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1.
J Cell Biol ; 220(7)2021 07 05.
Article in English | MEDLINE | ID: mdl-33886957

ABSTRACT

Membrane transport carriers fuse with target membranes through engagement of cognate vSNAREs and tSNAREs on each membrane. How vSNAREs are sorted into transport carriers is incompletely understood. Here we show that VAMP7, the vSNARE for fusing endosome-derived tubular transport carriers with maturing melanosomes in melanocytes, is sorted into transport carriers in complex with the tSNARE component STX13. Sorting requires either recognition of VAMP7 by the AP-3δ subunit of AP-3 or of STX13 by the pallidin subunit of BLOC-1, but not both. Consequently, melanocytes expressing both AP-3δ and pallidin variants that cannot bind their respective SNARE proteins are hypopigmented and fail to sort BLOC-1-dependent cargo, STX13, or VAMP7 into transport carriers. However, SNARE binding does not influence BLOC-1 function in generating tubular transport carriers. These data reveal a novel mechanism of vSNARE sorting by recognition of redundant sorting determinants on a SNARE complex by an AP-3-BLOC-1 super-complex.


Subject(s)
Adaptor Protein Complex 3/genetics , Adaptor Protein Complex delta Subunits/genetics , Nerve Tissue Proteins/genetics , Qa-SNARE Proteins/genetics , R-SNARE Proteins/genetics , Endosomes/genetics , Humans , Melanocytes/metabolism , Melanosomes/genetics , Protein Transport/genetics
2.
J Exp Med ; 214(7): 1901-1912, 2017 Jul 03.
Article in English | MEDLINE | ID: mdl-28550162

ABSTRACT

Prolonged exit from quiescence by hematopoietic stem cells (HSCs) progressively impairs their homeostasis in the bone marrow through an unidentified mechanism. We show that Rb proteins, which are major enforcers of quiescence, maintain HSC homeostasis by positively regulating thrombopoietin (Tpo)-mediated Jak2 signaling. Rb family protein inactivation triggers the progressive E2f-mediated transactivation of Socs3, a potent inhibitor of Jak2 signaling, in cycling HSCs. Aberrant activation of Socs3 impairs Tpo signaling and leads to impaired HSC homeostasis. Therefore, Rb proteins act as a central hub of quiescence and homeostasis by coordinating the regulation of both cell cycle and Jak2 signaling in HSCs.


Subject(s)
Hematopoietic Stem Cells/metabolism , Homeostasis/genetics , Retinoblastoma Protein/genetics , Retinoblastoma-Like Protein p107/genetics , Retinoblastoma-Like Protein p130/genetics , Suppressor of Cytokine Signaling 3 Protein/genetics , Animals , Cell Cycle/genetics , Cell Division/genetics , Cell Proliferation/genetics , E2F Transcription Factors/genetics , E2F Transcription Factors/metabolism , Gene Expression Profiling/methods , Immunoblotting , Janus Kinase 2/genetics , Janus Kinase 2/metabolism , Mice, Knockout , Mice, Transgenic , Phosphorylation/drug effects , RNA Interference , Retinoblastoma Protein/metabolism , Retinoblastoma-Like Protein p107/metabolism , Retinoblastoma-Like Protein p130/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Suppressor of Cytokine Signaling 3 Protein/metabolism , Thrombopoietin/pharmacology , Transcriptional Activation
3.
MEDICC Rev ; 14(4): 26-31, 2012 10.
Article in English | MEDLINE | ID: mdl-23154315

