Qualitative exploration of the views of healthy living champions from pharmacies in England.

BACKGROUND: In England, the 'Healthy Living Pharmacy (HLP)' initiative has been trialed; positive outcomes led to national roll-out across England to 20 pathfinder sites. A HLP provides health promotion/prevention services through a structured framework to meet local population need. Non-pharmacist staff receive additional training so that they can provide these services, and are known as Healthy Living Champions (HLCs). OBJECTIVES: To explore HLCs views on their role and to identify any barriers or facilitators in performing the role. METHODS: Fourteen semi-structured face-to-face interviews were conducted during February and March 2013 in NHS Dudley, and analysed using the principles of content analysis. RESULTS: Three themes emerged from the interviews; HLC job role; training; and public awareness. HLC staff showed high levels of motivation, a strong desire to help people and felt a sense of personal reward, resulting in increased levels of job satisfaction. Training had improved their confidence but they still had reservations in offering services such as alcohol intervention and weight management. All believed that public awareness was low despite advertising. CONCLUSION: HLCs were positive toward their new role and derived job satisfaction from helping people to improve their health, although on-going training and support was perceived as important

An alternative polyadenylation signal in TCF7L2 generates isoforms that inhibit T cell factor/lymphoid-enhancer factor (TCF/LEF)-dependent target genes.

Journal ArticleResearch Support, Non-U.S. Gov't© The Author(s) 2011. This article is published with open access at Springerlink.comAIMS/HYPOTHESIS: Intronic single nucleotide polymorphisms within the transcription factor 7-like 2 (TCF7L2) gene are associated with risk of type 2 diabetes. It is widely hypothesised that the predisposing variation is involved in cis-regulation of TCF7L2 activity. The aim of this study was to seek evidence for the existence of novel TCF7L2 isoforms encoded within the type 2 diabetes-associated genomic region. METHODS: We searched expressed sequence tag (EST) databases for novel TCF7L2 transcripts and sought to validate the function and integrity of any isoforms found using a combination of RT-PCR, western blotting and reporter gene techniques. RESULTS: Analysis of EST databases suggested the presence of an alternative polyadenylation site located in intron 4 of TCF7L2. We used 3' rapid amplification of cDNA ends and real-time PCR to validate the integrity of this polyadenylation signal and show its wide use across human tissues. Western blotting results are consistent with the use of this polyadenylation signal to generate novel protein isoforms. The alternative polyadenylation signal results in the production of isoforms that retain the β-catenin binding domain but do not possess the high-mobility group box DNA-binding domain. Promoter-reporter gene assays suggest that these isoforms inhibit TCF7L2-dependent target genes by sequestering β-catenin. CONCLUSIONS/INTERPRETATION: We have identified a novel polyadenylation signal within TCF7L2 that can result in the production of isoforms that act to repress TCF/LEF-dependent target genes. These findings may provide new insights into the association of TCF7L2 with susceptibility to type 2 diabetes.Wellcome TrustMRCEuropean Community’s Seventh Framework Programm

Proglucagon-derived peptides do not significantly affect acute exocrine pancreas in rat

Reports have suggested a link between treatment with glucagon-like peptide 1 (GLP-1) analogs and an increased risk of pancreatitis. Oxyntomodulin, a dual agonist of both GLP-1 and glucagon receptors, is currently being investigated as a potential antiobesity therapy, but little is known about its pancreatic safety. The aim of the study was to investigate the acute effect of oxyntomodulin and other proglucagon-derived peptides on the rat exocrine pancreas.Glucagon-like peptide 1, oxyntomodulin, glucagon, and exendin-4 were infused into anesthetized rats to measure plasma amylase concentration changes. In addition, the effect of each peptide on both amylase release and proliferation in rat pancreatic acinar (AR42J) and primary isolated ductal cells was determined.Plasma amylase did not increase postpeptide infusion, compared with vehicle and cholecystokinin; however, oxyntomodulin inhibited plasma amylase when coadministered with cholecystokinin. None of the peptides caused a significant increase in proliferation rate or amylase secretion from acinar and ductal cells.The investigated peptides do not have an acute effect on the exocrine pancreas with regard to proliferation and plasma amylase, when administered individually. Oxyntomodulin seems to be a potent inhibitor of amylase release, potentially making it a safer antiobesity agent regarding pancreatitis, compared with GLP-1 agonists

