bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absolute quantification of cohesin, CTCF and their regulators in human cells
Authors: Holzmann Johann , Politi Antonio Z. , Nagasaka Kota , Hantsche-Grininger Merle , Walther Nike , Koch Birgit , Fuchs Johannes , Dürnberger Gerhard , Tang Wen , Ladurner Rene , Stocsits Roman R. , Busslinger Georg A. , Novak Bela , Mechtler Karl , Davidson Iain F. , Ellenberg Jan , Peters Jan-Michael 
Published: February 2019

AbstractThe organisation of mammalian genomes into loops and topologically associating domains (TADs) contributes to chromatin structure, gene expression and recombination. Loops and TADs are formed by cohesin and positioned by CTCF. In proliferating cells, cohesin also mediates sister chromatid cohesion, which is essential for chromosome segregation. Current models of chromatin folding and cohesion are based on assumptions of how many cohesin and CTCF molecules organise the genome. Here we have measured absolute copy numbers and dynamics of cohesin, CTCF, NIPBL, WAPL and sororin by mass spectrometry, fluorescence-correlation spectroscopy and fluorescence recovery after photobleaching in HeLa cells. In G1-phase there are ~245,000 cohesin complexes, of which ~139,000 are on chromatin. Comparison with chromatin immunoprecipitation-sequencing data implies that some genomic cohesin and CTCF enrichment sites are unoccupied in single cells at any one time. We discuss the implications of these findings for how cohesin can contribute to genome organisation and cohesion.
BICORN: An R package for integrative inference of de novo cis-regulatory modules
Authors: Chen Xi 
Published: February 2019

AbstractBICORN is an R package developed to integrate prior transcription factor binding information and gene expression data for cis-regulatory module (CRM) inference. BICORN searches for a list of candidate CRMs from binary bindings on potential target genes. Applying Gibbs sampling, BICORN samples CRMs for each gene using the fitting performance of transcription factor activities and regulation strengths of TFs in each CRM on gene expression. Consequently, sparse regulatory networks are inferred as functional CRMs regulating target genes. The BICORN package is implemented in R and is available at https://cran.r-project.org/web/packages/BICORN/index.html.
Cardiac Metabolic Limitations Contribute to Diminished Performance of the Heart in Aging
Authors: Gao X. , Jakovljevic D. G. , Beard D. A. 
Published: February 2019

AbstractChanges in the myocardial energetics associated with aging—reductions in creatine phosphate (CrP)/ATP ratio, total creatine, and ATP—mirror changes observed in failing hearts compared to healthy controls. Similarly, both aging and heart failure are associated with significant reductions in cardiac performance and maximal left ventricular cardiac power output (CPO) compared to young healthy individuals. Based on these observations, we hypothesize that reductions in the concentrations cytoplasmic adenine nucleotide, creatine, and phosphate pools that occur with aging impair the myocardial capacity to synthesize ATP at physiological free energy levels, and that the resulting changes to myocardial energetic status impair the mechanical pumping ability of the heart. The purpose of this study is to test theses hypotheses using an age-structured population model for myocardial metabolism in the adult female population and to determine the potential impact of reductions in key myocardial metabolite pools in causing metabolic/energetic and cardiac mechanical dysfunction associated with aging. To test these hypotheses, we developed a population model for myocardial energetics to predict myocardial ATP, ADP, CrP, creatine, and inorganic phosphate concentrations as functions of cardiac work and age in the adult female population. Model predictions support our hypotheses and are consistent with previous experimental observations. The major findings provide a novel theoretical and computational framework for further probing complex relationships between the energetics and performance of the heart with aging.SignificanceNormal mechanical function of the heart requires that ATP be continuously synthesized at a hydrolysis potential of roughly −60 kJ mol−1. Yet in both the aging and diseased heart the relationships between cardiac work rate and concentrations of ATP, ADP, and inorganic phosphate are altered. Important outstanding questions are: To what extent do changes in metabolite concentrations that occur in aging and heart disease affect metabolic/molecular processes in the myocardium? How are systolic and diastolic functions affected by changes in metabolite concentrations? This study addresses these questions by analyzing relationships between cardiac energy demand and supply using an age-structured population model for human myocardial energetics in women.
Single cell q-PCR derived expression profiles of identified sensory neurons
Authors: Adelman Peter , Baumbauer Kyle , Friedman Robert , Shah Mansi , Wright Margaret , Young Erin , Jankowski Michael P. , Albers Kathryn M. , Koerber H. Richard 
Published: February 2019

