bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Export of Drosophila PERIOD contributes to temperature compensation of the circadian clock
Authors: Giesecke Astrid , Johnstone Peter S , Lamaze Angelique , Landskron Johannes , Atay Ezgi , Chen Ko-Fan , Top Deniz , Stanewsky Ralf 
Published: October 2021

AbstractCircadian clocks are self-sustained molecular oscillators controlling daily changes of behavioral activity and physiology. For functional reliability and precision the frequency of these molecular oscillations must be stable at different environmental temperatures, known as ‘temperature compensation’. Despite being an intrinsic property of all circadian clocks, this phenomenon is not well understood at the molecular level. Here we use behavioral and molecular approaches to characterize a novel mutation in the period (per) clock gene of Drosophila melanogaster, which alters a predicted nuclear export sequence (NES) of the PER protein. We show that this new perI530A allele leads to progressively longer behavioral periods and clock oscillations with increasing temperature in both clock neurons and peripheral clock cells. While the mutant PERI530A protein shows normal circadian fluctuations and post-translational modifications at cool temperatures, increasing temperatures lead to both, severe amplitude dampening and hypophosphorylation of PERI530A. We further show that PERI530A displays reduced repressor activity at warmer temperatures, presumably because it cannot inactivate the transcription factor CLOCK (CLK). With increasing temperatures nuclear accumulation of PERI530A within clock neurons is increased, suggesting that PER is normally exported out of the nucleus at warm temperatures. Consequently, downregulating the nuclear export factor CRM1 also leads to temperature-dependent changes of behavioral rhythms. In summary, our results suggest that the PER NES and the nuclear export of clock proteins play an important role in temperature compensation of the Drosophila circadian clock.
sumSTAAR: a flexible framework for gene-based association studies using GWAS summary statistics
Authors: Belonogova Nadezhda M. , Svishcheva Gulnara R. , Kirichenko Anatoly V. , Tsepilov Yakov A. , Axenovich Tatiana I. 
Published: October 2021

ABSTRACTGene-based association analysis is an effective gene mapping tool. Many gene-based methods have been proposed recently. However, their power depends on the underlying genetic architecture, which is rarely known in complex traits, and so it is likely that a combination of such methods could serve as a universal approach. Several frameworks combining different gene-based methods have been developed. However, they all imply a fixed set of methods, weights and functional annotations. Moreover, most of them use individual phenotypes and genotypes as input data. Here, we introduce sumSTAAR, a framework for gene-based association analysis using summary statistics obtained from genome-wide association studies (GWAS). It is an extended and modified version of STAAR framework proposed by Li and colleagues in 2020. The sumSTAAR framework offers a wider range of gene-based methods to combine. It allows the user to arbitrarily define a set of these methods, weighting functions and probabilities of genetic variants being causal. The methods used in the framework were adapted to analyse genes with large number of SNPs to decrease the running time. The framework includes the polygene pruning procedure to guard against the influence of the strong GWAS signals outside the gene. We also present new improved matrices of correlations between the genotypes of variants within genes. These matrices estimated on a sample of 265,000 individuals are a state-of-the-art replacement of widely used matrices based on the 1000 Genomes Project data.AUTHOR SUMMARYGene-based association analysis is an effective gene mapping tool. Quite a few frameworks have been proposed recently for gene-based association analysis using a combination of different methods. However, all of these frameworks have at least one of the disadvantages: they use a fixed set of methods, they cannot use functional annotations, or they use individual phenotypes and genotypes as input data. To overcome these limitations, we propose sumSTAAR, a framework for gene-based association analysis using GWAS summary statistics. Our framework allows the user to arbitrarily define a set of the methods and functional annotations. Moreover, we adopted the methods for the analysis of genes with a large number of SNPs to decrease the running time. The framework includes the polygene pruning procedure to guard against the influence of the strong GWAS signals outside the gene. We also present new improved matrices of correlations between the genotypes of variants within genes, which now allows to include ultra-rare variants in analysis.
Perception of a conserved family of plant signalling peptides by the receptor kinase HSL3
Authors: Rhodes Jack , Roman Andra-Octavia , Bjornson Marta , Brandt Benjamin , Derbyshire Paul , Wyler Michele , Schmid Marc , Menke Frank L.H. , Santiago Julia , Zipfel Cyril 
Published: October 2021

