bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analysis of microsatellite polymorphisms in human populations
Authors: Gochi Leo , Kawai Yosuke , Fujimoto Akihiro 
Published: June 2022

AbstractMicrosatellites (MS) are tandem repeats of short units and have been used for population genetics, individual identification, and medical genetics. However, studies of MS on a whole genome level are limited, and genotyping methods for MS have yet to be established. Here, we analyzed approximately 8.5 million MS regions using a previously developed MS caller (MIVcall method) for three large publicly available human genome sequencing data sets: the Korean Personal Genome Project (KPGP), Simons Genome Diversity Project (SGDP), and Human Genome Diversity Project (HGDP). Our analysis identified 253,114 polymorphic MS. A comparison among different populations suggests that MS in the coding region evolved by random genetic drift and natural selection. In an analysis of genetic structures, MS clearly revealed population structures as SNPs and detected clusters that were not found by SNPs in African and Oceanian populations. Based on the MS polymorphisms, we selected an effective MS set for individual identification. We also showed that our MS analysis method can be applied to ancient DNA samples. This study provides a comprehensive picture of MS polymorphisms and application to human population studies.
A machine learning based method for the identification of functionally important genes
Authors: Das Gourab , Ghosh Indira 
Published: June 2022

AbstractDeciphering complex mechanisms underlying communicable and non-communicable diseases require comprehensive analysis of genetic factors and interactions between them. Experimental identification of genes related to pathogen’s virulence and human diseases is effective but laborious, time consuming and costly. Consequently, many genetic factors associated with pathogenesis or disease still remain to be unknown. In present work, a normalized point wise mutual information (nPMI) driven computational method has been developed to identify the association between biological entities (genes) and physiological responses utilizing published literatures in PubMed. Association prediction models are then developed using machine learning approach for four different datasets including virulent genes from two bacterial species (E. coli and S. enterica) and stress responsive genes from two plant species (A. thaliana and O. sativa). This approach provides a generic platform for identifying association of genes in diverse biological systems (host and pathogen) and provide up-to-date estimate of association measures of the genes with stress, virulence. In future, the causal relation between them may be of research importance.
Multi-channel recordings reveal age-related differences in the sleep of juvenile and adult zebra finches
Authors: Yeganegi Hamed , Ondracek Janie M. 
Published: June 2022

AbstractDespite their phylogenetic differences and distinct pallial structures, mammals and birds show similar electroencephalography (EEG) traces during sleep, consisting of distinct rapid eye movement (REM) sleep and slow wave sleep (SWS) stages. Studies in human and a limited number of other mammalian species shows that this organization of sleep into interleaving stages undergoes radical changes during lifetime. Do these age-dependent variations in sleep patterns also occur in the avian brain? Does vocal learning have an effect on sleep patterns in birds? To answer this question, we recorded multi-channel sleep EEG from juveniles and adult zebra finches for several nights. Whereas adults spent more time in SWS and REM sleep, juveniles spent more time in intermediate sleep (IS). The amount of IS sleep was significantly larger in male juveniles engaged in vocal learning compared to female juveniles, which suggest that IS sleep could be important for learning. In addition, we observed that the functional connectivity increased rapidly during maturation of young juveniles, and was stable or declined at older ages. Synchronous activity during sleep was larger for recording sites in the left hemisphere for both juveniles and adults, and generally intra-hemispheric synchrony was larger than inter-hemispheric synchrony during sleep. A graph theory analysis revealed that in adults, highly correlated EEG activity tends to be distributed across fewer networks that are spread across a wider area of the brain, whereas in juveniles, highly correlated EEG activity is distributed across more numerous, albeit smaller, networks in the brain. Overall, our results reveal significant changes in the neural signatures of sleep during maturation in an avian brain.
Early adversity changes the economic conditions of structural brain network organisation
Authors: Carozza Sofia , Holmes Joni , Vértes Petra E. , Bullmore Ed , Arefin Tanzil M. , Pugliese Alexa , Zhang Jiangyang , Kaffman Arie , Akarca Danyal , Astle Duncan E. 
Published: June 2022

