has been associated with long-term neurocognitive deficits in children that persist into adulthood, with global costs to society that exceed US$20 billion 3 . The first global treaty on reductions in anthropogenic Hg emissions (the Minamata Convention on Mercury) entered into force in 2017. However, effects of ongoing changes in marine ecosystems on bioaccumulation of MeHg in marine predators that are frequently consumed by humans (for example, tuna, cod and swordfish) have not been considered when setting global policy targets. Here we use more than 30 years of data and ecosystem modelling to show that MeHg concentrations in Atlantic cod ( Gadus morhua ) increased by up to 23% between the 1970s and 2000s as a result of dietary shifts initiated by overfishing. Our model also predicts an estimated 56% increase in tissue MeHg concentrations in Atlantic bluefin tuna ( Thunnus thynnus ) due to increases in seawater temperature between a low point in 1969 and recent peak levels—which is consistent with 2017 observations. This estimated increase in tissue MeHg exceeds the modelled 22% reduction that was achieved in the late 1990s and 2000s as a result of decreased seawater MeHg concentrations. The recently reported plateau in global anthropogenic Hg emissions 4 suggests that ocean warming and fisheries management programmes will be major drivers of future MeHg concentrations in marine predators. Main The exploitation of fisheries in the northwestern Atlantic Ocean for hundreds of years has led to large fluctuations in herring, lobster and cod stocks, which has altered the structure of food webs and the availability of prey for remaining species 5 . We synthesized more than three decades of ecosystem data and MeHg concentrations in seawater, sediment and biological species that represent five trophic levels from the Gulf of Maine, a marginal sea in the northwestern Atlantic Ocean that has been exploited for commercial fisheries for more than 200 years. These data were used to develop and evaluate a mechanistic model for MeHg bioaccumulation that is based on bioenergetics and predator–prey interactions (see Methods ), to better understand the effects of ecosystem changes and overfishing 6 . A comparison of simulated MeHg concentrations based on extensive analysis of the stomach contents of two marine predators (Atlantic cod and spiny dogfish, Squalus acanthias ) in the 1970s and 2000s reveals that the effects of shifts in trophic structures caused by overfishing differed between these two species (Fig. 1a, b ). In the 1970s, cod consumed 8% more small clupeids than in the 2000s as a consequence of the overharvesting and reduced abundance of herring 7 . Simulated tissue MeHg concentrations in cod (larger than 10 kg) in the 1970s were 6–20% lower than for cod consuming a diet typical of the 2000s that relied more heavily on larger herring, lobster and other macroinvertebrates 7 . The 1970s diet for spiny dogfish when herring were limited included a higher proportion (around 20%) of squid and other cephalopods, which exhibit higher MeHg concentrations than many other prey fish. In contrast to cod, simulated MeHg concentrations in spiny dogfish were 33–61% higher in the 1970s than in the 2000s, when they consumed more herring and other clupeids 7 . These results illustrate that perturbations to the trophic structure of marine organisms from overfishing can have contrasting effects on MeHg concentrations across species. Such changes must therefore be assessed before concluding that temporal trends in biological MeHg concentrations reflect shifts in environmental Hg contamination. Fig. 1: Modelled effects of ecosystem change on MeHg concentrations in Atlantic cod and spiny dogfish. a , b , Differences in modelled MeHg concentrations in Atlantic cod ( a ) and spiny dogfish ( b ) based on a diet typical of the 1970s (dotted line) and the 2000s (solid line). Prey preferences for each time period were derived from the stomach contents of more than 2,000 fish 7 . c , d , Modelled changes in fish MeHg concentrations (relative to a diet typical of the 2000s) that result from a temperature increase of 1 °C; a shift in diet composition driven by overfishing of herring (represented by 1970s prey preferences when this last occurred); an assumed 20% decline in seawater MeHg concentration; the combination of both an