bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compensating for a shifting world: evolving reference frames of visual and auditory signals across three multimodal brain areas
Authors: Caruso Valeria C. , Pages Daniel S. , Sommer Marc A. , Groh Jennifer M. 
Published: June 2019

ABSTRACTStimulus locations are detected differently by different sensory systems, but ultimately they yield similar percepts and behavioral responses. How the brain transcends initial differences to compute similar codes is unclear. We quantitatively compared the reference frames of two sensory modalities, vision and audition, across three interconnected brain areas involved in generating saccades, namely the frontal eye fields (FEF), lateral and medial parietal cortex (M/LIP), and superior colliculus (SC). We recorded from single neurons in head-restrained monkeys performing auditory- and visually-guided saccades from variable initial fixation locations, and evaluated whether their receptive fields were better described as eye-centered, head-centered, or hybrid (i.e. not anchored uniquely to head- or eye-orientation). We found a progression of reference frames across areas and across time, with considerable hybrid-ness and persistent differences between modalities during most epochs/brain regions. For both modalities, the SC was more eye-centered than the FEF, which in turn was more eye-centered than the predominantly hybrid M/LIP. In all three areas and temporal epochs from stimulus onset to movement, visual signals were more eye-centered than auditory signals. In the SC and FEF, auditory signals became more eye-centered at the time of the saccade than they were initially after stimulus onset, but only in the SC at the time of the saccade did the auditory signals become predominantly eye-centered. The results indicate that visual and auditory signals both undergo transformations, ultimately reaching the same final reference frame but via different dynamics across brain regions and time.New and NoteworthyModels for visual-auditory integration posit that visual signals are eye-centered throughout the brain, while auditory signals are converted from head-centered to eye-centered coordinates. We show instead that both modalities largely employ hybrid reference frames: neither fully head-nor eye-centered. Across three hubs of the oculomotor network (intraparietal cortex, frontal eye field and superior colliculus) visual and auditory signals evolve from hybrid to a common eye-centered format via different dynamics across brain areas and time.
Activation of a nerve injury transcriptional signature in airway-innervating sensory neurons after LPS induced lung inflammation
Authors: Kaelberer Melanie Maya , Caceres Ana Isabel , Jordt Sven-Eric 
Published: June 2019

ABSTRACTThe lungs, the immune and nervous systems functionally interact to respond to respiratory environmental exposures and infections. The lungs are innervated by vagal sensory neurons of the jugular and nodose ganglia, fused together in smaller mammals as the jugular-nodose complex (JNC). While the JNC shares properties with the other sensory ganglia, the trigeminal (TG) and dorsal root ganglia (DRG), these sensory structures express differential sets of genes that reflect their unique functionalities. Here, we used RNAseq in mice to identify the differential transcriptomes of the three sensory ganglia types. Using a fluorescent retrograde tracer and fluorescence-activated cell sorting we isolated a defined population of airway-innervating JNC neurons and determined their differential transcriptional map after pulmonary exposure to lipopolysaccharide (LPS), a major mediator of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) after infection with Gram-negative bacteria or inhalation of organic dust. JNC neurons activated an injury response program leading to increased expression of gene products such as the G-protein coupled receptors, Cckbr, inducing functional changes in neuronal sensitivity to peptides, and Gpr151, also rapidly induced upon neuropathic nerve injury in pain models. Unique JNC-specific transcripts, present at only minimal levels in TG, DRG and other organs, were identified. These included TMC3, encoding for a putative mechanosensor, and Urotensin 2B, a hypertensive peptide. These findings highlight the unique properties of the JNC and reveal that ALI/ARDS rapidly induce a nerve-injury related state changing vagal excitability.SIGNIFICANCE STATEMENTThe lungs are innervated by sensory neurons of the jugular-nodose ganglia complex (JNC) that detect toxic exposures and interact with lung-resident cells and the immune system to respond to pathogens and inflammation. Here we report the expression of specific genes that differentiate these neurons from neurons in the other sensory ganglia, the trigeminal (TG) and dorsal root ganglia (DRG). Through nerve tracing we identified and isolated airway innervating JNC neurons and determined their differential transcriptional map after lung inflammation induced by a bacterial product, lipopolysaccharide (LPS). We observed the rapid activation of a nerve injury transcriptional program that increased nerve sensitivity to inflammation. This mechanism may result in more permanent nerve injury associated with chronic cough and other respiratory complications.
The thalamic basis of outcome and cognitive impairment in traumatic brain injury
Authors: Lutkenhoff Evan S. , Wright Matthew J. , Shrestha Vikesh , Real Courtney , McArthur David L. , Buitrago-Blanco Manuel , Vespa Paul M. , Monti Martin M. 
Published: June 2019

