bluuebunny/crossref_metadata_2025_split huggingface dataset:
Copy-scAT: Deconvoluting single-cell chromatin accessibility of genetic subclones in cancer
Authors: Nikolic Ana , Singhal Divya , Ellestad Katrina , Johnston Michael , Gillmor Aaron , Morrissy Sorana , Chan Jennifer A , Neri Paola , Bahlis Nizar , Gallo Marco 
Published: September 2020

ABSTRACTSingle-cell epigenomic assays have tremendous potential to illuminate mechanisms of transcriptional control in functionally diverse cancer cell populations. However, application of these techniques to clinical tumor specimens has been hampered by the current inability to distinguish malignant from non-malignant cells, which potently confounds data analysis and interpretation. Here we describe Copy-scAT, an R package that uses single-cell epigenomic data to infer copy number variants (CNVs) that define cancer cells. Copy-scAT enables studies of subclonal chromatin dynamics in complex tumors like glioblastoma. By deploying Copy-scAT, we uncovered potent influences of genetics on chromatin accessibility profiles in individual subclones. Consequently, some genetic subclones were predisposed to acquire stem-like or more differentiated molecular phenotypes, reminiscent of developmental paradigms. Copy-scAT is ideal for studies of the relationships between genetics and epigenetics in malignancies with high levels of intratumoral heterogeneity and to investigate how cancer cells interface with their microenvironment.
ELR is a true pattern recognition receptor that associates with elicitins from diversePhytophthoraspecies
Authors: Domazakis Emmanouil , Wouters Doret , Lochman Jan , Visser Richard G. F. , Joosten Matthieu H. A. J. , Vleeshouwers Vivianne G. A. A. 
Published: September 2020

SummaryThe first layer of plant immunity against pathogens is mediated by cell surface pattern recognition receptors (PRRs) that recognize pathogen molecules in the apoplast. Several pairs of PRRs and their matching extracellular ligands have been described but, in many cases, actual evidence for ligand binding by the PRR is lacking. The receptor-like protein ELR fromSolanum microdontum, which triggers cell death upon co-expression with elicitins of variousPhytophthoraspecies and enhances resistance to late blight caused byPhytophthora infestans, was previously identified as the elicitin receptor by forward genetic screenings employing the INF1 elicitin ofP. infestans. In this study, we investigated whether ELR associates with INF1 and other elicitins that are secreted by diversePhytophthoraspp. We performedin plantaandin vitroco-immunoprecipitation of ELR with several affinity-tagged elicitins, as well asin plantatransient co-expression assays. We found that ELR physically interacts with the class I elicitins INF1 and ParA1, fromP. infestansandPhytophthora parasitica, respectively, which is in line with their ability to cause cell death when co-expressed with ELR in potato. Together, we demonstrate that ELR is a genuine PRR that binds elicitins ofPhytophthoraspecies.
Perch selection of three species of kingfishers at the Pantanal wetland, Brazil
Authors: Peinado Laura C. , Ortega Zaida 
Published: September 2020

ABSTRACTAnimal movement and behavior depend on the distribution of resources on the habitat. Therefore, individual animals are constantly making decisions on resource selection based on different attributes of the resource or its associated environmental variables. For fish-eating birds as kingfishers, selecting a suitable perch can report many benefits, as improving fishing success or reducing predation risk. Nowadays, not only natural structures, as branches, are available for birds to perch but also artificial ones, as electric lines. Thus, we aimed to understand which variables drive kingfishers’ perch selection, including the potential effect of its anthropic origin. We studied perch selection of three species of kingfishers inhabiting the Pantanal of Miranda of Brazil:Megaceryle torquata, Chloroceryle amazonaandChloroceryle americana. They feed in temporary ponds that are rich in trophic resources, where they have both natural and artificial potential perches. We hypothesized that artificial perches could be strongly selected, as they are more stable than natural ones and go through the ponds, providing a long surface to select optimal conditions. We assessed how kingfishers are selecting perches based on four ecologically relevant traits: (1) being artificial or natural, perch height, (3) distance to the water, and (4) plant cover. We used a resource selection function (RSF) approach to quantify the effect of these variables in the probability of presence of kingfishers. The artificial origin of a perch was independent of the probability of selection for the three species. Furthermore, birds acted randomly to the other studied variables, except for individuals ofC. amazona, which select higher perches, above 3.20 m. We discuss the implications of these results for understanding the behavioral ecology and use of space of neotropical kingfishers, and how this affects their vulnerability to human habitat alterations.GRAPHICAL ABSTRACT
The evolutionary dynamics of genetic incompatibilities introduced by duplicated genes inArabidopsis thaliana
Authors: Jiao Wen-Biao , Patel Vipul , Klasen Jonas , Liu Fang , Pecinkova Petra , Ferrand Marina , Gy Isabelle , Camilleri Christine , Effgen Sigi , Koornneef Maarten , Pecinka Ales , Loudet Olivier , Schneeberger Korbinian 
Published: September 2020

