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Representative structures of glycans with elevated levels in cancer patients included the following small glycans related to sialyllactose; sialyl Lewis X; lactose- and N-acetyllactosamine (LacNAc) type-II-core glycans with LacNAc (type-I or II)-extensions and modifications of α1,3/4-fucose and/or 6-sulfate on the Glc/GlcNAc; free-N-glycans containing sialylation or β1,6-branch of 6-sulfo Lewis X; novel NeuAcα2-3Galβ1-4(+/-Fucα1-3)Xylα1-3Glc glycans. Our results provide further insight into urinary free-glycans and suggest the potential utility of these compounds as tumor markers.
It is a common practice in epigenetics research to profile DNA methylation on tissue samples, which is usually a mixture of different cell types. To properly account for the mixture, estimating cell compositions has been recognized as an important first step. Many methods were developed for quantifying cell compositions from DNA methylation data, but they mostly have limited applications due to lack of reference or prior information.
We develop Tsisal, a novel complete deconvolution method which accurately estimate cell compositions from DNA methylation data without any prior knowledge of cell types or their proportions. Tsisal is a full pipeline to estimate number of cell types, cell compositions, and identify cell-type-specific CpG sites. It can also assign cell type labels when (full or part of) reference panel is available. Extensive simulation studies and analyses of seven real data sets demonstrate the favorable performance of our proposed method compared with existing deconvolution methods serving similar purpose.
The proposed method Tsisal is implemented as part of the R/Bioconductor package TOAST at https//bioconductor.org/packages/TOAST.
[email protected] and [email protected].
Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.The dysregulation of circular RNAs (circRNAs) has been identified in various human diseases. Here, we probed into the potential mechanism of circRNA_0092516 in osteoarthritis (OA). The expression of circRNA_0092516 was tested by quantitative real-time PCR. MTT, flow cytometry, and Western blot were applied to confirm the functions of circRNA_0092516 in vitro. Besides, RNA pull-down and dual-luciferase reporter gene experiments were applied to probe into the mechanism. circRNA_0092516 was raised in the tissues of OA patients and chondrocytes stimulated by IL-1β. The potential mechanism analysis expounded that circRNA_0092516 bound to miR-337-3p, and the interference with circRNA_0092516 boosted chondrocyte proliferation and restrained cell apoptosis through the miR-337-3p/PTEN axis, thereby improving OA. In vivo experiments expounded that circRNA_0092516 regulated cartilage production through miR-337-3p. Overall, our data expounded that the interference with circRNA_0092516 boosted chondrocyte proliferation and restrained cell apoptosis through the miR-337-3p/PTEN axis, eventually slowed down the progress of OA.Vasculopathy is a pathological process occurring in the blood vessel wall, which could affect the haemostasis and physiological functions of all the vital tissues/organs and is one of the main underlying causes for a variety of human diseases including cardiovascular diseases. Current pharmacological interventions aiming to either delay or stop progression of vasculopathies are suboptimal, thus searching novel, targeted, risk-reducing therapeutic agents, or vascular grafts with full regenerative potential for patients with vascular abnormalities are urgently needed. Since first reported, pluripotent stem cells (PSCs), particularly human induced pluripotent stem cells, have open new avenue in all research disciplines including cardiovascular regenerative medicine and disease remodelling. Assisting with recent technological breakthroughs in tissue engineering, in vitro construction of tissue organoid made a tremendous stride in the past decade. In this review, we provide an update of the main signal pathways involved in vascular cell differentiation from human PSCs and an extensive overview of PSC-derived tissue organoids, highlighting the most recent discoveries in the field of blood vessel organoids as well as vascularization of other complex tissue organoids, with the aim of discussing the key cellular and molecular players in generating vascular organoids.
Burnout and compassion fatigue (CF) are common among mental health practitioners. Accredited Exercise Physiologists (AEPs) provide clinical services to individuals experiencing mental illness, increasing their likelihood of experiencing burnout and CF.
To examine the prevalence of burnout and CF among AEPs working with people experiencing mental illness.
An anonymous online cross-sectional survey of AEPs working with people experiencing mental illness was distributed via the Exercise and Sports Science Australia Mental Health Special Interest Group Facebook page between July and November 2019. In addition to demographics and caseload data, respondents completed the Professional Quality of Life scale and Oldenburg Burnout Inventory (OLBI). Results are reported using descriptive statistics.
Sixty-two AEPs (68%, n = 42 female) completed the survey. Most (n = 53, 86%) reported delivering services to consumers with severe mental health conditions. Less than half (n = 27, 44%) reported working in a dedicated mental health facility. Moderate levels of burnout and CF were experienced by 60% and 30% of respondents, respectively.
The prevalence of moderate burnout and CF symptoms in AEPs is comparable with other mental health professionals. Strategies to preserve psychological well-being such as enhancing mental health training for undergraduates and formalized supervision structures discussed.