AbstractObjectiveTo understand how, biologically, the acute event of traumatic brain injury gives rise to a long-term disease, we address the relationship between evolving cortical and subcortical brain damage and measures of functional outcome and cognitive functioning at six months post-injury.MethodsLongitudinal analysis of clinical and MRI data collected, in a tertiary neurointensive care setting, in a continuous sample of 157 patients surviving moderate to severe traumatic brain injury between 2000 and 2018. For each patient we collected T1- and T2-weighted MRI data, acutely and at a six-months follow-up, as well as acute measures of injury severity (Glasgow Coma Scale) and follow-up measures of functional impairment (Glasgow Outcome Scale extended), and, in a subset of patients, neuropsychological measures of attention, executive functions, and episodic memory.ResultsIn the final cohort of 113 subcortical and 92 cortical datasets that survived (blind) quality control, extensive atrophy was observed over the first six months post-injury across the brain. Nonetheless, only atrophy within subcortical regions, particularly in left thalamus, were associated with functional outcome and neuropsychological measures of attention, executive functions, and episodic memory. Furthermore, when brought together in an analytical model, longitudinal brain measurements could distinguish good versus bad outcome with 90% accuracy, whereas acute brain and clinical measurements alone could only achieve 20% accuracy.InterpretationDespite great injury heterogeneity, secondary thalamic pathology is a measurable minimum common denominator mechanism directly relating biology to clinical measures of outcome and cognitive functioning, potentially linking the acute “event” and the long(er)-term “disease” of TBI.
Resting state functional connectivity in early post-anesthesia recovery is characterized by globally reduced anticorrelations
Authors: Nir Tommer , Jacob Yael , Huang Kuang-Han , Schwartz Arthur E. , Brallier Jess W. , Ahn Helen , Kundu Prantik , Tang Cheuk Y. , Delman Bradley N. , McCormick Patrick J. , Sano Mary , Deiner Stacie G. , Baxter Mark G. , Mincer Joshua S. 
Published: June 2019

ABSTRACTThough a growing body of literature is addressing the possible longer-term cognitive effects of anesthetics, to date no study has delineated the normal trajectory of neural recovery due to anesthesia alone in older adults. We obtained resting state functional magnetic resonance imaging scans on 62 healthy human volunteers between ages forty and eighty before, during, and after sevoflurane (general) anesthesia, in the absence of surgery, as part of a larger study on cognitive function post-anesthesia. Resting state networks expression decreased consistently one hour after emergence from anesthesia. This corresponded to a global reduction in anticorrelated functional connectivity post-anesthesia, seen across individual regions-of-interest. Positively correlated functional connectivity remained constant across peri-anesthetic states. All measures returned to baseline 1 day later, with individual regions-of-interest essentially returning to their pre-anesthesia connectivity levels. These results define normal peri-anesthetic changes in resting state connectivity in healthy older adults.
Batch Effect Correction of RNA-seq Data through Sample Distance Matrix Adjustment
Authors: Fei Teng , Yu Tianwei 
Published: June 2019

