bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neural mechanisms underlying distractor suppression guided by spatial cues
Authors: Zhao Chenguang , Kong Yuanjun , Li Dongwei , Huang Jing , Li Xiaoli , Jensen Ole , Song Yan 
Published: May 2022

AbstractA growing body of research demonstrates that distracting inputs can be proactively suppressed via spatial cues, nonspatial cues, or experience, which are governed by more than one top-down mechanism of attention. However, how the neural mechanisms underlying spatial distractor cues guide proactive suppression of distracting inputs remains unresolved. Here, we recorded electroencephalography signals from 110 subjects in three experiments to identify the role of alpha activity in proactive distractor suppression induced by spatial cues and its influence on subsequent distractor inhibition. Behaviorally, we found novel spatial changes in spatial distractor cues: cueing distractors far away from the target improves search performance for the target while cueing distractors close to the target hampers performance. Crucially, we found dynamic characteristics of spatial representation for distractor suppression during anticipation. This result was further verified by alpha power increased relatively contralateral to the cued distractor. At both the between- and within-subjects levels, we found that these activities further predicted the decrement of subsequent PDcomponent, which was indicative of reduced distractor interference. Moreover, anticipatory alpha activity and its link with subsequent PDcomponent were specific to the high predictive validity of distractor cue. Together, these results provide evidence for the existence of proactive suppression mechanisms of spatial distractors, support the role of alpha activity as gating by proactive suppression and reveal the underlying neural mechanisms by which cueing the spatial distractor may contribute to reduced distractor interference. (235).SignificanceIn space, the attention-capturing distractors are obstacles to successfully identifying targets. How to sidestep task-irrelevant distractors that stand between the target and our focus in advance is essential but still unclear. This research investigated how dynamic spatial cues can help us proactively eliminate attention-capturing distractors. Using three cue-distractor tasks that manipulate the predictive validity of distractor occurrence, we provide a series of evidence for the presence of alpha power activity related to distractor anticipation. Critically, this was the first study linking cue-elicited alpha power and distractor-elicited PD, indicating that spatial modulation of alpha power may reduce distractor interference. These findings delineate the neural mechanisms of proactive suppression for spatial distractors. (109)
RAREFAN: A webservice to identify REPINs and RAYTs in bacterial genomes
Authors: Fortmann-Grote Carsten , von Irmer Julia , Bertels Frederic 
Published: May 2022

AbstractCompared to eukaryotes, repetitive sequences are rare in bacterial genomes and usually do not persist for long. Yet, there is at least one class of persistent prokaryotic mobile genetic elements: REPINs. REPINs are non-autonomous transposable elements replicated by single-copy transposases called RAYTs. REPIN-RAYT systems are mostly vertically inherited and have persisted in individual bacterial lineages for millions of years. Discovering and analyzing REPIN populations and their corresponding RAYT transposases in bacterial species can be rather laborious, hampering progress in understanding REPIN-RAYT biology and evolution. Here we present RAREFAN, a webservice that identifies REPIN populations and their corresponding RAYT transposase in a given set of bacterial genomes. We demonstrate RAREFAN’s capabilities by analyzing a set of 49Stenotrophomonas maltophiliagenomes, containing nine different REPIN-RAYT systems. We guide the reader through the process of identifying and analyzing REPIN-RAYT systems acrossS. maltophilia, highlighting erroneous associations between REPIN and RAYTs, and providing solutions on how to find correct associations. RAREFAN enables rapid, large-scale detection of REPINs and RAYTs, and provides insight into the fascinating world of intragenomic sequence populations in bacterial genomes. RAREFAN is available athttp://rarefan.evolbio.mpg.de.
Breastfeeding duration is associated with larger cortical gray matter volumes in children from the ABCD study
Authors: Núñez Christian , García-Alix Alfredo , Arca Gemma , Agut Thais , Carreras Nuria , Portella Maria J. , Stephan-Otto Christian 
Published: May 2022

