Multiple Phosphatidylinositol 3-Kinases Regulate Vaccinia Virus Morphogenesis

Poxvirus morphogenesis is a complex process that involves the successive wrapping of the virus in host cell membranes. We screened by plaque assay a focused library of kinase inhibitors for those that caused a reduction in viral growth and identified several compounds that selectively inhibit phosphatidylinositol 3-kinase (PI3K). Previous studies demonstrated that PI3Ks mediate poxviral entry. Using growth curves and electron microscopy in conjunction with inhibitors, we show that that PI3Ks additionally regulate morphogenesis at two distinct steps: immature to mature virion (IMV) transition, and IMV envelopment to form intracellular enveloped virions (IEV). Cells derived from animals lacking the p85 regulatory subunit of Type I PI3Ks (p85α−/−β−/−) presented phenotypes similar to those observed with PI3K inhibitors. In addition, VV appear to redundantly use PI3Ks, as PI3K inhibitors further reduce plaque size and number in p85α−/−β−/− cells. Together, these data provide evidence for a novel regulatory mechanism for virion morphogenesis involving phosphatidylinositol dynamics and may represent a new therapeutic target to contain poxviruses

The effect of the USPSTF PSA screening recommendation on prostate cancer incidence patterns in the USA

Guidelines conflict regarding recommendations for prostate-specific antigen (PSA) screening for early detection of prostate cancer. The United States Preventive Services Task Force (USPSTF) assigned a grade of D (recommending against screening) for men 75 and older in 2008 and for men of all ages in 2012. We reviewed temporal trends in rates of screening before and after the 2012 recommendation based on a literature search for studies published between 2011/01/01–2016/10/03 on PSA utilization patterns, changes in prostate cancer incidence and biopsy patterns, and how the recommendation has shaped physician and patient attitudes about PSA screening and subsequent ordering of other screening tests. Rates of PSA screening decreased by 3–10 percentage points among all age groups and within most U.S. geographic regions. Rates of prostate biopsy and prostate cancer incidence have declined in unison, with a notable shift towards higher grade, stage and risk upon detection. Despite the recommendation, some physicians reported ongoing willingness to screen appropriately selected men, and men largely reported intending to continue to ask for the PSA test. In the coming years, we expect to have a better picture of whether these decreased rates of screening will impact prostate cancer metastasis and mortality

Organic carbon transfers in the subtropical Red River system (Viet Nam): insights on CO2 sources and sinks

International audienceThe Red River, draining a 169,000 km2 watershed, is the second largest river in Viet Nam and constitutes the main source of water for a large percentage of the population of North Viet Nam. Here we present the results of an investigation into the spatial distribution and temporal dynamics of particulate and dissolved organic carbon (POC and DOC, respectively) in the Red River Basin. POC concentrations ranged from 0.24 to 5.80 mg C L-1 and DOC concentrations ranged from 0.26 to 5.39 mg C L-1. The application of the Seneque/Riverstrahler model to monthly POC and DOC measurements showed that, in general, the model simulations of the temporal variations and spatial distribution of organic carbon (OC) concentration followed the observed trends. They also show the impact of high population densities (up to 994 in-hab km-2 in the delta area) on OC inputs in surface runoff from the different land use classes and from urban point sources. A budget of the main fluxes of OC in the whole river network, including diffuse inputs from soil leaching and runoff and point sources from urban centers, as well as algal net primary production and heterotrophic respiration was established using the model results. It shows the predominantly heterotrophic character of the river system and provides an estimate of CO 2 emissions from the river of 330 Gg C year-1. This value is in reasonable agreement with the few available direct measurements of CO 2 fluxes in the downstream part of the river network