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  • Article
    Stegehuis C, van der Hofstad R, van Leeuwaarden JS.
    Sci Rep. 2016 07 21;6:29748.
    Many real-world networks display a community structure. We study two random graph models that create a network with similar community structure as a given network. One model preserves the exact community structure of the original network, while the other model only preserves the set of communities and the vertex degrees. These models show that community structure is an important determinant of the behavior of percolation processes on networks, such as information diffusion or virus spreading: the community structure can both enforce as well as inhibit diffusion processes. Our models further show that it is the mesoscopic set of communities that matters. The exact internal structures of communities barely influence the behavior of percolation processes across networks. This insensitivity is likely due to the relative denseness of the communities.
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  • Article
    Ha JH, Van Lith LM, Mallalieu EC, Chidassicua J, Pinho MD, Devos P, Wirtz AL.
    BMJ Open. 2019 10 07;9(10):e029748.
    OBJECTIVES: Increasing and sustaining engagement in HIV care for people living with HIV are critical to both individual therapeutic benefit and epidemic control. Men are less likely to test for HIV compared with women in sub-Saharan African countries, and ultimately have delayed entry to HIV care. Stigma is known to impede such engagement, placing an importance on understanding and addressing stigma to improve HIV testing and care outcomes. This study aimed to assess the gendered differences in the relationship between stigma and HIV testing.
    DESIGN AND SETTING: A cross-sectional, household probability survey was implemented between November and December 2016 in the Sofala province of Mozambique.
    PARTICIPANTS: Data were restricted to men and women participants who reported no prior diagnosis of HIV infection (N=2731).
    MEASURES: Measures of sociodemographic characteristics, stigma and past exposure to HIV interventions were included in gender-stratified logistic regression models to estimate the relationship between stigma and recent testing for HIV, as well as to identify other relevant correlates.
    RESULTS: Significantly fewer men (38.3%) than women (47.6%; p<0.001) had recently tested for HIV. Men who reported previous engagement in community group discussions about HIV had an increased odds of testing in the past 12 months compared to those who had not participated (adjusted OR (aOR)=1.92; 95% CI 1.51 to 2.44). Concerns about stigma were not a commonly reported barrier to HIV testing; however, men who expressed anticipated individual HIV stigma had a 35% lower odds of recent HIV testing (aOR=0.65; 95% CI 0.44 to 0.96). This association was not observed among women.
    CONCLUSIONS: Men have lower uptake of HIV testing in Mozambique when compared to women. Even amidst the beneficial effects of HIV messaging, individual stigma is negatively associated with recent HIV testing among men. Intervention efforts that target the unique challenges and needs of men are essential in promoting men's engagement into the HIV care continuum in sub-Saharan Africa.
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  • Article
    Lundberg P, Johansson E, Okello E, Allebeck P, Thorson A.
    PLoS One. 2012;7(1):e29748.
    Persons with severe mental illness (SMI) engage in risky sexual behaviours and have high prevalence of HIV in high-income countries. Little is known about sexual behaviours and HIV risk among persons with SMI in sub-Saharan Africa. In this qualitative study we explored how SMI may influence sexual risk behaviours and sexual health risks in Uganda. Individual semi-structured interviews were conducted with 7 male and 13 female psychiatric patients aged 18-49 years. Participants were interviewed in hospital when clinically stable and capable of giving informed consent. Interview transcripts were analysed using manifest content analysis, generating the categories: (1) casual sex during illness episodes, (2) rape by non-partners, (3) exploitation by partners, (4) non-monogamous partners, and (5) sexual inactivity. Our findings suggest that SMI exacerbated sexual vulnerability in the women interviewed, by contributing to casual sex, to exploitative and non-monogamous sexual relationships, and to sexual assault by non-partners. No link could be established between SMI and increased sexual risk behaviours in the men interviewed, due to a small sample of men, and given that men's accounts showed little variability. Our findings also suggest that SMI caused sexual inactivity due to decreased sexual desire, and in men, due to difficulties forming an intimate relationship. Overall, our study highlights how SMI and gender inequality can contribute to the shaping of sexual risk behaviours and sexual health risks, including HIV risk, among persons with SMI in this Ugandan setting.
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  • Article
    Kamura T, Burian D, Yan Q, Schmidt SL, Lane WS, Querido E, Branton PE, Shilatifard A, Conaway RC, Conaway JW.
    J Biol Chem. 2001 Aug 10;276(32):29748-53.
