永久型70kD热休克蛋白在白菜花发育过程中的免疫组织化学定位

利用免疫组织化学技术研究了永久型热休克蛋白ＨＳＣ７０在白菜花各组织中的分布。结果表明：在正常温度条件下,ＨＳＣ７０在小孢子母细胞、四分体细胞、花药壁绒毡层细胞中分布最多,在花原基、花托的维管组织、花粉母细胞以及发育早期的胚珠中的表达也较多。该结果与其他人用核酸杂交、同位素示踪等技术所得结果基本一致,本文对ＨＳＣ７０在白菜花不同组织中的分布与其功能的关系进行了初步讨论。     

Role of the Phenylalanine-Hydroxylating System in Aromatic Substance Degradation and Lipid Metabolism in the Oleaginous Fungus Mortierella alpina

Mortierella alpina is a filamentous fungus commonly found in soil that is able to produce lipids in the form of triacylglycerols that account for up to 50% of its dry weight. Analysis of the M. alpina genome suggests that there is a phenylalanine-hydroxylating system for the catabolism of phenylalanine, which has never been found in fungi before. We characterized the phenylalanine-hydroxylating system in M. alpina to explore its role in phenylalanine metabolism and its relationship to lipid biosynthesis. Significant changes were found in the profile of fatty acids in M. alpina grown on medium containing an inhibitor of the phenylalanine-hydroxylating system compared to M. alpina grown on medium without inhibitor. Genes encoding enzymes involved in the phenylalanine-hydroxylating system (phenylalanine hydroxylase [PAH], pterin-4α-carbinolamine dehydratase, and dihydropteridine reductase) were expressed heterologously in Escherichia coli, and the resulting proteins were purified to homogeneity. Their enzymatic activity was investigated by high-performance liquid chromatography (HPLC) or visible (Vis)-UV spectroscopy. Two functional PAH enzymes were observed, encoded by distinct gene copies. A novel role for tetrahydrobiopterin in fungi as a cofactor for PAH, which is similar to its function in higher life forms, is suggested. This study establishes a novel scheme for the fungal degradation of an aromatic substance (phenylalanine) and suggests that the phenylalanine-hydroxylating system is functionally significant in lipid metabolism.     

原发性十二指肠恶性肿瘤的临床分析

目的：探讨原发性十二指肠恶性肿瘤的临床特点、诊断方法和预后影响因素。方法：回顾性分析随访资料完整的45例原发性十二指肠恶性肿瘤患者的临床病理资料。结果：腺癌33例（73.3％）为主要的病理类型。主要临床表现为腹痛、上腹部不适、黄疸、消化道出血等。胃十二指肠镜、内镜逆行胰胆管造影（Endoscopic Retrograde Cholangio—Pancreatography,ERCP）、十二指肠低张造影、超声内镜、CT及B超确诊率分别为91．1％（41／45）,93．3％（42/45）,82．2％（37／45）,75．6％（34N5）,68．9％（31／45）及26．7％（12／45）。本组45例均行开腹手术,包括根治性手术,胰十二指肠切除术36例;姑息性手术,胃肠吻合术2例、肿瘤局部切除术5例、短路手术2例。根治术和姑息术后5年生存率分别为46．7％和4．4％,两组生存率差异有统计学意义（P〈O．05）。对全组45例患者的预后因素进行Cox回归分析的结果显示,手术方式、肿瘤浸润深度和淋巴节转移是影响预后的独立危险因素（均P〈0．05）。结论：原发性十二指肠恶性肿瘤缺乏特异性临床表现;胃十二指肠镜、ERCP以及十二指肠低张造影等联合检查可提高诊断率;根治性手术远期疗效较好;淋巴结转移和局部侵犯是肿瘤预后不良的重要影响因素。     

Hormonal control of androgen receptor function through SIRT1

The NAD-dependent histone deacetylase Sir2 plays a key role in connecting cellular metabolism with gene silencing and aging. The androgen receptor (AR) is a ligand-regulated modular nuclear receptor governing prostate cancer cellular proliferation, differentiation, and apoptosis in response to androgens, including dihydrotestosterone (DHT). Here, SIRT1 antagonists induce endogenous AR expression and enhance DHT-mediated AR expression. SIRT1 binds and deacetylates the AR at a conserved lysine motif. Human SIRT1 (hSIRT1) repression of DHT-induced AR signaling requires the NAD-dependent catalytic function of hSIRT1 and the AR lysine residues deacetylated by SIRT1. SIRT1 inhibited coactivator-induced interactions between the AR amino and carboxyl termini. DHT-induced prostate cancer cellular contact-independent growth is also blocked by SIRT1, providing a direct functional link between the AR, which is a critical determinant of progression of human prostate cancer, and the sirtuins.     

