Metabolomics Identifies multiple candidate biomarkers to diagnose and stage human African trypanosomiasis

Treatment for human African trypanosomiasis is dependent on the species of trypanosome causing the disease and the stage of the disease (stage 1 defined by parasites being present in blood and lymphatics whilst for stage 2, parasites are found beyond the blood-brain barrier in the cerebrospinal fluid (CSF)). Currently, staging relies upon detecting the very low number of parasites or elevated white blood cell numbers in CSF. Improved staging is desirable, as is the elimination of the need for lumbar puncture. Here we use metabolomics to probe samples of CSF, plasma and urine from 40 Angolan patients infected with Trypanosoma brucei gambiense, at different disease stages. Urine samples provided no robust markers indicative of infection or stage of infection due to inherent variability in urine concentrations. Biomarkers in CSF were able to distinguish patients at stage 1 or advanced stage 2 with absolute specificity. Eleven metabolites clearly distinguished the stage in most patients and two of these (neopterin and 5-hydroxytryptophan) showed 100% specificity and sensitivity between our stage 1 and advanced stage 2 samples. Neopterin is an inflammatory biomarker previously shown in CSF of stage 2 but not stage 1 patients. 5-hydroxytryptophan is an important metabolite in the serotonin synthetic pathway, the key pathway in determining somnolence, thus offering a possible link to the eponymous symptoms of “sleeping sickness”. Plasma also yielded several biomarkers clearly indicative of the presence (87% sensitivity and 95% specificity) and stage of disease (92% sensitivity and 81% specificity). A logistic regression model including these metabolites showed clear separation of patients being either at stage 1 or advanced stage 2 or indeed diseased (both stages) versus control

The US Southern Ocean Global Ocean Ecosystems Dynamics Program

The article presents information on the U.S. Southern Ocean Global Ocean Ecosystem Dynamics program (US SO GLOBEC). It was aimed at understanding the environmental and biological factors that contribute to enhanced Antarctic krill growth, reproduction, recruitment and survivorship, as well as the interactions between Antarctic krill and its predators and competitors. The highlights of US SO GLOBEC research are also discussed

Development of a New USDA Plant Hardiness Zone Map for the United States

In many regions of the world, the extremes of winter cold are a major determinant of the geographic distribution of perennial plant species and of their successful cultivation. In the United States, the U.S. Department of Agriculture (USDA) Plant Hardiness Zone Map (PHZM) is the primary reference for defining geospatial patterns of extreme winter cold for the horticulture and nursery industries, home gardeners, agrometeorologists, and plant scientists. This paper describes the approaches followed for updating the USDA PHZM, the last version of which was published in 1990. The new PHZM depicts 1976–2005 mean annual extreme minimum temperature, in 2.8°C (5°F) half zones, for the conterminous United States, Alaska, Hawaii, and Puerto Rico. Station data were interpolated to a grid with the Parameter-Elevation Regressions on Independent Slopes Model (PRISM) climate-mapping system. PRISM accounts for the effects of elevation, terrain-induced airmass blockage, coastal effects, temperature inversions, and cold-air pooling on extreme minimum temperature patterns. Climatologically aided interpolation was applied, based on the 1971–2000 mean minimum temperature of the coldest month as the predictor grid. Evaluation of a standard-deviation map and two 15-yr maps (1976–90 and 1991–2005 averaging periods) revealed substantial vertical and horizontal gradients in trend and variability, especially in complex terrain. The new PHZM is generally warmer by one 2.8°C (5°F) half zone than the previous PHZM throughout much of the United States, as a result of a more recent averaging period. Nonetheless, a more sophisticated interpolation technique, greater physiographic detail, and more comprehensive station data were the main causes of zonal changes in complex terrain, especially in the western United States. The updated PHZM can be accessed onlineKeywords: Climate classification/regimes, Winter/cool season, Agriculture, Land use, Societal impact

Managing climate change refugia for climate adaptation

Refugia have long been studied from paleontological and biogeographical perspectives to understand how populations persisted during past periods of unfavorable climate. Recently, researchers have applied the idea to contemporary landscapes to identify climate change refugia, here defined as areas relatively buffered from contemporary climate change over time that enable persistence of valued physical, ecological, and socio-cultural resources. We differentiate historical and contemporary views, and characterize physical and ecological processes that create and maintain climate change refugia. We then delineate how refugia can fit into existing decision support frameworks for climate adaptation and describe seven steps for managing them. Finally, we identify challenges and opportunities for operationalizing the concept of climate change refugia. Managing climate change refugia can be an important option for conservation in the face of ongoing climate change

Spatial and trophic overlap of marked and unmarked Columbia River Basin spring Chinook salmon during early marine residence with implications for competition between hatchery and naturally produced fish

Ecological interactions between natural and hatchery juvenile salmon during their early marine residence, a time of high mortality, have received little attention. These interactions may negatively influence survival and hamper the ability of natural populations to recover. We examined the spatial distributions and size differences of both marked (hatchery) and unmarked (a high proportion of which are natural) juvenile Chinook salmon in the coastal waters of Oregon andWashington from May to June 1999–2009. We also explored potential trophic interactions and growth differences between unmarked and marked salmon. Overlap in spatial distribution between these groups was high, although catches of unmarked fish were low compared to those of marked hatchery salmon. Peak catches of hatchery fish occurred in May, while a prolonged migration of small unmarked salmon entered our study area toward the end of June. Hatchery salmon were consistently longer than unmarked Chinook salmon especially by June, but unmarked salmon had significantly greater body condition (based on length-weight residuals) for over half of the May sampling efforts. Both unmarked and marked fish ate similar types and amounts of prey for small (station) and large (month, year) scale comparisons, and feeding intensity and growth were not significantly different between the two groups. There were synchronous interannual fluctuations in catch, length, body condition, feeding intensity, and growth between unmarked and hatchery fish, suggesting that both groups were responding similarly to ocean conditions.Keywords: Wild, Competition, Spatial, Marine, Hatchery, Columbia River Basin, Juvenile Chinook salmon, Trophi

TMEM258 Is a Component of the Oligosaccharyltransferase Complex Controlling ER Stress and Intestinal Inflammation

Summary - Significant insights into disease pathogenesis have been gleaned from population-level genetic studies; however, many loci associated with complex genetic disease contain numerous genes, and phenotypic associations cannot be assigned unequivocally. In particular, a gene-dense locus on chromosome 11 (61.5–61.65 Mb) has been associated with inflammatory bowel disease, rheumatoid arthritis, and coronary artery disease. Here, we identify TMEM258 within this locus as a central regulator of intestinal inflammation. Strikingly, Tmem258 haploinsufficient mice exhibit severe intestinal inflammation in a model of colitis. At the mechanistic level, we demonstrate that TMEM258 is a required component of the oligosaccharyltransferase complex and is essential for N-linked protein glycosylation. Consequently, homozygous deficiency of Tmem258 in colonic organoids results in unresolved endoplasmic reticulum (ER) stress culminating in apoptosis. Collectively, our results demonstrate that TMEM258 is a central mediator of ER quality control and intestinal homeostasis.Leona M. and Harry B. Helmsley Charitable Trust (2014PG-IBD016)Crohn's and Colitis Foundation of AmericaNational Institutes of Health (U.S.) (grant DK043351)National Institutes of Health (U.S.) (grant DK097485