AbstractSensory neurons are chemically and functionally heterogeneous and this heterogeneity has been examined extensively over the last several decades. These studies have employed a variety of different methodologies, including anatomical, electrophysiological and molecular approaches. Recent studies using next generation sequencing techniques have examined the transcriptome of single sensory neurons. Although, these reports have provided a wealth of exciting new information on the heterogeneity of sensory neurons, correlation with functional types is lacking. Here, we employed retrograde tracing of cutaneous and muscle afferents to examine the variety of mRNA expression profiles of individual, target-specific sensory neurons. In addition, we used an ex vivo skin/nerve/DRG/ spinal cord preparation to record and characterize the functional response properties of individual cutaneous sensory neurons that were then intracellularly labeled with fluorescent dyes, recovered from dissociated cultures and analyzed for gene expression. We found that by using single cell qPCR techniques and a limited set of genes, we can identify transcriptionally distinct groups. We have also used calcium imaging and single cell qPCR to determine the correlation between levels of mRNA expression and functional protein expression and how functional properties correlated with the different transcriptional groups. These studies show that although transcriptomics does map to functional types, within any one functional subgroup, there are highly variable patterns of gene expression. Thus, studies that rely on the expression pattern of one or a few genes as a stand in for physiological experiments, runs a high risk of data misinterpretation with respect to function.Significance statementExpression profiles of unidentified sensory neurons have been recently studied using RNASeq techniques. Here, we utilize a multifactorial approach to target identified cutaneous and muscle afferents to examine expression and functional levels of specific high priority candidate genes using ex vivo electrophysiology, Ca2+ imaging, and single cell qPCR. Using this methodology, we were able to identify specific groups of neurons with distinct functional properties that corresponded to unique transcriptional profiles. This represents the first attempt to relate neuronal phenotype with levels of gene expression in single identified afferents and highlights the importance of combining functional analysis with transcriptomics.
Prevalence of sleep-disordered breathing and associations with malocclusion in children
Authors: Aroucha Lyra Maria Carlla , Aguiar Débora , Paiva Mabel , Arnaud Manuela , Filho Arnoldo Alencar , Rosenblatt Aronita , Thérèse Innes Nicola Patricia , Heimer Mônica Vilela 
Published: February 2019

ABSTRACTObjectiveThis study aimed to determine the prevalence of sleep-disordered breathing (SDB) and its association with malocclusion among children in Recife, Brazil.Methods390 children aged seven to eight years took part in the study, comprised by the body mass measurement, orthodontic examination and parent’s information required by the Sleep Disturbance Scale for Children. Statistics tools were Pearson’s chi-square and Lemeshow test.ResultsSDB was found in 33.3% of the children and associated with overjet (p= 0.007), anterior open bite (p=0.008) and posterior crossbite (p= 0.001). There was no association between BMI and SDB. The multivariate logistic regression model indicated that the anterior open bite (p= 0.002) and posterior crossbite (p = 0.014) have an association with SDB.ConclusionsResults of this study indicated that the prevalence of SDB was high and highly associated with malocclusion; anterior open bite and posterior crossbite are risk factors for SDB.
Increased synaptic facilitation and exploratory behavior in mice lacking the presynaptic protein Mover
Authors: Viotti Julio S. , Ott Frederik W. , Schleicher Eva M. , Wagner Jannek M. , Bouter Yvonne , Bayer Thomas A. , Dresbach Thomas 
Published: February 2019

