HIV Status Communication with Sex Partners and Associated Factors Among High-Risk MSM and Transgender Women in Lima, Peru.

Men who have sex with men (MSM) and transgender women (TW) are key populations in the HIV epidemic. HIV status communication between sex partners can inform decisions regarding sexual behavior. MSM and TW were asked about HIV status communication with sex partners at baseline, 9- and 18-months. GEE models assessed associations with HIV status communication at baseline using prevalence ratios (PRs) and longitudinally using odds ratios (ORs). At baseline, those who had previously had an HIV test, disclosed their HIV status to 42 % of their sex partners. HIV status communication was associated with knowing their sex partner's HIV status at baseline (aPR 5.20) and longitudinally (aOR 1.86). HIV positivity at baseline was negatively associated with HIV status communication during follow-up (aOR 0.55). All reported aPRs and aORs have p < 0.05. Interventions promoting HIV status communication and more frequent HIV testing should be explored as current efforts are insufficient.

HIV and Sexually Transmitted Infection Incidence and Associated Risk Factors Among High-Risk MSM and Male-to-Female Transgender Women in Lima, Peru.

BACKGROUND: Men who have sex with men (MSM) and male-to-female transgender women (TW) are at increased risk of HIV and sexually transmitted infections (STIs). We evaluated factors associated with incidence of HIV, HSV-2, and chlamydia and gonorrhea (anal and pharyngeal). METHODS: We used data from the Comunidades Positivas trial with MSM/TW who have sex with men in Lima, Peru. Participants were asked about sexual risk behaviors and underwent HIV/STI testing at baseline and 9- and 18-month follow-ups. We used discrete time proportional hazards regression to calculate hazard ratios for variables associated with incidence of each STI. RESULTS: Among 718 MSM/TW, HIV incidence was 3.6 cases per 100 person-years. HIV incidence was associated with having an incident STI adjusted hazard ratio (aHR) of 3.73. Unprotected receptive anal intercourse was associated with incident anal chlamydia (aHR 2.20). An increased number of sexual partners increased incident HSV-2 (aHR 3.15 for 6-14 partners and 3.97 for 15-46 partners compared with 0-2 partners). The risk of anal gonorrhea decreased with each sexually active year (aHR 0.94) and increased for unprotected compensated sex (aHR 2.36). The risk of pharyngeal gonorrhea also decreased with each year since sexual debut (aHR 0.95). The risk of anal chlamydia decreased with each sexually active year (aHR 0.96); the risk increased with reports of unprotected sex work (aHR 1.61) and unprotected receptive anal sex (aHR 2.63). All aHRs have P values <0.05. CONCLUSIONS: MSM/TW experience high incidence of HIV. Up-to-date prevalence and incidence information and identifying factors associated with infection can help develop a more effective combination prevention response.

Magnetic resonance imaging of stem cell apoptosis in arthritic joints with a caspase activatable contrast agent.

About 43 million individuals in the U.S. encounter cartilage injuries due to trauma or osteoarthritis, leading to joint pain and functional disability. Matrix-associated stem cell implants (MASI) represent a promising approach for repair of cartilage defects. However, limited survival of MASI creates a significant bottleneck for successful cartilage regeneration outcomes and functional reconstitution. We report an approach for noninvasive detection of stem cell apoptosis with magnetic resonance imaging (MRI), based on a caspase-3-sensitive nanoaggregation MRI probe (C-SNAM). C-SNAM self-assembles into nanoparticles after hydrolysis by caspase-3, leading to 90% amplification of (1)H MR signal and prolonged in vivo retention. Following intra-articular injection, C-SNAM causes significant MR signal enhancement in apoptotic MASI compared to viable MASI. Our results indicate that C-SNAM functions as an imaging probe for stem cell apoptosis in MASI. This concept could be applied to a broad range of cell transplants and target sites.

Magnetic resonance imaging and tracking of stem cells.

To date, several stem cell labeling protocols have been developed, contributing to a fast growing and promising field of stem cell imaging by MRI (magnetic resonance imaging). Most of these methods utilize iron oxide nanoparticles (MION, SPIO, USPIO, VSIOP) for cell labeling, which provide negative (dark) signal effects on T2-weighted MR images. The following protocol describes stem cell labeling techniques with commercially available gadolinium chelates, which provide positive contrast on T1-weighted MR images, which can be advantageous for specific applications.

