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1.
Structure ; 24(4): 567-575, 2016 Apr 05.
Article in English | MEDLINE | ID: mdl-27021160

ABSTRACT

Empty virus-like particles (eVLPs) of Cowpea mosaic virus (CPMV) are currently being utilized as reagents in various biomedical and nanotechnology applications. Here, we report the crystal structure of CPMV eVLPs determined using X-ray crystallography at 2.3 Å resolution and compare it with previously reported cryo-electron microscopy (cryo-EM) of eVLPs and virion crystal structures. Although the X-ray and cryo-EM structures of eVLPs are mostly similar, there exist significant differences at the C terminus of the small (S) subunit. The intact C terminus of the S subunit plays a critical role in enabling the efficient assembly of CPMV virions and eVLPs, but undergoes proteolysis after particle formation. In addition, we report the results of mass spectrometry-based proteomics analysis of coat protein subunits from CPMV eVLPs and virions that identify the C termini of S subunits undergo proteolytic cleavages at multiple sites instead of a single cleavage site as previously observed.


Subject(s)
Capsid Proteins/chemistry , Comovirus/chemistry , Crystallography, X-Ray/methods , Proteomics/methods , Capsid Proteins/metabolism , Comovirus/metabolism , Cryoelectron Microscopy , Mass Spectrometry , Models, Molecular , Protein Structure, Secondary , Proteolysis , Viral Proteins/chemistry , Viral Proteins/metabolism , Virion/chemistry , Virion/metabolism
2.
Arch Sex Behav ; 44(2): 349-56, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25617010

ABSTRACT

This article examined the associations between three forms of homosexuality-related stigma (enacted, perceived, and internalized homosexual stigmas) with risky sexual behaviors, and to describe the mechanisms of these associations, among men who have sex with men (MSM) in Hanoi, Vietnam. We used respondent-driven sampling (RDS) to recruit 451 MSM into a cross-sectional study conducted from August 2010 to January 2011. Data were adjusted for recruitment patterns due to the RDS approach; logistic regression and path analyses were performed. Participants were young and single; most had attended at least some college. Nine out of ten participants engaged in sexual behaviors at moderate to high risk levels. Compared to those who had no enacted homosexual stigma, men having low and high levels of enacted homosexual stigma, respectively, were 2.23 times (95 % CI 1.35-3.69) and 2.20 times (95 % CI 1.04-4.76) more likely to engage in high levels of sexual risk behaviors. In addition, there was an indirect effect of perceived homosexual stigma and internalized homosexual stigma on sexual risk behaviors through depression and drug and alcohol use. Our study provides valuable information to our understanding of homosexual stigma in Vietnam, highlighting the need for provision of coping skills against stigma to the gay community and addressing drinking and drug use among MSM, to improve the current HIV prevention interventions in Vietnam.


Subject(s)
Homosexuality, Male , Risk-Taking , Social Stigma , Unsafe Sex/psychology , Adaptation, Psychological , Adolescent , Adult , Cross-Sectional Studies , Depression , HIV Infections/prevention & control , Humans , Logistic Models , Male , Risk , Vietnam , Young Adult
3.
FASEB J ; 18(11): 1176-84, 2004 Aug.
Article in English | MEDLINE | ID: mdl-15284217

ABSTRACT

Metal transcription factor-1 (MTF-1) is a ubiquitous transcriptional regulator and chromatin insulator with roles in cellular stress responses and embryonic development. The studies described herein establish for the first time the involvement of MTF-1 in tumor development. Genetically manipulated ras-transformed mouse embryonic fibroblasts (MEFs), wild-type (MTF-1+/+), or nullizygous for MTF-1 (MTF-1-/-) were used to develop fibrosarcoma tumors. Loss of MTF-1 resulted in delayed tumor growth associated with increased matrix collagen deposition and reductions in vasculature density. Molecular consequences of MTF-1 loss include increased expression and activation of the transforming growth factor-beta1 (TGF-beta1) and tissue transglutaminase (tTG), two proteins with documented roles in the production and stabilization of extracellular matrix (ECM). Our findings support the hypothesis that MTF-1 enhances the ability of the developing tumor mass to evade fibrosis and scarring of the tumor, a critical step in tumor cell proliferation.


Subject(s)
Fibrosarcoma/pathology , Transcription Factors/deficiency , Animals , Cell Division/genetics , Cell Line, Transformed , DNA-Binding Proteins , Disease Progression , Enzyme Induction , Extracellular Matrix/metabolism , Fibrinolysin/analysis , Fibroblasts/pathology , Fibroblasts/transplantation , Fibrosarcoma/blood supply , Fibrosarcoma/metabolism , Fibrosis , GTP-Binding Proteins/biosynthesis , GTP-Binding Proteins/genetics , Genes, ras , Male , Mice , Mice, Inbred BALB C , Mice, Knockout , Mice, Nude , Neoplasm Transplantation , Neovascularization, Pathologic/genetics , Protein Glutamine gamma Glutamyltransferase 2 , Transcription Factors/genetics , Transcription Factors/physiology , Transforming Growth Factor beta/biosynthesis , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta1 , Transglutaminases/biosynthesis , Transglutaminases/genetics , Transcription Factor MTF-1
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