bluuebunny/crossref_metadata_2025_split huggingface dataset:
ATP-sensitive K+channels control the spontaneous firing of a glycinergic interneuron in the auditory brainstem
Authors: Strazza Paulo S. , de Siqueira Daniela V.F. , Benites Nikollas M. , Leão Ricardo M. 
Published: June 2020

AbstractCartwheel neurons from the dorsal cochlear nucleus (DCN) are glycinergic interneurons and the primary source of inhibition on the fusiform neurons, the principal excitatory neuron in the DCN. Most cartwheel neurons present spontaneous firing (activeneurons), producing a steady inhibitory tone on fusiform neurons. In contrast, a smaller fraction does not fire spontaneously (quietneurons). Additionally, hyperactivity of fusiform neurons is seen in animals with behavioral evidence of tinnitus. Due to its relevance in controlling the excitability of fusiform neurons, we investigated the ion channels responsible for the spontaneous firing of cartwheel neurons. We found that quiet neurons express an outward conductance not seen in active neurons, which generates a stable resting potential. This current was sensitive to tolbutamide, an ATP-sensitive potassium channel (KATP) antagonist. After its inhibition, quiet neurons start to fire spontaneously, while the behavior of active neurons was not affected. On the other hand, in active neurons, KATPagonist diazoxide activated a conductance similar to the KATPconductance of quiet neurons and stopped spontaneous firing. According to the effect of KATPchannels on CW neuron firing, glycinergic neurotransmission in DCN was increased by tolbutamide and decreased by diazoxide. Finally, slices incubated with the tinnitus-inducing agent sodium salicylate presented more quiet neurons expressing the KATPconductance, which increased the proportion of quiet neurons. Our results reveal an unexpected role of KATPchannels in controlling the spontaneous firing of neurons. Additionally, changes in KATPchannel activity of cartwheel neurons can be related to the DCN hyperactivity seen in tinnitus.
Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs
Authors: Kern David M. , Sorum Ben , Mali Sonali S. , Hoel Christopher M. , Sridharan Savitha , Remis Jonathan P. , Toso Daniel B. , Kotecha Abhay , Bautista Diana M. , Brohawn Stephen G. 
Published: June 2020

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus that causes the coronavirus disease 2019 (COVID-19). SARS-CoV-2 encodes three putative ion channels: E, 8a, and 3a1,2. 3a is expressed in SARS patient tissue and anti-3a antibodies are observed in patient plasma3–6. 3a has been implicated in viral release7, inhibition of autophagy8, inflammasome activation9, and cell death10,11and its deletion reduces viral titer and morbidity in mice1, raising the possibility that 3a could be an effective vaccine or therapeutic target3,12. Here, we present the first cryo-EM structures of SARS-CoV-2 3a to 2.1 Å resolution and demonstrate 3a forms an ion channel in reconstituted liposomes. The structures in lipid nanodiscs reveal 3a dimers and tetramers adopt a novel fold with a large polar cavity that spans halfway across the membrane and is accessible to the cytosol and the surrounding bilayer through separate water- and lipid-filled openings. Electrophysiology and fluorescent ion imaging experiments show 3a forms Ca2+-permeable non-selective cation channels. We identify point mutations that alter ion permeability and discover polycationic inhibitors of 3a channel activity. We find 3a-like proteins in multipleAlphacoronavirusandBetacoronaviruslineages that infect bats and humans. These data show 3a forms a functional ion channel that may promote COVID-19 pathogenesis and suggest targeting 3a could broadly treat coronavirus diseases.
Single-cell RNA-seq reveals a concomitant delay in differentiation and cell cycle of aged hematopoietic stem cell
Authors: Hérault Léonard , Poplineau Mathilde , Mazuel Adrien , Platet Nadine , Remy Élisabeth , Duprez Estelle 
Published: June 2020

ABSTRACTHematopoietic stem cells (HSCs) are the guarantor of the proper functioning of hematopoiesis due to their incredible diversity of potential. During aging the heterogeneity of mouse HSCs evolves, which contributes to the deterioration of the immune system. Here we address the transcriptional plasticity of HSC upon aging at the single-cell resolution. Through the analysis of 15,000 young and aged transcriptomes, we reveal 15 clusters of HSCs unveiling rare and specific HSC abilities that change with age. Pseudotime ordering complemented with regulon analysis showed that the consecutive differentiation states of HSC are delayed upon aging. By analysing cell cycle at the single cell level we highlight an imbalance of cell cycle regulators of very immature aged HSC that may contribute to their accumulation in an undifferentiated state.Our results therefore establish a reference map of young and old mouse HSC differentiation and reveal a potential mechanism that delay aged HSC differentiation.
First report of the sexual stage of the flax pathogenMycosphaerella linicolain France and its impact on pasmo epidemiology
Authors: Paumier Delphine , Bammé Blandine , Penaud Annette , Valade Romain , Suffert Frédéric 
Published: June 2020

