bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thermodynamic stability of G-quadruplex and overlapping m6A: Position-dependent collaborators in allele frequency and fitness?
Authors: Gulec Cagri 
Published: April 2021

AbstractBackgroundPost-transcriptional modifications like m6A, and secondary structures like G-quadruplex (G4), play an important role in RNA processing. Despite an emerging number of studies focusing on m6A and G4 separately, there are less studies about their synergy.AimSince m6A is known to be enzymatically created in DRACH-motif, and genetic variants may create a novel DRACH-motif or abolish a pre-existing DRACH-motif, we can suppose that the variants may affect gene product level through modulating m6A-G4 colocalization, which consequently may affect fitness and change allele frequency. To test this hypothesis, rare and common variants in selected human genes were investigated in terms of their effect on m6A-G4 colocalization.MethodsGenomic sequences and variant features were fetched from GRCh37/hg19 and Biomart-Ensembl databases, respectively. Counting the number of putative m6A- and G4-motifs in sequences and statistical analysis were performed with appropriate libraries of Python3.7.ResultsCommon variants creating novel m6A-motif were found more frequently inside than outside G4, and displayed unequal distribution throughout pre-mRNA. Unequal distribution of m6A-creating variants seemed to be related to their effect on thermodynamic stability of the overlapping-G4.DiscussionSelective m6A-G4 colocalization suggests that m6A-motif is favorable when overlapping with G4. Besides, thermodynamic stability may lead to unequal distribution of m6A-G4 colocalization, because m6A-creating alleles seem to have lower frequency if stabilizes overlapping-G4 in 3-prime-side, but not in 5-prime-side. We can conclude that the fitness, and consequently frequency of an m6A-creating variant is prone to become higher or lower depending on its position and effect on the overlapping-G4 stability.
Striatal and prefrontal D2R and SERT distributions contrastingly correlate with default-mode connectivity
Authors: Ionescu Tudor M. , Amend Mario , Hafiz Rakibul , Biswal Bharat B. , Maurer Andreas , Pichler Bernd J. , Wehrl Hans F. , Herfert Kristina 
Published: April 2021

AbstractThe molecular substrate of resting-state functional connectivity (rs-FC) remains poorly understood. We aimed to elucidate interactions of dopamine D2 receptor (D2R) and serotonin transporter (SERT) availabilities in main dopaminergic and serotonergic projection areas with the default-mode network (DMN) and two other resting-state networks (RSNs), the salience (SN) and sensorimotor networks (SMN). We performed simultaneous PET/fMRI scans in rats using [11C]raclopride and [11C]DASB to image D2R and SERT distributions, showing for the first time direct relationships between rs-FC and molecular properties of the rodent brain. We found negative associations between CPu D2R availability and all RSNs investigated. Strikingly, medial prefrontal SERT correlated both positively with anterior DMN rs-FC and negatively with rs-FC between the other networks, underlining serotonin’s intricate role in this region. By further elucidating the link between molecular brain properties and its network-level function, our data support future diagnostic and therapeutic strategies.TeaserSimultaneous PET/fMRI indicates direct associations between monoaminergic neurotransmission and brain functional networks.
Cdc48 influence on separase levels is independent of mitosis and suggests translational sensitivity of separase
Authors: Vijayakumari Drisya , Müller Janina , Hauf Silke 
Published: April 2021

