Altered distribution of mucosal NK cells during HIV infection.

The human gut mucosa is a major site of human immunodeficiency virus (HIV) infection and infection-associated pathogenesis. Increasing evidence shows that natural killer (NK) cells have an important role in control of HIV infection, but the mechanism(s) by which they mediate antiviral activity in the gut is unclear. Here, we show that two distinct subsets of NK cells exist in the gut, one localized to intraepithelial spaces (intraepithelial lymphocytes, IELs) and the other to the lamina propria (LP). The frequency of both subsets of NK cells was reduced in chronic infection, whereas IEL NK cells remained stable in spontaneous controllers with protective killer immunoglobulin-like receptor/human leukocyte antigen genotypes. Both IEL and LP NK cells were significantly expanded in immunological non-responsive patients, who incompletely recovered CD4+ T cells on highly active antiretroviral therapy (HAART). These data suggest that both IEL and LP NK cells may expand in the gut in an effort to compensate for compromised CD4+ T-cell recovery, but that only IEL NK cells may be involved in providing durable control of HIV in the gut

Night Shift: Expansion of Temporal Niche Use Following Reductions in Predator Density

Predation shapes many fundamental aspects of ecology. Uncertainty remains, however, about whether predators can influence patterns of temporal niche construction at ecologically relevant timescales. Partitioning of time is an important mechanism by which prey avoid interactions with predators. However, the traits that control a prey organism's capacity to operate during a particular portion of the diel cycle are diverse and complex. Thus, diel prey niches are often assumed to be relatively unlikely to respond to changes in predation risk at short timescales. Here we present evidence to the contrary. We report results that suggest that the anthropogenic depletion of daytime active predators (species that are either diurnal or cathemeral) in a coral reef ecosystem is associated with rapid temporal niche expansions in a multi-species assemblage of nocturnal prey fishes. Diurnal comparisons of nocturnal prey fish abundance in predator rich and predator depleted reefs at two atolls revealed that nocturnal fish were approximately six (biomass) and eight (density) times more common during the day on predator depleted reefs. Amongst these, the prey species that likely were the most specialized for nocturnal living, and thus the most vulnerable to predation (i.e. those with greatest eye size to body length ratio), showed the strongest diurnal increases at sites where daytime active predators were rare. While we were unable to determine whether these observed increases in diurnal abundance by nocturnal prey were the result of a numerical or behavioral response, either effect could be ecologically significant. These results raise the possibility that predation may play an important role in regulating the partitioning of time by prey and that anthropogenic depletions of predators may be capable of causing rapid changes to key properties of temporal community architecture

Simian Immunodeficiency Virus Infection of Chimpanzees (Pan troglodytes) Shares Features of Both Pathogenic and Non-pathogenic Lentiviral Infections.

The virus-host relationship in simian immunodeficiency virus (SIV) infected chimpanzees is thought to be different from that found in other SIV infected African primates. However, studies of captive SIVcpz infected chimpanzees are limited. Previously, the natural SIVcpz infection of one chimpanzee, and the experimental infection of six chimpanzees was reported, with limited follow-up. Here, we present a long-term study of these seven animals, with a retrospective re-examination of the early stages of infection. The only clinical signs consistent with AIDS or AIDS associated disease was thrombocytopenia in two cases, associated with the development of anti-platelet antibodies. However, compared to uninfected and HIV-1 infected animals, SIVcpz infected animals had significantly lower levels of peripheral blood CD4+ T-cells. Despite this, levels of T-cell activation in chronic infection were not significantly elevated. In addition, while plasma levels of β2 microglobulin, neopterin and soluble TNF-related apoptosis inducing ligand (sTRAIL) were elevated in acute infection, these markers returned to near-normal levels in chronic infection, reminiscent of immune activation patterns in 'natural host' species. Furthermore, plasma soluble CD14 was not elevated in chronic infection. However, examination of the secondary lymphoid environment revealed persistent changes to the lymphoid structure, including follicular hyperplasia in SIVcpz infected animals. In addition, both SIV and HIV-1 infected chimpanzees showed increased levels of deposition of collagen and increased levels of Mx1 expression in the T-cell zones of the lymph node. The outcome of SIVcpz infection of captive chimpanzees therefore shares features of both non-pathogenic and pathogenic lentivirus infections.This work was supported by the Biotechnology and Biological Sciences Research Council and by the Wellcome Trust.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.ppat.100514