AbstractEarly adversity can change educational, cognitive, and mental health outcomes. However, the neural processes through which early adversity exerts these effects remain largely unknown. We used generative network modelling of the mouse connectome to test whether unpredictable postnatal stress shifts the constraints that govern the formation of the structural connectome. A model that trades off the wiring cost of long-distance connections with topological homophily (i.e. links between regions with shared neighbours) generated simulations that replicate the organisation of the rodent connectome. The imposition of early life adversity significantly shifted the best-performing parameter combinations toward zero, heightening the stochastic nature of the generative process. Put simply, unpredictable postnatal stress changes the economic constraints that shape network formation, introducing greater randomness into the structural development of the brain. While this change may constrain the development of cognitive abilities, it could also reflect an adaptive mechanism. In other words, neural development could harness heightened stochasticity to make networks more robust to perturbation, thereby facilitating effective responses to future threats and challenges.Significance statementChildren who experience adversity early in life – such as chronic poverty or abuse – show numerous neural differences that are linked to poorer cognition and mental health later in life. To effectively mitigate the burden of adversity, it is critical to identify how these differences arise. In this paper, we use computational modelling to test whether growing up in an impoverished and unpredictable environment changes the development of structural connections in the mouse brain. We found that early adversity appears to introduce more stochasticity in the formation of neural architecture. Our findings point to a potential mechanism for how early adversity could change the course of child development.
Efficient stabilization of imprecise statistical inference through conditional belief updating
Authors: Drevet Julie , Drugowitsch Jan , Wyart Valentin 
Published: June 2022

AbstractStatistical inference is the optimal process for forming and maintaining accurate beliefs about uncertain environments. However, human inference comes with costs due to its associated biases and limited precision. Indeed, biased or imprecise inference can trigger variable beliefs and unwarranted changes in behavior. Here, by studying decisions in a sequential categorization task based on noisy visual stimuli, we obtained converging evidence that humans reduce the variability of their beliefs by updating them only when the reliability of incoming sensory information is judged as sufficiently strong. Instead of integrating the evidence provided by all stimuli, participants actively discarded as much as a third of stimuli. This conditional belief updating strategy shows good test-retest reliability, correlates with perceptual confidence, and explains human behavior better than previously described strategies. This seemingly suboptimal strategy not only reduces the costs of imprecise computations, but counter-intuitively increases the accuracy of resulting decisions.
Lysine 27 of histone H3.3 is a fine modulator of developmental gene expression and stands as an epigenetic checkpoint for lignin biosynthesis in Arabidopsis
Authors: Fal Kateryna , Tomkova Denisa , Le Masson Marie , Faigenboim Adi , Pano Emeline , Ishkhneli Nickolay , Moyal Netta-Lee , Villette Claire , Chabouté Marie-Edith , Berr Alexandre , Williams Leor Eshed , Carles Cristel C. 
Published: June 2022

SummaryChromatin is a dynamic platform within which gene expression is controlled by epigenetic modifications, notably targeting amino acid residues of histone H3. Among them is Lysine 27 of H3 (H3K27), which trimethylation by the Polycomb Repressive Complex 2 (PRC2) is instrumental in regulating spatio-temporal patterns of key developmental genes. H3K27 is also subjected to acetylation, found at sites of active transcription. Most information on the function of histone residues and their associated modifications in plants was obtained from studies of loss-of-function mutants for the complexes that modify them.In order to decrypt the genuine function of H3K27, we expressed a non-modifiable variant of H3 at residue K27 (H3.3K27A) in Arabidopsis, and developed a multi-scale approach combining in-depth phenotypical and cytological analyses, with transcriptomics and metabolomics.We uncovered that the H3.3K27A variant causes severe developmental defects, part of them reminiscent of PRC2 mutants, part of them new. They include early flowering, increased callus formation, and short stems with thicker xylem cell layer. This latest phenotype correlates with mis-regulation of phenylpropanoid biosynthesis.Overall, our results reveal novel roles of H3K27 in plant cell fates and metabolic pathways, and highlight an epigenetic control point for elongation and lignin composition of the stem.
Immune gene variation associated with chromosome-scale differences among individual zebrafish genomes
Authors: McConnell Sean C. , Hernandez Kyle M. , Andrade Jorge , de Jong Jill L.O. 
Published: June 2022

