bluuebunny/crossref_metadata_2025_split huggingface dataset:
Large‐Scale Circulation Environment and Microphysical Characteristics of the Cloud Systems Over the Tibetan Plateau in Boreal Summer
Authors: Chen Jinghua , Wu Xiaoqing , Yin Yan , Lu Chunsong 
Published: April 2020

AbstractThe Tibetan Plateau (TP) experiences a particular dynamical and thermal environment due to its unique topography, which could affect the generation and development of its cloud and precipitation. Statistical results of 52‐year daily precipitation (1961 to 2012) show that the most frequent daily precipitation is about 3 mm day−1 over the eastern TP (ETP) in the warm season while it is less than 1 mm day−1 over the western TP (WTP). Circulation patterns for rainy and rainless conditions over both the ETP and WTP are investigated. The results show that the rainy weather over the TP is usually related to the moisture transported from the warm ocean by the southerly flow. Moreover, rainy weather in WTP can only appear when the strong southerly flow prevails over the Indian subcontinent. When the south flow is weak, the rainy weather can still develop in ETP under favorable conditions due to the local madid environment. CloudSat observations show that the strong convective system can extend to a level as high as 16 km above the sea level with a favorable dynamical and thermal environment. However, the depth of most precipitating convective clouds over the TP is in a range of 6–9 km. Due to the wetter condition, the precipitating convective cloud holds a lower cloud base in August in ETP than WTP. Compared with other regions, the precipitating convective clouds in both the ETP and WTP are thinner in cloud depth, smaller in cloud particles and weaker in precipitation capacity.
AE, DST, and Their SuperMAG Counterparts: The Effect of Improved Spatial Resolution in Geomagnetic Indices
Authors: Bergin A. , Chapman S. C. , Gjerloev J. W. 
Published: April 2020

AbstractFor decades, geomagnetic indices have been used extensively to parameterize space weather events, as input to various models and as space weather specifications. The auroral electrojet (AE) index and disturbance storm time index (DST) are two such indices that span multiple solar cycles and have been widely studied. The production of improved spatial coverage analogs to AE and DST is now possible using the SuperMAG collaboration of ground‐based magnetometers. SME is an electrojet index that shares methodology with AE. SMR is a ring current index that shares methodology with DST. As the number of magnetometer stations in the SuperMAG network increases over time, so does the spatial resolution of SME and SMR. Our statistical comparison between the established indices and their new SuperMAG counterparts finds that, for large excursions in geomagnetic activity, AE systematically underestimates SME for later cycles. The difference between distributions of recorded AE and SME values for a single solar maximum can be of the same order as changes in activity seen from one solar cycle to the next. We demonstrate that DST and SMR track each other but are subject to an approximate linear shift as a result of the procedure used to map stations to the magnetic equator. We explain the observed differences between AE and SME with the assistance of a simple model, based on the construction methodology of the electrojet indices. We show that in the case of AE and SME, it is not possible to simply translate between the two indices.
Hydrologically Induced Deformation in Long Valley Caldera and Adjacent Sierra Nevada
Authors: Silverii F. , Montgomery-Brown E. K. , Borsa A. A. , Barbour A. J. 
Published: April 2020

AbstractVertical and horizontal components of GNSS displacements in the Long Valley Caldera and adjacent Sierra Nevada range show a clear correlation with hydrological trends at both multiyear and seasonal time scales. We observe a clear vertical and horizontal seasonal deformation pattern primarily attributable to the solid earth response to hydrological surface loading at large‐to‐regional (Sierra Nevada range) scales. Several GNSS sites, located at the eastern edge of the Sierra Nevada along the southwestern rim of Long Valley Caldera, also show significant horizontal deformation that cannot be explained by elastic deformation from surface loading. Due to the location of these sites and the strong correlation between their horizontal displacements and spring discharge, we hypothesize that this deformation reflects poroelastic processes related to snowmelt runoff water infiltrating into the Sierra Nevada slopes around Long Valley Caldera. Interestingly, this is also an area where water infiltrates to feed the local hydrothermal system, and where snowmelt‐induced earthquake swarms have been recently detected.
miR-486-3p mediates hepatocellular carcinoma sorafenib resistance by targeting FGFR4 and EGFR
Authors: Ji Lin , Lin Zhongjie , Wan Zhe , Xia Shunjie , Jiang Shi , Cen Dong , Cai Liuxin , Xu Junjie , Cai Xiujun 
Published: April 2020