四川溪洛渡水库库区雷波至金阳段翼手类调查

1999年5～7月,对溪洛渡水库库区（雷波至金阳一线河谷地带〈包括永善〉,海拔2000 m以下）翼手类进行了调查.共计调查了20个洞穴和沿线房屋.调查结合历史资料确认溪洛渡水库库区有翼手类动物4科6属15种.优势种是大蹄蝠、小菊头蝠、双色蹄蝠;新发现的稀有种类是印度假吸血蝠.     

A pharmacophore-based evolutionary approach for screening selective estrogen receptor modulators

We developed a pharmacophore-based evolutionary approach for virtual screening. This tool, termed the Generic Evolutionary Method for molecular DOCKing (GEMDOCK), combines an evolutionary approach with a new pharmacophore-based scoring function. The former integrates discrete and continuous global search strategies with local search strategies to expedite convergence. The latter, integrating an empirical-based energy function and pharmacological preferences (binding-site pharmacological interactions and ligand preferences), simultaneously serves as the scoring function for both molecular docking and postdocking analyses to improve screening accuracy. We apply pharmacological interaction preferences to select the ligands that form pharmacological interactions with target proteins, and use the ligand preferences to eliminate the ligands that violate the electrostatic or hydrophilic constraints. We assessed the accuracy of our approach using human estrogen receptor (ER) and a ligand database from the comparative studies of Bissantz et al. (J Med Chem 2000;43:4759-4767). Using GEMDOCK, the average goodness-of-hit (GH) score was 0.83 and the average false-positive rate was 0.13% for ER antagonists, and the average GH score was 0.48 and the average false-positive rate was 0.75% for ER agonists. The performance of GEMDOCK was superior to competing methods such as GOLD and DOCK. We found that our pharmacophore-based scoring function indeed was able to reduce the number of false positives; moreover, the resulting pharmacological interactions at the binding site, as well as ligand preferences, were important to the screening accuracy of our experiments. These results suggest that GEMDOCK constitutes a robust tool for virtual database screening.     

产黄酮银杏内共生真菌的分离及其发酵条件的优化

本文从不同年龄、不同地域的银杏叶、茎、根部组织中分离得到20株银杏内共生真菌,经过发酵复筛有5株的产黄酮能力超过5μg/m L。实验对菌株的最佳发酵产黄酮条件进行了优化,优化条件为:3%葡萄糖、0.5%蛋白胨、0.4%酵母膏、0.3%KH2PO4、0.01%Mg SO4·7H2O;起始p H值7.0、最适发酵温度28℃、摇床转速为140 r/min、装液量125 m L/250 m L。在此条件下,该系列菌株在发酵7 d左右产黄酮量可达6.4μg/m L。     

ERK-mediated Cytoplasmic Retention of USP11 Contributes to Breast Cancer Cell Proliferation by Stabilizing Cytoplasmic p21

Breast cancer ranks as the most frequently diagnosed cancer among women worldwide. Elevated cytoplasmic p21 levels are often found in breast cancer tissues and related to a poor prognosis. However, the underlying mechanisms that lead to the stabilization of cytoplasmic p21 protein, which normally has a very short half-life, remain obscure. In this study, we found that there was a strong correlation between p21 and USP11 in the cytoplasm of breast cancer tissues and cells. Furthermore, we revealed that ERK1/2 phosphorylated USP11 at the Ser905 site, which promoted the cytoplasmic localization of USP11. In the cytoplasm, USP11 colocalized and interacted with p21. As a result, USP11 catalyzed the removal of polyubiquitin chains bound to cytoplasmic p21 and resulted in its stabilization. Functionally, USP11-mediated stabilization of cytoplasmic p21 induced breast cancer cell proliferation in vitro and in vivo. Our findings provide the first evidence that ubiquitinated p21 in the cytoplasm can be recycled through USP11-mediated deubiquitination, and we identified the USP11-p21 axis in the cytoplasm as a potential therapeutic target for breast cancer control.