Research on model of 6005A aluminum alloy

The deformation behavior of 6005A aluminum alloy at a strain rate of 0,01-10s-1, a deformation temperature of 673- 773K and a total strain of 0,8 was studied. Using the stress-strain data of 6005A aluminum alloy with a strain of 0,05-0,8, an Arrhenius-type constitutive model was established. And verified the accuracy of the model. The results show that: the flow stress of 6005A aluminum alloy increases with the increase of strain rate, and decreases with the increase of deformation temperature; Under different strains, the correlation coefficient (R) between the experimental value and the predicted value is as high as 98 %, and the average relative error (AARE) is less than 10 %, indicating that the established model has high predictability

First identification of PODXL nonsense mutations in autosomal dominant focal segmental glomerulosclerosis

Recently, a novel heterozygous missense mutation c.T1421G (p. L474R) in the PODXL gene encoding podocalyxin, was identified in an autosomal dominant focal segmental glomerulosclerosis (AD-FSGS) pedigree. However, this PODXL mutation appeared not to impair podocalyxin function and it is necessary to identify new PODXL mutations and determine their causative role for FSGS. In this study, we report the identification of a heterozygous nonsense PODXL mutations (Arg326X) in a Chinese pedigree featured by proteinuria and renal insufficiency with AD inheritance by whole exome sequencing (WES). Total mRNA and PODXL protein abundance were decreased in available peripheral blood cell samples of two affected patients undergoing hemodialysis, compared to those in healthy controls and hemodialysis controls without PODXL mutation. We identified another novel PODXL heterozygous nonsense mutation (c.C1133G; p.Ser378X) in a British-Indian pedigree of AD-FSGS by WES. In vitro study showed that, human embryonic kidney (HEK) 293T cells transfected with the pEGFP-PODXL-Arg326X or pEGFP-PODXL-Ser378X plasmid expressed significantly lower mRNA and PODXL protein compared to cells transfected with the wild-type plasmid. Blocking nonsense-mediated mRNA decay (NMD) significantly restored the amount of mutant mRNA and PODXL proteins, which indicated that the pathogenic effect of PODXL nonsense mutations is likely due to NMD, resulting in podocalyxin deficiency. Functional consequences caused by the PODXL nonsense mutations were inferred by siRNA knockdown in cultured podocytes and podocalyxin downregulation by siRNA resulted in decreased RhoA and ezrin activities, cell migration and stress fiber formation. Our results provided new data implicating heterozygous PODXL nonsense mutations in the development of FSGS