bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene flow influences the genomic architecture of local adaptation in six riverine fish species
Authors: Shi Yue , Bouska Kristen L. , McKinney Garrett J. , Dokai William , Bartels Andrew , McPhee Megan V. , Larson Wesley A. 
Published: May 2021

AbstractUnderstanding how gene flow influences adaptive divergence is important for predicting adaptive responses. Theoretical studies suggest that when gene flow is high, clustering of adaptive genes in fewer genomic regions would protect adaptive alleles from among-population recombination and thus be selected for, but few studies have tested this hypothesis with empirical data. Here, we used RADseq to generate genomic data for six fish species with contrasting life histories from six reaches of the Upper Mississippi River System, USA. We then conducted genome scans for genomic islands of divergence to examine the distribution of adaptive loci and investigated whether these loci were found in inversions. We found that gene flow varied among species, and adaptive loci were clustered more tightly in species with higher gene flow. For example, the two species with the highest overall FST (0.03 - 0.07) and therefore lowest gene flow showed little evidence of clusters of adaptive loci, with adaptive loci spread uniformly across the genome. In contrast, nearly all adaptive loci in the species with the lowest FST (0.0004) were found in a single large putative inversion. Two other species with intermediate gene flow (FST ~ 0.004) also showed clustered genomic architectures, with most islands of divergence clustered on a few chromosomes. These results provide important empirical evidence to support the hypothesis that increasingly clustered architectures of local adaptation are associated with high gene flow. Our study utilized a unique system with species spanning a large gradient of life histories to highlight the importance of gene flow in shaping adaptive divergence.
The FusX TALE Base Editor (FusXTBE) for rapid mitochondrial DNA programming of human cells in vitro and zebrafish disease models in vivo
Authors: Sabharwal Ankit , Kar Bibekananda , Restrepo-Castillo Santiago , Holmberg Shannon R. , Kendall Benjamin Luke , Cotter Ryan P. , WareJoncas Zachary , Clark Karl J. , Ekker Stephen C. 
Published: May 2021

AbstractFunctional analyses of mitochondria have been hampered by few effective approaches to manipulate mtDNA and a lack of existing animal models. Recently a TALE-derived base editor was shown to induce C-to-T (or G-to-A) sequence changes in mtDNA. We report here the FusX TALE Base Editor (FusXTBE) to facilitate broad-based access to TALE mitochondrial base editing technology. TALE Writer is a de novo in silico design tool to map potential mtDNA base editing sites. FusXTBE was demonstrated to function with comparable activity to the initial base editor in human cells in vitro. Zebrafish embryos were used as a pioneering in vivo test system, with FusXTBE inducing 90+% editing efficiency in mtDNA loci, the first example of majority mtDNA heteroplasmy induction in any system. Gene editing specificity as precise as a single nucleotide was observed in vivo for a protein-coding gene. Non-destructive genotyping enables single animal mtDNA analyses for downstream biological functional genomics applications. FusXTBE is a new gene editing toolkit for exploring important questions in mitochondrial biology and genetics.
Predictive uncertainty in mechanistic models of cellular processes calibrated to experimental data
Authors: Irvin Michael W. , Ramanathan Arvind , Lopez Carlos F. 
Published: May 2021

AbstractMathematical models are often used to explore network-driven cellular processes from a systems perspective. However, a dearth of quantitative data suitable for model calibration leads to models with parameter unidentifiability and questionable predictive power. Here we introduce a Bayesian and Machine-Learning based Measurement Model approach to explore how quantitative and non-quantitative data constrain models of apoptosis execution within a missing data context. We find two orders of magnitude more ordinal (e.g. immunoblot) data are necessary to achieve accuracy comparable to quantitative (e.g. fluorescence) data. Notably, ordinal and nominal (e.g. immunostain) non-quantitative data synergize to reduce model uncertainty and improve accuracy. Further, model prediction accuracy and certainty strongly depend on rigorous data-driven formulations of the measurement, and the size and make-up of the datasets. Finally, we demonstrate the potential of a data-driven Measurement Model approach to identify model features that could lead to informative experimental measurements and improve model predictive power.
Galbut virus infection minimally influences Drosophila melanogaster fitness traits in a strain and sex-dependent manner
Authors: Cross Shaun T. , Brehm Ali L. , Dunham Tillie J. , Rodgers Case P. , Borlee Grace I. , Stenglein Mark D. 
Published: May 2021