AbstractIn vertebrates and invertebrates, neurotransmitter release relies on a highly conserved molecular machinery. A surprisingly small number of presynaptic proteins evolved specifically in vertebrates. How they expand the power or versatility of the conserved core machinery is unclear. One of these vertebrate-specific proteins, called Mover / TPRGL / SVAP30, is heterogeneously expressed throughout the brain, suggesting that it adds special functions to subtypes of presynaptic terminals. In this study we generated Mover knockout mice to investigate the role of Mover from synaptic transmission to behavior. Deletion of Mover did not affect synaptic transmission at CA3 to CA1 synapses. In contrast, Mover deficient mice had strongly increased short-term facilitation at mossy fiber to CA3 synapses. This increase included frequency facilitation, a hallmark of mossy fiber terminal function. The effect was age- and Ca2+-dependent, and relied on the Kainate receptor/cAMP pathway in the mossy fiber terminals. Despite this change in presynaptic plasticity, the absence of Mover did not affect long-term spatial reference memory or working memory, but led to reduced anxiety. These discoveries suggest that Mover has distinct roles at different synapses. At mossy-fiber terminals, it acts to constrain the extent of presynaptic facilitation. Its role in activity-dependent neurotransmission could be necessary for normal anxiety responses.Significance StatementThe enormous increase in the complexity of brains during evolution is accompanied by a remarkably small number of new, vertebrate-specific presynaptic proteins. These proteins are unlikely to be essential for transmitter release, because invertebrate synapses do not need them. But what functions do they fulfill? We show that the vertebrate-specific protein Mover is involved in constraining the release of neurotransmitters in some synapses in the hippocampus, while not affecting others. We further demonstrate that the absence of this protein leads to decreased anxiety levels. Understanding the function of such a protein can help us further understand synaptic transmission, the specializations that are brought about in vertebrate synapses, and how this can help or hinder neurological or psychiatric disorders.
Interdependent Phenotypic and Biogeographic Evolution Driven by Biotic Interactions
Authors: Quintero Ignacio , Landis Michael J. 
Published: February 2019

AbstractBiotic interactions are hypothesized to be one of the main processes shaping trait and biogeographic evolution during lineage diversification. Theoretical and empirical evidence suggests that species with similar ecological requirements either spatially exclude each other, by preventing the colonization of competitors or by driving coexisting populations to extinction, or show niche divergence when in sympatry. However, the extent and generality of the effect of interspecific competition in trait and biogeographic evolution has been limited by a dearth of appropriate process-generating models to directly test the effect of biotic interactions. Here, we formulate a phylogenetic parametric model that allows interdependence between trait and biogeographic evolution, thus enabling a direct test of central hypotheses on how biotic interactions shape these evolutionary processes. We adopt a Bayesian data augmentation approach to estimate the joint posterior distribution of trait histories, range histories, and co-evolutionary process parameters under this analytically intractable model. Through simulations, we show that our model is capable of distinguishing alternative scenarios of biotic interactions. We apply our model to the radiation of Darwin’s finches—a classic example of adaptive divergence—and find support for in situ trait divergence in beak size, convergence in traits such as beak shape and tarsus length, and strong competitive exclusion throughout their evolutionary history. Our modeling framework opens new possibilities for testing more complex hypotheses about the processes underlying lineage diversification. More generally, it provides a robust probabilistic methodology to model correlated evolution of continuous and discrete characters.
Defining the neural correlates of spontaneous theory of mind (ToM): An fMRI mega-analytic investigation
Authors: Boccadoro Sara , Cracco Emiel , Hudson Anna R. , Bardi Lara , Nijhof Annabel D. , Wiersema Jan R. , Brass Marcel , Mueller Sven C. 
Published: February 2019