AbstractWe performed a three-year field survey in France to characterize the dynamics of sexual reproduction inMycosphaerella linicola, the causal agent of pasmo, during the interepidemic period. Cohorts of fruiting bodies were sampled from linseed straw during the autumn and winter and carefully observed, focusing on pseudothecia, asci and ascospores. A sequence of experimental steps corresponding to Koch’s postulates confirmed in July 2014, for the first time in France and continental Europe, the widespread presence of the sexual stage ofM. linicolain plant host tissues. The developmental dynamics of pseudothecia on straw, expressed as the change over time in the percentage of mature pseudothecia, was similar in all three years. Pseudothecia appeared in late summer, with peak maturity reached in October. A temporal shift, thought to be due to early autumn rainfall, was highlighted in one of the three years. These observations suggest that sexual reproduction plays a significant role in the epidemiology of pasmo in France. A resurgence ofM. linicolainfections in spring flax is thought to have occurred in recent years, due to the increase in the area under flax. The presence of the sexual stage of this pathogen probably increased the quantitative impact of residues of winter linseed (used for oil) and flax straw (left on the soil for retting and used for fibers) as an interepidemic ‘brown bridge’. This case study highlights how certain parts of a disease cycle, in this case the sexual phase, can become crucial due to changes in production conditions.
Chromatin accessibility landscapes activated by cell surface and intracellular immune receptors
Authors: Ding Pingtao , Sakai Toshiyuki , Shrestha Ram Krishna , Perez Nicolas Manosalva , Guo Wenbin , Ngou Bruno Pok Man , He Shengbo , Liu Chang , Feng Xiaoqi , Zhang Runxuan , Vandepoele Klaas , MacLean Dan , Jones Jonathan DG 
Published: June 2020

AbstractActivation of cell Surface and Intracellular Receptor-Mediated Immunity (SRMI and IRMI) results in rapid transcriptional reprogramming that underpins disease resistance. However, the mechanisms by which SRMI and IRMI lead to transcriptional changes are not clear. Here, we combine RNA-seq and ATAC-seq to define changes in gene expression and chromatin accessibility; both SRMI and IRMI increase chromatin accessibility at induced defense genes. Analysis of ATAC-seq and RNA-seq data combined with publicly available information on transcription factor DNA-binding motifs enabled comparison of individual gene regulatory networks activated by SRMI and IRMI, and by both. These results and analyses reveal overlapping and conserved transcriptional regulatory mechanism between the two immune systems.
Nutritional status and fecundity are synchronised by muscular exopheresis
Authors: Turek Michał , Piechota Małgorzata , Banasiak Katarzyna , Shanmugam Nilesh , Macias Matylda , Śliwińska Małgorzata Alicja , Niklewicz Marta , Kowalski Konrad , Nowak Natalia , Chacińska Agnieszka , Pokrzywa Wojciech 
Published: June 2020

AbstractOrganismal functionality and reproduction depend on metabolic rewiring and balanced energy resources. However, the crosstalk between organismal homeostasis and fecundity, and the associated paracrine signaling mechanisms are still poorly understood. Using theCaenorhabditis eleganswe discovered that large extracellular vesicles termed exophers, attributed in neurons and cardiomyocytes to the removal of damaged subcellular components, are released by body wall muscles to support embryonic growth. We found that exopher formation (exopheresis) is a non-cell autonomous process regulated by egg formation in the uterus. Our data suggest that exophers serve as transporters for muscle-generated yolk proteins used for nourishing and improving the growth rate of the next generation. We propose that the primary role of muscular exopheresis is to stimulate the reproductive capacity, thereby influencing the adaptation of worm populations to the current environmental conditions.
Validated removal of nuclear pseudogenes and sequencing artefacts from mitochondrial metabarcode data
Authors: Andújar C. , Creedy T. J. , Arribas P. , López H. , Salces-Castellano A. , Pérez-Delgado A. , Vogler A. P. , Emerson B. C. 
Published: June 2020

