bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal and ontogenetic variation, microbial selection, and predicted antifungal function in the skin-associated microbiome of a Rocky Mountain amphibian
Authors: Goodwin Kenen B. , Hutchinson Jaren D. , Gompert Zachariah 
Published: June 2022

ABSTRACTHost-associated microbiomes play important roles in host health and pathogen defense. In amphibians, the skin-associated microbiome serves as an innate immune defense with potential implications for disease management. Few studies have examined season-long temporal variation in the amphibian skin-associated microbiome, and the interactions between bacteria and fungi on amphibian skin remain poorly understood. We characterize season-long temporal variation in the skin-associated microbiome of the western tiger salamander (Ambystoma mavortium) for both bacteria and fungi between sites and across salamander life stages. 207 skin-associated microbiome samples were collected from salamanders at two Rocky Mountain lakes throughout the summer and fall of 2018, and 127 additional microbiome samples were collected from lake water and lake substrate. We used 16S and ITS next-generation sequencing data with Bayesian Dirichlet-multinomial regression to estimate the relative abundances of bacterial and fungal taxa, test for differential abundance, examine microbial selection, and derive alpha and beta diversity. The antifungal function of bacterial communities was predicted using stochastic character mapping and a database of antifungal bacterial isolates. We examined microbial absolute abundances using Bayesian negative binomial LASSO coupled with synthetic gene spike-ins. For both bacteria and fungi, we observed variation in community composition through time, between sites, and with salamander age and life stage. We found salamander skin to be selective for microbes, with many taxa disproportionately represented relative to the environment, and we observed selection for predicted antifungal bacteria. Ultimately, this ecological knowledge may assist in the conservation of amphibian species threatened by chytridiomycosis and other emerging diseases.
A Big Data COVID-19 literature pattern discovery using NLP
Authors: Petousis Panayiotis , Stylianou Vasilis 
Published: June 2022

AbstractAs our collective knowledge about COVID-19 continues to grow at an exponential rate, it becomes more difficult to organize and observe emerging trends. In this work, we built an open source methodology that uses topic modeling and a pretrained BERT model to organize large corpora of COVID-19 publications into topics over time and over location. Additionally, it assesses the association of medical keywords against COVID-19 over time. These analyses are then automatically pushed into an open source web application that allows a user to obtain actionable insights from across the globe.
NMDAR mediated dynamic changes in m6A inversely correlates with neuronal translation
Authors: Gowda Naveen Kumar Chandappa , Nawalpuri Bharti , Ramakrishna Sarayu , Jhaveri Vishwaja , Muddashetty Ravi S 
Published: June 2022

AbstractEpitranscriptome modifications are crucial in translation regulation and essential for maintaining cellular homeostasis. N6 methyladenosine (m6A) is one of the most abundant and well-conserved epitranscriptome modifications, which is known to play a pivotal role in diverse aspects of neuronal functions. However, the role of m6A modifications with respect to activity-mediated translation regulation and synaptic plasticity has not been studied. Here, we investigated the role of m6A modification in response to NMDAR stimulation. We have consistently observed that upon 5-minute NMDAR stimulation causes an increase in eEF2 phosphorylation. Correspondingly, NMDAR stimulation caused a significant increase in the m6A signal at 5 minutes time point, correlating with the global translation inhibition. The NMDAR induced increase in the m6A signal is accompanied by the redistribution of the m6A marked RNAs from translating to the non-translating pool of ribosomes. The increased m6A levels are well correlated with the reduced FTO levels observed on NMDAR stimulation. Additionally, we show that inhibition of FTO prevents NMDAR mediated changes in m6A levels. Overall, our results establish RNA-based molecular readout which corelates with the NMDAR-dependent translation regulation which helps in understanding changes in protein synthesis.
A Multitrait Locus Regulates Sarbecovirus Pathogenesis
Authors: Schäfer Alexandra , Leist Sarah R. , Gralinski Lisa E. , Martinez David R. , Winkler Emma S. , Okuda Kenichi , Hawkins Padraig E. , Gully Kendra L , Graham Rachel L. , Scobey D. Trevor , Bell Timothy A. , Hock Pablo , Shaw Ginger D. , Loome Jennifer F. , Madden Emily A. , Anderson Elizabeth , Baxter Victoria K. , Taft-Benz Sharon A. , Zweigart Mark R. , May Samantha R. , Dong Stephanie , Clark Matthew , Miller Darla R. , Lynch Rachel M , Heise Mark T. , Tisch Roland , Boucher Richard C. , Pardo Manuel de Villena Fernando , Montgomery Stephanie A. , Diamond Michael S. , Ferris Martin T. , Baric Ralph S. 
Published: June 2022

AbstractInfectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genome-wide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to SARS-CoV disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse Chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6 that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2 and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species.
Computationally-guided design and selection of ribosomal active site mutants with high activity
Authors: Kofman Camila , Watkins Andrew M. , Kim Do Soon , Wooldredge Alexandra C. , Karim Ashty S. , Das Rhiju , Jewett Michael C. 
Published: June 2022

AbstractUnderstanding how modifications to the ribosome affect function has implications for studying ribosome biogenesis, building minimal cells, and repurposing ribosomes for synthetic biology. However, efforts to design sequence-modified ribosomes have been limited because point mutations in the ribosomal RNA (rRNA), especially in the catalytic active site (peptidyl transferase center; PTC), are often functionally detrimental. Moreover, methods for directed evolution of rRNA are constrained by practical considerations (e.g., library size). Here, to address these limitations, we developed a computational rRNA design approach for screening guided libraries of mutant ribosomes. Our method includesin silicolibrary design and selection using a Rosetta stepwise Monte Carlo method (SWM), library construction andin vitrotesting, and functional characterizationin vivo. As a model, we apply our method to making modified ribosomes with mutant PTCs. We engineer ribosomes with as many as 30 mutations in their PTCs, highlighting previously unidentified epistatic interactions, and show that SWM helps identify sequences with beneficial phenotypes as compared to random library sequences. We further demonstrate that some variants improve cell growthin vivo, relative to wild type ribosomes. We anticipate that SWM design may serve as a powerful tool for high-resolution rRNA design.
Peripheral Auditory Nerve Impairment in a Mouse Model of Syndromic Autism
Authors: McChesney Nathan , Barth Jeremy L. , Rumschlag Jeffrey A. , Tan Junying , Harrington Adam J. , Noble Kenyaria V. , McClaskey Carolyn M. , Elvis Phillip , Vaena Silvia G. , Romeo Martin J. , Harris Kelly C. , Cowan Christopher W. , Lang Hainan 
Published: June 2022

AbstractDysfunction of the peripheral auditory nerve (AN) contributes to dynamic changes throughout the central auditory system, resulting in abnormal auditory processing, including hypersensitivity. Altered sound sensitivity is frequently observed in autism spectrum disorder (ASD), suggesting that AN deficits and changes in auditory information processing may contribute to ASD-associated symptoms, including social communication deficits and hyperacusis. The MEF2C transcription factor is associated with risk for several neurodevelopmental disorders, and mutations or deletions of MEF2C produce a haploinsufficiency syndrome characterized by ASD, language and cognitive deficits. A mouse model of this syndromic ASD (i.e., Mef2c+/- or Mef2c-Het) recapitulates many of the MEF2C Haploinsufficiency syndrome-linked behaviors including communication deficits. We show here that Mef2c-Het mice exhibit functional impairment of the peripheral AN and a modest reduction in hearing sensitivity. We find that MEF2C is expressed during development in multiple AN and cochlear cell types, and in Mef2c-Het mice, we observe multiple cellular and molecular alterations associated with the AN, including abnormal myelination, neuronal degeneration, neuronal mitochondria dysfunction, and increased macrophage activation and cochlear inflammation. These results reveal the importance of MEF2C function in inner ear development and function and the engagement of immune cells and other non-neuronal cells, which suggests that microglia/macrophages and other non-neuronal cells might contribute, directly or indirectly, to AN dysfunction and ASD-related phenotypes. Finally, our study establishes a comprehensive approach for characterizing AN function at the physiological, cellular, and molecular levels in mice, which can be applied to animal models with a wide range of human auditory processing impairments.Significance StatementThis is the first report of peripheral auditory nerve (AN) impairment in a mouse model of human MEF2C haploinsufficiency syndrome that has well-characterized ASD related behaviors including communication deficits, hyperactivity, repetitive behavior, and social deficits. We identify multiple underlying cellular, sub-cellular, and molecular abnormalities that may contribute to peripheral AN impairment. Our findings also highlight the important roles of immune cells (e.g., cochlear macrophages) and other non-neuronal elements (e.g., glial cells and cells in the stria vascularis) in auditory impairment in ASD. The methodological significance of the study is the establishment of a comprehensive approach for evaluating peripheral AN function and impact of peripheral AN deficits with minimal hearing loss.
VASH1-SVBP and VASH2-SVBP generate different detyrosination profiles on microtubules
Authors: Ramirez-Rios Sacnicte , Choi Sung Ryul , Sanyal Chadni , Blum Thorsten , Bosc Christophe , Krichen Fatma , Denarier Eric , Soleilhac Jean-Marc , Blot Béatrice , Janke Carsten , Stoppin-Mellet Virginie , Magiera Maria M. , Arnal Isabelle , Steinmetz Michel O. , Moutin Marie-Jo 
Published: June 2022