ABSTRACTImmune genes have evolved to maintain exceptional diversity, offering robust defense against pathogens. We performed genomic sequencing and assembly to examine immune gene variation among three zebrafish individuals. We identified remarkably high levels of sequence divergence as well as presence/absence variation among these zebrafish genomes, particularly when compared with the level of variation in human genomes. Gene pathway analysis identified zebrafish immune genes as significantly enriched among genes with evidence of positive selection. A large subset of genes was absent from analysis of coding sequences due to apparent lack of reads, prompting us to examine genes overlapping zero coverage regions (ZCRs), defined as 2kb stretches without mapped reads. Zebrafish immune genes were also identified as highly enriched within ZCRs, including over 60% of zebrafish major histocompatibility complex (MHC) genes and NOD-like receptor (NLR) genes, mediators of direct and indirect pathogen recognition. This variation was most highly concentrated throughout one arm of zebrafish chromosome 4 carrying a large cluster of NLR genes, associated with large-scale structural variation covering more than half of a vertebrate chromosome. While previous studies have shown marked variation in NLR genes between vertebrate species, our study highlights extensive variation between individuals of the same species. Our genomic assemblies also provide sequences for alternative haplotypes and distinct complements of immune genes among individual zebrafish, including the MHC Class II locus. Taken together, these findings provide evidence of immune gene variation on a scale previously unknown in other vertebrate species and raise questions about potential impact on immune function.
A phage weaponizes a satellite recombinase to subvert viral restriction
Authors: Nguyen Maria HT , Netter Zoe , Angermeyer Angus , Seed Kimberley D. 
Published: June 2022

ABSTRACTBacteria can acquire mobile genetic elements (MGEs) to combat infection by viruses (phages). Satellite viruses, including the PLEs (phage-inducible chromosomal island-like elements) in epidemic Vibrio cholerae, are MGEs that restrict phage replication to the benefit of their host bacterium. PLEs parasitize the lytic phage ICP1, unleashing multiple mechanisms to restrict phage replication and promote their own spread. In the arms race against PLE, ICP1 uses nucleases, including CRISPR-Cas, to destroy PLE’s genome during infection. However, through an unknown CRISPR-independent mechanism, specific ICP1 isolates subvert restriction by PLE. Here, we discover ICP1-encoded Adi that counteracts PLE by exploiting the PLE’s large serine recombinase (LSR), which normally mobilizes PLE in response to ICP1 infection. Unlike previously characterized ICP1-encoded anti-PLE mechanisms, Adi is not a nuclease itself but instead appears to modulate the activity of the LSR to promote destructive nuclease activity of the LSR’s specific attachment site, attP. The PLE LSR, its catalytic activity, and attP are additionally sufficient to sensitize a PLE encoding a resistant variant of the recombination module to Adi activity. This work highlights a unique type of adaptation arising from inter-genome conflicts, in which the intended activity of a protein can be weaponized to overcome the antagonizing genome.
Morphological integration and evolutionary potential of the primate shoulder: Variation among taxa and implications for genetic covariances with the basicranium, pelvis, and arm
Authors: Agosto Elizabeth R. , Auerbach Benjamin M. 
Published: June 2022