AbstractMetabarcoding of Metazoa using mitochondrial genes may be confounded by both the accumulation of PCR and sequencing artefacts and the co-amplification of nuclear mitochondrial pseudogenes (NUMTs). The application of read abundance thresholds and denoising methods is efficient in reducing noise accompanying authentic mitochondrial amplicon sequence variants (ASVs). However, these procedures do not fully account for the complex nature of concomitant sequences and the highly variable DNA contribution of individuals in a metabarcoding sample. We propose, as a complement to denoising, the metabarcoding Multidimensional Abundance Threshold Evaluation (metaMATE) framework, a novel approach that allows comprehensive examination of multiple dimensions of abundance filtering and the evaluation of the prevalence of unwanted concomitant sequences in denoised metabarcoding datasets.metaMATErequires a denoised set of ASVs as input, and designates a subset of ASVs as being either authentic (mtDNA haplotypes) or non-authentic ASVs (NUMTs and erroneous sequences) by comparison to external reference data and by analysing nucleotide substitution patterns.metaMATE(i) facilitates the application of read abundance filtering strategies, which are structured with regard to sequence library and phylogeny and applied for a range of increasing abundance threshold values, and (ii) evaluates their performance by quantifying the prevalence of non-authentic ASVs and the collateral effects on the removal of authentic ASVs. The output frommetaMATEfacilitates decision-making about required filtering stringency and can be used to improve the reliability of intraspecific genetic information derived from metabarcode data. The framework is implemented in themetaMATEsoftware, available athttps://github.com/tjcreedy/metamate).
Comparative assessment of the effects of bumped kinase inhibitors on early zebrafish embryo development and pregnancy in mice
Authors: Anghel Nicoleta , Winzer Pablo A. , Imhof Dennis , Müller Joachim , Langa Javier , Rieder Jessica , Barrett Lynn K. , Vidadala Rama Subba Rao , Huang Wenlin , Choi Ryan , Hulverson Mathew A. , Whitman Grant R. , Arnold Samuel L. , Van Voorhis Wesley C. , Ojo Kayode K. , Maly Dustin J. , Fan Erkang , Hemphill Andrew 
Published: June 2020

AbstractBumped kinase inhibitors (BKIs) are effective against a variety of apicomplexan parasites. Fifteen BKIs with promisingin vitroefficacy againstNeospora caninumtachyzoites, low cytotoxicity in mammalian cells, and no toxic effects in non-pregnant BALB/c mice, were assessed in pregnant mice. Drugs were emulsified in corn oil and applied by gavage for 5 days. Five BKIs did not affect pregnancy, 5 BKIs exhibited 15-35% of neonatal mortality, and 5 compounds caused strong effects (infertility, abortion, stillbirth and pup mortality). Additionally, the impact of these compounds on zebrafish (Danio rerio) embryo development was assessed by exposing freshly fertilized eggs to 0.2-50μM of BKIs and microscopical monitoring of embryo development in a blinded manner during 4 days. We propose an algorithm that includes quantification of malformations and embryo deaths, and established a scoring system that allows to calculate an impact score (Si) that indicates at which concentrations BKIs visibly affect zebrafish embryo development. Comparison of the two models showed that for 9 compounds no clear correlation between Siand pregnancy outcome was visible. However, those 3 BKIs affecting zebrafish embryos only at high concentrations (40μM or higher) did not impair mouse pregnancy at all, and those 3 compounds that inhibited zebrafish embryo development already at 0.2μM showed detrimental effects in the pregnancy model. Thus, the zebrafish embryo development test has a limited predictive value to foresee pregnancy outcome in BKI-treated mice. We conclude, that maternal health-related factors such as cardiovascular, pharmacokinetic and/or bioavailability properties also contribute to BKI-pregnancy effects.
Novel mTORC1 inhibitors kill Glioblastoma stem cells
Authors: Sandoval Jose , Tomilov Alexey , Datta Sandipan , Allen Sonia , O’Donnell Robert , Angelastro James , Cortopassi Gino 
Published: June 2020

