Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

四通道可编程数字下变频器HSP50216及其在软件无线电中的应用

HSP50216是Intersil公司推出的多通道可编程数字下变频器集成芯片。它有四个通道，且每个通道的参数均可独立通过微处理器进行编程。文中介绍了该芯片的结构、特点、工作原理及其在软件无线电中的应用。     

HSP50214在软件无线电中的应用

介绍了下变频器HSP50214的功能和主要特性，结合实际分析了他在常规通信系统、FDMA，TDMA和CDMA通信系统中的应用。     

HSP70基因在人胃癌、宫颈癌中高表达和癌变关系的研究

采用人的HSP70基因探针P17与人的胃癌、宫颈癌的癌组织中提取的RNA进行northern杂交，结果均出现了比正常组织较强的杂交信号。表明HSP70基因在癌变组织中呈现高表达，与组织的癌变程度表现出了很强的相关性，为进一步了解细胞的癌变机理和对癌症的预防及基因治疗提供了可靠的实验依据。     

Screening for novel essential genes of Saccharomyces cerevisiae involved in protein secretion

We describe here a screening procedure devised for searching new genes involved in protein secretion in Saccharomyces cerevisiae. The screening procedure takes advantage of yeast strains constructed within the EUROFAN project, in which the promoters of the novel essential genes were replaced by the doxycycline-regulated tetO(7)-CYC1 promoter. This promoter is active in normal growth medium but results in downregulation of the gene in the presence of doxycycline. The yeast cells were grown in the presence or absence of doxycycline, and both the growth and secretion of the heat shock protein, Hsp150p, into the culture medium were determined. In seven strains there was a specific effect on protein secretion. In a strain in which the RPN5 gene was downregulated, the level of secreted Hsp150p was increased compared to the control culture. When RER2 was downregulated, cells secreted Hsp150p that was not of the mature size. In five strains, secretion was more severely reduced than cell growth. One of these downregulated genes, YGL098w, was recently reported to encode an ER-located t-SNARE, USE1. Four of the genes detected, NOG2, NOP15, RRP40 and SDA1, encode proteins involved in ribosome assembly, suggesting a possible new signalling pathway between ribosome biogenesis and production of secreted proteins. The results obtained here indicate that the present screen could be successfully used in larger scale to identify novel secretion-related genes.     

人食管、胃、大肠癌组织中HSP70蛋白表达分析

采用Western Blot方法,检测、分析人食管、胃、大肠的正常组织、癌旁组织及癌组织中的HSP70蛋白表达差异。在不同器官的不同组织中,HSP70的表达情况有较大差异。在人胃、食管、大肠三个器官的正常组织、癌旁组织和癌组织中,HSP70的表达量依次升高。消化道癌组织中大量表达的HSP70蛋白可能在上述组织癌变进程中起一定作用,为深入研究消化道肿瘤的致病机理和治疗提供理论依据。     

A proteomic analysis of green and white sturgeon larvae exposed to heat stress and selenium

Temperature and selenium are two environmental parameters that potentially affect reproduction and stock recruitment of sturgeon in the San Francisco Bay/Delta Estuary. To identify proteins whose expression is modified by these environmental stressors, we performed a proteomic analysis on larval green and white sturgeons exposed to 18 or 26 °C and micro-injected with Seleno-L-Methionine to reach 8 µg g⁻¹ selenium body burden, with L-Methionine as a control. Selenium and high temperature induced mortalities and abnormal morphologies in both species, with a higher mortality in green sturgeon. Larval proteins were separated by two-dimensional gel electrophoresis and differential abundances were detected following spot quantitation and hierarchical cluster analysis. In green sturgeon, 34 of 551 protein spots detected on gels showed a variation in abundance whereas in white sturgeon only 9 of 580 protein spots were differentially expressed (P < 0.01). Gel replicates were first grouped according to heat treatment. Fifteen of these spots were identified using MALDI TOF/TOF mass spectrometry. Proteins involved in protein folding, protein synthesis, protein degradation, ATP supply and structural proteins changed in abundance in response to heat and/or selenium. 40S ribosomal protein SA, FK506-binding protein 10, 65 kDa regulatory subunit A of protein phosphatase 2, protein disulfide isomerase, stress-induced-phosphoprotein 1, suppression of tumorigenicity 13 and collagen type II alpha 1, were differentially expressed in high temperature treatment only. Serine/arginine repetitive matrix protein 1, creatine kinase, serine peptidase inhibitor Kazal type 5 and HSP90 were sensitive to combined temperature and selenium exposure. Valosin-containing protein, a protein involved in aggresome formation and in protein quality control decreased more than 50% in response to selenium treatment. Potential use of such proteins as biomarkers of environmental stressors in larval sturgeons could indicate early warning signals preceding population decline.     

Molecularly Targeted Agents as Radiosensitizers in Cancer Therapy—Focus on Prostate Cancer

As our understanding of the molecular pathways driving tumorigenesis improves and more druggable targets are identified, we have witnessed a concomitant increase in the development and production of novel molecularly targeted agents. Radiotherapy is commonly used in the treatment of various malignancies with a prominent role in the care of prostate cancer patients, and efforts to improve the therapeutic ratio of radiation by technologic and pharmacologic means have led to important advances in cancer care. One promising approach is to combine molecularly targeted systemic agents with radiotherapy to improve tumor response rates and likelihood of durable control. This review first explores the limitations of preclinical studies as well as barriers to successful implementation of clinical trials with radiosensitizers. Special considerations related to and recommendations for the design of preclinical studies and clinical trials involving molecularly targeted agents combined with radiotherapy are provided. We then apply these concepts by reviewing a representative set of targeted therapies that show promise as radiosensitizers in the treatment of prostate cancer.     

基于HSP50214B的侦察接收机数字解调模块设计

介绍数字下变频器HSP50214B的内部结构,设计一种数字解调分析模块,利用HSP50214B同HSP50210的配合．通过软件控制实现对不同调制样式信号的解调分析。     

基于HSP50214B的256QAM信号的下变频实现

本文介绍了可编程数字下变频器件HSP50214B的内部结构和功能模块,并结合一种实际信号的下变频要求,介绍了器件与应用相关的输出方式、控制端口,并详细说明功能模块的参数设计。最后,通过VHDL硬件描述语言编程,利用可编程逻辑器件CPLD完成对HSP50214B的设计的实现。通过一个完整的软件无线电系统中下变频HSPS0214B的设计过程,介绍了HSP50214B的一般应用方法。