细胞凋亡机制的研究进展

以线虫和哺乳动物为实验材料,综述近年来对细胞凋亡机制的研究进展。     

Isolated Skull Cryptococcosis in an Immunocompetent Patient

A 62-year-old immunocompetent rural woman who represents an isolated cryptococcal skull infection without systematic involvement is described. Diagnosis was based on positive India ink staining, positive histopathologic examination, and positive culture. Species identification was performed by growth on Sabouraud dextrose agar and CHROMagar medium and by sequencing of the intergenic and internal transcribed spacer regions of the rRNA genes. This case describes a rare presentation of Cryptococcus neoformans infection in a human immunodeficiency virus-negative patient. The lesions were significantly improved with treatment of daily oral itraconazole 400 mg. A maintenance therapy with a low-dose itraconazole was prescribed to warrant a clinical and mycological eradication. A two-year follow-up did not show any recurrence of infection.     

胜红蓟化感物质之间相互作用的研究

 通过柱层析从胜红蓟挥发油中分离出早熟素Ⅰ、早熟素Ⅱ、子丁香烯、3,3-二甲基-5-特丁基茚酮、红没药烯、乙酸葑醇酯等6种主要化感物质(占挥发油总量的97％),并研究了这些化感物质在挥发、淋溶(饱和水溶液)和土壤降解途径下对萝卜,番茄和绿豆幼苗的化感作用。结果表明：早熟素Ⅰ、早熟素Ⅱ、3,3-二甲基-5-特丁基茚酮及子丁香烯(挥发途径)虽有较强的化感活性,但均弱于挥发油的化感活性,而子丁香烯(淋溶途径),红没药烯和乙酸葑醇酯则基本无化感活性。但是,早熟素n和无活性的三个化感物质结合,则表现出强烈的化感活性,说明胜红蓟各化感物质之间存在着明显的协同作用。     

Selective degradation of AR-V7 to overcome castration resistance of prostate cancer

Androgen receptor splice variant 7 (AR-V7), a form of ligand-independent and constitutively activating variant of androgen receptor (AR), is considered as the key driver to initiate castration-resistant prostate cancer (CRPC). Because AR-V7 lacks ligand-binding domain, the AR-targeted therapies that aim to inactivate AR signaling through disrupting the interaction between AR and androgen are limited in CRPC. Thus, the emergence of AR-V7 has become the greatest challenge for treating CRPC. Targeting protein degradation is a recently proposed novel avenue for cancer treatment. Our previous studies have been shown that the oncoprotein AR-V7 is a substrate of the proteasome. Identifying novel drugs that can trigger the degradation of AR-V7 is therefore critical to cure CRPC. Here we show that nobiletin, a polymethoxylated flavonoid derived from the peel of Citrus fruits, exerts a potent anticancer activity via inducing G0/G1 phase arrest and enhancing the sensitivity of cells to enzalutamide in AR-V7 positive PC cells. Mechanically, we unravel that nobiletin selectively induces proteasomal degradation of AR-V7 (but not AR). This effect relies on its selective inhibition of the interactions between AR-V7 and two deubiquitinases USP14 and USP22. These findings not only enrich our understanding on the mechanism of AR-V7 degradation, but also provide an efficient and druggable target for overcoming CRPC through interfering the stability of AR-V7 mediated by the interaction between AR-V7 and deubiquitinase.Subject terms: Drug development, Translational research     

Verticillium dahliae VdBre1 is required for cotton infection by modulating lipid metabolism and secondary metabolites

The soil-borne ascomycete Verticillium dahliae causes wilt disease in more than two hundred dicotyledonous plants including the economically important crop cotton, and results in a severe reduction in cotton fiber yield and quality. During infection, V. dahliae secretes numerous secondary metabolites, which act as toxic factors to promote the infection process. However, the mechanism underlying how V. dahliae secondary metabolites regulate cotton infection remains largely unexplored. In this study, we report that VdBre1, an ubiquitin ligase (E3) enzyme to modify H2B, regulates radial growth and conidia production of V. dahliae. The VdBre1 deletion strains show nonpathogenic symptoms on cotton, and microscopic inspection and penetration assay indicated that penetration ability of the ∆VdBre1 strain was dramatically reduced. RNA-seq revealed that a total of 1643 differentially expressed genes between the ∆VdBre1 strain and the wild type strain V592, among which genes related to lipid metabolism were significantly overrepresented. Remarkably, the volume of lipid droplets in the ∆VdBre1 conidia was shown to be smaller than that of wild-type strains. Further metabolomics analysis revealed that the pathways of lipid metabolism and secondary metabolites, such as steroid biosynthesis and metabolism of terpenoids and polyketides, have dramatically changed in the ∆VdBre1 metabolome. Taken together, these results indicate that VdBre1 plays crucial roles in cotton infection and pathogenecity, by globally regulating lipid metabolism and secondary metabolism of V. dahliae.     

