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Protein arginine methyltransferase 6 (PRMT6) is a well-characterized epigenetic regulator that methylates histone H3 at arginine 2 (H3R2me2a) in both promoter and enhancer regions, thereby modulating transcriptional initiation. We report here that PRMT6 also regulates gene expression at the post-transcriptional level in the neural pluripotent state and during neuronal differentiation of NT2/D1 cells. PRMT6 knockout causes widespread alternative splicing changes in NT2/D1 cells, most frequently cassette exon alterations. Most of the PRMT6-dependent splicing targets are not transcriptionally affected by the enzyme and regulated in an H3R2me2a-independent manner. However, for a small subset of splicing events, the PRMT6-mediated deposition of H3R2me2a overlaps with the splice site, suggesting a potential dual function in both transcriptional and co-/post-transcriptional regulation. The splicing targets of PRMT6 include ribosomal proteins, splicing factors, and chromatin-modifying enzymes such as PRMT4, DNMT3B, and ASH2L, some of which are associated with differentiation decisions. Taken together, our results in NT2/D1 cells show that PRMT6 exerts predominantly H3R2me2a-independent functions in RNA splicing, which may contribute to pluripotency and neuronal identity., (© 2025 Eudenbach et al.)

RNA splicing enables the functional adaptation of cells to changing contexts. Impaired splicing has been associated with diseases, including retinitis pigmentosa, but the underlying molecular mechanisms and cellular responses remain poorly understood. In this work, we report that deficiency of ubiquitin-specific protease 39 (USP39) in human cell lines, zebrafish larvae, and mice led to impaired spliceosome assembly and a cytotoxic splicing profile characterized by the use of cryptic 5' splice sites. Disruptive cryptic variants evaded messenger RNA (mRNA) surveillance pathways and were translated into misfolded proteins, which caused proteotoxic aggregates, endoplasmic reticulum (ER) stress, and, ultimately, cell death. The detrimental consequence of splicing-induced proteotoxicity could be mitigated by up-regulating the ubiquitin-proteasome system and selective autophagy. Our findings provide insight into the molecular pathogenesis of spliceosome-associated diseases.

High purity natural quartz is used as raw material for the manufacture of quartz glass crucibles for solar-grade silicon ingots production. One key challenge for cost-effective ingot pulling is to maximise the ability of the crucible to withstand the process conditions ( i.e. , silicon load and temperature about 1500 °C) without deformation. In order to improve this glass property, aluminium was coated into the raw quartz materials. Our results showed that an addition of up to 1000 wt ppm Al substantially reduces deformation of glass and improves viscosity at high temperatures. This is likely due to the reduction of stability of OH groups in the quartz glass as well as a trapping effect of aluminium on oxygen vacancies. This hypothesis is also supported by atomistic models. In the presence of Al, formation energies of silanol groups (Si-O-H) were much higher than without. Furthermore, the presence of Al in the structure significantly reduces mobility of the oxygen vacancies. It was also found that formation of oxygen vacancies hinders cristobalite crystallisation, on the other hand, Al atoms themselves induce local weakening of the Si-O bond which accelerates the kinetics of the reconstructive phase transition from glassy state to crystalline phase. This was also confirmed experimentally in our study., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Direct current glow discharge mass spectrometry with an indium-based secondary cathode technique is used to analyze solid, nonconducting, fused high-purity quartz regarding metallic impurities of relevance to the solar industry. Details of the analytical routines are presented. In this work, the secondary cathode design and glow discharge conditions are optimized beyond the commonly applied practices. In addition, relative sensitivity factors (RSFs) for these optimized conditions are established and compared to previously published results. The results indicate that the technique enables stable measurements with detection limits down to the part per billion (ppb) range., (© 2021 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons Ltd.)

The mosquito Culex erythrothorax Dyar is a West Nile virus (WNV) vector that breeds in wetlands with emergent vegetation. Urbanization and recreational activities near wetlands place humans, birds and mosquitoes in close proximity, increasing the risk of WNV transmission. Adult Cx. erythrothorax abundance peaked in a wetland bordering the San Francisco Bay of California (USA) during the first 3 hours after sunset (5527 ± 4070 mosquitoes / trap night) while peak adult Culex tarsalis Coquillett abundance occurred during the subsequent 3 h period (83 ± 30 Cx. tarsalis). When insecticide resistance was assessed using bottle bioassay, Cx. erythrothorax was highly sensitive to permethrin, naled, and etofenprox insecticides compared to a strain of Culex pipiens that is susceptible to insecticides (LC50 = 0.35, 0.71, and 4.1 μg/bottle, respectively). The Cx. erythrothorax were 2.8-fold more resistant to resmethrin, however, the LC50 value was low (0.68 μg/bottle). Piperonyl butoxide increased the toxicity of permethrin (0.5 μg/bottle) and reduced knock down time, but a higher permethrin concentration (2.0 μg/bottle) did not have similar effects. Bulk mixed-function oxidase, alpha-esterase, or beta-esterase activities in mosquito homogenates were higher in Cx. erythrothorax relative to the Cx. pipiens susceptible strain. There was no difference in the activity of glutathione S-transferase between the two mosquito species and insensitive acetylcholine esterase was not detected. Larvicides that were applied to the site had limited impact on reducing mosquito abundance. Subsequent removal of emergent vegetation in concert with larvicide applications and reduced daily environmental temperature substantially reduced mosquito abundance. To control Cx. erythrothorax in wetlands, land managers should consider vegetation removal so that larvicide can efficiently enter the water. Vector control agencies may more successfully control adult viremic Cx. erythrothorax that enter nearby neighborhoods by applying adulticides during the 3 h that follow sunset., Competing Interests: The authors have declared that no competing interests exist.

We retrospectively investigated the efficacy of high dose omeprazole compared to a combined therapy of famotidine, pirenzepine and antacid for acute upper gastrointestinal hemorrhage (AUGIH) also adjuvant to endoscopic injection therapy if indicated. The clinical course of AUGIH was evaluated, if emergency endoscopy revealed lesions substantially dependent on intragastric acidity with respect to pathogenesis and/or healing (peptic ulcer, erosive gastroduodenitis, reflux-esophagitis, Mallory-Weiss tears) and patients either received a combined therapy of famotidine (20 mg i.v. every 12 hrs), pirenzepine (10 mg i.v. every 12 hrs) and antacid (control group: n = 96) or omeprazole (40 mg i.v. every 6 hrs; omeprazole group: n = 100). Rate of rebleeding was lower in the omeprazole group without reaching significance (12 vs. 21; p = 0.06). No difference was found for rates of operation (6 vs. 6; p = 0.94), death from bleeding (5 vs. 9; p = 0.22), transfusions ([mean +/- SD] 3.3 +/- 5.0 vs. 3.2 +/- 5.7; p = 0.51) and hospitalisation ([mean +/- SD] 26.8 +/- 12.1 vs. 27.8 +/- 16.0 days; p = 0.88). Considering prognostic risk factors (age > or = 65, actively bleeding lesion, initial state of shock) logistic regression showed that high dose omeprazole inhibited rebleeding (p = 0.01) but had no effect as regards surgery or mortality. Within two selected subgroups defined by additional criteria (no endoscopic treatment and anamnestic peptic lesion) omeprazole-treated cases showed lower rates of rebleeding (3/49 vs. 12/54, p " 0.02 and 3/44 vs. 13/48, p = 0.01 resp.) and death from bleeding (0/46 vs. 6/50, p = 0.03 and 0/43 vs. 5/45, p = 0.03 resp.).(ABSTRACT TRUNCATED AT 250 WORDS)