FK506-Binding Protein 2 Participates in Proinsulin Folding.

Apart from chaperoning, disulfide bond formation, and downstream processing, the molecular sequence of proinsulin folding is not completely understood. Proinsulin requires proline isomerization for correct folding. Since FK506-binding protein 2 (FKBP2) is an ER-resident proline isomerase, we hypothesized that FKBP2 contributes to proinsulin folding. We found that FKBP2 co-immunoprecipitated with proinsulin and its chaperone GRP94 and that inhibition of FKBP2 expression increased proinsulin turnover with reduced intracellular proinsulin and insulin levels. This phenotype was accompanied by an increased proinsulin secretion and the formation of proinsulin high-molecular-weight complexes, a sign of proinsulin misfolding. FKBP2 knockout in pancreatic ß-cells increased apoptosis without detectable up-regulation of ER stress response genes. Interestingly, FKBP2 mRNA was overexpressed in ß-cells from pancreatic islets of T2D patients. Based on molecular modeling and an in vitro enzymatic assay, we suggest that proline at position 28 of the proinsulin B-chain (P28) is the substrate of FKBP2's isomerization activity. We propose that this isomerization step catalyzed by FKBP2 is an essential sequence required for correct proinsulin folding.

Changes in Skiing and Snowboarding Injury Epidemiology and Attitudes to Safety in Big Sky, Montana, USA: A Comparison of 2 Cross-sectional Studies in 1996 and 2013.

BACKGROUND: Despite a risk of harm, the past 20 years have seen dramatically increased participation in snow sports such as skiing, and particularly, snowboarding. This period has also seen revolutions in piste maintenance and paradigm developments in the use of safety equipment. Consequently, the numbers and characteristics of injury may be very different from those traditionally quoted. PURPOSE: To compare and evaluate the injury patterns among skiers and snowboarders in a North American ski resort in 1996 and 2013. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Questionnaire-based cross-sectional studies were carried out independently in a North American ski resort between the dates of March 6 and April 11 in both 1996 and 2013. Demographic data and information about incident circumstances were collected from injured patients who visited the local on-site clinic. Data were compared statistically to assess for significant changes in injury characteristics between the 2 time periods. RESULTS: The 1996 report consisted of 148 injured participants, and the 2013 study included 156 participants. Results from 2013 demonstrated significant increases in helmet use, the number of snowboarders injured, and shoulder injuries. Injury was also more likely in those aged 46 to 55 years, those never having had professional instruction, or those with rented equipment. Significant reductions were seen in those injured with other people close by and in the 36- to 45-year age group. Overall, the knee was the most commonly injured body part in both periods (1996: 31%, n = 38; 2013: 33%, n = 36), although upper limb injuries were predominant in snowboarders. CONCLUSION: Snow sports injury characteristics of patients presenting to a ski resort medical clinic have changed between 1996 and 2013. These findings can be used to further inform safety recommendations and areas to target with further research.

A prototype mass spectrometer for in situ analysis of cave atmospheres.

Research in cave environments has many applications: studying local hydrogeologic activity, paleoclimate studies, analyzing white nose syndrome in bat populations, analogs for underground atmospheres in mining facilities, carbon sequestration efforts, and terrestrial analogs for planetary caves. The atmospheres of many caves contain tracers of current geological and biological activity, but up to this point, in situ studies have been limited to sensors that monitor individual components of the cave atmosphere. A prototype cave mass spectrometer system was assembled from commercial off-the-shelf parts to conduct surveys of atmospheric compositions inside four local Texas caves and to perform atmospheric analysis of two aquifer wellheads to a depth of 60 m. We found increased levels of CO(2) in all caves and, surprisingly, increased levels of O(2) in Bracken Bat Cave. Aquifer wellhead measurements showed indications of methane, other hydrocarbons, and other constituents not anticipated.

Soil-transmitted helminthiasis in rural south-west China: prevalence, intensity and risk factor analysis.

Only few studies in rural China have explored the epidemiology of intestinal helminth infections and identified risk factors for transmission. The study was carried out in Simao and Mengla counties, where single fecal samples were collected from 317 school-aged children and from 94 inhabitants of a single village. Fecal specimens were examined with the Kato-Katz thick smear method and examined for helminth eggs. Data regarding socio-demographic and behavioral risk factors were collected using questionnaires. In Simao County the overall soil-transmitted helminthes (STH) prevalence was 40.2% (2.7, 5.4 and 35.7% for ascariasis, trichuriasis and hookworm infection, respectively). The STH infection rates were significantly higher in Mengla County, with an overall prevalence of 68.3% (19.0, 34.6 and 47.3% for ascariasis, trichuriasis and hookworm infection, respectively). Females were less likely to be infected with Trichuris trichiura (OR 0.29; 95% CI 0.15-0.56) and with hookworms (OR 0.55; 95% CI 0.33-0.93) than males. Hookworm infections were more prevalent among those 12 years of age or older (OR 2.9; 95% CI 1.2-7.1). Children of mothers with educational attainment of secondary school or higher had a protective effect against T. trichiura (OR 0.18; 95% CI 0.06-0.54) and hookworm (OR 0.21; 95% CI 0.09-0.51) infections. In the village survey, hookworm was the most prevalent species (62.8%) with infection seen in those 50 years of age and older. Based on recommended intervention strategies by the World Health Organization, Simao County should opt for school-based deworming once each year, while Mengla County should implement a similar strategy biannually, but should include the elderly population.