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Increased chronic immune activation and inflammation are hallmarks of HIV/SIV infection and are highly correlated with progression to AIDS and development of non-AIDS comorbidities, such as hypercoagulability and cardiovascular disease. Intestinal dysfunction resulting in microbial translocation has been proposed as a lead cause of systemic immune activation and hypercoagulability in HIV/SIV infection. Our goal was to assess the biological and clinical impact of a therapeutic strategy designed to reduce microbial translocation through reduction of the microbial content of the intestine (Rifaximin-RFX) and of gut inflammation (Sulfasalazine-SFZ). RFX is an intraluminal antibiotic that was successfully used in patients with hepatic encephalopathy. SFZ is an antiinflammatory drug successfully used in patients with mild to moderate inflammatory bowel disease. Both these clinical conditions are associated with increased microbial translocation, similar to HIV-infected patients. Treatment was administered for 90 days to five acutely SIV-infected pigtailed macaques (PTMs) starting at the time of infection; seven untreated SIVsab-infected PTMs were used as controls. RFX+SFZ were also administered for 90 days to three chronically SIVsab-infected PTMs. RFX+SFZ administration during acute SIVsab infection of PTMs resulted in: significantly lower microbial translocation, lower systemic immune activation, lower viral replication, better preservation of mucosal CD4+ T cells and significantly lower levels of hypercoagulation biomarkers. This effect was clear during the first 40 days of treatment and was lost during the last stages of treatment. Administration of RFX+SFZ to chronically SIVsab-infected PTMs had no discernible effect on infection. Our data thus indicate that early RFX+SFZ administration transiently improves the natural history of acute and postacute SIV infection, but has no effect during chronic infection.

Four wave-propelled autonomous vehicles (Wave Gliders) instrumented with a variety of oceanographic and meteorological sensors were launched from San Francisco, CA in November 2011 for a trans-Pacific (Pac-X) voyage to test platform endurance. Two arrived in Australia, one in Dec 2012 and one in February 2013, while the two destined for Japan both ran into technical difficulties and did not arrive at their destination. The gliders were all equipped with sensors to measure temperature, salinity, turbidity, oxygen, and both chlorophyll and oil fluorescence. Here we conduct an initial assessment of the data set, noting necessary quality control steps and instrument utility. We conduct a validation of the Pac-X dataset by comparing the glider data to equivalent, or near-equivalent, satellite measurements. Sea surface temperature and salinity compared well to satellite measurements. Chl fluorescence from the gliders was more poorly correlated, with substantial between glider variability. Both turbidity and oil CDOM sensors were compromised to some degree by interfering processes. The well-known diel cycle in chlorophyll fluorescence was observed suggesting that mapping physiological data over large scales is possible. The gliders captured the Pacific Ocean's major oceanographic features including the increased chlorophyll biomass of the California Current and equatorial upwelling. A comparison of satellite sea surface salinity (Aquarius) and glider-measured salinity revealed thin low salinity lenses in the southwestern Pacific Ocean. One glider survived a direct passage through a tropical cyclone. Two gliders traversed an open ocean phytoplankton bloom; extensive spiking in the chlorophyll fluorescence data is consistent with aggregation and highlights another potential future use for the gliders. On long missions, redundant instrumentation would aid in interpreting unusual data streams, as well as a means to periodically image the sensor heads. Instrument placement is critical to minimize bubble-related problems in the data.

Background: Many HIV-2 and SIV isolates, as well as some HIV-1 strains, can use the orphan 7-transmembrane receptor GPR15 as co-receptor for efficient entry into host cells. GPR15 is expressed on central memory and effector memory CD4(+) T cells in healthy individuals and a subset of these cells is susceptible to HIV-1 and SIV infection. However, it has not been determined whether GPR15 expression is altered in the context of HIV-1 infection., Results: Here, we show that GPR15 expression in CD4(+) T cells is markedly up-regulated in some HIV-1 infected individuals compared to the rest of the infected patients and to healthy controls. Infection of the PM1 T cell line with primary HIV-1 isolates was found to up-regulate GPR15 expression on the infected cells, indicating that viral components can induce GPR15 expression. Up-regulation of GPR15 expression on CD4(+) T cells was induced by activation of Toll-like receptor 3 signalling via TIR-domain-containing adapter-inducing interferon-β (TRIF) and was more prominent on gut-homing compared to lymph node-homing CD4(+) T cells., Conclusion: These results suggest that infection-induced up-regulation of GPR15 expression could increase susceptibility of CD4(+) T cells to HIV infection and target cell availability in the gut in some infected individuals.

The summertime North Pacific subtropical gyre has widespread phytoplankton blooms between Hawaii and the subtropical front (∼30°N) that appear as chlorophyll (chl) increases in satellite ocean color data. Nitrogen-fixing diatom symbioses (diatom-diazotroph associations: DDAs) often increase 10(2)-10(3) fold in these blooms and contribute to elevated export flux. In 2008 and 2009, two cruises targeted satellite chlorophyll blooms to examine DDA species abundance, chlorophyll concentration, biogenic silica concentration, and hydrography. Generalized observations that DDA blooms occur when the mixed layer depth is < 70 m are supported, but there is no consistent relationship between mixed layer depth, bloom intensity, or composition; regional blooms between 22-34°N occur within a broader temperature range (21-26°C) than previously reported. In both years, the Hemiaulus-Richelia and Rhizosolenia-Richelia DDAs increased 10(2)-10(3) over background concentrations within satellite-defined bloom features. The two years share a common trend of Hemiaulus dominance of the DDAs and substantial increases in the >10 µm chl a fraction (∼40-90+% of total chl a). Integrated diatom abundance varied 10-fold over <10 km. Biogenic silica concentration tracked diatom abundance, was dominated by the >10 µm size fraction, and increased up to 5-fold in the blooms. The two years differed in the magnitude of the surface chl a increase (2009>2008), the abundance of pennate diatoms within the bloom (2009>2008), and the substantially greater mixed layer depth in 2009. Only the 2009 bloom had sufficient chl a in the >10 µm fraction to produce the observed ocean color chl increase. Blooms had high spatial variability; ocean color images likely average over numerous small events over time and space scales that exceed the individual event scale. Summertime DDA export flux noted at the Hawaii time-series Sta. ALOHA is probably a generalized feature of the eastern N. Pacific north to the subtropical front.