Recent Advances in Antidiabetic Drug Therapies Targeting the Enteroinsular Axis

The enteroinsular axis (EIA) constitutes a physiological signalling system whereby intestinal endocrine cells secrete incretin hormones following feeding that potentiate insulin secretion and contribute to the regulation of blood glucose homeostasis. The two key hormones responsible are named glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Recent years have witnessed sustained development of antidiabetic therapies that exploit the EIA. Current clinical compounds divide neatly into two classes. One concerns analogues or mimetics of GLP-1, such as exenatide (Byetta) or liraglutide (NN2211). The other group comprises the gliptins (e. g. sitagliptin and vildagliptin) which boost endogenous incretin activity by inhibiting the enzyme dipeptidyl peptidase 4 (DPP 4) that degrades both GLP-1 and GIP. Ongoing research indicates that further incretin and gliptin compounds will become available for clinical use in the near future, offering comparable or improved efficacy. For incretin analogues there is the prospect of prolonged duration of action and alternative routes of administration. This review focuses on recent advances in pre-clinical research and their translation into clinical studies to provide future therapies for type 2 diabetes targeting the EIA.

The broad-scale distribution of five jellyfish species across a temperate coastal environment

Jellyfish (medusae) are sometimes the most noticeable and abundant members of coastal planktonic communities, yet ironically, this high conspicuousness is not reflected in our overall understanding of their spatial distributions across large expanses of water. Here, we set out to elucidate the spatial (and temporal) patterns for five jellyfish species (Phylum Cnidaria, Orders Rhizostomeae and Semaeostomeae) across the Irish & Celtic Seas, an extensive shelf-sea area at Europe's northwesterly margin encompassing several thousand square kilometers. Data were gathered using two independent methods: (1) surface-counts of jellyfish from ships of opportunity, and (2) regular shoreline surveys for stranding events over three consecutive years. Jellyfish species displayed distinct species-specific distributions, with an apparent segregation of some species. Furthermore, a different species composition was noticeable between the northern and southern parts of the study area. Most importantly, our data suggests that jellyfish distributions broadly reflect the major hydrographic regimes (and associated physical discontinuities) of the study area, with mixed water masses possibly acting as a trophic barrier or non-favourable environment for the successful growth and reproduction of jellyfish species.

On the alignment of debris disks and their host stars' rotation axis -implications for spin-orbit misalignment in exoplanetary systems

It has been widely thought that measuring the misalignment angle between the orbital plane of a transiting exoplanet and the spin of its host star was a good discriminator between different migration processes for hot-Jupiters. Specifically, well-aligned hot-Jupiter systems (as measured by the Rossiter-McLaughlin effect) were thought to have formed via migration through interaction with a viscous disc, while misaligned systems were thought to have undergone a more violent dynamical history. These conclusions were based on the assumption that the planet-forming disc was well-aligned with the host star. Recent work by Lai et al. has challenged this assumption, and proposes that the star-disc interaction in the pre-main sequence phase can exert a torque on the star and change its rotation axis angle. We have estimated the stellar rotation axis of a sample of stars which host spatially resolved debris disks. Comparison of our derived stellar rotation axis inclination angles with the geometrically measured debris-disk inclinations shows no evidence for a misalignment between the two.

Rotation periods of exoplanet host stars

The stellar rotation periods of 10 exoplanet host stars have been determined using newly analysed CaII H&K flux records from the Mount Wilson Observatory and Strömgren b, y photometric measurements from Tennessee State University's automatic photometric telescopes at the Fairborn Observatory. Five of the rotation periods have not previously been reported, with that of HD 130322 very strongly detected at Prot = 26.1 +/- 3.5 d. The rotation periods of five other stars have been updated using new data. We use the rotation periods to derive the line-of-sight inclinations of the stellar rotation axes, which may be used to probe theories of planet formation and evolution when combined with the planetary orbital inclination found from other methods. Finally, we estimate the masses of 14 exoplanets under the assumption that the stellar rotation axis is aligned with the orbital axis. We calculate the mass of HD 92788 b (28 MJ) to be within the low-mass brown dwarf regime and suggest that this object warrants further investigation to confirm its true nature.