AbstractPlant genomes encode hundreds of secreted peptides; however, relatively few have been characterised. We report here an uncharacterised, stress-induced family of plant signalling peptides, which we call CTNIPs. Based on the role of the common co-receptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1) in CTNIP-induced responses, we identified the orphan receptor kinase HAESA-LIKE 3 (HSL3) as the CTNIP receptor via a proteomics approach. CTNIP binding, ligand-triggered complex formation with BAK1, and induced downstream responses all involve HSL3. Notably, the HSL3-CTNIP signalling module is evolutionarily ancient, predating the divergence of extant angiosperms. The identification of this signalling module will help establish its physiological role and provides a resource to understand further receptor-ligand co-evolution.
Long-range connections mirror and link microarchitectural and cognitive hierarchies in the human brain
Authors: Wang Yezhou , Royer Jessica , Park Bo-yong , de Wael Reinder Vos , Larivière Sara , Tavakol Shahin , Rodriguez-Cruces Raul , Paquola Casey , Hong Seok-Jun , Margulies Daniel S. , Smallwood Jonathan , Valk Sofie L. , Evans Alan C. , Bernhardt Boris C. 
Published: October 2021

AbstractCore features of higher-order cognition are hypothesized to be implemented via distributed cortical networks that are linked via long-range connections. However, these connections are biologically expensive, and it is unknown how the computational advantages long-range connections provide overcome the associated wiring costs. Our study investigated this question by exploring the relationship between long-range functional connections and local cortical microarchitecture. Specifically, our work (i) profiled distant cortical connectivity using resting-state fMRI and cortico-cortical geodesic distance mapping, (ii) assessed how long-range connections reflect local brain microarchitecture, and (iii) studied the microarchitectural similarity of regions connected through long-range connections. Analysis of two independent datasets indicated that sensory and motor areas had more clustered short-range connectivity patterns, while transmodal association cortices, including regions of the default mode network, were characterized by distributed, long-range connections. Confirmatory meta-analysis suggested that this topographical difference mirrored a shift in cognitive function, from perception/action towards emotional and social cognitive processing. Analysis of myelin-sensitive in vivo MRI in the same participants as well as post mortem histology and gene expression established that gradients in functional connectivity distance are paralleled by those present in cortical microarchitecture. Moreover, long-range connections were found to link together spatially remote regions of association cortex with an unexpectedly similar microarchitecture. These findings provide novel insights into how the organization of distributed functional networks in transmodal association cortex contribute to cognition, because they suggest that long-range connections link together distant islands of association cortex with similar microstructural features.
Multi-trait and multi-environment Bayesian analysis to predict the G x E interaction in flood-irrigated rice
Authors: da Silva Júnior Antônio Carlos , de Castro Sant’Anna Isabela , Silva Michele Jorge , Cruz Cosme Damião , Azevedo Camila Ferreira , Nascimento Moyses , Soares Plínio César 
Published: October 2021