AbstractHCC is a common malignancy worldwide and surgery or reginal treatments are deemed insufficient for advanced-stage disease. Sorafenib is an inhibitor of many kinases and was shown to benefit advanced HCC patients. However, resistance emerges soon after initial treatment, limiting the clinical benefit of sorafenib, and the mechanisms still remain elusive. Thus, this study aims to investigate the mechanisms of sorafenib resistance and to provide possible targets for combination therapies. Through miRNA sequencing, we found that miR-486-3p was downregulated in sorafenib resistant HCC cell lines. Cell viability experiments showed increased miR-486-3p expression could induce cell apoptosis while miR-486-3p knockdown by CRISPR-CAS9 technique could reduce cell apoptosis in sorafenib treatment. Clinical data also indicated that miR-486-3p level was downregulated in tumor tissue compared with adjacent normal tissue in HCC patients. Mechanism dissections showed that FGFR4 and EGFR were the targets of miR-486-3p, which was verified by luciferase reporter assay. Importantly, FGFR4 or EGFR selective inhibitor could enhance sorafenib efficacy in the resistant cells. Moreover, in vivo sorafenib resistant model identified that over-expressing miR-486-3p by lentivirus injection could overcome sorafenib resistance by significantly suppressing tumor growth in combination with the treatment of sorafenib. In conclusion, we found miR-486-3p was an important mediator regulating sorafenib resistance by targeting FGFR4 and EGFR, thus offering a potential target for HCC treatment.
Loss of AKAP1 triggers Drp1 dephosphorylation-mediated mitochondrial fission and loss in retinal ganglion cells
Authors: Edwards Genea , Perkins Guy A. , Kim Keun-Young , Kong YeEun , Lee Yonghoon , Choi Soo-Ho , Liu Yujia , Skowronska-Krawczyk Dorota , Weinreb Robert N. , Zangwill Linda , Strack Stefan , Ju Won-Kyu 
Published: April 2020

AbstractImpairment of mitochondrial structure and function is strongly linked to glaucoma pathogenesis. Despite the widely appreciated disease relevance of mitochondrial dysfunction and loss, the molecular mechanisms underlying mitochondrial fragmentation and metabolic stress in glaucoma are poorly understood. We demonstrate here that glaucomatous retinal ganglion cells (RGCs) show loss of A-kinase anchoring protein 1 (AKAP1), activation of calcineurin (CaN) and reduction of dynamin-related protein 1 (Drp1) phosphorylation at serine 637 (Ser637). These findings suggest that AKAP1-mediated phosphorylation of Drp1 at Ser637 has a critical role in RGC survival in glaucomatous neurodegeneration. Male mice lacking AKAP1 show increases in CaN and total Drp1 levels, as well as a decrease in Drp1 phosphorylation at Ser637 in the retina. Ultrastructural analysis of mitochondria shows that loss of AKAP1 triggers mitochondrial fragmentation and loss, as well as mitophagosome formation in RGCs. Loss of AKAP1 deregulates oxidative phosphorylation (OXPHOS) complexes (Cxs) by increasing CxII and decreasing CxIII-V, leading to metabolic and oxidative stress. Also, loss of AKAP1 decreases Akt phosphorylation at Serine 473 (Ser473) and threonine 308 (Thr308) and activates the Bim/Bax signaling pathway in the retina. These results suggest that loss of AKAP1 has a critical role in RGC dysfunction by decreasing Drp1 phosphorylation at Ser637, deregulating OXPHOS, decreasing Akt phosphorylation at Ser473 and Thr308, and activating the Bim/Bax pathway in glaucomatous neurodegeneration. Thus, we propose that overexpression of AKAP1 or modulation of Drp1 phosphorylation at Ser637 are potential therapeutic strategies for neuroprotective intervention in glaucoma and other mitochondria-related optic neuropathies.
Measurement and models accounting for cell death capture hidden variation in compound response
Authors: Bae Song Yi , Guan Ning , Yan Rui , Warner Katrina , Taylor Scott D. , Meyer Aaron S. 
Published: April 2020