SummaryCdc48 (p97/VCP) is a AAA-ATPase that can extract ubiquitinated proteins from their binding partners and channel substrates to the proteasome. A fission yeastcdc48mutant (cdc48-353) shows low levels of the cohesin protease, separase, and pronounced chromosome segregation defects in mitosis. Separase initiates chromosome segregation when its binding partner securin is ubiquitinated and degraded. The low separase levels in thecdc48-353mutant have been attributed to a failure to extract ubiquitinated securin from separase resulting in co-degradation of separase along with securin. If true, this establishes Cdc48 as a key regulator of mitosis. In contrast, we show here that low separase levels in thecdc48-353mutant are independent of mitosis. Moreover, we find no evidence of enhanced separase degradation in the mutant. Instead, we suggest that thecdc48-353mutant uncovers specific requirements for separase translation. Our results highlight a need to better understand how this key mitotic enzyme is synthesized.
The right time and place: time- and age-dependent vaccine-enhanced mucosal immunity to parasite infection
Authors: Liu Wei , McNeilly Tom N. , Mitchell Mairi , Burgess Stewart T.G. , Nisbet Alasdair J. , Matthews Jacqueline B. , Babayan Simon A. 
Published: April 2021

AbstractIndividuals vary broadly in their response to vaccination and subsequent exposure to infection, causing persistence of both infection and transmission. The prevalence of poor vaccine responders hampers the development of vaccines, especially against parasitic helminths. Yet despite having substantial economic and societal impact, the immune mechanisms that underlie such variability, especially at the site of parasite infection, remain poorly understood. Previous trials using a prototype vaccine for the control of the gastric parasiticTeladorsagia circumcincta, one of the highest impact parasites affecting sheep, revealed substantial variation in protection between individuals, which we hypothesised may in part be driven by age at vaccination. Here, to characterise how immunity at the mucosal site of infection developed in vaccinated lambs, we inserted gastric cannulae into the abomasa (true stomachs) of three-month- and six-month-old lambs before vaccination, and performed a longitudinal analysis of their local immune response during subsequent challenge infection. We found that the vaccine caused systemic changes in the baseline immune profile within the abomasum before any parasite exposure had occurred and reduced parasite burden and egg output once lambs were infected, regardless of age. However, age affected how vaccinated lambs responded to subsequent infection across multiple immune pathways, with only a minority of protective immune pathways being independent of age. This resulted in younger lambs being more susceptible to infection regardless of vaccine status. The identification of age-dependent (mostly adaptive) and age-independent (mostly innate) protective immune pathways should help refine the formulation of vaccines against these and potentially other helminth parasites of ruminants, and could indicate specificities of anti-helminth immunity more generally.
Feature-based attention enables robust, long-lasting location transfer in human perceptual learning
Authors: Hung Shao-Chin , Carrasco Marisa 
Published: April 2021

AbstractVisual perceptual learning (VPL) is typically specific to the trained location and feature. However, the degree of specificity depends upon particular training protocols. Manipulating covert spatial attention during training facilitates learning transfer to other locations. Here we investigated whether feature-based attention (FBA), which enhances the representation of particular features throughout the visual field, facilitates VPL transfer, and how long such an effect would last. To do so, we implemented a novel task in which observers discriminated a stimulus orientation relative to two reference angles presented simultaneously before each block. We found that training with FBA enabled remarkable location transfer, reminiscent of its global effect across the visual field, but preserved orientation specificity in VPL. Critically, both the perceptual improvement and location transfer persisted after one year. Our results reveal robust, long-lasting benefits induced by FBA in VPL, and have translational implications for improving generalization of training protocols in visual rehabilitation.
Above- and below-ground biodiversity responses to the prolonged flood pulse in central-western Amazonia, Brazil
Authors: Bredin Yennie K. , Hess Laura L. , Scabin Andressa B. , Dunthorn Micah , Haugaasen Torbjørn , Peres Carlos A. , Nilsson Henrik R. , Antonelli Alexandre , Ritter Camila D. 
Published: April 2021

