bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pig genome functional annotation enhances the biological interpretation of complex traits and human disease
Authors: Pan Zhangyuan , Yao Yuelin , Yin Hongwei , Cai Zexi , Wang Ying , Bai Lijing , Kern Colin , Halstead Michelle , Chanthavixay Ganrea , Trakooljul Nares , Wimmers Klaus , Sahana Goutam , Su Guosheng , Lund Mogens Sandø , Fredholm Merete , Karlskov-Mortensen Peter , Ernst Catherine W. , Ross Pablo , Tuggle Christopher K. , Fang Lingzhao , Zhou Huaijun 
Published: October 2021

AbstractThe functional annotation of livestock genomes is crucial for understanding the molecular mechanisms that underpin complex traits of economic importance, adaptive evolution and comparative genomics. Here, we provide the most comprehensive catalogue to date of regulatory elements in the pig (Sus scrofa) by integrating 223 epigenomic and transcriptomic data sets, representing 14 biologically important tissues. We systematically describe the dynamic epigenetic landscape across tissues by functionally annotating 15 different chromatin states and defining their tissue-specific regulatory activities. We demonstrate that genomic variants associated with complex traits and adaptive evolution in pig are significantly enriched in active promoters and enhancers. Furthermore, we reveal distinct tissue-specific regulatory selection between Asian and European pig domestication processes. Compared with human and mouse epigenomes, we show that porcine regulatory elements are more conserved in DNA sequence, under both rapid and slow evolution, than those under neutral evolution across pig, mouse, and human. Finally, we provide biological insights on tissue-specific regulatory conservation, and by integrating 47 human genome-wide association studies, we demonstrate that, depending on the traits, mouse or pig might be more appropriate biomedical models for different complex traits and diseases.
Tcf1 and Lef1 provide constant supervision to mature CD8+ T cell identity and function by organizing genomic architecture
Authors: Shan Qiang , Li Xiang , Chen Xia , Zeng Zhouhao , Zhu Shaoqi , Gai Kexin , Peng Weiqun , Xue Hai-Hui 
Published: October 2021

AbstractT cell identity is established during thymic development, but how it is maintained in the periphery remains unknown. Here we show that ablating Tcf1 and Lef1 transcription factors in mature CD8+ T cells aberrantly induces genes from non-T cell lineages. Using high-throughput chromosome-conformation-capture sequencing, we demonstrate that Tcf1/Lef1 are important for maintaining three-dimensional genome organization at multiple scales in CD8+ T cells. Comprehensive network analyses coupled with genome-wide profiling of chromatin accessibility and Tcf1 occupancy show the direct impact of Tcf1/Lef1 on the T cell genome is to promote formation of extensively interconnected hubs through enforcing chromatin interaction and accessibility. The integrative mechanisms utilized by Tcf1/Lef1 underlie activation of T cell identity genes and repression of non-T lineage genes, conferring fine control of various T cell functionalities. These findings suggest that Tcf1/Lef1 control global genome organization and help form intricate chromatin-interacting hubs to facilitate promoter-enhancer/silencer contact, hence providing constant supervision of CD8+ T cell identity and function.
Integrated omics networks reveal the temporal signaling events of brassinosteroid response in Arabidopsis
Authors: Clark Natalie M. , Nolan Trevor M. , Wang Ping , Song Gaoyuan , Montes Christian , Valentine Conner T. , Guo Hongqing , Sozzani Rosangela , Yin Yanhai , Walley Justin W. 
Published: October 2021

AbstractBrassinosteroids (BRs) are plant steroid hormones that regulate cell division and stress response. Here we use a systems biology approach to integrate multi-omic datasets and unravel the molecular signaling events of BR response in Arabidopsis. We profile the levels of 26,669 transcripts, 9,533 protein groups, and 26,617 phosphorylation sites from Arabidopsis seedlings treated with brassinolide (BL) for six different lengths of time. We then construct a network inference pipeline called Spatiotemporal Clustering and Inference of Omics Networks (SC-ION) to integrate these data. We use our network predictions to identify putative phosphorylation sites on BES1 and experimentally validate their importance. Additionally, we identify BRONTOSAURUS (BRON) as a transcription factor that regulates cell division, and we show that BRON expression is modulated by BR-responsive kinases and transcription factors. This work demonstrates the power of integrative network analysis applied to multi-omic data and provides fundamental insights into the molecular signaling events occurring during BR response.
Regio- and sequence-controlled conjugated topological oligomers and polymers via boronate-tag assisted solution-phase strategy
Authors: Xu Chaoran , He Congze , Li Ning , Yang Shicheng , Du Yuxuan , Matyjaszewski Krzysztof , Pan Xiangcheng 
Published: October 2021