AbstractWithin the primate order, the morphology of the shoulder girdle is immensely variable and has been shown to reflect the functional demands of the upper limb. The observed morphological variation among extant primate taxa consequently has been hypothesized to be driven by selection for different functional demands. Evolutionary analyses of the shoulder girdle often assess this anatomical region, and its traits, individually, therefore implicitly assuming independent evolution of the shoulder girdle. However, the primate shoulder girdle has developmental and functional covariances with the basicranium and pelvic girdle that have been shown to potentially influence its evolution. It is unknown whether these relationships are similar or even present across primate taxa, and how they may affect morphological variation among primates. This study evaluates the strength of covariance and evolutionary potential across four anatomical regions: shoulder girdle, basicranium, pelvis, and distal humerus. Measures of morphological integration and evolutionary potential (conditioned covariance, and evolutionary flexibility) are assessed across eight anthropoid primate taxa. Results demonstrate a consistent pattern of morphological constraint within paired anatomical regions across primates. Differences in evolutionary flexibility are observed among primate genera, with humans having the highest evolutionary potential overall. This pattern does not follow functional differences, but rather a separation between monkeys and apes. Therefore, evolutionary hypotheses of primate shoulder girdle morphological variation that evaluate functional demands alone may not account for the effect of these relationships. Collectively, our findings suggest differences in genetic covariance among anatomical regions may have contributed to the observable morphological variation among taxa.
Rescue of transcriptional pausing in metabolic genes jumpstarts Salmonella antioxidant defenses
Authors: Kant Sashi , Till James Karl A , Liu Lin , Kim Ju-Sim , Vazquez-Torres Andres 
Published: June 2022

ABSTRACTDetoxification, scavenging and repair systems embody the archetypical antioxidant defenses of prokaryotic and eukaryotic cells1–3. Metabolic rewiring is an emergent aspect in the adaptation of bacteria to oxidative stress4, 5. Evolutionarily diverse bacteria combat the toxicity of reactive oxygen species by actively engaging the stringent response6–8, a metabolic program activated at the level of transcription initiation via guanosine tetraphosphate and the α-helical DksA protein9. Studies herein with Salmonella demonstrate that the interactions of structurally related, but functionally unique, α-helical Gre factors with the secondary channel of RNA polymerase elicit the expression of metabolic signatures that are associated with resistance to oxidative killing. Gre proteins resolve pauses in ternary elongation complexes of Embden-Meyerhof-Parnas (EMP) glycolysis and aerobic respiration genes. The Gre-directed utilization of glucose in overflow and aerobic metabolism satisfies the energetic and redox demands of Salmonella, while preventing the occurrence of amino acid bradytrophies. Moreover, the simultaneous utilization of lower glycolysis, the methylglyoxal pathway and the electron transport chain curtails the noxious coexistence of reductive and electrophilic stress. The resolution of transcriptional pauses in EMP glycolysis and aerobic respiration genes by Gre factors safeguards Salmonella from the cytotoxicity of phagocyte NADPH oxidase in the innate host response. Control of transcriptional elongation represents a pivotal breakpoint in the regulation of metabolic programs underlying bacterial pathogenesis.
Beyond the foliage: Using non-destructive multimodal 3D imaging and AI to phenotype and diagnose trunk diseases
Authors: Fernandez Romain , Le Cunff Loïc , Mérigeaud Samuel , Verdeil Jean-Luc , Perry Julie , Larignon Philippe , Spilmont Anne-Sophie , Chatelet Philippe , Cardoso Maïda , Goze-Bac Christophe , Moisy Cédric 
Published: June 2022

ABSTRACTQuantifying healthy and degraded inner tissues in plants is of great interest in agronomy, for example, to assess plant health and quality and monitor physiological traits or diseases. However, detecting functional and degraded plant tissuesin-vivowithout harming the plant is extremely challenging. New solutions are needed in ligneous and perennial species, for which the sustainability of plantations is crucial. To tackle this challenge, we developed a novel approach based on multimodal 3D imaging and Artificial Intelligence (AI)-based image processing that allowed a noninvasive diagnosis of inner tissues in living plants. The method was successfully applied to the grapevine (Vitis viniferaL.) in vineyards where sustainability was threatened by trunk diseases, while the sanitary status of vines cannot be ascertained without injuring the plants. By combining MRI and X-ray CT 3D imaging with an automatic voxel classification, we could discriminate intact, degraded, and white rot tissues with a mean global accuracy of over 91%. Each imaging modality contribution to tissue detection was evaluated, and we identified quantitative structural and physiological markers characterizing wood degradation steps. The combined study of inner tissue distributionversusexternal foliar symptom history demonstrated that white rot and intact tissue contents are key measurements in evaluating vines’ sanitary status. We finally proposed a model for an accurate trunk disease diagnosis in grapevine. This work opens new routes for precision agriculture andin-situmonitoring of wood quality and plant health across plant species.
SARS-CoV-2 requires acidic pH to infect cells
Authors: Kreutzberger Alex J.B. , Sanyal Anwesha , Saminathan Anand , Bloyet Louis-Marie , Stumpf Spencer , Liu Zhuoming , Ojha Ravi , Patjas Markku T. , Geneid Ahmed , Scanavachi Gustavo , Doyle Catherine A. , Somerville Elliott , Bango Da Cunha Correira Ricardo , Di Caprio Giuseppe , Toppila-Salmi Sanna , Mäkitie Antti , Kiessling Volker , Vapalahti Olli , Whelan Sean P.J. , Balistreri Giuseppe , Kirchhausen Tom 
Published: June 2022

