Notes

Incidence and also molecular depiction of Cryptosporidium spp. as well as Giardia duodenalis among hostage animals from the Bangladesh Country wide Zoo.
Collectively, BrainBase integrates not only valuable curated disease-gene associations and drug-target interactions but also molecular profiles through multi-omics data analysis, accordingly bearing great promise to serve as a valuable knowledgebase for brain diseases.RNA-seq has been widely used in experimental studies and produced a massive amount of data deposited in public databases. New biological insights can be obtained by retrospective analyses of previously published data. However, the barrier to efficiently utilize these data remains high, especially for those who lack bioinformatics skills and computational resources. We present MetazExp (https//bioinfo.njau.edu.cn/metazExp), a database for gene expression and alternative splicing profiles based on 53 615 uniformly processed publicly available RNA-seq samples from 72 metazoan species. The gene expression and alternative splicing profiles can be conveniently queried by gene IDs, symbols, functional terms and sequence similarity. Users can flexibly customize experimental groups to perform differential and specific expression and alternative splicing analyses. A suite of data visualization tools and comprehensive links with external databases allow users to efficiently explore the results and gain insights. In conclusion, MetazExp is a valuable resource for the research community to efficiently utilize the vast public RNA-seq datasets.Non-canonical forms of nucleic acids represent challenging objects for both structure-determination and investigation of their potential role in living systems. In this work, we uncover a structure adopted by GA repetition locked in a parallel homoduplex by an i-motif. A series of DNA oligonucleotides comprising GAGA segment and C3 clip is analyzed by NMR and CD spectroscopies to understand the sequence-structure-stability relationships. We demonstrate how the relative position of the homopurine GAGA segment and the C3 clip as well as single-base mutations (guanine deamination and cytosine methylation) affect base pairing arrangement of purines, i-motif topology and overall stability. We focus on oligonucleotides C3GAGA and methylated GAGAC3 exhibiting the highest stability and structural uniformity which allowed determination of high-resolution structures further analyzed by unbiased molecular dynamics simulation. We describe sequence-specific supramolecular interactions on the junction between homoduplex and i-motif blocks that contribute to the overall stability of the structures. The results show that the distinct structural motifs can not only coexist in the tight neighborhood within the same molecule but even mutually support their formation. Our findings are expected to have general validity and could serve as guides in future structure and stability investigations of nucleic acids.Drug discovery relies on the knowledge of not only drugs and targets, but also the comparative agents and targets. These include poor binders and non-binders for developing discovery tools, prodrugs for improved therapeutics, co-targets of therapeutic targets for multi-target strategies and off-target investigations, and the collective structure-activity and drug-likeness landscapes of enhanced drug feature. However, such valuable data are inadequately covered by the available databases. In this study, a major update of the Therapeutic Target Database, previously featured in NAR, was therefore introduced. This update includes (a) 34 861 poor binders and 12 683 non-binders of 1308 targets; (b) 534 prodrug-drug pairs for 121 targets; (c) 1127 co-targets of 672 targets regulated by 642 approved and 624 clinical trial drugs; (d) the collective structure-activity landscapes of 427 262 active agents of 1565 targets; (e) the profiles of drug-like properties of 33 598 agents of 1102 targets. Moreover, a variety of additional data and function are provided, which include the cross-links to the target structure in PDB and AlphaFold, 159 and 1658 newly emerged targets and drugs, and the advanced search function for multi-entry target sequences or drug structures. The database is accessible without login requirement at https//idrblab.org/ttd/.The availability of genetic variants, together with phenotypic annotations from model organisms, facilitates comparing these variants with equivalent variants in humans. However, existing databases and search tools do not make it easy to scan for equivalent variants, namely 'matching variants' (MatchVars) between humans and other organisms. Climbazole mw Therefore, we developed an integrated search engine called ConVarT (http//www.convart.org/) for matching variants between humans, mice, and Caenorhabditis elegans. ConVarT incorporates annotations (including phenotypic and pathogenic) into variants, and these previously unexploited phenotypic MatchVars from mice and C. elegans can give clues about the functional consequence of human genetic variants. Our analysis shows that many phenotypic variants in different genes from mice and C. elegans, so far, have no counterparts in humans, and thus, can be useful resources when evaluating a relationship between a new human mutation and a disease.Large-scale multi-omics datasets, most prominently from the TCGA consortium, have been made available to the public for systematic characterization of human cancers. However, to date, there is a lack of corresponding online resources to utilize these valuable data to study gene expression dysregulation and viral infection, two major causes for cancer development and progression. To address these unmet needs, we established OncoDB, an online database resource to explore abnormal patterns in gene expression