AbstractAmazonia encompasses forests that grow in areas that are periodically inundated by overflowing rivers. The inundation depth and duration vary according to the slope of the terrain, creating a flooding gradient. This gradient directly affects the biota, but the effect on soil organisms remains elusive. Here, we use DNA metabarcoding to estimate prokaryote and eukaryote diversity from soil and litter samples in a seasonally flooded forest and its adjacent unflooded forest in central-western Amazonia using 16S and 18S gene sequences, respectively. We characterize the below-ground diversity and community composition based on Amplicon Sequence Variants (ASVs) along the flooding gradient. We test for the relationship of soil biota with the flooding gradient, soil properties and above-ground woody plant diversity. The flooding gradient did not explain below-ground biodiversity. Nor was the below-ground diversity explained by the above-ground woody plant diversity. However, we found taxonomic groups not previously reported in Amazonian seasonally flooded forests. Also, the flooding gradient and woody plant diversity did, in part, explain the community composition of soil bacteria. Although the effects of the flooding gradient, soil properties and above-ground woody plant diversity is hard to quantify, our results thus indicate that flood stress could influence below-ground bacterial community composition.
The brain integrates proprioceptive information to ensure robust locomotion
Authors: Santuz Alessandro , Laflamme Olivier D. , Akay Turgay 
Published: April 2021

AbstractRobust locomotion relies on information from proprioceptors: sensory organs that communicate the position of body parts to the spinal cord and brain. Proprioceptive circuits in the spinal cord are known to regulate locomotion in challenging environments. Yet, the regulatory importance of the brain remains less clear. Here, through mouse genetic studies and in vivo electrophysiology, we examined the role of the brain in integrating proprioceptive information during locomotion. The systemic removal of proprioceptors left the animals in a constantly perturbed state, similar to that observed during mechanically perturbed locomotion in wild type and characterised by longer and less accurate activation patterns. In contrast, after surgically interrupting the ascending proprioceptive projection to the brain through the dorsal column pathway, wild-type mice showed normal walking behaviour, but lost the ability to respond to external perturbations. Our findings provide direct evidence of a pivotal role for ascending proprioceptive information in achieving safe locomotion.
Prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine
Authors: Rathnasinghe Raveen , Salvatore Mirella , Zheng Hongyong , Jangra Sonia , Kehrer Thomas , Mena Ignacio , Schotsaert Michael , Muster Thomas , Palese Peter , García-Sastre Adolfo 
Published: April 2021

AbstractThe influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 (ΔNS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of ΔNS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a ΔNS1 virus results in an immediate antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that ΔNS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on ΔNS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.
In-scanner head motion and structural covariance networks
Authors: Pardoe Heath R. , Martin Samantha P. 
Published: April 2021

AbstractIn-scanner head motion systematically reduces estimated regional gray matter volumes obtained from structural brain MRI. Here, we investigate how head motion affects structural covariance networks that are derived from regional gray matter volumetric estimates. We acquired motion-affected and motion-free whole brain T1-weighted MRI in 29 healthy adult subjects and estimated relative regional gray matter volumes using a voxel-based morphometry approach. Structural covariance network analyses were undertaken while systematically increasing the number of motion-affected scans included in the analysis. We demonstrate that the standard deviation in regional gray matter estimates increases as the number of motion-affected scans increases. This subsequently increases pair-wise correlations between regions, a key determinant for construction of structural covariance networks. We further demonstrate that head motion systematically alters graph theoretic metrics derived from these networks. Our findings suggest that in-scanner head motion is a source of error that violates the assumption that structural covariance networks reflect neuroanatomical connectivity between brain regions. Results of structural covariance studies should be interpreted with caution, particularly when subject groups are likely to move their heads in the scanner.
Accurate Detection of RNA Stem-Loops in Structurome Data Reveals Widespread Association with Protein Binding Sites
Authors: Radecki Pierce , Uppuluri Rahul , Deshpande Kaustubh , Aviran Sharon 
Published: April 2021

