Reducing HIV Risk among Transgender Women in Thailand: A Quasi-Experimental Evaluation of the Sisters Program

Transgender women are particularly at risk of HIV infection, but little evidence exists on effective HIV prevention strategies with this population. We evaluated whether Sisters, a peer-led program for transgender women, could reduce HIV risks in Pattaya, Thailand. The study used time-location sampling to recruit 308 transgender women in Pattaya into a behavioral survey in 2011. Coarsened exact matching was used to create statistically equivalent groups of program participants and non-participants, based on factors influencing likelihood of program participation. Using multivariable logistic regression, we estimated effects of any program participation and participation by delivery channel on: condom use at last sex; consistent condom and condom/water-based lubricant use in the past 3 months with commercial, casual, and regular partners; and receipt of HIV testing in the past 6 months. Program coverage reached 75% of the population. In a matched sub-sample (n = 238), participation in outreach was associated with consistent condom/water-based lubricant use with commercial partners (AOR 3.22, 95% CI 1.64–6.31). Attendance at the Sisters drop-in center was associated with receiving an HIV test (AOR 2.58, 95% CI 1.47–4.52). Dedicated transgender-friendly programs are effective at reducing HIV risks and require expansion to better serve this key population and improve HIV prevention strategies.     

Insulin receptor monoclonal antibodies that mimic insulin action without activating tyrosine kinase

HTC rat hepatoma cells were transfected with human insulin receptor cDNA to a level of 40,000 receptors/cell. In these cells, as well as in nontransfected cells, insulin stimulated the uptake of alpha-aminoisobutyric acid. Two monoclonal antibodies directed against the human insulin receptor alpha subunit, like insulin, stimulated amino acid uptake in transfected HTC cells, but not in nontransfected HTC cells. The antibodies, in contrast to insulin, failed to stimulate insulin receptor tyrosine kinase activity, both in intact transfected cells and in cell free extracts prepared from them. These data suggest, therefore, that activation of insulin receptor tyrosine kinase may not be an obligatory step in all of the transmembrane signaling mechanisms of the insulin receptor.     

The cytolytic activity of pulmonary CD8+ lymphocytes, induced by infection with a vaccinia virus recombinant expressing the M2 protein of respiratory syncytial virus (RSV), correlates with resistance to RSV infection in mice.

Previous studies demonstrated that the pulmonary resistance to respiratory syncytial virus (RSV) challenge induced by immunization with a recombinant vaccinia virus expressing the M2 protein of RSV (vac-M2) was significantly greater 9 days after immunization than at 28 days and was mediated predominantly by CD8+ T cells. In this study, we have extended these findings and sought to determine whether the level of CD8+ cytotoxic T-lymphocyte (CTL) activity measured in vitro correlates with the resistance to RSV challenge in vivo. Three lines of evidence documented an association between the presence of pulmonary CTL activity and resistance to RSV challenge. First, vac-M2 immunization induced pulmonary CD8+ CTL activity and pulmonary resistance to RSV infection in BALB/c (H-2d) mice, whereas significant levels of pulmonary CTL activity and resistance to RSV infection were not seen in BALB.K (H-2k) or BALB.B (H-2b) mice. Second, pulmonary CD8+ CTL activity was not induced by infection with other vaccinia virus-RSV recombinants that did not induce resistance to RSV challenge. Third, the peak of pulmonary CTL activity correlated with the peak of resistance to RSV replication (day 6), with little resistance being observed 45 days after immunization. An accelerated clearance of virus was not observed when mice were challenged with RSV 45 days after immunization with vac-M2. The results indicate that resistance to RSV induced by immunization with vac-M2 is mainly mediated by primary pulmonary CTLs and that this resistance decreases to very low levels within 2 months following immunization. The implications for inclusion of CTL epitopes into RSV vaccines are discussed in the context of these observations.     

Proline transport increases growth efficiency in salt-stressed Streptomyces griseus.

Streptomyces griseus synthesizes proline for osmoregulation under salt stress. Uptake of exogenous [14C]proline and internal synthesis of proline were quantified in cells growing at salt concentrations from 0 to 1 M NaCl. Externally supplied proline accounted for an increased proportion of the intracellular pool of free proline as salt concentration was increased, but neither the concentration nor the composition of the internal amino acid pool was substantially altered by supply of exogenous proline. Uptake of exogenous proline significantly increased the specific growth yield of S. griseus growing under salt stress; the increased yield was proportional to reductions in proline synthesis.     

Pathway of degradation of nitrilotriacetate by a Pseudomonas species.

The pathway of degradation of nitrilotriacetate (NTA) was determined by using cell-free extracts and a 35-fold purification of NTA monooxygenase. The first step in the breakdown was an oxidative cleavage of the tertiary amine by the monooxygenase to form the aldo acid, glyoxylate, and the secondary amine, iminodiacetate (IDA). NTA N-oxide acted as a substrate analog for induction of the monooxygenase and was slowly metabolized by the enzyme, but was not an intermediate in the pathway. No intermediate before IDA was found, but an unstable alpha-hydroxy-NTA intermediate was postulated. IDA did undergo cleavage in the presence of the purified monooxygenase to give glyoxylate and glycine, but was not metabolized in cell-free extracts. Glyoxylate was further metabolized by cell-free extracts to yield CO2 and glycerate or glycine, products also found from NTA metabolism. Of the three bacterial isolates in which the NTA pathway has been studied, two strains, one isolated from a British soil and ours from a Michigan soil, appear to be almost identical.     

A nitrilotriacetic acid monooxygenase with conditional NADH-oxidase activity.

A tertiary amine monoxygenase from a Pseudomonas sp. was partially purified (35-fold) and characterized. In the presence of nitrilotriacetate (NTA), O₂, NADH, and Mn²⁺, the enzyme yielded two sets of products: iminodiacetate, glyoxylate, NAD⁺ and H₂O; or H₂O₂ and NAD⁺. Which set of products predominated was a function of enzyme concentration, ionic strength of solution, pH, and cation supplied. NTA functioned both as a modifiable substrate and as a stimulator of NADH oxidase activity. A requirement for preincubation with Mn²⁺ and NTA to eliminate enzyme hysteresis and the similar Km values for NTA and Mn²⁺ suggested that the substrate and metal were bound as a unit by the enzyme.     

Biodegradation of Metal-Nitrilotriacetate Complexes by a Pseudomonas Species: Mechanism of Reaction

A nitrilotriacetate (NTA)-degrading Pseudomonas species was shown to degrade Ca, Mn, Mg, Cu, Zn, Cd, Fe, and Na chelates of NTA at nearly equal rates when the appropriate metal concentrations are low enough to avoid toxicity from the freed metal. Ni-NTA, however, was not degraded. When higher concentrations of metal-NTA substrates were used, soil stimulated degradation of Cu, Zn, and Cd complexes, probably as a result of binding toxic freed metals. The metal associated with the NTA substrate does not appear to be transported into the cell, since metals do not accumulate in the cells and the presence of NTA reduces metal toxicity. The data are consistent with the hypothesis that an envelope-associated component, probably a transport protein involved in binding, is responsible for the disassociation of the metal from the NTA. Both soil and this NTA-degrading organism destabilize the metal-NTA complex, which suggests that in the natural environment both would act to limit mobilization of metals as soluble NTA chelates. Crude soluble enzyme preparations degrade Fe-, Mn-, and Na-NTA complexes but not Cu-NTA.