bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical Mechanisms Controlling the Offshore Propagation of Convection in the Tropics: 2. Influence of Topography
Authors: Coppin David , Bellon Gilles 
Published: September 2019

AbstractA set of idealized convection‐permitting simulations is performed to investigate the influence of topography on the physical mechanisms responsible for the nocturnal offshore propagation of convection around tropical islands. All simulations have an idealized island in the middle of a long channel oceanic domain, with constant sea surface temperature and without rotation. To diagnose the impact of topography, we compare a flat island simulation with two simulations with mountain ranges of different shapes. The topography over the island has a strong impact on the diurnal cycle of convection as clouds tend to remain all day over the highest topography. This weakens the diurnal cycle and the land breeze front and triggers a comparatively less frequent long‐distance offshore propagation of convection. As in the flat simulation, the distance of offshore propagation is particularly sensitive to humidity and temperature at the top of the boundary layer. A shallow circulation that is asymmetric with respect to the island influences the boundary layer top humidity and can favor propagation on one side of the island or the other. These results mimic cloud and precipitation patterns observed prior to the Madden‐Julian Oscillation propagation over the Maritime Continent. The shape of the topography does not seem to influence the offshore propagation of convection significantly except for mountain‐valley breezes that reinforce the land breeze and the establishment of the asymmetric shallow circulation.
Mechanisms and disease implications of sirtuin-mediated autophagic regulation
Authors: Lee In Hye 
Published: September 2019

AbstractAccumulating evidence has indicated that sirtuins are key components of diverse physiological processes, including metabolism and aging. Sirtuins confer protection from a wide array of metabolic and age-related diseases, such as cancer, cardiovascular and neurodegenerative diseases. Recent studies have also suggested that sirtuins regulate autophagy, a protective cellular process for homeostatic maintenance in response to environmental stresses. Here, we describe various biological and pathophysiological processes regulated by sirtuin-mediated autophagy, focusing on cancer, heart, and liver diseases, as well as stem cell biology. This review also emphasizes key molecular mechanisms by which sirtuins regulate autophagy. Finally, we discuss novel insights into how new therapeutics targeting sirtuin and autophagy may potentially lead to effective strategies to combat aging and aging-related diseases.
Metaproteomics reveal that rapid perturbations in organic matter prioritize functional restructuring over taxonomy in western Arctic Ocean microbiomes
Authors: Mikan Molly P , Harvey H Rodger , Timmins-Schiffman Emma , Riffle Michael , May Damon H , Salter Ian , Noble William S , Nunn Brook L 
Published: September 2019

Abstract
We examined metaproteome profiles from two Arctic microbiomes during 10-day shipboard incubations to directly track early functional and taxonomic responses to a simulated algal bloom and an oligotrophic control. Using a novel peptide-based enrichment analysis, significant changes (p-value &lt; 0.01) in biological and molecular functions associated with carbon and nitrogen recycling were observed. Within the first day under both organic matter conditions, Bering Strait surface microbiomes increased protein synthesis, carbohydrate degradation, and cellular redox processes while decreasing C1 metabolism. Taxonomic assignments revealed that the core microbiome collectively responded to algal substrates by assimilating carbon before select taxa utilize and metabolize nitrogen intracellularly. Incubations of Chukchi Sea bottom water microbiomes showed similar, but delayed functional responses to identical treatments. Although 24 functional terms were shared between experimental treatments, the timing, and degree of the remaining responses were highly variable, showing that organic matter perturbation directs community functionality prior to alterations to the taxonomic distribution at the microbiome class level. The dynamic responses of these two oceanic microbial communities have important implications for timing and magnitude of responses to organic perturbations within the Arctic Ocean and how community-level functions may forecast biogeochemical gradients in oceans.
Electrophysiological evaluation of extracellular spermine and alkaline pH on synaptic human GABAA receptors
Authors: Limon A. , Delbruck E. , Yassine A. , Pandya D. , Myers R. M. , Barchas J. D. , Lee F. , Schatzberg  , Watson S. J. , Akil H. , Bunney W. E. , Vawter M. P. , Sequeira A. 
Published: September 2019

