Notes

Globally epidemiology of neuro-coronavirus illness in children: instruction for one more outbreak.
pncRNA-D is an irradiation-induced 602-nt-long long noncoding RNA (lncRNA) transcribed from the promoter region of the cyclin D1 (CCND1) gene. CCND1 expression is predicted to be inhibited through an interplay between pncRNA-D and RNA-binding protein TLS/FUS. Since the pncRNA-D--TLS interaction is essential for pncRNA-D-stimulated CCND1 inhibition, here we studied the possible role of RNA modification in this interaction in HeLa cells. We found that osmotic stress induces pncRNA-D by recruiting RNA polymerase II to its promoter. pncRNA-D was highly m6A methylated in control cells, but osmotic stress reduced the methylation and also arginine methylation of TLS in the nucleus. Knockdown of the m6A modification enzyme methyltransferase like 3 (METTL3) prolonged the half-life of pncRNA-D, and among the known m6A recognition proteins, YTH domain containing 1 (YTHDC1) was responsible for binding m6A of pncRNA-D Knockdown of METTL3 or YTHDC1 also enhanced the interaction of pncRNA-D with TLS, and results from RNA pulldown assays implicated YTHDC1 in the inhibitory effect on the TLS-pncRNA-D interaction. buy Valproate CRISPR/Cas9-mediated deletion of candidate m6A site decreased the m6A level in pncRNA-D and altered its interaction with the RNA-binding proteins. Of note, a reduction in the m6A modification arrested the cell cycle at the G0/G1 phase, and pncRNA-D knockdown partially reversed this arrest. Moreover, pncRNA-D induction in HeLa cells significantly suppressed cell growth. Collectively, these findings suggest that m6A modification of the lncRNA pncRNA-D plays a role in the regulation of CCND1 gene expression and cell cycle progression. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.The peroxisome is a subcellular organelle that functions in essential metabolic pathways, including biosynthesis of plasmalogens, fatty acid β-oxidation of very-long-chain fatty acids, and degradation of hydrogen peroxide. Peroxisome biogenesis disorders (PBDs) manifest as severe dysfunction in multiple organs, including the central nervous system (CNS), but the pathogenic mechanisms in PBDs are largely unknown. Since CNS integrity is coordinately established and maintained by neural cells interactions, we here investigated whether cell-cell communication is impaired and responsible for the neurological defects associated with PBDs. Results from a noncontact co-culture system consisting of primary hippocampal neurons with glial cells revealed that a peroxisome-deficient astrocytic cell line secretes increased levels of brain-derived neurotrophic factor (BDNF), resulting in axonal branching of the neurons. Of note, the BDNF expression in astrocytes was not affected by defects in plasmalogen biosynthesis and peroxisomal fatty acid β-oxidation in the astrocytes. link2 Instead, we found that cytosolic reductive states caused by a mislocalized catalase in the peroxisome-deficient cells induce the elevation in BDNF secretion. Our results suggest that peroxisome deficiency dysregulates neuronal axogenesis by causing a cytosolic reductive state in astrocytes. We conclude that astrocytic peroxisomes regulate BDNF expression and thereby support neuronal integrity and function. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.We previously reported that overexpression of cytochrome P450 family 24 subfamily A member 1 (CYP24A1) increases lung cancer cell proliferation by activating RAS signaling and that CYP24A1 knockdown inhibits tumor growth. However, the mechanism of CYP24A1-mediated cancer cell proliferation remains unclear. Here, we conducted cell-synchronization and biochemical experiments in lung adenocarcinoma cells, revealing a link between CYP24A1 and anaphase-promoting complex (APC), a key cell cycle regulator. We demonstrate that CYP24A1 expression is cell cycle dependent; it was higher in the G2-M phase and diminished upon G1 entry. CYP24A1 has a functional destruction box (D-box) motif that allows binding with two APC adaptors, CDC20-homologue 1 (CDH1) and cell division cycle 20 (CDC20). Unlike other APC substrates, however, CYP24A1 acted as a "pseudo-substrate," inhibiting CDH1 activity and promoting mitotic progression. Conversely, overexpression of a CYP24A1 D-box mutant compromised CDH1 binding, allowing CDH1 hyperactivation, thereby hastening degradation of its substrates, cyclin B1 and CDC20, and accumulation of the CDC20 substrate p21, prolonging mitotic exit. These activities also occurred with a CYP24A1 isoform 2 lacking the catalytic cysteine (Cys-462), suggesting that CYP24A1's oncogenic potential is independent of its catalytic activity. CYP24A1 degradation reduced clonogenic survival of mutant KRAS-driven lung cancer cells, and calcitriol treatment increased CYP24A1 levels and tumor burden in Lsl-KRASG12D mice. These results disclose a catalytic activity-independent growth-promoting role of CYP24A1 in mutant KRAS-driven lung cancer. This suggests that CYP24A1 could be therapeutically targeted in lung cancers in which its expression is high. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.The vertebrate inner ear employs sensory hair cells and neurons to mediate hearing and balance. In mammals, damaged hair cells and neurons are not regenerated. In contrast, hair cells in the inner ear of zebrafish are produced throughout life and regenerate after trauma. However, it is unknown whether new sensory neurons are also formed in the adult zebrafish statoacoustic ganglion (SAG), the sensory ganglion connecting the inner ear to the brain. Using transgenic lines and marker analysis, we identify distinct cell populations and anatomical landmarks in the juvenile and adult SAG. In particular, we analyze a Neurod/Nestin-positive progenitor pool that produces large amounts of new neurons at juvenile stages, which transitions to a quiescent state in the adult SAG. Moreover, BrdU pulse chase experiments reveal the existence of a proliferative but otherwise marker-negative cell population that replenishes the Neurod/Nestin-positive progenitor pool at adult stages. Taken together, our study represents the first comprehensive characterization of the adult zebrafish SAG showing that zebrafish, in sharp contrast to mammals, display continued neurogenesis in the SAG well beyond embryonic and larval stages. © 2020. Published by The Company of Biologists Ltd.While the developing pancreas is exquisitely sensitive to nutrient supply in utero, it is not entirely clear how nutrient-driven post-translational modification of proteins impacts the pancreas during development. We hypothesized the nutrient-sensing enzyme O-GlcNAc transferase (Ogt) that catalyzes an O-GlcNAc-modification onto key target proteins integrates nutrient-signaling networks to regulate cell survival and development. We aimed to study the heretofore unknown role of Ogt in exocrine and endocrine islet development. By genetic manipulation in vivo and by using morphometric and molecular analyses such as immunofluorescence imaging and single cell RNA sequencing, we show the first evidence that Ogt regulates pancreas development. Genetic deletion of Ogt in pancreatic epithelium (OgtKOPanc) causes pancreas hypoplasia, in part by increased apoptosis and reduction of Pdx1 protein. Transcriptomic analysis of single-cell and bulk RNA-sequencing uncovered cell type heterogeneity and predicted upstream regulator proteins that mediate cell survival, including Pdx1, Ptf1a, p53, putative Ogt targets. In conclusion, these findings underscore the requirement of O-GlcNAcylation during pancreas development and show that Ogt is essential for pancreatic progenitor survival, providing a novel mechanistic link between nutrients and pancreas development. link3 © 2020. Published by The Company of Biologists Ltd.The WUSCHEL-CLAVATA3 pathway genes play essential role in shoot apical meristem maintenance and floral organ development, and under intense selection during crop domestication. The carpel number is an important fruit trait affecting fruit shape, size, and internal quality in cucumber, but the molecular mechanism remains elusive. Here, we found that CsCLV3 expression was negatively correlated with carpel number in cucumber cultivars. CsCLV3-RNAi led to increased number of petals and carpels, whereas overexpression of CsWUS resulted in more sepals, petals and carpels, suggesting that CsCLV3 and CsWUS function as a negative and a positive regulator for carpel number variation, respectively. Biochemical analyses indicated that CsWUS directly binds to the promoter of CsCLV3 and activates its expression. Overexpression of CsFUL1 A , a FRUITFULL-like MADS-box gene, resulted in more petals and carpels. CsFUL1A can directly bind to CsWUS promoter to stimulate its expression. Further, we found that auxin participates in carpel number variation in cucumber through interaction of CsARF14 with CsWUS. Therefore, we identified a gene regulatory pathway involving CsCLV3, CsWUS, CsFUL1 A and CsARF14 in determining carpel number variation in an important vegetable crop-cucumber. © 2020. Published by The Company of Biologists Ltd.Vitellogenin receptors (VgRs) play critical roles in oogenesis by mediating endocytosis of vitellogenin and other nutrients in ovipara. We conducted small RNA sequencing and screening with a luciferase reporter system, and found that bmo-miR-2739 and a novel miRNA (novel-miR-167) coordinately regulate the expression of VgR in Bombyx mori (BmVgR). Further analyses suggested that these two miRNAs direct target repression by binding directly to the BmVgR 3' untranslated region. Forced expression of either miRNA using the piggyBac system blocked vitellogenin (Vg) transport and retarded ovariole development. Antagomir silencing of bmo-miR-2739 or novel-miR-167 resulted in increased amounts of BmVgR protein in the ovaries and BmVgR mRNA in the fat body. This evidence combined with spatiotemporal expression profiles revealed that these two miRNAs function together to fine-tune the amount of BmVgR protein for ovarian development. Additionally, novel-miR-167 mainly switched on the posttranscriptional repression of BmVgR in non-ovarian tissues. The results of this study contribute to a better understanding of the function of miRNA during ovarian development of a lepidopteran and suggest a new strategy for controlling insect reproduction. © 2020. Published by The Company of Biologists Ltd.Comparative sequence analyses have been used to discover numerous classes of structured noncoding RNAs, some of which are riboswitches that specifically recognize small-molecule or elemental ion ligands and influence expression of adjacent downstream genes. Determining the correct identity of the ligand for a riboswitch candidate typically is aided by an understanding of the genes under its regulatory control. Riboswitches whose ligands were straightforward to identify have largely been associated with well-characterized metabolic pathways, such as coenzyme or amino acid biosynthesis. Riboswitch candidates whose ligands resist identification, collectively known as orphan riboswitches, are often associated with genes coding for proteins of unknown function, or genes for various proteins with no established link to one another. The cognate ligands for 16 former orphan riboswitch motifs have been identified to date. The successful pursuit of the ligands for these classes has provided insight into areas of biology that are not yet fully explored, such as ion homeostasis, signaling networks, and other previously underappreciated biochemical or physiological processes.
Read More: https://www.selleckchem.com/products/valproic-acid.html