bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomo-functional correlates of auditory development in infancy
Authors: Adibpour Parvaneh , Lebenberg Jessica , Kabdebon Claire , Dehaene-Lambertz Ghislaine , Dubois Jessica 
Published: March 2019

AbstractBrain development incorporates several intermingled mechanisms throughout infancy leading to intense and asynchronous maturation across cerebral networks and functional modalities. Combining electroencephalography (EEG) and diffusion magnetic resonance imaging (MRI), previous studies in the visual modality showed that the functional maturation of the event-related potentials (ERP) during the first postnatal semester relates to structural changes in the corresponding white matter pathways. Here we aimed to investigate similar issues in the auditory modality. We measured ERPs to syllables in 1-to 6-month-old infants and analyzed them in relation with the maturational properties of underlying neural substrates measured with diffusion tensor imaging (DTI). We first observed a decrease in the latency of the auditory P2, and a decrease of diffusivities in the auditory tracts and perisylvian regions with age. Secondly, we highlighted some of the early functional and structural substrates of lateralization. Contralateral responses to monoaural syllables were stronger and faster than ipsilateral responses, particularly in the left hemisphere. Besides, the acoustic radiations, arcuate fasciculus, middle temporal and angular gyri showed DTI asymmetries with a more complex and advanced microstructure in the left hemisphere, whereas the reverse was observed for the inferior frontal and superior temporal gyri. Finally, after accounting for the age-related variance, we correlated the inter-individual variability in P2 responses and in the microstructural properties of callosal fibers and inferior frontal regions. This study combining dedicated EEG and MRI approaches in infants highlights the complex relation between the functional responses to auditory stimuli and the maturational properties of the corresponding neural network.
Genome-wide association study of Parkinson’s disease progression biomarkers in 12 longitudinal patients’ cohorts
Authors: Iwaki Hirotaka , Blauwendraat Cornelis , Leonard Hampton L. , Kim Jonggeol J. , Liu Ganqiang , Maple-Grødem Jodi , Corvol Jean-Christophe , Pihlstrøm Lasse , van Nimwegen Marlies , Hutten Samantha J. , Khanh-Dung H. Nguyen , Rick Jacqueline , Eberly Shirley , Faghri Faraz , Auinger Peggy , Scott Kirsten M. , Wijeyekoon Ruwani , Van Deerlin Vivianna M. , Hernandez Dena G. , Gibbs J. Raphael , Chitrala Kumaraswamy Naidu , Day-Williams Aaron G. , Brice Alexis , Alves Guido , Noyce Alastair J. , Tysnes Ole-Bjørn , Evans Jonathan R. , Breen David P. , Estrada Karol , Wegel Claire E. , Danjou Fabrice , Simon David K. , Andreassen Ole , Ravina Bernard , Toft Mathias , Heutink Peter , Bloem Bastiaan R. , Weintraub Daniel , Barker Roger A. , Williams-Gray Caroline H. , van de Warrenburg Bart P. , Van Hilten Jacobus J. , Scherzer Clemens R. , Singleton Andrew B. , Nalls Mike A. 
Published: March 2019

AbstractBackgroundSeveral reports have identified different patterns of Parkinson’s disease progression in individuals carrying missense variants in theGBAorLRRK2genes. The overall contribution of genetic factors to the severity and progression of Parkinson’s disease, however, has not been well studied.ObjectivesTo test the association between genetic variants and the clinical features and progression of Parkinson’s disease on a genome-wide scale.MethodsWe accumulated individual data from 12 longitudinal cohorts in a total of 4,093 patients with 25,254 observations over a median of 3.81 years. Genome-wide associations were evaluated for 25 cross-sectional and longitudinal phenotypes. Specific variants of interest, including 90 recently-identified disease risk variants, were also investigated for the associations with these phenotypes.ResultsTwo variants were genome-wide significant. Rs382940(T>A), within the intron ofSLC44A1, was associated with reaching Hoehn and Yahr stage 3 or higher faster (HR 2.04 [1.58, 2.62], P-value = 3.46E-8). Rs61863020(G>A), an intergenic variant and eQTL forADRA2A, was associated with a lower prevalence of insomnia at baseline (OR 0.63 [0,52, 0.75], P-value = 4.74E-8). In the targeted analysis, we found nine associations between known Parkinson’s risk variants and more severe motor/cognitive symptoms. Also, we replicated previous reports ofGBAcoding variants (rs2230288: p.E365K, rs75548401: p.T408M) being associated with greater motor and cognitive decline over time, andAPOEE4 tagging variant (rs429358) being associated with greater cognitive deficits in patients.ConclusionsWe identified novel genetic factors associated with heterogeneity of progression in Parkinson’s disease. The results provide new insights into the pathogenesis of Parkinson’s disease as well as patient stratification for clinical trials.
Genetic structure of prey populations underlies the geographic mosaic of arms race coevolution
Authors: Hague Michael T.J. , Stokes Amber N. , Feldman Chris R. , Brodie Edmund D. , Brodie Edmund D. 
Published: March 2019

