bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Phosphorylation Status of NPH3 Affects Photosensory Adaptation During the Phototropic Response
Authors: Kimura Taro , Haga Ken , Nomura Yuko , Higaki Takumi , Nakagami Hirofumi , Sakai Tatsuya 
Published: December 2020

ABSTRACTPhotosensory adaptation, which can be classified as sensor or effector adaptation, optimizes the light sensing of living organisms by tuning their sensitivity to changing light conditions. During the phototropic response in Arabidopsis (Arabidopsis thaliana), the light-dependent expression controls of blue-light photoreceptor phototropin1 (phot1) and its modulator ROOT PHOTOTROPISM2 (RPT2) are known as the molecular mechanisms underlying sensor adaptation. However, little is known about effector adaption in plant phototropism. Here we show that control of the phosphorylation status of NONPHOTOTROPIC HYPOCOTYL3 (NPH3) leads to effector adaptation in hypocotyl phototropism. We identified seven phosphorylation sites of NPH3 proteins in the etiolated seedlings of Arabidopsis and generated unphosphorable and phosphomimetic NPH3 proteins on those sites. Unphosphorable NPH3 showed a shortening of its subcellular localization in the cytosol and caused an inability to adapt to very low fluence rates of blue light (∼10−5µmol m−2s−1) during the phototropic response. In contrast, the phosphomimetic NPH3 proteins had a lengthened subcellular localization in the cytosol and could not lead to the adaptation for blue light at fluence rates of 10−3µmol m−2s−1or more. Our results suggest that the activation levels of phot1 and the corresponding phosphorylation levels of NPH3 determine the rate of plasma membrane-cytosol shuttling of NPH3, which moderately maintains the active state of phot1 signaling across a broad range of blue-light intensities and contributes to the photosensory adaptation of phot1 signaling during the phototropic response in hypocotyls.One sentence summaryThe phosphorylation status of NON-PHOTOTROPIC HYPOCOTYL3 proteins affects their subcellular localization and the photosensory adaptation of phot1 signaling.
A competition of critics in human decision-making
Authors: Enkhtaivan Enkhzaya , Nishimura Joel , Ly Cheng , Cochran Amy 
Published: December 2020

AbstractRecent experiments and theories of human decision-making suggest positive and negative errors are processed and encoded differently by serotonin and dopamine, with serotonin possibly serving to oppose dopamine and protect against risky decisions. We introduce a temporal difference (TD) model of human decision-making to account for these features. Our model involves two critics, an optimistic learning system and a pessimistic learning system, whose predictions are integrated in time to control how potential decisions compete to be selected. Our model predicts that human decision-making can be decomposed along two dimensions: the degree to which the individual is sensitive to (1) risk and (2) uncertainty. In addition, we demonstrate that the model can learn about reward expectations and uncertainty, and provide information about reaction time despite not modeling these variables directly. Lastly, we simulate a recent experiment to show how updates of the two learning systems could relate to dopamine and serotonin transients, thereby providing a mathematical formalism to serotonin’s hypothesized role as an opponent to dopamine. This new model should be useful for future experiments on human decision-making.
COVID-19 genetic risk variants are associated with expression of multiple genes in diverse immune cell types
Authors: Schmiedel Benjamin J. , Chandra Vivek , Rocha Job , Gonzalez-Colin Cristian , Bhattacharyya Sourya , Madrigal Ariel , Ottensmeier Christian H. , Ay Ferhat , Vijayanand Pandurangan 
Published: December 2020

ABSTRACTCommon genetic polymorphisms associated with severity of COVID-19 illness can be utilized for discovering molecular pathways and cell types driving disease pathogenesis. Here, we assessed the effects of 679 COVID-19-risk variants on gene expression in a wide-range of immune cell types. Severe COVID-19-risk variants were significantly associated with the expression of 11 protein-coding genes, and overlapped with either target gene promoter orcis-regulatory regions that interact with target promoters in the cell types where their effects are most prominent. For example, we identified that the association between variants in the 3p21.31 risk locus and the expression ofCCR2in classical monocytes is likely mediated through an active cis-regulatory region that interacted withCCR2promoter specifically in monocytes. The expression of several other genes showed prominent genotype-dependent effects in non-classical monocytes, NK cells, B cells, or specific T cell subtypes, highlighting the potential of COVID-19 genetic risk variants to impact the function of diverse immune cell types and influence severe disease manifestations.
Strength in numbers: Large-scale integration of single-cell transcriptomic data reveals rare, transient muscle progenitor cell states in muscle regeneration
Authors: McKellar David W. , Walter Lauren D. , Song Leo T. , Mantri Madhav , Wang Michael F.Z. , De Vlaminck Iwijn , Cosgrove Benjamin D. 
Published: December 2020