AbstractCancer cell sensitivity or resistance is almost universally quantified through a direct or surrogate measure of cell number. However, compound responses can occur through many distinct phenotypic outcomes, including changes in cell growth, apoptosis, and non-apoptotic cell death. These outcomes have divergent effects on the tumor microenvironment, immune response, and resistance mechanisms. Here, we show that quantifying cell viability alone is insufficient to distinguish between these compound responses. Using an alternative assay and drug-response analysis amenable to high-throughput measurement, we find that compounds with identical viability outcomes can have very different effects on cell growth and death. Moreover, additive compound pairs with distinct growth/death effects can appear synergistic when only assessed by viability. Overall, these results demonstrate an approach to incorporating measurements of cell death when characterizing a pharmacologic response.
HSD11B1 is upregulated synergistically by IFNγ and TNFα and mediates TSG-6 expression in human UC-MSCs
Authors: Huang Peiqing , Li Yinghong , Xu Chenchang , Melino Gerry , Shao Changshun , Shi Yufang 
Published: April 2020

AbstractInflammatory factors such as IFNγ and TNFα could endow mesenchymal stem cells (MSCs) a potent immunomodulatory property, a process called licensing, but the mechanisms are not fully understood. We here found that glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive cortisone to the active cortisol and thereby regulates tissue glucocorticoid (GC) levels, was greatly upregulated by IFNγ and TNFα in human umbilical cord-derived MSCs (UC-MSCs) in a synergistic manner. While IFNγ alone was not able to induce HSD11B1, it could increase the activity of NF-kB and thus augment the upregulation of HSD11B1 by TNFα. Interestingly, the upregulation of HSD11B1 by IFNγ and TNFα also required glucocorticoid receptor. Furthermore, HSD11B1 was shown to be required for the expression of TNF-stimulated gene 6 (TSG-6), an important anti-inflammatory effector molecule of MSCs. Therefore, the inflammatory factors IFNγ and TNFα can promote GC metabolism and thereby drive the expression of anti-inflammatory factor TSG-6 in human UC-MSCs, forming a potential negative feedback loop. These findings help to understand the relationship between inflammation and GC metabolism.
Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells
Authors: Alim Md Abdul , Grujic Mirjana , Ackerman Paul W. , Kristiansson Per , Eliasson Pernilla , Peterson Magnus , Pejler Gunnar 
Published: April 2020

AbstractMast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system. However, it is not clear the mechanism by which mast cells communicate with peripheral nerves. We previously found that mast cells located within healing tendons can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling. To evaluate this hypothesis, we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type (NMDAR1, NMDAR2A, and NMDAR2B) and the metabotropic type (mGluR2 and mGluR7) at both the mRNA and protein levels. The binding of glutamate to glutamate receptors on the mast cell surface was confirmed. Further, glutamate had extensive effects on gene expression in the mast cells, including the upregulation of pro-inflammatory components such as IL-6 and CCL2. Glutamate also induced the upregulation of transcription factors, including Egr2, Egr3 and, in particular, FosB. The extensive induction of FosB was confirmed by immunofluorescence assessment. Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate, supporting the supposition of a functional glutamate–glutamate receptor axis in mast cells. Finally, we provide in vivo evidence supporting a functional glutamate–glutamate receptor axis in the mast cells of injured tendons. Together, these findings establish glutamate as an effector of mast cell function, thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.
Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes
Authors: Omar-Hmeadi Muhmmad , Lund Per-Eric , Gandasi Nikhil R. , Tengholm Anders , Barg Sebastian 
Published: April 2020

AbstractGlucagon is released from pancreatic α-cells to activate pathways that raise blood glucose. Its secretion is regulated by α-cell-intrinsic glucose sensing and paracrine control through insulin and somatostatin. To understand the inadequately high glucagon levels that contribute to hyperglycemia in type-2 diabetes (T2D), we analyzed granule behavior, exocytosis and membrane excitability in α-cells of 68 non-diabetic and 21 T2D human donors. We report that exocytosis is moderately reduced in α-cells of T2D donors, without changes in voltage-dependent ion currents or granule trafficking. Dispersed α-cells have a non-physiological V-shaped dose response to glucose, with maximal exocytosis at hyperglycemia. Within intact islets, hyperglycemia instead inhibits α-cell exocytosis, but not in T2D or when paracrine inhibition by insulin or somatostatin is blocked. Surface expression of somatostatin-receptor-2 is reduced in T2D, suggesting a mechanism for the observed somatostatin resistance. Thus, elevated glucagon in human T2D may reflect α-cell insensitivity to paracrine inhibition at hyperglycemia.
Aquaculture at the crossroads of global warming and antimicrobial resistance
Authors: Reverter Miriam , Sarter Samira , Caruso Domenico , Avarre Jean-Christophe , Combe Marine , Pepey Elodie , Pouyaud Laurent , Vega-Heredía Sarahi , de Verdal Hugues , Gozlan Rodolphe E. 
Published: April 2020

