Spiraling Risk: Visualizing the multilevel factors that socially pattern HIV risk among gay, bisexual & other men who have sex with men using Complex Systems Theory.

PURPOSE OF REVIEW: Global disparities in HIV infection, particularly among gay, bisexual, and other men who have sex with men (GBMSM), indicate the importance of exploring the multi-level processes that shape HIV's spread. We used Complex Systems Theory and the PRISMA guidelines to conduct a systematic review of 63 global reviews to understand how HIV is socially patterned among GBMSM. The purpose was to conduct a thematic analysis of the reviews to (1) synthesize the multi-level risk factors of HIV risk, (2) categorize risk across the socioecological model, and (3) develop a conceptual model that visualizes the interrelated factors that shape GBMSMS's HIV "risk." RECENT FINDINGS: We included 49 studies of high and moderate quality studies. Results indicated that GBMSM's HIV risk stems from the individual, interpersonal, and structural levels of the socioecological model. We identified a few themes that shape GBMSM's risk of HIV infection related to biomedical prevention methods; sexual and sex-seeking behaviors; behavioral prevention methods; individual-level characteristics and syndemic infections; lived experiences and interpersonal relationships; country-level income; country-level HIV prevalence; and structural stigma. The multi-level factors, in tandem, serve to perpetuate GBMSM's risk of HIV infection globally. The amalgamation of our thematic analyses from our systematic reviews of reviews suggests that the risk of HIV infection operates in an emergent, dynamic, and complex nature across multiple levels of the socioecological model. Applying complex systems theory indicates how multilevel factors create a dynamic and reinforcing system of HIV risk among GBMSM.

Conformational analysis of the tachykinins in solution: substance P and physalaemin.

A determination of the solution conformational behavior of two tachykinins, substance P and physalaemin, is described. Two-dimensional homonuclear Hartmann-Hahn (HOHAHA) and rotating-frame cross relaxation spectroscopy (ROESY) are used to obtain complete proton resonance assignments. Interproton distance restraints obtained from ROESY spectroscopy are used to characterize the conformational behavior. These data show that in solution both substance P and physalaemin exist in a mixture of conformational states, rather than as a single three-dimensional structure. In water both peptides prefer to be in an extended chain structure. In methanol, their behavior is described as a mixture of beta-turn conformations in dynamic equilibrium. Solvent titration data and chemical shift temperature coefficients complement the NMR estimate of interproton distances by locating hydrogen bonds and serving to identify predominant conformational states. The C-terminal tetrapeptide segment has the same conformational behavior for both substance P and physalaemin. In physalaemin, the midsegment of the peptide may also be constrained by formation of a salt bridge. The conformational behavior of substance P and physalaemin is discussed in relation to potency and receptor binding properties.

Methylation of RNA purine bases by methyl radicals.

During the metabolism of 1,2-dimethylhydrazine (a colon carcinogen) in rats, methyl radicals (.CH3) are produced. To gain an insight into the nature of .CH3 interactions with biomolecules in vivo, we conducted in vitro studies using RNA as a model compound. RNA was incubated in a system where .CH3 was generated from the oxidation of dimethyl sulfoxide by hydroxyl radicals (.OH); .OH was produced from a Fenton-type reaction between Fe(2+)-EDTA and H2O2. Four new products were detected from acid hydrolysates of .CH3-treated RNA: 8-methylguanine, 2-methyladenine, 8-methyladenine, and a highly unstable compound of unknown structure. The production was significantly affected by pH. The concentrations of Fe2+ and H2O2 influenced the production of methylated purine residues in a dose-dependent manner. Catalase, ethanol, alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone, and O2 inhibited the production of methylated nucleobases.

Solution conformation of the actinomycin D related pentapeptide lactone using NMR and molecular modeling.

A detailed description of the two observed solution conformations of the pentapeptide lactone fragment of actinomycin D is presented using the distance constraints obtained from two-dimensional nuclear Overhauser enhancement spectra in combination with minimum energy calculations. Low energy conformational states that are compatible with the experimental distances are found for each of the two conformers. For one conformer, an all trans peptide bond conformer, is found with no intramolecular hydrogen bonds. For the other conformer, the D-Val-Pro and Pro-Sar peptide bonds were cis; this solution conformation is the same as that found in both the crystal structure of the pentapeptide lactone as well as of the native actinomycin D itself. These results are discussed in terms of the combined influence of conformation and the effects of mutual intramolecular association of the pentapeptide lactone moieties in native actinomycin D on its cytotoxic activity.