ABSTRACTRNA molecules are known to fold into specific structures which often play a central role in their functions and regulation.In silicofolding of RNA transcripts, especially when assisted with structure profiling (SP) data, is capable of accurately elucidating relevant structural conformations. However, such methods scale poorly to the swaths of SP data generated by transcriptome-wide experiments, which are becoming more commonplace and advancing our understanding of RNA structure and its regulation at global and local levels. This has created a need for tools capable of rapidly deriving structural assessments from SP data in a scalable manner. One such tool we previously introduced that aims to process such data ispatteRNA, a statistical learning algorithm capable of rapidly mining big SP datasets for structural elements. Here, we present a reformulation ofpatteRNA’s pattern recognition scheme that sees significantly improved precision without major compromises to computational overhead. Specifically, we developed a data-driven logistic classifier which interpretspatteRNA’s statistical characterizations of SP data in addition to local sequence properties as measured with a nearest neighbor thermodynamic model. Application of the classifier to human structurome data reveals a marked association between detected stem-loops and RNA binding protein (RBP) footprints. The results of our application demonstrate that upwards of 30% of RBP footprints occur within loops of stable stem-loop elements. Overall, our work arrives at a rapid and accurate method for automatically detecting families of RNA structure motifs and demonstrates the functional relevance of identifying them transcriptome-wide.
SPIRE, Surface Projection Image Recognition Environment for bicontinuous phases: application for plastid cubic membranes
Authors: Hain Tobias M. , Bykowski Michał K. , Saba Matthias , Evans Myfanwy E. , Schröder-Turk Gerd E. , Kowalewska Łucja M. 
Published: April 2021

AbstractBicontinuous membranes in cell organelles epitomise nature’s ability to create complex functional nanostructures. Like their synthetic counterparts, these membranes are characterised by continuous membrane sheets draped onto topologically complex saddle-shaped surfaces with a periodic network-like structure. In cell organelles, their structure sizes around 50–500 nm and fluid nature make Transmission Electron Microscopy (TEM) the analysis method of choice to decipher nanostructural features. Here we present a tool to identify bicontinuous structures from TEM sections by comparison to mathematical “nodal surface” models, including the hexagonal lonsdaleite geometry. Our approach, following pioneering work by Deng and Mieczkowski (1998), creates synthetic TEM images of known bicontinuous geometries for interactive structure identification. We apply the method to the inner membrane network in plant cell chloroplast precursors and achieve a robust identification of the bicontinuous diamond surface as the dominant geometry in several plant species. This represents an important step in understanding their as yet elusive structure-function relationship.
Fetal maturation revealed by amniotic fluid cell-free transcriptome in rhesus macaques
Authors: Schmidt Augusto F. , Schnell Daniel , Eaton Kenneth , Chetal Kashish , Kannan Paranthaman S. , Miller Lisa A. , Chougnet Claire A. , Swarr Daniel T. , Jobe Alan H. , Salomonis Nathan , Kamath-Rayne Beena D. 
Published: April 2021

SummaryAccurate estimate of fetal maturity could provide individualized guidance for delivery of complicated pregnancies. However, current methods are invasive, have low accuracy, and are limited to fetal lung maturation. To identify diagnostic gestational biomarkers, we performed transcriptomic profiling of lung and brain, as well as cell-free RNA from amniotic fluid of preterm and term rhesus macaque fetuses. These data predict new and prior associated gestational age differences in distinct lung and neuronal cell populations when compared to existing single-cell and bulk RNA-Seq data. Comparative analyses found over 200 genes coincidently induced in lung and amniotic fluid, and dozens in brain and amniotic fluid. This data enabled creation of computational models that accurately predicted lung compliance from amniotic fluid and lung transcriptome of preterm fetuses treated with antenatal corticosteroids. Cell-free RNA in amniotic fluid may provide a substrate of global fetal maturation markers for personalized management of at-risk pregnancies.
Refined quantification of infection bottlenecks and pathogen dissemination with STAMPR
Authors: Hullahalli Karthik , Pritchard Justin R. , Waldor Matthew K. 
Published: April 2021

