Lesterjacobson2113

Meanwhile, LPS reduced m6A levels in oocytes, but MV restored these epigenetic modifications. Furthermore, MV reduced reactive oxygen species (ROS) levels and early apoptosis in oocytes exposed to LPS. In summary, our study demonstrates that MV can protect oocytes from LPS-induced meiotic defects in part by reducing oxidative stress and maintaining m6A levels.Lung adenocarcinoma (LUAD) is the main histological type of lung cancer, which is the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) were recently revealed to be involved in various cancers. However, the clinical relevance and potential biological roles of most lncRNAs in LUAD remain unclear. Here, we identified a prognosis-related lncRNA ITGB1-DT in LUAD. ITGB1-DT was upregulated in LUAD and high expression of ITGB1-DT was correlated with advanced clinical stages and poor overall survival and disease-free survival. Enhanced expression of ITGB1-DT facilitated LUAD cellular proliferation, migration, and invasion, and also lung metastasis in vivo. Knockdown of ITGB1-DT repressed LUAD cellular proliferation, migration, and invasion. Domatinostat ITGB1-DT interacted with EZH2, repressed the binding of EZH2 to ITGB1 promoter, reduced H3K27me3 levels at ITGB1 promoter region, and therefore activated ITGB1 expression. Through upregulating ITGB1, ITGB1-DT activated Wnt/β-catenin pathway and its downstream target MYC in LUAD. The expressions of ITGB1-DT, ITGB1, and MYC were positively correlated with each other in LUAD tissues. Intriguingly, ITGB1-DT was found as a transcriptional target of MYC. MYC directly transcriptionally activated ITGB1-DT expression. Thus, ITGB1-DT formed a positive feedback loop with ITGB1/Wnt/β-catenin/MYC. The oncogenic roles of ITGB1-DT were reversed by depletion of ITGB1 or inhibition of Wnt/β-catenin pathway. In summary, these findings revealed ITGB1-DT as a prognosis-related and oncogenic lncRNA in LUAD via activating the ITGB1-DT/ITGB1/Wnt/β-catenin/MYC positive feedback loop. These results implicated ITGB1-DT as a potential prognostic biomarker and therapeutic target for LUAD.LrrkA is a Dictyostelium discoideum kinase with leucine-rich repeats. LrrkA stimulates Kil2 and intra-phagosomal killing of ingested bacteria in response to folate. In this study, we show that genetic inactivation of lrrkA also causes a previously unnoticed phenotype lrrkA KO cells exhibit enhanced phagocytosis and cell motility compared to parental cells. This phenotype is cell autonomous, is reversible upon re-expression of LrrkA, and is not due to an abnormal response to inhibitory quorum-sensing factors secreted by D. discoideum in its medium. In addition, folate increases motility in parental D. discoideum cells, but not in lrrkA KO cells, suggesting that LrrkA plays a pivotal role in the cellular response to folate. On the contrary, lrrkA KO cells regulate gene transcription in response to folate in a manner indistinguishable from parental cells. Overall, based on analysis of mutant phenotypes, we identify gene products that participate in the control of intracellular killing, cell motility, and gene transcription in response to folate. These observations reveal a mechanism by which D. discoideum encountering bacterially-secreted folate can migrate, engulf, and kill bacteria more efficiently.Spermatogenesis requires a large number of proteins to be properly expressed at certain stages, during which post-transcriptional regulation plays an important role. RNA-binding proteins (RBPs) are key players in post-transcriptional regulation, but only a few RBPs have been recognized and preliminary explored their function in spermatogenesis at present. Here we identified a new RBP tubby-like protein 2 (TULP2) and found three potential deleterious missense mutations of Tulp2 gene in dyszoospermia patients. Therefore, we explored the function and mechanism of TULP2 in male reproduction. TULP2 was specifically expressed in the testis and localized to spermatids. Studies on Tulp2 knockout mice demonstrated that the loss of TULP2 led to male sterility; on the one hand, increases in elongated spermatid apoptosis and restricted spermatid release resulted in a decreased sperm count; on the other hand, the abnormal differentiation of spermatids induced defective sperm tail structures and reduced ATP contents, influencing sperm motility. Transcriptome sequencing of mouse testis revealed the potential target molecular network of TULP2, which played its role in spermatogenesis by regulating specific transcripts related to the cytoskeleton, apoptosis, RNA metabolism and biosynthesis, and energy metabolism. We also explored the potential regulator of TULP2 protein function by using immunoprecipitation and mass spectrometry analysis, indicating that TUPL2 might be recognized by CCT8 and correctly folded by the CCT complex to play a role in spermiogenesis. Our results demonstrated the important role of TULP2 in spermatid differentiation and male fertility, which could provide an effective target for the clinical diagnosis and treatment of patients with oligo-astheno-teratozoospermia, and enrich the biological theory of the role of RBPs in male reproduction.Nonsense variants in KIDINS220/ARMS were identified as the main cause of spastic paraplegia, intellectual disability, nystagmus, and obesity (SINO) syndrome, a rare disease with birth defects in brachycephaly, neurological disorder, and obesity. The cause of neural cell dysfunction by KIDINS220/ARMS were extensively studied while the cause of obesity in SINO syndrome remains elusive. Here, we identified KIDINS220/ARMS as an adipocyte differentiation-regulating gene. A Chinese family, mother and her two sons, all showed severe symptoms of SINO syndrome. G-banding karyotyping, chromosome microarray analysis, and whole exome sequencing revealed a novel amber mutation, c.3934G>T (p. E1312X), which was close to the C-terminal region of KIDINS220/ARMS and resulted in the premature of the protein. Both the mRNA and protein levels of KIDINS220/ARMS gradually decreased during adipocyte differentiation. Knockdown of KINDINS220/ARMS could prompt adipocyte differentiation and lipid accumulation while overexpression of KIDINS220/ARMS decrease the rate of matured adipocytes.