AbstractGalbut virus (family Partitiviridae) infects Drosophila melanogaster and can be transmitted vertically from infected mothers or infected fathers with near perfect efficiency. This form of super-Mendelian inheritance should drive infection to 100% prevalence, and indeed galbut virus is ubiquitous in wild D. melanogaster populations. But on average only about 60% of individual flies are infected. One possible explanation for this apparent paradox is that a subset of flies are resistant to infection. Although galbut virus infected flies seem healthy, infection may be sufficiently costly to drive selection for resistant hosts, thereby decreasing overall prevalence. To test this hypothesis, we quantified a variety of fitness-related traits in galbut virus infected flies from two lines from the Drosophila Genetic Reference Panel (DGRP). Galbut virus infected flies had slightly decreased average lifespan and total offspring production, but these decreases were mostly not statistically significant. Galbut virus DGRP-517 flies pupated and eclosed slightly faster than their uninfected counterparts. Some galbut virus infected flies exhibited altered sensitivity to viral, bacterial, and fungal pathogens. Galbut virus infection produced minimal changes to host mRNA levels as measured by RNA sequencing, consistent with minimal phenotypic changes. The microbiome composition of flies was not measurably perturbed by galbut virus infection. Differences in phenotype attributable to galbut virus infection varied as a function of fly sex and DGRP strain and were generally dwarfed by larger differences attributable to strain and sex. Thus, galbut virus infection does produce measurable phenotypic changes, with changes being minor, offsetting, and possibly net negative.ImportanceVirology has largely focused on viruses that cause unmistakable phenotypic changes. But metagenomic surveys are revealing that persistent virus infections are extremely common, even in apparently healthy organisms. The extent to which these persistent viruses impact host fitness and evolution remains largely unclear. Here we study fitness impacts of a partitivirus named galbut virus that is ubiquitous in wild D. melanogaster populations. Despite efficient biparental vertical transmission, galbut virus is present in only just over half of wild flies. We quantified various fitness-related traits in galbut virus infected and uninfected fly lines and found that infection produced small but measurable changes in host phenotype that in aggregate may reduce fly fitness. Further studies that take advantage of this virus that naturally infects a premier model organism that is easy to study in the wild will shed further light on the persistent virus-host dynamics that may actually represent most viral infections.
School start times and academic achievement - a systematic review on grades and test scores
Authors: Biller Anna M. , Meissner Karin , Winnebeck Eva C. , Zerbini Giulia 
Published: May 2021

AbstractSchool start times have been at the centre of many scientific and political debates given the accumulating evidence that bell times are generally too early, and thus lead to an epidemic of sleep restriction in the student population. Recent media attention has conveyed the message that later school starts not only improve sleep but also result in better academic achievement. Several studies have been recently published on this topic requiring a comprehensive review of the results to clarify the relationship between later school start times and academic achievement to inform the general public and policy makers.To this end, we conducted a systematic review of the current literature on school starting times and academic achievement in middle and high school students, considering grades and standardised test scores as achievement measures. We followed the PRISMA guidelines for searching, including, and reporting relevant literature and identified 21 studies for detailed analysis. Evidence quality of included studies was assessed with a pre-defined risk of bias assessment using modified items from the GRADE scheme and ROBINS-I tool.About half of the reviewed studies reported no (positive or negative) effect of delaying school times on grades and test scores, while the other half reported either mixed or positive results. Given the strong heterogeneity of included studies, we grouped them according to various characteristics, such as academic outcomes, dose of delay, evidence quality, or study design to identify potential hidden effects. Despite this, we could not identify any generalisable effect beyond single studies as to whether delaying school times has clear beneficial effects on academic performance.Given that grades and scores determine future career trajectories and predict future success, the question whether school start times contribute to academic achievement is of great interest for the general public and needs to be further clarified. Mechanistically, it is very likely that improved sleep leads to or mediates improved cognitive performance and learning, but definitive conclusions on whether this also translates into better grades and scores across all students requires better evidence at this stage. Importantly, this does not preclude other positive outcomes of later start times such as improved sleep (quality), motivation or learning but draws attention on current gaps and shortcomings. To this end, we also highlight critical methodological aspects and provide suggestions to increase the evidence-level and to guide the direction of research in future studies.
A baseline transcriptional signature associates with clinical malaria risk in RTS,S/AS01-vaccinated African children
Authors: Moncunill Gemma , Carnes Jason , Young William Chad , Carpp Lindsay N. , Rosa Stephen De , Campo Joseph J. , Nhabomba Augusto J. , Mpina Maximillian , Jairoce Chenjerai , Finak Greg , Haas Paige , Murie Carl , Van Phu , Sanz Héctor , Dutta Sheetij , Mordmüller Benjamin , Agnandji Selidji T. , Díez-Padrisa Núria , Williams Nana A. , Aponte John J. , Valim Clarissa , Neafsey Daniel E. , Daubenberger Claudia , McElrath Juliana , Dobaño Carlota , Stuart Ken , Gottardo Raphael 
Published: May 2021