AbstractPolyamines have fundamental roles in brain homeostasis as key modulators of cellular excitability. Several studies have suggested alterations in polyamine metabolism in stress related disorders, suicide, depression, and neurodegeneration, making the pharmacological modulation of polyamines a highly appealing therapeutic strategy. Polyamines are small aliphatic molecules that can modulate cationic channels involved in neuronal excitability. Previous indirect evidence has suggested that polyamines can modulate anionic GABAA receptors (GABAARs), which mediate inhibitory signaling and provide a direct route to reduce hyperexcitability. Here, we attempted to characterize the effect that spermine, the polyamine with the strongest reported effect on GABAARs, has on human postmortem native GABAARs. We microtransplanted human synaptic membranes from the dorsolateral prefrontal cortex of four cases with no history of mental or neurological disorders, and directly recorded spermine effects on ionic GABAARs responses on microtransplanted oocytes. We show that in human synapses, inhibition of GABAARs by spermine was better explained by alkalization of the extracellular solution. Additionally, spermine had no effect on the potentiation of GABA-currents by diazepam, indicating that even if diazepam binding is enhanced by spermine, it does not translate to changes in functional activity. Our results clearly demonstrate that while extracellular spermine does not have direct effects on human native synaptic GABAARs, spermine-mediated shifts of pH inhibit GABAARs. Potential spermine-mediated increase of pH in synapses in vivo may therefore participate in increased neuronal activity observed during physiological and pathological states, and during metabolic alterations that increase the release of spermine to the extracellular milieu.
Retrotransposon insertions can initiate colorectal cancer and are associated with poor survival
Authors: Cajuso Tatiana , Sulo Päivi , Tanskanen Tomas , Katainen Riku , Taira Aurora , Hänninen Ulrika A. , Kondelin Johanna , Forsström Linda , Välimäki Niko , Aavikko Mervi , Kaasinen Eevi , Ristimäki Ari , Koskensalo Selja , Lepistö Anna , Renkonen-Sinisalo Laura , Seppälä Toni , Kuopio Teijo , Böhm Jan , Mecklin Jukka-Pekka , Kilpivaara Outi , Pitkänen Esa , Palin Kimmo , Aaltonen Lauri A. 
Published: September 2019

AbstractGenomic instability pathways in colorectal cancer (CRC) have been extensively studied, but the role of retrotransposition in colorectal carcinogenesis remains poorly understood. Although retrotransposons are usually repressed, they become active in several human cancers, in particular those of the gastrointestinal tract. Here we characterize retrotransposon insertions in 202 colorectal tumor whole genomes and investigate their associations with molecular and clinical characteristics. We find highly variable retrotransposon activity among tumors and identify recurrent insertions in 15 known cancer genes. In approximately 1% of the cases we identify insertions in APC, likely to be tumor-initiating events. Insertions are positively associated with the CpG island methylator phenotype and the genomic fraction of allelic imbalance. Clinically, high number of insertions is independently associated with poor disease-specific survival.
Caspase-11 signaling enhances graft-versus-host disease
Authors: Lu Yanyan , Meng Ran , Wang Xiangyu , Xu Yajing , Tang Yiting , Wu Jianfeng , Xue Qianqian , Yu Songlin , Duan Mingwu , Shan Dongyong , Wang Qingde , Wang Haichao , Billiar Timothy R. , Xiao Xianzhong , Chen Fangping , Lu Ben 
Published: September 2019

AbstractAcute graft-versus-host disease (GVHD) remains a major obstacle for the wider usage of allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is an effective therapy for hematopoietic malignancy. Here we show that caspase-11, the cytosolic receptor for bacterial endotoxin (lipopolysaccharide: LPS), enhances GVHD severity. Allo-HSCT markedly increases the LPS-caspase-11 interaction, leading to the cleavage of gasdermin D (GSDMD). Caspase-11 and GSDMD mediate the release of interleukin-1α (IL-1α) in allo-HSCT. Deletion of Caspase-11 or Gsdmd, inhibition of LPS-caspase-11 interaction, or neutralizing IL-1α uniformly reduces intestinal inflammation, tissue damage, donor T cell expansion and mortality in allo-HSCT. Importantly, Caspase-11 deficiency does not decrease the graft-versus-leukemia (GVL) activity, which is essential to prevent cancer relapse. These findings have major implications for allo-HSCT, as pharmacological interference with the caspase-11 signaling might reduce GVHD while preserving GVL activity.
Rapid metabolic shifts occur during the transition between hunger and satiety in Drosophila melanogaster
Authors: Wilinski Daniel , Winzeler Jasmine , Duren William , Persons Jenna L. , Holme Kristina J. , Mosquera Johan , Khabiri Morteza , Kinchen Jason M. , Freddolino Peter L. , Karnovsky Alla , Dus Monica 
Published: September 2019