HTS Machines as Enabling Technology for All-Electric Airborne Vehicles

Environmental protection has now become paramount as evidence mounts to support the thesis of human activity-driven global warming. A global reduction of the emissions of pollutants into the atmosphere is therefore needed and new technologies have to be considered. A large part of the emissions come from transportation vehicles, including cars, trucks and airplanes, due to the nature of their combustion-based propulsion systems. Our team has been working for several years on the development of high power density superconducting motors for aircraft propulsion and fuel cell based power systems for aircraft. This paper investigates the feasibility of all-electric aircraft based on currently available technology. Electric propulsion would require the development of high power density electric propulsion motors, generators, power management and distribution systems. The requirements in terms of weight and volume of these components cannot be achieved with conventional technologies; however, the use of superconductors associated with hydrogen-based power plants makes possible the design of a reasonably light power system and would therefore enable the development of all-electric aero-vehicles. A system sizing has been performed both for actuators and for primary propulsion. Many advantages would come from electrical propulsion such as better controllability of the propulsion, higher efficiency, higher availability and less maintenance needs. Superconducting machines may very well be the enabling technology for all-electric aircraft development.

Area of residence and alcohol-related mortality risk: a five-year follow-up study

Aims

Genome-wide association study identifies five new schizophrenia loci

We examined the role of common genetic variation in schizophrenia in a genome-wide association study of substantial size: a stage 1 discovery sample of 21,856 individuals of European ancestry and a stage 2 replication sample of 29,839 independent subjects. The combined stage 1 and 2 analysis yielded genome-wide significant associations with schizophrenia for seven loci, five of which are new (1p21.3, 2q32.3, 8p23.2, 8q21.3 and 10q24.32-q24.33) and two of which have been previously implicated (6p21.32-p22.1 and 18q21.2). The strongest new finding (P = 1.6 x 10(-11)) was with rs1625579 within an intron of a putative primary transcript for MIR137 (microRNA 137), a known regulator of neuronal development. Four other schizophrenia loci achieving genome-wide significance contain predicted targets of MIR137, suggesting MIR137-mediated dysregulation as a previously unknown etiologic mechanism in schizophrenia. In a joint analysis with a bipolar disorder sample (16,374 affected individuals and 14,044 controls), three loci reached genome-wide significance: CACNA1C (rs4765905, P = 7.0 x 10(-9)), ANK3 (rs10994359, P = 2.5 x 10(-8)) and the ITIH3-ITIH4 region (rs2239547, P = 7.8 x 10(-9)).

Molecular abundances in the magellanic clouds .1. A multiline study of five cloud cores

Nine H II regions of the LMC were mapped in (CO)-C-13(1-0) and three in (CO)-C-12(1-0) to study the physical properties of the interstellar medium in the Magellanic Clouds. For N113 the molecular core is found to have a peak position which differs from that of the associated H II region by 20 ''. Toward this molecular core the (CO)-C-12 and (CO)-C-13 peak T-MB line temperatures of 7.3 K and 1.2 K are the highest so far found in the Magellanic Clouds. The molecular concentrations associated with N113, N44BC, N159HW, and N214DE in the LMC and LIRS 36 in the SMC were investigated in a variety of molecular species to study the chemical properties of the interstellar medium. I(HCO+)/I(HCN) and I(HCN)/I(HNC) intensity ratios as well as lower limits to the I((CO)-C-13)/I((CO)-O-18) ratio were derived for the rotational 1-0 transitions. Generally, HCO+ is stronger than HCN, and HCN is stronger than HNC. The high relative HCO+ intensities are consistent with a high ionization flux from supernovae remnants and young stars, possibly coupled with a large extent of the HCO+ emission region. The bulk of the HCN arises from relatively compact dense cloud cores. Warm or shocked gas enhances HCN relative to HNC. From chemical model calculations it is predicted that I(HCN)/I(HNC) close to one should be obtained with higher angular resolution (less than or similar to 30 '') toward the cloud cores. Comparing virial masses with those obtained from the integrated CO intensity provides an H-2 mass-to-CO luminosity conversion factor of 1.8 x 10(20) mol cm(-2) (K km s(-1))(-1) for N113 and 2.4 x 10(20) mol cm(-2) (K km s(-1))(-1) for N44BC. This is consistent with values derived for the Galactic disk.