A diterpenoid derivate compound targets selenocysteine of thioredoxin reductases and induces Bax/Bak-independent apoptosis

We have previously shown that the natural diterpenoid derivative S3 induced Bim upregulation and apoptosis in a Bax/Bak-independent manner. However, the exact molecular target(s) of S3 and the mechanism controlling Bim upregulation are still not clear. Here, we identify that S3 targets the selenoproteins TrxR1 and TrxR2 at the selenocysteine residue of the reactive center of the enzymes and inhibits their antioxidant activities. Consequently, cellular ROS is elevated, leading to the activation of FOXO3a, which contributes to Bim upregulation in Bax/Bak-deficient cells. Moreover, S3 retards tumor growth in subcutaneous xenograft tumors by inhibiting TrxR activity in vivo. Our studies delineate the signaling pathway controlling Bim upregulation, which results in Bax/Bak-independent apoptosis and provide evidence that the compounds can act as anticancer agents based on mammalian TrxRs inhibition.     

Prion Interaction with the 37-kDa/67-kDa Laminin Receptor on Enterocytes as a Cellular Model for Intestinal Uptake of Prions

Enterocytes, a major cell population of the intestinal epithelium, represent one possible barrier to the entry of prions after oral exposure. We established a cell culture system employing enterocytes from different species to study alimentary prion interaction with the 37-kDa/67-kDa laminin receptor LRP/LR. Human, bovine, porcine, ovine, and cervid enterocytes were cocultured with brain homogenates from cervid, sheep, and cattle suffering from chronic wasting disease (CWD), scrapie, and bovine spongiform encephalopathy (BSE), respectively. PrP^CWD, ovine PrP^Sc, and PrP^BSE all colocalized with LRP/LR on human enterocytes. PrP^CWD failed to colocalize with LRP/LR on bovine, porcine, and ovine enterocytes. Ovine PrP^Sc colocalized with the receptor on bovine enterocytes, but failed to colocalize with LRP/LR on cervid and porcine enterocytes. PrP^BSE failed to colocalize with the receptor on cervid and ovine enterocytes. These data suggest possible oral transmissibility of CWD and sheep scrapie to humans and may confirm the oral transmissibility of BSE to humans, resulting in zoonotic variant Creutzfeldt-Jakob disease. CWD might not be transmissible to cattle, pigs, and sheep. Sheep scrapie might have caused BSE, but may not cause transmissible spongiform encephalopathy in cervids and pigs. BSE may not be transmissible to cervids. Our data recommend the enterocyte model system for further investigations of the intestinal pathophysiology of alimentary prion infections.     

Secretion of the glucose-regulated selenoprotein SEPS1 from hepatoma cells

SEPS1 (also called selenoprotein S, SelS, Tanis or VIMP) is a selenoprotein, localized predominantly in the ER membrane and also on the cell surface. In this report, we demonstrate that SEPS1 protein is also secreted from hepatoma cells but not from five other types of cells examined. The secretion can be abolished by the ER-Golgi transport inhibitor Brefeldin A and by the protein synthesis inhibitor cycloheximide. Using a sandwich ELISA, SEPS1 was detected in the sera of 65 out of 209 human subjects (31.1%, average=15.7+/-1.1 ng/mL). Fractionation of human serum indicated that SEPS1 was associated with LDL and possibly with VLDL. The function of plasma SEPS1 is unclear but may be related to lipoprotein metabolism.     

转基因玉米生物育种技术的专利分析及产业发展建议

通过研究转基因玉米育种技术的专利文献,可分析各国转基因玉米生物育种技术的发展趋势、研发领域的分布、跨国种业集团的产业布局。利用MS Excel和Innography等分析软件,采用图表分析方法对世界转基因玉米生物育种的专利文献进行定性分析和定量分析。结果发现,中国是转基因玉米生物育种的主要研发国家之一,其中基因编辑技术处于领先地位;我国创新主体仍以大专院校、科研院所为主,缺乏科研成果的转化动力,需要加大对转基因技术产业的扶植力度和知识产权服务。研究结果旨在为研究者确定研究方向、跟踪竞争对手的研究进展、分析跨国种业集团的产业布局、制定产业发展政策等提供参考建议。     

NOTES ON THE BREEDING OF THE BOKMAKIRI

Counting Saddle-billed Storks in a study area the size of the Kruger National Park, at 2.2 million ha, is difficult because the birds are long-lived, sparse in the landscape and have large home ranges. Aerial surveys conducted to date provide an estimate with no measure of data dispersion, thence precision. The aim of this study was to estimate the population size within associated confidence limits using a modified mark–recapture field method. The vehicle survey, conducted shortly after rainfall in the area, did not produce results with known precision under these conditions. A repeat of this census in spring, after the peak breeding season and when surface water is confined to the larger rivers and dams, should yield different results. A photographic census technique yielded sufficient information to construct a population registration database. Individual identification profiles indicate that there are at least 40 adult Saddle-billed Storks in the southern part of the Kruger National Park. This is considered the minimum number of known-to-be-alive individuals in this area. In this paper, the Cormack–Jolly–Seber mark– recapture model was used to return an estimate of the population size for each capture occasion.     

Effects of air pressure oscillation amplitude on oxygen transfer rate and biomass productivity in a solid-state fermenter

The modified sulfite oxidation method was adapted for estimation of the overall oxygen transfer rate in a pressure oscillating, solid-state fermenter. At 4.5 atm and 30 °C, the oxygen transfer rate reached 717 mmol kg^–1 initial dry matter h^–1 in this system against 37 mmol kg^–1 initial dry matter h^–1 in a static tray fermenter. At 30 °C and 3 atm, Azotobacter vinelandii grew on wheat straw and reached 4.7×10¹⁰ c.f.u. g^–1 substrate dry matter after 36 h, while only 8.2×10⁹ c.f.u. g^–1 substrate dry matter was obtained in a static tray system.     

A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H

Naphthoquinone derivatives have been reported to possess various pharmacological activities, such as antiplatelet, anticancer, antifungal, and antiviral properties. In this study, we investigated the effects of a newly-synthesized naphthoquinone derivative, 2-decylamino-5,8-dimethoxy-1,4-naphthoquinone (2-decylamino-DMNQ), on VSMC proliferation and examined the molecular basis of the underlying mechanism. In a dose-dependent manner, 2-decylamino-DMNQ inhibited PDGF-stimulated VSMC proliferation with no apparent cytotoxic effect. While 2-decylamino-DMNQ did not affect PDGF-Rβ or Akt, it did inhibit the phosphorylation of Erk1/2 and PLCγ1 induced by PDGF. Moreover, 2-decylamino-DMNQ suppressed DNA synthesis through the arrest of cell cycle progression at the G₀/G₁ phase, including the suppression of pRb phosphorylation and a decrease in PCNA expression, which was related to the downregulation of cell cycle regulatory factors, such as cyclin D1/E and CDK 2/4. It was demonstrated that both U0126, an Erk1/2 inhibitor, and U73122, a PLCγ inhibitor, increased the proportion of cells in the G₀/G₁ phase of the cell cycle. Thus, these results suggest that 2-decylamino DMNQ has an inhibitory effect on PDGF-induced VSMC proliferation and the mechanism of this action is through cell cycle arrest at the G₀/G₁ phase. This may be a useful tool for studying interventions for vascular restenosis in coronary revascularization procedures and stent implantation.