increase in temperature and a decrease in seawater MeHg; and the simultaneous combination of all three factors. Source data Full size image Northward migration of the Gulf Stream and decadal oscillations in ocean circulation have led to unprecedented seawater warming in the Gulf of Maine between a low point in 1969 and 2015, which places this region in the top 1% of documented seawater temperature anomalies 8 . Both laboratory and field mesocosm data have demonstrated that rising temperatures lead to increases in MeHg concentrations in estuarine and freshwater fish 9 , 10 , but the magnitudes of potential changes in wild species are poorly understood. The effects of seawater warming are complicated by the narrow temperature niches of many marine fish species, which we account for in our food web model (see Methods ). Seawater warming of greater than 1–2 °C can lead to shifts in preferred foraging territory to higher latitudes or deeper in the water column, which alters the availability of prey for remaining species 11 . The effects of ecosystem changes on MeHg bioaccumulation vary across species and are not additive for predatory fish because of feeding relationships<|im_end|> <|im_start|>assistant Add another item to the ever-growing list of the dangerous impacts of global climate change: Warming oceans are leading to an increase in the harmful neurotoxicant methylmercury in popular seafood, including cod, Atlantic bluefin tuna and swordfish, according to research led by the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Harvard T. H. Chan School of Public Health (HSPH). Researchers developed a first-of-its-kind, comprehensive model that simulates how environmental factors, including increasing sea temperatures and overfishing, impact levels of methylmercury in fish. The researchers found that while the regulation of mercury emissions have successfully reduced methylmercury levels in fish, spiking temperatures are driving those levels back up and will play a major role in the methylmercury levels of marine life in the future. The research is published in Nature. "This research is a major advance in understanding how and why ocean predators, such as tuna and swordfish, are accumulating mercury," said Elsie Sunderland, the Gordon McKay Professor of Environmental Chemistry at SEAS and HSPH, and senior author of the paper. "Being able to predict the future of mercury levels in fish is the holy grail of mercury research," said Amina Schartup, former research associate at SEAS and HSPH and first author of the paper. "That question has been so difficult to answer because, until now, we didn't have a good understanding of why methylmercury levels were so high in big fish." It's been long understood that methylmercury, a type of organic mercury, bioaccumulates in food webs, meaning organisms at the top of the food chain have higher levels of methylmercury than those at the bottom. But to understand all the factors that influence the process, you have to understand how fish live. If you've ever owned a goldfish, you know that fish do pretty much two things: eat and swim. What they eat, how much they eat, and how much they swim all affect how much methylmercury fish will accumulate in the wild. Let's start with what fish eat. The researchers collected and analyzed 30 years of ecosystem data from the Gulf of Maine, including an extensive analysis of the stomach contents of two marine predators, Atlantic cod and spiny dogfish from the 1970s to 2000s. The researchers found that methylmercury levels in cod were 6 to 20 percent lower in 1970 than they were in 2000. Spiny dogfish, however, had levels 33 to 61 percent higher in 1970 compared to 2000 despite living in the same ecosystem and occupying a similar place in the food web. What accounts for these differences? A 1-degree increase in seawater temperature and a collapse in the herring population result in a 10-percent decrease in methylmercury levels in cod and a 70-percent increase in spiny dogfish. Credit: Harvard SEAS In the 1970s, the Gulf of Maine was experiencing a dramatic loss in herring population due to overfishing. Both cod and spiny dogfish eat herring. Without it, each turned to a different substitute. Cod ate other small fish such as shads and sardines, which are low in methylmercury. Spiny dogfish however, substituted herring with