bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tyrosyl phosphorylation of KRAS stalls GTPase cycle via alteration of switch I and II conformation
Authors: Kano Yoshihito , Gebregiworgis Teklab , Marshall Christopher B. , Radulovich Nikolina , Poon Betty P. K. , St-Germain Jonathan , Cook Jonathan D. , Valencia-Sama Ivette , Grant Benjamin M. M. , Herrera Silvia Gabriela , Miao Jinmin , Raught Brian , Irwin Meredith S. , Lee Jeffrey E. , Yeh Jen Jen , Zhang Zhong-Yin , Tsao Ming-Sound , Ikura Mitsuhiko , Ohh Michael 
Published: January 2019

AbstractDeregulation of the RAS GTPase cycle due to mutations in the three RAS genes is commonly associated with cancer development. Protein tyrosine phosphatase SHP2 promotes RAF-to-MAPK signaling pathway and is an essential factor in RAS-driven oncogenesis. Despite the emergence of SHP2 inhibitors for the treatment of cancers harbouring mutant KRAS, the mechanism underlying SHP2 activation of KRAS signaling remains unclear. Here we report tyrosyl-phosphorylation of endogenous RAS and demonstrate that KRAS phosphorylation via Src on Tyr32 and Tyr64 alters the conformation of switch I and II regions, which stalls multiple steps of the GTPase cycle and impairs binding to effectors. In contrast, SHP2 dephosphorylates KRAS, a process that is required to maintain dynamic canonical KRAS GTPase cycle. Notably, Src- and SHP2-mediated regulation of KRAS activity extends to oncogenic KRAS and the inhibition of SHP2 disrupts the phosphorylation cycle, shifting the equilibrium of the GTPase cycle towards the stalled ‘dark state’.
The mediodorsal pulvinar coordinates the macaque fronto-parietal network during rhythmic spatial attention
Authors: Fiebelkorn Ian C. , Pinsk Mark A. , Kastner Sabine 
Published: January 2019

AbstractSpatial attention is discontinuous, sampling behaviorally relevant locations in theta-rhythmic cycles (3–6 Hz). Underlying this rhythmic sampling are intrinsic theta oscillations in frontal and parietal cortices that provide a clocking mechanism for two alternating attentional states that are associated with either engagement at the presently attended location (and enhanced perceptual sensitivity) or disengagement (and diminished perceptual sensitivity). It has remained unclear, however, how these theta-dependent states are coordinated across the large-scale network that directs spatial attention. The pulvinar is a candidate for such coordination, having been previously shown to regulate cortical activity. Here, we examined pulvino-cortical interactions during theta-rhythmic sampling by simultaneously recording from macaque frontal eye fields (FEF), lateral intraparietal area (LIP), and pulvinar. Neural activity propagated from pulvinar to cortex during periods of engagement, and from cortex to pulvinar during periods of disengagement. A rhythmic reweighting of pulvino-cortical interactions thus defines functional dissociations in the attention network.
The structured backbone of temporal social ties
Authors: Kobayashi Teruyoshi , Takaguchi Taro , Barrat Alain 
Published: January 2019

AbstractIn many data sets, information on the structure and temporality of a system coexists with noise and non-essential elements. In networked systems for instance, some edges might be non-essential or exist only by chance. Filtering them out and extracting a set of relevant connections is a non-trivial task. Moreover, mehods put forward until now do not deal with time-resolved network data, which have become increasingly available. Here we develop a method for filtering temporal network data, by defining an adequate temporal null model that allows us to identify pairs of nodes having more interactions than expected given their activities: the significant ties. Moreover, our method can assign a significance to complex structures such as triads of simultaneous interactions, an impossible task for methods based on static representations. Our results hint at ways to represent temporal networks for use in data-driven models.
Optogenetic stimulation of medial prefrontal cortex Drd1 neurons produces rapid and long-lasting antidepressant effects
Authors: Hare Brendan D. , Shinohara Ryota , Liu Rong Jian , Pothula Santosh , DiLeone Ralph J. , Duman Ronald S. 
Published: January 2019