AbstractThe regulation of polymer topology and the precise control over the monomer sequence is crucial and challenging in polymer science. Herein, we report an efficient solution-phase synthetic strategy to prepare regio- and sequence-controlled conjugated polymers with topological variations via the usage of methyliminodiacetic acid (MIDA) boronates. Based on the solubility of MIDA boronates and their unusual binary affinity for silica gel, the synthesized regio- and sequence-defined conjugated oligomers can be rapidly purified via precipitation or automatic liquid chromatography. These synthesized discrete oligomers can be used for iterative exponential and sequential growth to obtain linear and dendrimer-like star polymers. Moreover, different topological sequence-controlled conjugated polymers are conveniently prepared from these discrete oligomers via condensation polymerization. By investigating the structure-property relationship of these polymers, we find that the optical properties are strongly influenced by the regiochemistry, which may give inspiration to the design of optoelectronic polymeric materials.
SOIL-WATERGRIDS, mapping dynamic changes in soil moisture and depth of water table from 1970 to 2014
Authors: Guglielmo Magda , Tang Fiona H. M. , Pasut Chiara , Maggi Federico 
Published: October 2021

AbstractWe introduce here SOIL-WATERGRIDS, a new dataset of dynamic changes in soil moisture and depth of water table over 45 years from 1970 to 2014 globally resolved at 0.25 × 0.25 degree resolution (about 30 × 30 km at the equator) along a 56 m deep soil profile. SOIL-WATERGRIDS estimates were obtained using the BRTSim model instructed with globally gridded soil physical and hydraulic properties, land cover and use characteristics, and hydrometeorological variables to account for precipitation, ecosystem-specific evapotranspiration, snowmelt, surface runoff, and irrigation. We validate our estimates against independent observations and re-analyses of the soil moisture, water table depth, wetland occurrence, and runoff. SOIL-WATERGRIDS brings into a single product the monthly mean water saturation at three depths in the root zone and the depth of the highest and lowest water tables throughout the reference period, their long-term monthly averages, and data quality. SOIL-WATERGRIDS can therefore be used to analyse trends in water availability for agricultural abstraction, assess the water balance under historical weather patterns, and identify water stress in sensitive managed and unmanaged ecosystems.
A scalable open-source MATLAB toolbox for reconstruction and analysis of multispectral optoacoustic tomography data
Authors: O’Kelly Devin , Campbell James , Gerberich Jeni L. , Karbasi Paniz , Malladi Venkat , Jamieson Andrew , Wang Liqiang , Mason Ralph P. 
Published: October 2021

AbstractMultispectral photoacoustic tomography enables the resolution of spectral components of a tissue or sample at high spatiotemporal resolution. With the availability of commercial instruments, the acquisition of data using this modality has become consistent and standardized. However, the analysis of such data is often hampered by opaque processing algorithms, which are challenging to verify and validate from a user perspective. Furthermore, such tools are inflexible, often locking users into a restricted set of processing motifs, which may not be able to accommodate the demands of diverse experiments. To address these needs, we have developed a Reconstruction, Analysis, and Filtering Toolbox to support the analysis of photoacoustic imaging data. The toolbox includes several algorithms to improve the overall quantification of photoacoustic imaging, including non-negative constraints and multispectral filters. We demonstrate various use cases, including dynamic imaging challenges and quantification of drug effect, and describe the ability of the toolbox to be parallelized on a high performance computing cluster.
Transcriptomic profiling and functional prediction reveal aberrant expression of circular RNAs during osteogenic differentiation in human umbilical cord mesenchymal stromal cells
Authors: Su Cheng , Zheng Xiao , He Yanjin , Long Li , Chen Wenchuan 
Published: October 2021