AbstractBatch effect is a frequent challenge in deep sequencing data analysis that can lead to misleading conclusions. We present scBatch, a numerical algorithm that conducts batch effect correction on the count matrix of RNA sequencing (RNA-seq) data. Different from traditional methods, scBatch starts with establishing an ideal correction of the sample distance matrix that effectively reflect the underlying biological subgroups, without considering the actual correction of the raw count matrix itself. It then seeks an optimal linear transformation of the count matrix to approximate the established sample pattern. The benefit of such an approach is the final result is not restricted by assumptions on the mechanism of the batch effect. As a result, the method yields good clustering and gene differential expression (DE) results. We compared the new method, scBatch, with leading batch effect removal methods ComBat and mnnCorrect on simulated data, real bulk RNA-seq data, and real single-cell RNA-seq data. The comparisons demonstrated that scBatch achieved better sample clustering and DE gene detection results.
Circuit-Specific Early Impairment of Proprioceptive Sensory Neurons in the SOD1G93AMouse Model for ALS
Authors: Seki Soju , Yamamoto Toru , Quinn Kiara , Spigelman Igor , Pantazis Antonios , Olcese Riccardo , Wiedau-Pazos Martina , Chandler Scott H. , Venugopal Sharmila 
Published: June 2019

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease in which motor neurons degenerate resulting in muscle atrophy, paralysis and fatality. Studies using mouse models of ALS indicate a protracted period of disease development with progressive motor neuron pathology, evident as early as embryonic and postnatal stages. Key missing information includes concomitant alterations in the sensorimotor circuit essential for normal development and function of the neuromuscular system. Leveraging unique brainstem circuitry, we showin vitroevidence for reflex circuit-specific postnatal abnormalities in the jaw proprioceptive sensory neurons in the well-studied SOD1G93Amouse. These include impaired and arrhythmic action potential burst discharge associated with a deficit in Nav1.6 Na+channels. However, the mechanoreceptive and nociceptive trigeminal ganglion neurons and the visual sensory retinal ganglion neurons were resistant to excitability changes in age matched SOD1G93Amice. Computational modeling of the observed disruption in sensory patterns predicted asynchronous self-sustained motor neuron discharge suggestive of imminent reflexive defects such as muscle fasciculations in ALS. These results demonstrate a novel reflex circuit-specific proprioceptive sensory abnormality in ALS.Significance StatementNeurodegenerative diseases have prolonged periods of disease development and progression. Identifying early markers of vulnerability can therefore help devise better diagnostic and treatment strategies. In this study, we examined postnatal abnormalities in the electrical excitability of muscle spindle afferent proprioceptive neurons in the well-studied SOD1G93Amouse model for neurodegenerative motor neuron disease, ALS. Our findings suggest that these proprioceptive sensory neurons are exclusively afflicted early in the disease process relative to sensory neurons of other modalities. Moreover, they presented Nav1.6 Na+channel deficiency which contributed to arrhythmic burst discharge. Such sensory arrhythmia could initiate reflexive defects such as muscle fasciculations in ALS as suggested by our computational model.
Single Cell Analysis Reveals Immune Cell-Adipocyte Crosstalk Regulating the Transcription of Thermogenic Adipocytes
Authors: Rajbhandari Prashant , Arneson Douglas , Feng An-Chieh , Ahn In Sook , Diamante Graciel , Zaghari Nima , Thomas Brandon J. , Vergnes Laurent , Lee Stephen D. , Reue Karen , Smale Stephen T. , Yang Xia , Tontonoz Peter 
Published: June 2019

