bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Factor I in neurons, glia and during the formation of Müller glia-derived progenitor cells in avian, porcine and primate retinas
Authors: El-Hodiri Heithem M. , Campbell Warren A. , Kelly Lisa E. , Hawthorn Evan C. , Schwartz Maura , Jalligampala Archana , McCall Maureen A. , Meyer Kathrin , Fischer Andy J. 
Published: July 2021

AbstractThe regenerative potential of Müller glia (MG) is extraordinary in fish, poor in chick and terrible in mammals. In the chick model, MG readily reprogram into proliferating Müller glia-derived progenitor cells (MGPCs), but neuronal differentiation is very limited. The factors that suppress the neurogenic potential of MGPCs in the chick are slowly being revealed. Isoforms of Nuclear Factor I (NFI) are cell-intrinsic factors that limit neurogenic potential; these factors are required for the formation of MG in the developing mouse retina (Clark et al., 2019) and deletion of these factors reprograms MG into neuron-like cells in mature mouse retina (Hoang et al., 2020). Accordingly, we sought to characterize the patterns of expression NFIs in the developing, mature and damaged chick retina. In addition, we characterized patterns of expression of NFIs in the retinas of large mammals, pigs and monkeys. Using a combination of single cell RNA-sequencing (scRNA-seq) and immunolabeling we probed for patterns of expression. In embryonic chick, levels of NFIs are very low in early E5 (embryonic day 5) retinal progenitor cells (RPCs), up-regulated in E8 RPCs, further up-regulated in differentiating MG at E12 and E15. NFIs are maintained in mature resting MG, microglia and neurons. Levels of NFIs are reduced in activated MG in retinas treated with NMDA and/or insulin+FGF2, and further down-regulated in proliferating MGPCs. However, levels of NFIs in MGPCs were significantly higher than those seen in RPCs. Immunolabeling for NFIA and NFIB closely matched patterns of expression revealed in different types of retinal neurons and glia, consistent with findings from scRNA-seq. In addition, we find expression of NFIA and NFIB through progenitors in the circumferential marginal zone at the far periphery of the retina. We find similar patterns of expression for NFIs in scRNA-seq databases for pig and monkey retinas. Patterns of expression of NFIA and NFIB were validated with immunofluorescence in pig and monkey retinas wherein these factors were predominantly detected in MG and a few types of inner retinal neurons. In summary, NFIA and NFIB are prominently expressed in developing chick retina and by mature neurons and glia in the retinas of chicks, pigs and monkeys. Although levels of NFIs are decreased in chick, in MGPCs these levels remain higher than those seen in neurogenic RPCs. We propose that the neurogenic potential of MGPCs in the chick retina is suppressed by NFIs.
The Burkholderia cenocepacia type VI secretion system effector TecA is a virulence factor during lung infection
Authors: Loeven Nicole A. , Perault Andrew I. , Cotter Peggy A. , Hodges Craig A. , Schwartzman Joseph D. , Hampton Thomas H. , Bliska James B. 
Published: July 2021