AbstractPathogen population dynamics during infection are critical determinants of infection susceptibility and define patterns of dissemination. However, deciphering these dynamics, particularly founding population sizes in host organs and patterns of dissemination between organs, is difficult because measuring bacterial burden alone is insufficient to observe these patterns. Introduction of allelic diversity into otherwise identical bacteria using DNA barcodes enables sequencing-based measurements of these parameters, in a method known as STAMP (Sequence Tag-Based Analysis of Microbial Population dynamics). However, bacteria often undergo unequal expansion within host organs, resulting in marked differences in the frequencies of barcodes in input and output libraries. Here, we show that these differences confound STAMP-based analyses of founding population sizes and dissemination patterns. We present STAMPR, a successor to STAMP that accounts for such population expansions. Using data from systemic infection of barcoded Extraintestinal PathogenicE. coliwe show that this new framework along with the metrics it yields enhances the fidelity of measurements of bottlenecks and dissemination patterns. STAMPR was also validated on an independent, barcodedPseudomonas aeruginosadataset, uncovering new patterns of dissemination within the data. This framework (available athttps://github.com/hullahalli/stampr_rtisan), when coupled with barcoded datasets, enables a more complete assessment of within-host bacterial population dynamics.ImportanceBarcoded bacteria are often employed to monitor pathogen population dynamics during infection. The accuracy of these measurements is diminished by unequal bacterial expansion rates. Here, we develop computational tools to circumvent this limitation and establish additional metrics that collectively enhance the fidelity of measuring within-host pathogen founding population sizes and dissemination patterns. These new tools will benefit future studies of the dynamics of pathogens and symbionts within their respective hosts and may have additional barcode-based applications beyond host-microbe interactions.
Genomic imprinting drives eusociality
Authors: Matsuura Kenji , Ito Hiromu , Kobayashi Kazuya , Osaki Haruka , Yoshimura Jin , Vargo Edward L. 
Published: April 2021

AbstractThe origin of eusociality, altruistically foregoing personal reproduction to help others, has been a long-standing paradox ever since Darwin. Most eusocial insects and rodents likely evolved from subsocial precursors, in which older offspring “helpers” contribute to the development of younger siblings without a permanent sterile caste. The driving mechanism for the transition from subsociality (with helpers) to eusociality (with lifelong sterile workers) remains an enigma because individuals in subsocial groups are subject to direct natural selection rather than kin selection. Our genomic imprinting theory demonstrates that natural selection generates eusociality in subsocial groups when parental reproductive capacity is linked to a delay in the sexual development of offspring due to sex-antagonistic action of transgenerational epigenetic marks. Focusing on termites, our theory provides the missing evolutionary link to explain the evolution of eusociality from their subsocial wood-feeding cockroach ancestors, and provides a novel framework for understanding the origin of eusociality.
Gene Family Complexity and Expression Divergence as a Mechanism of Adaptation In Coral
Authors: Dimos Bradford , Emery Madison , MacKnight Nicholas , Brandt Marilyn , Demuth Jeffery , Mydlarz Laura 
Published: April 2021

AbstractGene family complexity and its influence on expression dynamics has long been theorized to be an important source of adaptation in natural systems through providing novel genetic material and influencing gene dosage. There is now growing empirical support for this theory; however, this process has only been demonstrated in a limited number of systems typically using recently diverged species or populations. In particular, examples of how this process operates in basal animals with deeper species splits has not been well explored. To address this issue, we investigated the evolution of gene family complexity in five species of common Caribbean coral. We demonstrate widespread divergence in gene repertoires owing to slow rates of gene turnover occurring along deep species splits. The resulting differences in gene family complexity involve numerous biologic processes, shedding light on to the selective forces that have influenced the evolution of each species. By coupling these findings with gene expression data, we show that increased gene family complexity promotes increased expression divergence between species, indicating an interplay between gene family complexity and expression divergence. Finally, we show that immune genes are evolving particularly fast demonstrating the importance of interactions with other organisms in the evolutionary history of Caribbean corals. Overall, these findings provide support for gene copy number change as an important evolutionary force in Caribbean corals, which may influence their ability to persist in a rapidly changing environment.