AbstractCircular RNAs (circRNAs) are crucial elements of non-coding RNA, that regulate various biological processes. To date, expression patterns and functional roles of circRNAs during osteogenic differentiation of human umbilical cord mesenchymal stromal cells (hUCMSCs) remain unknown. In this study, we analyzed RNA-sequence data to reveal expression profiles of circRNAs during osteogenesis of hUCMSCs, then elucidated the underlying mechanisms of action. We identified a total of 5457 circRNAs in hUCMSCs, of which 34 and 33 were upregulated and downregulated, respectively. We applied Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to determine functions and related pathways of differentially expressed circRNAs. Moreover, we applied bioinformatics tools to construct competing endogenous RNA networks, comprising 10 circRNAs, 46 micro RNAs and 413 mRNAs. Furthermore, we predicted protein-coding potential of the upregulated circRNAs then constructed a co-expression network comprising the top 5 upregulated circRNAs and 75 RNA-binding proteins. Next, we validated 6 differentially-expressed circRNAs and found that overexpressing circ‐CTTN could promote osteogenesis of hUCMSCs. Overall, our findings indicate that clusters of circRNAs are aberrantly expressed in hUCMSCs during osteogenic differentiation, hence lay a foundation for future research into promoting hUCMSCs osteogenic differentiation and bone regeneration.
Activators of alpha synuclein expression identified by reporter cell line-based high throughput drug screen
Authors: Stahl Fabian , Denner Philip , Piston Dominik , Evert Bernd O. , de Boni Laura , Schmitt Ina , Breuer Peter , Wüllner Ullrich 
Published: October 2021

AbstractMultiplications, mutations and dysregulation of the alpha synuclein gene (SNCA) are associated with the demise of dopaminergic neurons and are considered to play important roles in the pathogenesis of familial and sporadic forms of Parkinson’s disease. Regulation of SNCA expression might thus be an appropriate target for treatment. We aimed to identify specific modulators of SNCA transcription, generated CRISPR/Cas9 modified SNCA-GFP-luciferase (LUC) genomic fusion- and control cell lines and screened a library of 1649 bioactive compounds, including the FDA approved drugs. We found no inhibitors but three selective activators which increased SNCA mRNA and protein levels.
Music video emotion classification using slow–fast audio–video network and unsupervised feature representation
Authors: Pandeya Yagya Raj , Bhattarai Bhuwan , Lee Joonwhoan 
Published: October 2021

AbstractAffective computing has suffered by the precise annotation because the emotions are highly subjective and vague. The music video emotion is complex due to the diverse textual, acoustic, and visual information which can take the form of lyrics, singer voice, sounds from the different instruments, and visual representations. This can be one reason why there has been a limited study in this domain and no standard dataset has been produced before now. In this study, we proposed an unsupervised method for music video emotion analysis using music video contents on the Internet. We also produced a labelled dataset and compared the supervised and unsupervised methods for emotion classification. The music and video information are processed through a multimodal architecture with audio–video information exchange and boosting method. The general 2D and 3D convolution networks compared with the slow–fast network with filter and channel separable convolution in multimodal architecture. Several supervised and unsupervised networks were trained in an end-to-end manner and results were evaluated using various evaluation metrics. The proposed method used a large dataset for unsupervised emotion classification and interpreted the results quantitatively and qualitatively in the music video that had never been applied in the past. The result shows a large increment in classification score using unsupervised features and information sharing techniques on audio and video network. Our best classifier attained 77% accuracy, an f1-score of 0.77, and an area under the curve score of 0.94 with minimum computational cost.
Neurocognitive development of novelty and error monitoring in children and adolescents
Authors: Kang Kathleen , Alexander Nina , Wessel Jan R. , Wimberger Pauline , Nitzsche Katharina , Kirschbaum Clemens , Li Shu-Chen 
Published: October 2021

