bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of oxidized β-carotene-oxygen copolymer compound on health and performance of pre- and post-weaned pigs
Authors: Van Kinh La , Riley William W. , Nickerson James G. , Vinh Doan , Van Phu Nguyen , Van Nguyen Thanh , Huyen La Thi Thanh , Burton Graham W. 
Published: August 2020

AbstractThe discovery that a naturally occurring, biologically active β-carotene-oxygen copolymer compound is the main product formed in spontaneously oxidized β-carotene has stimulated interest in its potential health benefits. The copolymer, formed in nature or synthetically by the air-oxidation of β-carotene, possesses beneficial immune modulating activities that previously had been attributed to β-carotene itself. Support for these benefits is provided by previous studies showing that supplementation in feed with low parts-per-million levels of copolymer-rich, fully oxidized β-carotene (OxBC) helped reduce the negative impact of subclinical necrotic enteritis in broilers and improved growth in weaned piglets. To further assess these potential benefits, two trials were conducted in swine raised under commercial conditions in Vietnam. Trial 1, a 140-day full-grow, post-wean study with 500 28-day-old pigs, compared 2, 4 or 8 ppm OxBC against both an unsupplemented and an antibiotic control group. OxBC and antibiotics each improved growth rate, feed efficiency, and body weight compared to the control (P<0.001). Animals receiving 4 and 8 ppm OxBC performed better than did animals on antibiotics (P<0.001). In starter pigs, OxBC reduced the occurrence of diarrhea dose-dependently (4 and 8 ppm) and to a greater extent than did antibiotics (P<0.001). Trial 2, a 49-day study with 420 piglets, was conducted in two-stages. In Stage 1 (pre-wean), OxBC in the transition (creep) feed produced a dose-dependent trend toward increased body weight over 21 days, reaching significance at the highest inclusion level (16 ppm) (P<0.001). In Stage 2 (post-wean), body weight gain showed a dose-dependent trend and was significant for both 8 ppm OxBC and the antibiotics at 28 days post-wean (P<0.001). Feed conversion was better at 8 ppm OxBC and for the antibiotic group (P<0.001). These findings support the concept that β-carotene-oxygen copolymers help optimize immune function, and provide validation for the effectiveness of this strategy in enhancing animal performance in the absence of in-feed antibiotics.
Hybrid diffuse optical monitoring of hemodynamic changes following acute cerebral ischemia in a porcine model
Authors: Wang Detian , Wang Long , Wang Jinyu , Gao Peng , Zhu Liguo , Li Zeren , Chen Tunan , Li Fei , Hua Feng 
Published: August 2020

AbstractRapid screening for stroke in pre-hospital settings may improve patient outcomes by allowing early deployment of thrombolytic therapies. Near-infrared hybrid diffuse optical screening devices may fill this need. This study seeks to determine whether hybrid diffuse optical measurements can measure hemodynamic changes associated with cerebral ischemia within the first few hours of the onset of acute ischemia in a large animal model. A hybrid diffuse optical device combining of near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) was fabricated to measure total hemoglobin concentration (HbT), tissue oxygen saturation (StO2) and blood flow index (BFI). Cerebral ischemia was induced by ligation of the bilateral common carotid arteries (CCA) in five miniature pigs. Additionally, a fatal stroke was induced in two pigs by injecting 5ml air emboli into both CCA. Cerebral hemodynamic parameters were monitored continuously throughout the study with the hybrid optical device. Relative changes BFI showed the good repeatability both of the ligation and fatal stroke experiments. During bilateral CCA ligation, the BFI decreased by up to about 66% of baseline values; during the fatal stroke experiment, the BFI decreased by up to about 95%, with a temporal resolution of 20 seconds. To the best of our knowledge, there are not existing methods which can measure the cerebral ischemia within the first few hours of the onset noninvasively. The MRI scanning was conducted at 24 h post injury. However, the images showed no abnormality. The results show the hybrid diffuse optical method can immediately measure the hemodynamic changes of miniature pigs in the first few hours of each single cerebral ischemia onset, and the BFI may be the promising biomarker to distinguish the cerebral ischemia and cerebral death.
KANSL1 Deficiency Causes Neuronal Dysfunction by Oxidative Stress-Induced Autophagy
Authors: Linda Katrin , Lewerissa EIly I. , Verboven Anouk H. A. , Gabriele Michele , Frega Monica , Gunnewiek Teun M. Klein , Devilee Lynn , Ulferts Edda , Oudakker Astrid , Schoenmaker Chantal , van Bokhoven Hans , Schubert Dirk , Testa Giuseppe , Koolen David A. , de Vries Bert B.A. , Kasri Nael Nadif 
Published: August 2020

