bluuebunny/crossref_metadata_2025_split huggingface dataset:
A physiological role for GABAAreceptor desensitization – induction of long-term potentiation at inhibitory synapses
Authors: Field Martin , Thomas Philip , Smart Trevor G 
Published: June 2020

AbstractGABAAreceptors (GABAARs) are pentameric ligand-gated ion channels distributed throughout the brain where they mediate synaptic and tonic inhibition. Following activation, these receptors undergo desensitization which involves entry into long-lived agonist-bound closed states. Although the kinetic effects of this state are recognised and its structural basis has been uncovered, the physiological impact of desensitization on inhibitory neurotransmission remains unknown. Here we describe an enduring new form of long-term potentiation at inhibitory synapses that elevates synaptic current amplitude for 24 hrs following desensitization of GABAARs in response to prolonged agonist exposure or allosteric modulation. Using receptor mutants and allosteric modulators we demonstrate that desensitization of GABAARs facilitates their phosphorylation by PKC, which increases the number of receptors at inhibitory synapses. These observations provide a new physiological relevance to the desensitized state of GABAARs, acting as a signal to regulate the efficacy of inhibitory synapses during prolonged periods of inhibitory neurotransmission.
Magnetosomes could be protective shields against metal stress in magnetotactic bacteria
Authors: Muñoz D. , Marcano L. , Martín-Rodríguez R. , Simonelli L. , Serrano A. , García-Prieto A. , Fdez-Gubieda M.L. , Muela A. 
Published: June 2020

AbstractMagnetotactic bacteria are aquatic microorganisms with the ability to biomineralise membrane-enclosed magnetic nanoparticles, called magnetosomes. These magnetosomes are arranged into a chain that behaves as a magnetic compass, allowing the bacteria to align in and navigate along the Earth’s magnetic field lines. According to the magneto-aerotactic hypothesis, the purpose of producing magnetosomes is to provide the bacteria with a more efficient movement within the stratified water column, in search of the optimal positions that satisfy their nutritional requirements. However, magnetosomes could have other physiological roles, as proposed in this work. Here we analyse the role of magnetosomes in the tolerance ofMagnetospirillum gryphiswaldenseMSR-1 to transition metals (Co, Mn, Ni, Zn, Cu). By exposing bacterial populations with and without magnetosomes to increasing concentrations of metals in the growth medium, we observe that the tolerance is significantly higher when bacteria have magnetosomes. The resistance mechanisms triggered in magnetosome-bearing bacteria under metal stress have been investigated by means of x-ray absorption near edge spectroscopy (XANES). XANES experiments were performed both on magnetosomes isolated from the bacteria and on the whole bacteria, aimed to assess whether bacteria use magnetosomes as metal storages, or whether they incorporate the excess metal in other cell compartments. Our findings reveal that the tolerance mechanisms are metal-specific: Mn, Zn and Cu are incorporated in both the magnetosomes and other cell compartments; Co is only incorporated in the magnetosomes, and Ni is incorporated in other cell compartments. In the case of Co, Zn and Mn, the metal is integrated in the magnetosome magnetite mineral core.
Paleoclimate and current climate collectively shape the phylogenetic and functional diversity of trees worldwide
Authors: Guo Wen-Yong , Serra-Diaz Josep M. , Schrodt Franziska , Eiserhardt Wolf L. , Maitner Brian S. , Merow Cory , Violle Cyrille , Blach-Overgaard Anne , Zhang Jian , Anand Madhur , Belluau Michaël , Bruun Hans Henrik , Byun Chaeho , Catford Jane A. , Cerabolini Bruno E. L. , Chacón-Madrigal Eduardo , Ciccarelli Daniela , Cornelissen Johannes H. C. , Dang-Le Anh Tuan , de Frutos Angel , Dias Arildo S. , Giroldo Aelton B. , Gutiérrez Alvaro G. , Hattingh Wesley , He Tianhua , Hietz Peter , Hough-Snee Nate , Jansen Steven , Kattge Jens , Klein Tamir , Komac Benjamin , Kraft Nathan , Kramer Koen , Lavorel Sandra , Lusk Christopher H. , Martin Adam R. , Mencuccini Maurizio , Michaletz Sean T. , Minden Vanessa , Mori Akira S. , Niinemets Ülo , Onoda Yusuke , Onstein Renske E. , Peñuelas Josep , Pillar Valério D. , Pisek Jan , Pound Matthew J. , Robroek Bjorn J.M. , Schamp Brandon , Slot Martijn , Sosinski Ênio , Soudzilovskaia Nadejda A. , Thiffault Nelson , van Bodegom Peter , van der Plas Fons , Wright Ian J. , Zheng Jingming , Enquist Brian J. , Svenning Jens-Christian 
Published: June 2020