ABSTRACT

INTRODUCTION: Globally, population surveys on HIV/AIDS and other sensitive topics have been using audio computer-assisted self interview for many years. This interview technique, however, is still new to Vietnam and little is known about its application and impact in general population surveys. One plausible hypothesis is that residents of Vietnam interviewed using this technique may provide a higher response rate and be more willing to reveal their true behaviors than if interviewed with traditional methods. OBJECTIVE: This study aims to compare audio computer-assisted self interview with traditional face-to-face personal interview and self-administered interview with regard to rates of refusal and affirmative responses to questions on sensitive topics related to HIV/AIDS. METHODS: In June 2010, a randomized study was conducted in three cities (Ha Noi, Da Nan and Can Tho), using a sample of 4049 residents aged 15 to 49 years. Respondents were randomly assigned to one of three interviewing methods: audio computer-assisted self interview, personal face-to-face interview, and self-administered paper interview. Instead of providing answers directly to interviewer questions as with traditional methods, audio computer-assisted self-interview respondents read the questions displayed on a laptop screen, while listening to the questions through audio headphones, then entered responses using a laptop keyboard. A MySQL database was used for data management and SPSS statistical package version 18 used for data analysis with bivariate and multivariate statistical techniques. Rates of high risk behaviors and mean values of continuous variables were compared for the three data collection methods. RESULTS: Audio computer-assisted self interview showed advantages over comparison techniques, achieving lower refusal rates and reporting higher prevalence of some sensitive and risk behaviors (perhaps indication of more truthful answers). Premarital sex was reported by 20.4% in the audio computer-assisted self-interview survey group, versus 11.4% in the face-to-face group and 11.1% in the self-administered paper questionnaire group. The pattern was consistent for both male and female respondents and in both urban and rural settings. Men in the audio computer-assisted self-interview group also reported higher levels of high-risk sexual behavior--such as sex with sex workers and a higher average number of sexual partners--than did women in the same group. Importantly, item refusal rates on sensitive topics tended to be lower with audio computer-assisted self interview than with the other two methods. CONCLUSIONS: Combined with existing data from other countries and previous studies in Vietnam, these findings suggest that researchers should consider using audio computer-assisted self interview for future studies of sensitive and stigmatized topics, especially for men.


Subject(s)
HIV Infections , Health Behavior , Qualitative Research , User-Computer Interface , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , Interviews as Topic , Male , Middle Aged , Vietnam , Young Adult
4.
MEDICC Rev ; 13(3): 23-8, 2011 07.
Article in English | MEDLINE | ID: mdl-21778955

ABSTRACT

INTRODUCTION: Violent acts in young people constitute one of the most serious forms of violence in any society. Violence by young people in schools, on the streets, and in their families has been documented in many studies worldwide. Homicide and non-fatal assaults involving young people have been reported as a great global burden of premature death, injury and disability. Adolescents and young people are both the main victims and perpetrators of such violence. In Vietnam, an emerging pattern of health problems in adolescents related to intentional injury and violence is drawing increasingly more attention from government and the public. OBJECTIVE: Describe the situation of intentional injury among Vietnamese youth, including risk and protective factors, in order to suggest policy implications. METHODS: The 2003 Survey Assessment of Vietnamese Youth was used as a data source, providing a nationally representative sample of 7584 youth aged 14-25 years, resident in 42 of the country's 61 provinces. This sample was drawn from the 45,000 households in the 2002 Vietnam Living Standards Survey, with a multi-staged and stratified design, using the probability-proportional-to-size method to maintain representativity. Data were analyzed using bivariate and multivariate statistical techniques. RESULTS: Of the sample of young people, 2.2% reported injury resulting from violent behavior by a family member and 8.0% by non-family members, the latter demonstrating a significantly higher rate among males than females (13.6% vs. 2.4%). Characteristics of youth most likely to hurt others included: male sex, inebriation at some point, victims of intentional injury, group riot participants and carriers of weapons. Youth who had been members of mass social organizations or clubs in the community were half as likely to hurt other people as those who were unaffiliated with such groups. Females were almost four times more likely than males to attempt suicide. Other risk factors for suicide attempts were past inebriation (OR 2.7, 95% CI 1.3-5.4), ever having been a victim of intentional injury by a family member (OR 3.3, 95% CI 1.1-11.5) or ever having had feelings of hopelessness (OR 6.5, 95% CI 3.3-13.6). CONCLUSIONS: Prevalence of violence and self-harm among Vietnamese youth is comparatively less than in Western and other Asian countries. Risk and protective factors appear similar to those found in most populations. In particular, this study indicated a possible protective effect of membership in social groups. National policy for injury prevention should include strategies to reduce violence and self-harm within this population group.


Subject(s)
Self-Injurious Behavior/epidemiology , Self-Injurious Behavior/prevention & control , Violence/prevention & control , Violence/statistics & numerical data , Adolescent , Cross-Sectional Studies , Domestic Violence/prevention & control , Domestic Violence/statistics & numerical data , Female , Humans , Logistic Models , Male , Multivariate Analysis , Prevalence , Risk Factors , Risk-Taking , Socioeconomic Factors , Suicide/statistics & numerical data , Vietnam/epidemiology , Young Adult , Suicide Prevention
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