Impaired Glucose Tolerance in Sleep Disorders

BACKGROUND: Recent epidemiological and experimental data suggest a negative influence of shortened or disturbed night sleep on glucose tolerance. Due to the high prevalence of sleep disorders this might be a major health issue. However, no comparative studies of carbohydrate metabolism have been conducted in clinical sleep disorders. METHODOLOGY/PRINCIPAL FINDINGS: We performed oral glucose tolerance tests (OGTT) and assessed additional parameters of carbohydrate metabolism in patients suffering from obstructive sleep apnea syndrome (OSAS, N = 25), restless legs syndrome (RLS, N = 18) or primary insomnia (N = 21), and in healthy controls (N = 33). Compared to controls, increased rates of impaired glucose tolerance were found in OSAS (OR: 4.9) and RLS (OR: 4.7) patients, but not in primary insomnia patients (OR: 1.6). In addition, HbA1c values were significantly increased in the same two patient groups. Significant positive correlations were found between 2-h plasma glucose values measured during the OGTT and the apnea-arousal-index in OSAS (r = 0.56; p<0.05) and the periodic leg movement-arousal-index in RLS (r = 0.56, p<0.05), respectively. Sleep duration and other quantitative aspects of sleep were similar between patient groups. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that some, but not all sleep disorders considerably compromise glucose metabolism. Repeated arousals during sleep might be a pivotal causative factor deserving further experimental investigations to reveal potential novel targets for the prevention of metabolic diseases

JWST/NIRSpec Observations of the Planetary Mass Companion TWA 27B

We present 1-5um spectroscopy of the young planetary mass companion TWA 27B (2M1207B) performed with NIRSpec on board the James Webb Space Telescope. In these data, the fundamental band of CH_4 is absent and the fundamental band of CO is weak. The nondetection of CH_4 reinforces a previously observed trend of weaker CH_4 with younger ages among L dwarfs, which has been attributed to enhanced non-equilibrium chemistry among young objects. The weakness of CO may reflect an additional atmospheric property that varies with age, such as the temperature gradient or cloud thickness. We are able to reproduce the broad shape of the spectrum with an ATMO cloudless model that has T=1300 K, non-equilibrium chemistry, and a temperature gradient reduction caused by fingering convection. However, the fundamental bands of CH_4 and CO are somewhat stronger in the model. In addition, the model temperature of 1300 K is higher than expected from evolutionary models given the luminosity and age of TWA 27B (T=1200 K). Previous models of young L-type objects suggest that the inclusion of clouds could potentially resolve these issues; it remains to be seen whether cloudy models can provide a good fit to the 1-5um data from NIRSpec. TWA 27B exhibits emission in Paschen transitions and the He I triplet at 1.083um, which are signatures of accretion that provide the first evidence of a circumstellar disk. We have used the NIRSpec data to estimate the bolometric luminosity of TWA 27B (log L/L_sun=-4.466+/-0.014), which implies a mass of 5-6 MJup according to evolutionary models.Comment: Astrophysical Journal Letters, in pres

Safety Profile of a Virus-Like Particle-Based Vaccine Targeting Self-Protein Interleukin-5 in Horses

Background: Insect bite hypersensitivity (IBH) is an eosinophilic allergic dermatitis of horses caused by type I/IVb reactions against mainly Culicoides bites. The vaccination of IBH-affected horses with equine IL-5 coupled to the Cucumber mosaic virus-like particle (eIL-5-CuMVTT) induces IL-5-specific auto-antibodies, resulting in a significant reduction in eosinophil levels in blood and clinical signs. Objective: the preclinical and clinical safety of the eIL-5-CuMVTT vaccine. Methods: The B cell responses were assessed by longitudinal measurement of IL-5- and CuMVTT-specific IgG in the serum and plasma of vaccinated and unvaccinated horses. Further, peripheral blood mononuclear cells (PBMCs) from the same horses were re-stimulated in vitro for the proliferation and IFN-γ production of specific T cells. In addition, we evaluated longitudinal kidney and liver parameters and the general blood status. An endogenous protein challenge was performed in murine IL-5-vaccinated mice. Results: The vaccine was well tolerated as assessed by serum and cellular biomarkers and also induced reversible and neutralizing antibody titers in horses and mice. Endogenous IL-5 stimulation was unable to re-induce anti-IL-5 production. The CD4+ T cells of vaccinated horses produced significantly more IFN-γ and showed a stronger proliferation following stimulation with CuMVTT as compared to the unvaccinated controls. Re-stimulation using E. coli-derived proteins induced low levels of IFNγ+CD4+ cells in vaccinated horses; however, no IFN-γ and proliferation were induced following the HEK-eIL-5 re-stimulation. Conclusions: Vaccination using eIL-5-CuMVTT induces a strong B-cell as well as CuMVTT-specific T cell response without the induction of IL-5-specific T cell responses. Hence, B-cell unresponsiveness against self-IL-5 can be bypassed by inducing CuMVTT carrier-specific T cells, making the vaccine a safe therapeutic option for IBH-affected horses