AbstractTrees are of vital importance for ecosystem functioning and services at local to global scales, yet we still lack a detailed overview of the global patterns of tree diversity and the underlying drivers, particularly the imprint of paleoclimate. Here, we present the high-resolution (110 km) worldwide mapping of tree species richness, functional and phylogenetic diversities based on ∼7 million quality-assessed occurrences for 46,752 tree species (80.5% of the estimated total number of tree species), and subsequent assessments of the influence of paleo-climate legacies on these patterns. All three tree diversity dimensions exhibited the expected latitudinal decline. Contemporary climate emerged as the strongest driver of all diversity patterns, with Pleistocene and deeper-time (>107years) paleoclimate as important co-determinants, and, notably, with past cold and drought stress being linked to reduced current diversity. These findings demonstrate that tree diversity is affected by paleoclimate millions of years back in time and highlight the potential for tree diversity losses from future climate change.
Development and application of a metabolomic tool to assess exposure of an estuarine amphipod to pollutants in the environment
Authors: Yanagihara Miina , Nakajima Fumiyuki , Tobino Tomohiro 
Published: June 2020

ABSTRACTIdentifying substances in sediment that cause adverse effects on benthic organisms has been implemented as an effective source-control strategy. However, the identification of such substances is difficult due to the complicated interactions between liquid and solid phases and organisms. Metabolomic approaches have been utilized to assess the effects of toxicants on various organisms; however, the relationships between the toxicants and metabolomic profiles have not been generalized, and it makes impractical to identify major toxicants from metabolomic information. In this study, we used partial least squares discriminant analysis (PLS-DA) to investigate these relationships. The objective of this study was to construct PLS-DA models using the metabolomic profiles of the benthic amphipodGrandidierella japonicato assess the exposure effects of target toxicants and to demonstrate the utility of these models to assess the effects of chemicals in environmental samples. The PLS-DA models were constructed from the metabolomic profiles ofG. japonicato discriminate the exposure ofG. japonicato chromium, nickel, copper, zinc, cadmium, fluoranthene, nicotine, and osmotic stress. The models had high predictive power for the presumptive exposure to each chemical and were able to detect exposures in mixed chemical samples. These results suggest that the metabolomic responses can provide important information for the assessment of chemical effects on organisms. We applied the models to the metabolomic profiles ofG. japonicaexposed to river sediment and road dust, and the results demonstrated the applicability of the models. The control groups were not classified as exposure groups, and no samples were presumed to belong to any exposure group. These results suggest that the target chemicals were not toxic in the samples and conditions we investigated. This study demonstrates a method to assess the relationships between chemical exposure and metabolomic responses. To the best our knowledge, this is the first study to apply metabolomics for identification of toxicants.
Structural basis for neutralization of SARS-CoV-2 and SARS-CoV by a potent therapeutic antibody
Authors: Lv Zhe , Deng Yong-Qiang , Ye Qing , Cao Lei , Sun Chun-Yun , Fan Changfa , Huang Weijin , Sun Shihui , Sun Yao , Zhu Ling , Chen Qi , Wang Nan , Nie Jianhui , Cui Zhen , Zhu Dandan , Shaw Neil , Li Xiao-Feng , Li Qianqian , Xie Liangzhi , Wang Youchun , Rao Zihe , Qin Cheng-Feng , Wang Xiangxi 
Published: June 2020