AbstractIn many developing countries, aquaculture is key to ensuring food security for millions of people. It is thus important to measure the full implications of environmental changes on the sustainability of aquaculture. We conduct a double meta-analysis (460 articles) to explore how global warming and antimicrobial resistance (AMR) impact aquaculture. We calculate a Multi-Antibiotic Resistance index (MAR) of aquaculture-related bacteria (11,274 isolates) for 40 countries, of which mostly low- and middle-income countries present high AMR levels. Here we show that aquaculture MAR indices correlate with MAR indices from human clinical bacteria, temperature and countries’ climate vulnerability. We also find that infected aquatic animals present higher mortalities at warmer temperatures. Countries most vulnerable to climate change will probably face the highest AMR risks, impacting human health beyond the aquaculture sector, highlighting the need for urgent action. Sustainable solutions to minimise antibiotic use and increase system resilience are therefore needed.
Dual functionality of the amyloid protein TasA in Bacillus physiology and fitness on the phylloplane
Authors: Cámara-Almirón Jesús , Navarro Yurena , Díaz-Martínez Luis , Magno-Pérez-Bryan María Concepción , Molina-Santiago Carlos , Pearson John R. , de Vicente Antonio , Pérez-García Alejandro , Romero Diego 
Published: April 2020

AbstractBacteria can form biofilms that consist of multicellular communities embedded in an extracellular matrix (ECM). InBacillus subtilis, the main protein component of the ECM is the functional amyloid TasA. Here, we study further the roles played by TasA inB. subtilisphysiology and biofilm formation on plant leaves and in vitro. We show that ΔtasAcells exhibit a range of cytological symptoms indicative of excessive cellular stress leading to increased cell death. TasA associates to the detergent-resistant fraction of the cell membrane, and the distribution of the flotillin-like protein FloT is altered in ΔtasAcells. We propose that, in addition to a structural function during ECM assembly and interactions with plants, TasA contributes to the stabilization of membrane dynamics as cells enter stationary phase.
Doping-free complementary WSe2 circuit via van der Waals metal integration
Authors: Kong Lingan , Zhang Xiaodong , Tao Quanyang , Zhang Mingliang , Dang Weiqi , Li Zhiwei , Feng Liping , Liao Lei , Duan Xiangfeng , Liu Yuan 
Published: April 2020

AbstractTwo-dimensional (2D) semiconductors have attracted considerable attention for the development of ultra-thin body transistors. However, the polarity control of 2D transistors and the achievement of complementary logic functions remain critical challenges. Here, we report a doping-free strategy to modulate the polarity of WSe2 transistors using same contact metal but different integration methods. By applying low-energy van der Waals integration of Au electrodes, we observed robust and optimized p-type transistor behavior, which is in great contrast to the transistors fabricated on the same WSe2 flake using conventional deposited Au contacts with pronounced n-type characteristics. With the ability to switch majority carrier type and to achieve optimized contact for both electrons and holes, a doping-free logic inverter is demonstrated with higher voltage gain of 340, at the bias voltage of 5.5 V. Furthermore, the simple polarity control strategy is extended for realizing more complex logic functions such as NAND and NOR.
The chloroalkaloid (−)-acutumine is biosynthesized via a Fe(II)- and 2-oxoglutarate-dependent halogenase in Menispermaceae plants
Authors: Kim Colin Y. , Mitchell Andrew J. , Glinkerman Christopher M. , Li Fu-Shuang , Pluskal Tomáš , Weng Jing-Ke 
Published: April 2020