AbstractDespite the numerous studies in favor of breastfeeding for its benefits in cognition and mental health, the long-term effects of breastfeeding on brain structure are still largely unknown. Here we analyzed 7,860 MRI images of children 9 to 11 years of age from the Adolescent Brain Cognitive Development (ABCD) dataset in order to study the relationship between breastfeeding duration and cerebral gray matter volumes. We also explored the potential mediatory role of brain volumes on behavior. Whole-brain voxel-based morphometry analyses revealed an association mainly between breastfeeding duration and larger bilateral volumes of the pars orbitalis and the lateral orbitofrontal cortex. In particular, the association with the left pars orbitalis and the lateral orbitofrontal cortex proved to be very robust, and it appeared to mediate the relationship between breastfeeding duration and the negative urgency dimension of the UPPS-P Impulsive Behavior Scale. Global gray matter volumes were also significant mediators for behavioral problems as measured with the Child Behavior Checklist. Overall, our findings suggest that breastfeeding is an important factor in the proper development of the brain, particularly for the pars orbitalis and lateral orbitofrontal regions. This, in turn, may impact impulsive personality and mental health in early puberty.
Nab3 nuclear granule accumulation is driven by respiratory capacity
Authors: Hutchinson Katherine M. , Hunn Jeremy C. , Reines Daniel 
Published: May 2022

ABSTRACTNumerous biological processes involve proteins capable of transiently assembling into subcellular compartments necessary for cellular functions. One process is the RNA polymerase II transcription cycle which involves initiation, elongation, co-transcriptional modification of nascent RNA, and termination. The essential yeast transcription termination factor Nab3 is required for termination of small non-coding RNAs and accumulates into a compact nuclear granule upon glucose removal. Nab3 nuclear granule accumulation varies in penetrance across yeast strains and a higher Nab3 granule accumulation phenotype is associated with petite strains, suggesting a possible ATP-dependent mechanism for granule disassembly. Here, we demonstrate the uncoupling of mitochondrial oxidative phosphorylation by drug treatment or deletions of nuclear-encoded ATP synthase subunit genes, were sufficient to increase Nab3 granule accumulation and led to an inability to proliferate during prolonged glucose deprivation, which requires respiration. Additionally, by enriching for respiration competent cells from a petite-prone strain, we generated a low granule-accumulating strain from a relatively high one, providing another link between respiratory competency and Nab3 granules. Consistent with the resulting idea that ATP is involved in granule accumulation, the addition of extracellular ATP to semi-permeabilized cells was sufficient to reduce Nab3 granule accumulation. Deleting the SKY1 gene, which encodes a kinase that phosphorylates nuclear SR repeat-containing proteins and is involved in efficient stress granule disassembly, also resulted in increased granule accumulation. This observation implicates Sky1 in Nab3 granule biogenesis. Taken together, these findings suggest there is normally an equilibrium between termination factor granule assembly and disassembly mediated by ATP-requiring nuclear machinery.
Predictions of immunogenicity reveal potent SARS-CoV-2 CD8+ T-cell epitopes
Authors: Gfeller David , Schmidt Julien , Croce Giancarlo , Guillaume Philippe , Bobisse Sara , Genolet Raphael , Queiroz Lise , Cesbron Julien , Racle Julien , Harari Alexandre 
Published: May 2022

