23 research outputs found

    Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies

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    Recognition of N-linked glycan at residue N276 (glycan276) at the periphery of the CD4-binding site (CD4bs) on the HIV-envelope trimer is a formidable challenge for many CD4bs-directed antibodies. To understand how this glycan can be recognized, here we isolate two lineages of glycan276-dependent CD4bs antibodies. Antibody CH540-VRC40.01 (named for donor-lineage.clone) neutralizes 81% of a panel of 208 diverse strains, while antibody CH314-VRC33.01 neutralizes 45%. Cryo-electron microscopy (cryo-EM) structures of these two antibodies and 179NC75, a previously identified glycan276-dependent CD4bs antibody, in complex with HIV-envelope trimer reveal substantially different modes of glycan276 recognition. Despite these differences, binding of glycan276-dependent antibodies maintains a glycan276 conformation similar to that observed in the absence of glycan276-binding antibodies. By contrast, glycan276-independent CD4bs antibodies, such as VRC01, displace glycan276 upon binding. These results provide a foundation for understanding antibody recognition of glycan276 and suggest its presence may be crucial for priming immunogens seeking to initiate broad CD4bs recognition

    Mudança organizacional: uma abordagem preliminar

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    Does Physical Intimate Partner Violence Affect Sexual Health?: A Systematic Review

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    Forty years of published research (1966-2006) addressing physical intimate partner violence (IPV) and sexual health was reviewed (51 manuscripts) and synthesized to determine (a) those sexual health indicators for which sufficient evidence is available to suggest a causal association and (b) gaps in the literature for which additional careful research is needed to establish causality and explain mechanisms for these associations. Sexual health was defined as a continuum of indicators of gynecology and reproductive health. IPV was consistently associated with sexual risk taking, inconsistent condom use, or partner nonmonogamy (23 of 27 studies), having an unplanned pregnancy or induced abortion (13 of 16 studies), having a sexually transmitted infection (17 of 24 studies), and sexual dysfunction (17 of 18 studies). A conceptual model was presented to guide further needed research addressing direct and indirect mechanisms by which physical, sexual, and psychological IPV affects sexual health
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