ABSTRACTThe detyrosination/tyrosination cycle of α-tubulin is critical for proper cell functioning. VASH1-SVBP and VASH2-SVBP are ubiquitous enzyme complexes involved in microtubule detyrosination. However, little is known about their mode of action. Here, we show in reconstituted systems and in cells that VASH1-SVBP and VASH2-SVBP drive global and local detyrosination of microtubules, respectively. We solved the cryo-electron microscopy structure of human VASH2-SVBP bound to microtubules, revealing a different microtubule-binding configuration of its central catalytic region compared to VASH1-SVBP. We further show that the divergent mode of detyrosination between the two enzymes is correlated with the microtubule-binding properties of their disordered N- and C-terminal regions. Specifically, the N-terminal region is responsible for a significantly longer residence time of VASH2-SVBP on microtubules compared to VASH1-SVBP. We suggest that this VASH domain is critical for microtubule-detachment and diffusion of VASH-SVBP enzymes on the lattice. Together, our results suggest a mechanism by which these enzymes could generate distinct microtubule subpopulations and confined areas of detyrosinated lattices to drive various microtubule-based cellular functions.SUMMARYVASH1-SVBP and VASH2-SVBP produce global and local detyrosination patterns of microtubule lattices, respectively. These activities rely on the interplay between the N- and C-terminal disordered regions of the enzymes, which determine their differential molecular mechanism of action.GRAPHICAL ABSTRACTSchematic representation of divergent molecular mechanisms of action of VASH-SVBP detyrosination complexes.
Plant phase extraction (PPE): A novel method for enhanced discovery of RNA-binding proteome in plants
Authors: Zhang Yong , Xu Ye , Skaggs Todd H. , Ferreira Jorge F.S. , Chen Xuemei , Sandhu Devinder 
Published: June 2022

AbstractRNA-binding proteins (RBPs) are versatile effectors in posttranscriptional gene regulation. Systematic profiling of RBPs in plants has been limited to proteins interacting with polyadenylated (poly(A)) RNAs due to the lack of an efficient method of isolating RBPs associated with non-poly(A) RNAs. Here we reported the establishment and application of plant phase extraction (PPE) as a novel method to comprehensively discover the RNA-binding proteome in Arabidopsis leaf tissues, leading to the isolation of 1,169 RBPs, of which 673 corroborate with previously reported RBPs and 496 are novel RBPs. PPE showed unmatched ability in capturing 374 diverse RNA-binding domains (RBDs), while 44% of the RBPs lack recognized RBDs. PPE recovered far more ribosomal and tRNA-related RBPs and metabolic enzymes with moonlighting RBP functions than any other individual report from plants, signifying its advantage in unbiasedly retrieving non-poly(A) and unconventional RBPs. We proposed that intrinsically disordered regions (IDRs) contributed to the non-classical binding of some novel RBPs, and provided the first evidence that enzymatic domains from metabolic enzymes have additional roles in RNA-binding. Taken together, our findings demonstrated that PPE is an effective approach to identifying a wide range of RBPs in complex plant tissues and may have broad biological implications.
Developing and adult reef fish show rapid, reversible light-induced plasticity in their visual system
Authors: Fogg Lily G. , Cortesi Fabio , Gache Camille , Lecchini David , Marshall N. Justin , de Busserolles Fanny 
Published: June 2022