AbstractThere is a major debate in the theory of mind (ToM) field, concerning whether spontaneous and explicit ToM are based on the same or two distinct cognitive systems. While there is extensive research on the neural correlates of explicit ToM, revealing consistent activation of the temporo-parietal junction (TPJ) and medial prefrontal cortex (mPFC), few studies investigated spontaneous ToM, with conflicting results, probably due to having small samples of participants. Here, we implemented a mega-analytic approach by pooling data from three fMRI studies, to achieve enough statistical power to better define the neurocognitive mechanisms underlying spontaneous ToM. Participants watched videos in which an agent acquires a true or false belief about the location of a ball. By analysing the blood-oxygen level dependent signal during the belief formation phase for false versus true beliefs, we found a cluster of activation in the right, and to a lesser extent, left posterior parietal cortex spanning the TPJ, but no mPFC activation. Region of interest (ROI) analysis on bilateral TPJ and mPFC confirmed these results and added evidence to the content-selectivity for false beliefs with positive content and asymmetry in laterality of the spontaneous ToM system. Interestingly, the whole brain analysis, supported by an overlap with brain maps, revealed maximum activation in areas involved in visuospatial working memory and attention switching functions, such as the supramarginal gyrus, the middle temporal gyrus, and the inferior frontal gyrus. Taken together, these findings suggest that spontaneous and explicit ToM rely on partially overlapping brain systems. However, spontaneous ToM tasks also show clear differences with explicit ToM tasks.
Serial femtosecond X-ray diffraction of HIV-1 Gag MA-IP6 microcrystals at ambient temperature
Authors: Ciftci Halil I , Sierra Raymond G , Yoon Chun Hong , Su Zhen , Tateishi Hiroshi , Koga Ryoko , Kotaro Koiwai , Yumoto Fumiaki , Senda Toshiya , Liang Mengling , Wakatsuki Soichi , Otsuka Masami , Fujita Mikako , DeMirci Hasan 
Published: February 2019

AbstractThe Human immunodeficiency virus-1 (HIV-1) matrix (MA) domain is involved in the highly regulated assembly process of the virus particles that occur at the host cell’s plasma membrane. High-resolution structures of the MA domain determined using cryo X- ray crystallography have provided initial insights into the possible steps in the viral assembly process. However, these structural studies have relied on large and frozen crystals in order to reduce radiation damage caused by the intense X-rays. Here, we report the first XFEL study of the HIV-1 MA domain’s interaction with inositol hexaphosphate (IP6), a phospholipid headgroup mimic. We also describe the purification, characterization and microcrystallization of two MA crystal forms obtained in the presence of IP6. In addition, we describe the capabilities of serial femtosecond X-ray crystallography (SFX) using X-ray free-electron laser (XFEL) to elucidate the diffraction data of MA-IP6 complex microcrystals in liquid suspension at ambient temperature. Two different microcrystal forms of MA-IP6 complex both diffracted to beyond 3.5 Å resolution, demonstrating the feasibility of using SFX to study the complexes of MA domain of HIV-1 Gag polyprotein with IP6 at near-physiological temperatures. Further optimization of the experimental and data analysis procedures will lead to better understanding of the MA domain of HIV-1 Gag and IP6 interaction at high resolution and provide basis for optimization of the lead compounds for efficient inhibition of the Gag protein recruitment to the plasma membrane prior to virion formation.
Bridging micro and macro: accurate registration of the BigBrain dataset with the MNI PD25 and ICBM152 atlases
Authors: Xiao Yiming , Lau Jonathan C. , Anderson Taylor , DeKraker Jordan , Collins D. Louis , Peters Terry , Khan Ali R. 
Published: February 2019

AbstractBrain atlases that encompass detailed anatomical or physiological features are instrumental in the research and surgical planning of various neurological conditions. Magnetic resonance imaging (MRI) has played important roles in neuro-image analysis while histological data remain crucial as a gold standard to guide and validate such analyses. With cellular-scale resolution, the BigBrain atlas offers 3D histology of a complete human brain, and is highly valuable to the research and clinical community. To bridge the insights at macro- and micro-levels, accurate mapping of BigBrain and established MRI brain atlases is necessary, but the existing registration is unsatisfactory. The described dataset includes co-registration of the BigBrain atlas to the MNI PD25 atlas and the ICBM152 2009b atlases (symmetric and asymmetric versions) in addition to manual segmentation of the basal ganglia, red nucleus, and hippocampus for all mentioned atlases. The dataset intends to provide the bridge between insights from histological data and MRI studies in research and neurosurgical planning. The registered atlases, anatomical segmentations, and deformation matrices are available at:nist.mni.mcgill.ca/?p=1209.
Carnivore endozoochory of a dry-fruited tree can benefit quarry passive restoration
Authors: Salgueiro Vânia , Silva Carmo , Eufrázio Sofia , Salgueiro Pedro , Vaz Pedro G. 
Published: February 2019