AbstractGlioblastoma Multiforme (GBM) is an aggressive tumor of the brain, with an average post-diagnosis survival of 15 months. GBM stem cells (GBMSC) resist the standard-of-care therapy, temozolomide, and are considered a major contributor to tumor resistance. mTORC1 regulates cell proliferation and has been shown by others to have reduced activity in GBMSC. We recently identified a novel chemical series of human-safe piperazine-based brain-penetrant mTORC1-specific inhibitors. We assayed piperazine-mTOR binding strength by two biophysical measurements-- biolayer interferometry and field effect biosensing, and these confirmed each other and demonstrated a structure-activity relationship. Since mTORC1 is reduced in human GBMSC, and as mTORC1 inhibitors have been tested in previous GBM clinical trials, we tested the killing potency of the tightest-binding piperazines and observed these were potent GBMSC killers. GBMSCs are resistant to the standard-of-care temozolomide therapy--but temozolomide supplemented with tight-binding piperazine meclizine and flunarizine greatly enhanced GBMSC death over temozolomide alone. Lastly, we investigated IDH1-mutated GBMSC mutations that are known to affect mitochondrial and mTORC1 metabolism, the tight-binding Meclizine provoked ‘synthetic lethality’ in IDH1-mutant GBMSCs. These data tend to support a novel clinical strategy for GBM, i.e. the co-administration of meclizine or flunarizine as adjuvant therapy in the treatment of GBM, and IDH1-mutant GBM.
Life under quartz: Hypolithic mosses in the Mojave Desert
Authors: Ekwealor Jenna T. B. , Fisher Kirsten M. 
Published: June 2020

AbstractSeveral species of dryland cyanobacteria are known to occur as hypoliths under semi-translucent rocks. In the Mojave Desert, these organisms find refuge from intense solar radiation under milky quartz where moisture persists for a longer period of time than in adjacent soil surface habitat. Desert mosses, which are extremely desiccation-tolerant, can also occur in these hypolithic spaces, though little is known about this unique moss microhabitat and how species composition compares to that of adjacent soil surface communities. To address this question, we deployed microclimate dataloggers and collected moss samples from under and adjacent to 18 milky quartz rocks (quartz mean center thickness 26 ± 15 mm) in a western high elevation Mojave Desert site. Light transmission through Mojave quartz rocks may be as low as 1.2%, and data from microclimate loggers deployed for five months support the hypothesis that quartz provides thermal buffering and higher relative humidity compared to the soil surface. Of the 53 samples collected from hypolith and surface microhabitats, 68% wereSyntrichia caninervis, the dominant bryophyte of the Mojave Desert biological soil crust.Tortula inermisaccounted for 28% of the samples and 4% wereBryum argenteum. In a comparison of moss community composition, we found thatS. caninerviswas more likely to be on the soil surface, though it was abundant in both microhabitats, whileT. inermiswas more restricted to hypoliths, perhaps due to protection from temperature extremes. In our study site, the differences between hypolithic and surface microhabitats enable niche partitioning betweenT. inermisandS. caninervis, enhancing alpha diversity. This work points to the need to thoroughly consider microhabitats when assessing bryophyte species diversity and modelling species distributions. This focus is particularly important in extreme environments, where mosses may find refuge from the prevailing macroclimatic conditions in microhabitats such as hypoliths.
Team flow is a unique brain state associated with enhanced information integration and neural synchrony
Authors: Shehata Mohammad , Cheng Miao , Leung Angus , Tsuchiya Naotsugu , Wu Daw-An , Tseng Chia-huei , Nakauchi Shigeki , Shimojo Shinsuke 
Published: June 2020

ABSTRACTTeam flow occurs when a group of people reaches high task engagement while sharing a common goal as in sports teams and music bands. While team flow is a superior enjoyable experience to individuals experiencing flow or regular socialization, the neural basis for such superiority is still unclear. Here, we addressed this question utilizing a music rhythm task and electroencephalogram hyper-scanning. Experimental manipulations held the motor task constant while disrupted the hedonic musical correspondence to blocking flow or occluded the partner’s body and task feedback to block social interaction. The manipulations’ effectiveness was confirmed using psychometric ratings and an objective measure for the depth of flow experience through the inhibition of the auditory-evoked potential to a task-irrelevant stimulus. Spectral power analysis revealed higher beta/gamma power specific to team flow at the left temporal cortex. Causal interaction analysis revealed that the left temporal cortex receives information from areas encoding individual flow or socialization. The left temporal cortex was also significantly involved in integrated information at both the intra- and inter-brains levels. Moreover, team flow resulted in enhanced global inter-brain integrated information and neural synchrony. Thus, our report presents neural evidence that team flow results in a distinct brain state and suggests a neurocognitive mechanism by which the brain creates this unique experience.Data AvailabilityAll data and analysis codes used in the preparation of this article are available athttps://osf.io/3b4hp.
The SARS-CoV-2 nucleocapsid protein is dynamic, disordered, and phase separates with RNA
Authors: Cubuk Jasmine , Alston Jhullian J. , Incicco J. Jeremías , Singh Sukrit , Stuchell-Brereton Melissa D. , Ward Michael D. , Zimmerman Maxwell I. , Vithani Neha , Griffith Daniel , Wagoner Jason A. , Bowman Gregory R. , Hall Kathleen B. , Soranno Andrea , Holehouse Alex S. 
Published: June 2020

