Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of gastric inhibitory polypeptide: N-acetyl-GIP and pGlu-GIP

Aims/hypothesis: This study examined the plasma stability, biological activity and antidiabetic potential of two novel N-terminally modified analogues of gastric inhibitory polypeptide (GIP).

Methods: Degradation studies were carried out on GIP, N-acetyl-GIP (Ac-GIP) and N-pyroglutamyl-GIP (pGlu-GIP) in vitro following incubation with either dipeptidylpeptidase IV or human plasma. Cyclic adenosine 3'5' monophosphate (cAMP) production was assessed in Chinese hamster lung fibroblast cells transfected with the human GIP receptor. Insulin-releasing ability was assessed in vitro in BRIN-BD11 cells and in obese diabetic (ob/ob) mice.

Results: GIP was rapidly degraded by dipeptidylpeptidase IV and plasma (t1/2 2.3 and 6.2 h, respectively) whereas Ac-GIP and pGlu-GIP remained intact even after 24 h. Both Ac-GIP and pGlu-GIP were extremely potent (p<0.001) at stimulating cAMP production (EC50 values 1.9 and 2.7 nmol/l, respectively), almost a tenfold increase compared to native GIP (18.2 nmol/l). Both Ac-GIP and pGlu-GIP (10–13–10–8 mmol/l) were more potent at stimulating insulin release compared to the native GIP (p<0.001), with 1.3-fold and 1.2-fold increases observed at 10–8 mol/l, respectively. Administration of GIP analogues (25 nmol/kg body weight, i.p.) together with glucose (18 mmol/kg) in (ob/ob) mice lowered (p<0.001) individual glucose values at 60 min together with the areas under the curve for glucose compared to native GIP. This antihyperglycaemic effect was coupled to a raised (p<0.001) and more prolonged insulin response after administration of Ac-GIP and pGlu-GIP (AUC, 644±54 and 576±51 ng·ml–1·min, respectively) compared with native GIP (AUC, 257±29 ng·ml–1·min).

Conclusion/interpretation: Ac-GIP and pGlu-GIP, show resistance to plasma dipeptidylpeptidase IV degradation, resulting in enhanced biological activity and improved antidiabetic potential in vivo, raising the possibility of their use in therapy of Type II (non-insulin-dependent) diabetes mellitus.

Individual trade-offs between nutrition and risk of interspecific transmission of disease by grazing: cows, badger latrines and bovine tuberculosis

1. We examine whether various measures of herbivore current physiological state (age, breeding and immune status) and genetic potential can be used as indicators of exposure to and risk from disease. We use dairy cattle and the risks of tuberculosis (TB) transmission posed to them by pasture contaminated with badger excreta (via the fecal-oral route) as a model system to address our aim.

Algal epiphytes of Zostera marina: Variation in assemblage structure from individual leaves to regional scale

Data from a hierarchical study of four Zostera marina beds in Wales were used to identify the spatial scales of variation in epiphyte assemblages. There were significant within and among bed differences in assemblage structure. The differences in assemblage structure with spatial scale generally persisted when species identifications were aggregated into functional groups. There was also significant within and among bed variability in Zostera density and average length. Local variations in Zostera canopy variables at the quadrat scale (total leaf length, average leaf length and leaf density per quadrat) were not related to epiphyte species richness nor to the structure of the assemblage. In contrast, individual leaf length was significantly related to species richness in two of the beds and the structure of epiphyte assemblages was always related to individual leaf lengths. The absence of links between quadrat scale measurements of canopy variables and assemblage structure may reflect the high turnover of individual Zostera leaves. Experimental work is required to discriminate further between the potential causes of epiphyte assemblage variation within and between beds. No bed represented a refuge where a rare species was abundant. If a species was uncommon at the bed scale, it was also uncommon in beds where it occurred. The heterogeneous assemblages found in this study suggest that a precautionary approach to conservation is advisable.

Imaging the cool stars in the interacting binaries AE Aqr, BV Cen and V426 Oph

It is well known that magnetic activity in late-type stars increases with increasing rotation rate. Using inversion techniques akin to medical imaging, the rotationally broadened profiles from such stars can be used to reconstruct `Doppler images' of the distribution of cool, dark starspots on their stellar surfaces. Interacting binaries, however, contain some of the most rapidly rotating late-type stars known and thus provide important tests of stellar dynamo models. Furthermore, magnetic activity is thought to play a key role in their evolution, behaviour and accretion dynamics. Despite this, we know comparatively little about the magnetic activity and its influence on such binaries. In this review we summarise the concepts behind indirect imaging of these systems, and present movies of the starspot distributions on the cool stars in some interacting binaries. We conclude with a look at the future opportunities that such studies may provide.

