bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic signatures of a major adaptive event in the pathogenic fungusMelampsora larici-populina
Authors: Persoons Antoine , Maupetit Agathe , Louet Clémentine , Andrieux Axelle , Lipzen Anna , Barry Kerrie W. , Na Hyunsoo , Adam Catherine , Grigoriev Igor V. , Segura Vincent , Duplessis Sébastien , Frey Pascal , Halkett Fabien , De Mita Stéphane 
Published: April 2021

AbstractBackgroundThe recent availability of genome-wide sequencing techniques has allowed systematic screening for molecular signatures of adaptation, including in non-model organisms. Host-pathogen interactions constitute good models due to the strong selective pressures that they entail. We focused on an adaptive event which affected the poplar rust fungusMelampsora larici-populinawhen it overcame a resistance gene borne by its host, cultivated poplar. Based on 76 virulent and avirulent isolates framing narrowly the estimated date of the adaptive event, we examined the molecular signatures of selection.ResultsUsing an array of genome scan methods, we detected a single locus exhibiting a consistent pattern suggestive of a selective sweep in virulent individuals (excess of differentiation between virulent and avirulent samples, linkage disequilibrium, genotype-phenotype statistical association and long-range haplotypes). Our study pinpoints a single gene and further a single amino acid replacement which may have allowed the adaptive event. Although the selective sweep occurred only four years earlier, it does not seem to have affected genome diversity further than the immediate vicinity of the causal locus.ConclusionsOur results suggest thatM. larici-populinaunder-went a soft selective sweep and possibly a prominent effect of outbreeding and recombination, which we speculate have increased the efficiency of selection.
Microglia and perivascular macrophages act as antigen presenting cells to promote CD8 T cell infiltration of the brain
Authors: Goddery Emma N. , Fain Cori E , Lipovsky Chloe G , Ayasoufi Katayoun , Yokanovich Lila T. , Malo Courtney S. , Khadka Roman H. , Tritz Zachariah P. , Jin Fang , Hansen Michael J. , Johnson Aaron J. 
Published: April 2021

ABSTRACTCD8 T cell infiltration of the central nervous system (CNS) is necessary for host protection but contributes to neuropathology. Antigen presenting cells (APCs) situated at CNS borders are thought to mediate T cell entry into the parenchyma during neuroinflammation. The identity of the CNS-resident APC that presents antigen via major histocompatibility complex (MHC) class I to CD8 T cells is unknown. Herein, we characterize MHC class I expression in the naïve and virally infected brain and identify microglia and macrophages (CNS-myeloid cells) as APCs that upregulate H-2Kband H-2Dbupon infection. Conditional ablation of H-2Kband H-2Dbfrom CNS-myeloid cells allowed us to determine that antigen presentation via H-2Db, but not H-2Kb, was required for CNS immune infiltration during Theiler’s murine encephalomyelitis virus (TMEV) infection and drives brain atrophy as a consequence of infection. These results demonstrate that CNS-myeloid cells are key APCs mediating CD8 T cell brain infiltration.
State-dependent network interactions differentially gate sensory input at the motor and command neuron level inCaenorhabditis elegans
Authors: Cecere Zachary T. , Quach Kathleen T. , Yemini Eviatar , How Javier J. , Sharpee Tatyana O. , Chalasani Sreekanth H. 
Published: April 2021