ABSTRACTSkeletal muscle repair is driven by the coordinated self-renewal and fusion of myogenic stem and progenitor cells. Single-cell gene expression analyses of myogenesis have been hampered by the poor sampling of rare and transient cell states that are critical for muscle repair, and do not provide spatial information that is needed to understand the context in which myogenic differentiation occurs. Here, we demonstrate how large-scale integration of new and public single-cell and spatial transcriptomic data can overcome these limitations. We created a large-scale single-cell transcriptomic dataset of mouse skeletal muscle by integration, consensus annotation, and analysis of 23 newly collected scRNAseq datasets and 79 public single-cell (scRNAseq) and single-nucleus (snRNAseq) RNA-sequencing datasets. The resulting compendium includes nearly 350,000 cells and spans a wide range of ages, injury, and repair conditions. Combined, these data enabled identification of the predominant cell types in skeletal muscle with robust, consensus gene expression profiles, and resolved cell subtypes, including endothelial subtypes distinguished by vessel-type of origin, fibro/adipogenic progenitors marked by stem potential, and many distinct immune populations. The representation of different experimental conditions and the depth of transcriptome coverage enabled robust profiling of sparsely expressed genes. We built a densely sampled transcriptomic model of myogenesis, from stem-cell quiescence to myofiber maturation and identified rare, short-lived transitional states of progenitor commitment and fusion that are poorly represented in individual datasets. We performed spatial RNA sequencing of mouse muscle at three time points after injury and used the integrated dataset as a reference to achieve a high-resolution, local deconvolution of cell subtypes. This analysis identified the temporal variation in the colocalization of immune cell subtype interactions with myogenic progenitors during injury recovery. We provide a public web tool to enable interactive exploration and visualization of this rich single-cell transcriptomic resource. Our work supports the utility of large-scale integration of single-cell transcriptomic data as a tool for biological discovery.
Pan-genome analysis of Mycobacterium tuberculosis identifies accessory genome sequences deleted in modern Beijing lineage
Authors: Rufai Syed Beenish , Ozer Egon A. , Singh Sarman 
Published: December 2020

AbstractBeijing sub-lineage of Mycobacterium tuberculosis has been reported to have increased transmissibility and drug resistance. This led us to get insights of genomic landscape of modern Beijing sub-lineages in comparison with other lineages of M. tuberculosis utilizing pan-genomics approach. Pangenome analysis was performed using software Spine (v0.2.3), AGEnt (v0.2.3) and ClustAGE (v0.7.6). The average pangenome size was 45,40,849 bp with 4,391 coding sequences (CDS), with a GC content of 65.4%. The size of the core genome was 36,83,161 bp, contained 3,698 CDS and had an average GC content of 65.1%. The average accessory genome size was 6,96,320.9 bp, with 539.4 CDS and GC content of 67.9%. Among the accessory elements complete deletion of CRISPR-associated endoribonuclease cas1 (Rv2817c), cas2 (Rv2816c), CRISPR type III-a/mtube-associated protein csm6 (Rv2818c), CRISPR type III-a/mtube-associated ramp protein csm5 (Rv2819c) and partial deletion (61.5%) CRISPR type III-a/mtube-associated ramp protein csm4 (Rv2820c) sequences was found specifically in modern Beijing lineages taken in assortment. The sequences were validated using conventional PCR method, which precisely amplified the corresponding targets of sequence elements with 100% sensitivity and specificity. Deletion of accessory CRISPR sequence elements amongst the modern Beijing sub-lineage of M. tuberculosis suggest more defective DNA-repair in these strains which may enhance virulence of the strains. Further, the developed conventional PCR approach for detection of virulent modern Beijing lineage may be of interest to public health and outbreak control organizations for rapid detection of modern Beijing lineage.
Climate change impacts on the phylogenetic diversity of the world’s terrestrial birds: more than species numbers
Authors: Voskamp Alke , Hof Christian , Biber Matthias F. , Hickler Thomas , Niamir Aidin , Willis Stephen G. , Fritz Susanne A. 
Published: December 2020