AbstractAutophagy is a finely tuned process of programmed degradation and recycling of proteins and cellular components, which is crucial in neuronal function and synaptic integrity. Mounting evidence implicates chromatin remodelling in fine-tuning autophagy pathways. However, this epigenetic regulation is poorly understood in neurons. Here, we investigate the role in autophagy of KANSL1, a member of the nonspecific lethal complex, which acetylates histone H4 on lysine 16 (H4K16ac) to facilitate transcriptional activation. Loss-of-function of KANSL1 is strongly associated with the neurodevelopmental disorder Koolen-de Vries Syndrome (KdVS).Starting from KANSL1-deficient human induced-pluripotent stem cells, both from KdVS patients and genome-edited lines, we identified superoxide dismutase 1, an antioxidant enzyme, to be significantly decreased, leading to a subsequent increase in oxidative stress and autophagosome accumulation. In KANSL1-deficient neurons, autophagosome accumulation at excitatory synapses resulted in reduced synaptic density, reduced AMPA receptor-mediated transmission and impaired neuronal network activity. Furthermore, we found that increased oxidative stress-mediated autophagosome accumulation leads to increased mTOR activation and decreased lysosome function, further preventing the clearing of autophagosomes. Finally, by pharmacologically reducing oxidative stress, we could rescue the aberrant autophagosome formation as well as synaptic and neuronal network activity in KANSL1-deficient neurons. Our findings thus point towards an important relation between oxidative stress-induced autophagy and synapse function, and demonstrate the importance of H4K16ac-mediated changes in chromatin structure to balance reactive oxygen species- and mTOR-dependent autophagy.
Identifying Transcriptomic Correlates of Histology using Deep Learning
Authors: Badea Liviu , Stănescu Emil 
Published: August 2020

AbstractLinking phenotypes to specific gene expression profiles is an extremely important problem in biology, which has been approached mainly by correlation methods or, more fundamentally, by studying the effects of gene perturbations. However, genome-wide perturbations involve extensive experimental efforts, which may be prohibitive for certain organisms. On the other hand, the characterization of the various phenotypes frequently requires an expert’s subjective interpretation, such as a histopathologist’s description of tissue slide images in terms of complex visual features (e.g. ‘acinar structures’). In this paper, we use Deep Learning to eliminate the inherent subjective nature of these visual histological features and link them to genomic data, thus establishing a more precisely quantifiable correlation between transcriptomes and phenotypes. Using a dataset of whole slide images with matching gene expression data from 39 normal tissue types, we first developed a Deep Learningtissue classifierwith an accuracy of 94%. Then we searched forgenes whose expression correlates with features inferred by the classifierand demonstrate that Deep Learning can automatically derive visual (phenotypical) features that are well correlated with the transcriptome and thereforebiologically interpretable. As we are particularly concerned withinterpretabilityandexplainabilityof the inferred histological models, we also developvisualizationsof the inferred features and compare them with gene expression patterns determined by immunohistochemistry. This can be viewed as a first step toward bridging the gap between the level of genes and the cellular organization of tissues.
Exploring the Causal Effects of Shear Stress Associated DNA Methylation on Cardiovascular Risk
Authors: Methorst Ruben , de Borst Gert Jan , Pasterkamp Gerard , van der Laan Sander W. 
Published: August 2020