AbstractNeural responses are influenced by both external stimuli and internal network states. While network states have been linked to behavioral and stimulus states, little is known about how sensory inputs are filtered by whole-brain activity to affect motor and command neurons. Here, we recorded whole-brain activity ofCaenorhabditis elegansexperiencing bacterial food stimuli, and modeled how sensory inputs affect motor and command neurons in a network state-dependent manner. First, we classified active neurons into six functional clusters: two sensory neuron clusters (ON, OFF), and four motor/command neuron clusters (AVA, RME, SMDD, SMDV). Using encoding models, we found that ON and OFF sensory neurons that respond to onset and removal of bacteria, respectively, employ different adaptation strategies. Next, we used decoding models to show that bacterial onset and removal differentially drive AVA and RME cluster activity. To explore state-dependent effects on AVA and RME clusters, we developed a model that identified network states and fitted submodels for each state to predict how each of the six functional clusters drive AVA and RME cluster activity. We also identified network states in which AVA and RME clusters were either largely unperturbed by or receptive to bacterial sensory input. Furthermore, this model allowed us to disentangle the state-dependent contributions of stimulus timescales and bacterial content to neural activity. Collectively, we present an interpretable approach for modeling network dynamics that goes beyond implication of neurons in particular states, and moves toward explicitly dissecting how neural populations work together to produce state dependence.Significance StatementA major function of the brain is to transform sensory information into behavior. As the first receiver of sensory input, sensory neuron activity is often most correlated with stimulus features. However, this high-fidelity representation of sensory input becomes diluted as it travels to downstream neurons, where sensory information is integrated with network activity. By the time sensory information reaches motor neurons, it is often difficult to dissociate the influence of sensory input from the influence of network activity. Here, we describe a method that is fully interpretable such that we can show how neural populations on a whole-brain scale interact to produce network states. From there, we can attribute motor neuron activity to network history and sensory input.
Hedgehog pathway members Patched and Costal-2 exhibit differences in overgrowth autonomy inDrosophila melanogaster
Authors: Moore Shannon L. , Adamini Frank C. , Coopes Erik S. , Godoy Dustin , Northington Shyra J. , Stewart Jordan M. , Tillet Richard L. , Bieser Kayla L. , Kagey Jacob D. 
Published: April 2021

AbstractGenetic screens are used inDrosophila melanogasterto identify genes key in the regulation of organismal development and growth. These screens have defined signaling pathways necessary for tissue and organismal development which are evolutionarily conserved across species, includingDrosophila. Here we have used a Flp/FRT mosaic system to screen for conditional regulators of cell growth and cell division in theDrosophilaeye. The conditional nature of this screen utilizes a block in the apoptotic pathway to prohibit the mosaic mutant cells from dying via apoptosis. From this screen, we identified two different mutants that mapped to the Hedgehog signaling pathway. Previously, we described a novelPtcmutation and here we add to the understanding of disrupting the Hh pathway with a novel allele ofCos2. Both of these Hh components are negative regulators of the pathway, yet they depict mutant differences in the type of overgrowth.Ptcmutations lead to overgrowth consisting of almost entirely wild type issue (non-autonomous overgrowth), while theCos2mutation results in tissue that is overgrown in both the mutant and wild type clones (both autonomous and non-autonomous). These differences in tissue overgrowth are consistent in theDrosophilaeye and wing. The observed difference is correlated with a different pattern of deregulation of Mad, the downstream effector of DPP signaling. This finding provides insight into pathway specific differences that may help to better understand intricacies of developmental processes and human disease.
Double-observer approach with camera traps: Towards an unbiased density estimation of unmarked animal populations
Authors: Nakashima Yoshihiro , Hongo Shun , Mizuno Kaori , Yajima Gota , Dzefck Zeun’s C.B. 
Published: April 2021

AbstractCamera traps are a powerful tool for wildlife surveys. However, camera traps may not always detect animals passing in front. This constraint may create a substantial bias in estimating critical parameters such as the density of unmarked populations. We proposed the ‘double-observer approach’ with camera traps to counter the constraint, which involves setting up a paired camera trap at a station and correcting imperfect detection with a hierarchal capture-recapture model for stratified populations. We performed simulations to evaluate this approach’s reliability and determine how to obtain desirable data for this approach. We then applied it to 12 mammals in Japan and Cameroon. The results showed that the approach could correct imperfect detection as long as paired camera traps detect animals nearly independently (Correlation coefficient < 0.2). Camera traps should be installed to monitor a predefined small focal area from different directions to satisfy this requirement. The field surveys showed that camera trap might miss animals by 3 %–40%, suggesting that current density estimation models relying on perfect detection may underestimate animal density by the same order of magnitude. We hope that our approach will be incorporated into existing density estimation models to improve their accuracy.
Sensing hand position in Ehlers-Danlos Syndrome
Authors: Clayton Holly A. , ’t Hart Bernard Marius , Henriques Denise Y. P. 
Published: April 2021