AbstractBurkholderia cenocepacia (Bc) is a member of the Burkholderia cepacia complex (Bcc), a group of bacteria with members responsible for causing lung infections in cystic fibrosis (CF) patients. The most severe outcome of Bcc infection in CF patients is cepacia syndrome, a disease characterized by necrotizing pneumonia with bacteremia and sepsis. Bc is strongly associated with cepacia syndrome making it one of the most virulent members of the Bcc. Mechanisms underlying the pathogenesis of Bc in lung infections and cepacia syndrome remain to be uncovered. Bc is primarily an intracellular pathogen, and encodes the type VI secretion system (T6SS) anti-host effector TecA, which is translocated into host cells. TecA is a deamidase that inactivates multiple Rho GTPases, including RhoA. Inactivation of RhoA by TecA triggers assembly of the pyrin inflammasome, leading to secretion of proinflammatory cytokines such as IL-1β from macrophages. Previous work with the Bc clinical isolate J2315 showed that TecA increases immunopathology during acute lung infection in C57BL/6 mice and suggested that this effector acts as a virulence factor by triggering assembly of the pyrin inflammasome. Here, we extend these results using a second Bc clinical isolate, AU1054, to demonstrate that TecA exacerbates weight loss and lethality during lung infection in C57BL/6 mice and CF mice. Unexpectedly, pyrin was dispensable for TecA virulence activity in both mouse infection models. Our findings establish that TecA is a Bc virulence factor that exacerbates lung inflammation, weight loss, and lethality in a mouse lung infection model.ImportanceBc is often considered the most virulent species in the Bcc because of its close association with cepacia syndrome in addition to its capacity to cause chronic lung infections in CF patients (Loutet and Valvano 2010). Prior to this study virulence factors of Bc important for causing lethal disease had not been identified in a CF animal model of lung infection. Results of this study describe a CF mouse model and its use in demonstrating that the T6SS effector TecA of Bc exacerbates inflammatory cell recruitment and weight loss and is required for lethality and thus acts as a key virulence factor during lung infection. This model will be important in further studies to better understand TecA’s role as a virulence factor and in investigating ways to prevent or treat Bc infections in CF patients. Additionally, TecA may be the founding member of a family of virulence factors in opportunistic pathogens.
Climate and mountains shaped human ancestral genetic lineages
Authors: Delser Pierpaolo Maisano , Krapp Mario , Beyer Robert , Jones Eppie R , Miller Eleanor F , Hovhannisyan Anahit , Parker Michelle , Siska Veronika , Vizzari Maria Teresa , Pearmain Elizabeth J. , Imaz-Rosshandler Ivan , Leonardi Michela , Somma Gian Luigi , Hodgson Jason , Tysall Eirlys , Xue Zhe , Cassidy Lara , Bradley Daniel G , Eriksson Anders , Manica Andrea 
Published: July 2021

AbstractExtensive sequencing of modern and ancient human genomes has revealed that contemporary populations can be explained as the result of recent mixing of a few distinct ancestral genetic lineages1. But the small number of aDNA samples that predate the Last Glacial Maximum means that the origins of these lineages are not well understood. Here, we circumvent the limited sampling by modelling explicitly the effect of climatic changes and terrain on population demography and migrations through time and space, and show that these factors are sufficient to explain the divergence among ancestral lineages. Our reconstructions show that the sharp separation between African and Eurasian lineages is a consequence of only a few limited periods of connectivity through the arid Arabian peninsula, which acted as the gate out of the Arican continent. The subsequent spread across Eurasia was then mostly shaped by mountain ranges, and to a lesser extent deserts, leading to the split of European and Asians, and the further diversification of these two groups. A high tolerance to cold climates allowed the persistence at high latitudes even during the Last Glacial Maximum, maintaining a pocket in Beringia that led to the later, rapid colonisation of the Americas. The advent of food production was associated with an increase in movement2, but mountains and climate have been shown to still play a major role even in this latter period3,4, affecting the mixing of the ancestral lineages that we have shown to be shaped by those two factors in the first place.
Muscle effort is best minimized by the right-dominant arm in the gravity field
Authors: Poirier Gabriel , Lebigre Mélanie , Mourey France , Papaxanthis Charalambos , Gaveau Jeremie 
Published: July 2021

AbstractThe central nervous system (CNS) is thought to develop motor strategies that minimize various hidden criteria, such as end-point variance or effort. A large body of literature suggests that the dominant arm is specialized for such open-loop optimization-like processes whilst the non-dominant arm is specialized for closed-loop control. Building on recent results suggesting that the brain plans arm movements that takes advantage of gravity effects to minimize muscle effort, the present study tests the hypothesized superiority of the dominant arm motor system for effort minimization. Thirty participants (22.5 ± 2.1 years old; all right-handed) performed vertical arm movements between two targets (40° amplitude), in two directions (upwards and downwards) with their two arms (dominant and non-dominant). We recorded the arm kinematics and the electromyographic activity of the anterior and posterior deltoid to compare two motor signatures of the gravity-related optimization process; i.e., directional asymmetries and negative epochs on phasic muscular activity. We found that these motor signatures were still present during movements performed with the non-dominant arm, indicating that the effort-minimization process also occurs for the non-dominant motor system. However, these markers were reduced compared with movements performed with the dominant arm. This difference was especially prominent during downward movements, where the optimization of gravity effects occurs early in the movement. Assuming that the dominant arm is optimal to minimize muscle effort, as suggested by previous studies, the present results support the hypothesized superiority of the dominant arm motor system for effort-minimization.
Equatorial to Polar genomic variability of the microalgae Bathycoccus prasinos
Authors: Leconte Jade , Timsit Youri , Delmont Tom O. , Lescot Magali , Piganeau Gwenael , Wincker Patrick , Jaillon Olivier 
Published: July 2021