AbstractThe COVID-19 pandemic caused by the SARS-CoV-2 virus has resulted in an unprecedented public health crisis. There are no approved vaccines or therapeutics for treating COVID-19. Here we reported a humanized monoclonal antibody, H014, efficiently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 at nM level by engaging the S receptor binding domain (RBD). Importantly, H014 administration reduced SARS-CoV-2 titers in the infected lungs and prevented pulmonary pathology in hACE2 mouse model. Cryo-EM characterization of the SARS-CoV-2 S trimer in complex with the H014 Fab fragment unveiled a novel conformational epitope, which is only accessible when the RBD is in open conformation. Biochemical, cellular, virological and structural studies demonstrated that H014 prevents attachment of SARS-CoV-2 to its host cell receptors. Epitope analysis of available neutralizing antibodies against SARS-CoV and SARS-CoV-2 uncover broad cross-protective epitopes. Our results highlight a key role for antibody-based therapeutic interventions in the treatment of COVID-19.One sentence summaryA potent neutralizing antibody conferred protection against SARS-CoV-2 in an hACE2 humanized mouse model by sterically blocking the interaction of the virus with its receptor.
Evaluation of a large-scale flow manipulation to the upper San Francisco Estuary: Response of habitat conditions for an endangered native fish
Authors: Sommer Ted , Hartman Rosemary , Koller Michal , Koohafkan Michael , Conrad J. Louise , MacWilliams Michael , Bever Aaron , Burdi Christina , Beakes Michael P. 
Published: June 2020

AbstractWhile flow is known to be a major driver of estuarine ecosystems, targeted flow manipulations are rare because tidal systems are extremely variable in space and time, and because the necessary infrastructure is rarely available. In summer 2018 we used a unique water control structure in the San Francisco Estuary (SFE) to direct a managed flow pulse into Suisun Marsh, one of the largest contiguous tidal marshes on the west coast of the United States. The action was designed to increase habitat suitability for the endangered Delta SmeltHypomesus transpacificus, a small osmerid fish endemic to the upper SFE. The approach was to operate the Suisun Marsh Salinity Control Gates (SMSCG) in conjunction with increased Sacramento River tributary inflow to direct an estimated 160 × 106m3pulse of low salinity water into Suisun Marsh during August, a critical time period for juvenile Delta Smelt rearing. Three-dimensional modeling showed that directing additional low salinity water into Suisun Marsh (“Flow Action”) substantially increased the area of low salinity habitat for Delta Smelt that persisted beyond the period of SMSCG operations. Field monitoring showed that turbidity and chlorophyll were at higher levels in Suisun Marsh, representing better habitat conditions, than the upstream Sacramento River region throughout the study period. The Flow Action had no substantial effects on zooplankton abundance, nor did Suisun Marsh show enhanced levels of these prey species in comparison to the Sacramento River. Fish monitoring data suggested that small numbers of Delta Smelt colonized Suisun Marsh from the Sacramento River during the Flow Action, further supporting our hypothesis that the Flow Action would benefit this rare species. Our study provides insight into both the potential use of targeted flow manipulations to support endangered fishes such as Delta Smelt, and into the general response of estuarine habitat to flow management.
Competition and growth inAedes aegyptilarvae: effects of distributing food inputs over time
Authors: Steinwascher Kurt 
Published: June 2020

AbstractMale and female mosquito larvae compete for different subsets of the yeast food resource in laboratory microcosms. Males compete more intensely with males and females with females. The amount and timing of food inputs alters both growth and competition, but the effects are different between sexes. Increased density increases competition among males. Among females, density operates primarily by changing the food/larva or total food; this affects competition in some interactions and growth in others. Food added earlier in the life span contributes more to mass than the same quantity added later. After a period of starvation larvae appear to use some of the subsequent food input to rebuild physiological reserves in addition to building mass. The timing of pupation is affected by the independent factors and competition, but not in the same way for the two sexes, and not in the same way as mass at pupation for the two sexes. There is an effect of density on the timing of pupation for females independent of competition or changes in food/larva or total food. Male and female larvae have different larval life history strategies. Males grow quickly to a minimum size, then pupate, depending on the amount of food available. Males that do not grow quickly enough may delay pupation further to grow larger, resulting in a bimodal distribution of sizes and ages. Males appear to have a maximum size determined by the early food level. Females grow faster than males and grow larger than males on the same food inputs. Females affect the growth and competition among males by manipulating the number of particles in the microcosm through changes in feeding behavior. Mosquito larvae appear to have evolved to survive periods of starvation and take advantage of intermittent inputs of food into containers.
Development of an absolute assignment predictor for triple-negative breast cancer subtyping using machine learning approaches
Authors: Azzouz Fadoua Ben , Michel Bertrand , Lasla Hamza , Gouraud Wilfried , François Anne-Flore , Girka Fabien , Lecointre Théo , Guérin-Charbonnel Catherine , Juin Philippe P. , Campone Mario , Jézéquel Pascal 
Published: June 2020