AbstractImpaired function in the medial prefrontal cortex (mPFC) contributes to depression, and the therapeutic response produced by novel rapid-acting antidepressants such as ketamine are mediated by mPFC activity. The mPFC contains multiple types of pyramidal cells, but it is unclear whether a particular subtype mediates the rapid antidepressant actions of ketamine. Here we tested two major subtypes, Drd1 and Drd2 dopamine receptor expressing pyramidal neurons and found that activating Drd1 expressing pyramidal cells in the mPFC produces rapid and long-lasting antidepressant and anxiolytic responses. In contrast, photostimulation of Drd2 expressing pyramidal cells was ineffective across anxiety-like and depression-like measures. Disruption of Drd1 activity also blocked the rapid antidepressant effects of ketamine. Finally, we demonstrate that stimulation of mPFC Drd1 terminals in the BLA recapitulates the antidepressant effects of somatic stimulation. These findings aid in understanding the cellular target neurons in the mPFC and the downstream circuitry involved in rapid antidepressant responses.
Biophysical feedback of global forest fires on surface temperature
Authors: Liu Zhihua , Ballantyne Ashley P. , Cooper L. Annie 
Published: January 2019

AbstractThe biophysical feedbacks of forest fire on Earth’s surface radiative budget remain uncertain at the global scale. Using satellite observations, we show that fire-induced forest loss accounts for about 15% of global forest loss, mostly in northern high latitudes. Forest fire increases surface temperature by 0.15 K (0.12 to 0.19 K) one year following fire in burned area globally. In high-latitudes, the initial positive climate-fire feedback was mainly attributed to reduced evapotranspiration and sustained for approximately 5 years. Over longer-term (> 5 years), increases in albedo dominated the surface radiative budget resulting in a net cooling effect. In tropical regions, fire had a long-term weaker warming effect mainly due to reduced evaporative cooling. Globally, biophysical feedbacks of fire-induced surface warming one year after fire are equivalent to 62% of warming due to annual fire-related CO2 emissions. Our results suggest that changes in the severity and/or frequency of fire disturbance may have strong impacts on Earth’s surface radiative budget and climate, especially at high latitudes.
Blood Biochemistry Analysis to Detect Smoking Status and Quantify Accelerated Aging in Smokers
Authors: Mamoshina Polina , Kochetov Kirill , Cortese Franco , Kovalchuk Anna , Aliper Alexander , Putin Evgeny , Scheibye-Knudsen Morten , Cantor Charles R. , Skjodt Neil M. , Kovalchuk Olga , Zhavoronkov Alex 
Published: January 2019

AbstractThere is an association between smoking and cancer, cardiovascular disease and all-cause mortality. However, currently, there are no affordable and informative tests for assessing the effects of smoking on the rate of biological aging. In this study we demonstrate for the first time that smoking status can be predicted using blood biochemistry and cell count results andthe recent advances in artificial intelligence (AI). By employing age-prediction models developed using supervised deep learning techniques, we found that smokers exhibited higher aging rates than nonsmokers, regardless of their cholesterol ratios and fasting glucose levels. We further used those models to quantify the acceleration of biological aging due to tobacco use. Female smokers were predicted to be twice as old as their chronological age compared to nonsmokers, whereas male smokers were predicted to be one and a half times as old as their chronological age compared to nonsmokers. Our findings suggest that deep learning analysis of routine blood tests could complement or even replace the current error-prone method of self-reporting of smoking status and could be expanded to assess the effect of other lifestyle and environmental factors on aging.
High-Throughput Video Processing of Heart Rate Responses in Multiple Wild-type Embryonic Zebrafish per Imaging Field
Authors: Martin W. Kyle , Tennant Alan H. , Conolly Rory B. , Prince Katya , Stevens Joey S , DeMarini David M. , Martin Brandi L. , Thompson Leslie C. , Gilmour M. Ian , Cascio Wayne E. , Hays Michael D. , Hazari Mehdi S. , Padilla Stephanie , Farraj Aimen K. 
Published: January 2019