AbstractAlthough gene duplications provide genetic backup and allow genomic changes under relaxed selection, they may potentially limit gene flow. When different copies of a duplicated gene are pseudo-functionalized in different genotypes, genetic incompatibilities can arise in their hybrid offspring. While such cases have been reported after manual crosses, it remains unclear whether they occur in nature and how they affect natural populations. Here we identified four duplicated-gene based incompatibilities including one previously not reported within an artificial Arabidopsis intercross population. Unexpectedly, however, for each of the genetic incompatibilities we also identified the incompatible alleles in natural populations based on the genomes of 1,135 Arabidopsis accessions published by the 1001 Genomes Project. Using the presence of incompatible allele combinations as phenotypes for GWAS, we mapped genomic regions which included additional gene copies which likely rescue the genetic incompatibility. Reconstructing the geographic origins and evolutionary trajectories of the individual alleles suggested that incompatible alleles frequently co-exist, even in geographically closed regions, and that their effects can be overcome by additional gene copies collectively shaping the evolutionary dynamics of duplicated genes during population history.
Optimized cultivar deployment improves the efficiency and stability of sunflower crop production at national scale
Authors: Casadebaig Pierre , Gauffreteau Arnaud , Landré Amélia , Langlade Nicolas B. , Mestries Emmanuelle , Sarron Julien , Trépos Ronan , Vincourt Patrick , Debaeke Philippe 
Published: September 2020

AbstractPlant breeding programs design new crop cultivars which, while developed for distinct populations of environments, are nevertheless grown over large areas during their time in the market. Over its cultivation area, the crop is exposed to highly diverse stress patterns caused by climatic uncertainty and multiple management options, which often leads to decreased expected crop performance.In this study, we aim is to assess how finer spatial management of genetic resources could reduce the yield variance explained by genotype × environment interactions in a set of cropping environments and ultimately improve the efficiency and stability of crop production. We used modeling and simulation to predict the crop performance resulting from the interaction between cultivar growth and development, climate and soil conditions, and management practices. We designed a computational experiment that evaluated the performance of a collection of commercial sunflower cultivars in a realistic population of cropping conditions in France, built from extensive agricultural surveys. Distinct farming locations sharing similar simulated abiotic stress patterns were clustered together to specify environment types. We then used optimization methods to search for cultivars × environments combinations leading to increased yield expectations.Results showed that a single cultivar choice adapted to the most frequent environment-type in the population is a robust strategy. However, the relevance of cultivar recommendations to specific locations was gradually increasing with the knowledge of pedo-climatic conditions. We argue that this approach while being operational on current genetic material could act synergistically with plant breeding as more diverse material could enable access to cultivars with distinctive traits, more adapted to specific conditions.Key messageCrop simulation helps to analyze environmental impacts on crops and provides year-independent context information. This information is of major importance when deciding which cultivar to choose at sowing time.
Characterization of Wnt Signaling Genes inDiaphorina citri, Asian Citrus Psyllid
Authors: Vosburg Chad , Reynolds Max , Noel Rita , Shippy Teresa , Hosmani Prashant S , Flores-Gonzalez Mirella , Mueller Lukas A , Hunter Wayne B , Brown Susan J , D’Elia Tom , Saha Surya 
Published: September 2020

