In this study, we used insurance claims for over a third of the entire United States population to create a subset of 128,989 families (481,657 unique individuals). We then used these data to: 1) estimate the heritability and familial environmental patterns of 149 diseases, and; 2) infer the genetic and environmental correlations between disease pairs from a set of 29 complex diseases. The majority (52 out of 65) of our study’s heritability estimates matched earlier reports, and 84 of our estimates appear to be obtained for the first time. We used correlation matrices to compute environmental and genetic disease classifications and corresponding reliability measures. Among unexpected observations, we found that migraine, typically classified as a disease of the central nervous system, appeared to be most genetically similar to irritable bowel syndrome and most environmentally similar to cystitis and urethritis, all of which are inflammatory diseases.

Summary Tyro3, Axl and Mertk (TAM) receptors are candidate entry receptor for infection of Zika virus (ZIKV), an emerging flavivirus of global public health concern. To investigate the requirement of TAM receptors for ZIKV infection, we employed several routes of viral inoculation and compared viral replication in wild-type vs. Axl−/−, Mertk−/−, Axl−/−Mertk−/−, and Axl−/−Tyro3−/− mice in various organs. Pregnant and non-pregnant mice treated with interferon α receptor (IFNAR)-blocking (MAR1-5A3) antibody infected subcutaneously with ZIKV showed no reliance on TAMs for infection. In the absence of IFNAR blocking antibody, adult female mice challenged intravaginally with ZIKV showed no difference in mucosal viral titers. Similarly, in young mice that were infected with ZIKV intracranially or intraperitoneally, ZIKV replication occurred in the absence of TAM receptors, and no differences in cell tropism was observed. These findings indicate that in mice, TAM receptors are not required for ZIKV entry and infection.

We report the results of searches for strong gravitational lens systems in the Dark Energy Survey (DES) Science Verification and Year 1 observations. The Science Verification data span approximately 250 sq. deg. with a median i-band limiting magnitude for extended objects (10σ) of 23.0. The Year 1 data span approximately 2000 sq. deg. and have an i-band limiting magnitude for extended objects (10σ) of 22.9. As these data sets are both wide and deep, they are particularly useful for identifying strong gravitational lens candidates. Potential strong gravitational lens candidate systems were initially identified based on a color and magnitude selection in the DES The Astrophysical Journal Supplement Series, 232:15 (28pp), 2017 September https://doi.org/10.3847/1538-4365/aa8667 © 2017. The American Astronomical Society. All rights reserved.1 object catalogs or because the system is at the location of a previously identified galaxy cluster. Cutout images of potential candidates were then visually scanned using an object viewer and numerically ranked according to whether or not we judged them to be likely strong gravitational lens systems. Having scanned nearly 400,000 cutouts, we present 374 candidate strong lens systems, of which 348 are identified for the first time. We provide the R.A. and decl., the magnitudes and photometric properties of the lens and source objects, and the distance (radius) of the source(s) from the lens center for each system.

Saliva from the mosquito vector of flaviviruses is capable of changing the local immune environment, leading to an increase in flavivirus-susceptible cells at the infected bite site. In addition, an antibody response to specific salivary gland (SG) components changes the pathogenesis of flaviviruses in human populations. To investigate whether antigenic SG proteins are capable of enhancing infection with Zika virus (ZIKV), a reemerging flavivirus primarily transmitted by the Aedes aegypti mosquito, we screened for antigenic SG proteins using a yeast display library and demonstrate that a previously undescribed SG protein we term neutrophil stimulating factor 1 (NeSt1) activates primary mouse neutrophils ex vivo. Passive immunization against NeSt1 decreases pro-interleukin-1␤ and CXCL2 expression, prevents macrophages from infiltrating the bite site, protects susceptible IFNAR Ϫ/Ϫ IFNGR -/-(AG129) mice from early ZIKV replication, and ameliorates virus-induced pathogenesis. These findings indicate that NeSt1 stimulates neutrophils at the mosquito bite site to change the immune microenvironment, allowing a higher level of early viral replication and enhancing ZIKV pathogenesis. IMPORTANCE When a Zika virus-infected mosquito bites a person, mosquito saliva is injected into the skin along with the virus. Molecules in this saliva can make virus infection more severe by changing the immune system to make the skin a better place for the virus to replicate. We identified a molecule that activates immune cells, called neutrophils, to recruit other immune cells, called macrophages, that the virus can infect. We named this molecule neutrophil-stimulating factor 1 (NeSt1). When we used antibodies to block NeSt1 in mice and then allowed Zika virus-infected mosquitoes to feed on these mice, they survived much better than mice that do not have antibodies against NeSt1. These findings give us more information about how mosquito saliva enhances virus infection, and it is possible that a vaccine against NeSt1 might protect people against severe Zika virus infection.

The deregulation of energetic and cellular metabolism is a signature of cancer cells. Thus, drugs targeting cancer cell metabolism may have promising therapeutic potential. Previous reports demonstrate that the widely used normoglycemic agent, metformin, can decrease the risk of cancer in type 2 diabetics and inhibit cell growth in various cancers, including pancreatic, colon, prostate, ovarian, and breast cancer. While metformin is a known adenosine monophosphate-activated protein kinase (AMPK) agonist and an inhibitor of the electron transport chain complex I, its mechanism of action in cancer cells as well as its effect on cancer metabolism is not clearly established. In this review, we will give an update on the role of metformin as an antitumoral agent and detail relevant evidence on the potential use and mechanisms of action of metformin in cancer. Analyzing antitumoral, signaling, and metabolic impacts of metformin on cancer cells may provide promising new therapeutic strategies in oncology.