AbstractThe SARS-CoV-2 nucleocapsid (N) protein is an abundant RNA binding protein critical for viral genome packaging, yet the molecular details that underlie this process are poorly understood. Here we combine single-molecule spectroscopy with all-atom simulations to uncover the molecular details that contribute to N protein function. N protein contains three dynamic disordered regions that house putative transiently-helical binding motifs. The two folded domains interact minimally such that full-length N protein is a flexible and multivalent RNA binding protein. N protein also undergoes liquid-liquid phase separation when mixed with RNA, and polymer theory predicts that the same multivalent interactions that drive phase separation also engender RNA compaction. We offer a simple symmetry-breaking model that provides a plausible route through which single-genome condensation preferentially occurs over phase separation, suggesting that phase separation offers a convenient macroscopic readout of a key nanoscopic interaction.
Membrane Insertion of MoS2Nanosheets: Fresh vs. Aged
Authors: Ye Rui , Song Wei , Gu Zonglin , Zhou Ruhong 
Published: June 2020

AbstractFresh two-dimensional (2D) molybdenum disulfide (MoS2) can absorb the hydrocarbon contamination from the ambient air and cause surface aging. Thus, understanding how the surface aging process of MoS2affects the interaction with biomolecules is crucial for its applications in the biomedical field. Here, we employed atomistic molecular dynamics simulations to investigate the interactions of fresh and aged MoS2nanosheets with POPE lipid membranes. Our results show that even though both the fresh and aged MoS2nanosheets are capable of spontaneous insertion into the POPE bilayer membrane, the fresh MoS2nanosheet displays significantly more robust interaction than the aged one. The potential mean force (PMF) calculations further confirm that the fresh MoS2nanosheet is more energetically favorable than the aged one in penetrating into the POPE lipid membranes, with the former having ~17 kJ/mol stronger binding affinity than the later. This work provides a deeper understanding of the surface-aging-dependent interaction of MoS2nanosheet with biomolecules, which might help the design of better MoS2-based nanodevices with appropriate surface properties.
Portieragives new clues on the evolutionary history of whiteflies
Authors: Santos-Garcia D. , Mestre-Rincon N. , Ouvrard D. , Zchori-Fein E. , Morin S. 
Published: June 2020

AbstractWhiteflies (Hemiptera: Sternorrhyncha: Aleyrodidae) are a superfamily of small phloem-feeding insects. Their taxonomy is currently based on the morphology of nymphal stages that display phenotypic plasticity, which produces inconsistencies. To overcome this limitation, we developed a new phylogenetic framework that targets five genes ofCandidatusPortiera aleyrodidarum, the primary endosymbiont of whiteflies.Portieralineages have been co-diverging with whiteflies since their origin and therefore reflect their host evolutionary history. We also studied the origin of stability and instability inPortieragenomes by testing for the presence of two alternative gene rearrangements and the loss of a functional polymerase proofreading subunit (dnaQ), previously associated with genome instability. We present two phylogenetic reconstructions. One using the sequences of all five target genes from 22 whitefly species belonging to 17 genera. The second uses only two genes to include additional publishedPortierasequences of 21 whitefly species, increasing our sampling size to 42 species from 25 genera. The developed framework showed low signal saturation, specificity to whitefly samples, and efficiency in solving inter-genera relationships and standing inconsistencies in the current taxonomy of the superfamily. Genome instability was found to be present only in the Aleurolobini tribe containing theSinghiella, AleurolobusandBemisiagenera. This suggests thatPortieragenome instability likely arose in the Aleurolobini tribe’s common ancestor, around 70 Mya. We propose a link between the switch from multi-bacteriocyte to a single-bacteriocyte mode of inheritance in the Aleurolobini tribe and the appearance of genome instability inPortiera.