Although combination antiretroviral therapy has resulted in a considerable improvement in the treatment of human immunodeficiency virus (HIV) type 1 (HIV-1) infection, the emergence of resistant virus is a significant obstacle to the effective management of HIV infection and AIDS. We have developed a novel phenotypic drug susceptibility assay that may be useful in guiding therapy and improving long-term suppression of HIV replication. Susceptibility to protease (PR) and reverse transcriptase (RT) inhibitors is measured by using resistance test vectors (RTVs) that contain a luciferase indicator gene and PR and RT sequences derived from HIV-1 in patient plasma. Cells are transfected with RTV DNA, resulting in the production of virus particles that are used to infect target cells. Since RTVs are replication defective, luciferase activity is measured following a single round of replication. The assay has been automated to increase throughput and is completed in 8 to 10 days. Test results may be useful in facilitating the selection of optimal treatment regimens for patients who have failed prior therapy or drug-naive patients infected with drug-resistant virus. In addition, the assay can be used to evaluate candidate drugs and assist in the development of new drugs that are active against resistant strains of HIV-1.

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BackgroundSeveral prospective studies have been conducted to examine the relationship between fruit juice intake and risk of incident type 2 diabetes, but results have been mixed. In the present study, we aimed to estimate the association between fruit juice intake and risk of type 2 diabetes.MethodsPubMed and Embase databases were searched up to December 2013. All prospective cohort studies of fruit juice intake with risk of type 2 diabetes were included. The pooled relative risks (RRs) with 95% confidence intervals (CIs) for highest vs. lowest category of fruit juice intake were estimated using a random-effects model.ResultsA total of four studies (191,686 participants, including 12,375 with type 2 diabetes) investigated the association between sugar-sweetened fruit juice and risk of incident type 2 diabetes, and four studies (137,663 participants and 4,906 cases) investigated the association between 100% fruit juice and risk of incident type 2 diabetes. A higher intake of sugar-sweetened fruit juice was significantly associated with risk of type 2 diabetes (RR = 1.28, 95%CI = 1.04–1.59, p = 0.02), while intake of 100% fruit juice was not associated with risk of developing type 2 diabetes (RR = 1.03, 95% CI = 0.91–1.18, p = 0.62).ConclusionsOur findings support dietary recommendations to limit sugar-sweetened beverages, such as fruit juice with added sugar, to prevent the development of type 2 diabetes.

Appressorium formation plays a critical role in Magnaporthe oryzae. Mst50 is an adapter protein of the Mst11-Mst7-Pmk1 cascade that is essential for appressorium formation. To further characterize its functions, affinity purification was used to identify Mst50-interacting proteins (MIPs) in this study. Two of the MIPs are Mst11 and Mst7 that are known to interact with Mst50 for Pmk1 activation. Surprisingly, two other MIPs are Mck1 and Mkk2 that are the upstream kinases of the Mps1 pathway. Domain deletion analysis showed that the sterile alpha-motif of Mst50 but not the Ras-association domain was important for its interaction with Mck1 and responses to cell wall and oxidative stresses. The mst50 mutant was reduced in Mps1 activation under stress conditions. MIP11 encodes a RACK1 protein that also interacted with Mck1. Deletion of MIP11 resulted in defects in cell wall integrity, Mps1 phosphorylation and plant infection. Furthermore, Mst50 interacted with histidine kinase Hik1, and the mst50 mutant was reduced in Osm1 phosphorylation. These results indicated that Mst50 is involved in all three MAPK pathways in M. oryzae although its functions differ in each pathway. Several MIPs are conserved hypothetical proteins and may be involved in responses to various signals and crosstalk among signaling pathways.

Protein tyrosine phosphorylation is a common mechanism of signaling in pathways that regulate T cell receptor-mediated cell activation, cell proliferation, and the cell cycle. Because human immunodeficiency virus (HIV) is though to affect normal cell signaling, tyrosine phosphorylation may be associated with HIV cytopathicity. In both HIV-infected cells and transfected cells that stably express HIV envelope glycoproteins undergoing HIVgp41-induced cell fusion, a 30-kilodalton protein was phosphorylated on tyrosine with kinetics similar to those of syncytium formation and cell death. When tyrosine phosphorylation was inhibited by the protein tyrosine kinase inhibitor herbimycin A, envelope-mediated syncytium formation was coordinately reduced. These studies show that specific intracellular signals, which apparently participate in cytopathicity, are generated by HIV and suggest strategies by which the fusion process might be interrupted.