higher in methylmercury food such as squid and other cephalopods. When the herring population bounced back in 2000, cod reverted to a diet higher in methylmercury while spiny dogfish reverted to a diet lower in methylmercury. There's another factor that impacts what fish eat: mouth size. Unlike humans, fish can't chew—so most fish can only eat what fits in their mouth whole. However, there are a few exceptions. Swordfish, for example, use their titular bills to knock down large prey so they can eat it without resistance. Cephalopods catch prey with their tentacles and use their sharp beaks to rip off mouthfuls. "There's always been a problem modeling methylmercury levels in organisms like cephalopods and swordfish because they don't follow typical bioaccumulation patterns based on their size," said Sunderland. "Their unique feeding patterns means they can eat bigger prey, which means they're eating things that have bioaccumulated more methylmercury. We were able to represent that in our model." But what fish eat isn't the only thing that impacts their methylmercury levels. When Schartup was developing the model, she was having trouble accounting for the methylmercury levels in tuna, which are among the highest of all marine fish. Its place on the top of the food web accounts for part of this but doesn't fully explain just how high its levels are. Schartup solved that mystery with inspiration from an unlikely source: swimmer Michael Phelps. "I was watching the Olympics and the TV commentators were talking about how Michael Phelps consumes 12,000 calories a day during the competition," Schartup remembered. "I thought, that's six times more calories than I consume. If we were fish, he would be exposed to six times more methylmercury than me." As it turns out, high-speed hunters and migratory fish use a lot more energy than scavengers and other fish, which requires they consume more calories. "These Michael Phelps-style fish eat a lot more for their size but, because they swim so much, they don't have compensatory growth that dilutes their body burden. So, you can model that as a function," said Schartup. A 20-percent decrease in emissions, with no change in seawater temps, decreases methylmercury levels in both cod and spiny dogfish by 20 percent. Credit: Harvard SEAS Another factor that comes into play is water temperature; as waters get warmer, fish use more energy to swim, which requires more calories. The Gulf of Maine is one of the fastest warming bodies of water in the world. The researchers found that between 2012 and 2017, methylmercury levels in Atlantic bluefin tuna increased by 3.5 percent per year despite decreasing emissions of mercury. Based on their model, the researchers predict that an increase of 1 degree Celsius in seawater temperature relative to the year 2000 would lead to a 32 percent increase in methylmercury levels in cod and a 70-percent increase in spiny dogfish. The model allows the researchers to simulate different scenarios at once. For example: A 1-degree increase in seawater temperature and a 20-percent decrease in mercury emissions result in increases in methylmercury levels of 10 percent in cod and 20 percent levels in spiny dogfish. A 1-degree increase in seawater temperature and a collapse in the herring population result in a 10-percent decrease in methylmercury levels in cod and a 70-percent increase in spiny dogfish. A 20-percent decrease in emissions, with no change in seawater temps, decreases methylmercury levels in both cod and spiny dogfish by 20 percent. "This model allows us to look at all these different parameters at the same time, just as it happens in the real world," said Schartup. "We have shown that the benefits of reducing mercury emissions holds, irrespective of what else is happening in the ecosystem. But if we want to continue the trend of reducing methylmercury exposure in the future, we need a two-pronged approach," said Sunderland. "Climate change is going to exacerbate human exposure to methylmercury through seafood, so to protect ecosystems and human health, we need to regulate both mercury emissions and greenhouse gases." <|im_end|>

