Insulin receptor substrate-4 enhances insulin-like growth factor-I-induced cell proliferation.

The insulin receptor substrates (IRSs)-1-4 play important roles in signal transduction emanating from the insulin and insulin-like growth factor (IGF)-I receptors. IRS-4 is the most recently characterized member, which has been found primarily in human cells and tissues. It interacts with SH2-containing proteins such as phosphatidylinositol 3'-kinase (PI3K), Grb2, Crk-II, and CrkL. In this study, we transfected IRS-4 in mouse NIH-3T3 cells that overexpress IGF-I receptors. Clones expressing IRS-4 showed enhanced cellular proliferation when cells were cultured in 1% fetal bovine serum without added IGF-I. Addition of IGF-I enhanced cellular proliferation in cells overexpressing the IGF-I receptor alone but had an even greater proliferative effect in cells overexpressing both the IGF-I receptors and IRS-4. When etoposide and methylmethane sulfonate (MMS), both DNA damaging agents, were added to the cells, they uniformly induced cell cycle arrest. Fluorescence-activated cell sorter analysis demonstrated that the arrest of the cell cycle occurred at the G(1) checkpoint, and furthermore no significant degree of apoptosis was demonstrated with the use of either agent. In cells, overexpressing IGF-I receptors alone, IGF-I addition enhanced cellular proliferation, even in the presence of etoposide and MMS. In cells overexpressing IGF-I receptors and IRS-4, the effect of IGF-I in overcoming the cell cycle arrest was even more pronounced. These results suggest that IRS-4 is implicated in the IGF-I receptor mitogenic signaling pathway.     

Solution structure of the N‐terminal domain of DC‐UbP/UBTD2 and its interaction with ubiquitin

DC‐UbP/UBTD2 is a ubiquitin (Ub) domain‐containing protein first identified from dendritic cells, and is implicated in ubiquitination pathway. The solution structure and backbone dynamics of the C‐terminal Ub‐like (UbL) domain were elucidated in our previous work. To further understand the biological function of DC‐UbP, we then solved the solution structure of the N‐terminal domain of DC‐UbP (DC‐UbP_N) and studied its Ub binding properties by NMR techniques. The results show that DC‐UbP_N holds a novel structural fold and acts as a Ub‐binding domain (UBD) but with low affinity. This implies that the DC‐UbP protein, composing of a combination of both UbL and UBD domains, might play an important role in regulating protein ubiquitination and delivery of ubiquitinated substrates in eukaryotic cells.     

Primate stem cells: bridge the translation from basic research to clinic application

A growing body of literature has shown that stem cells are very effective for the treatment of degenerative diseases in rodents but these exciting results have not translated to clinical practice. The difference results from the divergence in genetic, metabolic, and physiological phenotypes between rodents and humans. The high degree of similarity between non-human primates(NHPs) and humans provides the most accurate models for preclinical studies of stem cell therapy. Using a NHP model to understand the following key issues, which cannot be addressed in humans or rodents, will be helpful for extending stem cell applications in the basic science and the clinic. These issues include pluripotency of primate stem cells, the safety and efficiency of stem cell therapy, and transplantation procedures of stem cells suitable for clinical translation. Here we review studies of the above issues in NHPs and current challenges of stem cell applications in both basic science and clinical therapies. We propose that the use of NHP models, in particular combining the serial production and transplantation procedures of stem cells is the most useful for preclinical studies designed to overcome these challenges.     

Host-Parasite Interactions and Purifying Selection in a Microsporidian Parasite of Honey Bees

To clarify the mechanisms of Nosema ceranae parasitism, we deep-sequenced both honey bee host and parasite mRNAs throughout a complete 6-day infection cycle. By time-series analysis, 1122 parasite genes were significantly differently expressed during the reproduction cycle, clustering into 4 expression patterns. We found reactive mitochondrial oxygen species modulator 1 of the host to be significantly down regulated during the entire infection period. Our data support the hypothesis that apoptosis of honey bee cells was suppressed during infection. We further analyzed genome-wide genetic diversity of this parasite by comparing samples collected from the same site in 2007 and 2013. The number of SNP positions per gene and the proportion of non-synonymous substitutions per gene were significantly reduced over this time period, suggesting purifying selection on the parasite genome and supporting the hypothesis that a subset of N. ceranae strains might be dominating infection.     

植物蛋白SUMO化修饰检测方法

SUMO化是一种重要的蛋白质翻译后修饰,对植物正常生长发育不可或缺。到目前为止已筛选到上千个可能的SUMO底物,但由于SUMO化修饰水平普遍很低,其生物学功能研究相对较少。该文详细描述了检测蛋白SUMO化修饰的常用方法,包括体外和体内SUMO化实验,以及SUMO化修饰位点的检测方法,旨在为深入研究植物蛋白SUMO化修饰提供技术支持。     

Modulatory effect of Lactobacillus acidophilus KLDS 1.0738 on intestinal short‐chain fatty acids metabolism and GPR41/43 expression in β‐lactoglobulin–sensitized mice

We investigated the correlation between the beneficial effect of Lactobacillus acidophilus on gut microbiota composition, metabolic activities, and reducing cow's milk protein allergy. Mice sensitized with β‐lactoglobulin (β‐Lg) were treated with different doses of L. acidophilus KLDS 1.0738 for 4 weeks, starting 1 week before allergen induction. The results showed that intake of L. acidophilus significantly suppressed the hypersensitivity responses, together with increased fecal microbiota diversity and short‐chain fatty acids (SCFAs) concentration (including propionate, butyrate, isobutyrate, and isovalerate) when compared with the allergic group. Moreover, treatment with L. acidophilus induced the expression of SCFAs receptors, G‐protein–coupled receptors 41 (GPR41) and 43 (GPR43), in the spleen and colon of the allergic mice. Further analysis revealed that the GPR41 and GPR43 messenger RNA expression both positively correlated with the serum concentrations of transforming growth factor‐β and IFN‐γ (p < .05), but negatively with the serum concentrations of IL‐17, IL‐4, and IL‐6 in the L. acidophilus–treated group compared with the allergic group (p < .05). These results suggested that L. acidophilus protected against the development of allergic inflammation by improving the intestinal flora, as well as upregulating SCFAs and their receptors GPR41/43.