AbstractThe Asian citrus psyllid,Diaphorina citri, is an insect vector that transmitsCandidatusLiberibacter asiaticus, the causal agent of the Huanglongbing (HLB) or citrus greening disease. This disease has devastated Florida’s citrus industry and threatens California’s industry as well as other citrus producing regions around the world. To find novel solutions to the disease, a better understanding of the vector is needed. TheD. citrigenome has been used to identify and characterize genes involved in Wnt signaling pathways. Wnt signaling is utilized for many important biological processes in metazoans, such as patterning and tissue generation. Curation based on RNA sequencing data and sequence homology confirm twenty four Wnt signaling genes within theD. citrigenome, including homologs for beta-catenin, Frizzled receptors, and seven Wnt-ligands. Through phylogenetic analysis, we classifyD. citriWnt-ligands asWg/Wnt1, Wnt5, Wnt6, Wnt7, Wnt10, Wnt11, andWntA. TheD. citriversion 3.0 genome with chromosomal length scaffolds reveals a conservedWnt1-Wnt6-Wnt10gene cluster with gene configuration similar to that inDrosophila melanogaster. These findings provide a greater insight into the evolutionary history ofD. citriand Wnt signaling in this important hemipteran vector. Manual annotation was essential for identifying high quality gene models. These gene models can further be used to develop molecular systems, such as CRISPR and RNAi, that target and controlD. citripopulations, to manage the spread of HLB. Manual annotation of Wnt signaling pathways was done as part of a collaborative community annotation project (https://citrusgreening.org/annotation/index).
Model guided trait-specific co-expression network estimation as a new perspective for identifying molecular interactions and pathways
Authors: Kontio Juho A. J. , Pyhäjärvi Tanja , Sillanpää Mikko J. 
Published: September 2020

AbstractA wide variety of parametric approaches and co-expression networks have been developed for finding gene-by-gene interactions underlying complex traits from expression data. However, a little is known about the practical correspondence and synergistic potential of these different schemes. We provide a framework for parallel consideration of parametric interaction models with quantitative traits and co-expression networks based on a previously uncharacterized link between them. Resulting trait-specific co-expression network estimation method 1) serves to enhance the interpretation of biological networks in a more parametric sense and 2) exploits the underlying parametric model itself in the estimation process. It is tailored for simultaneous identification and classification of molecular interactions and pathways regulating complex traits by accounting for common characteristics of genetic architectures due to which the mainstream methods often lack efficiency. A remarkable advance over the state-of-art methods is illustrated theoretically and through comprehensive simulated scenarios. In particular, prognostically important novel findings in acute myeloid leukemia analysis demonstrate the method’s immediate practical relevance.Author summaryHere we built up a mathematically justified bridge between parametric approaches and co-expression networks that have become prevalent for identifying molecular interactions underlying complex traits. We first shared our concern that methodological improvements around these schemes adjusting only their power and scalability are bounded by more fundamental scheme-specific limitations. Subsequently, our theoretical results were exploited to overcome these limitations to find gene-by-gene interactions neither of which can capture alone. We also aimed to illustrate theoretically and empirically how this framework enables the interpretation of co-expression networks in a more parametric sense to achieve systematic insights into complex biological processes more reliably. The main procedure was fit for various types of biological applications and high-dimensional data to cover the area of systems biology as broadly as possible. In particular, we chose to illustrate the method’s applicability for gene-profile based risk-stratification in cancer research using public acute myeloid leukemia datasets.
Therapeutic inhibition of keratinocyte TRPV3 sensory channel by local anesthetic dyclonine
Authors: Liu Qiang , Hu Juan , Wang Jin , Wei Xin , Ping Conghui , Gao Yue , Xie Chang , Yu Ye , Li Dongdong , Yao Jing 
Published: September 2020