AbstractOngoing climate change is a major threat to biodiversity and impacts on species distributions and abundances are already evident. Heterogenous responses of species due to varying abiotic tolerances and dispersal abilities have the potential to further amplify or ameliorate these impacts through changes in species assemblages. Here we investigate the impacts of climate change on terrestrial bird distributions and, subsequently, on species richness as well as on different aspects of phylogenetic diversity of species assemblages across the globe. We go beyond previous work by disentangling the potential impacts on assemblage phylogenetic diversity of species gains vs. losses under climate change and compare the projected impacts to randomized assemblage changes.We show that climate change might not only affect species numbers and composition of global species assemblages but could also have profound impacts on assemblage phylogenetic diversity, which, across extensive areas, differ significantly from random changes. Both the projected impacts on phylogenetic diversity and on phylogenetic structure vary greatly across the globe. Projected increases in the evolutionary history contained within species assemblages, associated with either increasing phylogenetic diversification or clustering, are most frequent at high northern latitudes. By contrast, projected declines in evolutionary history, associated with increasing phylogenetic over-dispersion or homogenisation, are projected across all continents.The projected widespread changes in the phylogenetic structure of species assemblages show that changes in species richness do not fully reflect the potential threat from climate change to ecosystems. Our results indicate that the most severe changes to the phylogenetic diversity and structure of species assemblages are likely to be caused by species range shifts rather than range reductions and extinctions. Our findings highlight the importance of considering diverse measures in climate impact assessments and the value of integrating species-specific responses into assessments of entire community changes.
Alpha activity neuromodulation induced by individual alpha-based neurofeedback learning in ecological context: A double-blind randomized study
Authors: Grosselin Fanny , Breton Audrey , Yahia-Cherif Lydia , Wang Xi , Spinelli Giuseppe , Hugueville Laurent , Fossati Philippe , Attal Yohan , Navarro-Sune Xavier , Chavez Mario , George Nathalie 
Published: December 2020

AbstractThe neuromodulation induced by neurofeedback training (NFT) remains a matter of debate. Investigating the modulation of brain activity specifically associated with NF requires controlling for multiple factors, such as reward, performance, congruency between task and targeted brain activity. This can be achieved using sham feedback (FB) control condition, equating all aspects of the experiment but the link between brain activity and FB. We aimed at investigating the modulation of individual alpha EEG activity induced by NFT in a double-blind, randomized, sham-controlled study. Forty-eight healthy participants were assigned to either NF (n=25) or control (n=23) group and performed alpha upregulation training (over 12 weeks) with a wearable EEG device. Participants of the NF group received FB based on their individual alpha activity. The control group received the auditory FB of participants of the NF group. An increase of alpha activity across training sessions was observed in the NF group only (p<0.001). This neuromodulation was selective in that it was not observed for theta (4-8Hz) and low beta (13-18Hz) activities. While alpha upregulation was found in the NF group only, psychological outcome variables showed increased feeling of control, decreased anxiety level and increased relaxation feeling in both the NF and control groups, without any significant difference between groups. This is interpreted in terms of learning context and placebo effects. Our results pave the way to self-learnt, NF-based neuromodulation with light-weighted, wearable EEG systems.
Scalable production of tissue-like vascularised liver organoids from human PSCs
Authors: Harrison Sean P , Siller Richard , Tanaka Yoshiaki , Xiang Yangfei , Patterson Benjamin , Kempf Henning , Melum Espen , Åsrud Kathrine S , Chollet Maria E , Andersen Elisabeth , Sandset Per Morten , Baumgarten Saphira , Bonanini Flavio , Kurek Dorota , Mathapati Santosh , Almaas Runar , Sharma Kulbhushan , Wilson Steven R , Skottvoll Frøydis S , Boger Ida C , Bogen Inger L , Nyman Tuula A , Wu Jun J , Bezrouk Ales , Cizkova Dana , Mokry Jaroslav , Zweigerdt Robert , Park In-Hyun , Sullivan Gareth J 
Published: December 2020

