HIV Among MSM and Heterosexual Women in the United States: An Ecologic Analysis.

Phylogenetic studies show links between heterosexual women and men who have sex with men (MSM) that are more numerous than from heterosexual men to women suggesting that HIV infections among heterosexual women may stem from MSM. Poor communities have been associated with high rates of HIV among heterosexual women. Our analysis investigates potential transmission of HIV between MSM and female heterosexuals. National HIV Behavioral Surveillance data describe transmission risk behaviors of MSM, and HIV case reporting data describe the percentages of cases that are attributed to transmission risk categories. We examined correlations between the percentages of men who were MSM who also have sex with women and female heterosexual cases. We also examined census data to characterize each city in terms of poverty level and race/ethnicity makeup. There was a high correlation (0.93) between the percentage of reported living HIV cases attributed to male heterosexual contact and female heterosexual contact and a moderate nonsignificant correlation (0.49) between the percentage of MSM who were men who have sex with men and women (MSMW) in National HIV Behavioral Surveillance and the percentage of reported cases that were attributed to female heterosexual contact suggesting some potential overlap. Cities with high levels of poverty and African American/Black residents had higher levels of MSMW and higher levels of heterosexual female cases. Addressing HIV in cities with high levels of MSMW may have the dual effect of improving the health of MSM populations that have a high burden of HIV and to improve the health of their larger communities

Structural and mechanistic insights into an extracytoplasmic copper trafficking pathway in <i>Streptomyces lividans</i>

In Streptomyces lividans an extracytoplasmic copper-binding Sco protein plays a role in two unlinked processes: (i) initiating a morphological development switch and (ii) facilitating the co-factoring of the CuA domain of CcO (cytochrome c oxidase). How Sco obtains copper once secreted to the extracytoplasmic environment is unknown. In the present paper we report on a protein possessing an HX6MX21HXM motif that binds a single cuprous ion with subfemtomolar affinity. High-resolution X-ray structures of this extracytoplasmic copper chaperone-like protein (ECuC) in the apo- and Cu(I)-bound states reveal that the latter possesses a surface-accessible cuprous-ion-binding site located in a dish-shaped region of β-sheet structure. A cuprous ion is transferred under a favourable thermodynamic gradient from ECuC to Sco with no back transfer occurring. The ionization properties of the cysteine residues in the Cys86xxxCys90 copper-binding motif of Sco, together with their positional locations identified from an X-ray structure of Sco, suggests a role for Cys86 in initiating an inter-complex ligand-exchange reaction with Cu(I)–ECuC. Generation of the genetic knockouts, Δsco, Δecuc and Δsco/ecuc, and subsequent in vivo assays lend support to the existence of a branched extracytoplasmic copper-trafficking pathway in S. lividans. One branch requires both Sco and to a certain extent ECuC to cofactor the CuA domain, whereas the other uses only Sco to deliver copper to a cuproenzyme to initiate morphological development.</jats:p