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Ward Shaffer posted an update 3 weeks, 4 days ago
Novel candidate gene findings included the MAT1A gene that encodes an enzyme involved in the sulphur metabolism pathway critical to production of wool proteins, and the ESRP1 gene. We also discovered a significant wrinkle variant upstream of the HAS2 gene, which in dogs is associated with the exaggerated skin folds in the Shar-Pei breed.
The wool and skin wrinkle traits studied here appear to be highly polygenic with many putative candidate variants showing considerable pleiotropy. Our CM-GWAS identified many highly plausible candidate genes for wool traits as well as breech wrinkle and breech area wool cover.
The wool and skin wrinkle traits studied here appear to be highly polygenic with many putative candidate variants showing considerable pleiotropy. Our CM-GWAS identified many highly plausible candidate genes for wool traits as well as breech wrinkle and breech area wool cover.
The topology of metabolic networks is both well-studied and remarkably well-conserved across many species. The regulation of these networks, however, is much more poorly characterized, though it is known to be divergent across organisms-two characteristics that make it difficult to model metabolic networks accurately. While many computational methods have been built to unravel transcriptional regulation, there have been few approaches developed for systems-scale analysis and study of metabolic regulation. Here, we present a stepwise machine learning framework that applies established algorithms to identify regulatory interactions in metabolic systems based on metabolic data stepwise classification of unknown regulation, or SCOUR.
We evaluated our framework on both noiseless and noisy data, using several models of varying sizes and topologies to show that our approach is generalizable. We found that, when testing on data under the most realistic conditions (low sampling frequency and high noise), SCOUR coully reduce the amount of time needed to identify and experimentally validate metabolic regulatory interactions. As high-throughput experimental methods for testing these interactions are further developed, SCOUR will provide critical impact in the development of predictive metabolic models in new organisms and pathways.
SCOUR uses a novel approach to synthetically generate the training data needed to identify regulators of reaction fluxes in a given metabolic system, enabling metabolomics and fluxomics data to be leveraged for regulatory structure inference. Adenosine 5′-diphosphate clinical trial By identifying and triaging the most likely candidate regulatory interactions, SCOUR can drastically reduce the amount of time needed to identify and experimentally validate metabolic regulatory interactions. As high-throughput experimental methods for testing these interactions are further developed, SCOUR will provide critical impact in the development of predictive metabolic models in new organisms and pathways.
Circular RNAs (circRNAs) play critical roles in the development of atherosclerosis (AS). This study investigated the role of circMTO1 in the progression of AS.
Serum samples from AS patients and healthy volunteers and vascular smooth muscle cells (VSMCs) were used as the study materials. The expressions of circMTO1 and miR-182-5p were measured by RT-qPCR. The effects of circMTO1, miR-182-5p, and RASA1 on VSMC proliferation and apoptosis were examined by MTT and BrdU assays and wound healing and flow cytometric analyses, respectively. Downstream target genes of circMTO1 and miR-182-5p were predicted using target gene prediction and screening and confirmed using a luciferase reporter assay. RASA1 expression was detected by RT-qPCR and Western blot.
circMTO1 expression was decreased, while miR-182-5p expression was increased in human AS sera and oxidized low-density lipoprotein (ox-LDL)-stimulated VSMCs. CircMTO1 overexpression inhibited the proliferation and promoted the apoptosis of ox-LDL-stimulated VSMCs. CircMTO1 was found to be served as a sponge of miR-182-5p and RASA1 as a target of miR-182-5p. Moreover, circMTO1 acted as a ceRNA of miR-182-5p to enhance RASA1 expression. Furthermore, miR-182-5p overexpression and RASA1 knockdown reversed the effects of circMTO1 overexpression on the proliferation, migration, and apoptosis of ox-LDL-stimulated VSMCs.
CircMTO1 inhibited the proliferation and promoted the apoptosis of ox-LDL-stimulated VSMCs by regulating miR-182-5p/RASA1 axis. These results suggest that circMTO1 has potential in AS treatment.
CircMTO1 inhibited the proliferation and promoted the apoptosis of ox-LDL-stimulated VSMCs by regulating miR-182-5p/RASA1 axis. These results suggest that circMTO1 has potential in AS treatment.
Accumulating evidences have demonstrated that long non-coding RNAs (lncRNAs) are involved in the pathophysiology of diabetic nephropathy (DN). lncRNA SOX2OT plays an essential role in many diseases, including diabetes. Herein, we aim to investigate the underlying mechanism of lncRNA SOX2OT in DN pathogenesis.
Streptozotocin-induced DN mouse models and high glucose-induced mouse mesangial cells were constructed to examine the expression pattern of lncRNA SOX2OT. The activation of autophagy was evaluated using immunohistochemistry, immunofluorescence and western blot analysis, respectively. SOX2OT overexpressing plasmid was applied to further verify the functional role of SOX2OT in DN pathogenesis. CCK-8 and EDU assays were performed to the proliferation of mesangial cells. Additionally, rapamycin, the inhibitor of mTOR signaling, was used to further clarify whether SOX2OT controls DN development through Akt/mTOR pathway.
lncRNA SOX2OT was markedly down-regulated both in streptozotocin-induced DN mice and high glucose-induced mouse mesangial cells. Moreover, overexpression of lncRNA SOX2OT was able to diminish the suppression of autophagy and alleviate DN-induced renal injury. Functionally, CCK-8 and EDU assays indicated that lncRNA SOX2OT overexpression significantly suppressed the proliferation and fibrosis of mesangial cells. Additionally, an obvious inhibition of Akt/mTOR was also observed with lncRNA SOX2OT overexpression, which was then further verified in vivo.
In summary, we demonstrated that lncRNA SOX2OT alleviates the pathogenesis of DN via regulating Akt/mTOR-mediated autophagy, which may provide a novel target for DN therapy.
In summary, we demonstrated that lncRNA SOX2OT alleviates the pathogenesis of DN via regulating Akt/mTOR-mediated autophagy, which may provide a novel target for DN therapy.