The major facilitator superfamily (MFS) revisited.

The major facilitator superfamily (MFS) is the largest known superfamily of secondary carriers found in the biosphere. It is ubiquitously distributed throughout virtually all currently recognized organismal phyla. This superfamily currently (2012) consists of 74 families, each of which is usually concerned with the transport of a certain type of substrate. Many of these families, defined phylogenetically, do not include even a single member that is functionally characterized. In this article, we probe the evolutionary origins of these transporters, providing evidence that they arose from a single 2-transmembrane segment (TMS) hairpin structure that triplicated to give a 6-TMS unit that duplicated to a 12-TMS protein, the most frequent topological type of these permeases. We globally examine MFS protein topologies, focusing on exceptional proteins that deviate from the norm. Nine distantly related families appear to have members with 14 TMSs in which the extra two are usually centrally localized between the two 6-TMS repeat units. They probably have arisen by intragenic duplication of an adjacent hairpin. This alternative topology probably arose multiple times during MFS evolution. Convincing evidence for MFS permeases with fewer than 12 TMSs was not forthcoming, leading to the suggestion that all 12 TMSs are required for optimal function. Some homologs appear to have 13, 14, 15 or 16 TMSs, and the probable locations of the extra TMSs were identified. A few MFS permeases are fused to other functional domains or are fully duplicated to give 24-TMS proteins with dual functions. Finally, the MFS families with no known function were subjected to genomic context analyses leading to functional predictions.

Functional Promiscuity of Homologues of the Bacterial ArsA ATPases.

The ArsA ATPase of E. coli plays an essential role in arsenic detoxification. Published evidence implicates ArsA in the energization of As(III) efflux via the formation of an oxyanion-translocating complex with ArsB. In addition, eukaryotic ArsA homologues have several recognized functions unrelated to arsenic resistance. By aligning ArsA homologues, constructing phylogenetic trees, examining ArsA encoding operons, and estimating the probable coevolution of these homologues with putative transporters and auxiliary proteins unrelated to ArsB, we provide evidence for new functions for ArsA homologues. They may play roles in carbon starvation, gas vesicle biogenesis, and arsenic resistance. The results lead to the proposal that ArsA homologues energize four distinct and nonhomologous transporters, ArsB, ArsP, CstA, and Acr3.

The bacterial intimins and invasins: a large and novel family of secreted proteins.

BACKGROUND: Gram-negative bacteria have developed a limited repertoire of solutions for secreting proteins from the cytoplasmic compartment to the exterior of the cell. Amongst the spectrum of secreted proteins are the intimins and invasins (the Int/Inv family; TC# 1.B.54) which are characterized by an N-terminal ß-barrel domain and a C-terminal surface localized passenger domain. Despite the important role played by members of this family in diseases mediated by several species of the Enterobacteriaceae, there has been little appreciation for the distribution and diversity of these proteins amongst Gram-negative bacteria. Furthermore, there is little understanding of the molecular events governing secretion of these proteins to the extracellular milieu. PRINCIPAL FINDINGS: In silico approaches were used to analyze the domain organization and diversity of members of this secretion family. Proteins belonging to this family are predominantly associated with organisms from the γ-proteobacteria. Whilst proteins from the Chlamydia, γ-, ß- and ε-proteobacteria possess ß-barrel domains and passenger domains of various sizes, Int/Inv proteins from the α-proteobacteria, cyanobacteria and chlorobi possess only the predicted ß-barrel domains. Phylogenetic analyses revealed that with few exceptions these proteins cluster according to organismal type, indicating that divergence occurred contemporaneously with speciation, and that horizontal transfer was limited. Clustering patterns of the ß-barrel domains correlate well with those of the full-length proteins although the passenger domains do so with much less consistency. The modular subdomain design of the passenger domains suggests that subdomain duplication and deletion have occurred with high frequency over evolutionary time. However, all repeated subdomains are found in tandem, suggesting that subdomain shuffling occurred rarely if at all. Topological predictions for the ß-barrel domains are presented. CONCLUSION: Based on our in silico analyses we present a model for the biogenesis of these proteins. This study is the first of its kind to describe this unusual family of bacterial adhesins.