Quantifying the Spatial Ecology of Wide-Ranging Marine Species in the Gulf of California: Implications for Marine Conservation Planning

There is growing interest in systematic establishment of marine protected area (MPA) networks and representative conservation sites. This movement toward networks of no-take zones requires that reserves are deliberately and adequately spaced for connectivity. Here, we test the network functionality of an ecoregional assessment configuration of marine conservation areas by evaluating the habitat protection and connectivity offered to wide-ranging fauna in the Gulf of California (GOC, Mexico). We first use expert opinion to identify representative species of wide-ranging fauna of the GOC. These include leopard grouper, hammerhead sharks, California brown pelicans and green sea turtles. Analyzing habitat models with both structural and functional connectivity indexes, our results indicate that the configuration includes large proportions of biologically important habitat for the four species considered (25–40%), particularly, the best quality habitats (46–57%). Our results also show that connectivity levels offered by the conservation area design for these four species may be similar to connectivity levels offered by the entire Gulf of California, thus indicating that connectivity offered by the areas may resemble natural connectivity. The selected focal species comprise different life histories among marine or marine-related vertebrates and are associated with those habitats holding the most biodiversity values (i.e. coastal habitats); our results thus suggest that the proposed configuration may function as a network for connectivity and may adequately represent the marine megafauna in the GOC, including the potential connectivity among habitat patches. This work highlights the range of approaches that can be used to quantify habitat protection and connectivity for wide-ranging marine species in marine reserve networks

Relationship between Regulatory T Cells and Immune Activation in Human Immunodeficiency Virus-Infected Patients Interrupting Antiretroviral Therapy

Persistent immune activation plays a central role in driving Human Immunodeficiency Virus (HIV) disease progression. Whether CD4+CD25+ regulatory T cells (Tregs) are harmful by suppressing HIV-specific immune responses and/or beneficial through a decrease in immune activation remains debatable. We analysed the relationship between proportion and number of regulatory T cells (Tregs) and immune activation in HIV-infected patients interrupting an effective antiretroviral therapy (ART). Twenty-five patients were included in a substudy of a prospective multicenter trial of treatment interruption (TI) (ANRS 116). Proportions and numbers of Tregs and the proportion of activated CD4 and CD8 T cells were assessed at baseline and month 12 (M12) of TI. Specific anti-HIV CD4 and CD8 responses were investigated at baseline and M12. Non parametric univariate analyses and multivariate linear regression models were conducted. At baseline, the proportion of Tregs negatively correlated with the proportion of HLA-DR+CD8+T cells (r = −0.519). Following TI, the proportion of Tregs increased from 6.3% to 7.2% (p = 0.029); absolute numbers of Tregs decreased. The increase in the proportion of HLA-DR+CD38+CD8+T cells was significantly related to the increase in proportion of Tregs (p = 0.031). At M12, the proportion of Tregs did not negatively correlate with CD8 T-cell activation. Nevertheless, Tregs retain a suppressive function since depletion of Treg-containing CD4+CD25+ cells led to an increase in lymphoproliferative responses in most patients studied. Our data suggest that Tregs are efficient in controlling residual immune activation in patients with ART-mediated viral suppression. However, the insufficient increase in the proportion and/or the decrease in the absolute number of Tregs result in a failure to control immune activation following TI