AbstractBackground and aimsAtherosclerosis is a lipid-driven inflammatory disease presumably initiated by endothelial activation. Low vascular shear stress is known for its ability to activate endothelial cells. Differential DNA methylation (DNAm) is a relatively unexplored player in atherosclerotic disease development and endothelial dysfunction. Literature search revealed that expression of 11 genes have been found to be associated with differential DNAm due to low shear stress in endothelial cells. We hypothesized a causal relationship between DNAm of shear stress associated genes in human carotid plaque and increased risk of cardiovascular disease.MethodsUsing Mendelian randomisation (MR) analysis, we explored the potential causal role of DNAm of shear stress associated genes on cardiovascular disease risk. We used genetic and DNAm data of 442 carotid endarterectomy derived advanced plaques from the Athero-Express Biobank Study for quantitative trait loci (QTL) discovery and performed MR analysis using these QTLs and GWAS summary statistics of coronary artery disease (CAD) and ischemic stroke (IS).ResultsWe discovered 9 methylation QTLs in plaque for differentially methylated shear stress associated genes. We found no significant effect of shear stress gene promotor methylation and increased risk of CAD and IS.ConclusionsDifferential methylation of shear stress associated genes in advanced atherosclerotic plaques in unlikely to increase cardiovascular risk.Highlights-Plaque-derived DNA methylation in shear stress associated genes shows no significant effect on cardiovascular disease-Genetic variants in shear stress associated genes affect DNA methylation in human carotid plaque-Human validation of atherosclerotic associated genes in murine models
Memory Trace Imbalance in Reinforcement and Punishment Systems Can Reinforce Implicit Choices Leading to Obsessive-Compulsive Behavior
Authors: Sakai Yuki , Sakai Yutaka , Abe Yoshinari , Narumoto Jin , Tanaka Saori C. 
Published: August 2020

SummaryWe may view most of our daily activities as rational action selections; however, we sometimes reinforce maladaptive behaviors despite having explicit environmental knowledge. In this study, we model obsessive-compulsive disorder (OCD) symptoms as implicitly learned maladaptive behaviors. Simulations in the reinforcement learning framework show that agents implicitly learn to respond to intrusive thoughts when the memory trace signal for past actions decays differently for positive and negative prediction errors. Moreover, this model extends our understanding of therapeutic effects of behavioral therapy in OCD. Using empirical data, we confirm that patients with OCD show extremely imbalanced traces, which are normalized by serotonin enhancers. We find that healthy participants also vary in their obsessive-compulsive tendencies, consistent with the degree of imbalanced traces. These behavioral characteristics can be generalized to variations in the healthy population beyond the spectrum of clinical phenotypes.
Convergent acoustic community structure in South Asian dry and wet grassland birds
Authors: Lahiri Sutirtha , Pathaw Nafisa A. , Krishnan Anand 
Published: August 2020

AbstractAlthough the study of bird acoustic communities has great potential to provide valuable conservation data, many aspects of their assembly and dynamics remain poorly understood. Grassland habitats in South Asia comprise distinct biomes with a unique avifauna, presenting an opportunity to address how community-level patterns in acoustic signal space arise. Similarity in signal space of different grassland bird communities may be due to phylogenetic similarity, or because different bird groups partition the acoustic resource, resulting in convergent distributions in signal space. Here, we quantify the composition, signal space and phylogenetic diversity of bird acoustic communities from the dry semiarid grasslands of Northwest India and the wet floodplain grasslands of Northeast India. We find that acoustic communities occupying these distinct biomes exhibit convergent signal space. However, dry grasslands exhibit higher phylogenetic diversity, and the two communities are not phylogenetically more similar than expected by chance. The Sylvioidea encompasses half the species in the wet grassland acoustic community, with an expanded signal space compared to the dry grasslands. Thus, dry and wet grassland communities are convergent in signal space despite differences in phylogenetic diversity. We therefore hypothesize that different clades colonizing grasslands partition the acoustic resource, resulting in convergent community structure across biomes. Many of the birds we recorded are highly threatened, and acoustic monitoring will support conservation measures in these imperiled, yet poorly-studied habitats.
Improving prediction and assessment of global wildfires using neural networks
Authors: Joshi Jaideep , Sukumar Raman 
Published: August 2020

