Distinct Patterns of HIV-1 Evolution within Metastatic Tissues in Patients with Non-Hodgkins Lymphoma

Despite highly active antiretroviral therapy (HAART), AIDS related lymphoma (ARL) occurs at a significantly higher rate in patients infected with the Human Immunodeficiency Virus (HIV) than in the general population. HIV-infected macrophages are a known viral reservoir and have been shown to have lymphomagenic potential in SCID mice; therefore, there is an interest in determining if a viral component to lymphomagenesis also exists. We sequenced HIV-1 envelope gp120 clones obtained post mortem from several tumor and non-tumor tissues of two patients who died with AIDS-related Non-Hodgkin''s lymphoma (ARL-NH). Similar results were found in both patients: 1) high-resolution phylogenetic analysis showed a significant degree of compartmentalization between lymphoma and non-lymphoma viral sub-populations while viral sub-populations from lymph nodes appeared to be intermixed within sequences from tumor and non-tumor tissues, 2) a 100-fold increase in the effective HIV population size in tumor versus non-tumor tissues was associated with the emergence of lymphadenopathy and aggressive metastatic ARL, and 3) HIV gene flow among lymph nodes, normal and metastatic tissues was non-random. The different population dynamics between the viruses found in tumors versus the non-tumor associated viruses suggest that there is a significant relationship between HIV evolution and lymphoma pathogenesis. Moreover, the study indicates that HIV could be used as an effective marker to study the origin and dissemination of lymphomas in vivo.     

Feeding and trophic ecology of Antarctic toothfish Dissostichus mawsoni in the Amundsen and Dumont D’Urville Seas (Antarctica)

Hydrobiologia - Fisheries ecosystem-based management is an important tool for sustainable harvesting of fisheries worldwide. Knowledge of trophic interactions is crucial since changes in trophic...     

Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221) as a functional antagonist of the apelin (APJ) receptor

The recently discovered apelin/APJ system has emerged as a critical mediator of cardiovascular homeostasis and is associated with the pathogenesis of cardiovascular disease. A role for apelin/APJ in energy metabolism and gastrointestinal function has also recently emerged. We disclose the discovery and characterization of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221), a potent APJ functional antagonist in cell-based assays that is >37-fold selective over the closely related angiotensin II type 1 (AT1) receptor. ML221 was derived from an HTS of the ～330,600 compound MLSMR collection. This antagonist showed no significant binding activity against 29 other GPCRs, except to the κ-opioid and benzodiazepinone receptors (<50/<70%I at 10 μM). The synthetic methodology, development of structure–activity relationship (SAR), and initial in vitro pharmacologic characterization are also presented.     

Shearwater Foraging in the Southern Ocean: The Roles of Prey Availability and Winds

Background

Sooty (Puffinus griseus) and short-tailed (P. tenuirostris) shearwaters are abundant seabirds that range widely across global oceans. Understanding the foraging ecology of these species in the Southern Ocean is important for monitoring and ecosystem conservation and management.

Methodology/Principal Findings

Tracking data from sooty and short-tailed shearwaters from three regions of New Zealand and Australia were combined with at-sea observations of shearwaters in the Southern Ocean, physical oceanography, near-surface copepod distributions, pelagic trawl data, and synoptic near-surface winds. Shearwaters from all three regions foraged in the Polar Front zone, and showed particular overlap in the region around 140°E. Short-tailed shearwaters from South Australia also foraged in Antarctic waters south of the Polar Front. The spatial distribution of shearwater foraging effort in the Polar Front zone was matched by patterns in large-scale upwelling, primary production, and abundances of copepods and myctophid fish. Oceanic winds were found to be broad determinants of foraging distribution, and of the flight paths taken by the birds on long foraging trips to Antarctic waters.

Conclusions/Significance

The shearwaters displayed foraging site fidelity and overlap of foraging habitat between species and populations that may enhance their utility as indicators of Southern Ocean ecosystems. The results highlight the importance of upwellings due to interactions of the Antarctic Circumpolar Current with large-scale bottom topography, and the corresponding localised increases in the productivity of the Polar Front ecosystem.     

Modeling Seasonal Influenza Outbreak in a Closed College Campus: Impact of Pre-Season Vaccination,In-Season Vaccination and Holidays/Breaks

Background

College and university students experience substantial morbidity from influenza and influenza-like illness, and they can benefit substantially from vaccination. Public health authorities encourage vaccination not only before the influenza season but also into and even throughout the influenza season. We conducted the present study to assess the impact of various vaccination strategies including delayed (i.e., in-season) vaccination on influenza outbreaks on a college campus.

Methods/Findings

We used a Susceptible → Infected → Recovered (SIR) framework for our mathematical models to simulate influenza epidemics in a closed, college campus. We included both students and faculty/staff in the model and derived values for the model parameters from the published literature. The values for key model parameters were varied to assess the impact on the outbreak of various pre-season and delayed vaccination rates; one-way sensitivity analyses were conducted to test the sensitivity of the model outputs to changes in selected parameter values. In the base case, with a pre-season vaccination rate of 20%, no delayed vaccination, and 1 student index case, the total attack rate (total percent infected, TAR) was 45%. With higher pre-season vaccination rates TARs were lower. Even if vaccinations were given 30 days after outbreak onset, TARs were still lower than the TAR of 69% in the absence of vaccination. Varying the proportions of vaccinations given pre-season versus delayed until after the onset of the outbreak gave intermediate TAR values. Base case outputs were sensitive to changes in infectious contact rates and infectious periods and a holiday/break schedule.

Conclusion

Delayed vaccination and holidays/breaks can be important adjunctive measures to complement traditional pre-season influenza vaccination for controlling and preventing influenza in a closed college campus.