A monomeric structure of human TMEM63A protein.

OSCA/TMEM63 is a newly identified family of mechanically activated (MA) ion channels in plants and animals, respectively, which convert physical forces into electrical signals or trigger intracellular cascades and are essential for eukaryotic physiology. OSCAs and related TMEM16s and transmembrane channel-like (TMC) proteins form homodimers with two pores. However, the molecular architecture of the mammalian TMEM63 proteins remains unclear. Here we elucidate the structure of human TMEM63A in the presence of calcium by single particle cryo-EM, revealing a distinct monomeric architecture containing eleven transmembrane helices. It has structural similarity to the single subunit of the Arabidopsis thaliana OSCA proteins. We locate the ion permeation pathway within the monomeric configuration and observe a nonprotein density resembling lipid. These results lay a foundation for understanding the structural organization of OSCA/TMEM63A family proteins.

The mechanism of ferroptosis and its related diseases.

Ferroptosis, a regulated form of cellular death characterized by the iron-mediated accumulation of lipid peroxides, provides a novel avenue for delving into the intersection of cellular metabolism, oxidative stress, and disease pathology. We have witnessed a mounting fascination with ferroptosis, attributed to its pivotal roles across diverse physiological and pathological conditions including developmental processes, metabolic dynamics, oncogenic pathways, neurodegenerative cascades, and traumatic tissue injuries. By unraveling the intricate underpinnings of the molecular machinery, pivotal contributors, intricate signaling conduits, and regulatory networks governing ferroptosis, researchers aim to bridge the gap between the intricacies of this unique mode of cellular death and its multifaceted implications for health and disease. In light of the rapidly advancing landscape of ferroptosis research, we present a comprehensive review aiming at the extensive implications of ferroptosis in the origins and progress of human diseases. This review concludes with a careful analysis of potential treatment approaches carefully designed to either inhibit or promote ferroptosis. Additionally, we have succinctly summarized the potential therapeutic targets and compounds that hold promise in targeting ferroptosis within various diseases. This pivotal facet underscores the burgeoning possibilities for manipulating ferroptosis as a therapeutic strategy. In summary, this review enriched the insights of both investigators and practitioners, while fostering an elevated comprehension of ferroptosis and its latent translational utilities. By revealing the basic processes and investigating treatment possibilities, this review provides a crucial resource for scientists and medical practitioners, aiding in a deep understanding of ferroptosis and its effects in various disease situations.

Antibacterial effect of synthetic ultra-short lipopeptide on Streptococcus agalactiae and its active on bacterial mastitis in mice.

Streptococcus agalactiae mastitis is one of the significant threats to the milk industry. The traditional antibiotic treatment method is easy to cause the emergence of resistant strains, and the problem of drug residue is increasingly severe. In this study, we designed and synthesized five lipopeptides. The antibacterial activity of different molecular structure lipopeptides against Streptococcus agalactiae was detected. Furthermore, the mouse mastitis model was established using Streptococcus agalactiae. The lipopeptides with better antibacterial effect were selected for the treatment experiment to evaluate the application value in the treatment of mastitis. The results showed that 4 of the synthesized lipopeptides had specific antibacterial activity. SLP3 and SLP4 have an excellent antibacterial effect and can treat murine mastitis caused by Streptococcus agalactiae infection within the safe concentration range. The results of this study can provide an excellent experimental basis for new antibiotics and clinical application in the treatment of dairy cow mastitis.

Identification of G protein-coupled receptors required for vitellogenesis and egg development in an insect with panoistic ovary.

G protein-coupled receptors (GPCRs), a superfamily of integral transmembrane proteins regulate a variety of physiological processes in insects. Juvenile hormone (JH) is known to stimulate Vitellogenin (Vg) synthesis in the fat body, secretion into the hemolymph and uptake by developing oocytes. However, the role of GPCRs in JH-dependent insect vitellogenesis and oocyte maturation remains elusive. In the present study, we performed transcriptomic analysis and RNA interference (RNAi) screening in vitellogenic females of the migratory locust Locusta migratoria. Of 22 GPCRs identified in ovarian transcriptome, LGR4, OR-A1, OR-A2, Mthl1, Mthl5 and Smo were most abundant in the ovary. By comparison, mAChR-C expressed at higher levels in the fat body, whereas Oct/TyrR, OARß, AdoR and ADGRA3 were at higher expression levels in the brain. Our RNAi screening demonstrated that knockdown of six GPCRs resulted in defective phenotypes of Vg accumulation in developing oocytes, accompanied by blocked ovarian development and impaired oocyte maturation. While LGR4 and Oct/TyrR appeared to control Vg synthesis in the fat body, OR-A1, OR-A2, mAChR-C and CirlL regulated Vg transportation and uptake. The findings provide fundamental evidence for deciphering the regulatory mechanisms of GPCRs in JH-stimulated insect reproduction.

[Recurrent Angelman syndrome caused by a rare partial deletion of UBE3A gene].

OBJECTIVE: To provide genetic testing for two brothers with mental retardation and epilepsy. METHODS: Array comparative genomic hybridization (aCGH) was used to detect copy number variations in the two patients, their parents and maternal grandparents. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) was utilized to delineate the deleted region in the pedigree. RESULTS: A 138 kb deletion in 15q11.2 region was detected by aCGH in both patients, which encompassed part of the UBE3A gene. MS-MLPA has narrowed down the region to exons 8 to 14 of the UBE3A gene. The same deletion was also found in their mother and grandfather. CONCLUSION: The pathogenesis of this rare form of recurrent Angelman syndrome may be attributed to the partial deletion of maternal UBE3A gene.

Serial expression and activity analysis of LNK-16: a bovine antimicrobial peptide analogue.

Indolicidin is a broad-spectrum antimicrobial peptide (AMP) with great therapeutic potential; however, high manufacturing costs associated with industrial-scale chemical synthesis have limited its delivery. Therefore, the use of recombinant DNA technology to produce this peptide is urgently needed. In this study, a new methodology for the large-scale production of a novel bovine AMP was developed. LNK-16 is an analogue of indolicidin that contains a kallikrein protease site at its C-terminus. The amino acid sequence of LNK-16 was synthesized using Escherichia coli-preferred codons. Three copies of the target gene were assembled in series by overlapping PCR and cloned into pET-30a(+) for the expression of His-(LNK-16)(3) in E. coli BL21 (DE3) cells. The expressed fusion protein His-(LNK-16)(3) was purified by Ni(2+)-chelating chromatography and then cleaved by kallikrein to release LNK-16. The recombinant LNK-16 peptide showed antimicrobial activity similar to that of chemically synthesized LNK-16 and indolicidin. Together, these data indicate that the use of serial expression can improve the large-scale production of AMPs for clinical and research applications.