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Annick Bórquez Anne Cori Erica L. Pufall Jingo Kasule Emma Slaymaker Alison Price Jocelyn Elmes Basia Zaba Amelia C. Crampin Joseph Kagaayi Tom Lutalo Mark Urassa Simon Gregson Timothy B. Hallett 《PLoS medicine》2016,13(9)
BackgroundProgrammatic planning in HIV requires estimates of the distribution of new HIV infections according to identifiable characteristics of individuals. In sub-Saharan Africa, robust routine data sources and historical epidemiological observations are available to inform and validate such estimates.ConclusionsIt is possible to reliably predict the distribution of new HIV infections acquired using data routinely available in many countries in the sub-Saharan African region with a single relatively simple mathematical model. This tool would complement more specific analyses to guide resource allocation, data collection, and programme planning. 相似文献
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Erica L. Pufall Constance Nyamukapa Jeffrey W. Eaton Reggie Mutsindiri Godwin Chawira Shungu Munyati Laura Robertson Simon Gregson 《PloS one》2014,9(11)
Background
There are an estimated half-million children living with HIV in sub-Saharan Africa. The predominant source of infection is presumed to be perinatal mother-to-child transmission, but general population data about paediatric HIV are sparse. We characterise the epidemiology of HIV in children in sub-Saharan Africa by describing the prevalence, possible source of infection, and effects of paediatric HIV in a southern African population.Methods
From 2009 to 2011, we conducted a household-based survey of 3389 children (aged 2–14 years) in Manicaland, eastern Zimbabwe (response rate: 73.5%). Data about socio-demographic correlates of HIV, risk factors for infection, and effects on child health were analysed using multi-variable logistic regression. To assess the plausibility of mother-to-child transmission, child HIV infection was linked to maternal survival and HIV status using data from a 12-year adult HIV cohort.Results
HIV prevalence was (2.2%, 95% CI: 1.6–2.8%) and did not differ significantly by sex, socio-economic status, location, religion, or child age. Infected children were more likely to be underweight (19.6% versus 10.0%, p = 0.03) or stunted (39.1% versus 30.6%, p = 0.04) but did not report poorer physical or psychological ill-health. Where maternal data were available, reported mothers of 61/62 HIV-positive children were deceased or HIV-positive. Risk factors for other sources of infection were not associated with child HIV infection, including blood transfusion, vaccinations, caring for a sick relative, and sexual abuse. The observed flat age-pattern of HIV prevalence was consistent with UNAIDS estimates which assumes perinatal mother-to-child transmission, although modelled prevalence was higher than observed prevalence. Only 19/73 HIV-positive children (26.0%) were diagnosed, but, of these, 17 were on antiretroviral therapy.Conclusions
Childhood HIV infection likely arises predominantly from mother-to-child transmission and is associated with poorer physical development. Overall antiretroviral therapy uptake was low, with the primary barrier to treatment appearing to be lack of diagnosis. 相似文献3.
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Serafimova IM Pufall MA Krishnan S Duda K Cohen MS Maglathlin RL McFarland JM Miller RM Frödin M Taunton J 《Nature chemical biology》2012,8(5):471-476
Targeting noncatalytic cysteine residues with irreversible acrylamide-based inhibitors is a powerful approach for enhancing pharmacological potency and selectivity. Nevertheless, concerns about off-target modification motivate the development of reversible cysteine-targeting strategies. Here we show that electron-deficient olefins, including acrylamides, can be tuned to react with cysteine thiols in a rapidly reversible manner. Installation of a nitrile group increased the olefins' intrinsic reactivity, but, paradoxically, eliminated the formation of irreversible adducts. Incorporation of these electrophiles into a noncovalent kinase-recognition scaffold produced slowly dissociating, covalent inhibitors of the p90 ribosomal protein S6 kinase RSK2. A cocrystal structure revealed specific noncovalent interactions that stabilize the complex by positioning the electrophilic carbon near the targeted cysteine. Disruption of these interactions by protein unfolding or proteolysis promoted instantaneous cleavage of the covalent bond. Our results establish a chemistry-based framework for engineering sustained covalent inhibition without accumulating permanently modified proteins and peptides. 相似文献
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Structural analysis of the autoinhibition of Ets-1 and its role in protein partnerships 总被引:3,自引:0,他引:3
Garvie CW Pufall MA Graves BJ Wolberger C 《The Journal of biological chemistry》2002,277(47):45529-45536
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A new study identifies the long noncoding RNA Pint as a regulator of cellular proliferation and a target of the p53 pathway. See related Research, http://genomebiology.com/2013/14/9/R104 相似文献