Genetic Variation in OAS1 Is a Risk Factor for Initial Infection with West Nile Virus in Man

West Nile virus (WNV) is a re-emerging pathogen that can cause fatal encephalitis. In mice, susceptibility to WNV has been reported to result from a single point mutation in oas1b, which encodes 2′–5′ oligoadenylate synthetase 1b, a member of the type I interferon-regulated OAS gene family involved in viral RNA degradation. In man, the human ortholog of oas1b appears to be OAS1. The ‘A’ allele at SNP rs10774671 of OAS1 has previously been shown to alter splicing of OAS1 and to be associated with reduced OAS activity in PBMCs. Here we show that the frequency of this hypofunctional allele is increased in both symptomatic and asymptomatic WNV seroconverters (Caucasians from five US centers; total n = 501; OR = 1.6 [95% CI 1.2–2.0], P = 0.0002 in a recessive genetic model). We then directly tested the effect of this SNP on viral replication in a novel ex vivo model of WNV infection in primary human lymphoid tissue. Virus accumulation varied markedly among donors, and was highest for individuals homozygous for the ‘A’ allele (P<0.0001). Together, these data identify OAS1 SNP rs10774671 as a host genetic risk factor for initial infection with WNV in humans

Occludin S408 phosphorylation regulates tight junction protein interactions and barrier function

Occludin S408 phosphorylation regulates interactions between occludin, ZO-1, and select claudins to define tight junction molecular structure and barrier function

Extracellular Vesicles and Their Emerging Roles as Cellular Messengers in Endocrinology: An Endocrine Society Scientific Statement

During the last decade, there has been great interest in elucidating the biological role of extracellular vesicles (EVs), particularly, their hormone-like role in cell-to-cell communication. The field of endocrinology is uniquely placed to provide insight into the functions of EVs, which are secreted from all cells into biological fluids and carry endocrine signals to engage in paracellular and distal interactions. EVs are a heterogeneous population of membrane-bound vesicles of varying size, content, and bioactivity. EVs are specifically packaged with signaling molecules, including lipids, proteins, and nucleic acids, and are released via exocytosis into biofluid compartments. EVs regulate the activity of both proximal and distal target cells, including translational activity, metabolism, growth, and development. As such, EVs signaling represents an integral pathway mediating intercellular communication. Moreover, as the content of EVs is cell-type specific, it is a "fingerprint"of the releasing cell and its metabolic status. Recently, changes in the profile of EV and bioactivity have been described in several endocrine-related conditions including diabetes, obesity, cardiovascular diseases, and cancer. The goal of this statement is to highlight relevant aspects of EV research and their potential role in the field of endocrinology

Targeted Conservation to Safeguard a Biodiversity Hotspot from Climate and Land-Cover Change

Responses of biodiversity to changes in both land cover and climate are recognized [1] but still poorly understood [2]. This poses significant challenges for spatial planning as species could shift, contract, expand, or maintain their range inside or outside protected areas [2, 3 and 4]. We examine this problem in Borneo, a global biodiversity hotspot [5], using spatial prioritization analyses that maximize species conservation under multiple environmental-change forecasts. Climate projections indicate that 11%–36% of Bornean mammal species will lose ?30% of their habitat by 2080, and suitable ecological conditions will shift upslope for 23%–46%. Deforestation exacerbates this process, increasing the proportion of species facing comparable habitat loss to 30%–49%, a 2-fold increase on historical trends. Accommodating these distributional changes will require conserving land outside existing protected areas, but this may be less than anticipated from models incorporating deforestation alone because some species will colonize high-elevation reserves. Our results demonstrate the increasing importance of upland reserves and that relatively small additions (16,000–28,000 km2) to the current conservation estate could provide substantial benefits to biodiversity facing changes to land cover and climate. On Borneo, much of this land is under forestry jurisdiction, warranting targeted conservation partnerships to safeguard biodiversity in an era of global change