ABSTRACTReciprocal adaptation is the hallmark of arms race coevolution, but the symmetry of evolutionary change between interacting species is often untested, even in the best-studied battles of natural enemies. We tested whether prey and predator exhibit symmetrical local co-adaptation in the example of a geographic mosaic of coevolution between toxic newts (Taricha granulosa) and resistant garter snakes (Thamnophis sirtalis). Prior work showing a tight correlation between levels of newt toxin and snake resistance is regarded as textbook evidence of the intense arms race between natural enemies. Here, we similarly found that toxin and resistance are functionally matched in prey and predator populations, further suggesting that mosaic variation in the armaments of both species results from the local pressures of reciprocal selection. Contrary to conventional wisdom, however, we found that local variation in newt toxin is best predicted by neutral population divergence rather than the resistance of co-occurring predators. Snake resistance, on the other hand, is clearly explained by local levels of prey toxin. Prey populations seem to structure variation in defensive toxin levels across the geographic mosaic, which in turn determines selection on predator resistance. Exaggerated armaments suggest that coevolution occurs in certain hotspots, but our results imply that neutral processes like gene flow—rather than reciprocal adaptation—structure the greatest source of variation across the landscape. This pattern supports the predicted role of “trait remixing” in the geographic mosaic of coevolution, the process by which non-adaptive forces dictate spatial variation in the interactions among species.SIGNIFICANCE STATEMENTWhen the weapons of natural enemies like prey toxins and predator resistance are matched across the geographic landscape, they are usually presumed to result from arms race coevolution. In the textbook example of an arms race, matched levels of newt toxin and garter snake resistance have long been regarded as evidence of such local co-adaptation. To the contrary, we found that local variation in newt toxicity is best explained by the neutral geographic structure of newt populations. This spatial variation of prey in turn dictates local selection on garter snakes, structuring the geographic pattern of predator resistance. These results demonstrate how landscape patterns of phenotypic variation are determined by a mixture of natural selection, historical biogeography, and gene flow that comprise the geographic mosaic of coevolution.
A multi-omic cohort as a reference point for promoting a healthy human gut microbiome
Authors: Jie Zhuye , Liang Suisha , Ding Qiuxia , Li Fei , Tang Shanmei , Wang Dan , Lin Yuxiang , Chen Peishan , Cai Kaiye , Qiu Xuemei , Li Qiang , Liao Yunli , Zhou Dongsheng , Lian Heng , Zuo Yong , Chen Xiaomin , Rao Weiqiao , Ren Yan , Wang Yuan , Zi Jin , Wang Rong , Zhou Hongcheng , Lu Haorong , Wang Xiaohan , Zhang Wei , Zhang Tao , Xiao Liang , Zong Yang , Liu Weibin , Yang Huanming , Wang Jian , Hou Yong , Liu Xiao , Kristiansen Karsten , Zhong Huanzi , Jia Huijue , Xu Xun 
Published: March 2019

AbstractMore than a decade of gut microbiome studies have a common goal for human health. As most of the disease studies sample the elderly or the middle-aged, a reference cohort for young individuals has been lacking. It is also not clear what other omics data need to be measured to better understand the gut microbiome. Here we present high-depth metagenomic shotgun sequencing data for the fecal microbiome together with other omics data in a cohort of 2,183 adults, and observe a number of vitamins, hormones, amino acids and trace elements to correlate with the gut microbiome and cluster with T cell receptors. Associations with physical fitness, sleeping habits and dairy consumption are identified in this large multi-omic cohort. Many of the associations are validated in an additional cohort of 1,404 individuals. Our comprehensive data are poised to advise future study designs to better understand and manage our gut microbiome both in population and in mechanistic investigations.
Germline features associated with immune infiltration in solid tumors
Authors: Shahamatdar Sahar , He Meng Xiao , Reyna Matthew , Gusev Alexander , AlDubayan Saud H. , Van Allen Eliezer M. , Ramachandran Sohini 
Published: March 2019