AbstractIn a phase 3 trial in African infants/children, the RTS,S/AS01 (GSK) vaccine showed moderate efficacy against clinical malaria. We aimed to identify RTS,S/AS01-induced signatures associated with clinical malaria by analyzing antigen-stimulated peripheral blood mononuclear cells sampled from a subset of trial participants at baseline and month 3 (one month post-third dose). RTS,S/AS01 vaccination was associated with downregulation of B-cell and monocyte-related blood transcriptional modules (BTMs) and upregulation of T-cell related BTMs, as well as higher month 3 (vs baseline) circumsporozoite protein (CSP)-specific CD4+T-cell responses. There were few RTS,S/AS01-associated BTMs whose month 3 levels correlated with malaria risk. In contrast, baseline levels of BTMs associated with dendritic cells and with monocytes (among others) correlated with malaria risk. A cross-study analysis supported generalizability of the baseline dendritic cell- and monocyte-related BTM correlations with malaria risk to healthy, malaria-naïve adults, suggesting inflammatory monocytes may inhibit protective RTS,S/AS01-induced responses.
One year of SARS-CoV-2: Genomic characterization of COVID-19 outbreak in Qatar
Authors: Benslimane Fatiha M. , Al Khatib Hebah A. , Al-Jamal Ola , Albatesh Dana , Boughattas Sonia , Ahmed Ayeda A , Bensaad Meryem , Younuskunju Shameem , Mohamoud Yasmin A , Badr Mashael Al , Mohamed Abdalla A. , El-Kahlout Reham A. , Al-Hamad Tasneem , Elgakhlab Dina , Al-Kuwari Fatima H. , Saad Chadi , Jeremijenko Andrew , Al-Khal Abdullatif , Al-Maslamani Muna A. , Bertollini Roberto , Al-Kuwari Einas A. , Al-Romaihi Hamad E. , Al-Marri Salih , Al-Thani Mohammed , Badji Radja M. , Mbarek Hamdi , Al-Sarraj Yasser , Malek Joel A , Ismail Said I. , Abu-Raddad Laith J. , Coyle Peter V. , Al Thani Asmaa A. , Yassine Hadi M. 
Published: May 2021

AbstractQatar, a state that has a diverse population consisting mainly of foreign residents, has experienced a large COVID19 outbreak. In this study, we report on 2634 SARS-CoV-2 whole-genome sequences from infected patients in Qatar between March-2020 and March-2021, representing 1.5% of all positive cases in this period. Despite the restrictions on international travel, the viruses sampled from the populace of Qatar mirrored nearly the entire global population’s genomic diversity with nine predominant viral lineages that were sustained by local transmission chains and the emergence of mutations that are likely to have originated in Qatar. We reported an increased number of mutations and deletions in B.1.1.7 and B.1.351 lineages in a short period. These findings raise the imperative need to continue the ongoing genomic surveillance that has been an integral part of the national response to monitor the SARS-CoV-2 profile and re-emergence in Qatar.
An approximate Bayesian approach for estimation of the reproduction number under misreported epidemic data
Authors: Gressani Oswaldo , Faes Christel , Hens Niel 
Published: May 2021