AbstractTriple-negative breast cancer (TNBC) heterogeneity represents one of the main impediment to precision medicine for this disease. Recent concordant transcriptomics studies have shown that TNBC could be splitted into at least three subtypes with potential therapeutic implications. Although, a few studies have been done to predictTNBC subtypeby means oftranscriptomics data, subtyping was partially sensitive and limited by batch effect and dependence to a given dataset, which may penalize the switch to routine diagnostic testing. Therefore, we sought to build an absolute predictor (i.e. intra-patient diagnosis) based onmachine learningalgorithm with a limited number of probes. To this end, we started by introducing probe binary comparison for each patient (indicators). We based predictive analysis on this transformed data. Probe selection was first performed by combining both filter and wrapper methods forvariable selectionusing cross validation. We thus tested threeprediction models(random forest, gradient boosting [GB] and extreme gradient boosting) using this optimal subset of indicators as inputs. Nested cross-validation allowed us to consistently choose the best model. Results showed that the 50 selected indicators highlighted biological characteristics associated with each TNBC subtype. The GB based on this subset of indicators has better performances as compared to the other models.
Neutralizing effects of small molecule inhibitors and metal chelators on coagulopathicViperinaesnake venom toxins
Authors: Xie Chunfang , Albulescu Laura , Bittenbinder Matyas A , Somsen Govert , Vonk Freek , Casewell Nicholas R , Kool Jeroen 
Published: June 2020

AbstractAnimal-derived antivenoms are the only specific therapies currently available for the treatment of snake envenoming, but these products have a number of limitations associated with their efficacy, safety and affordability for use in tropical snakebite victims. Small molecule drugs and drug candidates are regarded as promising alternatives for filling the critical therapeutic gap between snake envenoming and effective treatment. In this study, by using an advanced analytical technique that combines chromatography, mass spectrometry and bioassaying, we investigated the effect of several small molecule inhibitors that target phospholipase A2(varespladib) and snake venom metalloproteinase (marimastat, dimercaprol and DMPS) toxin families on inhibiting the activities of coagulopathic toxins found inViperinaesnake venoms. The venoms ofEchis carinatus, Echis ocellatus, Daboia russeliiandBitis arietans, which are known for their potent coagulopathic toxicities, were fractionated in high resolution onto 384-well plates using liquid chromatography followed by coagulopathic bioassaying of the obtained fractions. Bioassay activities were correlated to parallel recorded mass spectrometric and proteomics data to assign the venom toxins responsible for coagulopathic activity and assess which of these toxins could be neutralized by the inhibitors under investigation. Our results showed that the phospholipase A2-inhibitor varespladib neutralized the vast majority of anticoagulation activities found across all of the tested snake venoms. Of the snake venom metalloproteinase inhibitors, marimastat demonstrated impressive neutralization of the procoagulation activities detected in all of the tested venoms, whereas dimercaprol and DMPS could only partially neutralize these activities at the doses tested. Our results provide additional support for the concept that combination of small molecules, particularly the combination of varespladib with marimastat, serve as a drug-repurposing opportunity to develop new broad-spectrum inhibitor-based therapies for snakebite envenoming.
Neural signatures of arbitration between Pavlovian and instrumental action selection
Authors: Gershman Samuel J. , Guitart-Masip Marc , Cavanagh James F. 
Published: June 2020

