Spatial clustering and common regulatory elements correlate with coordinated gene expression

Many cellular responses to surrounding cues require temporally concerted transcriptional regulation of multiple genes. In prokaryotic cells, a single-input-module motif with one transcription factor regulating multiple target genes can generate coordinated gene expression. In eukaryotic cells, transcriptional activity of a gene is affected by not only transcription factors but also the epigenetic modifications and three-dimensional chromosome structure of the gene. To examine how local gene environment and transcription factor regulation are coupled, we performed a combined analysis of time-course RNA-seq data of TGF-\b{eta} treated MCF10A cells and related epigenomic and Hi-C data. Using Dynamic Regulatory Events Miner (DREM), we clustered differentially expressed genes based on gene expression profiles and associated transcription factors. Genes in each class have similar temporal gene expression patterns and share common transcription factors. Next, we defined a set of linear and radial distribution functions, as used in statistical physics, to measure the distributions of genes within a class both spatially and linearly along the genomic sequence. Remarkably, genes within the same class despite sometimes being separated by tens of million bases (Mb) along genomic sequence show a significantly higher tendency to be spatially close despite sometimes being separated by tens of Mb along the genomic sequence than those belonging to different classes do. Analyses extended to the process of mouse nervous system development arrived at similar conclusions. Future studies will be able to test whether this spatial organization of chromosomes contributes to concerted gene expression.Comment: 30 pages, 9 figures, accepted in PLoS Computational Biolog

The Relationship Between Big Five Personality Traits and Psychotic Experience in a Large Non-clinical Youth Sample: The Mediating Role of Emotion Regulation

Objective: Despite a long history of interest in personality traits and psychosis, the association between personality traits and psychotic experiences in the general population is not yet well understood. One possible factor that could influence the degree of distress from psychotic experiences is emotion regulation. The purpose of this study was to explore whether the association between personality and psychotic symptoms is already apparent in non-clinical youth as well as the mediating role of emotion regulation strategies between personality traits and psychotic experiences.Methods: Three thousand one hundred and forty seven college students were surveyed via self-report questionnaires measuring the Five-Factor model of personality, emotion regulation strategies, and psychotic experiences.Results: Neuroticism was found to be significantly positively correlated with psychotic experiences, while Extraversion, Openness, Agreeableness, and Conscientiousness were found to be significantly negatively correlated. Both the suppression and reappraisal strategies mediated the relationship between personality traits and psychotic experiences.Conclusion: Our findings suggest that youth with certain personality traits are more likely to have psychotic experiences. The reappraisal emotion regulation strategy could serve as a protective factor against the distress of psychotic experiences

M-estimation in Low-rank Matrix Factorization: a General Framework

Many problems in science and engineering can be reduced to the recovery of an unknown large matrix from a small number of random linear measurements. Matrix factorization arguably is the most popular approach for low-rank matrix recovery. Many methods have been proposed using different loss functions, for example the most widely used L_2 loss, more robust choices such as L_1 and Huber loss, quantile and expectile loss for skewed data. All of them can be unified into the framework of M-estimation. In this paper, we present a general framework of low-rank matrix factorization based on M-estimation in statistics. The framework mainly involves two steps: firstly we apply Nesterov's smoothing technique to obtain an optimal smooth approximation for non-smooth loss function, such as L_1 and quantile loss; secondly we exploit an alternative updating scheme along with Nesterov's momentum method at each step to minimize the smoothed loss function. Strong theoretical convergence guarantee has been developed for the general framework, and extensive numerical experiments have been conducted to illustrate the performance of proposed algorithm

Complete chloroplast genome sequences of three aroideae species (Araceae): lights into selective pressure, marker development and phylogenetic relationships

Background: Colocasia gigantea, Caladium bicolor and Xanthosoma sagittifolium are three worldwide famous ornamental and/or vegetable plants in the Araceae family, these species in the subfamily Aroideae are phylogenetically perplexing due to shared interspecifc morphological traits and variation. Result: This study, for the frst time ever, assembled and analyzed complete chloroplast genomes of C. gigantea, C. bicolor and X. sagittifolium with genome sizes of 165,906bp, 153,149bp and 165,169bp in length, respectively. The genomes were composed of conserved quadripartite circular structures with a total of 131 annotated genes, including 8 rRNA, 37 tRNA and 86 protein-coding genes. A comparison within Aroideae showed seven protein-coding genes (accD, ndhF, ndhK, rbcL, rpoC1, rpoC2 and matK) linked to environmental adaptation. Phylogenetic analysis confrmed a close relationship of C. gigantea with C. esculenta and S. colocasiifolia, and the C. bicolor with X. sagittifolium. Furthermore, three DNA barcodes (atpH-atpI+psaC-ndhE, atpH-atpI+trnS-trnG, atpH-atpI+psaC-ndhE+trnS-trnG) harbored highly variable regions to distinguish species in Aroideae subfamily. Conclusion: These results would be benefcial for species identifcation, phylogenetic relationship, genetic diversity, and potential of germplasm resources in Aroidea

Cytotoxic necrotizing factor 1 promotes bladder cancer angiogenesis through activating RhoC