AbstractThe biggest challenge for the reproduction of flood-irrigated rice is to identify superior genotypes that present development of high-yielding varieties with specific grain qualities, resistance to abiotic and biotic stresses in addition to superior adaptation to the target environment.Thus, the objectives of this study were to propose a multi-trait and multi-environment Bayesian model to estimate genetic parameters for the flood-irrigated rice crop. To this end, twenty-five rice genotypes belonging to the flood-irrigated rice breeding program were evaluated. Grain yield and flowering were evaluated in the agricultural year 2017/2018. The experimental design used in all experiments was a randomized block design with three replications. The Markov Chain Monte Carlo algorithm was used to estimate genetic parameters and genetic values. The flowering is highly heritable by the Bayesian credibility interval:h2= 0.039-0.80, and 0.02-0.91, environment 1 and 2, respectively. The genetic correlation between traits was significantly different from zero in the two environments (environment 1: −0.80 to 0.74; environment 2: −0.82 to 0.86. The relationship ofCVeandCVghigher for flowering in the reduced model (CVg/CVe= 5.83 and 13.98, environments 1 and 2, respectively). For the complete model, this trait presented an estimate of the relative variation index of:CVe= 4.28 and 4.21, environments 1 and 2, respectively. In summary, the multi-trait and multi-environment Bayesian model allowed a reliable estimate of the genetic parameter of flood-irrigated rice. Bayesian analyzes provide robust inference of genetic parameters. Therefore, we recommend this model for genetic evaluation of flood-irrigated rice genotypes, and their generalization, in other crops. Precise estimates of genetic parameters bring new perspectives on the application of Bayesian methods to solve modeling problems in the genetic improvement of flood-irrigated rice.
Investigating the genetic and environmental basis of head micromovements during MRI
Authors: Beyer Frauke , Horn Katrin , Frenzel S. , Hofer Edith , Knol Maria J. , Morys Filip , Vainik Uku , Van der Auwera Sandra , Wittfeld Katharina , Saba Yasaman , Adams Hieab HH , Bülow Robin , Grabe Hans , Homuth Georg , Koini Marisa , Loeffler Markus , Schmidt Helena , Schmidt Reinhold , Teumer Alexander , Vernooij MW , Villringer Arno , Völzke Henry , Zonneveld Hazel , Dagher A. , Scholz Markus , Witte AV 
Published: October 2021

AbstractIntroductionHead motion during magnetic resonance imaging is heritable. Further, it shares phenotypical and genetic variance with body mass index (BMI) and impulsivity. Yet, to what extent this trait is related to single genetic variants and physiological or behavioral features is unknown. We investigated the genetic basis of head motion in a meta-analysis of genome-wide association studies. Further, we tested whether physiological or psychological measures, such as respiratory rate or impulsivity, mediated the relationship between BMI and head motion.MethodsWe conducted a genome-wide association meta-analysis for mean and maximal framewise head displacement (FD) in seven population neuroimaging cohorts (UK Biobank, LIFE-Adult, Rotterdam Study cohort 1-3, Austrian Stroke Prevention Family Study, Study of Health in Pomerania; total N = 35.109). We performed a pre-registered analysis to test whether respiratory rate, respiratory volume, self-reported impulsivity and heart rate mediated the relationship between BMI and mean FD in LIFE-Adult.ResultsNo variant reached genome-wide significance for neither mean nor maximal FD. Neither physiological nor psychological measures mediated the relationship between BMI and head motion.ConclusionBased on these findings from a large meta-GWAS and pre-registered follow-up study, we conclude that the previously reported genetic correlation between BMI and head motion relies on polygenic variation, and that neither psychological nor simple physiological parameters explain a substantial amount of variance in the association of BMI and head motion. Future imaging studies should thus rigorously control for head motion at acquisition and during preprocessing.
Plasmodium sporozoites require the protein B9 to invade hepatocytes
Authors: Fernandes Priyanka , Loubens Manon , Marinach Carine , Coppée Romain , Grand Morgane , Andre Thanh-Phuc , Hamada Soumia , Langlois Anne-Claire , Briquet Sylvie , Bun Philippe , Silvie Olivier 
Published: October 2021