AbstractThe multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. Nevertheless, whether and how TRPV3 could be therapeutically targeted remains to be elucidated. We here report that mouse and human TRPV3 channel is selectively targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Accordingly, dyclonine rescued cell death caused by gain-of-function TRPV3 mutations and suppressed pruritus symptoms in vivo in mouse model. At the single-channel level, dyclonine inhibited TRPV3 open probability but not the unitary conductance. By molecular docking and mutagenesis, we further uncovered single residues in TRPV3 pore region that could toggle the inhibitory efficiency of dyclonine. The functional and mechanistic insights obtained on dyclonine-TRPV3 interaction will help to conceive updated therapeutics for skin inflammation.
Diverse myeloid cells are recruited to the developing and inflamed mammary gland
Authors: Wilson Gillian J , Fukuoka Ayumi , Vidler Francesca , Graham Gerard J 
Published: September 2020

AbstractThe immune system plays fundamental roles in the mammary gland, shaping developmental processes and controlling inflammation during infection and cancer. Here we reveal unanticipated heterogeneity in the myeloid cell compartment during development of virgin, pregnant and involuting mouse mammary glands, and in milk. We investigate the functional consequences of individual and compound chemokine receptor deficiency on cell recruitment. Diverse myeloid cell recruitment was also shown in models of sterile inflammation and bacterial infection. Strikingly, we have shown that inflammation and infection can alter the abundance of terminal end buds, a key developmental structure, within the pubertal mammary gland. This previously unknown effect of inflammatory burden during puberty could have important implications for understanding the control of pubertal timing.
Environmental influences and individual characteristics that affect learner-centered teaching practices
Authors: Emery Nathan , Maher Jessica Middlemis , Ebert-May Diane 
Published: September 2020

AbstractResearch-based teaching practices can improve student learning outcomes in a variety of complex educational environments. The implementation of learner-centered teaching practices in STEM can both benefit or be constrained by different factors related to individual instructors and the teaching environment. However, we know little of how the instructional climate varies across institutions and how this climate affects teaching practices. Our study sought to describe the relative importance of environmental influences and individual characteristics on learner- centered teaching practices across institutions. We also assessed departmental climate for 35 US higher education institutions. We found that self-efficacy in teaching and professional development exert a strong influence on faculty teaching practices. While departmental climate did not emerge as a significant predictor of teaching practices, there was consistently low support for teaching, and institution size was negatively correlated with leadership and evaluation of effective teaching. We also found that professional development may prepare instructors to teach learner-centered courses in different collegial teaching climates. Our results suggest that through cultivating self-efficacy and participating in iterative professional development, instructors can implement effective teaching practices across institutional environments.
Ultra-sensitive measurement of brain penetration mechanics and blood vessel rupture with microscale probes
Authors: Obaid Abdulmalik , Wu Yu-Wei , Hanna Mina , Jáidar Omar , Nix William , Ding Jun , Melosh Nicholas 
Published: September 2020

AbstractMicroscale electrodes, on the order of 10-100 μm, are rapidly becoming critical tools for neuroscience and brain-machine interfaces (BMIs) for their high channel counts and spatial resolution, yet the mechanical details of how probes at this scale insert into brain tissue are largely unknown. Here, we performed quantitative measurements of the force and compression mechanics together with real-time microscopy forin vivoinsertion of a systematic series of microelectrode probes as a function of diameter (7.5–100 μm and rectangular Neuropixels) and tip geometry (flat, angled, and electrochemically sharpened). Results elucidated the role of tip geometry, surface forces, and mechanical scaling with diameter. Surprisingly, the insertion force post-pia penetration was constant with distance and did not depend on tip shape. Real-time microscopy revealed that at small enough lengthscales (<25 μm), blood vessel rupture and bleeding during implantation could be entirely avoided. This appears to occur via vessel displacement, avoiding capture on the probe surface which led to elongation and tearing for larger probes. We propose a new, three-zone model to account for the probe size dependence of bleeding, and provide mechanistic guidance for probe design.
An Integrated Multimodal Model of Alcohol Use Disorder Generated by Data-Driven Causal Discovery Analysis
Authors: Rawls Eric , Kummerfeld Erich , Zilverstand Anna 
Published: September 2020