Long-Term Climate Forcing in Loggerhead Sea Turtle Nesting

The long-term variability of marine turtle populations remains poorly understood, limiting science and management. Here we use basin-scale climate indices and regional surface temperatures to estimate loggerhead sea turtle (Caretta caretta) nesting at a variety of spatial and temporal scales. Borrowing from fisheries research, our models investigate how oceanographic processes influence juvenile recruitment and regulate population dynamics. This novel approach finds local populations in the North Pacific and Northwest Atlantic are regionally synchronized and strongly correlated to ocean conditions—such that climate models alone explain up to 88% of the observed changes over the past several decades. In addition to its performance, climate-based modeling also provides mechanistic forecasts of historical and future population changes. Hindcasts in both regions indicate climatic conditions may have been a factor in recent declines, but future forecasts are mixed. Available climatic data suggests the Pacific population will be significantly reduced by 2040, but indicates the Atlantic population may increase substantially. These results do not exonerate anthropogenic impacts, but highlight the significance of bottom-up oceanographic processes to marine organisms. Future studies should consider environmental baselines in assessments of marine turtle population variability and persistence

A Low T Regulatory Cell Response May Contribute to Both Viral Control and Generalized Immune Activation in HIV Controllers

HIV-infected individuals maintaining undetectable viremia in the absence of therapy (HIV controllers) often maintain high HIV-specific T cell responses, which has spurred the development of vaccines eliciting HIV-specific T cell responses. However, controllers also often have abnormally high T cell activation levels, potentially contributing to T cell dysfunction, CD4+ T cell depletion, and non-AIDS morbidity. We hypothesized that a weak T regulatory cell (Treg) response might contribute to the control of viral replication in HIV controllers, but might also contribute to generalized immune activation, contributing to CD4+ T cell loss. To address these hypotheses, we measured frequencies of activated (CD38+ HLA-DR+), regulatory (CD4+CD25+CD127dim), HIV-specific, and CMV-specific T cells among HIV controllers and 3 control populations: HIV-infected individuals with treatment-mediated viral suppression (ART-suppressed), untreated HIV-infected “non-controllers” with high levels of viremia, and HIV-uninfected individuals. Despite abnormally high T cell activation levels, controllers had lower Treg frequencies than HIV-uninfected controls (P = 0.014). Supporting the propensity for an unusually low Treg response to viral infection in HIV controllers, we observed unusually high CMV-specific CD4+ T cell frequencies and a strong correlation between HIV-specific CD4+ T cell responses and generalized CD8+ T cell activation levels in HIV controllers (P≤0.001). These data support a model in which low frequencies of Tregs in HIV controllers may contribute to an effective adaptive immune response, but may also contribute to generalized immune activation, potentially contributing to CD4 depletion

Defective Membrane Remodeling in Neuromuscular Diseases: Insights from Animal Models

Proteins involved in membrane remodeling play an essential role in a plethora of cell functions including endocytosis and intracellular transport. Defects in several of them lead to human diseases. Myotubularins, amphiphysins, and dynamins are all proteins implicated in membrane trafficking and/or remodeling. Mutations in myotubularin, amphiphysin 2 (BIN1), and dynamin 2 lead to different forms of centronuclear myopathy, while mutations in myotubularin-related proteins cause Charcot-Marie-Tooth neuropathies. In addition to centronuclear myopathy, dynamin 2 is also mutated in a dominant form of Charcot-Marie-Tooth neuropathy. While several proteins from these different families are implicated in similar diseases, mutations in close homologues or in the same protein in the case of dynamin 2 lead to diseases affecting different tissues. This suggests (1) a common molecular pathway underlying these different neuromuscular diseases, and (2) tissue-specific regulation of these proteins. This review discusses the pathophysiology of the related neuromuscular diseases on the basis of animal models developed for proteins of the myotubularin, amphiphysin, and dynamin families. A better understanding of the common mechanisms between these neuromuscular disorders will lead to more specific health care and therapeutic approaches

Innate immunity against HIV: a priority target for HIV prevention research

This review summarizes recent advances and current gaps in understanding of innate immunity to human immunodeficiency virus (HIV) infection, and identifies key scientific priorities to enable application of this knowledge to the development of novel prevention strategies (vaccines and microbicides). It builds on productive discussion and new data arising out of a workshop on innate immunity against HIV held at the European Commission in Brussels, together with recent observations from the literature