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30, 362, 220, 16, 38775, 5376, 304, 67329, 977, 9499, 323, 264, 18678, 304, 279, 305, 14782, 7187, 1121, 304, 264, 220, 605, 71724, 18979, 304, 79574, 1195, 26533, 5990, 304, 20950, 323, 264, 220, 2031, 71724, 5376, 304, 993, 6577, 5679, 18668, 13, 16666, 25, 25996, 5161, 1950, 763, 279, 220, 4468, 15, 82, 11, 279, 27945, 315, 30890, 574, 25051, 264, 22520, 4814, 304, 305, 14782, 7187, 4245, 311, 927, 69, 11218, 13, 11995, 20950, 323, 993, 6577, 5679, 18668, 8343, 305, 14782, 13, 17586, 433, 11, 1855, 6656, 311, 264, 2204, 28779, 13, 34777, 30912, 1023, 2678, 7795, 1778, 439, 559, 7819, 323, 274, 569, 1572, 11, 902, 527, 3428, 304, 79574, 1195, 26533, 13, 3165, 6577, 5679, 18668, 4869, 11, 63196, 305, 14782, 449, 5190, 304, 79574, 1195, 26533, 3691, 1778, 439, 90275, 323, 1023, 63190, 12130, 454, 30797, 13, 3277, 279, 305, 14782, 7187, 70904, 1203, 304, 220, 1049, 15, 11, 20950, 94693, 311, 264, 10173, 5190, 304, 79574, 1195, 26533, 1418, 993, 6577, 5679, 18668, 94693, 311, 264, 10173, 4827, 304, 79574, 1195, 26533, 13, 2684, 596, 2500, 8331, 430, 25949, 1148, 7795, 8343, 25, 11013, 1404, 13, 27140, 12966, 11, 7795, 649, 956, 37433, 2345, 708, 1455, 7795, 649, 1193, 8343, 1148, 18809, 304, 872, 11013, 4459, 13, 4452, 11, 1070, 527, 264, 2478, 20157, 13, 36751, 18668, 11, 369, 3187, 11, 1005, 872, 81205, 19123, 311, 14459, 1523, 3544, 37693, 779, 814, 649, 8343, 433, 2085, 13957, 13, 356, 752, 12130, 454, 30797, 2339, 37693, 449, 872, 16006, 18709, 323, 1005, 872, 17676, 387, 10011, 311, 24169, 1022, 11013, 1285, 82, 13, 330, 3947, 596, 2744, 1027, 264, 3575, 34579, 79574, 1195, 26533, 5990, 304, 44304, 1093, 63190, 12130, 454, 30797, 323, 20827, 18668, 1606, 814, 1541, 956, 1833, 14595, 17332, 40031, 2987, 12912, 3196, 389, 872, 1404, 1359, 1071, 83765, 13, 330, 35897, 5016, 26040, 12912, 3445, 814, 649, 8343, 11493, 37693, 11, 902, 3445, 814, 2351, 12459, 2574, 430, 617, 17332, 40031, 7913, 810, 79574, 1195, 26533, 13, 1226, 1051, 3025, 311, 4097, 430, 304, 1057, 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2,980

[ { "content": "You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it", "role": "system" }, { "content": "Abstract Strong electronic interactions in condensed-matter systems often lead to unusual quantum phases. One such phase occurs in the Kondo insulator YbB 12 , the insulating state of which exhibits phenomena that are characteristic of metals, such as magnetic quantum oscillations 1 , a gapless fermionic contribution to heat capacity 2 , 3 and itinerant-fermion thermal transport 3 . To understand these phenomena, it is informative to study their evolution as the energy gap of the Kondo insulator state is closed by a large magnetic field. Here we show that clear quantum oscillations are observed in the resulting high-field metallic state in YbB 12 ; this is despite it possessing relatively high resistivity, large effective masses and huge Kadowaki–Woods ratio, a combination that normally precludes quantum oscillations. Both quantum oscillation frequency and cyclotron mass display a strong field dependence. By tracking the Fermi surface area, we conclude that the same quasiparticle band gives rise to quantum oscillations in both insulating and metallic states. These data are understood most simply by using a two-fluid picture in which neutral quasiparticles—contributing little or nothing to charge transport—coexist with charged fermions. Our observations of the complex field-dependent behaviour of the fermion ensemble inhabiting YbB 12 provide strong constraints for existing theoretical models. Main In Kondo insulators (KIs), an energy gap is opened up by strong coupling between a lattice of localized moments and the extended electronic states. The resulting Kondo gap E g is usually narrow (typically E g ≃ 5–20 meV), yet the role it plays in charge transport is more complicated than that of the bandgap in conventional semiconductors. A low-temperature ( T ) saturation of resistivity has long been known in two prototypical KIs, namely, samarium hexaboride (SmB 6 ) and ytterbium dodecaboride (YbB 12 ) (refs. 4 , 5 ); both are mixed-valence compounds with strong f – d hybridization that defines the band structure close to the Fermi energy. While the saturation might suggest additional metallic conduction channels, the high resistivity value within the weakly T -dependent ‘plateau’ implies that these are highly unconventional 1 , 4 ; one interpretation is the presence of topologically protected surface states 6 . Recently, magnetic quantum oscillations, suggestive of a Fermi surface (FS) and thus totally unexpected in an insulator, have been detected in both SmB 6 and YbB 12 (refs. 1 , 7 , 8 , 9 , 10 ). Whilst some have attributed the oscillations in SmB 6 to residual flux 11 , the flux-free growth process of YbB 12 (Methods) excludes such a contribution. The oscillations in YbB 12 are observed in both resistivity ρ (the Shubnikov–de Haas (SdH) effect) and magnetization M (the de Haas–van Alphen (dHvA) effect) at applied magnetic fields H where the gap is still finite. The T dependence of the oscillation amplitude follows the Lifshitz–Kosevich (LK) formula, which is based on the Fermi liquid theory 1 . Moreover, a contribution from gapless quasiparticle excitations to the heat capacity C has been detected in both KIs 2 , 3 , 9 . Though the thermal transport observations remain controversial in SmB 6 9 , 12 , 13 , YbB 12 shows a T -linear zero-field thermal conductivity κ x x , a characteristic of itinerant fermions 3 . Agreement among the FS parameters derived from quantum oscillations, heat capacity and thermal conductivity in YbB 12 suggests that the same quasiparticle band is responsible 3 . Despite this apparent consistency, the mystery remains: how can itinerant fermions exist in a gapped insulator and transport heat but not charge? In response, many theoretical models entered the fray, including magnetoexcitons 14 , Majorana fermions 15 , 16 , emergent fractionalized quasiparticles 17 , 18 and non-Hermitian states 19 . As these scenarios frequently envisage some form of exotic in-gap states, it is potentially invaluable to observe how the properties of KIs evolve as the energy gap E g closes. The cubic rare-earth compound YbB 12 is an excellent platform to carry out such studies. In YbB 12 , the Kondo gap ( E g ≈ 15 meV (ref. 20 )) is closed by large H , leading to an insulator-to-metal (I–M) transition at fields ranging from μ 0 H I–M ≃ 45–47 T ( μ 0 is the vacuum permeability; field vector, H ∥ [100]) to 55–59 T ( H ∥ [110]) (refs. 1 , 21 , 22 ). As revealed by a large Sommerfeld coefficient γ of the heat capacity 2 , Kondo correlation does not break down at the I–M transition, remaining strong to 60 T and beyond in the high-field metallic state; hence, this can be termed a Kondo metal (KM) 23 . In this study, we apply both transport and thermodynamic measurements, including ρ , penetration depth, M and magnetostriction, to YbB 12 . By resolving quantum oscillations and tracking their T and H dependence in the KM state, we trace the fate of the possible neutral quasiparticles at fields above the gap closure and expose their interactions with more conventional charged fermions. In our YbB 12 samples, M and magnetostriction data show that the I–M transition occurs at μ 0 H I–M = 46.3 T ( H ∥ [100]); the tiny valence increase in Yb ions at the transition suggested by the magnetostriction reinforces the KM nature of the high-field metallic state (Methods and Extended Data Fig. 1 ). To probe the electronic structure of the KM state, a proximity detector oscillator (PDO) was used (Methods) for contactless SdH effect studies. The PDO technique is sensitive to the sample skin depth, providing a direct probe of changes in conductivity of the metallic KM state. The setup illustrated in the inset of Fig. 1a was rotated on a cryogenic goniometer to achieve H -orientation-dependent measurements. Fig. 1a summarizes the H dependence of the PDO frequency f as H rotates from [100] to [110]. Fig. 1: The SdH effect in YbB 12 . a , The PDO frequency f for a YbB 12 single-crystal sample,", "role": "user" }, { "content": "A recent series of experiments at the National High Magnetic Field Laboratory (National MagLab) at Los Alamos National Laboratory leveraged some of the nation's highest-powered nondestructive magnets to reveal an exotic new phase of matter at high magnetic fields. The experiments studied the unusual Kondo insulator ytterbium dodecaboride (or YbB12) and were the first results from the new 75-tesla duplex magnet housed at the National MagLab's Pulsed Field Facility at Los Alamos. \"This magnet and the resulting experiments are the first fruits of the National Science Foundation-supported pulsed magnet surge,\" said Michael Rabin, director of the Pulsed Field Facility at Los Alamos. \"The surge is creating new science capabilities in the 75-85 tesla range—leading eventually to an expanded portfolio of some of the most powerful nondestructive magnetic fields in the world.