AbstractPhytoplankton plays a fundamental role in the ecology of ocean systems and is the key player in the global carbon cycle. At a time of global warming, understanding the mechanisms of its adaptation to temperature is therefore of paramount importance. Cosmopolitan planktonic species abundant in different marine environments provide both a unique opportunity and an efficient methodological tool to study the genomic bases of their adaptation. This is the case for the eukaryotic picoalga Bathycoccus prasinos, whose genomic variability we chose to study in temperate and polar oceanic waters. Using multiple metagenomic datasets, we found that ~5% of B. prasinos genomic positions are variable, with an overwhelming majority of biallelic motifs. Cold and temperate waters are clearly associated with changes in variant frequencies, whereas in transitional waters we found more balanced polymorphism at most of these positions. Mesophilic and psychrophilic gene variants are distinguished by only a few amino acid changes located at positions critical for physical and functional protein properties. These results provide new information on the genomic diversity of a cosmopolitan eukaryotic planktonic specie and reveal “minimal mutational strategies” which finely tune the properties of specific proteins at different temperatures.
Statistics of the number of equilibria in random social dilemma evolutionary games with mutation
Authors: Duong Manh Hong , Han The Anh 
Published: July 2021

AbstractIn this paper, we study analytically the statistics of the number of equilibria in pairwise social dilemma evolutionary games with mutation where a game’s payoff entries are random variables. Using the replicator-mutator equations, we provide explicit formulas for the probability distributions of the number of equilibria as well as other statistical quantities. This analysis is highly relevant assuming that one might know the nature of a social dilemma game at hand (e.g., cooperation vs coordination vs anti-coordination), but measuring the exact values of its payoff entries is difficult. Our delicate analysis shows clearly the influence of the mutation probability on these probability distributions, providing insights into how varying this important factor impacts the overall behavioural or biological diversity of the underlying evolutionary systems.
Stochastic model of T Cell repolarization during target elimination (II)
Authors: Hornak Ivan , Rieger Heiko 
Published: July 2021

AbstractCytotoxic T lymphocytes (T cells) and natural killer cells form a tight contact, the immunological synapse (IS), with target cells, where they release their lytic granules containing perforin/granzyme and cytokine containing vesicles. During this process the cell repolarizes and moves the microtubule organizing center (MTOC) towards the IS. In the first part of our work we developed a computational model for the molecular-motor-driven motion of the MT cytoskeleton during T cell polarization and analyzed effects of cortical sliding and capture-shrinkage mechanisms. Here we use this model to analyze the dynamics of the MTOC repositioning in situations in which a) the IS is in an arbitrary position with respect to the initial position of the MTOC and b) the T cell has two IS at two arbitrary positions. In the case of one IS, we found that the initial position determines which mechanism is dominant and that the time of repositioning does not rise monotonously with the MTOC-IS distance. In the case of two IS, we observe several scenarios that have also been reported experimentally: the MTOC alternates stochastically (but with a well defined average transition time) between the two IS; it wiggles in between the two IS without transiting to one of the two; or it is at some point pulled to one of the two IS and stays there. Our model allows to predict which scenario emerges in dependency of the mechanisms in action and the number of dyneins present. We report that the presence of capture-shrinkage mechanism at least in one IS is necessary to assure the transitions in every cell configuration. Moreover, the frequency of transitions does not decrease with the distance between the two IS and is the highest when both mechanisms are present in both IS.
Neo-sex chromosome evolution shapes sex-dependent asymmetrical introgression barrier
Authors: Wang Silu , Nalley Matthew J. , Chatla Kamalakar , Aldaimalani Reema , MacPherson Ailene , Wei Kevin , Corbett Russ , Mai Dat , Bachtrog Doris 
Published: July 2021