TRIM37 prevents formation of condensate-organized ectopic spindle poles to ensure mitotic fidelity

Centrosomes are composed of a centriolar core surrounded by pericentriolar material that nucleates microtubules. The ubiquitin ligase TRIM37 localizes to centrosomes, but its centrosomal roles are not yet defined. We show that TRIM37 does not control centriole duplication, structure, or the ability of centrioles to form cilia but instead prevents assembly of an ectopic centrobin-scaffolded structured condensate that forms by budding off of centrosomes. In ∼25% of TRIM37-deficient cells, the condensate organizes an ectopic spindle pole, recruiting other centrosomal proteins and acquiring microtubule nucleation capacity during mitotic entry. Ectopic spindle pole–associated transient multipolarity and multipolar segregation in TRIM37-deficient cells are suppressed by removing centrobin, which interacts with and is ubiquitinated by TRIM37. Thus, TRIM37 ensures accurate chromosome segregation by preventing the formation of centrobin-scaffolded condensates that organize ectopic spindle poles. Mutations in TRIM37 cause the disorder mulibrey nanism, and patient-derived cells harbor centrobin condensate-organized ectopic poles, leading us to propose that chromosome missegregation is a pathological mechanism in this disorder.     

香港嘉道理农场次生林区碰撞诱捕网和黑光灯捕虫器采集所得鞘翅目甲虫多样性比较

本文根据1990-1995年在香港嘉道理农场次生林区采集的昆虫标本,首次分析了鞘翅目及其优势科的种类、数量和季节性变化,以及由碰撞诱捕网和黑光灯捕虫器采集所得甲虫在种类、数量和季节性上的差异。在13260号标本中,已鉴定到科的有13253号,分属45科,231种。其中,朽木甲科(Alleculidae)、毛蕈甲科(Biphyllidae)、丸甲科(Byrrhidae)、坚甲科(Colydiidae)、拟球甲科(Corylophidae)、隐食甲科(Cryptophagidae)、水缨甲科(Hydroscaphidae)、伪叶甲科(Lagliidae)、薪甲科(Lathridiidae)、泽甲科(Limnichidae)、黑蕈甲科(Zopheridae)等11个科为香港地区的首次报道,约占本次调查科总数的25％。分析表明：(1)该次生林区的鞘翅目甲虫以蛀木性为主。天牛科(Cerambycidae)、瓢虫科(Coccinellidae)、象甲科(Curculionidae)、花蚤科(Mordellidae)、金龟甲科(Scarabaeidae)、小蠹科(Scolytidae)等6科均为多样性较高(种类≥15或者个体数量≥200)的优势科。(2)鞘翅目个体数量季节性明显,每年自2月开始数量逐渐增加,6—7月为甲虫发生的高峰期,8月显著减少。各优势科甲虫的季节性也存在一定的差异,庞大的小蠹标本数量(85％)说明在此调查期间该科正处于大发生时期。(3)黑光灯捕虫器所捕的甲虫科类和种类较之碰撞诱捕网所捕不尽相同,黑光灯捕虫器所捕的甲虫数量发生高峰期比碰撞诱捕网所捕的甲虫提前一个月。(4)各项多样性指数对不同捕虫器采集所得鞘翅目的测度差异明显,黑光灯捕虫器所捕甲虫的多样度和均匀度指数高于碰撞诱捕网。     

不同微生物大鼠腹腔注射模型尿液蛋白组学的比较

不同的微生物都可以引起腹腔感染,文中尝试利用尿液来区分不同的微生物感染.通过在大鼠腹腔内分别注射大肠杆菌、金黄色葡萄球菌和白色念球菌建立3种模型,收集感染后0、12、36、72h的尿液,并使用液相色谱串联质谱技术(LC-MS/MS)对尿蛋白进行分析.与感染前相比,在大肠杆菌腹腔注射模型中共鉴定到69个差异蛋白,在金黄色...