ABSTRACTThe recognition of pathogen or cancer-specific epitopes by CD8+ T cells is crucial for the clearance of infections and the response to cancer immunotherapy. This process requires epitopes to be presented on class I Human Leukocyte Antigen (HLA-I) molecules and recognized by the T-Cell Receptor (TCR). Machine learning models capturing these two aspects of immune recognition are key to improve epitope predictions. Here we assembled a high-quality dataset of naturally presented HLA-I ligands and experimentally verified neo-epitopes. We then integrated these data with new algorithmic developments to improve predictions of both antigen presentation and TCR recognition. Applying our tool to SARS-CoV-2 proteins enabled us to uncover several epitopes. TCR sequencing identified a monoclonal response in effector/memory CD8+ T cells against one of these epitopes and cross-reactivity with the homologous SARS-CoV-1 peptide.
Cellular segregation in co-cultures driven by differential adhesion and contractility on distinct time scales
Authors: Skamrahl Mark , Schünemann Justus , Mukenhirn Markus , Pang Hongtao , Gottwald Jannis , Jipp Marcel , Ferle Maximilian , Rübeling Angela , Oswald Tabea A. , Honigmann Alf , Janshoff Andreas 
Published: May 2022

AbstractCellular sorting and pattern formation are crucial for many biological processes such as development, tissue regeneration, and cancer progression. Prominent physical driving forces for cellular sorting are differential adhesion and contractility. Here, we studied the segregation of epithelial co-cultures containing highly contractile, ZO1/2-depleted MDCKII cells (dKD) and their wildtype (WT) counterparts using multiple quantitative, high-throughput methods to monitor their dynamical and mechanical properties. We observe a time-dependent segregation process, governed mainly by differential contractility on short (< 5 h) and differential adhesion on long (> 5 h) time scales, respectively. The overly contractile dKD cells exert strong lateral forces on their WT neighbors, thereby apically depleting their surface area. This is reflected in a six-fold difference in excess surface area between both cell types. The lateral forces lead to a four-to sixfold increase in tension at all junctions that are in contact with the contractile cells including the interface between heterotypic cell-cell contacts. Concomitantly, the tight junction-depleted, contractile cells exhibit weaker cell-cell adhesion and lower traction force. Drug-induced contractility reduction and partial calcium depletion delay the initial segregation but cease to change the final demixed state, rendering differential adhesion the dominant segregation force at longer time scales.This well-controlled model system shows how cell sorting is accomplished through a complex interplay between differential adhesion and contractility and can be explained largely by generic physical driving forces.Significance StatementFundamental biological processes, such as tissue morphogenesis during development, rely on the correct sorting of cells. Cellular sorting is governed by basic physical properties such as the adhesion between cells and their individual contractility. Here, we study the impact of these parameters in co-cultures consisting of epithelial wildtype cells and overly contractile, less adhesive tight junction-depleted ones. We find time-dependent segregation into clusters: differential contractility drives fast segregation on short-time scales, while differential adhesion dominates the final segregated state over longer times.
Computational epitope mapping of class I fusion proteins using Bayes classification
Authors: Fischer Marion F.S. , Crowe James E. , Meiler Jens 
Published: May 2022

