Sotomarcher9145

An atlas of TBK1 substrates is in constant expanding, setting TBK1 as a key node of signaling network and a dominant player in contexts of cell biology, animal models, and human diseases. Here, we review recent advancements of activation, regulations, and functions of TBK1 under these physiological and pathological contexts.The gill proteome of threespine sticklebacks (Gasterosteus aculeatus) differs greatly in populations that inhabit diverse environments characterized by different temperature, salinity, food availability, parasites, and other parameters. To assess the contribution of a specific environmental parameter to such differences it is necessary to isolate its effects from those of other parameters. In this study the effect of environmental salinity on the gill proteome of G. aculeatus was isolated in controlled mesocosm experiments. Salinity-dependent changes in the gill proteome were analyzed by LC/MSMS data-independent acquisition (DIA) and Skyline. Relative abundances of 1691 proteins representing the molecular phenotype of stickleback gills were quantified using previously developed MSMS spectral and assay libraries in combination with DIA quantitative proteomics. Non-directional stress responses were distinguished from osmoregulatory protein abundance changes by their consistent occurrence during both hypo- and hgradation, purine metabolism, focal adhesion, mRNA surveillance, phagosome, endocytosis, and associated intracellular signaling KEGG pathways. These results demonstrate that G. aculeatus responds to salinity changes by adjusting osmoregulatory mechanisms that are distinct from transient non-directional stress responses to control compatible osmolyte synthesis, transepithelial ion transport, and oxidative energy metabolism. Furthermore, this study establishes salinity as a key factor for causing the regulation of numerous proteins and KEGG pathways with established functions in proteostasis, immunity, and tissue remodeling. We conclude that the corresponding osmoregulatory gill proteins and KEGG pathways represent molecular phenotypes that promote transepithelial ion transport, cellular osmoregulation, and gill epithelial remodeling to adjust gill function to environmental salinity.Women who carry the BRCA mutation are at high lifetime risk of breast cancer, but there is no consensus regarding an effective and safe chemoprevention strategy. A large body of evidence suggests that 3,3-diindolylmethane (DIM), a dimer of indole-3-carbinol (I3C) found in cruciferous vegetables, can potentially prevent carcinogenesis and tumor development. The primary aim of this prospective single-arm study was to investigate the effect of DIM supplementation on breast density, a recognized predictive factor of breast-cancer risk. Participants were 23 healthy female BRCA carriers (median age 47 years; 78% postmenopausal) who were treated with oral DIM 100 mgx1/d for one year. The amount of fibroglandular tissue (FGT) and background parenchymal enhancement (BPE) on magnetic resonance imaging (MRI) performed before and after the intervention were scored by two independent expert radiologists using the Breast Imaging and Reporting Data System (BI-RADS). The results showed a decrease in the average score for FGT amount from 2.8±0.8 at onset to 2.65±0.842.8 after one year (p=0.031), with no significant change in BPE (p=0.429). A group of DIM-untreated age- and menopausal-status-matched clinic women did not show a significant change in FGT amount (p=0.33) or BPE (p=0.814) in a parallel year. Mean estradiol level decreased from 159 to 102 pmol/L (p=0.01), and mean testosterone level, from 0.42 to 0.31 pmol/L (p=0.007). Side effects were grade 1. In conclusion, one year's supplementation with DIM 100 mgX1/d in BRCA carriers was associated with a significant decline in FGT amount on MRI. Larger randomized studies are warranted to corroborate these findings.Campylobacter jejuni (C. jejuni) is considered to be one of the most frequent causes of bacterial gastroenteritis globally, especially in young children. The genome of C. jejuni contains many proteins with unknown functions termed as hypothetical proteins (HPs). These proteins might have essential biological role to show the full spectrum of this bacterium. Hence, our study aimed to determine the functions of HPs, pertaining to the genome of C. jejuni. An in-silico work flow integrating various tools were performed for functional assignment, three-dimensional structure determination, domain architecture predictors, subcellular localization, physicochemical characterization, and protein-protein interactions (PPIs). Sequences of 267 HPs of C. jejuni were analyzed and successfully attributed the function of 49 HPs with higher confidence. Here, we found proteins with enzymatic activity, transporters, binding and regulatory proteins as well as proteins with biotechnological interest. Assessment of the performance of various tools used in this analysis revealed an accuracy of 95% using receiver operating characteristic (ROC) curve analysis. Functional and structural predictions and the results from ROC analyses provided the validity of in-silico tools used in the present study. The approach used for this analysis leads us to assign the function of unknown proteins and relate them with the functions that have already been described in previous literature.Objectives Myelodysplastic syndromes (MDS) are a group of myeloid neoplasms that are often difficult to diagnose due to their pathologic and clinical heterogeneity. The key features of MDS are peripheral blood cytopenias, ineffective hematopoiesis manifesting as morphologic dysplasia, and clonal genetic abnormalities. read more The most difficult diagnostic dilemmas often arise in low-grade MDS cases (lacking excess blasts), which can be difficult to distinguish from other causes