as well as viral infection that are correlated to clinical features in cancer. Specifically, OncoDB integrated RNA-seq, DNA methylation, and related clinical data from over 10 000 cancer patients in the TCGA study as well as from normal tissues in the GTEx study. Another unique aspect of OncoDB is its focus on oncoviruses. By mining TCGA RNA-seq data, we have identified six major oncoviruses across cancer types and further correlated viral infection to changes in host gene expression and clinical outcomes. All the analysis results are integratively presented in OncoDB with a flexible web interface to search for data related to RNA expression, DNA methylation, viral infection, and clinical features of the cancer patients. OncoDB is freely accessible at http//oncodb.org.RNA-binding proteins regulate mRNA processing and translation and are often aberrantly expressed in cancer. The RNA-binding motif protein 6, RBM6, is a known alternative splicing factor that harbors tumor suppressor activity and is frequently mutated in human cancer. Here, we identify RBM6 as a novel regulator of homologous recombination (HR) repair of DNA double-strand breaks (DSBs). Mechanistically, we show that RBM6 regulates alternative splicing-coupled nonstop-decay of a positive HR regulator, Fe65/APBB1. RBM6 knockdown leads to a severe reduction in Fe65 protein levels and consequently impairs HR of DSBs. Accordingly, RBM6-deficient cancer cells are vulnerable to ATM and PARP inhibition and show remarkable sensitivity to cisplatin. Concordantly, cisplatin administration inhibits the growth of breast tumor devoid of RBM6 in mouse xenograft model. Furthermore, we observe that RBM6 protein is significantly lost in metastatic breast tumors compared with primary tumors, thus suggesting RBM6 as a potential therapeutic target of advanced breast cancer. Collectively, our results elucidate the link between the multifaceted roles of RBM6 in regulating alternative splicing and HR of DSBs that may contribute to tumorigenesis, and pave the way for new avenues of therapy for RBM6-deficient tumors.mBodyMap is a curated database for microbes across the human body and their associations with health and diseases. Its primary aim is to promote the reusability of human-associated metagenomic data and assist with the identification of disease-associated microbes by consistently annotating the microbial contents of collected samples using state-of-the-art toolsets and manually curating the meta-data of corresponding human hosts. mBodyMap organizes collected samples based on their association with human diseases and body sites to enable cross-dataset integration and comparison. To help users find microbes of interest and visualize and compare their distributions and abundances/prevalence within different body sites and various diseases, the mBodyMap database is equipped with an intuitive interface and extensive graphical representations of the collected data. So far, it contains a total of 63 148 runs, including 14 401 metagenomes and 48 747 amplicons related to health and 56 human diseases, from within 22 human body sites across 136 projects. Also available in the database are pre-computed abundances and prevalence of 6247 species (belonging to 1645 genera) stratified by body sites and diseases. mBodyMap can be accessed at https//mbodymap.microbiome.cloud.The advent of single-cell sequencing opened a new era in transcriptomic and genomic research. To understand cell composition using single-cell studies, a variety of cell markers have been widely used to label individual cell types. However, the specific database of cell markers for use by the plant research community remains very limited. To overcome this problem, we developed the Plant Cell Marker DataBase (PCMDB, http//www.tobaccodb.org/pcmdb/), which is based on a uniform annotation pipeline. By manually curating over 130 000 research publications, we collected a total of 81 117 cell marker genes of 263 cell types in 22 tissues across six plant species. Tissue- and cell-specific expression patterns can be visualized using multiple tools eFP Browser, Bar, and UMAP/TSNE graph. The PCMDB also supports several analysis tools, including SCSA and SingleR, which allows for user annotation of cell types. To provide information about plant species currently unsupported in PCMDB, potential marker genes for other plant species can be searched based on homology with the supported species. PCMDB is a user-friendly hierarchical platform that contains five built-in search engines. We believe PCMDB will constitute a useful resource for researchers working on cell type annotation and the prediction of the biological function of individual cells.We have previously described two flow cytometry-based in vitro genotoxicity tests micronucleus (MN) scoring (MicroFlow ®) and a multiplexed DNA damage response biomarker assay (MultiFlow ®). Here, we describe a strategy for combining the assays in order to efficiently supplement MN analyses with a panel of biomarkers that comment on cytotoxicity (i.e., relative nuclei count, relative increased nuclei count, cleaved PARP-positive chromatin, and ethidium monoazide-positive chromatin) and genotoxic mode of action (i.e., γH2AX, phospho-histone H3, p53 activation, and polyploidy). For these experiments, human TK6 cells were exposed to each of 32 well-studied reference chemicals in 96-well plates for 24 continuous hr. The test chemicals were evaluated over a range of concentrations in the presence and absence of a rat liver S9-based metabolic activation system. MultiFlow assay data were acquired at 4 and 24 hr, and MN were scored at 24 hr. Testing 32 chemicals in two metabolic activation arms translated into 64 a priori calls 42 genotoxicants and 22 non-genotoxicants.
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