AbstractMetabolites are active controllers of cellular physiology, but their role in complex behaviors is less clear. Here we report metabolic changes that occur during the transition between hunger and satiety in Drosophila melanogaster. To analyze these data in the context of fruit fly metabolic networks, we developed Flyscape, an open-access tool. We show that in response to eating, metabolic profiles change in quick, but distinct ways in the heads and bodies. Consumption of a high sugar diet dulls the metabolic and behavioral differences between the fasted and fed state, and reshapes the way nutrients are utilized upon eating. Specifically, we found that high dietary sugar increases TCA cycle activity, alters neurochemicals, and depletes 1-carbon metabolism and brain health metabolites N-acetyl-aspartate and kynurenine. Together, our work identifies the metabolic transitions that occur during hunger and satiation, and provides a platform to study the role of metabolites and diet in complex behavior.
Liquefaction of water on the surface of anisotropic two-dimensional atomic layered black phosphorus
Authors: Zhao Jinlai , Zhu Jiajie , Cao Rui , Wang Huide , Guo Zhinan , Sang David K. , Tang Jiaoning , Fan Dianyuan , Li Jianqing , Zhang Han 
Published: September 2019

AbstractThe growth and wetting of water on two-dimensional(2D) materials are important to understand the development of 2D material based electronic, optoelectronic, and nanomechanical devices. Here, we visualize the liquefaction processes of water on the surface of graphene, MoS2 and black phosphorus (BP) via optical microscopy. We show that the shape of the water droplets forming on the surface of BP, which is anisotropic, is elliptical. In contrast, droplets are rounded when they form on the surface of graphene or MoS2, which do not possess orthometric anisotropy. Molecular simulations show that the anisotropic liquefaction process of water on the surface of BP is attributed to the different binding energies of H2O molecules on BP along the armchair and zigzag directions. The results not only reveal the anisotropic nature of water liquefaction on the BP surface but also provide a way for fast and nondestructive determination of the crystalline orientation of BP.
Functional disease architectures reveal unique biological role of transposable elements
Authors: Hormozdiari Farhad , van de Geijn Bryce , Nasser Joseph , Weissbrod Omer , Gazal Steven , Ju Chelsea J. -T. , Connor Luke O’ , Hujoel Margaux L. A. , Engreitz Jesse , Hormozdiari Fereydoun , Price Alkes L. 
Published: September 2019

AbstractTransposable elements (TE) comprise roughly half of the human genome. Though initially derided as junk DNA, they have been widely hypothesized to contribute to the evolution of gene regulation. However, the contribution of TE to the genetic architecture of diseases remains unknown. Here, we analyze data from 41 independent diseases and complex traits to draw three conclusions. First, TE are uniquely informative for disease heritability. Despite overall depletion for heritability (54% of SNPs, 39 ± 2% of heritability), TE explain substantially more heritability than expected based on their depletion for known functional annotations. This implies that TE acquire function in ways that differ from known functional annotations. Second, older TE contribute more to disease heritability, consistent with acquiring biological function. Third, Short Interspersed Nuclear Elements (SINE) are far more enriched for blood traits than for other traits. Our results can help elucidate the biological roles that TE play in the genetic architecture of diseases.
Tropane alkaloids biosynthesis involves an unusual type III polyketide synthase and non-enzymatic condensation
Authors: Huang Jian-Ping , Fang Chengli , Ma Xiaoyan , Wang Li , Yang Jing , Luo Jianying , Yan Yijun , Zhang Yu , Huang Sheng-Xiong 
Published: September 2019