ABSTRACTPlasmodium sporozoites are transmitted to a mammalian host during blood feeding by an infected mosquito and invade hepatocytes for initial replication of the parasite in the liver. This leads to the release of thousands of merozoites into the blood circulation and initiation of the pathogenic blood stages of malaria. Merozoite invasion of erythrocytes has been well characterized at the molecular and structural levels. In sharp contrast, the molecular mechanisms of sporozoite invasion of hepatocytes are poorly characterized. Here we report a new role during sporozoite entry for the B9 protein, a member of the 6-cysteine domain protein family. Using genetic tagging and gene deletion approaches in rodent malaria parasites, we show that B9 is secreted from sporozoite micronemes and is required for productive invasion of hepatocytes. Structural modelling indicates that the N-terminus of B9 forms a beta-propeller domain structurally related to CyRPA, a cysteine-rich protein forming an invasion complex with Rh5 and RIPR in P. falciparum merozoites. We provide evidence that the beta-propeller domain of B9 is essential for protein function during sporozoite entry and interacts with P36 and P52, both also essential for productive invasion of hepatocytes. Our results suggest that, despite using distinct sets of parasite and host entry factors, Plasmodium sporozoites and merozoites may share common structural modules to assemble protein complexes for invasion of host cells.
The Atomic-Level Physiochemical Determinants of T Cell Receptor Dissociation Kinetics
Authors: Rollins Zachary A. , Huang Jun , Tagkopoulos Ilias , Faller Roland , George Steven C. 
Published: October 2021

ABSTRACTThe rational design of T Cell Receptors (TCRs) for immunotherapy has stagnated due to a limited understanding of the dynamic physiochemical features of the TCR that elicit an immunogenic response. The physiochemical features of the TCR-peptide major histocompatibility complex (pMHC) bond dictate bond lifetime which, in turn, correlates with immunogenicity. Here, we: i) characterize the force-dependent dissociation kinetics of the bond between a TCR and a set of pMHC ligands using Steered Molecular Dynamics (SMD); and ii) implement a machine learning algorithm to identify which physiochemical features of the TCR govern dissociation kinetics. Our results demonstrate that the total number of hydrogen bonds between the CDR2β-MHCα(β), CDR1α-Peptide, and CDR3β-Peptide are critical features that determine bond lifetime. We propose that amino acid substitutions to these hypervariable regions of the TCR can efficiently manipulate immunogenicity and thus be used in the rational design of TCRs for immunotherapy.
Social-affective features drive human representations of observed actions
Authors: Dima Diana C. , Tomita Tyler M. , Honey Christopher J. , Isik Leyla 
Published: October 2021

AbstractHumans observe actions performed by others in many different visual and social settings. What features do we extract and attend when we view such complex scenes, and how are they processed in the brain? To answer these questions, we curated two large-scale sets of naturalistic videos of everyday actions and estimated their perceived similarity in two behavioral experiments. We normed and quantified a large range of visual, action-related and social-affective features across the stimulus sets. Using a cross-validated variance partitioning analysis, we found that social-affective features predicted similarity judgments better than, and independently of, visual and action features in both behavioral experiments. Next, we conducted an electroencephalography (EEG) experiment, which revealed a sustained correlation between neural responses to videos and their behavioral similarity. Visual, action, and social-affective features predicted neural patterns at early, intermediate and late stages respectively during this behaviorally relevant time window. Together, these findings show that social-affective features are important for perceiving naturalistic actions, and are extracted at the final stage of a temporal gradient in the brain.
Natural age-related sleep-wake alterations onset prematurely in the Tg2576 mouse model of Alzheimer’s disease
Authors: Kollarik Sedef , Moreira Carlos G. , Dias Inês , Bimbiryte Dorita , Miladinovic Djordje , Buhmann Joachim M. , Baumann Christian R. , Noain Daniela 
Published: October 2021

