世居及移居高原青少年最大有氧能力的特征

本文报道海拔３４１７ｍ和４２８０ｍ地区世居藏族和移居汉族青少年运动状态下心肺功能的对比研究。结果显示：３４１７ｍ和４２８０ｍ世居藏族的最大氧耗量、无氧阈值及最大心输出量都明显大于汉族,血氧饱和度（Ｓａｏ２）随运动负荷的增加而降低。海拔３４１７ｍ藏、汉族的△Ｓａｏ２分别为７．４６％和１０．０３％,４２８０ｍ处为８．５７％和１３．７５％,最大心率随海拔升高而下降。研究提示,藏族青少年有较高的最大有氧能力,反映了他们对低氧环境的适应优势。     

A novel peroxiredoxin from the antagonistic endophytic bacterium Enterobacter sp. V1 contributes to cotton resistance against Verticillium dahliae

Plant and Soil - [Aims] To reveal the molecular mechanism of endophytic bacteria in Verticillium wilt-resistant cottons and deeply understand the interaction between soil and plants. [Methods]...     

AAV-Mediated Clarin-1 Expression in the Mouse Retina: Implications for USH3A Gene Therapy

Usher syndrome type III (USH3A) is an autosomal recessive disorder caused by mutations in clarin-1 (CLRN1) gene, leading to progressive retinal degeneration and sensorineural deafness. Efforts to develop therapies for preventing photoreceptor cell loss are hampered by the lack of a retinal phenotype in the existing USH3 mouse models and by conflicting reports regarding the endogenous retinal localization of clarin-1, a transmembrane protein of unknown function. In this study, we used an AAV-based approach to express CLRN1 in the mouse retina in order to determine the pattern of its subcellular localization in different cell types. We found that all major classes of retinal cells express AAV-delivered CLRN1 driven by the ubiquitous, constitutive small chicken β-actin promoter, which has important implications for the design of future USH3 gene therapy studies. Within photoreceptor cells, AAV-expressed CLRN1 is mainly localized at the inner segment region and outer plexiform layer, similar to the endogenous expression of other usher proteins. Subretinal delivery using a full strength viral titer led to significant loss of retinal function as evidenced by ERG analysis, suggesting that there is a critical limit for CLRN1 expression in photoreceptor cells. Taken together, these results suggest that CLRN1 expression is potentially supported by a variety of retinal cells, and the right combination of AAV vector dose, promoter, and delivery method needs to be selected to develop safe therapies for USH3 disorder.     

HPLC with cellulose Tris (3,5‐DimethylPhenylcarbamate) chiral stationary phase: Influence of coating times and coating amount on chiral discrimination

Coating cellulose tris (3,5‐dimethylphenylcarbamate) (CDMPC) on silica gels with large pores have been demonstrated as an efficient way for the preparation of chiral stationary phase (CSP) for high‐performance liquid chromatography (HPLC). During the process, a number of parameters, including the type of coating solvent, amount of coating, and the method for subsequent solvent removing, have been proved to affect the performance of the resultant CSPs. Coating times and the concentration of coating solution, however, also makes a difference to CSPs' performance by changing the arrangement of cellulose derivatives while remaining the coating amount constant, have much less been studied before, and thereby, were systematically investigated in this work. Results showed that CSPs with more coating times exhibited higher chiral recognition and column efficiency, suggesting that resolution was determined by column efficiency herein. Afterwards, we also investigated the effect of coating amount on the performance of CSPs, and it was shown that the ability of enantio‐recognition did not increase all the time as the coating amount; and four of seven racemates achieved best resolution when the coating amount reached to 18.37%. At the end, the reproducibility of CDMPC‐coated CSPs were further confirmed by two methods, ie, reprepared the CSP‐0.15‐3 and reevaluated the effect of coating times.     