AbstractThe skeleton of tropane alkaloids is derived from ornithine-derived N-methylpyrrolinium and two malonyl-CoA units. The enzymatic mechanism that connects N-methylpyrrolinium and malonyl-CoA units remains unknown. Here, we report the characterization of three pyrrolidine ketide synthases (PYKS), AaPYKS, DsPYKS, and AbPYKS, from three different hyoscyamine- and scopolamine-producing plants. By examining the crystal structure and biochemical activity of AaPYKS, we show that the reaction mechanism involves PYKS-mediated malonyl-CoA condensation to generate a 3-oxo-glutaric acid intermediate that can undergo non-enzymatic Mannich-like condensation with N-methylpyrrolinium to yield the racemic 4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoic acid. This study therefore provides a long sought-after biosynthetic mechanism to explain condensation between N-methylpyrrolinium and acetate units and, more importantly, identifies an unusual plant type III polyketide synthase that can only catalyze one round of malonyl-CoA condensation.
Auxin-sensitive Aux/IAA proteins mediate drought tolerance in Arabidopsis by regulating glucosinolate levels
Authors: Salehin Mohammad , Li Baohua , Tang Michelle , Katz Ella , Song Liang , Ecker Joseph R. , Kliebenstein Daniel J. , Estelle Mark 
Published: September 2019

AbstractA detailed understanding of abiotic stress tolerance in plants is essential to provide food security in the face of increasingly harsh climatic conditions. Glucosinolates (GLSs) are secondary metabolites found in the Brassicaceae that protect plants from herbivory and pathogen attack. Here we report that in Arabidopsis, aliphatic GLS levels are regulated by the auxin-sensitive Aux/IAA repressors IAA5, IAA6, and IAA19. These proteins act in a transcriptional cascade that maintains expression of GLS levels when plants are exposed to drought conditions. Loss of IAA5/6/19 results in reduced GLS levels and decreased drought tolerance. Further, we show that this phenotype is associated with a defect in stomatal regulation. Application of GLS to the iaa5,6,19 mutants restores stomatal regulation and normal drought tolerance. GLS action is dependent on the receptor kinase GHR1, suggesting that GLS may signal via reactive oxygen species. These results provide a novel connection between auxin signaling, GLS levels and drought response.
Central nicotine induces browning through hypothalamic κ opioid receptor
Authors: Seoane-Collazo Patricia , Liñares-Pose Laura , Rial-Pensado Eva , Romero-Picó Amparo , Moreno-Navarrete José María , Martínez-Sánchez Noelia , Garrido-Gil Pablo , Iglesias-Rey Ramón , Morgan Donald A. , Tomasini Naoki , Malone Samuel Andrew , Senra Ana , Folgueira Cintia , Medina-Gomez Gema , Sobrino Tomás , Labandeira-García José L. , Nogueiras Rubén , Domingos Ana I. , Fernández-Real José-Manuel , Rahmouni Kamal , Diéguez Carlos , López Miguel 
Published: September 2019

AbstractIncreased body weight is a major factor that interferes with smoking cessation. Nicotine, the main bioactive compound in tobacco, has been demonstrated to have an impact on energy balance, since it affects both feeding and energy expenditure at the central level. Among the central actions of nicotine on body weight, much attention has been focused on its effect on brown adipose tissue (BAT) thermogenesis, though its effect on browning of white adipose tissue (WAT) is unclear. Here, we show that nicotine induces the browning of WAT through a central mechanism and that this effect is dependent on the κ opioid receptor (KOR), specifically in the lateral hypothalamic area (LHA). Consistent with these findings, smokers show higher levels of uncoupling protein 1 (UCP1) expression in WAT, which correlates with smoking status. These data demonstrate that central nicotine-induced modulation of WAT browning may be a target against human obesity.
Mechanism of centromere recruitment of the CENP-A chaperone HJURP and its implications for centromere licensing
Authors: Pan Dongqing , Walstein Kai , Take Annika , Bier David , Kaiser Nadine , Musacchio Andrea 
Published: September 2019

AbstractNucleosomes containing the histone H3 variant CENP-A are the epigenetic mark of centromeres, the kinetochore assembly sites required for chromosome segregation. HJURP is the CENP-A chaperone, which associates with Mis18α, Mis18β, and M18BP1 to target centromeres and deposit new CENP-A. How these proteins interact to promote CENP-A deposition remains poorly understood. Here we show that two repeats in human HJURP proposed to be functionally distinct are in fact interchangeable and bind concomitantly to the 4:2:2 Mis18α:Mis18β:M18BP1 complex without dissociating it. HJURP binds CENP-A:H4 dimers, and therefore assembly of CENP-A:H4 tetramers must be performed by two Mis18αβ:M18BP1:HJURP complexes, or by the same complex in consecutive rounds. The Mis18α N-terminal tails blockade two identical HJURP-repeat binding sites near the Mis18αβ C-terminal helices. These were identified by photo-cross-linking experiments and mutated to separate Mis18 from HJURP centromere recruitment. Our results identify molecular underpinnings of eukaryotic chromosome inheritance and shed light on how centromeres license CENP-A deposition.
Gene networks that compensate for crosstalk with crosstalk
Authors: Müller Isaak E. , Rubens Jacob R. , Jun Tomi , Graham Daniel , Xavier Ramnik , Lu Timothy K. 
Published: September 2019