AbstractSleep insufficiency or decreased quality have been associated with Alzheimer’s disease (AD) already in its preclinical stages. Whether such traits are also present in rodent models of the disease has been poorly addressed, somewhat disabling the preclinical exploration of sleep-based therapeutic interventions for AD. We investigated age-dependent sleep-wake phenotype of a widely used mouse model of AD, the Tg2576 line. We implanted electroencephalography/ electromyography headpieces into 6 months old (plaque-free, n=10) and 11 months old (moderate plaque-burdened, n=10) Tg2576 and age-matched wild-type (WT) mice and recorded vigilance states for 24 hours. Tg2576 mice exhibited significantly increased wakefulness and decreased non-rapid eye movement sleep over a 24-hour period compared to WT mice at 6, but not at 11 months of age. Concomitantly, delta power appeared decreased in 6-month old Tg2576 mice in comparison to age-matched WT controls, yielding a reduced slow-wave energy phenotype in the young mutants. Lack of genotype-related differences over 24 hours in overall sleep-wake phenotype at 11 months of age appears to be the result of the natural aging of WT mice. Therefore, our results indicate that at plaque-free stages of the disease, diminished sleep quality is present in Tg2576 mice which resembles aged healthy controls, suggesting an early-onset of sleep-wake deterioration in murine AD. Whether such disturbances in the natural patterns of sleep could in turn worsen disease progression warrants further exploration.
Identification of new growth regulators using cross-species network analysis in plants
Authors: Curci Pasquale Luca , Zhang Jie , Mähler Niklas , Seyfferth Carolin , Mannapperuma Chanaka , Diels Tim , Hautegem Tom Van , Jonsen David , Street Nathaniel , Hvidsten Torgeir R. , Hertzberg Magnus , Nilsson Ove , Inze Dirk , Nelissen Hilde , Vandepoele Klaas 
Published: October 2021

AbstractWith the need to increase plant productivity, one of the challenges plant scientists are facing is to identify genes playing a role in beneficial plant traits. Moreover, even when such genes are found, it is generally not trivial to transfer this knowledge about gene function across species to identify functional orthologs. Here, we focused on the leaf to study plant growth. First, we built leaf growth transcriptional networks in Arabidopsis thaliana, maize (Zea mays), and aspen (Populus tremula). Next, known growth regulators, here defined as genes that when mutated or ectopically expressed alter plant growth, together with cross-species conserved networks, were used as guides to predict novel Arabidopsis growth regulators. Using an in-depth literature screening, 34 out of 100 top predicted growth regulators were confirmed to affect leaf phenotype when mutated or overexpressed and thus represent novel potential growth regulators. Globally, these new growth regulators were involved in cell cycle, plant defense responses, gibberellin, auxin, and brassinosteroid signaling. Phenotypic characterization of loss-of-function lines confirmed two newly predicted growth regulators to be involved in leaf growth (NPF6.4 and LATE MERISTEM IDENTITY2). In conclusion, the presented network approach offers an integrative cross-species strategy to identify new genes involved in plant growth and development.One-sentence summaryCross-species network analysis results in the identification and validation of new growth regulators in Arabidopsis.
Characterization of dissolved organic matter from temperate wetlands: field dynamics and photoreactivity changes driven by natural inputs and diagenesis along the hydroperiod
Authors: García Patricia E. , Ferro Carolina F. Mansilla , Diéguez María C. 
Published: October 2021

AbstractWetlands store large amounts of C in biomass, sediments and water. A major C fraction is in the dissolved organic matter (DOM) pool and has multiple regulatory functions in the ecosystem. Patagonian wetlands undergo profound changes in their water cycle due to warming and reduced precipitation, causing shorter hydroperiods and reduced landscape connectivity and overall affecting their C budgets. In this study we characterized the DOM pool of a temporary wetland of North Patagonia during a hydroperiod, using optical DOM proxies obtained by absorption and fluorescence spectroscopy. DOM components were modeled through EEM-PARAFAC. DOC varied between ∼4 and ∼9 mg L-1, displaying aromatic signals and terrestrial/sediment fingerprints. The humic components C1 (microbial and/or vegetation derived) and C2 (soil/sediment derived) prevailed in the DOM pool, whereas the non-humic component C3 (derived from aquatic production) showed lower contribution. Along the hydroperiod DOM optical proxies allowed identifying allochthonous inputs, degradation and an increasing contribution of the internal production to the DOM pool. Photodegradation experiments showed that exposure to PAR+UVR produced slight changes in the DOC concentration and a reduction in DOM molecular weight/size. The contribution of humic vs. non-humic components influenced DOM photoreactivity. The prevalence of humic components determined high DOM photorecalcitrance.