The prevalence of moderate burnout and CF symptoms in AEPs is comparable with other mental health professionals. Strategies to preserve psychological well-being such as enhancing mental health training for undergraduates and formalized supervision structures discussed.
Predicting the residues controlling a protein's interaction specificity is important not only to better understand its interactions, but to design mutations aimed at fine-tuning or swapping them as well.
In this work, we present a methodology that combines sequence information (in the form of multiple sequence alignments) with interactome information to detect that kind of residues in paralogous families of proteins. WAY-316606 research buy The interactome is used to define pairwise similarities of interaction contexts for the proteins in the alignment. The method looks for alignment positions with patterns of amino-acid changes reflecting the similarities/differences in the interaction neighborhoods of the corresponding proteins. We tested this new methodology in a large set of human paralogous families with structurally characterized interactions, and discuss in detail the results for the RasH family. We show that this approach is a better predictor of interfacial residues than both, sequence conservation and an equivalent "unsupervised" method that does not use interactome information.
http//csbg.cnb.csic.es/pazos/Xdet/.
[email protected].
Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
High-throughput sequencing data can be affected by different technical errors, e.g. from probe preparation or false base calling. As a consequence, reproducibility of experiments can be weakened. In virus metagenomics, technical errors can result in falsely identified viruses in samples from infected hosts. We present a new resampling approach based on bootstrap sampling of sequencing reads from FASTQ-files in order to generate artificial replicates of sequencing runs which can help to judge the robustness of an analysis. In addition, we evaluate a mixture model on the distribution of read counts per virus to identify potentially false positive findings.
The evaluation of our approach on an artificially generated data set with known viral sequence content shows in general a high reproducibility of uncovering viruses in sequencing data. I.e., the correlation between original and mean bootstrap read count was highly correlated. However, the bootstrap read counts can also indicate reduced or increased evidence for the presence of a virus in the biological sample. We also found that the mixture model fits well to the read counts, and furthermore, it provides a higher accuracy on the original or on the bootstrap read counts than on the difference between both. The usefulness of our methods is further demonstrated on two freely available real world data sets from harbour seals.
We provide a Phyton tool, called RESEQ, available from https//github.com/babaksaremi/RESEQ that allows efficient generation of bootstrap reads from an original FASTQ-file.
[email protected].
Supplementary data are available at Bioinformatics online.
Supplementary data are available at Bioinformatics online.
Chronic kidney disease (CKD) is an independent risk factor for the development of coronary artery disease (CAD). For both, CKD and CAD, the intercellular transfer of microRNAs (miR) through extracellular vesicles (EVs) is an important factor of disease development. Whether the combination of CAD and CKD affects endothelial function through cellular crosstalk of EV-incorporated miRs is still unknown.
Out of 172 screened CAD patients, 31 patients with CAD+CKD were identified and matched with 31 CAD patients without CKD. Additionally, 13 controls without CAD and CKD were included. Large EVs from CAD+CKD patients contained significantly lower levels of the vasculo-protective miR-130a-3p and miR-126-3p compared to CAD patients and controls. Flow cytometric analysis of plasma-derived EVs revealed significantly higher numbers of endothelial cell-derived EVs in CAD and CAD+CKD patients compared to controls. EVs from CAD+CKD patients impaired target human coronary artery endothelial cell (HCAEC) proliferation uponan therefore be used as a target to influence vesicular microRNA levels to improve endothelial healing.
In the present study we identify a novel hnRNPU-dependent mechanism of how kidney disease and uremia reduce endothelial proliferation. HnRNPU can therefore be used as a target to influence vesicular microRNA levels to improve endothelial healing.
During atherosclerosis, smooth muscle cells (SMCs) accumulate in the intima where they switch from a contractile to a synthetic phenotype. From porcine coronary artery, we isolated spindle-shaped (S) SMCs exhibiting features of the contractile phenotype and rhomboid (R) SMCs typical of the synthetic phenotype. S100A4 was identified as a marker of R-SMCs in vitro and intimal SMCs, in pig and man. S100A4 exhibits intra- and extracellular functions. In this study, we investigated the role of extracellular S100A4 in SMC phenotypic transition.
S-SMCs were treated with oligomeric recombinant S100A4 (oS100A4), which induced nuclear factor (NF)-κB activation. Treatment of S-SMCs with oS100A4 in combination with platelet-derived growth factor (PDGF)-BB induced a complete SMC transition toward a pro-inflammatory R-phenotype associated with NF-κB activation, through toll-like receptor-4. RNA sequencing of cells treated with oS100A4/PDGF-BB revealed a strong upregulation of pro-inflammatory genes and enrichment of transcription factor binding sites essential for SMC phenotypic transition.
Read More: https://www.selleckchem.com/products/way-316606.html
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