AbstractThe abilities to monitor one’s actions and novel information in the environment are crucial for behavioural and cognitive control. This study investigated the development of error and novelty monitoring and their electrophysiological correlates by using a combined flanker with novelty-oddball task in children (7–12 years) and adolescents (14–18 years). Potential moderating influences of prenatal perturbation of steroid hormones on these performance monitoring processes were explored by comparing individuals who were prenatally exposed and who were not prenatally exposed to synthetic glucocorticoids (sGC). Generally, adolescents performed more accurately and faster than children. However, behavioural adaptations to error or novelty, as reflected in post-error or post-novelty slowing, showed different developmental patterns. Whereas post-novelty slowing could be observed in children and adolescents, error-related slowing was absent in children and was marginally significant in adolescents. Furthermore, the amplitude of error-related negativity was larger in adolescents, whereas the amplitude of novelty-related N2 was larger in children. These age differences suggest that processes involving top-down processing of task-relevant information (for instance, error monitoring) mature later than processes implicating bottom-up processing of salient novel stimuli (for instance, novelty monitoring). Prenatal exposure to sGC did not directly affect performance monitoring but initial findings suggest that it might alter brain-behaviour relation, especially for novelty monitoring.
Identification of splice regulators of fibronectin-EIIIA and EIIIB by direct measurement of exon usage in a flow-cytometry based CRISPR screen
Authors: Hensel Jessica A. , Heineman Brent D. , Kimble Amy L. , Jellison Evan R. , Reese Bo , Murphy Patrick A. 
Published: October 2021

AbstractThe extracellular matrix protein fibronectin (FN) is alternatively spliced in a variety of inflammatory conditions, resulting in increased inclusion of alternative exons EIIIA and EIIIB. Inclusion of these exons affects fibril formation, fibrosis, and inflammation. To define upstream regulators of alternative splicing in FN, we have developed an in vitro flow-cytometry based assay, using RNA-binding probes to determine alternative exon inclusion level in aortic endothelial cells. This approach allows us to detect exon inclusion in the primary transcripts themselves, rather than in surrogate splicing reporters. We validated this assay in cells with and without FN-EIIIA and -EIIIB expression. In a small-scale CRISPR KO screen of candidate regulatory splice factors, we successfully detected known regulators of EIIIA and EIIIB splicing, and detected several novel regulators. Finally, we show the potential in this approach to broadly interrogate upstream signaling pathways in aortic endothelial cells with a genome-wide CRISPR-KO screen, implicating the TNFalpha and RIG-I-like signaling pathways and genes involved in the regulation of fibrotic responses. Thus, we provide a novel means to screen the regulation of splicing of endogenous transcripts, and predict novel pathways in the regulation of FN-EIIIA inclusion.
Mapping thalamocortical functional connectivity with large-scale brain networks in patients with first-episode psychosis
Authors: Kwak Yoo Bin , Cho Kang Ik Kevin , Hwang Wu Jeong , Kim Ahra , Ha Minji , Park Hyungyou , Lee Junhee , Lee Tae Yong , Kim Minah , Kwon Jun Soo 
Published: October 2021

AbstractAbnormal thalamocortical networks involving specific thalamic nuclei have been implicated in schizophrenia pathophysiology. While comparable topography of anatomical and functional connectivity abnormalities has been reported in patients across illness stages, previous functional studies have been confined to anatomical pathways of thalamocortical networks. To address this issue, we incorporated large-scale brain network dynamics into examining thalamocortical functional connectivity. Forty patients with first-episode psychosis and forty healthy controls underwent T1-weighted and resting-state functional magnetic resonance imaging. Independent component analysis of voxelwise thalamic functional connectivity maps parcellated the cortex into thalamus-related networks, and thalamic subdivisions associated with these networks were delineated. Functional connectivity of (1) networks with the thalamus and (2) thalamic subdivision seeds were examined. In patients, functional connectivity of the salience network with the thalamus was decreased and localized to the ventrolateral (VL) and ventroposterior (VP) thalamus, while that of a network comprising the cerebellum, temporal and parietal regions was increased and localized to the mediodorsal (MD) thalamus. In patients, thalamic subdivision encompassing the VL and VP thalamus demonstrated hypoconnectivity and that encompassing the MD and pulvinar regions demonstrated hyperconnectivity. Our results extend the implications of disrupted thalamocortical networks involving specific thalamic nuclei to dysfunctional large-scale brain network dynamics in schizophrenia pathophysiology.
Cardiac tyrosine hydroxylase activation and MB-COMT in dyskinetic monkeys
Authors: Cuenca-Bermejo Lorena , Almela Pilar , Gallo-Soljancic Pablo , Yuste José E. , de Pablos Vicente , Bautista-Hernández Víctor , Fernández-Villalba Emiliano , Laorden María-Luisa , Herrero María-Trinidad 
Published: October 2021