ABSTRACTFires determine vegetation patterns, impact human societies, and provide complex feedbacks into the global climate system. Empirical and process-based models differ in their scale and mechanistic assumptions, giving divergent predictions of fire drivers and extent. Especially, the role of anthropogenic drivers remains less understood. Taking a data-driven approach, we use an artificial neural network to learn region-specific relationships between fire and its socio-environmental drivers across the globe. As a result, our models achieve higher predictability than previously reported, with global spatial correlation of 0.92, temporal correlation of 0.76, interannual correlation of 0.69, and grid-cell level correlation of 0.6, between predicted and observed burned area. Our analysis reveals universal global patterns in fire-climate interactions, coupled with strong regional differences in fire-human relationships. Given the current socio-anthropogenic conditions, Equatorial Asia, southern Africa, and Australia show a strong sensitivity of fire extent to temperature whereas northern Africa shows a strong negative sensitivity. Overall, forests and shrublands, show a stronger sensitivity of burned area to temperature compared to savannas, potentially weakening their status as carbon sinks under future climate-change scenarios.
Multiomics analysis reveals extensive epigenome remodeling during cortical development
Authors: Noack Florian , Vangelisti Silvia , Carido Madalena , Chong Faye , Bonev Boyan 
Published: August 2020

AbstractDespite huge advances in stem-cell, single-cell and epigenetic technologies, the precise molecular mechanisms that determine lineage specification remain largely unknown. Applying an integrative multiomics approach, e.g. combining single-cell RNA-seq, single-cell ATAC-seq together with cell-type-specific DNA methylation and 3D genome measurements, we systematically map the regulatory landscape in the mouse neocortexin vivo. Our analysis identifies thousands of novel enhancer-gene pairs associated with dynamic changes in chromatin accessibility and gene expression along the differentiation trajectory. Crucially, we provide evidence that epigenetic remodeling generally precedes transcriptional activation, yet true priming appears limited to a subset of lineage-determining enhancers. Notably, we reveal considerable heterogeneity in both contact strength and dynamics of the generally cell-type-specific enhancer-promoter contacts. Finally, our work suggests a so far unrecognized function of several key transcription factors which act as putative “molecular bridges” and facilitate the dynamic reorganization of the chromatin landscape accompanying lineage specification in the brain.
The Vagus Nerve Mediates the Physiological but not Pharmacological Effects of PYY3-36on Food Intake
Authors: Alonso A Martin , Cork SC , Ma Y , Arnold M , Herzog H , Bloom SR , Distaso W , Murphy KG , Salem V 
Published: August 2020

AbstractPeptide YY (PYY3-36) is a post-prandially released gut hormone with potent appetite-reducing activity mediated by the neuropeptide Y (NPY) Y2 receptor (Y2R). However, the neuronal pathways by which PYY3-36acts to supress appetite are unclear. Determining how the PYY3-36system physiologically regulates food intake may help exploit its therapeutic potential. Here we demonstrate that germline and post-natal targeted knockdown of the Y2R in the afferent vagus nerve inhibits the anorectic effects of physiologically-released PYY3-36, but not peripherally-administered higher doses. Post-natal knockdown of the Y2R results in a transient body weight phenotype that is compensated for in the germline model. Loss of vagal Y2R signalling also alters meal patterning and accelerates gastric emptying. These results may facilitate the design of PYY-based anti-obesity agents.Abstract Figure
mRNA induced expression of human angiotensin-converting enzyme 2 in mice for the study of the adaptive immune response to severe acute respiratory syndrome coronavirus 2
Authors: Hassert Mariah , Geerling Elizabeth , Stone E. Taylor , Steffen Tara L. , Feldman Madi S. , Class Jacob , Richner Justin M. , Brien James D. , Pinto Amelia K. 
Published: August 2020