AbstractPlant halogenated natural products are rare and harbor various interesting bioactivities, yet the biochemical basis for the involved halogenation chemistry is unknown. While a handful of Fe(II)- and 2-oxoglutarate-dependent halogenases (2ODHs) have been found to catalyze regioselective halogenation of unactivated C–H bonds in bacteria, they remain uncharacterized in the plant kingdom. Here, we report the discovery of dechloroacutumine halogenase (DAH) from Menispermaceae plants known to produce the tetracyclic chloroalkaloid (−)-acutumine. DAH is a 2ODH of plant origin and catalyzes the terminal chlorination step in the biosynthesis of (−)-acutumine. Phylogenetic analyses reveal that DAH evolved independently in Menispermaceae plants and in bacteria, illustrating an exemplary case of parallel evolution in specialized metabolism across domains of life. We show that at the presence of azide anion, DAH also exhibits promiscuous azidation activity against dechloroacutumine. This study opens avenues for expanding plant chemodiversity through halogenation and azidation biochemistry.
Observation of an unpaired photonic Dirac point
Authors: Liu Gui-Geng , Zhou Peiheng , Yang Yihao , Xue Haoran , Ren Xin , Lin Xiao , Sun Hong-xiang , Bi Lei , Chong Yidong , Zhang Baile 
Published: April 2020

AbstractAt photonic Dirac points, electromagnetic waves are governed by the same equations as two-component massless relativistic fermions. However, photonic Dirac points are known to occur in pairs in “photonic graphene” and other similar photonic crystals, which necessitates special precautions to excite only one valley state. Systems hosting unpaired photonic Dirac points are significantly harder to realize, as they require broken time-reversal symmetry. Here, we report on the observation of an unpaired Dirac point in a planar two-dimensional photonic crystal. The structure incorporates gyromagnetic materials, which break time-reversal symmetry; the unpaired Dirac point occurs when a parity-breaking parameter is fine-tuned to a topological transition between a photonic Chern insulator and a conventional photonic insulator phase. Evidence for the unpaired Dirac point is provided by transmission and field-mapping experiments, including a demonstration of strongly non-reciprocal reflection. This unpaired Dirac point may have applications in valley filters and angular selective photonic devices.
Connecting concepts in the brain by mapping cortical representations of semantic relations
Authors: Zhang Yizhen , Han Kuan , Worth Robert , Liu Zhongming 
Published: April 2020

AbstractIn the brain, the semantic system is thought to store concepts. However, little is known about how it connects different concepts and infers semantic relations. To address this question, we collected hours of functional magnetic resonance imaging data from human subjects listening to natural stories. We developed a predictive model of the voxel-wise response and further applied it to thousands of new words. Our results suggest that both semantic categories and relations are represented by spatially overlapping cortical patterns, instead of anatomically segregated regions. Semantic relations that reflect conceptual progression from concreteness to abstractness are represented by cortical patterns of activation in the default mode network and deactivation in the frontoparietal attention network. We conclude that the human brain uses distributed networks to encode not only concepts but also relationships between concepts. In particular, the default mode network plays a central role in semantic processing for abstraction of concepts.
Reactions of CO2 and ethane enable CO bond insertion for production of C3 oxygenates
Authors: Xie Zhenhua , Xu Yuanguo , Xie Meng , Chen Xiaobo , Lee Ji Hoon , Stavitski Eli , Kattel Shyam , Chen Jingguang G. 
Published: April 2020

AbstractReacting CO2 and ethane to synthesize value-added oxygenate molecules represents opportunities to simultaneously reduce CO2 emissions and upgrade underutilized ethane in shale gas. Herein, we propose a strategy to produce C3 oxygenates using a tandem reactor. This strategy is achieved with a Fe3Ni1/CeO2 catalyst (first reactor at 600–800 °C) for CO2-assisted dehydrogenation and reforming of ethane to produce ethylene, CO, and H2, and a RhCox/MCM-41 catalyst (second reactor at 200 °C) enabling CO insertion for the production of C3 oxygenates (propanal and 1-propanol) via the heterogeneous hydroformylation reaction at ambient pressure. In-situ characterization using synchrotron spectroscopies and density functional theory (DFT) calculations reveal the effect of Rh–Co bimetallic formation in facilitating the production of C3 oxygenates. The proposed strategy provides an opportunity for upgrading light alkanes in shale gas by reacting with CO2 to produce aldehydes and alcohols.