AbstractIn epidemic models, the effective reproduction number is of central importance to assess the transmission dynamics of an infectious disease and to orient health intervention strategies. Publicly shared data during an outbreak often suffers from two sources of misreporting (underreporting and delay in reporting) that should not be overlooked when estimating epidemiological parameters. The main statistical challenge in models that intrinsically account for a misreporting process lies in the joint estimation of the time-varying reproduction number and the delay/underreporting parameters. Existing Bayesian approaches typically rely on Markov chain Monte Carlo (MCMC) algorithms that are extremely costly from a computational perspective. We propose a much faster alternative based on Laplacian-P-splines (LPS) that combines Bayesian penalized B-splines for flexible and smooth estimation of the time-varying reproduction number and Laplace approximations to selected posterior distributions for fast computation. Assuming a known generation interval distribution, the incidence at a given calendar time is governed by the epidemic renewal equation and the delay structure is specified through a composite link framework. Laplace approximations to the conditional posterior of the spline vector are obtained from analytical versions of the gradient and Hessian of the log-likelihood, implying a drastic speed-up in the computation of posterior estimates. Furthermore, the proposed LPS approach can be used to obtain point estimates and approximate credible intervals for the delay and reporting probabilities. Simulation of epidemics with different combinations for the underreporting rate and delay structure (one-day, two-day and weekend delays) show that the proposed LPS methodology delivers fast and accurate estimates outperforming existing methods that do not take into account underreporting and delay patterns. Finally, LPS is illustrated on two real case studies of epidemic outbreaks.
Clinical characteristics and COVID-19 outcomes in a regional cohort of pediatric patients with rheumatic diseases
Authors: Clemente Daniel , Udaondo Clara , de Inocencio Jaime , Nieto Juan Carlos , del Río Pilar Galán , Fernández Antía García , Palomo Jaime Arroyo , Bachiller-Corral Javier , Robledillo Juan Carlos Lopez , Leon Leticia , Abasolo Lydia , Boteanu Alina 
Published: May 2021

AbstractBackgroundThis study aimed to assess the baseline characteristics and clinical outcomes of coronavirus disease 2019 (COVID-19) in pediatric patients with rheumatic and musculoskeletal diseases (RMD) and identify the risk factors associated with symptomatic or severe disease defined as hospital admission, intensive care admission or death.MethodsAn observational longitudinal study was conducted during the first year of pandemic SARS-CoV-2 (1stMarch 2020 to 1stMarch 2021). All pediatric patients attended at the rheumatology outpatient clinic of six tertiary hospital in Madrid, Spain, with a medical diagnosis of RMD and COVID-19 were included. Main outcomes were symptomatic disease and hospital admission. The covariates were sociodemographic, clinical, and treatments. We ran a multivariable logistic regression model to assess risk factors for outcomes.ResultsThe study population included 77 pediatric patients. Mean age was 11.88 (4.04) years Of these, 30 patients were asymptomatic, 41 had a mild or moderate disease and other 6 patients (7.79%) required hospital admission related to COVID-19. The median length of stay was 5 (2–20) days and there was no death. Previous comorbidities increased the risk for symptomatic disease and hospital admission. Compared with outpatients, the factor independently associated with hospital admission was the use of glucocorticoids (OR 1.08; p=0.00). No statistically significant findings for symptomatic COVID-19 were found in the final model.ConclusionOur data found no differences in COVID-19 outcomes between children-onset rheumatic diseases. Our results suggest that associated comorbidities and being in treatment with glucocorticoids increase the risk of hospital admission.
The microbiome of Lotus nodules varies with plant health in a species-specific manner
Authors: Crosbie Duncan B. , Mahmoudi Maryam , Radl Viviane , Brachmann Andreas , Schloter Michael , Kemen Eric , Marín Macarena 
Published: May 2021