AbstractAntibody epitope mapping of viral proteins plays a vital role in understanding immune system mechanisms of protection. In the case of class I viral fusion proteins, recent advances in cryo-electron microscopy and protein stabilization techniques have highlighted the importance of cryptic or ‘alternative’ conformations that expose epitopes targeted by potent neutralizing antibodies. Thorough epitope mapping of such metastable conformations is difficult, but is critical for understanding sites of vulnerability in class I fusion proteins that occur as transient conformational states during viral attachment and fusion. We introduce a novel method Accelerated class I fusion protein Epitope Mapping (AxIEM) that accounts for fusion protein flexibility to significantly improve out-of-sample prediction of discontinuous antibody epitopes. Harnessing data from previous experimental epitope mapping efforts of several class I fusion proteins, we demonstrate that accuracy of epitope prediction depends on residue environment and allows for the precise prediction of conformation-dependent antibody target residues. We also show that AxIEM can to identify common epitopes and provide structural insights for the development and rational design of vaccines.Author SummaryEfficient determination of neutralizing epitopes of viral fusion proteins is paramount in the development of antibody-based therapeutics against rapidly evolving or undercharacterized viral pathogens. Advances in the determination of viral fusion proteins in multiple conformations with ‘cryptic epitopes’ during attachment and fusion has highlighted the importance of epitope accessibility due to viral fusion protein flexibility, a physical trait not accounted for in previous B-cell epitope prediction methods. Given the relatively limited number of viral fusion proteins that have been determined in multiple conformations that also have been extensively subjected to epitope mapping techniques,, which are predominantly class I fusion proteins, we chose a limited feature set in combination with a low-complexity Bayesian classifier model to avoid overfitting. We show that this model demonstrates higher accuracy in out-of-sample performance than publicly available epitope prediction methods. Additionally, due to limited structural annotation of neutralizing epitope residues, we provide examples of how our model better discerns conformation-specific epitopes, which is critical for subunit vaccine design, and how this may provide a novel approach to assess the structural changes of antigenicity of viral fusion protein homologues.
Regulation by cyclic-di-GMP attenuates dynamics and enhances robustness of bimodal curli gene activation in Escherichia coli
Authors: Lamprecht Olga , Ratnikava Maryia , Jacek Paulina , Kaganovitch Eugen , Buettner Nina , Fritz Kirstin , Biazruchka Ina , Köhler Robin , Pietsch Julian , Sourjik Victor 
Published: May 2022

AbstractCurli amyloid fibers are a major constituent of the extracellular biofilm matrix formed by bacteria of the Enterobacteriaceae family. Within Escherichia coli biofilms, curli gene expression is limited to a subpopulation of bacteria, leading to heterogeneity of extracellular matrix synthesis. Here we show that bimodal activation of curli expression occurs not only in submerged and macrocolony biofilms, but also in well-mixed planktonic cultures of E. coli, resulting in all-or-none stochastic differentiation into distinct subpopulations of curli-positive and curli-negative cells at the entry into the stationary phase of growth. Stochastic curli activation in individual E. coli cells could further be observed during continuous growth in a conditioned medium in a microfluidic device, which further revealed that the curli-positive state is only metastable. In agreement with previous reports, regulation of curli gene expression by c-di-GMP via two pairs of diguanylate cyclase and phosphodiesterase enzymes, DgcE/PdeH and DgcM/PdeR, modulates the fraction of curli-positive cells under all tested growth conditions. Unexpectedly, removal of this regulatory network does not abolish the bimodality of curli gene expression, although it affects dynamics of activation and increases heterogeneity of expression levels among individual cells. Moreover, the fraction of curli-positive cells within an E. coli population shows stronger dependence on growth conditions in the absence of c-di-GMP regulation. We thus conclude that, while not required for the emergence of bimodal curli gene expression in E. coli, this c-di-GMP regulatory network attenuates the frequency and dynamics of gene activation and increases its robustness to cellular heterogeneity and environmental variation.
Intrinsic excitability in layer IV-VI anterior insula to basolateral amygdala projection neurons encodes the confidence of taste valence
Authors: Chandran Sailendrakumar Kolatt , Yiannakas Adonis , Kayyal Haneen , Salalha Randa , Cruciani Federica , Mizrahi Liron , Khamaisy Mohammad , Stern Shani , Rosenblum Kobi 
Published: May 2022

AbstractAvoiding potentially harmful, and consuming safe food is crucial for the survival of living organisms. However, sensory information can change its valence following conflicting experiences. Novelty and aversiveness are the two crucial parameters defining the currently perceived valence of taste. Importantly, the ability of a given taste to serve as CS in conditioned taste aversion (CTA) is dependent on its valence. Activity in anterior insula (aIC) layer IV-VI pyramidal neurons projecting to the basolateral amygdala (BLA) is correlative and necessary for CTA learning and retrieval, as well as the expression of neophobia towards novel tastants, but not learning taste familiarity. Yet, the cellular mechanisms underlying the updating of taste valence representation in this specific pathway are poorly understood. Here, using retrograde viral tracing and whole cell patch-clamp electrophysiology in trained mice, we demonstrate that the intrinsic properties of deep-lying layer IV-VI, but not superficial layer I-III aIC-BLA neurons, are differentially modulated by both novelty and valence, reflecting the subjective predictability of taste valence arising from prior experience. These correlative changes in the profile of intrinsic properties of LIV-VI aIC-BLA neurons were detectable following both simple taste experiences, as well as following memory retrieval, extinction learning and reinstatement.
Video-based automated analysis of MDS-UPDRS III parameters in Parkinson disease
Authors: Vignoud Gaëtan , Desjardins Clément , Salardaine Quentin , Mongin Marie , Garcin Béatrice , Venance Laurent , Degos Bertrand 
Published: May 2022

