A depauperate immune repertoire precedes evolution of sociality in bees

Background Sociality has many rewards, but can also be dangerous, as high population density and low genetic diversity, common in social insects, is ideal for parasite transmission. Despite this risk, honeybees and other sequenced social insects have far fewer canonical immune genes relative to solitary insects. Social protection from infection, including behavioral responses, may explain this depauperate immune repertoire. Here, based on full genome sequences, we describe the immune repertoire of two ecologically and commercially important bumblebee species that diverged approximately 18 million years ago, the North American Bombus impatiens and European Bombus terrestris. Results We find that the immune systems of these bumblebees, two species of honeybee, and a solitary leafcutting bee, are strikingly similar. Transcriptional assays confirm the expression of many of these genes in an immunological context and more strongly in young queens than males, affirming Bateman’s principle of greater investment in female immunity. We find evidence of positive selection in genes encoding antiviral responses, components of the Toll and JAK/STAT pathways, and serine protease inhibitors in both social and solitary bees. Finally, we detect many genes across pathways that differ in selection between bumblebees and honeybees, or between the social and solitary clades. Conclusions The similarity in immune complement across a gradient of sociality suggests that a reduced immune repertoire predates the evolution of sociality in bees. The differences in selection on immune genes likely reflect divergent pressures exerted by parasites across social contexts

Improving care of chronic conditions for women veterans: identifying opportunities for comparative effectiveness research

This article aims to critically analyze research focused on the findings for five chronic conditions: chronic pain, diabetes, cardiovascular disease, HIV and cancer among women veterans to identify opportunities for comparative effectiveness research. We provide a descriptive analysis from the relevant articles in prior systematic reviews. In order to identify potential gaps in research for these specific conditions, we also conducted a literature search to highlight studies focusing on women veterans published since the last systematic review. While the scientific knowledge base has grown for these chronic conditions among women veterans, the vast majority of the published literature remains descriptive and/or observational, with only a few studies examining gender differences and even fewer clinical trials. There is a need to conduct comparative effectiveness research on chronic conditions among women veterans to improve health and healthcare

Elevation of 20-carbon long chain bases due to a mutation in serine palmitoyltransferase small subunit b results in neurodegeneration.

Sphingolipids typically have an 18-carbon (C18) sphingoid long chain base (LCB) backbone. Although sphingolipids with LCBs of other chain lengths have been identified, the functional significance of these low-abundance sphingolipids is unknown. The LCB chain length is determined by serine palmitoyltransferase (SPT) isoenzymes, which are trimeric proteins composed of two large subunits (SPTLC1 and SPTLC2 or SPTLC3) and a small subunit (SPTssa or SPTssb). Here we report the identification of an Sptssb mutation, Stellar (Stl), which increased the SPT affinity toward the C18 fatty acyl-CoA substrate by twofold and significantly elevated 20-carbon (C20) LCB production in the mutant mouse brain and eye, resulting in surprising neurodegenerative effects including aberrant membrane structures, accumulation of ubiquitinated proteins on membranes, and axon degeneration. Our work demonstrates that SPT small subunits play a major role in controlling SPT activity and substrate affinity, and in specifying sphingolipid LCB chain length in vivo. Moreover, our studies also suggest that excessive C20 LCBs or C20 LCB-containing sphingolipids impair protein homeostasis and neural functions. Proc Natl Acad Sci U S A 2015 Oct 6; 112(42):12962-7

Inhibiting glucosylceramide synthase exacerbates cisplatin-induced acute kidney injury

Acute kidney injury (AKI), resulting from chemotherapeutic agents such as cisplatin, remains an obstacle in the treatment of cancer. Cisplatin-induced AKI involves apoptotic and necrotic cell death, pathways regulated by sphingolipids such as ceramide and glucosylceramide. Results from this study indicate that C57BL/6J mice treated with cisplatin had increased ceramide and hexosylceramide levels in the renal cortex 72 h following cisplatin treatment. Pretreatment of mice with inhibitors of acid sphingomyelinase and de novo ceramide synthesis (amitriptyline and myriocin, respectively) prevented accumulation of ceramides and hexosylceramide in the renal cortex and protected from cisplatin-induced AKI. To determine the role of ceramide metabolism to hexosylceramides in kidney injury, we treated mice with a potent and highly specific inhibitor of glucosylceramide synthase, the enzyme responsible for catalyzing the glycosylation of ceramides to form glucosylceramides. Inhibition of glucosylceramide synthase attenuated the accumulation of the hexosylceramides and exacerbated ceramide accumulation in the renal cortex following treatment of mice with cisplatin. Increasing ceramides and decreasing glucosylceramides in the renal cortex sensitized mice to cisplatin-induced AKI according to markers of kidney function, kidney injury, inflammation, cell stress, and apoptosis. Under conditions of high ceramide generation, data suggest that metabolism of ceramides to glucosylceramides buffers kidney ceramides and helps attenuate kidney injury.-Dupre, T. V., M. A. Doll, P. P. Shah, C. N. Sharp, D. Siow, J. Megyesi, J. Shayman, A.Bielawska, J. Bielawski, L. J. Beverly, M. Hernandez-Corbacho, C. J. Clarke, A. J. Snider, R. G. Schnellmann, L. M. Obeid, Y. A. Hannun, and L. J. Siskind. Inhibiting glucosylceramide synthase exacerbates cisplatin-induced acute kidney injury.National Institute of Diabetes and Digestive and Kidney Diseases [R01-DK093462]; National Institutes of Health [P30 CA138313, P20RR017677, UH2NS092981, 1R01HD076004-04, GM097741, PO1CA097132]; Veterans Affairs Merit Awards [1I01BX002021-04, CAMM-011-13S]12 month embargo; Published online: May 10, 2017,This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Genetic Divergence and Effective Size among Lane Snapper in U.S. Waters of the Western Atlantic Ocean

Population structure of lane snapper Lutjanus synagris in U.S. waters in the northern Caribbean Sea was assessed using nuclear-encoded microsatellites and mitochondrial DNA (mtDNA) from samples from four localities in the U.S. Caribbean and one locality in the Florida Keys. Significant heterogeneity was detected for both allele and genotype distributions (microsatellites) and for haplotype distribution (mtDNA). Pairwise comparisons revealed that fish in the Florida Keys differed significantly from fish in the U.S. Caribbean with respect to both microsatellites and mtDNA. A parsimony network of mtDNA haplotypes was consistent with division of the five sample localities into two distinct populations. Genetic diversity at both microsatellites and mtDNA was greater among fish from the Florida Keys. The average, long-term migration rate from the U.S. Caribbean westward to the Florida Keys was approximately 1.75-fold greater than the reverse, suggesting that the elevated genetic variability among fish from the Florida Keys reflects the westward movement of alleles as a function of westward-flowing surface currents in the region. Bayesian coalescent analysis (microsatellites) indicated that each of the two populations has experienced a 10-fold decline in effective population size (Ne). Estimates of long-term effective size, generated using a coalescent, maximum-likelihood method, were 1,671.9 (Florida Keys) and 2,923.2 (U.S. Caribbean). Estimates of contemporaneous effective size, generated using a linkage-disequilibrium approach with minor alleles (those with frequencies of 0.02 or less) being excluded, were 275.6 (Florida Keys) and 668.9 (U.S. Caribbean) and differed significantly from one another. Because the samples contained mixed cohorts, the short-term estimates reflect the effective number of breeders (Nb) that produced the cohort(s) from which the samples were taken. The difference between the long-term and short-term estimates of Ne (or Nb) suggests that the declines in the effective size of both populations are relatively recent and that management concern over lane snapper in the Florida Keys is justified