\" Researchers from the University of Michigan, Kyoto University and Los Alamos conducted the research, published last week in Nature Physics. In Kondo insulators, there is an unusual quantum-mechanical mixing of mobile electrons and magnetic atoms, making these materials attractive as model systems for basic science, electronic devices, and possibly quantum computing. Unlike simple metals and insulators, YbB12 exhibits properties of both—its electrical resistance behaves like that of an insulator, but it also clearly shows quantum oscillations at high magnetic fields that are a fundamental metallic property. \"A plethora of theories has emerged to account for such behavior,\" said John Singleton, a fellow at the MagLab's Los Alamos campus and co-author on the paper. \"Some physicists believe this is a condensed-matter incarnation of neutral Majorana fermions, entities normally explored in particle physics.\" To test these theories, the research team wanted to observe how the neutral fermions that they found in YbB12 responded to extreme conditions. The high magnetic fields in the new 75-tesla duplex magnet available at the National MagLab's Pulsed Field Facility were used to suppress the insulating properties of YbB12 and measure quantum oscillations and various properties that are affected by the presence of the neutral fermions. \"The extra 10 tesla above our standard pulsed magnets provided by the duplex magnet enabled this new state of matter—exotic fermions gradually being drowned in a sea of normal electrons—to be tracked across a wide range of magnetic fields for the first time,\" said Singleton. This confirmed that the phenomena observed were definitely associated with the neutral fermions and provided a test of the various theoretical models. The duplex magnet is a result of a Pulsed Field Facility \"magnet surge\" supported by the National Science Foundation. The purpose of the surge is to create new and expanded science capabilities in the 75-85 tesla range. The duplex magnet system is available to researchers from around the world to conduct their own experiments, and an 85-tesla duplex magnet and necessary supporting technology are under development. These new pulsed magnets are powered solely by capacitor banks without relying on the Los Alamos generator that powers the much larger 100 tesla magnet. The generator is currently offline for repairs and maintenance, so magnets from the surge fill an important gap for condensed-matter physics in high magnetic fields. The new magnets are called duplex magnets because they are made from two concentric electromagnet coils (solenoids) that are powered independently from separate capacitor-bank modules. When the generator is back online, technology developed by the pulsed magnet surge will be combined with Los Alamos' largest magnets to further expand the MagLab's science capabilities. ", "role": "assistant" } ]

<|im_start|>system You are a great journalist. Users will give you a scientific paper paper and ask you to write down a journalistic report of it<|im_end|> <|im_start|>user Abstract Strong electronic interactions in condensed-matter systems often lead to unusual quantum phases. One such phase occurs in the Kondo insulator YbB 12 , the insulating state of which exhibits phenomena that are characteristic of metals, such as magnetic quantum oscillations 1 , a gapless fermionic contribution to heat capacity 2 , 3 and itinerant-fermion thermal transport 3 . To understand these phenomena, it is informative to study their evolution as the energy gap of the Kondo insulator state is closed by a large magnetic field. Here we show that clear quantum oscillations are observed in the resulting high-field metallic state in YbB 12 ; this is despite it possessing relatively high resistivity, large effective masses and huge Kadowaki–Woods ratio, a combination that normally precludes quantum oscillations. Both quantum oscillation frequency and cyclotron mass display a strong field dependence. By tracking the Fermi surface area, we conclude that the same quasiparticle band gives rise to quantum oscillations in both insulating and metallic states. These data are understood