AbstractPavlovian associations drive approach towards reward-predictive cues, and avoidance of punishment-predictive cues. These associations “misbehave” when they conflict with correct instrumental behavior. This raises the question of how Pavlovian and instrumental influences on behavior are arbitrated. We test a computational theory according to which Pavlovian influence will be stronger when inferred controllability of outcomes is low. Using a model-based analysis of a Go/NoGo task with human subjects, we show that theta-band oscillatory power in frontal cortex tracks inferred controllability, and that these inferences predict Pavlovian action biases. Functional MRI data revealed an inferior frontal gyrus correlate of action probability and a ventromedial prefrontal correlate of outcome valence, both of which were modulated by inferred controllability.
Optimizing the molecular diagnosis of Covid-19 by combining RT-PCR and a pseudo-convolutional machine learning approach to characterize virus DNA sequences
Authors: Gomes Juliana Carneiro , Masood Aras Ismael , de S. Silva Leandro Honorato , Ferreira Janderson , Júnior Agostinho A. F. , dos Santos Rocha Allana Lais , Castro Letícia , da Silva Nathália R. C. , Fernandes Bruno J. T. , dos Santos Wellington Pinheiro 
Published: June 2020

AbstractThe proliferation of the SARS-Cov-2 virus to the whole world caused more than 250,000 deaths worldwide and over 4 million confirmed cases. The severity of Covid-19, the exponential rate at which the virus proliferates, and the rapid exhaustion of the public health resources are critical factors. The RT-PCR with virus DNA identification is still the benchmark Covid-19 diagnosis method. In this work we propose a new technique for representing DNA sequences: they are divided into smaller sequences with overlap in a pseudo-convolutional approach, and represented by co-occurrence matrices. This technique analyzes the DNA sequences obtained by the RT-PCR method, eliminating sequence alignment. Through the proposed method, it is possible to identify virus sequences from a large database: 347,363 virus DNA sequences from 24 virus families and SARS-Cov-2. Experiments with all 24 virus families and SARS-Cov-2 (multi-class scenario) resulted 0.822222±0.05613 for sensitivity and 0.99974±0.00001 for specificity using Random Forests with 100 trees and 30% overlap. When we compared SARS-Cov-2 with similar-symptoms virus families, we got 0.97059±0.03387 for sensitivity, and 0.99187±0.00046 for specificity with MLP classifier and 30% overlap. In the real test scenario, in which SARS-Cov-2 is compared to Coronaviridae and healthy human DNA sequences, we got 0.98824±001198 for sensitivity and 0.99860±0.00020 for specificity with MLP and 50% overlap. Therefore, the molecular diagnosis of Covid-19 can be optimized by combining RT-PCR and our pseudo-convolutional method to identify SARS-Cov-2 DNA sequences faster with higher specificity and sensitivity.
Molecular Determinants of Liquid Demixing and Amyloidogenesis in Human CPEB3
Authors: de Mingo Daniel Ramírez , López-García Paula , Hervás Rubén , Laurents Douglas V. , Carrión-Vázquez Mariano 
Published: June 2020

AbstractThe cytoplasmic polyadenylation element-binding protein 3 (CPEB3), is an RNA-binding protein which in its soluble state is localized in membraneless neuronal RNA granules keeping target mRNAs in a repressed state. The stimulus-dependent aggregation of CPEB3 activates target mRNAs translation, a central event for the maintenance of long-term memory-related synaptic plasticity in mammals. To date, the molecular determinants that govern both connected events remain unclear. Here, to gain insight into these processes, the biophysical properties of the human CPEB3 (hCPEB3) are characterized. We found that hCPEB3 homotypic condensation is mainly driven by hydrophobic interactions and occurs under physiological conditions. Moreover, hCPEB3 biomolecular condensates are dynamic inside living cells, whose localization and stabilization are mediated by its RNA-recognition domains. In contrast, the hCPEB3 polar N-terminal region is crucial for hCPEB3 amyloid-like aggregationin vitro, which is disrupted by the polyglutamine binding peptide 1 (QBP1), Aβ42seeds and Hsp70, highlighting the importance of the Q4RQ4tract as well as the hydrophobic residues for hCPEB3 functional aggregation. Based on these findings, we postulate a model for hCPEB3’s role in memory persistence that advances a rather sophisticated control for hCPEB3 condensate dissociation and amyloid-like formation to achieve its physiological function.HighlightshCPEB3 forms toxic intermediates that persist longer than in other functional amyloids.RNA-recognition domains stabilize hCPEB3 granule formation and dynamics.Different segments within hCPEB3 promote amyloidogenesis and liquid demixing.hCPEB3 amyloid formation requires both hydrophobic and polyQ segments.Graphical Abstract