The Role of Autophagy in Lamellar Body Formation and Surfactant Production in Type 2 Alveolar Epithelial Cells

The lamellar body (LB), a concentric structure loaded with surfactant proteins and phospholipids, is an organelle specific to type 2 alveolar epithelial cells (AT2). However, the origin of LBs has not been fully elucidated. We have previously reported that autophagy regulates Weibel-Palade bodies (WPBs) formation, and here we demonstrated that autophagy is involved in LB maturation, another lysosome-related organelle. We found that during development, LBs were transformed from autophagic vacuoles containing cytoplasmic contents such as glycogen. Fusion between LBs and autophagosomes was observed in wild-type neonate mice. Moreover, the markers of autophagic activity, microtubule-associated protein 1 light chain 3B (LC3B), largely co-localized on the limiting membrane of the LB. Both autophagy-related gene 7 (Atg7) global knockout and conditional Atg7 knockdown in AT2 cells in mice led to defects in LB maturation and surfactant protein B production. Additionally, changes in autophagic activity altered LB formation and surfactant protein B production. Taken together, these results suggest that autophagy plays a critical role in the regulation of LB formation during development and the maintenance of LB homeostasis during adulthood.     

Comparison of pulmonary vascular response to endogenous nitric oxide inhibition in sheep and pigs living at 2,300 m

To compare the role of nitric oxide in an adaptive process to chronic hypoxia, we examined the effects of endogenous nitric oxide synthase inhibition on pulmonary vascular tone in conscious sheep and pigs living at high altitude. Unanesthetized male sheep (n=6) and pigs (n=5), born and residing in the highlands of Qinghai Province, China (2,300–3,000 m a.s.l.) were studied at that altitude. Pulmonary artery pressure (P_pa), pulmonary artery wedge pressure (P_cwp), and cardiac output (CO) were measured. Pulmonary vascular resistance (PVR) was calculated as (P_pa—P_cwp)/CO. Using a climatic chamber, hemodynamic measurements during exposures to atmospheric pressures corresponding to altitudes of 0, 2,300, and 4,500 m a.s.l. were performed with and without NO inhibition, using N^w-nitro-l-argine (NLA; 20 mg kg^–1), a potent stereospecific competitive inhibitor of nitric oxide synthase. P_pa and PVR at baseline (2,300 m) and during hypoxic exposure (4,500 m) were significantly higher in pigs than in sheep. After NLA administration, P_pa increased and CO decreased in both animals, resulting in significantly increased PVR at baseline and during hypoxic exposure. However, there were no significant differences in the percent increase in basal or hypoxic PVR after NLA administration between sheep and pigs. We conclude that augmented endogenous NO production could contribute to the regulation of pulmonary vascular tone at high altitude in sheep and pigs. However, it is unlikely that NO is responsible for the different pulmonary vascular tones between sheep and pigs at basal condition at moderately high altitude.Communicated by G. Heldmaier     

PFTK1 Promotes Gastric Cancer Progression by Regulating Proliferation,Migration and Invasion

PFTK1, also known as PFTAIRE1, CDK14, is a novel member of Cdc2-related serine/threonine protein kinases. Recent studies show that PFTK1 is highly expressed in several malignant tumors such as hepatocellular carcinoma, esophageal cancer, breast cancer, and involved in regulation of cell cycle, tumors proliferation, migration, and invasion that further influence the prognosis of tumors. However, the expression and physiological significance of PFTK1 in gastric cancer remain unclear. In this study, we analyzed the expression and clinical significance of PFTK1 by Western blot in 8 paired fresh gastric cancer tissues, nontumorous gastric mucosal tissues and immunohistochemistry on 161 paraffinembedded slices. High PFTK1 expression was correlated with the tumor grade, lymph node invasion as well as Ki-67. Through Cell Counting Kit (CCK)-8 assay, flow cytometry, colony formation, wound healing and transwell assays, the vitro studies demonstrated that PFTK1 overexpression promoted proliferation, migration and invasion of gastric cancer cells, while PFTK1 knockdown led to the opposite results. Our findings for the first time supported that PFTK1 might play an important role in the regulation of gastric cancer proliferation, migration and would provide a novel promising therapeutic strategy against human gastric cancer.     

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.