ABSTRACTA lack of physiological parity between 2D cell culture andin vivo, has paved the way towards more organotypic models. Organoids exist for a number of tissues, including the liver. However, current approaches to generate hepatic organoids suffer drawbacks, including a reliance on extracellular matrices (ECM), the requirement to pattern in 2D culture, costly growth factors and a lack of cellular diversity, structure and organisation. Current hepatic organoid models are generally simplistic, composed of hepatocytes or cholangiocytes, which renders them less physiologically relevant when compared to native tissue. Here we aim to address these drawbacks. To address this, we have developed an approach that does not require 2D patterning, is ECM independent combined with small molecules to mimic embryonic liver development that produces massive quantities of liver like organoids. Using single-cell RNA sequencing and immunofluorescence we demonstrate a liver-like cellular repertoire, a higher order cellular complexity, presenting with vascular luminal structures, innervation and a population of resident macrophage – the Kupffer cells. The organoids exhibit key liver functions including drug metabolism, serum protein production, coagulation factor production, bilirubin uptake and urea synthesis. The organoids can be transplanted and maintained in mice producing human albumin long term. The organoids exhibit a complex cellular repertoire reflective of the organ, havede novovascularization and innervation, enhanced function and maturity. This is a pre-requisite for a myriad of applications from cellular therapy, tissue engineering, drug toxicity assessment, disease modeling, to basic developmental biology.
Cobamide sharing drives skin microbiome dynamics
Authors: Swaney Mary Hannah , Sandstrom Shelby , Kalan Lindsay R 
Published: December 2020

ABSTRACTThe human skin microbiome is a key player in human health, with diverse functions ranging from defense against pathogens to education of the immune system. While recent studies have begun to shed light on the valuable role that skin microorganisms have in maintaining a healthy skin barrier, a detailed understanding of the complex interactions that shape healthy skin microbial communities is limited. Cobamides, the vitamin B12 class of cofactor, are essential for organisms across the tree of life. Because this vitamin is only produced by a limited fraction of prokaryotes, cobamide sharing has been shown to mediate community dynamics within microbial communities. Here, we provide the first large-scale unbiased metagenomic assessment of cobamide biosynthesis and utilization in the skin microbiome. We show that while numerous and diverse taxa across the major bacterial phyla on the skin are cobamide dependent, relatively few species encode for de novo cobamide biosynthesis. We find that cobamide sharing shapes the network structure in microbial communities across the different microenvironments of the skin and that changes in community structure and microbiome diversity are driven by the abundance of cobamide producers in the Corynebacterium genus, in both healthy and disease skin states. Lastly, we find that de novo cobamide biosynthesis is enriched only in host-associated Corynebacterium species, including those prevalent on human skin. We confirm that the cofactor is produced in excess through quantification of cobamide production by skin-associated species isolated in the laboratory. Taken together, our results support a role for cobamide sharing within skin microbial communities, which we predict stabilizes the microbiome and mediates host interactions.
Effect of Variations in the Conserved Residues E371 and S359 on the Structural Dynamics of Protein Z Dependent Protease Inhibitor (ZPI): A Molecular Dynamic Simulation Study
Authors: Subash Chellam Gayathri , Gupta Suchetana , Suresh Aravind , Senapati Sanjib , Sengupta Tanusree 
Published: December 2020