ABSTRACTBackgroundAmong motor symptoms of Parkinson’s disease (PD), including rigidity and resting tremor, bradykinesia is a mandatory feature to define the parkinsonian syndrome. MDS-UPDRS III is the worldwide reference scale to evaluate the parkinsonian motor impairment, especially bradykinesia. However, MDS-UPDRS III constitutes an agent-based score making reproducible measurements and follow-up challenging.ObjectivesUsing a deep learning approach, we developed a tool to compute an objective score of bradykinesia based on the gold-standard MDS-UPDRS III.MethodsIn the Movement Disorder unit of Avicenne University Hospital, we acquired a large database of videos of parkinsonian patients performing MDS-UPDRS III protocols. We applied two deep learning algorithms to detect a two-dimensional (2D) skeleton of the hand composed of 21 predefined points, and transposed it into a three-dimensional (3D) skeleton.ResultsWe developed a 2D and 3D automated analysis tool to study the evolution of several key parameters during the protocol repetitions of the MDS-UPDRS III. Scores from 2D automated analysis showed a significant correlation with gold-standard ratings of MDS-UPDRS III, measured with coefficients of determination for the tapping (0.609) and hand movements (0.701) protocols using decision tree algorithms. The individual correlations of the different parameters measured with MDS-UPDRS III scores carry meaningful information and are consistent with MDS-UPDRS III guidelines.ConclusionWe developed a deep learning-based tool to reliably score and analyze bradykinesia for parkinsonian patients.
Molecular and developmental signatures of genital size macro-evolution in bugs
Authors: Genevcius Bruno C. , Callandrielo Denis C. , Torres Tatiana T. 
Published: May 2022

AbstractWith the advance of the evo-devo research program, our understanding of the genes and pathways that determine the architecture of novel traits has experienced drastic growth. Nevertheless, single-species approaches are insufficient to understand the processes by which evolution shapes morphological changes after their emergence. As such, we still have an elusive knowledge of how these genetic-developmental architectures evolve themselves for most of the structures, as well as how their evolution is mirrored in the phenotypic change across large time scales. Here, we tackle this gap by reconstructing the evolution of male genital size, one of the most complex traits in insects, together with its underlying genetic architecture. Using the order Hemiptera as a model, which spans over 350 million years of evolution, we estimate the correlation between genital size and three features: development rate, body size, and rates of DNA substitution in 68 genes previously associated with genital development. We demonstrate that genital size macro-evolution has been largely dependent on body size and weakly influenced by development rate and the phylogenetic history. Our results further revealed positive correlations between mutation rates and genital size for 18 genes. Interestingly, there is great diversity in the function of these genes, in the signaling pathways that they participate in, and in the specific genital parts that they control. These results suggest that fast genital size evolution has been enabled by molecular changes associated with diverse morphogenetic processes, such as cuticle composition, patterning of sensory apparatus, and organ growth itself. Our data further demonstrate that the majority of DNA evolution correlated with the genitalia has been shaped by negative selection or neutral evolution. This indicates that genital changes are predominantly facilitated by relaxation of constraints rather than positive selection, possibly due to the high pleiotropic nature of the morphogenetic genes.