SummaryPurposeTo explore the effect of joint hypermobility on acuity, and plasticity, of hand proprioception.Materials and MethodsWe compared proprioceptive acuity between EDS patients and controls. We then measured any changes in their estimate of hand position after participants adapted their reaches in response to altered visual feedback of their hand. The Beighton Scale was used to quantify the magnitude of joint hypermobility.ResultsThere were no differences between the groups in the accuracy of estimates of hand location, nor in the visually-induced changes in hand location. However, EDS patients’ estimates were less precise when based purely on proprioception and could be partially predicted by Beighton score.ConclusionsEDS patients are less precise at estimating their hand’s location when only afferent information is available, but the presence of efferent signalling may reduce this imprecision. Those who are more hypermobile are more likely to be imprecise.
Immunophenotyping and transcriptional profiling of human plasmablasts in dengue
Authors: Aggarwal Charu , Saini Keshav , Reddy Elluri Seetharami , Singla Mohit , Nayak Kaustuv , Chawla Yadya M. , Maheshwari Deepti , Singh Prabhat , Sharma Pragati , Bhatnagar Priya , Kumar Sanjeev , Gottimukkala Kamalvishnu , Panda Harekrushna , Gunisetty Sivaram , Davis Carl W , Kissick Haydn Thomas , Kabra Sushil Kumar , Lodha Rakesh , Medigeshi Guruprasad R , Ahmed Rafi , MuraliKrishna Kaja , Chandele Anmol 
Published: April 2021

AbstractPrevious studies have shown that plasmablasts expand massively in dengue patients as compared to many other situations such as influenza infection or vaccination. However, a detailed understanding of the phenotypes and transcriptional features of these cells is lacking. Moreover, despite India having nearly a third of global dengue disease burden, there is virtually no information on plasmablasts responses in dengue patients from India. Here, we provide a detailed characterization of plasmablast responses from dengue confirmed febrile children in India. Immunophenotyping and RNA seq analysis showed that in addition to secreting dengue specific antibodies, these massively expanding cells expressed several adhesion molecules, chemokines and chemokine receptors that are involved in endothelial interactions, homing to skin or mucosal tissues including intestine. Surprisingly, we found that these cells also upregulated expression of several cytokine genes that are involved in angiogenesis, leukocyte extravasation and vascular permeability. These transcriptional features were qualitatively similar to plasmablasts from influenza vaccinees. Interestingly, the expansion of the plasmablasts in dengue patients was significantly lower in patients with primary dengue infection compared to those with secondary dengue. Moreover, within the primary dengue patients, their expansion was significantly lower in patients with mild dengue infection (DI) compared to patients with dengue with warning signs (DW) or severe dengue (SD). These results significantly improve our understanding of human plasmablast responses in dengue.ImportanceDengue is a globally spreading with over 100 million clinical cases annually with symptoms ranging from mild self-limiting febrile illness to more severe and sometimes life-threatening dengue hemorrhagic fever or shock, especially among children. India contributes nearly a third of global dengue disease burden. The pathophysiology of dengue is complex and remains poorly understood despite many advances indicating a key role for antibody dependent enhancement of infection. While serum antibodies have been extensively studied, the characteristics of the cellular factories responsible for antibody production, i.e., plasmablasts, are only beginning to emerge. This study provides a comprehensive understanding of the magnitude, phenotype, functional and transcriptional profiles of human plasmablasts from dengue patients in India.
Reinforcement Learning Based Approach for Ligand Pose Prediction
Authors: Jose Justin , Gupta Kritika , Alam Ujjaini , Jatana Nidhi , Arora Pooja 
Published: April 2021