AbstractThe impact of age-associated disorders is increasing as the life expectancy of the population increments. Cardiovascular diseases and neurodegenerative disorders, such as Parkinson’s disease, have the highest social and economic burden and increasing evidence show interrelations between them. Particularly, dysfunction of the cardiovascular nervous system is part of the dysautonomic symptoms of Parkinson’s disease, although more studies are needed to elucidate the role of cardiac function on it. We analyzed the dopaminergic system in the nigrostriatal pathway of Parkinsonian and dyskinetic monkeys and the expression of some key proteins in the metabolism and synthesis of catecholamines in the heart: total and phosphorylated (phospho) tyrosine hydroxylase (TH), and membrane (MB) and soluble (S) isoforms of catechol-O-methyl transferase (COMT). The dopaminergic system was significantly depleted in all MPTP-intoxicated monkeys. MPTP- and MPTP + L-DOPA-treated animals also showed a decrease in total TH expression in both right (RV) and left ventricle (LV). We found a significant increase of phospho-TH in both groups (MPTP and MPTP + L-DOPA) in the LV, while this increase was only observed in MPTP-treated monkeys in the RV. MB-COMT analysis showed a very significant increase of this isoform in the LV of MPTP- and MPTP + L-DOPA-treated animals, with no significant differences in S-COMT levels. These data suggest that MB-COMT is the main isoform implicated in the cardiac noradrenergic changes observed after MPTP treatment, suggesting an increase in noradrenaline (NA) metabolism. Moreover, the increase of TH activity indicates that cardiac noradrenergic neurons still respond despite MPTP treatment.
Peripheral blood microbial signatures in current and former smokers
Authors: Morrow Jarrett D. , Castaldi Peter J. , Chase Robert P. , Yun Jeong H. , Lee Sool , Liu Yang-Yu , Hersh Craig P. 
Published: October 2021

AbstractThe human microbiome has a role in the development of multiple diseases. Individual microbiome profiles are highly personalized, though many species are shared. Understanding the relationship between the human microbiome and disease may inform future individualized treatments. We hypothesize the blood microbiome signature may be a surrogate for some lung microbial characteristics. We sought associations between the blood microbiome signature and lung-relevant host factors. Based on reads not mapped to the human genome, we detected microbial nucleic acids through secondary use of peripheral blood RNA-sequencing from 2,590 current and former smokers with and without chronic obstructive pulmonary disease (COPD) from the COPDGene study. We used the Genome Analysis Toolkit (GATK) microbial pipeline PathSeq to infer microbial profiles. We tested associations between the inferred profiles and lung disease relevant phenotypes and examined links to host gene expression pathways. We replicated our analyses using a second independent set of blood RNA-seq data from 1,065 COPDGene study subjects and performed a meta-analysis across the two studies. The four phyla with highest abundance across all subjects were Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. In our meta-analysis, we observed associations (q-value < 0.05) betweenAcinetobacter,Serratia,StreptococcusandBacillusinferred abundances and Modified Medical Research Council (mMRC) dyspnea score. Current smoking status was associated (q < 0.05) withAcinetobacter,SerratiaandCutibacteriumabundance. All 12 taxa investigated were associated with at least one white blood cell distribution variable. Abundance for nine of the 12 taxa was associated with sex, and seven of the 12 taxa were associated with race. Host-microbiome interaction analysis revealed clustering of genera associated with mMRC dyspnea score and smoking status, through shared links to several host pathways. This study is the first to identify a bacterial microbiome signature in the peripheral blood of current and former smokers. Understanding the relationships between systemic microbial signatures and lung-related phenotypes may inform novel interventions and aid understanding of the systemic effects of smoking.