AbstractProtein Z (PZ) dependent protease inhibitor (ZPI) is a natural anticoagulant inhibiting blood coagulation proteases fXa and fXIa. Despite being a member of the serpin superfamily, it possesses unique structural features such as activation by PZ that regulate its inhibitory function. It is well known that effecient protease inhibition by serpins is dependent on the dynamics of its reactive center loop (RCL). In order to understand the RCL dynamics of ZPI, we performed Molecular Dynamics (MD) simulation on ZPI and its E371 and S359 variants located at important conserved functional sites. Unexpectedly, the RCL of E371 variants, such as E371K, E371R, and E371Q, were shown to be very stable due to compensatory interactions at the proximal end of RCL. Interestingly, RCL flexibility was shown to be enhanced in the double mutant K318-E371 due to the repulsive effect of increased negative charge on top of the breach region. Principal component analysis (PCA) coupled with residue wise interaction network (RIN) revealed correlated motion between the RCL and the PZ binding regions in the WT. Whereas the analysis revealed a loss of regulation in correlated motion between RCL and PZ binding hotspot Tyr240 in the double mutant. Additionally, the S359F and S359I mutations also resulted in increased RCL flexibility owing to the disruption of stabilizing hydrogen bonding interaction at the N terminal end of S5A. Thus, the current study proposes that the overall stabilizing interactions of S5A is a major regulator of proper loop movement of ZPI for protease inhibition and therefore its activity. The results would be beneficial to engineer activity compromised ZPI mutants as a prophylactic agent for the treatment of hemophilia.
Mistakes can stabilise the dynamics of rock-paper-scissors games
Authors: Kleshnina Maria , Streipert Sabrina S. , Filar Jerzy A. , Chatterjee Krishnendu 
Published: December 2020

AbstractA game of rock-paper-scissors is an interesting example of an interaction where none of the pure strategies strictly dominates all others, leading to a cyclic pattern. In this work, we consider an unstable version of rock-paper-scissors dynamics and allow individuals to make behavioural mistakes during the strategy execution. We show that such an assumption can break a cyclic relationship leading to a stable equilibrium emerging with only one strategy surviving. We consider two cases: completely random mistakes when individuals have no bias towards any strategy and a general form of mistakes. Then, we determine conditions for a strategy to dominate all other strategies. However, given that individuals who adopt a dominating strategy are still prone to behavioural mistakes in the observed behaviour, we may still observe extinct strategies. That is, behavioural mistakes in strategy execution stabilise evolutionary dynamics leading to an evolutionary stable and, potentially, mixed co-existence equilibrium.Author summaryA game of rock-paper-scissors is more than just a children’s game. This type of interactions is often used to describe competition among animals or humans. A special feature of such an interaction is that none of the pure strategies dominates, resulting in a cyclic pattern. However, in wild communities such interactions are rarely observed by biologists. Our results suggest that this lack of cyclicity may stem from imperfectness of interacting individuals. In other words, we show analytically that heterogeneity in behavioural patterns may break a cyclic relationship and lead to a stable equilibrium in pure or mixed strategies.
Optimal CD8+T-cell memory formation following subcutaneous cytomegalovirus infection requires virus replication but not early dendritic cell responses
Authors: Dimonte Sandra , Gimeno-Brias Silvia , Marsden Morgan , Chapman Lucy , Sabberwal Pragati , Clement Mathew , Humphreys Ian R 
Published: December 2020

AbstractCytomegalovirus (CMV) induction of large frequencies of highly functional memory T-cells has attracted much interest in the utility of CMV-based vaccine vectors, with exciting preclinical data obtained in models of infectious diseases and cancer. However, pathogenesis of human CMV (HCMV) remains a concern. Attenuated CMV-based vectors, such as replication- or spread-deficient viruses potentially offer an alternative to fully replicating vectors. However, it is not well-understood how CMV attenuation impacts vector immunogenicity, in particularly when administered via relevant routes of immunization such as the skin. Herein we used the murine cytomegalovirus (MCMV) model to investigate the impact of vector attenuation on T-cell memory formation following subcutaneous administration. We found that the spread deficient virus (ΔgL-MCMV) was impaired in its ability to induce memory CD8+T-cells reactive to some (M38, IE1) but not all (IE3) viral antigens. Impaired memory T-cell development was associated with a preferential and pronounced loss of polyfunctional (IFN-γ+TNF-α+) T-cells, and was not rescued by increasing the dose of replication-defective MCMV. Finally, whilst vector attenuation reduced dendritic cell (DC) recruitment to skindraining lymph nodes, systematic depletion of multiple DC subsets during acute subcutaneous MCMV infection had a negligible impact on T-cell memory formation, implying that attenuated responses induced by replication-deficient vectors were likely not a consequence of impaired initial DC activation. Thus, overall, these data imply that the choice of antigen and/or cloning strategy of exogenous antigen in combination with the route of immunization may influence the ability of attenuated CMV vectors to induce robust functional T-cell memory.