Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice

Glucosedependent insulinotropic polypeptide (GIP) is an incretin hormone secreted by endocrine Kcells in response to nutrient absorption. In this study we have utilized a specific and enzymatically stable GIP receptor antagonist, (Pro(3))GIP, to evaluate the contribution of endogenous GIP to insulin secretion and glucose homeostasis in mice. Daily injection of (Pro(3))GIP (25 nmol/kg body weight) for 11 days had no effect on food intake or body weight. Nonfasting plasma glucose concentrations were significantly raised (p

The present-day chemical composition of the LMC

High-resolution observations of five OB-type main-sequence stars in the Large Magellanic Cloud (LMC) have been obtained with the UCL echelle spectrograph on the 3.9-m Anglo-Australian Telescope. These spectra have been analysed using LTE model- atmosphere techniques, to derive stellar atmospheric parameters and chemical compositions. As these stars are located within the hydrogen burning main-sequence band, their surface abundances should reflect those of the present-day interstellar medium. Detailed line-by-line differential analyses have been undertaken relative to Galactic comparison stars. We conclude that there exists a general metal deficiency of - 0.31 +/- 0.04 dex within the LMC, and find no significant abundance variations between cluster and field stars. There is also tentative evidence to suggest a lower oxygen to iron abundance ratio, and an over-deficiency of magnesium relative to the other alpha-elements. These are discussed in terms of previous abundance analyses and models of discontinuous (or bursting) star formation within the LMC. Finally, there is some evidence to suggest a greater chemical enrichment of material within the H. region LH104.

The present-day chemical composition of the SMC from UVES spectra of the sharp-lined, B-type dwarf AV 304

High-resolution spectroscopic VLT/UVES observations are presented for the B-type main-sequence star, AV 304, in the Small Magellanic Cloud (SMC). These spectra have been analysed using LTE model-atmosphere techniques, to derive stellar atmospheric parameters and chemical compositions. As AV 304 is located within the hydrogen burning main-sequence band, its chemical composition should reflect that of the SMC interstellar medium (ISM). A detailed line-by-line differential analysis has been undertaken relative to a Galactic comparison star. A general metal deficiency for the a-process elements O, Si & S of -0.43 +/- 0.05 dex is found for AV 304, with iron having a similar underabundance. Oxygen may be relatively over- abundant by similar to0.1 dex and carbon and aluminium underabundant by similar to0.2 dex. A large nitrogen underabundance (of -1.2 dex relative to hydrogen and -0.7 dex relative to iron) is found. This is interpreted in terms of the CNO bi-cycle having been suppressed in the SMC. Furthermore, the large nitrogen deficiency is in excellent agreement with that found for SMC H II regions. Indeed, this represents a first for stellar astrophysics - confirming the low base-line nitrogen composition of the SMC ISM (viz. 12+log(N/H) similar to 6.66 +/- 0.10 dex).

A NEW CHEMICAL-MODEL OF THE CIRCUMSTELLAR ENVELOPE SURROUNDING IRC+10216

A new chemical model of the circumstellar envelope surrounding the carbon-rich star IRC+10216 has been developed. This model incorporates a variety of newly measured rapid neutral-neutral reactions between carbon atoms and hydrocarbons and between the radical CN and a variety of stable neutral molecules. In addition, other neutral-neutral reactions in the above two classes or involving atoms such as N or radicals such as C(2n)H have been included with large rate coefficients although they have not yet been studied in the laboratory. Unlike the interstellar case, where the inclusion of these neutral-neutral reactions destroys molecular complexity, our model results for IRC+10216 show that sufficient abundances of large hydrocarbon radicals and cyanpolyynes can be produced to explain observations. We also discuss the formation of H2CN and NH2CN, two potentially observable molecules in IRC+10216.

The activity of a putative polyisoprenol-linked sugar translocase (Wzx) involved in Escherichia coli O antigen assembly is independent of the chemical structure of the O repeat

During O antigen lipopolysaccharide (LPS) synthesis in bacteria, transmembrane migration of undecaprenylpyrophosphate (Und-P-P)-bound O antigen subunits occurs before their polymerization and ligation to the rest of the LPS molecule. Despite the general nature of the translocation process, putative O-antigen translocases display a low level of amino acid sequence similarity. In this work, we investigated whether complete O antigen subunits are required for translocation. We demonstrate that a single sugar, GlcNAc, can be incorporated to LPS of Escherichia coli K-12. This incorporation required the functions of two O antigen synthesis genes, wecA (UDP-GlcNAc:Und-P GlcNAc-1-P transferase) and wzx (O-antigen translocase). Complementation experiments with putative O-antigen translocases from E. coli O7 and Salmonella enterica indicated that translocation of O antigen subunits is independent of the chemical structure of the saccharide moiety. Furthermore, complementation with putative translocases involved in synthesis of exopolysaccharides demonstrated that these proteins could not participate in O antigen assembly. Our data indicate that recognition of a complete Und-P-P-bound O antigen subunit is not required for translocation and suggest a model for O antigen synthesis involving recognition of Und-P-P-linked sugars by a putative complex made of Wzx translocase and other proteins involved in the processing of O antigen.