AbstractIt is increasingly recognized that sex chromosomes are not only the “battlegrounds” between sexes, but also the “Great Walls” fencing-off introgression between diverging lineages. Here we describe conflicting roles of nascent sex chromosomes on patterns of introgression in an experimental hybrid swarm. Drosophila nasuta and D. albomicans are recently diverged, fully fertile sister species that have different sex chromosome systems. The fusion between an autosome (Muller CD) with the ancestral X and Y gave rise to neo-sex chromosomes in D. albomicans, while Muller CDs remains unfused in D. nasuta. We found that a large block containing overlapping inversions on the neo-sex chromosome stood out as the strongest barrier to introgression. Intriguingly, the neo-sex chromosome introgression barrier is asymmetrical in a sex-dependent manner. Female hybrids showed significant D. albomicans biased introgression on Muller CD (neo-X excess), while males showed heterosis with excessive (neo-X, D. nasuta Muller CD) genotypes. While the neo-Y is a more compatible pairing partner of the neo-X, it also shows moderate levels of degeneration and may thus be selectively disfavored, and sex ratio assay revealed heterospecific meiotic drive. We used a population genetic model to dissect the interplay of sex chromosome drive, heterospecific pairing incompatibility between the neo-sex chromosomes and unfused Muller CD, neo-Y disadvantage, and neo-X advantage in generating the observed neo-X excess in females and heterozygous (neo-X, D. nasuta Muller CD) genotypes in males. We show that moderate neo-Y disadvantage and D. albomicans specific meiotic drive are required to counteract the effect of heterospecific meiotic drive observed in our cross, in concert with pairing incompatibility and neo-X advantage to explain observed genotype frequencies. Together, this hybrid swarm between a young species pair shed light onto the dual roles of neo-sex chromosome evolution in creating a sex-dependent asymmetrical introgression barrier at species boundary.
+microstate: A MATLAB toolbox for brain microstate analysis in sensor and cortical EEG/MEG
Authors: Tait Luke , Zhang Jiaxiang 
Published: July 2021

Abstract+microstate is a MATLAB toolbox for brain functional microstate analysis. It builds upon previous EEG microstate literature and toolboxes by including algorithms for microstate analysis for other neuroimaging modalities such as sensor-space MEG and source-space data. +microstate includes codes for performing individual- and group-level brain microstate analysis in resting-state and task-based data including event-related potentials/fields. Functions are included to visualise and perform statistical analysis of microstate sequences, including novel advanced statistical approaches such as microstate-segmented functional connectivity analysis, cluster-permutation topographic ANOVAs, and χ2 analysis of microstate probabilities in response to stimuli. Additionally, codes for simulating microstate sequences and their associated M/EEG data are included in the toolbox, which can be used to generate artificial data with ground truth microstates and to validate the methodology. +microstate integrates with widely used toolboxes for M/EEG processing including Fieldtrip, SPM, LORETA/sLORETA, EEGLAB, and Brainstorm to aid with accessibility, and includes wrappers for pre-existing toolboxes for brain-state estimation such as Hidden Markov modelling (HMM-MAR) and independent component analysis (FastICA) to aid with direct comparison with these techniques. In this paper, we first introduce +microstate before subsequently performing example analyses using open access datasets to demonstrate and validate the methodology. MATLAB live scripts for each of these analyses are included in +microstate, to act as a tutorial and to aid with reproduction of the results presented in this manuscript.
The evolutionary conserved complex CEP90, FOPNL and OFD1 specifies the future location of centriolar distal appendages, and promotes their assembly
Authors: Le Borgne Pierrick , Greibill Logan , Laporte Marine Hélène , Lemullois Michel , Bouhouche Khaled , Temagoult Mebarek , Rosnet Olivier , Le Guennec Maeva , Lignières Laurent , Chevreux Guillaume , Koll France , Hamel Virginie , Guichard Paul , Tassin Anne-Marie 
Published: July 2021