most simply by using a two-fluid picture in which neutral quasiparticles—contributing little or nothing to charge transport—coexist with charged fermions. Our observations of the complex field-dependent behaviour of the fermion ensemble inhabiting YbB 12 provide strong constraints for existing theoretical models. Main In Kondo insulators (KIs), an energy gap is opened up by strong coupling between a lattice of localized moments and the extended electronic states. The resulting Kondo gap E g is usually narrow (typically E g ≃ 5–20 meV), yet the role it plays in charge transport is more complicated than that of the bandgap in conventional semiconductors. A low-temperature ( T ) saturation of resistivity has long been known in two prototypical KIs, namely, samarium hexaboride (SmB 6 ) and ytterbium dodecaboride (YbB 12 ) (refs. 4 , 5 ); both are mixed-valence compounds with strong f – d hybridization that defines the band structure close to the Fermi energy. While the saturation might suggest additional metallic conduction channels, the high resistivity value within the weakly T -dependent ‘plateau’ implies that these are highly unconventional 1 , 4 ; one interpretation is the presence of topologically protected surface states 6 . Recently, magnetic quantum oscillations, suggestive of a Fermi surface (FS) and thus totally unexpected in an insulator, have been detected in both SmB 6 and YbB 12 (refs. 1 , 7 , 8 , 9 , 10 ). Whilst some have attributed the oscillations in SmB 6 to residual flux 11 , the flux-free growth process of YbB 12 (Methods) excludes such a contribution. The oscillations in YbB 12 are observed in both resistivity ρ (the Shubnikov–de Haas (SdH) effect) and magnetization M (the de Haas–van Alphen (dHvA) effect) at applied magnetic fields H where the gap is still finite. The T dependence of the oscillation amplitude follows the Lifshitz–Kosevich (LK) formula, which is based on the Fermi liquid theory 1 . Moreover, a contribution from gapless quasiparticle excitations to the heat capacity C has been detected in both KIs 2 , 3 , 9 . Though the thermal transport observations remain controversial in SmB 6 9 , 12 , 13 , YbB 12 shows a T -linear zero-field thermal conductivity κ x x , a characteristic of itinerant fermions 3 . Agreement among the FS parameters derived from quantum oscillations, heat capacity and thermal conductivity in YbB 12 suggests that the same quasiparticle band is responsible 3 . Despite this apparent consistency, the mystery remains: how can itinerant fermions exist in a gapped insulator and transport heat but not charge? In response, many theoretical models entered the fray, including magnetoexcitons 14 , Majorana fermions 15 , 16 , emergent fractionalized quasiparticles 17 , 18 and non-Hermitian states 19 . As these scenarios frequently envisage some form of exotic in-gap states, it is potentially invaluable to observe how the properties of KIs evolve as the energy gap E g closes. The cubic rare-earth compound YbB 12 is an excellent platform to carry out such studies. In YbB 12 , the Kondo gap ( E g ≈ 15 meV (ref. 20 )) is closed by large H , leading to an insulator-to-metal (I–M) transition at fields ranging from μ 0 H I–M ≃ 45–47 T ( μ 0 is the vacuum permeability; field vector, H ∥ [100]) to 55–59 T ( H ∥ [110]) (refs. 1 , 21 , 22 ). As revealed by a large Sommerfeld coefficient γ of the heat capacity 2 , Kondo correlation does not break down at the I–M transition, remaining strong to 60 T and beyond in the high-field metallic state; hence, this can be termed a Kondo metal (KM) 23 . In this study, we apply both transport and thermodynamic measurements, including ρ , penetration depth, M and magnetostriction, to YbB 12 . By resolving quantum oscillations and tracking their T and H dependence in the KM state, we trace the fate of the possible neutral quasiparticles at fields above the gap closure and expose their interactions with more conventional charged fermions. In our YbB 12 samples, M and magnetostriction data show that the I–M transition occurs at μ 0 H I–M = 46.3 T ( H ∥ [100]); the tiny valence increase in Yb ions at the transition suggested by the magnetostriction reinforces the KM nature of the high-field metallic state (Methods and Extended Data Fig. 1 ). To probe the electronic structure of the KM state, a proximity detector oscillator (PDO) was