AbstractIdentification of the potential binding site and the correct ligand pose are two crucial steps among the various steps in protein ligand interaction for a novel or known target. Currently most of the deep learning methods work on protein ligand pocket datasets for various predictions. In this study, we propose a reinforcement learning (RL) based method for predicting the optimized ligand pose where the RL agent also identifies the binding site based on its training. In order to apply various reinforcement learning techniques, we suggest a novel approach to represent the protein ligand complex using graph CNN which would help utilize both atomic and spatial features. To the best of our knowledge, this is the first time an RL based approach has been put forward for predicting optimized ligand pose.
Multi-scale phenological niches of seed fall in diverse Amazonian plant communities
Authors: Pak Damie , Swamy Varun , Alvarez-Loayza Patricia , Cornejo Fernando , Queenborough Simon A. , Metz Margaret R. , Terborgh John , Valencia Renato , Wright S. Joseph , Garwood Nancy C. , Lasky Jesse R. 
Published: April 2021

AbstractPhenology has long been hypothesized as an avenue for niche partitioning or interspecific facilitation, both promoting species coexistence. Tropical plant communities exhibit striking diversity in reproductive phenology, but many are also noted for large synchronous reproductive events. Here we study whether the phenology of seed fall in such communities is non-random, what are the temporal scales of phenological patterns, and ecological factors that drive reproductive phenology. We applied multivariate wavelet analyses to test for phenological synchrony versus compensatory dynamics (i.e. anti-synchronous patterns where one species’ decline is compensated by the rise of another) among species and across temporal scales. We used data from long-term seed rain monitoring of hyperdiverse plant communities in the western Amazon. We found significant synchronous whole-community phenology at multiple time scales, consistent with shared environmental responses or positive interactions among species. We also observed both compensatory and synchronous phenology within groups of species likely to share traits (confamilials) and seed dispersal mechanisms. Wind-dispersed species exhibited significant synchrony at ~6 mo scales, suggesting these species share phenological niches to match seasonality of wind. Our results suggest that community phenology is shaped by shared environmental responses but that the diversity of tropical plant phenology may partly result from temporal niche partitioning. The scale-specificity and time-localized nature of community phenology patterns highlights the importance of multiple and shifting drivers of phenology.Open research statementData are provided as private-for-peer review. Code and data can be found athttps://github.com/pakdamie/treephenologywhich is currently public.This submission does not use novel code.
RNA-seq of the medusavirus suggests remodeling of the host nuclear environment at an early infection stage
Authors: Zhang Ruixuan , Endo Hisashi , Takemura Masaharu , Ogata Hiroyuki 
Published: April 2021

AbstractNucleo–cytoplasmic large DNA viruses (NCLDVs) undergo a cytoplasmic or nucleo–cytoplasmic cycle, and the latter involves both nuclear and cytoplasmic compartments to proceed viral replication. Medusavirus, a recently isolated NCLDV, has a nucleo–cytoplasmic replication cycle in amoebas during which the host nuclear membrane apparently remains intact, a unique feature among amoeba–infecting giant viruses. The medusavirus genome lacks most transcription genes but encodes a full set of histone genes. To investigate the infection strategy, we performed a time–course RNA–seq experiment. All the viral genes were transcribed and classified into five temporal expression clusters. The immediate early genes (cluster 1, 42 genes) were mostly (83%) of unknown functions, frequently (95%) associated with a palindromic promoter–like motif, and enriched (45%) in putative nuclear–targeting genes. The later genes (clusters 2–5) were assigned to various functional categories. The viral linker histone H1 gene was in cluster 1, whereas the four core histone genes were in cluster 3, suggesting they had distinct roles during the course of the virus infection. The transcriptional profile of the host amoeba,Acanthamoeba castellanii, genes was greatly altered post–infection. Several encystment–related host genes showed increased representation levels at 48 hours post–infection, which is consistent with the previously reported amoeba encystment upon medusavirus infection. Overall, the transcriptional landscape during the course of medusavirus infection suggests that the virus modifies the host nuclear environment immediately after the initiation of infection. –ImportanceMedusavirus is an amoeba-infecting giant virus that was isolated from a hot spring in Japan. It belongs to the proposed family “Medusaviridae” in the phylumNucleocytoviricota. Unlike other amoeba-infecting giant viruses, medusavirus initiates its DNA replication in the host nucleus without disrupting the nuclear membrane. Our RNA-seq analysis of its infection course uncovered ordered viral gene expression profiles. We identified temporal expression clusters of viral genes and associated putative promoter motifs. The subcellular localization prediction showed a clear spatiotemporal correlation between gene expression timing and localization of the encoded proteins. Notably, the immediate early expression cluster was enriched in genes targeting the nucleus, suggesting the priority of remodeling the host intra-nuclear environment during infection. The transcriptional profile of the amoeba genes was greatly altered post-infection. Notably, the expression of encystment-related genes increased 48 hours post-infection, suggesting that encystment may be an antiviral strategy of amoeba.
Plasmid fitness costs are caused by specific genetic conflicts
Authors: Hall James P. J. , Wright Rosanna C. T. , Harrison Ellie , Muddiman Katie J. , Wood A. Jamie , Paterson Steve , Brockhurst Michael A. 
Published: April 2021