ABSTRACTGiven the clinical success of immune checkpoint blockade (ICB) across a diverse set of solid tumors, and the emerging role for different immune infiltrates in contributing to response to ICB, a comprehensive assessment of the properties that dictate immune infiltrations may reveal new biological insights and inform the development of new effective therapies. Multiple studies have examined somatic and functional immune properties associated with different tumor infiltrates; however, germline features that associate with specific immune infiltrates in cancers have been incompletely characterized. Here, we analyzed over 7 million autosomal germline variants in the TCGA cohort (5788 European-ancestry samples across 30 cancer types) and tested for pan-cancer association with established immune-related phenotypes that describe the tumor immune microenvironment. We identified: one SNP associated with the fraction of follicular helper T cells in bulk tumor; 77 unique candidate genes, some of which are involved in cytokine-mediated signaling (e.g. CNTF and TRIM34) and cancer pathogenesis (e.g. ATR and AKAP9); and subnetworks with genes that are part of DNA repair (RAD51 and XPC) and transcription elongation (CCNT2) pathways. We found a positive association between polygenic risk for rheumatoid arthritis and absolute fraction of infiltrating CD8 T cells. Overall, we identified multiple germline genetic features associated with specific tumor-immune phenotypes across cancer, and developed a framework for probing inherited features that contribute to variation in immune infiltration.
Formalizing metabolic-regulatory networks by hybrid automata
Authors: Liu Lin , Bockmayr Alexander 
Published: March 2019

AbstractComputational approaches in systems biology have become a powerful tool for understanding the fundamental mechanisms of cellular metabolism and regulation. However, the interplay between the regulatory and the metabolic system is still poorly understood. In particular, there is a need for formal mathematical frameworks that allow analyzing metabolism together with dynamic enzyme resources and regulatory events. Here, we introduce a metabolic-regulatory network model (MRN) that allows integrating metabolism with transcriptional regulation, macromolecule production and enzyme resources. Using this model, we show that the dynamic interplay between these different cellular processes can be formalized by a hybrid automaton, combining continuous dynamics and discrete control.
Genetic dissection of the redundant and divergent functions of histone chaperone paralogs in yeast
Authors: Savic Neda , Shortill Shawn P. , Bilenky Misha , Dilworth David , Hirst Martin , Nelson Christopher J. 
Published: March 2019

AbstractGene duplications increase organismal robustness by providing freedom for gene divergence or by increasing gene dosage. The yeast histone chaperones Fpr3 and Fpr4 are paralogs that can assemble nucleosomesin vitro, however the genomic locations they target and their functional relationship is poorly understood. We refined the yeast synthetic genetic array (SGA) approach to enable the functional dissection of gene paralogs. Applying this method to Fpr3 and Fpr4 uncovered their redundant and divergent functions: while Fpr3 is uniquely involved in chromosome segregation, Fpr3 and Fpr4 co-operate on some genes and are redundant on others where they impact gene expression and transcriptional processivity. We find that the TRAMP5 RNA exosome is essential inΔfpr3Δfpr4yeast and leverage this information to identify Fpr3/4 target loci. Amongst these are the non-transcribed spacers of ribosomal DNA where either paralog is sufficient to establish chromatin that is both transcriptionally silent and refractory to recombination. These data provide evidence that Fpr3 and Fpr4 have shared chromatin-centric functions, especially at nucleolar rDNA. However, their distinct genetic interaction profiles show they also have evolved separate functions outside of the nucleolus.
The mechanisms of dynamin-actin interaction
Authors: Zhang Ruihui , Gerassimov Nathalie , Lee Donghoon M. , Jimah John R. , Kim Sangjoon , Luvsanjav Delgermaa , Winkelman Jonathan , Mettlen Marcel , Abrams Michael E. , Kalia Raghav , Keene Peter , Pandey Pratima , Ravaux Benjamin , Kim Ji Hoon , Ditlev Jonathon A. , Zhang Guofeng , Rosen Michael K. , Frost Adam , Alto Neal M. , Gardel Margaret , Schmid Sandra L. , Hinshaw Jenny E. , Chen Elizabeth H. 
Published: March 2019