AbstractThe visual capabilities of fish are optimised for their ecology and light environment over evolutionary time. Similarly, fish vision can adapt to regular changes in light conditions within their lifetime, e.g., ontogenetic or seasonal variation. However, we do not fully understand how vision responds to irregular short-term changes in the light environment, e.g., algal blooms and light pollution. In this study, we investigated the effect of short-term exposure to unnatural light conditions on opsin gene expression and retinal cell densities in larval and adult diurnal reef fish (convict surgeonfish; Acanthurus triostegus). Results revealed phenotypic plasticity in the retina across ontogeny, particularly in the larvae. The most substantial differences at both molecular and cellular levels were found under constant dim light, while constant bright light or simulated artificial light at night had a lesser effect. Under dim light, larvae and adults increased expression of the cone opsin genes, sws2a, rh2c and lws, within a few days and larvae also decreased densities of cones, inner nuclear layer cells and ganglion cells. These changes likely enhanced vision under the altered light conditions. Thus, our study suggests that plasticity mainly comes into play when conditions are extremely different to the species’ natural light environment, i.e., a diurnal fish in ‘constant night’. Finally, in a rescue experiment on adults, shifts in opsin expression were reverted within 24 hours. Overall, our study showed rapid, reversible light-induced changes in the retina of A. triostegus, demonstrating phenotypic plasticity in the visual system of a reef fish throughout life.
PRC2 clock: a universal epigenetic biomarker of aging and rejuvenation
Authors: Moqri Mahdi , Cipriano Andrea , Nachun Daniel , Murty Tara , de Sena Brandine Guilherme , Rasouli Sajede , Tarkhov Andrei , Aberg Karolina A. , van den Oord Edwin , Zhou Wanding , Smith Andrew , Mackall Crystal , Gladyshev Vadim , Horvath Steve , Snyder Michael P. , Sebastiano Vittorio 
Published: June 2022

AbstractDNA methylation (DNAm) is one of the most reliable biomarkers for aging across many mammalian tissues. While the age-dependent global loss of DNAm has been well characterized, age-dependent DNAm gain is less specified. Multiple studies have demonstrated that polycomb repressive complex 2 (PRC2) targets are enriched among the CpG sites which gain methylation with age. However, a systematic whole-genome examination of all PRC2 targets in the context of aging methylome as well as whether these associations are pan-tissue or tissue-specific is lacking. Here, by analyzing DNAm data from different assays and from multiple young and old human and mouse tissues, we found that low-methylated regions (LMRs) which are highly bound by PRC2 in embryonic stem cells gain methylation with age in all examined somatic mitotic cells. We also estimated that this epigenetic change represents around 90% of the age-dependent DNAm gain genome-wide. Therefore, we propose the “PRC2 clock,” defined as the average DNAm in PRC2 LMRs, as a universal biomarker of cellular aging in somatic cells. In addition, we demonstrate the application of this biomarker in the evaluation of different anti-aging interventions, including dietary restriction and partial epigenetic reprogramming.
Temperature modifies trait-mediated infection outcomes in a Daphnia-fungal parasite system
Authors: Sun Syuan-Jyun , Dziuba Marcin K. , Jaye Riley N. , Duffy Meghan A. 
Published: June 2022