Infrared Echoes near the Supernova Remnant Cassiopeia A

Two images of Cassiopeia A obtained at 24 micrometer with the Spitzer Space Telescope over a one year time interval show moving structures outside the shell of the supernova remnant to a distance of more than 20 arcmin. Individual features exhibit apparent motions of 10 to 20 arcsec per year, independently confirmed by near-infrared observations. The observed tangential velocities are at roughly the speed of light. It is likely that the moving structures are infrared echoes, in which interstellar dust is heated by the explosion and by flares from the compact object near the center of the remnant.Comment: To be published in Science on June 10, 2005. 11 pages, 4 figures. Additional information available at http://www.spitzer.caltech.edu/Media/releases/ssc2005-14/index.shtm

Detection of Prion Protein Particles in Blood Plasma of Scrapie Infected Sheep

Prion diseases are transmissible neurodegenerative diseases affecting humans and animals. The agent of the disease is the prion consisting mainly, if not solely, of a misfolded and aggregated isoform of the host-encoded prion protein (PrP). Transmission of prions can occur naturally but also accidentally, e.g. by blood transfusion, which has raised serious concerns about blood product safety and emphasized the need for a reliable diagnostic test. In this report we present a method based on surface-FIDA (fluorescence intensity distribution analysis), that exploits the high state of molecular aggregation of PrP as an unequivocal diagnostic marker of the disease, and show that it can detect infection in blood. To prepare PrP aggregates from blood plasma we introduced a detergent and lipase treatment to separate PrP from blood lipophilic components. Prion protein aggregates were subsequently precipitated by phosphotungstic acid, immobilized on a glass surface by covalently bound capture antibodies, and finally labeled with fluorescent antibody probes. Individual PrP aggregates were visualized by laser scanning microscopy where signal intensity was proportional to aggregate size. After signal processing to remove the background from low fluorescence particles, fluorescence intensities of all remaining PrP particles were summed. We detected PrP aggregates in plasma samples from six out of ten scrapie-positive sheep with no false positives from uninfected sheep. Applying simultaneous intensity and size discrimination, ten out of ten samples from scrapie sheep could be differentiated from uninfected sheep. The implications for ante mortem diagnosis of prion diseases are discussed

Developing an impact library for forecasting surface water flood risk

During surface water flooding events, emergency responders require detailed information on the risks posed in order to provide an appropriate and effective response. Few early warning systems quantitatively estimate the risk and impacts of surface water flooding. Improvements in computational processing capability, availability of new datasets and developments in forecasting models means that the forecasting information currently being supplied by the Flood Forecasting Centre can be improved upon through the application of a timely, impact‐based model. This article presents a novel approach to collating receptor datasets into a pre‐calculated Impact Library for use in a Hazard Impact Model (HIM) that will operate using real‐time probabilistic rainfall and surface runoff forecasts for England and Wales. The HIM provides an approach suitable for modelling flood impacts. Initial results are presented for a case study covering the 2012 floods in the North East of England. Information generated by the HIM provides additional benefits beyond current methods. Features include operator access to 1 km 15 min spatial–temporal data, analysis of individual impact criteria and modular refinement of the Impact Library to suit different situations. The HIM has been developed in partnership via the Natural Hazards Partnership

Molecular Interactions between Prions as Seeds and Recombinant Prion Proteins as Substrates Resemble the Biological Interspecies Barrier In Vitro

Prion diseases like Creutzfeldt-Jakob disease in humans, Scrapie in sheep or bovine spongiform encephalopathy are fatal neurodegenerative diseases, which can be of sporadic, genetic, or infectious origin. Prion diseases are transmissible between different species, however, with a variable species barrier. The key event of prion amplification is the conversion of the cellular isoform of the prion protein (PrPC) into the pathogenic isoform (PrPSc). We developed a sodiumdodecylsulfate-based PrP conversion system that induces amyloid fibril formation from soluble α-helical structured recombinant PrP (recPrP). This approach was extended applying pre-purified PrPSc as seeds which accelerate fibrillization of recPrP. In the present study we investigated the interspecies coherence of prion disease. Therefore we used PrPSc from different species like Syrian hamster, cattle, mouse and sheep and seeded fibrillization of recPrP from the same or other species to mimic in vitro the natural species barrier. We could show that the in vitro system of seeded fibrillization is in accordance with what is known from the naturally occurring species barriers