    The heterodimeric Elongin BC complex has been shown to interact in vitro and in mammalian cells with a conserved BC-box motif found in a growing number of proteins including RNA polymerase II elongation factor Elongin A, SOCS-box proteins, and the von Hippel-Lindau (VHL) tumor suppressor protein. Recently, the VHL-Elongin BC complex was found to interact with a module composed of Cullin family member Cul2 and RING-H2 finger protein Rbx1 to reconstitute a novel E3 ubiquitin ligase that activates ubiquitylation by the E2 ubiquitin-conjugating enzymes Ubc5 and Cdc34. In the context of the VHL ubiquitin ligase, Elongin BC functions as an adaptor that links the VHL protein to the Cul2/Rbx1 module, raising the possibility that the Elongin BC complex could function as an integral component of a larger family of E3 ubiquitin ligases by linking alternative BC-box proteins to Cullin/Rbx1 modules. In this report, we describe identification and purification from rat liver of a novel leucine-rich repeat-containing BC-box protein, MUF1, which we demonstrate is capable of assembling with a Cullin/Rbx1 module containing the Cullin family member Cul5 to reconstitute ubiquitin ligase activity. In addition, we show that the additional BC-box proteins Elongin A, SOCS1, and WSB1 are also capable of assembling with the Cul5/Rbx1 module to reconstitute potential ubiquitin ligases. Taken together, our findings identify MUF1 as a new member of the BC-box family of proteins, and they predict the existence of a larger family of Elongin BC-based E3 ubiquitin ligases.
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  • Article
    Janssen GM, Maassen JA, van Den Ouweland JM.
    J Biol Chem. 1999 Oct 15;274(42):29744-8.
    Cells harboring patient-derived mitochondria with an A-to-G transition at nucleotide position 3243 of their mitochondrial DNA display severe loss of respiration when compared with cells containing the wild-type adenine but otherwise identical mitochondrial DNA sequence. The amount and degree of leucylation of tRNA(Leu(UUR)) were both found to be highly reduced in mutant cells. Despite the low level of leucyl-tRNA(Leu(UUR)), the rate of mitochondrial translation was not seriously affected by this mutation. Therefore, decrease of mitochondrial protein synthesis as such does not appear to be a necessary prerequisite for loss of respiration. Rather, the mitochondrially encoded proteins seem subject to elevated degradation, leading to a severe reduction in their steady state levels. Our results favor a scheme in which the 3243 mutation causes loss of respiration through accelerated protein degradation, leading to a disequilibrium between the levels of mitochondrial and nuclear encoded respiratory chain subunits and thereby a reduction of functional respiratory chain complexes. The possible mechanisms underlying the pathogenesis of mitochondrial diabetes is discussed.
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  • Article
    Scherrer KJN, Harrison CS, Heneghan RF, Galbraith E, Bardeen CG, Coupe J, Jägermeyr J, Lovenduski NS, Luna A, Robock A, Stevens J, Stevenson S, Toon OB, Xia L.
    Proc Natl Acad Sci U S A. 2020 11 24;117(47):29748-29758.
    Nuclear war, beyond its devastating direct impacts, is expected to cause global climatic perturbations through injections of soot into the upper atmosphere. Reduced temperature and sunlight could drive unprecedented reductions in agricultural production, endangering global food security. However, the effects of nuclear war on marine wild-capture fisheries, which significantly contribute to the global animal protein and micronutrient supply, remain unexplored. We simulate the climatic effects of six war scenarios on fish biomass and catch globally, using a state-of-the-art Earth system model and global process-based fisheries model. We also simulate how either rapidly increased fish demand (driven by food shortages) or decreased ability to fish (due to infrastructure disruptions), would affect global catches, and test the benefits of strong prewar fisheries management. We find a decade-long negative climatic impact that intensifies with soot emissions, with global biomass and catch falling by up to 18 ± 3% and 29 ± 7% after a US-Russia war under business-as-usual fishing-similar in magnitude to the end-of-century declines under unmitigated global warming. When war occurs in an overfished state, increasing demand increases short-term (1 to 2 y) catch by at most ∼30% followed by precipitous declines of up to ∼70%, thus offsetting only a minor fraction of agricultural losses. However, effective prewar management that rebuilds fish biomass could ensure a short-term catch buffer large enough to replace ∼43 ± 35% of today's global animal protein production. This buffering function in the event of a global food emergency adds to the many previously known economic and ecological benefits of effective and precautionary fisheries management.
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  • Article
    Ota K, Sakaguchi M, Hamasaki N, Mihara K.
    J Biol Chem. 2000 Sep 22;275(38):29743-8.
    We have investigated the topogenic rules of multispanning membrane proteins using erythrocyte band 3. Here, the fine structural requirements for the correct disposition of its second transmembrane segment (TM2) were assessed. We made fusion proteins where TM1 and the loop sequence preceding TM2 were changed and fused to prolactin. They were expressed in a cell-free system supplemented with rough microsomal membrane, and their topologies on the membrane were assessed by protease sensitivity and N-glycosylation. TM1 was demonstrated to be a signal-anchor sequence that mediates translocation of the downstream portion, and thus TM2 should be responsible to halt the translocation to acquire TM topology. When the loop between TM1 and TM2 was elongated, however, TM2 was readily translocated through the membrane and not integrated. For the membrane integration of TM2, TM2 must be in close proximity to TM1. The TM1 can be replaced with another signal-anchor sequence with a long hydrophobic segment but not with a signal sequence with shorter hydrophobic stretch. The length of the hydrophobic segment affected final topology of TM2. We concluded that the two TM segments work synergistically within the translocon to acquire the correct topology and that the length of the preceding signal sequence is critical for stable transmembrane assembly of TM2. We propose that direct interaction among the TM segments is one of the critical factors for the transmembrane topogenesis of multispanning membrane proteins.
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