The effect of star-spots on eclipse timings of binary stars

We investigate the effects that star-spots have on the light curves of eclipsing binaries, and in particular how they may affect the accurate measurement of eclipse timings. Concentrating on systems containing a low-mass main-sequence star and a white dwarf, we find that if star-spots exhibit the Wilson depression they can alter the times of primary eclipse ingress and egress by several seconds for typical binary parameters and star-spot depressions. In addition, we find that the effect on the eclipse ingress/egress times becomes more profound for lower orbital inclinations. We show how it is possible, in principle, to determine estimates of both the binary inclination and the depth of the Wilson depression from light curve analysis.

Roche tomography of the secondary stars in CVs

The secondary stars in cataclysmic variables (CVs) are key to our understanding of the origin, evolution and behaviour of this class of interacting binary. In seeking a fuller understanding of these objects, the challenge for observers is to obtain images of the secondary star. This goal can be achieved through Roche tomography, an indirect imaging technique that can be used to map the Roche-lobe-filling secondary. The review begins with a description of the basic principles that underpin Roche tomography, including methods for determining the system parameters. Finally, we conclude with a look at the main scientific highlights to date, including the first unambiguous detection of starspots on AE Aqr B, and consider the future prospects of this technique.

Roche tomography of cataclysmic variables - II. Images of the secondary stars in AM Her, QQ Vul, IP Peg and HU Aqr

We present a set of Roche tomography reconstructions of the secondary stars in the cataclysmic variables AM Her, QQ Vul, IP Peg and HU Aqr. The image reconstructions show distinct asymmetries in the irradiation pattern for all four systems that can be attributed to shielding of the secondary star by the accretion stream/column in AM Her, QQ Vul and HU Aqr, and increased irradiation by the bright-spot in IP Peg. We use the entropy landscape technique to derive accurate system parameters (M-1, M-2, i and gamma) for the four binaries. In principle, this technique should provide the most reliable mass determinations available, since the intensity distribution across the secondary star is known. We also find that the intensity distribution can systematically affect the value of gamma derived from circular orbit fits to radial velocity variations.

Submillimeter wave frequency selective surface with polarisation independent spectral responses

This paper reports the design, construction and electromagnetic performance of a new freestanding frequency selective surface (FSS) structure which generates coincident spectral responses for dual polarisation excitation at oblique angles of incidence. The FSS is required to allow transmission of 316.5 - 325.5 GHz radiation with a loss = 0.6 dB and to achieve = 30 dB rejection from 349.5 - 358.5 GHz. It should also exhibit crosspolarisation levels below -25 dB, all criteria being satisfied simultaneously for TE and TM polarisations at 45° incidence. The filter consists of two identical, 30 mm diameter, 12.5 ?m thick, optically flat, perforated metal screens separated by 450 ?m. Each of the ˜5000 unit cells contains two nested, short circuited, rectangular loop slots and a rectangular dipole slot. The nested elements provide a passband spectral response centred at 320 GHz in the TE and TM planes; the dipole slot increases the filter roll-off above resonance. The FSS was fabricated from silicon-on-insulator wafers using precision micromachining and plating processes including the use of Deep Reactive Ion Etching (DRIE) to pattern the individual slots and remove the substrate under the periodic arrays. Quasi–optical transmission measurements in the 250 – 360 GHz range yielded virtually identical copolarised spectral responses, with the performance meeting or exceeding the above specifications. Experimental results are in excellent agreement with numerical predictions.

The VLT-FLAMES survey of massive stars: atmospheric parameters and rotational velocity distributions for B-type stars in the Magellanic Clouds (vol 457, pg 265, 2006)

We correct the estimates of the dispersions in the rotational velocities for early-type stars in our Galaxy (Dufton et al. 2006, A&A, 457, 265) and the Magellanic Clouds (Hunter et al. 2008, A&A, 479, 541). The corrected values are pi(1/4) (i.e. approximately 33%) larger than those published in the original papers.