AbstractCell-cell fusion is an indispensable process in the conception, development and physiology of multicellular organisms. Here we demonstrate a direct and noncanonical role for dynamin, best known as a fission GTPase in endocytosis, in cell-cell fusion. Our genetic and cell biological analyses show that dynamin colocalizes within the F-actin-enriched podosome-like structures at the fusogenic synapse, which is required for generating invasive membrane protrusions and myoblast fusion in vivo, in an endocytosis-independent manner. Biochemical, negative stain EM and cryo-electron tomography (cryo-ET) analyses revealed that dynamin forms helices that directly bundles actin filaments by capturing multiple actin filaments at their outer rim via interactions with dynamin’s proline-rich domain. GTP hydrolysis by dynamin triggers disassembly of the dynamin helix, exposes the sides of the actin filaments, promotes dynamic Arp2/3-mediated branched actin polymerization, and generates a mechanically stiff actin network. Thus, dynamin functions as a unique actin-bundling protein that enhances mechanical force generation by the F-actin network in a GTPase-dependent manner. Our findings have universal implications for understanding dynamin-actin interactions in various cellular processes beyond cell-cell fusion.
FcγRIIB I232T polymorphic change allosterically suppresses ligand binding
Authors: Hu Wei , Zhang Yong , Sun Xiaolin , Xu Liling , Xie Hengyi , Li Zhanguo , Liu Wanli , Lou Jizhong , Chen Wei 
Published: March 2019

AbstractFcγRIIB bindings to its ligand suppress immune cell activation. A single-nucleotide polymorphic (SNP) change, I232T, in the transmembrane (TM) domain of FcγRIIB loses its suppression function, which clinically associates with systemic lupus erythematosus (SLE). Previously, we reported that I232T tilts FcγRIIB’s TM domain. In this study, combining with molecular dynamics simulations and single-cell FRET assay, we further revealed that such tilting by I232T unexpectedly bends the FcγRIIB’s ectodomain towards plasma membrane to allosterically impede FcγRIIB’s ligand association. We then used single-cell biomechanical assay to further find out that I232T also reduces two-dimensional in-situ binding affinities and association rates of FcγRIIB interacting with its ligands by three-folds. This allosteric regulation by a SNP provides an intrinsic molecular mechanism for functional loss of FcγRIIB-I232T in SLE patients.
Automated reconstruction of all gene histories in large bacterial pangenome datasets and search for co-evolved gene modules with Pantagruel
Authors: Lassalle Florent , Veber Philippe , Jauneikaite Elita , Didelot Xavier 
Published: March 2019

AbstractThe availability of bacterial pangenome data grows exponentially, requiring efficient new methods of analysis. Currently popular approaches for the fast comparison of genomes have the drawback of not being based on explicit evolutionary models of diversification. Making sense of bacterial genome evolution, and notably in the accessory genome, requires however to take into account the complex processes by which the genomes evolve. Here we present the Pantagruel bioinformatic software pipeline, which enables the construction of a complete bacterial pangenome database geared towards the inference of gene evolution scenarios using gene tree/species tree reconciliation. Pantagruel is a modular pipeline that combines state-of-the-art external software with unique new methods. It can be executed with no supervision to perform a standard pangenome analysis, or be configured by advanced users to integrate methods of choice. A relational database underlies its data structure, allowing efficient retrieval of the large-scale data generated by integrative analyses of pangenome evolutionary history. From the reconstructed gene evolution scenarios, two main outputs are derived: firstly the gene tree-aware assignation of orthology, allowing the fine analysis of gene gain and loss history over the species phylogeny, and secondly a network of gene-to-gene association based on correlated events in scenarios of gene evolution, leading to the definition of co-evolved gene modules. Pantagruel is available as an open source software package at https://github.com/flass/pantagruel.
Endosymbiotic bacteria are prevalent and diverse in agricultural spiders
Authors: White Jennifer A. , Styer Alexander , Rosenwald Laura C. , Curry Meghan M. , Welch Kelton D. , Athey Kacie J. , Chapman Eric G. 
Published: March 2019