AbstractHeart rate assays in wild-type zebrafish embryos have been limited to analysis of one embryo per video/imaging field. Here we present for the first time a platform for high-throughput derivation of heart rate from multiple zebrafish (Danio rerio) embryos per imaging field, which is capable of quickly processing thousands of videos and ideal for multi-well platforms with multiple fish/well. This approach relies on use of 2-day post fertilization wild-type embryos, and uses only bright-field imaging, circumventing requirement for anesthesia or restraint, costly software/hardware, or fluorescently-labeled animals. Our original scripts (1) locate the heart and record pixel intensity fluctuations generated by each cardiac cycle using a robust image processing routine, and (2) process intensity data to derive heart rate. To demonstrate assay utility, we exposed embryos to the drugs epinephrine and clonidine, which increased or decreased heart rate, respectively. Exposure to organic extracts of air pollution-derived particulate matter, including diesel or biodiesel exhausts, or wood smoke, all complex environmental mixtures, decreased heart rate to varying degrees. Comparison against an established lower-throughput method indicated robust assay fidelity. As all code and executable files are publicly available, this approach may expedite cardiotoxicity screening of compounds as diverse as small molecule drugs and complex chemical mixtures.
Genetically diverse Plasmodium falciparum infections, within-host competition and symptomatic malaria in humans
Authors: Sondo Paul , Derra Karim , Lefevre Thierry , Diallo-Nakanabo Seydou , Tarnagda Zekiba , Zampa Odile , Kazienga Adama , Valea Innocent , Sorgho Hermann , Ouedraogo Jean-Bosco , Guiguemde Tinga Robert , Tinto Halidou 
Published: January 2019

AbstractThere is a large genetic diversity of Plasmodium falciparum strains that infect people causing diverse malaria symptoms. This study was carried out to explore the effect of mixed-strain infections and the extent to which some specific P. falciparum variants are associated with particular malaria symptoms. P. falciparum isolates collected during pharmacovigilance study in Nanoro, Burkina Faso were used to determine allelic variation in two polymorphic antigens of the merozoite surface (msp1 and msp2). Overall, parasite density did not increase with additional strains, suggesting the existence of within-host competition. Parasite density was influenced by msp1 allelic families with highest parasitaemia observed in MAD20 allelic family. However, when in mixed infections with allelic family K1, MAD20 could not grow to the same levels as it would alone, suggesting competitive suppression in these mixed infections. Host age was associated with parasite density. Overall, older patients exhibited lower parasite densities than younger patients, but this effect varied with the genetic composition of the isolates for the msp1 gene. There was no effect of msp1 and msp2 allelic family variation on body temperature. Haemoglobin level was influenced by msp2 family with patients harboring the FC27 allele showing lower haemoglobin level than mono-infected individuals by the 3D7 allele. This study provides evidence that P. falciparum genetic diversity influenced the severity of particular malaria symptoms and supports the existence of within-host competition in genetically diverse P. falciparum.
High-risk infrastructure projects pose imminent threats to forests in Indonesian Borneo
Authors: Alamgir Mohammed , Campbell Mason J. , Sloan Sean , Suhardiman Ali , Supriatna Jatna , Laurance William F. 
Published: January 2019

AbstractIndonesian Borneo (Kalimantan) sustains ~37 million hectares of native tropical forest. Numerous large-scale infrastructure projects aimed at promoting land-development activities are planned or ongoing in the region. However, little is known of the potential impacts of this new infrastructure on Bornean forests or biodiversity. We found that planned and ongoing road and rail-line developments will have many detrimental ecological impacts, including fragmenting large expanses of intact forest. Assuming conservatively that new road and rail projects will influence only a 1 km buffer on either side, landscape connectivity across the region will decline sharply (from 89% to 55%) if all imminently planned projects proceed. This will have particularly large impacts on wide-ranging, rare species such as rhinoceros, orangutans, and elephants. Planned developments will impact 42 protected areas, undermining Indonesian efforts to achieve key targets under the Convention on Biological Diversity. New infrastructure will accelerate expansion in intact or frontier regions of legal and illegal logging and land colonization as well as illicit mining and wildlife poaching. The net environmental, social, financial, and economic risks of several imminent projects—such as parallel border roads in West, East, and North Kalimantan, new Trans-Kalimantan road developments in Central Kalimantan and North Kalimantan, and freeways and rail lines in East Kalimantan—could markedly outstrip their overall benefits. Such projects should be reconsidered in light of rigorous cost-benefit frameworks.
Downregulated Caveolin-1 expression in circulating monocytes may contribute to the pathogenesis of psoriasis
Authors: Takamura Naoko , Yamaguchi Yukie , Watanabe Yuko , Asami Miho , Komitsu Noriko , Aihara Michiko 
Published: January 2019

