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th acute (LPS) and chronic (high-fat diet) inflammation models, reiterated the adverse effects of abnormal macrophages activation on cardiac function. Our Sectm1a knockout mouse model showed exacerbated cardiac and systemic inflammatory responses, resulting in further aggravation of contractile dysfunction on the heart after endotoxin challenge. We also demonstrated Sectm1a as a new regulator of macrophage function through LXRα pathway. These data suggest a novel approach to regulate macrophage-elicited inflammation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email journals.permissions@oup.com.SUMMARY The R/Bioconductor package primirTSS is a fast and convenient tool that allows implementation of the analytical method to identify transcription start sites of microRNAs by integrating ChIP-seq data of H3K4me3 and Pol II. It further ensures the precision by employing the conservation score and sequence features. The tool showed a good performance when using H3K4me3 or Pol II Chip-seq data alone as input, which brings convenience to applications where multiple data sets are hard to acquire. This flexible package is provided with both R-programming interfaces as well as graphical web interfaces. AVAILABILITY primirTSS is available at http//bioconductor.org/packages/primirTSS The documentation of the package including an accompanying tutorial was deposited at https//bioconductor.org/packages/release/bioc/vignettes/primirTSS/inst/doc/primirTSS.html. SUPPLEMENTARY INFORMATION Supplementary Data are available at Bioinformatics online. © The Author(s) (2020). Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.MOTIVATION Multiple sequence alignment (MSA) is important and challenging problem of computational biology. Most of the existing methods can only provide a short length multiple alignments in an acceptable time. Nevertheless, when the researchers confront the genome size in the multiple alignments, the process has required a huge processing space/time. Accordingly, using the method that can align genome size rapidly and precisely has a great effect, especially on the analysis of the very long alignments. Herein, we have proposed an efficient method, called FAME, which vertically divides sequences from the places that they have common areas; then they are arranged in consecutive order. Then these common areas are shifted and placed under each other, and the subsequences between them are aligned using any existing MSA tool. RESULTS The results demonstrate that the combination of FAME and the MSA methods and deploying minimizer are capable to be executed on personal computer and finely align long length sequences with much higher sum-of-pair (SP) score compared to the standalone MSA tools. As we select genomic datasets with longer length, the SP score of the combinatorial methods is gradually improved. The calculated computational complexity of methods supports the results in a way that combining FAME and the MSA tools leads to at least four times faster execution on the datasets. AVAILABILITY The source code and all datasets and run-parameters are accessible free on http//github.com/naznoosh/msa. © The Author(s) (2020). Published by Oxford University Press. All rights reserved. For Permissions, please email journals.permissions@oup.com.Heterogeneous macrophage lineages are present in the aortic and mitral valves of the heart during development and disease. These populations include resident macrophages of embryonic origins and recruited monocyte-derived macrophages prevalent in disease. Soon after birth, macrophages from hematopoietic lineages are recruited to the heart valves, and bone marrow transplantation studies in mice demonstrate that hematopoietic-derived macrophages continue to invest adult valves. During myxomatous heart valve disease, monocyte-derived macrophages are recruited to the heart valves and they contribute to valve degeneration in a mouse model of Marfan syndrome. Here we review recent studies of macrophage lineages in heart valve development and disease with discussion of clinical significance and therapeutic applications. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions please email journals.permissions@oup.com.SUMMARY The flood of recent cancer genomic data requires a coherent model that can sort out the findings to systematically explain clonal evolution and the resultant intra-tumor heterogeneity (ITH). Here, we present a new mathematical model designed to computationally simulate the evolution of cancer cells. The model connects the well-known hallmarks of cancer with the specific mutational states of tumor-related genes. The cell behavior phenotypes are stochastically determined and the hallmarks probabilistically interfere with the phenotypic probabilities. In turn, the hallmark variables depend on the mutational states of tumor-related genes. Thus, our software can deepen our understanding of cancer-cell evolution and generation of ITH. AVAILABILITY AND IMPLEMENTATION The open-source code is available in the repository https//github.com/nagornovys/Cancer_cell_evolution. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online. Oxidized glutathione © The Author(s) 2020. Published by Oxford University Press.BACKGROUND Detection of specific antinuclear-antibodies is very importance in term of diagnosis, prognosis and management of patients with systemic lupus erythematosus (SLE). To date, Line immunoassay (LIA), enzyme-linked immunosorbent assay (ELISA) and Crithidia luciliae indirect immunofluorescence (CLIF) assay are commonly used for detection of specific antinuclear-antibodies. OBJECTIVE To determine the performance of LIA, ELISA and CLIF for the detection of anti-double-stranded DNA (dsDNA), anti-nucleosome, and anti-extractable nuclear antigens (ENA) antibodies in patients with SLE. METHODS A total 100 sera from 50 patients with SLE, 25 patients with disease control and 25 healthy control subjects were tested for anti-dsDNA, anti-nucleosome, and anti-ENA antibodies by LIA, ELISA, and CLIF assay. Agreement and diagnostic performance of each assay were analyzed using Cohen's kappa coefficient and receiver operating characteristic curve analysis. RESULTS For the detection of anti-dsDNA antibody, ELISA had a substantial agreement with CLIF assay (? = 0.

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