AbstractCrosstalk is a major challenge to engineering sophisticated synthetic gene networks. A common approach is to insulate signal-transduction pathways by minimizing molecular-level crosstalk between endogenous and synthetic genetic components, but this strategy can be difficult to apply in the context of complex, natural gene networks and unknown interactions. Here, we show that synthetic gene networks can be engineered to compensate for crosstalk by integrating pathway signals, rather than by pathway insulation. We demonstrate this principle using reactive oxygen species (ROS)-responsive gene circuits in Escherichia coli that exhibit concentration-dependent crosstalk with non-cognate ROS. We quantitatively map the degree of crosstalk and design gene circuits that introduce compensatory crosstalk at the gene network level. The resulting gene network exhibits reduced crosstalk in the sensing of the two different ROS. Our results suggest that simple network motifs that compensate for pathway crosstalk can be used by biological networks to accurately interpret environmental signals.
Polyunsaturated fatty acid production by Yarrowia lipolytica employing designed myxobacterial PUFA synthases
Authors: Gemperlein Katja , Dietrich Demian , Kohlstedt Michael , Zipf Gregor , Bernauer Hubert S. , Wittmann Christoph , Wenzel Silke C. , Müller Rolf 
Published: September 2019

AbstractLong-chain polyunsaturated fatty acids (LC-PUFAs), particularly the omega-3 LC-PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), have been associated with beneficial health effects. Consequently, sustainable sources have to be developed to meet the increasing demand for these PUFAs. Here, we demonstrate the design and construction of artificial PUFA biosynthetic gene clusters (BGCs) encoding polyketide synthase-like PUFA synthases from myxobacteria adapted for the oleaginous yeast Yarrowia lipolytica. Genomic integration and heterologous expression of unmodified or hybrid PUFA BGCs yielded different yeast strains with specific LC-PUFA production profiles at promising yield and thus valuable for the biotechnological production of distinct PUFAs. Nutrient screening revealed a strong enhancement of PUFA production, when cells were phosphate limited. This represents, to the best of our knowledge, highest concentration of DHA (16.8 %) in total fatty acids among all published PUFA-producing Y. lipolytica strains.
ARID1A promotes genomic stability through protecting telomere cohesion
Authors: Zhao Bo , Lin Jianhuang , Rong Lijie , Wu Shuai , Deng Zhong , Fatkhutdinov Nail , Zundell Joseph , Fukumoto Takeshi , Liu Qin , Kossenkov Andrew , Jean Stephanie , Cadungog Mark G. , Borowsky Mark E. , Drapkin Ronny , Lieberman Paul M. , Abate-Shen Cory T. , Zhang Rugang 
Published: September 2019

AbstractARID1A inactivation causes mitotic defects. Paradoxically, cancers with high ARID1A mutation rates typically lack copy number alterations (CNAs). Here, we show that ARID1A inactivation causes defects in telomere cohesion, which selectively eliminates gross chromosome aberrations during mitosis. ARID1A promotes the expression of cohesin subunit STAG1 that is specifically required for telomere cohesion. ARID1A inactivation causes telomere damage that can be rescued by STAG1 expression. Colony formation capability of single cells in G2/M, but not G1 phase, is significantly reduced by ARID1A inactivation. This correlates with an increase in apoptosis and a reduction in tumor growth. Compared with ARID1A wild-type tumors, ARID1A-mutated tumors display significantly less CNAs across multiple cancer types. Together, these results show that ARID1A inactivation is selective against gross chromosome aberrations through causing defects in telomere cohesion, which reconciles the long-standing paradox between the role of ARID1A in maintaining mitotic integrity and the lack of genomic instability in ARID1A-mutated cancers.