Design, recruitment, logistics, and data management of the GEHA (Genetics of Healthy Ageing) project

In 2004, the integrated European project GEHA (Genetics of Healthy Ageing) was initiated with the aim of identifying genes involved in healthy ageing and longevity. The first step in the project was the recruitment of more than 2500 pairs of siblings aged 90 years or more together with one younger control person from 15 areas in 11 European countries through a coordinated and standardised effort. A biological sample, preferably a blood sample, was collected from each participant, and basic physical and cognitive measures were obtained together with information about health, life style, and family composition. From 2004 to 2008 a total of 2535 families comprising 5319 nonagenarian siblings were identified and included in the project. In addition, 2548 younger control persons aged 50-75 years were recruited. A total of 2249 complete trios with blood samples from at least two old siblings and the younger control were formed and are available for genetic analyses (e.g. linkage studies and genome-wide association studies). Mortality follow-up improves the possibility of identifying families with the most extreme longevity phenotypes. With a mean follow-up time of 3.7 years the number of families with all participating siblings aged 95 years or more has increased by a factor of 5 to 750 families compared to when interviews were conducted. Thus, the GEHA project represents a unique source in the search for genes related to healthy ageing and longevity.

Chemical tuning of the interlayer magnetic coupling in TlCo2Se2-xSx

The system TlCo2Se2-xSx has been thoroughly investigated by neutron powder diffraction and SQUID magnetometry. TlCo2Se2-xSx is a layered tetragonal structure containing atomic cobalt layers separated by a distance of 6.4 angstrom in the sulphide and 6.8 angstrom in the selenide. The solid solubility of isovalent selenium and sulphur atoms in the structure makes it possible to continuously vary the interlayer distance and thereby tune the magnetic coupling between the Co-layers. At low temperatures, the Co-atoms are ferromagnetically ordered within the layers and magnetic moments lie in the ab-plane. However, these Co-moments form a helical magnetic structure that prevails for 0 <= x <= 1.5 with a gradual decrease of the angle between adjacent Co-layers from 122 degrees to 39 degrees. For x >= 1.75, a collinear ferromagnetic structure is stable. The relationship between the coupling angle and the Co-interlayer separation shows an almost linear behaviour. The helical phase contains no net spontaneous magnetic moment up to TlCo2SeS, where a small net magnetic moment appears that increases until the ferromagnetic structure is found for 1.75 <= x <= 2.0. (C) 2005 Elsevier B.V. All rights reserved.

General practitioners’ management of the long-term sick role

In this paper, we use qualitative research techniques to examine the role of general practitioners in the management of the long-term sickness absence. In order to uncover the perspectives of all the main agents affected by the actions of general practitioners, a case study approach focussing on one particular employment sector, the public health service, is adopted. The role of family physicians is viewed from the perspectives of health service managers, occupational health physicians, employees / patients, and general practitioners. Our argument is theoretically framed by Talcott Parsons’s model of the medical contribution to the sick role, along with subsequent conceptualisations of the social role and position of physicians. Sixty one semi-structured interviews and three focus group interviews were conducted in three Health and Social Care Trusts in Northern Ireland between 2010 and 2012. There was a consensus among respondents that general practitioners put far more weight on the preferences and needs of their patients than they did on the requirements of employing organisations. This was explained by respondents in terms of the propinquity and longevity of relationships between doctors and their patients, and by the ideology of holistic care and patient advocacy that general practitioners viewed as providing the foundations of their approach to patients. The approach of general practitioners was viewed negatively by managers and occupational health physicians, and more positively by general practitioners and patients. However, there is some evidence that general practitioners would be prepared to forfeit their role as validators of sick leave. Given the imperatives of both state and capital to reduce the financial burden of long-term sickness, this preparedness puts into doubt the continued role of general practitioners as gatekeepers to legitimate long-term sickness absence.