ABSTRACTNitrogen fixation is carried out inside nodules of legumes by symbiotic rhizobia. Rhizobia dominate the nodule microbiome, however other non-rhizobial bacteria also colonise root nodules. It is not clear whether these less abundant nodule colonisers impact nodule function. In order to investigate the relationship between the nodule microbiome and nodule function as influenced by the soil microbiome, we used a metabarcoding approach to characterise the communities inside Lotus burttii, Lotus japonicus and Lotus corniculatus nodules from plants that were either starved or healthy resulting from inoculations with different soil suspensions in a closed pot experiment. We found that the nodule microbiome of all tested Lotus species differed according to inoculum, but only that of L. burttii varied with plant health. Using a machine learning algorithm, we also found that among the many non-rhizobial bacteria inside the nodule, amplicon sequence variants that were related to Pseudomonas were the most indicative signatures of a healthy plant nodule microbiome. These results support the hypothesis that legume nodule endophytes may play a role in the overall success of root-nodule symbiosis, albeit in a plant host specific manner.
Concurrent invasions by European starlings (Sturnus vulgaris) suggest selection on shared genomic regions even after genetic bottlenecks
Authors: Hofmeister Natalie R. , Stuart Katarina , Warren Wesley C. , Werner Scott J. , Bateson Melissa , Ball Gregory F. , Buchanan Katherine L. , Burt David W. , Cardilini Adam P.A. , Cassey Phillip , De Meyer Tim , George Julia , Meddle Simone L. , Rowland Hannah M. , Sherman Craig D.H. , Sherwin William , Berghe Wim Vanden , Rollins Lee Ann , Clayton David F. 
Published: May 2021

AbstractA species’ success during the invasion of new areas hinges on an interplay between demographic processes and the outcome of localized selection. Invasive European Starlings (Sturnus vulgaris) established populations in Australia and North America in the 19th century. Here, we compare whole-genome sequences among native and independently introduced European Starling populations from three continents to determine how demographic processes interact with rapid adaptive evolution to generate similar genetic patterns in these recent and replicated invasions. Our results confirm that a post-bottleneck expansion may in fact support local adaptation. We find that specific genomic regions have differentiated even on this short evolutionary timescale, and suggest that selection best explains differentiation in at least two of these regions. This infamous and highly mobile invader adapted to novel selection (e.g., extrinsic factors), perhaps in part due to the demographic boom intrinsic to many invasions.
Corticotropin-Releasing Factor Induces Functional And Structural Synaptic Remodelling In Acute Stress
Authors: Vandael Dorien , Wierda Keimpe , Vints Katlijn , Baatsen Pieter , De Groef Lies , Moons Lieve , Rybakin Vasily , Gounko Natalia V. 
Published: May 2021

AbstractBiological responses to internal and external stress factors involve highly conserved mechanisms, using a tightly coordinated interplay of many factors. Corticotropin-releasing factor (CRF) plays a central role in organizing these lifesaving physiological responses to stress. We show that CRF rapidly and reversibly changes Schaffer Collateral input into hippocampal CA1 pyramidal cells (PC), by modulating both functional and structural aspects of these synapses. Host exposure to acute stress, in vivo CRF injection, and ex vivo CRF application all result in fast de novo formation and remodeling of existing dendritic spines. Functionally, CRF leads to a rapid increase in synaptic strength of Schaffer collateral input into CA1 neurons, e.g. increase in spontaneous neurotransmitter release, paired-pulse facilitation and repetitive excitability and improves long-term synaptic plasticity: LTP and LTD. In line with the changes in synaptic function, CRF increases the number of presynaptic vesicles, induces redistribution of vesicles towards the active zone increases active zone size, and improves the alignment of the pre- and post-synaptic compartments. Together, CRF rapidly enhances synaptic communication in the hippocampus, potentially playing a crucial role in the enhanced memory consolidation in acute stress.
Tetraspanin Cd9b and Cxcl12a/Cxcr4b have a synergistic effect on the control of collective cell migration
Authors: Marsay KS , Greaves S , Mahabaleshwar H , Ho CM , Roehl H , Monk PN , Carney T. J. , Partridge LJ 
Published: May 2021

AbstractCollective cell migration is essential for embryonic development and homeostatic processes. During zebrafish development, the posterior lateral line primordium (pLLP) navigates along the embryo flank by collective cell migration. The chemokine receptors, Cxcr4b and Cxcr7b, as well as their cognate ligand, Cxcl12a, are essential for this process. We corroborate that knockdown of the zebrafish cd9 tetraspanin orthologue, cd9b, results in mild pLL abnormalities. Through generation of CRISPR and TALEN mutants, we show that cd9a and cd9b function partially redundantly in pLLP migration, which is delayed in the cd9b single and cd9a; cd9b double mutants. This delay led to a transient reduction in neuromast numbers. Loss of both Cd9a and Cd9b sensitized embryos to reduced Cxcr4b and Cxcl12a levels. Together these results provide evidence that Cd9 modulates collective cell migration of the pLLP during zebrafish development. One interpretation of these observations is that Cd9 contributes to more effective chemokine signalling.