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Therapy of sulfatase deficiencies
No full textThe present invention related to improved gene therapy to treat sulfatase deficiencies, preferably via co-delivery of Sulfatase enzymes and SUMF1 protein
Zinc-α2-glycoprotein hinders cell proliferation and reduces cdc2 expression
No full textZinc-α2-glycoprotein (Znα2gp) is widely distributed in body fluids and epithelia. Its expression in stratified epithelia increases with differentiation. We previously showed that Zn α2gp has ribonuclease activity, and that squamous tumor cells grown on a matrix of Znα2gp were growth-inhibited. Here we demonstrate, both by adding Znα2gp to the culture medium and, more unequivocally, by stably transfecting SiHa cells with Znα2gp cDNA, that the introduction of Znα2gp into SiHa tumor cells reduces proliferation. In response to Znα2gp, we find an accumulation of the cell population in G2/M by flow cytometry, paralleling the reduction of proliferation. In order to distinguish growth inhibition by cell cycle arrest from that produced by apoptosis or differentiation, we examine by RT-PCR how Znα2gp affects the expression of genes commonly used as markers of these properties. No changes are observed for PCNA, p53, c-myc, or bcl-2. Only cdc2 expression responds to Znα2gp, with a reduction of up to over a factor of two. Cdc2 is the only cyclin-dependent kinase regulating the G2/M transition without redundancy and is required as a rate-limiting step in the cell cycle. Its increased expression has been directly linked to increased proliferation and decreased differentiation of advanced tumors; conversely, its downregulation by Znα2gp might hinder tumor progression. © 2001 Wiley-Liss, Inc
Distinct regions of cyclinT1 are required for binding to Cdk9 and for recruitment to the HIV-1 Tat/TAR complex.
No full textDistinct regions of cyclinT1 are required for binding to CDK9 and for recruitment to the HIV-1 Tat/TAR complex
No full textTat-mediated activation of the HIV-1 promoter activity requires Tat-dependent recruitment of the cyclinT1/CDK9 complex (P-TEFb) to the transacting element (TAR) RNA. Tat interaction with the cyclinT1, the regulatory partner of CDK9, results in a specific recruitment of the heterodimer CycT1/CDK9 complex to TAR, whereby it promotes transcription elongation of the HIV-1 LTR-mediated transcription. Using the yeast two-hybrid protein interaction assay we analyzed the binding between cyclinT1 and CDK9. Moreover, using a modified three-hybrid yeast interaction system, we analyzed the recruitment of CycT1 to the Tat/TAR complex. The data presented here demonstrated that distinct domains of cyclinT1 interact with CDK9 and Tat/TAR in vivo. These findings will be instrumental for the designing of proper dominant-negative P-TEFb components capable to interfere with Tat function. © 2001 Wiley-Liss, Inc
Distinct regions of cyclinT1 are required for binding to Cdk9 and for recruitment to the HIV-1 Tat/TAR complex.
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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