Novel mutation of type-1 insulin-like growth factor receptor (IGF-1R) gene in a severe short stature pedigree identified by targeted next-generation sequencing

Insulin-like growth factor receptor (IGF-1R) deficiency is a rare form of short stature, and is difficult to clinically diagnose. Targeted next-generation sequencing (NGS) allows for the rapid and inexpensive assessment of short stature. We identified mutations in the pedigree of a Chinese boy with severe short stature using targeted NGS; we then assessed the clinical characteristicsand evaluated the efficacy of growth hormone therapy. NGS analysis revealed a novel heterozygous missense mutation in exon3 (c.926C>T, p.S309L) of the type-I IGF-1R gene in the proband, which was inherited from the mother. The proband, mother and grandfather suffered from severe growth failure. After recombinant human growth hormone therapy, the patient’s growth rate increased. The novel missensemutation in IGF-1R (c.926C > T, p.S309L) is associated with severe short stature in Chinese individuals. Targeted NGS may enable efficient diagnosis and genetic consultation of children with short stature.

The Expression and Activity of MMPs Are Increased in Residual Tumor Tissues after the Termination of Immunotherapy / 华中科技大学学报（医学）（英德文版）

To investigate the invasive ability of the residual tumor cells after immunotherapy and explore the feasible approach suppressing the invasion, mice were inoculated with B16 cells, and then treated by gene therapy with p4-1BBL/psPD-1 or IFN-γ. The production and activities of MMP-9 and MMP-2 in residual tumor tissues were analyzed with gelatin zymography 1 day and 7 days after the termination of the immunotherapy. The production of MMP-9 and MMP-2 by B16 cells treated with IFN-γ was also analyzed. IFN-γ-treated B 16 cells were inoculated to mice via subcutaneous injection.The invasion of tumor to muscular tissue was analyzed. Gene therapy with CH50 was used to suppress the invasive growth of tumor. The results showed that the expression and the activities of MMP-9 and MMP-2 were significantly increased 7 days after the end of immunotherapy. The response of tumor cells to ECM molecules was intensified after the removal of IFN-γ, resulting in significant increase of both the production and activities of MMP-9 and MMP-2, and the increased invasion of tumor. Gene therapy with CH50 effectively suppressed the invasive growth of tumor. It is concluded that the termination of immunotherapy may result in a higher metastatic potential of residual tumor cells. Suppressing tumor invasion by suitable treatment will improve the efficacy of immunotherapy.

The Progress on The Ubiquitin 26S Proteasome Pathway in Plants / 中国生物工程杂志

Selective protein degradation by the ubiquitin 26S proteasome pathway has emerged as a key regulatory mechanism in a wide variety of cellular processes.The ubiquitin/26S proteosome pathway mainly consists of ubiquitin activating enzyme(E1),ubiquitin conjugating enzyme(E2),ubiquitin protein ligase(E3),and 26S proteasome.In an ATP-dependent reaction,uibquitin(Ub) is conjugated to E1,the activated Ub is then transferred to an E2.Finally,the Ub-E2 intermediate delivers the Ub to the target protein by E3 recognition.Polyubiquinated proteins are eventually degraded by the 26S proteasome.In plants,regulated protein degradation by /26S proteasome pathway contributes significantly to development by affecting a wide range of progress,including hormone signaling,photomorphogenesis,self-incompatibility and cell cycle.The recent progress towards understanding the role of the Ub/26S proteasome pathway during plant development was reviewed.