of cytopenia. This distinction requires the integration of information from the peripheral blood (both CBC parameters and morphology), bone marrow morphology, genetic studies, and interrogation of the clinical record to exclude secondary causes. Methods We discuss the approach to the diagnosis of low-grade MDS (cases lacking increased blasts), including a diagnostic algorithm and two illustrative cases. Results The appropriate use of ancillary studies is important to support or dispute the likelihood of low-grade MDS in conjunction with the findings of morphologic dysplasia. Interpreting the results of cytogenetics and next-generation sequencing can be challenging and must incorporate the emerging knowledge of clonal hematopoiesis of indeterminate potential. Conclusions The role of pathologists in integrating data from multiple sources in the diagnosis of low-grade MDS is evolving and becoming increasingly complex; in this challenging diagnostic setting, it is important to feel comfortable with uncertainty and maintain a conservative approach.Motivation Per-base quality values in NGS data take a significant portion of storage even after compression. Lossy compression technologies could further reduce the space used by quality values. However, in many applications lossless compression is still desired. Hence, sequencing data in multiple file formats have to be prepared for different applications. Results We developed a scalable lossy to lossless compression solution for quality values named ScaleQC. ScaleQC is able to provide the so-called bit-stream level scalability that the losslessly compressed bit-stream by ScaleQC can be further truncated to lower data rates without incurring an expensive transcoding operation. Despite its scalability, ScaleQC still achieves comparable compression performance at both lossless and lossy data rates compared to the existing lossless or lossy compressors. Availability ScaleQC has been integrated with SAMtools as a special quality value encoding mode for CRAM. Its source codes can be obtained from our integrated SAMtools (https//github.com/xmuyulab/samtools) with dependency on integrated HTSlib (https//github.com/xmuyulab/htslib). Supplementary information Supplementary data are available at Bioinformatics online.This study aimed to investigate the effect of SIK2 on cisplatin resistance induced by aerobic glycolysis in breast cancer cells and its potential mechanism. qRt-PCR and Western blot were used to detect SIK2 mRNA and protein levels, and cisplatin (DDP) resistant cell lines of breast cancer cells were established. Viability was measured and evaluated via CCK-8, cell invasion capability was evaluated via Transwell, and apoptosis rate was assessed via Flow cytometry. The glycolysis level was evaluated by measuring glucose consumption and lactic acid production. The protein levels of p-PI3K, p- protein kinase B (Akt) and p-mTOR were determined by western blot. SIK2 was highly expressed in breast cancer tissues and cells compared with adjacent tissues and normal human breast epithelial cells, and it had higher diagnostic value for breast cancer. Silencing SIK2 expression can inhibit proliferation and invasion of breast cancer cells and induce their apoptosis. In addition, SIK2 knockdown inhibits glycolysis, reverses the resistance of drug-resistant cells to cisplatin, and inhibits PI3K/AKT/mTOR signaling pathway. When LY294002 was used to inhibit PI3K/AKT/mTOR signaling pathway, the effect of pcDNA3.1-SIK2 on aerobic glycolysis of breast cancer cells could be reversed. SIK2 can promote cisplatin resistance caused by aerobic glycolysis of breast cancer cells through PI3K/AKT/mTOR signaling pathway, which may be a new target to improve cisplatin resistance of breast cancer cells.Secretory and membrane proteins synthesized in the endoplasmic reticulum (ER) are folded with intramolecular disulfide bonds, viz. oxidative folding, catalyzed by the protein disulfide isomerase (PDI) family proteins. Here, we identified a novel soybean PDI family protein, GmPDIL6. GmPDIL6 has a single thioredoxin-domain with a putative N-terminal signal peptide and an active center (CKHC). Recombinant GmPDIL6 forms various oligomers binding iron. Oligomers with or without iron binding, and monomers exhibited a dithiol oxidase activity level comparable to those of other soybean PDI family proteins. However, they displayed no disulfide reductase and extremely low oxidative refolding activity. Interestingly, GmPDIL6 was mainly expressed in the cotyledon during synthesis of seed storage proteins and GmPDIL6 mRNA was upregulated under ER stress. GmPDIL6 may play a role in the formation of disulfide bonds in nascent proteins for oxidative folding in the ER.Metastasis is the main cause of cancer-associated deaths, yet this complex process is still not well understood. Many studies have shown that acetate is involved in cancer metastasis, but the molecular mechanisms remain to be elucidated. In the present study, we first measured the effect of acetate on zinc finger transcriptional repressor SNAI1 and acetyl-CoA synthetase 2 (ACSS2) under glucose limitation in renal cell carcinoma cell lines, 786-O and ACHN. Then, RNA interference and overexpression of ACSS2 were used to detect the role of acetate on SNAI1 expression and cell migration. Finally, chromatin immunoprecipitation assay (ChIP) was used to investigate the regulatory mechanism of acetate on SNAI1 expression. The results showed that acetate increased the expressions of SNAI1 and ACSS2 under glucose limitation. ACSS2 knockdown significantly decreased acetate-induced SNAI1 expression and cell migration, whereas overexpression of ACSS2 increased SNAI1 level and histone H3K27 acetylation (H3K27ac). ChIP results revealed that acetate increased H3K27ac levels in regulatory region of SNAI1, but did not increase ACSS2-binding ability.