AbstractIn metazoa, cilia assembly is a cellular process that starts with centriole to basal body maturation, migration to the cell surface and docking to the plasma membrane. Basal body docking involves the interaction of both the distal end of the basal body and the transition fibers / distal appendages, with the plasma membrane. Mutations in numerous genes involved in basal body docking and transition zone assembly are associated with the most severe ciliopathies, highlighting the importance of these events in cilium biogenesis. In this context, the ciliateParameciumhas been widely used as a model system to study basal body and cilia assembly. However, despite the apparent evolutionary conservation of cilia assembly events across phyla, whether the same molecular players are functionally conserved, is not fully known. Here, we demonstrated that CEP90, FOPNL and OFD1 form an evolutionary conserved complex that is crucial for ciliogenesis. Using ultrastructure expansion microscopy, we unveiled that these proteins localize at the distal end of both centrioles/basal bodies inParameciumand mammalian cells. Moreover, we found that these proteins are recruited early after centriole duplication on the external surface of the procentriole and define the future location of the distal appendages. Functional analysis performed both inParameciumand mammalian cells demonstrate the requirement of this complex for distal appendage assembly and basal body docking. Finally, we show that mammals require another component, Moonraker (MNR), to recruit OFD1, FOPNL, and CEP90, which will then recruits the distal appendage protein CEP83. Altogether, we propose that this ternary complex is required to determine the future position of distal appendages.
Inferring viral occurrence patterns through a synthetic data simulation
Authors: Pimenoff Ville N. , Cleries Ramon 
Published: July 2021

AbstractViruses infecting humans are manifold and several of them provoke significant morbidity and mortality. Simulations creating large synthetic datasets from observed multiple viral strain infections in a limited population sample can be a powerful tool to infer significant pathogen occurrence and interaction patterns, particularly if limited number of observed data units is available. Here, to demonstrate diverse human papillomavirus (HPV) strain occurrence patterns, we used log-linear models combined with Bayesian framework for graphical independence network (GIN) analysis. That is, to simulate datasets based on modeling the probabilistic associations between observed viral data points, i.e different viral strain infections in a set of population samples. Our GIN analysis outperformed in precision all oversampling methods tested for simulating large synthetic viral strain-level prevalence dataset from observed set of HPVs data. Altogether, we demonstrate that network modeling is a potent tool for creating synthetic viral datasets for comprehensive pathogen occurrence and interaction pattern estimations.
Fifteen shades of clay: distinct microbial community profiles obtained from bentonite samples by cultivation and direct nucleic acid extraction
Authors: Vachon Melody A. , Engel Katja , Beaver Rachel C. , Slater Greg W. , Binns W. Jeffrey , Neufeld Josh D. 
Published: July 2021

AbstractCharacterizing the microbiology of swelling bentonite clays can help predict the long-term behaviour of deep geological repositories (DGRs), which are proposed as a solution for the management of used nuclear fuel worldwide. Such swelling clays represent an important component of several proposed engineered barrier system designs and, although cultivation-based assessments of bentonite clay are routinely conducted, direct nucleic acid detection from these materials has been difficult due to technical challenges. In this study, we generated direct comparisons of microbial abundance and diversity captured by cultivation and direct nucleic acid analyses using 15 reference bentonite clay samples. Regardless of clay starting material, the corresponding profiles from cultivation-based approaches were consistently associated with phylogenetically similar sulfate-reducing bacteria, denitrifiers, aerobic heterotrophs, and fermenters, demonstrating that any DGR-associated growth may be consistent, regardless of the specific bentonite clay starting material selected for its construction. Furthermore, dominant nucleic acid sequences in the as-received clay microbial profiles did not correspond with the bacteria that were enriched or isolated in culture. Few core taxa were shared among cultivation and direct nucleic acid analysis profiles, yet those in common were primarily affiliated with Streptomyces, Micrococcaceae, Bacillus, and Desulfosporosinus genera. These putative desiccation-resistant bacteria associated with diverse bentonite clay samples can serve as targets for experiments that evaluate microbial viability and growth within DGR-relevant conditions. Our data will be important for global nuclear waste management organizations, demonstrating that identifying appropriate design conditions with suitable clay swelling properties will prevent growth of the same subset of clay-associated bacteria, regardless of clay origin or processing conditions.