Increased expression of miR-187 in human islets from individuals with type 2 diabetes is associated with reduced glucose-stimulated insulin secretion

Journal ArticleThis article is published with open access at Springerlink.com Electronic supplementary material. The online version of this article (doi:10.1007/s00125-013-3089-4) contains peer-reviewed but unedited supplementary material, which is available to authorised usersAims/hypothesis: Type 2 diabetes is characterised by progressive beta cell dysfunction, with changes in gene expression playing a crucial role in its development. MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression and therefore alterations in miRNA levels may be involved in the deterioration of beta cell function. Methods: Global TaqMan arrays and individual TaqMan assays were used to measure islet miRNA expression in discovery (n = 20) and replication (n = 20) cohorts from individuals with and without type 2 diabetes. The role of specific dysregulated miRNAs in regulating insulin secretion, content and apoptosis was subsequently investigated in primary rat islets and INS-1 cells. Identification of miRNA targets was assessed using luciferase assays and by measuring mRNA levels. Results: In the discovery and replication cohorts miR-187 expression was found to be significantly increased in islets from individuals with type 2 diabetes compared with matched controls. An inverse correlation between miR-187 levels and glucose-stimulated insulin secretion (GSIS) was observed in islets from normoglycaemic donors. This correlation paralleled findings in primary rat islets and INS-1 cells where overexpression of miR-187 markedly decreased GSIS without affecting insulin content or apoptotic index. Finally, the gene encoding homeodomain-interacting protein kinase-3 (HIPK3), a known regulator of insulin secretion, was identified as a direct target of miR-187 and displayed reduced expression in islets from individuals with type 2 diabetes. Conclusions/interpretation: Our findings suggest a role for miR-187 in the blunting of insulin secretion, potentially involving regulation of HIPK3, which occurs during the pathogenesis of type 2 diabetes. © 2013 The Author(s).This work was supported by the Wellcome Trust (project grant number 089845/Z/09/Z). GAR is the recipient of Royal Society Wolfson Research and Wellcome Trust Senior Investigator (WT098424AIA) Awards, and thanks the Medical Research Council (MRC) for Programme Grant MR/J0003042/1. GdSX and GAR were supported by a project grant from Diabetes UK (BDA 13/0004672) and HDR by MRC grant G1001644

Modifying the stereochemistry of an enzyme-catalyzed reaction by directed evolution

Aldolases have potential as tools for the synthesis of stereochemically complex carbohydrates. Here, we show that directed evolution can be used to alter the stereochemical course of the reaction catalyzed by tagatose-1,6-bisphosphate aldolase. After three rounds of DNA shuffling and screening, the evolved aldolase showed an 80-fold improvement in k-cat/K-m toward the non-natural substrate fructose 1,6-bisphosphate, resulting in a 100-fold change in stereospecificity. (31)P NMR spectroscopy was used to show that, in the synthetic direction, the evolved aldolase catalyzes the formation of carbon—carbon bonds with unnatural diastereoselectivity, where the >99:<1 preference for the formation of tagatose 1,6-bisphosphate was switched to a 4:1 preference for the diastereoisomer, fructose 1,6-bisphosphate. This demonstration is of considerable significance to synthetic chemists requiring efficient syntheses of complex stereoisomeric products, such as carbohydrate mimetics

Cubic Augmentation of Planar Graphs

In this paper we study the problem of augmenting a planar graph such that it becomes 3-regular and remains planar. We show that it is NP-hard to decide whether such an augmentation exists. On the other hand, we give an efficient algorithm for the variant of the problem where the input graph has a fixed planar (topological) embedding that has to be preserved by the augmentation. We further generalize this algorithm to test efficiently whether a 3-regular planar augmentation exists that additionally makes the input graph connected or biconnected. If the input graph should become even triconnected, we show that the existence of a 3-regular planar augmentation is again NP-hard to decide.Comment: accepted at ISAAC 201