SummaryImmune cells are vital constituents of the adipose microenvironment that influence both local and systemic lipid metabolism. Mice lacking IL10 have enhanced thermogenesis, but the roles of specific cell types in the metabolic response to IL10 remain to be defined. We demonstrate here that selective loss of IL10 receptor α in adipocytes recapitulates the beneficial effects of global IL10 deletion, and that local crosstalk between IL10-producing immune cells and adipocytes is a determinant of thermogenesis and systemic energy balance. Single Nuclei Adipocyte RNA-sequencing (SNAP-seq) of subcutaneous adipose tissue defined a metabolically-active mature adipocyte subtype characterized by robust expression of genes involved in thermogenesis whose transcriptome was selectively responsive to IL10Rα deletion. Furthermore, single-cell transcriptomic analysis of adipose stromal populations identified lymphocytes as a key source of IL10 production in response to thermogenic stimuli. These findings implicate adaptive immune cell-adipocyte communication in the maintenance of adipose subtype identity and function.
Mycobacteria fecal shedding in wild boars (Sus scrofa), South-eastern France
Authors: Fellag Mustapha , Drancourt Michel , Marié Jean-Lou , Davoust Bernard 
Published: June 2019

ABSTRACTThe recent recrudescence of tuberculosis in cattle has implicated wild boar as a reservoir and vector of this disease, which led to the investigation of fecal shedding of the causativeMycobacterium bovis. In the Provence region of France, wild boars are very abundant, and the current study was carried out to assess the presence of tuberculous and nontuberculous mycobacteria in feces of wild boar population. W e developed an original protocol allowing the fast isolation of mycobacteria by combining a 1%-chlorhexidine decontamination of fecal matter with culture on MOD9 medium. Colonies were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, combined with DNA sequencing. This protocol yielded no tuberculous mycobacteria among ninety-nine wild boar fecal samples collected in the Provence region. However, non-tuberculous mycobacteria were isolated from five samples (5.05%), includingMycobacterium peregrinum, Mycobacterium vaccaeandMycobacterium setense, the last species being previously unreported in the wild boar; in addition to two positive samples forNocardiaspp. In conclusion, wild boars in southeastern France are not shedding tuberculosis agents, but they could constitute a reservoir of human non-tuberculous mycobacteriosis in selected populations directly exposed to wild boars.
Distinct Contribution of DNA Methylation and Histone Acetylation to the Genomic Occupancy of Transcription Factors
Authors: Cusack Martin , King Hamish W. , Spingardi Paolo , Kessler Benedikt M. , Klose Robert J. , Kriaucionis Skirmantas 
Published: June 2019

AbstractEpigenetic modifications on chromatin play important roles in regulating gene expression. While chromatin states are often governed by multi-layered structure, how individual pathways contribute to gene expression remains poorly understood. For example, DNA methylation is known to regulate transcription factor binding but also to recruit methyl-CpG binding proteins that affect chromatin structure through the activity of histone deacetylase complexes (HDACs). Both of these mechanisms can potentially affect gene expression, but the importance of each, and whether these activities are integrated to achieve appropriate gene regulation, remains largely unknown. To address this important question, we measured gene expression, chromatin accessibility, and transcription factor occupancy in wild-type or DNA methylation-deficient mouse embryonic stem cells following HDAC inhibition. Interestingly, we observe widespread increases in chromatin accessibility at repeat elements when HDACs are inhibited, and this is magnified when cells also lack DNA methylation. A subset of these elements have elevated binding of the YY1 and GABPA transcription factors and increased expression. The pronounced additive effect of HDAC inhibition in DNA methylation deficient cells demonstrate that DNA methylation and histone deacetylation act largely independently to suppress transcription factor binding and gene expression.
Potential of host serum protein biosignatures in the diagnosis of tuberculous meningitis in children
Authors: Manyelo Charles M , Solomons Regan S , Snyders Candice I , Stanley Kim , Walzl Gerhard , Chegou Novel N 
Published: June 2019