used (Methods) for contactless SdH effect studies. The PDO technique is sensitive to the sample skin depth, providing a direct probe of changes in conductivity of the metallic KM state. The setup illustrated in the inset of Fig. 1a was rotated on a cryogenic goniometer to achieve H -orientation-dependent measurements. Fig. 1a summarizes the H dependence of the PDO frequency f as H rotates from [100] to [110]. Fig. 1: The SdH effect in YbB 12 . a , The PDO frequency f for a YbB 12 single-crystal sample,<|im_end|> <|im_start|>assistant A recent series of experiments at the National High Magnetic Field Laboratory (National MagLab) at Los Alamos National Laboratory leveraged some of the nation's highest-powered nondestructive magnets to reveal an exotic new phase of matter at high magnetic fields. The experiments studied the unusual Kondo insulator ytterbium dodecaboride (or YbB12) and were the first results from the new 75-tesla duplex magnet housed at the National MagLab's Pulsed Field Facility at Los Alamos. "This magnet and the resulting experiments are the first fruits of the National Science Foundation-supported pulsed magnet surge," said Michael Rabin, director of the Pulsed Field Facility at Los Alamos. "The surge is creating new science capabilities in the 75-85 tesla range—leading eventually to an expanded portfolio of some of the most powerful nondestructive magnetic fields in the world." Researchers from the University of Michigan, Kyoto University and Los Alamos conducted the research, published last week in Nature Physics. In Kondo insulators, there is an unusual quantum-mechanical mixing of mobile electrons and magnetic atoms, making these materials attractive as model systems for basic science, electronic devices, and possibly quantum computing. Unlike simple metals and insulators, YbB12 exhibits properties of both—its electrical resistance behaves like that of an insulator, but it also clearly shows quantum oscillations at high magnetic fields that are a fundamental metallic property. "A plethora of theories has emerged to account for such behavior," said John Singleton, a fellow at the MagLab's Los Alamos campus and co-author on the paper. "Some physicists believe this is a condensed-matter incarnation of neutral Majorana fermions, entities normally explored in particle physics." To test these theories, the research team wanted to observe how the neutral fermions that they found in YbB12 responded to extreme conditions. The high magnetic fields in the new 75-tesla duplex magnet available at the National MagLab's Pulsed Field Facility were used to suppress the insulating properties of YbB12 and measure quantum oscillations and various properties that are affected by the presence of the neutral fermions. "The extra 10 tesla above our standard pulsed magnets provided by the duplex magnet enabled this new state of matter—exotic fermions gradually being drowned in a sea of normal electrons—to be tracked across a wide range of magnetic fields for the first time," said Singleton. This confirmed that the phenomena observed were definitely associated with the neutral fermions and provided a test of the various theoretical models. The duplex magnet is a result of a Pulsed Field Facility "magnet surge" supported by the National Science Foundation. The purpose of the surge is to create new and expanded science capabilities in the 75-85 tesla range. The duplex magnet system is available to researchers from around the world to conduct their own experiments, and an 85-tesla duplex magnet and necessary supporting technology are under development. These new pulsed magnets are powered solely by capacitor banks without relying on the Los Alamos generator that powers the much larger 100 tesla magnet. The generator is currently offline for repairs and maintenance, so magnets from the surge fill an important gap for condensed-matter physics in high magnetic fields. The new magnets are called duplex magnets because they are made from two concentric electromagnet coils (solenoids) that are powered independently from separate capacitor-bank modules. When the generator is back online, technology developed by the pulsed magnet surge will be combined with Los Alamos' largest magnets to further expand the MagLab's science capabilities. <|im_end|>

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