AbstractCaveolin-1 (CAV-1) is the principal component of caveolae that regulates a variety of signaling molecules and receptors. Our previous study revealed CAV-1 reduction in the epidermis of patients with psoriasis, which leads to enhanced Janus kinase/signal transducer and activator of transcription activation and cytokine production, suggesting that aberrant CAV-1 expression may contribute to psoriatic inflammation. This study aimed to investigate whether abnormal modulation of CAV-1 on immune cells is involved in the pathogenesis of psoriasis. We observed that CAV-1 level in psoriasis patients was apparently reduced in peripheral blood mononuclear cells (PBMCs) and it was prominent in CD14+ monocytes. CAV-1 silencing in monocytes represented elevated levels of interleukin (IL)-1β and IL-6, and those had enhanced chemotaxis activity. In a murine model of psoriasis-like inflammation induced by imiquimod, we observed a significant CAV-1 reduction in PBMCs. Systemic administration of CAV-1 scaffolding domain peptide significantly improved the skin phenotype with less macrophage infiltration. Taken together, aberrant CAV-1 expression in monocytes may be involved in the pathogenesis of psoriasis.
Submarine Landslides Induce Massive Waves in Subsea Brine Pools
Authors: Sawyer Derek E. , Mason R. Alan , Cook Ann E. , Portnov Alexey 
Published: January 2019

AbstractSubsea hypersaline anoxic brine pools are among the most extreme habitable environments on Earth that offer clues to life on other planets. Brine is toxic to macrofauna as remotely operated vehicles commonly observe dead and preserved remains in brine pools. While brine pools are often assumed to be stable stratified systems, we show that underwater landslides can cause significant disturbances. Moreover, landslides create large-amplitude waves upon impact with the brine pool, similar to tsunami waves. We focus on the Orca Basin brine pool in the deepwater Gulf of Mexico, which contains numerous landslide deposits and blocks that originated from scarps several hundred meters above the brine pool. The impact of massive fast-moving landslides generated waves with amplitude on the order of 100 s of meters, which rival the largest known ocean waves. Brine waves can negatively affect biological communities and potentially overspill to spread hypersaline brine into surrounding basins.
Effect of standard light illumination on electrolyte’s stability of lithium-ion batteries based on ethylene and di-methyl carbonates
Authors: Bouteau Gaspard , Van-Nhien Albert Nguyen , Sliwa Michel , Sergent Nicolas , Lepretre Jean-Claude , Gachot Grégory , Sagaidak Iryna , Sauvage Frédéric 
Published: January 2019

AbstractCombining energy conversion and storage at a device and/or at a molecular level constitutes a new research field raising interest. This work aims at investigating how prolonged standard light exposure (A.M. 1.5G) interacts with conventional batteries electrolyte, commonly used in the photo-assisted or photo-rechargeable batteries, based on 1 mol.L−1 LiPF6 EC/DMC electrolyte. We demonstrate the intrinsic chemical robustness of this class of electrolyte in absence of any photo-electrodes. However, based on different steady-state and time-resolved spectroscopic techniques, it is for the first time highlighted that the solvation of lithium and hexafluorophosphate ions by the carbonates are modified by light exposure leading to absorbance and ionic conductivity modifications without detrimental effects onto the electrochemical properties.
Bile acid supplementation decreases body mass gain in C57BL/6J but not 129S6/SvEvTac mice without increasing energy expenditure
Authors: Fromme Tobias , Hüttinger Kristina , Maurer Stefanie , Li Yongguo , Gantert Thomas , Fiamoncini Jarlei , Daniel Hannelore , Westphal Sören , Klingenspor Martin 
Published: January 2019

