Molecular characterization of two pedigrees with maternally inherited diabetes mellitus

Mutations in mitochondrial DNA (mtDNA), especially in mitochondrial tRNA (mt-tRNAs) genes, play important roles in maternally inherited type 2 diabetes mellitus (T2DM), but the molecular mechanism remains unclear. In this study, two families with maternally transmitted T2DM are underwent clinical, genetic and molecular assessments. The mtDNA mutations are screened by direct sequencing. Furthermore, the phylogenetic conservation analysis and pathogenicity scoring system were used to evaluate the pathogenic status of mt-tRNA mutations. Interestingly, matrilineal relatives exhibit variable severity of DM, in particular, the age at onset of DM varies from 39 to 60 years, with an average of 50 years. Screening for the entire mitochondrial genomes identifies the existence of tRNAThr A15901G and C15926T mutations, as well as 59 variants belonging to mtDNA haplogroups D2 and C4c. Notably, the m.A15901G mutation is located at D-arm of tRNAThr, whereas the m.C15926T mutation resides in the anticodon loop of tRNAThr, both of these positions are well conserved and critical for tRNA functions. Thus, the m.A15901G and m.C15926T mutations may impair mitochondrial translation and lead to mitochondrial dysfunctions. However, the fail to identify any other functional variants indicate that mitochondrial haplogroup may not play a role in T2DM. Hence, tRNAThr A15901G and C15926T may be the novel mutations associated with T2DM

Softening due to Grain Boundary Cavity Formation and its Competition with Hardening in Helium Implanted Nanocrystalline Tungsten

Abstract The unique ability of grain boundaries to act as effective sinks for radiation damage plays a significant role in nanocrystalline materials due to their large interfacial area per unit volume. Leveraging this mechanism in the design of tungsten as a plasma-facing material provides a potential pathway for enhancing its radiation tolerance under fusion-relevant conditions. In this study, we explore the impact of defect microstructures on the mechanical behavior of helium ion implanted nanocrystalline tungsten through nanoindentation. Softening was apparent across all implantation temperatures and attributed to bubble/cavity loaded grain boundaries suppressing the activation barrier for the onset of plasticity via grain boundary mediated dislocation nucleation. An increase in fluence placed cavity induced grain boundary softening in competition with hardening from intragranular defect loop damage, thus signaling a new transition in the mechanical behavior of helium implanted nanocrystalline tungsten