AbstractBackgroundTuberculous meningitis (TBM) is the most severe form of tuberculosis and results in high morbidity and mortality in children. Diagnostic delay contributes to the poor outcome. There is an urgent need for new tools for the rapid diagnosis of TBM, especially in children.MethodsWe collected serum samples from children in whom TBM was suspected at a tertiary hospital in Cape Town, South Africa. Children were subsequently classified as having TBM or no TBM using a published uniform research case-definition. Using a multiplex cytokine array platform, we investigated the concentrations of serum biomarkers comprising 7-markers that were previously found to be of value in the diagnosis of adult pulmonary TB (CRP, SAA, CFH, IFN-γ, IP-10, Apo-AI and transthyretin) plus other potentially useful host biomarkers as diagnostic candidates for TBM.FindingsOf 47 children included in the study, 23 (48.9%) had a final diagnosis of TBM of which six had HIV co-infection. A modified version of the adult 7-marker biosignature in which transthyretin was replaced by NCAM1, diagnosed TBM in children with AUC of 0.80 (95% CI, 0.67-0.92), sensitivity of 73.9% (95% CI, 51.6-89.8%) and specificity of 66.7% (95% CI, 44.7-84.4%). A new childhood TBM specific 3-marker biosignature (adipsin, Aβ42 and IL-10) showed potential in the diagnosis of TBM, with AUC of 0.84 (95% CI, 0.73-0.96), sensitivity of 82.6% (95 CI, 61.2-95.0%) and specificity of 75.0% (95% CI, 53.3-90.2%) after leave-one-out cross validation.ConclusionAn adult 7-marker serum protein biosignature showed potential in the diagnosis of TBM in children. However, a smaller childhood TBM-specific biosignature demonstrated improved performance characteristics. Our data indicates that blood-based biomarkers may be useful in the diagnosis of childhood TBM and require further investigation.
Phylogenomic analysis ofClostridium perfringensidentifies isogenic strains in gastroenteritis outbreaks, and novel virulence-related features
Authors: Kiu Raymond , Caim Shabhonam , Pickard Derek , Painset Anais , Swift Craig , Dougan Gordon , Mather Alison E , Amar Corinne , Hall Lindsay J 
Published: June 2019

AbstractClostridium perfringensis a major enteric pathogen known to cause gastroenteritis in human adults. Although major outbreak cases are frequently reported, limited Whole Genome Sequencing (WGS) based studies have been performed to understand the genomic epidemiology and virulence gene content ofC. perfringens-associated outbreak strains. We performed both genomic and phylogenetic analysis on 109C. perfringensstrains (human and food) isolated from disease cases in England and Wales between 2011-2017. Initial findings highlighted the enhanced discriminatory power of WGS in profiling outbreakC. perfringensstrains, when compared to the current Public Health England referencing laboratory technique of Fluorescent Amplified Fragment Length Polymorphism (fAFLP). Further analysis identified that isogenicC. perfringensstrains were associated with nine distinct care home-associated outbreaks over the course of a 5-year interval, indicating a potential common source linked to these outbreaks or transmission over time and space. As expected the enterotoxin CPE gene was encoded in all but 4 isolates (96.4%; 105/109), with virulence plasmids encodingcpe(particularly pCPF5603- and pCPF4969-family plasmids) extensively distributed (82.6%;90/109). Genes encoding accessory virulence factors, such as beta-2 toxin, were commonly detected (46.7%; 50/109), and genes encoding phage proteins were also frequently identified, with additional analysis indicating their contribution to increased virulence determinants within the genomes of gastroenteritis-associatedC. perfringens. Overall this large-scale genomic study of gastroenteritis-associatedC. perfringenssuggested that 3 major sub-types underlie these outbreaks: strains carrying (1) pCPF5603 plasmid, (2) pCPF4969 plasmid, and (3) strains carryingcpeon transposable element Tn5565(usually integrated into chromosome). Our findings indicate that further studies will be required to fully probe this enteric pathogen, particularly in relation to developing intervention and prevention strategies to reduce food poisoning disease burden in vulnerable patients, such as the elderly.