AbstractOne major concern related to climate change is that elevated temperatures will drive increases in parasite outbreaks. Increasing temperature is known to alter host traits and host-parasite interactions, but we know relatively little about how these are connected mechanistically – that is, about how elevated temperatures impact the relationship between epidemiologically relevant host traits and infection outcomes. Here, we used a zooplankton-fungus (Daphnia dentifera-Metschnikowia bicuspidata) disease system to investigate whether temperature interacted with host susceptibility traits in determining infection outcomes. We did this by exposing D. dentifera to M. bicuspidata or leaving them unexposed at either control (20°C) or warming temperatures (24°C) in a fully factorial design. We found that elevated temperatures altered the physical barrier and immune responses to parasites during the initial infection process, and that infected hosts at elevated temperatures suffered a greater reduction of fecundity and lifespan. Furthermore, the relationship between a key trait – gut epithelium thickness, which is a physical barrier – and the likelihood of terminal infection reversed at warmer temperatures. Together, our results highlight the complex ways that temperatures can modulate host-parasite interactions, and the importance of considering key host susceptibility traits when predicting disease dynamics in a warmer world.This article is part of the theme issue ‘Infectious disease and evolution in a changing world’.
A Theoretical Comparison of Alternative Male Mating Strategies in Cephalopods and Fishes
Authors: Landsittel Joseph , Ermentrout G. Bard , Stiefel Klaus M. 
Published: June 2022

AbstractWe used computer simulations of growth, mating and death of cephalopods and fishes to explore the effect of different life-history strategies on the relative prevalence of alternative male mating strategies. Specifically, we investigated the consequences of single or multiple matings per lifetime, mating strategy switching, cannibalism, resource stochasticity, and altruism towards relatives. We found that a combination of single (semelparous) matings, cannibalism and an absence of mating strategy changes in one lifetime led to a more strictly partitioned parameter space, with a reduced region where the two mating strategies co-exist in similar numbers.Explicitly including Hamilton’s rule in simulations of the social system of a Cichlid led to an increase of dominant males, at the expense of both sneakers and dwarf males (“super-sneakers”). Our predictions provide general bounds on the viable ratios of alternative male mating strategies with different life-histories, and under possibly rapidly changing ecological situations.
Single-cell imaging reveals non-cooperative and cooperative infection strategies ofListeria monocytogenesin macrophages
Authors: Moran Josephine , Feltham Liam , Bagnall James , Goldrick Marie , Lord Elizabeth , Nettleton Catherine , Spiller David G. , Roberts Ian , Paszek Pawel 
Published: June 2022

AbstractPathogens have developed intricate strategies to overcome the host’s innate immune responses. In this paper we use live-cell microscopy with a single bacterium resolution to follow in real time interactions between the food-borne pathogenL. monocytogenesand host macrophages, a key event controlling the infectionin vivo. We demonstrate that infection results in heterogeneous outcomes, with only a subset of bacteria able to establish a replicative invasion of macrophages. The fate of individual bacteria in the same host cell was independent from each other and non-cooperative, but a higher multiplicity of infection resulted in a reduced probability of replication. Using internalisation assays and conditional probabilities to mathematically describe the multi-stage invasion process, we demonstrate that the secreted Listeriolysin toxin (LLO) of the PrfA regulon regulates replication probability by compromising the ability to phagocytose bacteria. Using strains expressing fluorescent reporters to follow transcription of either the LLO-encodinghlyoractAgenes, we show that replicative bacteria exhibited higher PrfA regulon expression in comparison to those bacteria that did not replicate, however elevated PrfA expressionper sewas not sufficient to increase the probability of replication. Overall, this demonstrates a new role for the population-level, but not single cell PrfA-mediated cooperativity to regulate outcomes of host pathogen interactions.Key pointsL. monocytogenesinvasion of innate immune macrophages results in heterogeneous infection outcomes at the single cell levelFate of individual bacteria in the same host cell is independent from each other and non-cooperativeBacterial populations coordinate host cell uptake via the rate of phagocytosis to reduce internalization at high MOIThe PrfA regulon system is necessary but not sufficient forL. monocytogenesreplication, but population-level PrfA virulence regulates single cell outcome probability