ABSTRACTSARS-CoV-2 cell entry starts with membrane attachment and ends with spike-protein (S) catalyzed membrane fusion depending on two cleavage steps, one usually by furin in producing cells and the second by TMPRSS2 on target cells. Endosomal cathepsins can carry out both. Using real-time 3D single virion tracking, we show fusion and genome penetration requires virion exposure to an acidic milieu of pH 6.2-6.8, even when furin and TMPRSS2 cleavages have occurred. We detect the sequential steps of S1-fragment dissociation, fusion, and content release from the cell surface in TMPRRS2 overexpressing cells only when exposed to acidic pH. We define a key role of an acidic environment for successful infection, found in endosomal compartments and at the surface of TMPRSS2 expressing cells in the acidic milieu of the nasal cavity.Significance StatementInfection by SARS-CoV-2 depends upon the S large spike protein decorating the virions and is responsible for receptor engagement and subsequent fusion of viral and cellular membranes allowing release of virion contents into the cell. Using new single particle imaging tools, to visualize and track the successive steps from virion attachment to fusion, combined with chemical and genetic perturbations of the cells, we provide the first direct evidence for the cellular uptake routes of productive infection in multiple cell types and their dependence on proteolysis of S by cell surface or endosomal proteases. We show that fusion and content release always require the acidic environment from endosomes, preceded by liberation of the S1 fragment which depends on ACE2 receptor engagement.One sentence summaryDetailed molecular snapshots of the productive infectious entry pathway of SARS-CoV-2 into cells
Solid-state NMR of paired helical filaments formed by the core tau fragment tau(297-391)
Authors: Al-Hilaly Youssra K. , Hurt Connor , Rickard Janet E. , Harrington Charles R. , Storey John M.D. , Wischik Claude M. , Serpell Louise C. , Siemer Ansgar B. 
Published: June 2022

AbstractAggregation of the tau protein into fibrillar cross-β aggregates is a hallmark of Alzheimer’s diseases (AD) and many other neurodegenerative tauopathies. Recently, several core structures of patient-derived tau paired helical filaments (PHFs) have been solved revealing a structural variability that often correlates with a specific tauopathy. To further characterize the dynamics of these fibril cores, to screen for strain-specific small molecules as potential biomarkers and therapeutics, and to develop strain-specific antibodies, recombinant in-vitro models of tau filaments are needed. We recently showed that a 95-residue fragment of tau (from residue 297 to 391), termed dGAE, forms filaments in vitro in the absence of polyanionic co-factors often used for in vitro aggregation of full length tau. Tau(297-391) was identified as the proteolytic resistant core of tau PHFs and overlaps with the structures characterized by cryo-electron microscopy in ex-vivo PHFs, making it a promising model for the study of AD tau filaments in vitro. In the present study, we used solid-state NMR to characterize tau(297-391) filaments and show that such filaments assembled under non-reducing conditions are more dynamic and less ordered than those made in the presence of the reducing agent, DTT. We further report the resonance assignment of tau(297-392)+DTT filaments and compare it to existing core structures of tau.