CHIP facilitates ubiquitination of inducible nitric oxide synthase and promotes its proteasomal degradation

Inducible nitric oxide synthase (iNOS) is responsible for nitric oxide (NO) synthesis from l-arginine in response to inflammatory mediators. It is reported that iNOS is degraded mainly by the ubiquitin-proteasome pathway in RAW264.7 cells and human embryonic kidney (HEK) 293 cells. In this study, we showed that iNOS was ubiquitinated and degraded dependent on CHIP (COOH terminus of heat shock protein 70-interacting protein), a chaperone-dependent ubiquitin ligase. The results from overexpression and RNAi experiments demonstrated that CHIP decreased the protein level of iNOS, shortened the half-life of iNOS and attenuated the production of NO. Furthermore, CHIP promoted ubiquitination and proteasomal degradation of iNOS by associating with iNOS. These results suggest that CHIP plays an important role in regulation iNOS activity.     

鄂西清风藤化学成分及其α-葡萄糖苷酶抑制活性研究

为了研究鄂西清风藤在降低血糖方面的物质基础,该研究采用硅胶柱色谱、Sephadex LH-20凝胶柱色谱、半制备型高效液相色谱和重结晶等分离纯化方法从鄂西清风藤中提取分离化合物,并采用PNPG法筛选体外活性。结果表明:从鄂西清风藤95%乙醇提取物中分离得到10个单体化合物,分别为Pronuciferine (1)、(6R, 6aS, P)-Isocorydine (2)、N-methylhernovine (3)、N-formyldehydroanonain (4)、Roemerine(5)、(-)-Tetrahydropalmatine(6)、N-feruloyltyramine (7)、N-p-coumaroyltyramine (8)、Quercetin(9)、Dibutylphthalate(10)。所有化合物均为首次从该植物中分离得到。采用PNPG法筛选体外活性,研究结果显示化合物7、8、9具有明显的α-葡萄糖苷酶抑制活性,IC_(50)值为6.1～38.8μmol·L~(-1),其中化合物7、8的活性是阳性药阿卡波糖的40倍。该研究结果丰富了鄂西清风藤化学成分研究,为该植物在降血糖方面的开发提供了科学依据。     

新生儿病房铜绿假单胞菌感染状况及耐药性的5年监测

目的监测2005年至2009年间铜绿假单胞菌在新生儿病房的分离情况及其耐药趋势,为临床感染的预防和治疗提供实验室依据。方法回顾分析2005年至2009年间新生儿病房所有标本中铜绿假单胞菌的分离率,菌株在标本中的分布以及对常见的13种抗菌药物的耐药性。结果铜绿假单胞菌的分离率有逐年升高的趋势,从2005年的1.19%增至2009年的5.16%;其在呼吸道标本中的分离率最高(86.3%),在其他标本中的检出率都相对较低。铜绿假单胞菌的耐药株也有逐年增多的趋势,特别是对复方新诺明的耐药性已发展成为全部耐药。结论铜绿假单胞菌在新生儿病房的分离率在不断地增加,其对多种抗菌药物有较高的耐药性,加之新生儿免疫系统发育不完善,应引起临床医师的高度重视。     

A novel protein,Rsf1/Pxd1, is critical for the single‐strand annealing pathway of double‐strand break repair in Schizosaccharomyces pombe

The process of single‐strand annealing (SSA) repairs DNA double‐strand breaks that are flanked by direct repeat sequences through the coordinated actions of a series of proteins implicated in recombination, mismatch repair and nucleotide excision repair (NER). Many of the molecular and mechanistic insights gained in SSA repair have principally come from studies in the budding yeast Saccharomyces cerevisiae. However, there is little molecular understanding of the SSA pathway in the fission yeast Schizosaccharomyces pombe. To further our understanding of this important process, we established a new chromosome‐based SSA assay in fission yeast. Our genetic analyses showed that, although many homologous components participate in SSA repair in these species indicating that some evolutionary conservation, Saw1 and Slx4 are not principal agents in the SSA repair pathway in fission yeast. This is in marked contrast to the function of Saw1 and Slx4 in budding yeast. Additionally, a novel genus‐specific protein, Rsf1/Pxd1, physically interacts with Rad16, Swi10 and Saw1 in vitro and in vivo. We find that Rsf1/Pxd1 is not required for NER and demonstrate that, in fission yeast, Rsf1/Pxd1, but not Saw1, plays a critical role in SSA recombination.     