AbstractAs more work assert passive restoration as a complementary approach to technical reclamation, it is imperative to know its drivers. Although the consequences of endozoochory are crucial to predict passive restoration success, few experimental studies assess the use of heavily disturbed sites by seed dispersers such as carnivores and how the seeds they bring in emerge and survive. Using an indoor sowing experiment conductedin situ, we examined for the first time how carnivore endozoochorous seeds collected in a quarry potentially influence its passive restoration, through effects on plant emergence and survival. Also, we tested whether sowing date and water soaking, relevant factors when sowings are to be carried out, would affect seedling emergence and survival rates when compared with the effect of endozoochory. Most interesting in our analysis were the results for Carob tree (Ceratonia siliqua), a dry-fruited species being used in an ongoing action of artificial revegetation of this quarry located within a natural park in Portugal. Irrespective of the carnivore species, endozoochorous carob seeds collected in the quarry performed similarly to untreated seeds regarding emergence rates. Endozoochorous carob seedlings showed greater mortality rates but the net result for the plant can still be the colonization of recently vacant habitats by a large proportion of viable seeds. The later carob seeds were sown, the faster seedlings emerged, including endozoochorous seedlings. As expected, water soaking implied faster emergences. Broadly, plantings, sowings with previous soaking, and carnivore-mediated seed dispersal of this dry-fruited tree can jointly enhance quarry restoration.Implications for practiceRestorers can undertake pilot sowing experiments similar to ours prior to large scale revegetation campaigns to identify which species can benefit the most from endozoochory.Carnivores in the surroundings of a quarry contribute a large proportion of viable seeds, likely assisting quarry passive restoration.Carnivores ingesting carob seeds later in the fruiting season may assist quarry passive revegetation more readily as seeds ingested around that time emerge earlier.Immersion in tap water seems to be a simple, inexpensive, and a highly efficient method to break physical dormancy when carob seed sowings are to be carried out in degraded sites.
Blood metabolome signature predicts gut microbiome α-diversity in health and disease
Authors: Wilmanski Tomasz , Rappaport Noa , Earls John C. , Magis Andrew T. , Manor Ohad , Lovejoy Jennifer , Omenn Gilbert S. , Hood Leroy , Gibbons Sean M. , Price Nathan D. 
Published: February 2019

AbstractDefining a ‘healthy’ gut microbiome has been a challenge in the absence of detailed information on both host health and microbiome composition. Here, we analyzed a multi-omics dataset from hundreds of individuals (discovery n=399, validation n=540) enrolled in a consumer scientific wellness program to identify robust associations between host physiology and gut microbiome structure. We attempted to predict gut microbiome α-diversity from nearly 1000 analytes measured from blood, including clinical laboratory tests, proteomics and metabolomics. While a broad panel of 77 standard clinical laboratory tests and a set of 263 proteins from blood could not accurately predict gut microbial α-diversity, we found that 45% of the variance in microbial community diversity was explained by a subset of 40 blood metabolites, many of microbial origin. This relationship between the host metabolome and gut microbiome α-diversity was very robust, persisting across disease conditions and antibiotics use. Several of these novel metabolic biomarkers of gut microbial diversity were previously associated with host health (e.g. cardiovascular disease risk, diabetes, and kidney function). A subset of 11 metabolites classified participants with potentially problematic low α-diversity (ROC AUC=0.88, Precision-Recall AUC=0.76). Relationships between host metabolites and α-diversity remained consistent across most of the Body Mass Index (BMI) spectrum, but were modified in extreme obesity (class II/III, but not class I), suggesting a significant metabolic shift. Out-of-sample prediction accuracy of α-diversity from the 40 identified blood metabolites in a validation cohort, whose microbiome samples were analyzed by a different vendor, confirmed the robust correspondence between gut microbiome structure and host physiology. Collectively, our results reveal a strong coupling between the human blood metabolome and gut microbial diversity, with implications for human health.