AbstractThe novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic resulting in nearly 20 million infections across the globe, as of August 2020. Critical to the rapid evaluation of vaccines and antivirals is the development of tractable animal models of infection. The use of common laboratory strains of mice to this end is hindered by significant divergence of the angiotensin-converting enzyme 2 (ACE2), which is the receptor required for entry of SARS-CoV-2. In the current study, we designed and utilized an mRNA-based transfection system to induce expression of the hACE2 receptor in order to confer entry of SARS-CoV-2 in otherwise non-permissive cells. By employing this expression system in an in vivo setting, we were able to interrogate the adaptive immune response to SARS-CoV-2 in type 1 interferon receptor deficient mice. In doing so, we showed that the T cell response to SARS-CoV-2 is enhanced when hACE2 is expressed during infection. Moreover, we demonstrated that these responses are preserved in memory and are boosted upon secondary infection. Interestingly, we did not observe an enhancement of SARS-CoV-2 specific antibody responses with hACE2 induction. Importantly, using this system, we functionally identified the CD4+ and CD8+ peptide epitopes targeted during SARS-CoV-2 infection in H2brestricted mice. Antigen-specific CD8+ T cells in mice of this MHC haplotype primarily target peptides of the spike and membrane proteins, while the antigen-specific CD4+ T cells target peptides of the nucleocapsid, membrane, and spike proteins. The functional identification of these T cell epitopes will be critical for evaluation of vaccine efficacy in murine models of SARS-CoV-2. The use of this tractable expression system has the potential to be used in other instances of emerging infections in which the rapid development of an animal model is hindered by a lack of host susceptibility factors.
Sex and estrogen receptor β have modest effects on gene expression in the mouse brain posterior cortex
Authors: Fels Jasmine A , Casalena Gabriella A , Manfredi Giovanni 
Published: August 2020

AbstractIntroductionSex differences in brain cortical function affect cognition, behavior, and susceptibility to neural diseases, but the molecular basis of sexual dimorphism in cortical function is still largely unknown. Estrogen and estrogen receptors (ERs), specifically ERβ, the most abundant ER in the cortex, may play a role in determining sex differences in gene expression, which could underlie functional sex differences. However, further investigation is needed to address brain region specificity of the effects of sex and ERβ on gene expression. The goal of this study was to investigate sex differences in gene expression in the mouse posterior cortex, where sex differences in transcription have never been examined, and to determine how genetic ablation of ERβ affects transcription.MethodsIn this study, we performed unbiased transcriptomics on RNA from the posterior cortex of adult wild-type and ERβ knockout mice (n=4/sex/genotype). We used unbiased clustering to analyze whole-transcriptome changes between the groups. We also performed differential expression analysis on the data using DESeq2 to identify specific changes in gene expression.ResultsWe found only 27 significantly differentially expressed genes (DEGs) in wild-type (WT) males vs females, of which 17 were autosomal genes. Interestingly, in ERβKO males vs females all the autosomal DEGs were lost. Gene Ontology analysis of the subset of DEGs with sex differences only in the WT cortex revealed a significant enrichment of genes annotated with the function ‘cation channel activity’. Moreover, within each sex we found only a few DEGs in ERβKO vs WT mice (8 and 5 in males and females, respectively).ConclusionsOverall, our results suggest that in the adult mouse posterior cortex there are surprisingly few sex differences in gene expression, and those that exist are mainly related to cation channel activity. Additionally, they indicate that brain region-specific functional effects of ERβ may be largely post-transcriptional.
Genome-based targeted sequencing as a reproducible microbial community profiling assay
Authors: Benjamino Jacquelynn , Leopold Benjamin , Phillips Daniel , Adams Mark D. 
Published: August 2020

AbstractCurrent sequencing-based methods for profiling microbial communities rely on marker gene (e.g. 16S rRNA) or metagenome shotgun sequencing (mWGS) analysis. We present a new approach based on highly multiplexed oligonucleotide probes designed from reference genomes in a pooled primer-extension reaction during library construction to derive relative abundance data. This approach, termed MA-GenTA: Microbial Abundances from Genome Tagged Analysis, enables quantitative, straightforward, cost-effective microbiome profiling that combines desirable features of both 16S rRNA and mWGS strategies. To test the utility of the MA-GenTA assay, probes were designed for 830 genome sequences representing bacteria present in mouse stool specimens. Comparison of the MA-GenTA data with mWGS data demonstrated excellent correlation down to 0.01% relative abundance and a similar number of organisms detected per sample. Despite the incompleteness of the reference database, NMDS clustering based on the Bray-Curtis dissimilarity metric of sample groups was consistent between MA-GenTA, mWGS and 16S rRNA datasets. MA-GenTA represents a potentially useful new method for microbiome community profiling based on reference genomes.