Modeling Coevolution between Language and Memory Capacity during Language Origin

Memory is essential to many cognitive tasks including language. Apart from empirical studies of memory effects on language acquisition and use, there lack sufficient evolutionary explorations on whether a high level of memory capacity is prerequisite for language and whether language origin could influence memory capacity. In line with evolutionary theories that natural selection refined language-related cognitive abilities, we advocated a coevolution scenario between language and memory capacity, which incorporated the genetic transmission of individual memory capacity, cultural transmission of idiolects, and natural and cultural selections on individual reproduction and language teaching. To illustrate the coevolution dynamics, we adopted a multi-agent computational model simulating the emergence of lexical items and simple syntax through iterated communications. Simulations showed that: along with the origin of a communal language, an initially-low memory capacity for acquired linguistic knowledge was boosted; and such coherent increase in linguistic understandability and memory capacities reflected a language-memory coevolution; and such coevolution stopped till memory capacities became sufficient for language communications. Statistical analyses revealed that the coevolution was realized mainly by natural selection based on individual communicative success in cultural transmissions. This work elaborated the biology-culture parallelism of language evolution, demonstrated the driving force of culturally-constituted factors for natural selection of individual cognitive abilities, and suggested that the degree difference in language-related cognitive abilities between humans and nonhuman animals could result from a coevolution with language.     

Increased Notch Signaling Enhances Radioresistance of Malignant Stromal Cells Induced by Glioma Stem/ Progenitor Cells

Background

Host malignant stromal cells induced by glioma stem/progenitor cells were revealed to be more radiation-resistant than the glioma stem/progenitor cells themselves after malignant transformation in nude mice. However, the mechanism underlying this phenomenon remains unclear.

Methods

Malignant stromal cells induced by glioma stem/progenitor cell 2 (GSC-induced host brain tumor cells, ihBTC2) were isolated and identified from the double color-coded orthotopic glioma nude mouse model. The survival fraction at 2 Gy (SF2) was used to evaluate the radiation resistance of ihBTC2, the human glioma stem/progenitor cell line SU3 and its radiation-resistant sub-strain SU3-5R and the rat C6 glioma cell line. The mRNA of Notch 1 and Hes1 from ihBTC2 cells were detected using qPCR before and after 4 Gy radiation. The expression of the Notch 1, pAkt and Bcl-2 proteins were investigated by Western blot. To confirm the role of the Notch pathway in the radiation resistance of ihBTC2, Notch signaling blocker gamma secretase inhibitors (GSIs) were used.

Results

The ihBTC2 cells had malignant phenotypes, such as infinite proliferation, hyperpentaploid karyotype, tumorigenesis in nude mice and expression of protein markers of oligodendroglia cells. The SF2 of ihBTC2 cells was significantly higher than that of any other cell line (P<0.05, n = 3). The expression of Notch 1 and Hes1 mRNAs from ihBTC2 cells was significantly increased after radiation. Moreover, the Notch 1, pAkt and Bcl-2 proteins were significantly increased after radiation (P<0.05, n = 3). Inhibition of Notch signaling markedly enhanced the radiosensitivity of ihBTC2 cells.

Conclusions

In an orthotopic glioma model, the malignant transformation of host stromal cells was induced by glioma stem/progenitor cells. IhBTC2 cells are more radiation-resistant than the glioma stem/progenitor cells, which may be mediated by activation of the Notch signaling pathway.