The severe acute respiratory syndrome (SARS) has been one of the most epidemic diseases threatening human health all over the world. Based on clinical studies, SARSCoV (the SARS-associated coronavirus), a novel coronavirus, is reported as the pathogen responsible for the disease. To date, no e¡ective and speci¢c therapeutic method can be used to treat patients su¡ering from SARS-CoV infection. RNA interference (RNAi) is a process by which the introduced small interfering RNA (siRNA) could cause the degradation of mRNA with identical sequence speci¢city. The RNAi methodology has been used as a tool to silence genes in cultured cells and in animals. Recently, this technique was employed in anti-virus infections in human immunode¢ciency virus and hepatitis C/B virus. In this study, RNAi technology has been applied to explore the possibility for prevention of SARS-CoV infection. We constructed speci¢c siRNAs targeting the S gene in SARS-CoV. We demonstrated that the siRNAs could e¡ectively and speci¢cally inhibit gene expression of Spike protein in SARS-CoV-infected cells. Our study provided evidence that RNAi could be a tool for inhibition of SARS-CoV. ß 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.

Impaired phosphatase activity contributes to the persistent activation of STAT3 in tumors. Given that STAT family members with various or even opposite functions are often phosphorylated or dephosphorylated by the same enzymes, the mechanism for STAT3-specific dephosphorylation in cells remains largely unknown. Here, we report that GdX (UBL4A) promotes STAT3 dephosphorylation via mediating the interaction between TC45 (the nuclear isoform of TC-PTP) and STAT3 specifically. GdX stabilizes the TC45-STAT3 complex to bestow upon STAT3 an efficient dephosphorylation by TC45. Inasmuch, GdX suppresses tumorigenesis and tumor development by reducing the level of phospho-STAT3 (p-STAT3), whereas deletion of GdX results in a high level of p-STAT3 and accelerated colorectal tumorigenesis induced by AOM/DSS. Thus, GdX converts TC45, a nonspecific phosphatase, into a STAT3-specific phosphatase by bridging an association between TC45 and STAT3.

Transcription factor Wilms' tumor 1 (WT1) was originally identified as a tumor suppressor for Wilms' tumor, but it is also overexpressed in a variety of cancer cells, suggesting a potential oncogenic function of WT1. It is important to understand molecular mechanisms underlying these dual functions of WT1 in tumorigenesis. In the current study, we report a synergistic role for signal transducers and activators of transcription 3 (STAT3) and WT1 in tumor development, including Wilms' tumor. STAT3 interacts with WT1 through its conserved domains both in vitro and in vivo. When STAT3 is activated, expression of WT1 enhances STAT3 transcriptional activity. Overexpression of WT1 and STAT3CA in NIH 3T3 increases the expression level of STAT3 target genes, including cyclin D1 and Bcl-xL, which results in an advantage of cell proliferation. Our results suggest that in the presence of activated STAT3, WT1 promotes cell proliferation instead of suppressing cell proliferation. Strikingly, STAT3 translocates to the nucleus and interacts with WT1 in a variety of primary Wilms' tumor cells, raising the hypothesis that WT1 and activated STAT3 in Wilms' tumor accelerate tumorigenesis.

GdX (also named Ubl4A) is a house-keeping gene located on the X chromosome and encodes a protein harboring an ubiquitin-like domain in human and mouse. Although identified in 1988, the function of GdX remains unknown. To elucidate the role of GdX in vivo, we generated a conditional GdX knockout mouse in which Exon 2 was flanked by two loxP sites. We obtained viable and fertile mice with homozygous GdX(flox/flox) or GdX(flox/Y) allele. Germ-line transmission was confirmed by crossing the mouse bearing conditionally targeted allele with an EIIα-Cre transgenic mouse. GdX was successfully depleted in tissues of EIIα-Cre-GdX-null mice. GdX(-/-) and GdX(-/Y) mice are viable and exhibit normal development compared with wild-type littermates within 6 months during our observation. We also observed that GdX knockout male mice were functionally normal in the reproductive system where Ubl4B was specifically expressed. GdX(flox/flox) and GdX(flox/Y) conditional mice provide a tool for further tissue-specific function analysis of the GdX protein under different conditions.

In this paper, a specific type of vertical-axis wind turbine is discussed. For the complex structure of this specific vertical-axis wind turbine, the structures of certain parts are optimized and improved. Size of bolts that connect the root of blade with the vertical shaft is designed. Also, the improved structure is proved reasonable using Solidworks Simulation. Through the optimization and improvement of structure, the blade of the discussed vertical-axis wind turbine becomes simper and lighter. As a result, the transportation and installation costs of blade are reduced.