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Sexual dimorphism affects various biological functions, including immune responses. However, the mechanisms by which sex alters immunity remain largely unknown. Using Caenorhabditis elegans as a model species, we showed that males exhibit enhanced immunity against various pathogenic bacteria through the upregulation of HLH-30 (Helix Loop Helix 30/TFEB (transcription factor EB)), a transcription factor crucial for macroautophagy/autophagy. Compared with hermaphroditic C. elegans, males displayed increased activity of HLH-30/TFEB, which contributed to enhanced antibacterial immunity. atg-2 (AuTophaGy (yeast Atg homolog) 2) upregulated by HLH-30/TFEB mediated increased immunity in male C. elegans. Thus, the males appear to be equipped with enhanced HLH-30/TFEB-mediated autophagy, which increases pathogen resistance, and this may functionally prolong mate-searching ability with reduced risk of infection.Abbreviations: atg-2: AuTophaGy (yeast Atg homolog) 2; FUDR: 5-fluoro-2’-deoxyuridine; GSEA: gene set enrichment analysis; HLH-30: Helix Loop Helix 30; LC3: microtubule associated protein 1 light chain 3; NGM: nematode growth media; RNA-seq: RNA sequencing; SEM: standard error of the mean; TFEB: transcription factor EB; WT: wild-type [ABSTRACT FROM AUTHOR]

Classical genetic analysis is invaluable for understanding the genetic interactions underlying specific phenotypes, but requires laborious and subjective experiments to characterize polygenic and quantitative traits. Contrarily, transcriptomic analysis enables the simultaneous and objective identification of multiple genes whose expression changes are associated with specific phenotypes. Here, we conducted transcriptomic analysis of genes crucial for longevity using datasets with daf‐2/insulin/IGF‐1 receptor mutant Caenorhabditis elegans. Our analysis unraveled multiple epistatic relationships at the transcriptomic level, in addition to verifying genetically established interactions. Our combinatorial analysis also revealed transcriptomic changes associated with longevity conferred by daf‐2 mutations. In particular, we demonstrated that the extent of lifespan changes caused by various mutant alleles of the longevity transcription factor daf‐16/FOXO matched their effects on transcriptomic changes in daf‐2 mutants. We identified specific aging‐regulating signaling pathways and subsets of structural and functional RNA elements altered by different genes in daf‐2 mutants. Lastly, we elucidated the functional cooperation between several longevity regulators, based on the combination of transcriptomic and molecular genetic analysis. These data suggest that different biological processes coordinately exert their effects on longevity in biological networks. Together our work demonstrates the utility of transcriptomic dissection analysis for identifying important genetic interactions for physiological processes, including aging and longevity. [ABSTRACT FROM AUTHOR]

Abstract: This paper suggests a novel method for improving the ductility of magnesium alloy sheets using a laser scanning treatment combined with a defocusing technique. The crystallographic orientation on both surface regions of the AZ31B magnesium alloy sheet processed using this method was changed from a strong basal texture to an almost random texture. The laser-scanned magnesium alloy sheet showed enhanced tensile elongation of up to 50% with a similar a tensile strength. [Copyright &y& Elsevier]

The evolutionary trajectory of glioblastoma (GBM) is a multifaceted biological process that extends beyond genetic alterations alone. Here, we perform an integrative proteogenomic analysis of 123 longitudinal glioblastoma pairs and identify a highly proliferative cellular state at diagnosis and replacement by activation of neuronal transition and synaptogenic pathways in recurrent tumors. Proteomic and phosphoproteomic analyses reveal that the molecular transition to neuronal state at recurrence is marked by post-translational activation of the wingless-related integration site (WNT)/ planar cell polarity (PCP) signaling pathway and BRAF protein kinase. Consistently, multi-omic analysis of patient-derived xenograft (PDX) models mirror similar patterns of evolutionary trajectory. Inhibition of B-raf proto-oncogene (BRAF) kinase impairs both neuronal transition and migration capability of recurrent tumor cells, phenotypic hallmarks of post-therapy progression. Combinatorial treatment of temozolomide (TMZ) with BRAF inhibitor, vemurafenib, significantly extends the survival of PDX models. This study provides comprehensive insights into the biological mechanisms of glioblastoma evolution and treatment resistance, highlighting promising therapeutic strategies for clinical intervention. [Display omitted] • Longitudinal proteogenomic analysis reveals increased neuronal state at recurrence • Neuronal transition associates with activation of WNT/PCP pathway and BRAF kinase • Resistance to therapy via neuronal transition is recapitulated in GBM PDX models • BRAF kinase inhibition impairs the neuronal transition of GBM at recurrence Kim et al. reveal that glioblastoma develops therapeutic resistance through a neuronal transition caused by changes in the WNT/PCP pathway and BRAF kinase, as shown by extensive proteogenomic analysis. Notably, inhibiting BRAF kinase disrupts this lethal transformation, offering potential therapeutic avenues. [ABSTRACT FROM AUTHOR]