Proteomics and metabolomics of Arabidopsis responses to perturbation of glucosinolate biosynthesis

To understand plant molecular networks of glucosinolate metabolism, perturbation of aliphatic glucosinolate biosynthesis was established using inducible RNA interference (RNAi) in Arabidopsis. Two RNAi lines were chosen for examining global protein and metabolite changes using complementary proteomics and metabolomics approaches. Proteins involved in metabolism including photosynthesis and hormone metabolism, protein binding, energy, stress, and defense showed marked responses to glucosinolate perturbation. In parallel, metabolomics revealed major changes in the levels of amino acids, carbohydrates, peptides, and hormones. The metabolomics data were correlated with the proteomics results and revealed intimate molecular connections between cellular pathways/processes and glucosinolate metabolism. This study has provided an unprecedented view of the molecular networks of glucosinolate metabolism and laid a foundation towards rationale glucosinolate engineering for enhanced defense and quality.     

真空负压和常规ABC法显示HPV—1抗原的应用比较

应用真空负压 ABC 法显示 HPV-1抗原比常规 ABC 法效果好,敏感性高,时间短,整个过程只需一个多小时,阳性物明显突出,颗粒均匀,色泽鲜艳,呈黄棕色,背景清晰等优点。还可提高抗体的稀释度,降低成本。与微波技术相比,具有设备简单,易于操作,安全可靠,不受条件限制,经对26例尖锐湿疣的病例进行多层次稀释度的研究,取得了满意的结果,认为该法值得推广应用。     

MiR-942 Mediates Hepatitis C Virus-Induced Apoptosis via Regulation of ISG12a

The interaction between hepatitis C virus (HCV) and human hepatic innate antiviral responses is unclear. The aim of this study was to examine how human hepatocytes respond to HCV infection. An infectious HCV isolate, JFH1, was used to infect a newly established human hepatoma cell line HLCZ01. Viral RNA or NS5A protein was examined by real-time PCR or immunofluorescence respectively. The mechanisms of HCV-induced IFN-β and apoptosis were explored. Our data showed that HLCZ01 cells supported the entire HCV lifecycle and IFN-β and interferon-stimulated genes (ISGs) were induced in HCV-infected cells. Viral infection caused apoptosis of HLCZ01 cells. Silencing of RIG-I, IRF3 or TRAIL inhibited ISG12a expression and blocked apoptosis of viral-infected HLCZ01 cells. Knockdown ISG12a blocked apoptosis of viral-infected cells. MiR-942 is a candidate negative regulator of ISG12a predicted by bioinformatics search. Moreover, HCV infection decreased miR-942 expression in HLCZ01 cells and miR-942 was inversely correlated with ISG12a expression in both HCV-infected cells and liver biopsies. MiR-942 forced expression in HLCZ01 cells decreased ISG12a expression and subsequently suppressed apoptosis triggered by HCV infection. Conversely, silencing of miR-942 expression by anti-miR-942 increased ISG12a expression and enhanced apoptosis in HCV-infected cells. Induction of Noxa by HCV infection contributed to ISG12a-mediated apoptosis. All the data indicated that innate host response is intact in HCV-infected hepatocytes. MiR-942 regulates HCV-induced apoptosis of human hepatocytes by targeting ISG12a. Our study provides a novel mechanism by which human hepatocytes respond to HCV infection.     

Comparative study of metal resistance and accumulation of lead and zinc in two poplars

In our study, we tested two poplars, Populus beijingensis and Populus cathayana, as model species for their potential for phytoremediation by measuring changes in biomass, pigments, superoxide radicals (O₂^?), cellular ultrastructure and their ability for O₂^? quenching and heavy metal accumulation when exposed to Pb, Zn and their interaction in a hydroponic system. Exposure to Pb did not cause a significant decrease in biomass in either P. beijingensis or P. cathayana. Correspondingly, no obvious impairment in cellular organelles was observed in either species, although the former species translocated a higher fraction of Pb to its shoots than the latter. In contrast, there were significant decreases in biomass and pigment content, and serious impairments in ultrastructure in both species when exposed to either Zn alone or to a combined treatment. Under such conditions, P. beijingensis showed smaller losses of biomass and pigments but a greater ability to quench O₂^? and maintained relatively intact cellular organelles compared with P. cathayana. Under the combined stress, there were no obvious additive effects on biomass, pigments or cellular impairment, whereas synergistic effects on metal absorption and accumulation in both species were observed when compared with exposure to either alone. Thus, the attribute of synergistic uptake and translocation in both species validates their potential to remediate soil contaminated by multiple metals. Moreover, our results indicated that P. beijingensis is a better potential candidate for phytoremediation than P. cathayana, due to its greater phytoremediation efficiency as well as its higher tolerance capacity.     