AbstractObjectiveAlcohol use disorder (AUD) has high prevalence and adverse societal impacts, but our understanding of the factors driving AUD is hampered by a lack of studies that describe the complex multifactorial mechanisms driving AUD.MethodsWe used Causal Discovery Analysis (CDA) with data from the Human Connectome Project (HCP; n = 926 [54% female], 22% AUD [37% female]). Our outcome variable was number of AUD symptoms. We applied exploratory factor analysis (EFA) to parse phenotypic measures into underlying constructs, and assessed functional connectivity within 12 resting-state brain networks as an indicator of brain function. We then employed data-driven CDA to generate an integrated model relating phenotypic factors, fMRI network connectivity, and AUD symptom severity.ResultsEFA extracted 18 factors representing the wide HCP phenotypic space (100 measures). CDA produced an integrated multimodal model, highlighting a limited set of causes of AUD. The model proposed a hierarchy with causal influence propagating from brain function to cognition (fluid/crystalized cognition, language & working memory) to social (agreeableness/social support) to affective/psychiatric function (negative affect, low conscientiousness/attention, externalizing symptoms) and ultimately AUD severity. Every edge in the model was present atp< .001, and the SEM model overall provided a good fit (RMSEA = .06, Tucker-Lewis Index = .91).ConclusionsOur data-driven model confirmed hypothesized influences of cognitive and affective factors on AUD, while underscoring that traditional addiction models need to be expanded to highlight the importance of social factors, amongst others. Results further demonstrated that it is possible to extract a limited set of causal factors of AUD, which can inform future research aimed at tracking factors that dynamically predict alcohol use trajectories. Lastly, the presented model identified potential treatment targets for AUD, including neuromodulation of the frontoparietal network, cognitive/affective interventions, and social interventions.
Host evolutionary history and ecological context modulate the adaptive potential of the microbiome
Authors: Henry Lucas P. , Fernandez Michael , Webb Andrew , Ayroles Julien F. 
Published: September 2020

AbstractCan the microbiome serve as a reservoir of adaptive potential for hosts? To address this question, we leveraged ∼150 generations of experimental evolution inDrosophila melanogasterin a stressful, high-sugar (HS) diet. We performed a fully reciprocal transplant experiment using the control and evolved HS bacteria. If the microbiome confers benefits to hosts, then transplant recipients should gain fitness benefits compared to controls. Interestingly, we found that benefits do exist, but mismatches between fly evolution and microbiome exerted fitness costs by slowing development and reducing fecundity, especially in the stressful HS diet. The dominant HS bacteria (Acetobacter pasteurianus) uniquely encoded several genes to enable uric acid degradation, mediating the toxic effects of uric acid accumulation due to the HS diet for flies. Our study demonstrates that host genotype x microbiome x environment interactions have substantial effects on host phenotype, highlighting how host evolution and ecological context together shape the adaptive potential of the microbiome.
Stable but not rigid: Long-termin vivoSTED nanoscopy uncovers extensive remodeling of stable spines and indicates multiple drivers of structural plasticity
Authors: Steffens Heinz , Mott Alexander C. , Li Siyuan , Wegner Waja , Švehla Pavel , Kan Vanessa W. Y. , Wolf Fred , Liebscher Sabine , Willig Katrin I. 
Published: September 2020

ABSTRACTExcitatory synapses on dendritic spines of pyramidal neurons are considered a central memory locus. To foster both continuous adaption as well as the storage of long-term information, spines need to be plastic and stable at the same time. Here we advancedin vivoSTED nanoscopy to superresolve distinct features of dendritic spines (head size, neck length and width) in mouse neocortex for up to one month. While LTP-dependent changes predict highly correlated modifications of spine geometry, we find both, uncorrelated dynamics, as well as correlated changes, indicating multiple independent drivers of spine remodeling. The magnitude of this remodeling suggests substantial fluctuations in synaptic strength, and is exaggerated in a mouse model of neurodegeneration. Despite this high degree of volatility, all spine features also exhibit persistent components that are maintained over long periods of time. Thus, at the nanoscale, stable dendritic spines exhibit a delicate balance of stability and volatility.