AbstractPlasmids play an important role in bacterial genome evolution by transferring genes between lineages. Fitness costs associated with plasmid acquisition are expected to be a barrier to gene exchange, but the causes of plasmid fitness costs are poorly understood. Single compensatory mutations are often sufficient to completely ameliorate plasmid fitness costs, suggesting that such costs are caused by specific genetic conflicts rather than generic properties of plasmids, such as their size, metabolic burden, or expression level. Here we show — using a combination of experimental evolution, reverse genetics, and transcriptomics — that fitness costs of two divergent large plasmids inPseudomonas fluorescensare caused by inducing maladaptive expression of a chromosomal tailocin toxin operon. Mutations in single genes unrelated to the toxin operon, and located on either the chromosome or the plasmid, ameliorated the disruption associated with plasmid acquisition. We identify one of these compensatory loci, the chromosomal genePFLU4242, as the key mediator of the fitness costs of both plasmids, with the other compensatory loci either reducing expression of this gene or mitigating its deleterious effects by upregulating a putative plasmid-borne ParAB operon. The chromosomal mobile genetic element Tn6291, which uses plasmids for transmission, remained upregulated even in compensated strains, suggesting that mobile genetic elements communicate through pathways independent of general physiological disruption. Plasmid fitness costs caused by specific genetic conflicts are unlikely to act as a long-term barrier to horizontal gene transfer due to their propensity for amelioration by single compensatory mutations, explaining why plasmids are so common in bacterial genomes.
NOTCH1 drives immune-escape mechanisms in B cell malignancies
Authors: Mangolini Maurizio , Maiques-Diaz Alba , Charalampopoulou Stella , Gerhard-Hartmann Elena , Bloehdorn Johannes , Moore Andrew , Lu Junyan , Franklin Valar Nila Roamio , Chilamakuri Chandra Sekkar Reddy , Moutsoupoulos Ilias , Rosenwald Andreas , Stilgenbauer Stephan , Zenz Thorsten , Mohorianu Irina , D’Santos Clive , Deaglio Silvia , Martin-Subero Jose I. , Ringshausen Ingo 
Published: April 2021

AbstractNOTCH1is a recurrently mutated gene in Chronic Lymphocytic Leukemia (CLL) and Mantle Cell Lymphoma (MCL). Functional studies to investigate its role have been hampered by the inability to genetically manipulate primary human lymphoma cells, attributed to low transduction-efficacy and procedure-associated toxicity. To overcome these limitations, we have developed a novel method to retrovirally transfer genes into malignant human B cells. We generated isogenic human tumor cells from patients with CLL and MCL, differing only in their expression of NOTCH1. Our data demonstrate that NOTCH1 facilitates immune-escape of malignant B cells by up-regulating PD-L1, partly dependent on autocrine interferon-γ signaling. In addition, NOTCH1 causes silencing of the entire HLA-class II locus via suppression of the transcriptional co-activator CIITA. These NOTCH1-mediated immune escape mechanisms are associated with the expansion of CD4+T cellsin vivo, further contributing to the poor clinical outcome ofNOTCH1-mutated CLL and MCL.