Uropathogenic Escherichia coli (UPEC), a leading cause of urinary tract infections, is associated with prostate and bladder cancers. Cytotoxic necrotizing factor 1 (CNF1) is a key UPEC toxin; however, its role in bladder cancer is unknown. In the present study, we found CNF1 induced bladder cancer cells to secrete vascular endothelial growth factor (VEGF) through activating Ras homolog family member C (RhoC), leading to subsequent angiogenesis in the bladder cancer microenvironment. We then investigated that CNF1- mediated RhoC activation modulated the stabilization of hypoxia- inducible factor 1α (HIF1α) to upregulate the VEGF. We demonstrated in vitro that active RhoC increased heat shock factor 1 (HSF1) phosphorylation, which induced the heat shock protein 90α (HSP90α) expression, leading to stabilization of HIF1α. Active RhoC elevated HSP90α, HIF1α, VEGF expression, and angiogenesis in the human bladder cancer xenografts. In addition, HSP90α, HIF1α, and VEGF expression were also found positively correlated with the human bladder cancer development. These results provide a potential mechanism through which UPEC contributes to bladder cancer progression, and may provide potential therapeutic targets for bladder cancer.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155984/1/fsb220522.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155984/2/fsb220522-sup-0001-Supinfo.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155984/3/fsb220522_am.pd

Vanadium-Based Superconductivity in a Breathing Kagome Compound Ta2V3.1Si0.9

Superconductivity in V-based kagome metals has recently raised great interest as they exhibit the competing ground states associated with the flat bands and topological electronic structures. Here we report the discovery of superconductivity in Ta2V3.1Si0.9 with a superconducting transition temperature Tc of 7.5 K, much higher than those in previously reported kagome metals at ambient pressure. While the V ions form a two-dimensional breathing kagome structure, the length difference between two different V-V bonds is just 0.04, making it very close to the perfect kagome structure. Our results show that Ta2V3.1Si0.9 is a moderate-coupled superconductor with a large upper critical field that is close to the Pauli limit. DFT calculations give a van-Hove-singularity band located at Fermi energy, which may explain the relatively high Tc observed in this material.Comment: 19 pages, 5 figure

Cytotoxic Necrotizing Factor 1 Downregulates CD36 Transcription in Macrophages to Induce Inflammation During Acute Urinary Tract Infections

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) induce cystitis, pyelonephritis, and can cause kidney scarring and failure if inflammation is not under control. The detailed effects of cytotoxic necrotizing factor 1 (CNF1), the key UPEC toxin, on the pathogenicity of UPEC remain unclear. CD36 is an important scavenger receptor, responsible for pathogen and apoptotic cell clearance, and plays an essential role in host immune defense and homeostasis. Regulation of CD36 by bacterial toxins has not been reported. In this study, using a pyelonephritis mouse model, CNF1 was observed to contribute to increasing neutrophils and bacterial titers in infected bladder and kidney tissues, resulting in severe inflammation and tissue damage. CD36 expression in macrophages was found to be decreased by CNF1 in vitro and in vivo. We demonstrated that CNF1 attenuated CD36 transcription by decreasing expressions of its upstream transcription factors LXRβ and C/EBPα and their recruitment to the CD36 promotor. In addition, Cdc42 was found to be involved in CNF1-mediated downregulation of LXRβ. Our study investigated the pathogenesis of cnf1-carrying UPEC, which affected host innate immune defenses and homeostasis through regulation of CD36 in macrophages during acute UTIs

Impaired reverse cholesterol transport and hepatic steatosis contribute to pathogenesis of high fat dietinduced hyperlipidemia in murine models

Purpose: To investigate the pathogenesis of high fat diet (HFD)-induced hyperlipidemia (HLP) in mice, rats and hamsters and to comparatively evaluate their sensitivity to HFD.Methods: Mice, rats and hamsters were fed with high-fat diet formulation (HFD, n = 8) or a control diet (control, n = 8) for 4 weeks. Changes in body weight, relative liver weight, serum lipid profile, expressions of hepatic marker gene of lipid metabolism and liver morphology were observed in three hyperlipidemic models.Results: Elevated total cholesterol (TC), triglyceride, low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C) levels and body weight were observed in all hyperlipidemic animals (p < 0.05), while hepatic steatosis was manifested in rat and hamster HLP models, and increased hepatic TC level was only seen (p < 0.05) in hamster HLP model. Suppression of HMG-CoA reductase and up-regulation of lipoproteinlipase were observed in all HFD groups. Hepatic gene expression of LDLR, CYP7A1, LCAT, SR-B1, and ApoA I, which are a response to reverse cholesterol transport (RCT), were inhibited by HFD in the three models. Among these models, simultaneous suppression of HMG-CR, LCAT, LDLR and SR-BI and elevated LPL were features of the hamster model.Conclusion: As the results show, impaired RCT and excessive fat accumulation are major contributors to pathogenesis of HFD-induced murine HLP. Thus, the hamster model is more appropriate for hyperlipidemia research.Keywords: Hyperlipidemic model, Murine, Hamster, mRNA, Reverse cholesterol transport, High-fat diet, Pathogenesi