AbstractMaternally inherited bacterial endosymbionts are common in arthropods, but their distribution and prevalence is poorly characterized in many host taxa. For example, spiders (Araneae) have received little attention, but initial surveys suggest that vertically transmitted symbionts may be common. Here, we characterized endosymbiont infection in a community of agricultural spiders. Using a combination of diagnostic PCR and high-throughput sequencing of the bacterial microbiome, we evaluated symbiont infection in 267 individual spiders representing 14 species in 3 families. We found 27 Operational Taxonomic Units (OTUs) that are likely endosymbiotic, including several strains of Wolbachia, Rickettsia and Cardinium, all of which are vertically transmitted and frequently associated with reproductive manipulation of arthropod hosts. Seventy percent of spider species had individuals that tested positive for one or more endosymbiotic OTUs, and specimens frequently contained multiple symbiotic strain types. The most symbiont-rich species, Idionella rugosa, had eight endosymbiotic OTUs, with as many as five present in the same specimen. Individual specimens within infected spider species had a variety of symbiotypes, differing from one another in the presence or absence of symbiotic strains. Our sample included both starved and unstarved specimens, and dominant bacterial OTUs were consistent per host species, regardless of feeding status. We conclude that spiders contain a remarkably diverse symbiotic microbiota. Spiders would be an informative group for investigating endosymbiont population dynamics in time and space, and unstarved specimens collected for other purposes (e.g., food web studies) could be used, with caution, for such investigations.
Affordable Remote Monitoring of Plant Growth and Facilities using Raspberry Pi Computers
Authors: Grindstaff Brandin , Mabry Makenzie E. , Blischak Paul D. , Quinn Micheal , Pires J. Chris 
Published: March 2019

ABSTRACTPremise of the study: Environmentally controlled facilities, such as growth chambers, are essential tools for experimental research. Automated remote monitoring of such facilities with low-cost hardware can greatly improve both the reproducibility and the accurate maintenance of their conditions.Methods and Results: Using a Raspberry Pi computer, open-source software, environmental sensors, and a camera, we developed a cost-effective system for monitoring growth chamber conditions, which we have called ‘GMpi.’ Coupled with our software, GMpi_Pack, our setup automates sensor readings, photography, alerts when conditions fall out of range, and data transfer to cloud storage services.Conclusions: The GMpi offers low-cost access to environmental data logging, improving reproducibility of experiments, as well as reinforcing the stability of controlled environmental facilities. The device is also flexible and scalable, allowing customization and expansion to include other features such as machine vision.
Single-cell interactomes of the human brain reveal cell-type specific convergence of brain disorders
Authors: Mohammadi Shahin , Davila-Velderrain Jose , Kellis Manolis 
Published: March 2019

AbstractThe reference human interactome has been instrumental in the systems-level study of the molecular inner workings of the cell, providing a framework to analyze the network context of disease associated gene perturbations. However, reference organismal interactomes do not capture the tissue- and cell type-specific context in which proteins and modules preferentially act. Emerging single-cell profiling technologies, which survey the transcriptional cell-state distribution of complex tissues, could be used to infer the single-cell context of gene interactions. Here we introduce SCINET (Single-Cell Imputation and NETwork construction), a computational framework that reconstructs an ensemble of cell type-specific interactomes by integrating a global, context-independent reference interactome with a single-cell gene expression profile. SCINET addresses technical challenges of single-cell data by robustly imputing, transforming, and normalizing the initially noisy and sparse expression data. Subsequently, cell-level gene interaction probabilities and group-level gene interaction strengths are computed, resulting in cell type specific interactomes. We use SCINET to analyze the human cortex, reconstructing interactomes for the major cell types of the adult human brain. We identify network neighborhoods composed of topologically-specific genes that are central for cell-type influence but not for global interactome connectivity. We use the reconstructed interactomes to analyze the specificity and modularity of perturbations associated with neurodegenerative, neuropsychiatric, and neoplastic brain disorders; finding high variability across diseases, yet overall consistency in patterns of cell-type convergence for diseases of the same group. We infer for each disorder group disease gene networks with preferential cell-type specific activity that can aid the design and interpretation of cell-type resolution experiments. Finally, focusing on the pleiotropy of schizophrenia and bipolar disorder, we show how cell type specific interactomes enable the identification of disease genes with preferential influence on neuronal, glial, or glial-neuronal cells. The SCINET framework is applicable to any organism, cell-type/tissue, and reference network; it is freely available athttps://github.com/shmohammadi86/SCINET.