AbstractSupplementation of cholate to a high fat diet can protect mice from diet-induced, increased body mass gain. It has been hypothesized that uncoupling protein 1 dependent, non-shivering thermogenesis in brown adipocytes provides the mechanism of increased energy expenditure to counteract excessive energy intake. We scrutinized this conjecture in wildtype mice and mice genetically devoid of a functional uncoupling protein 1 gene (C57BL/6J) as well as mice of the 129S6/SvEvTac strain that, in comparison, display an extraordinary capacity to recruit ectopic brown adipocytes. Protection from diet-induced, increased body mass gain by cholate supplementation was absent in 129S6/SvEvTac mice, a consequence of much lower bile acid absorption and spillover in this strain. Conversely, Ucp1-KO mice did not differ from C57BL/6J wildtype controls in any parameter assessed. Daily energy expenditure and resting metabolic rate of C57BL/6J mice remained unaffected by cholate supplementation. We conclude that protection of mice from diet-induced, increased body mass gain by cholate supplementation depends on the specific genetic background of C57BL/6J mice, does not involve increased energy expenditure and is independent of uncoupling protein 1 dependent non-shivering thermogenesis.
HOXD8/DIAPH2-AS1 epigenetically regulates PAX3 and impairs HTR-8/SVneo cell function under hypoxia
Authors: Feng Yaling , Wang Jianxia , He Yue , Zhang Heng , Jiang Minhui , Cao Dandan , Wang Aiping 
Published: January 2019

Abstract
The present study aimed to unravel the molecular basis underlying PAX3 down-regulation, known to be involved in pre-eclampsia (PE) occurrence and development. Data obtained from databases suggested that Pax3 methylation levels in the promoter region are high in the placentas of PE patients. However, the expression of methylation-adjusting enzymes, including DNMT1, LSD1, and EZH2, did not change. Since lncRNAs enhance the function of methylation-related enzymes independently of expression, we selected three lncRNAs, RP11-269F21.2, DIAPH2-AS1, and RP11-445K13.2, predicted to interact with methylation-adjusting enzymes. Two transcription factors, HOXD8 and Lhx3, predicted to regulate the expression of lncRNAs, were also selected. Using RNA interference technology, HOXD8 and Lhx3 were found to positively regulate DIAPH2-AS1 and RP11-445K13.2 in HTR-8/SVneo cells. Chromatin immunoprecipitation assays determined that DIAPH2-AS1 recruited LSD1 to histone 3, increasing DNMT1 stability at H3. The HOXD8/DIAPH2-AS1 network regulated HTR-8/SVneo cell function under hypoxia by epigenetically regulating PAX3. This regulatory network may thus be responsible for PAX3 down-regulation in the placentas of PE patients.
Possibility of chromospheric back-radiation influencing the lithium line formation in Spite plateau stars
Authors: Takeda Y. 
Published: January 2019

Context.Spectroscopically determined lithium abundances of metal-poor turn-off dwarfs are known to be nearly constant (Spite plateau), but manifestly lower than the primordial value expected from the standard cosmological model. However, abundance determination by using conventional model atmospheres may not necessarily be correct since the existence of high-temperature chromosphere even in very old stars has been confirmed.Aims.The aim of this study is to examine how the extra UV flux possibly irradiated from the chromosphere could affect the formation of the Li I6708 line, and whether or not its influence might lead to a solution of the Li abundance discrepancy.Methods.A simple model chromosphere of a uniform thin gray slab emitting only thermal radiation is assumed, characterized by optical thickness and temperature. By taking into account this incident radiation in the surface boundary condition, non-local thermodynamical equilibrium calculations for neutral Li atoms are carried out in order to see how the equivalent widths and the resulting abundances are affected by these parameters.Results.If the parameters are appropriately chosen, the strength of the Li I6708 line can be reduced by a factor of ~2–3 due to overionization caused by enhanced UV radiation, leading to an apparent lowering of the abundance by ~0.3–0.5 dex, which is consistent with the discrepancy in question. Moreover, the observed slight metallicity-dependent trend of the plateau can also be reproduced as a result of the change in atmospheric transparency.Conclusions.Superficial underestimation of Li abundances due to considerable overionization caused by chromospheric radiation may be regarded as a ponderable interpretation for the cosmological Li problem. The touchstone to verify this model would be to check the existence of significantly enhanced UV radiation in these Spite plateau stars, which should be detected if this scenario is valid, although very few such UV spectrophotometric observations have been done to date.