Investigation of Gallic Acid Induced Anticancer Effect in Human Breast Carcinoma MCF‐7 Cells

Gallic acid (GA), a polyhydroxylphenolic compound abundantly distributed in plants, fruits, and foods, has been reported to have various biological activities including an anticancer effect. In this study, we extensively investigated the anticancer effect of GA in human breast carcinoma MCF‐7 cells. Our study indicated that treatment with GA resulted in inhibition of proliferation and induction of apoptosis in MCF‐7 cells. Then, the molecular mechanism of GA's apoptotic action in MCF‐7 cells was further investigated. The results revealed that GA induced apoptosis by triggering the extrinsic or Fas/FasL pathway as well as the intrinsic or mitochondrial pathway. Furthermore, the apoptotic signaling induced by GA was amplified by cross‐link between the two pathways. Taken together, our findings may be useful for understanding the mechanism of action of GA on breast cancer cells and provide new insights into the possible application of such compound and its derivatives in breast cancer therapy.     

Heterogeneity of Tumor Vasculature and Antiangiogenic Intervention: Insights from MR Angiography and DCE-MRI

Purpose

Solid tumor vasculature is highly heterogeneous, which presents challenges to antiangiogenic intervention as well as the evaluation of its therapeutic efficacy. The aim of this study is to evaluate the spatial tumor vascular changes due to bevacizumab/paclitaxel therapy using a combination approach of MR angiography and DCE-MRI method.

Experimental Design

Tumor vasculature of MCF-7 breast tumor mouse xenografts was studied by a combination of MR angiography and DCE-MRI with albumin-Gd-DTPA. Tumor macroscopic vasculature was extracted from the early enhanced images. Tumor microvascular parameters were obtained from the pharmacokinetic modeling of the DCE-MRI data. A spatial analysis of the microvascular parameters based on the macroscopic vasculature was used to evaluate the changes of the heterogeneous vasculature induced by a 12 day bevacizumab/paclitaxel treatment in mice bearing MCF-7 breast tumor.

Results

Macroscopic vessels that feed the tumors were not affected by the bevacizumab/paclitaxel combination therapy. A higher portion of the tumors was within close proximity of these macroscopic vessels after the treatment, concomitant with tumor growth retardation. There was a significant decrease in microvascular permeability and vascular volume in the tumor regions near these vessels.

Conclusion

Bevacizumab/paclitaxel combination therapy did not block the blood supply to the MCF-7 breast tumor. Such finding is consistent with the modest survival benefits of adding bevacizumab to current treatment regimens for some types of cancers.     

Identification of 3-phenylaminoquinolinium and 3-phenylaminopyridinium salts as new agents against opportunistic fungal pathogens

Previous studies on the indoloquinoline alkaloid, cryptolepine (2), revealed that it has antii-nfective properties among other activities. Using Structure-activity relationship (SAR) techniques, several ring-opened analogs of cryptolepine (3-phenylaminopyridinium and 3-phenylaminoquinolinium derivatives) were designed to improve the potency and lower the cytotoxicity shown by several of the precursor agents. Results indicate that these ring-opened analogs constitute new anti-infective agents with over a 100-fold potency and several fold lower cytotoxicity than cryptolepine from which they are derived.     

Nudel modulates kinetochore association and function of cytoplasmic dynein in M phase

The microtubule-based motor cytoplasmic dynein/dynactin is a force generator at the kinetochore. It also transports proteins away from kinetochores to spindle poles. Regulation of such diverse functions, however, is poorly understood. We have previously shown that Nudel is critical for dynein-mediated protein transport, whereas mitosin, a kinetochore protein that binds Nudel, is involved in retention of kinetochore dynein/dynactin against microtubule-dependent stripping. Here we demonstrate that Nudel is required for robust localization of dynein/dynactin at the kinetochore. It localizes to kinetochores after nuclear envelope breakdown, depending mostly ( approximately 78%) on mitosin and slightly on dynein/dynactin. Depletion of Nudel by RNA interference (RNAi) or overexpression of its mutant incapable of binding either Lis1 or dynein heavy chain abolishes the kinetochore protein transport and mitotic progression. Similar to mitosin RNAi, Nudel RNAi also leads to increased stripping of kinetochore dynein/dynactin in the presence of microtubules. Taking together, our results suggest a dual role of kinetochore Nudel: it activates dynein-mediated protein transport and, when interacting with both mitosin and dynein, stabilizes kinetochore dynein/dynactin against microtubule-dependent stripping to facilitate the force generation function of the motor.     

一类三维非线性系统空间周期解的存在性及唯一性

本文研究了一类描述天然林内红松林种群变化的三维非线性教学模型