Evaluation of Amino Acid Composition as a Geochronometer in Buried Soils on Mount Kenya, East Africa

A sequence of surface and buried paleosols from the slopes of Mount Kenya, East Africa, has been identified and dated by radiocarbon and amino acid dating techniques in order to elucidate the Quaternary history of the area. Buried paleosols vary in radiocarbon age from 900 to > 40,000 yrs BP. They have developed in glacial and periglacial deposits of variable texture, consisting of a high percentage of clasts of phonolite, basalt and syenite. All but two paleosols are located in the Afroalpine zone (above 3200 m). D/L ratios of amino acids in Ab horizons were determined in order to establish their reliability for relative age dating. Alanine, aspartic acid, glutamic acid, leucine, valine, and phenylalanine were routinely analyzed. Aspartic acid, as in other cases, proved reliable yielding remarkably consistent results, with higher ratios corresponding to increasing age. Other acids analyzed showed distinct trends, although not as convincing as aspartic acid. In most cases, the aspartic acid ratio/ age relationships were supported by radiocarbon dates. D/L ratios of aspartic acid varied from approximately 0.07 for modern samples, to approximately 0.45 in samples > 40,000 years old.On a identifié et daté, au radiocarbone et à l'aide de techniques de datations à l'acide aminé, des paléosols enfouis et de surface afin de comprendre l'évolution quaternaire de la région. Les datations au radiocarbone des paléosols enfouis varient de 900 à plus de 40 000 BP. Les sols se sont développés dans des dépôts glaciaires et périglaciaires de différentes textures, constitués de fragments de roches détritiques, de phonolite, de basalte et de syénite. Tous les paléosols, sauf deux, sont situés dans la zone afroalpine (au-dessus de 3200 m). On a déterminé par racémisation les rapports D/L des acides aminés dans les horizons Ab en vue d'évaluer leur fiabilité pour la datation des âges relatifs. On a fait l'analyse de l'alaline, de l'acide aspartique, de l'acide glutamique, de la leucine, de la valine et du phénylalaline. L'acide aspartique, comme dans d'autres cas, a donné des résultats particulièrement satisfaisants, les quotients plus élevés correspondant aux âges les plus anciens. D'autres acides montraient des tendances bien distinctes, mais moins convaincantes que dans le cas de l'acide aspartique. Ainsi, dans la plupart des cas, les relations quotients/âges de l'acide aspartique étaient corroborées par les datations au radiocarbone. Les rapports D/L de l'acide aspartique variaient d'environ 0,07 pour les échantillons modernes à environ 0,45 pour les échantillons de plus de 40 000 ans.Eine Série von an der Oberflâche Negenden und begrabenen Palàobôden von den Hàngen des Mount Kenya, Ost-Afrika, wurde mittels Radiokarbon- und Aminosâuredatierungs-techniken identifiziert und datiert, um die Geschichte dieses Gebiets im Quaternàr zu erhellen. Das durch Radiokarbon bestimmte Alter der begrabenen Palàobôden variiert von 900 bis > 40,000 Jahren v.u.Z. Dièse Bôden haben sich in glazialen und periglazialen Ablagerungen verschiedener Beschaffenheit entwickelt, welche zu einem hohen Prozentsatz aus Trùmmern von Phonolith, Basait und Syenit bestehen. AuBer zweien befinden sich aile Palàobôden in der afroalpinen Zone (oberhalb 3200 m). Die D/L Anteile der Aminosâuren in den Ab-Horizonten wurden bestimmt, um ihre Verlâpiichkeit bei der relativen Altersbestimmung festzustellen. Alamin, aspartische Sàure, Glutamin-Sàure, Leuzin, Valin und Phenylalanin wurden laufend analysiert. Wie in anderen Fallen erwies sich die aspartische Sàure als verlàpiich, indem sie bemerkenswert bestàndige Ergebnisse ergab, bei denen die hôheren Quotienten dem hôheren Alter entsprachen. Andere analysierte Sàuren zeigten ausgepràgte Trends, wenn auch nicht so ùberzeugend wie die aspartische Sàure. In den meisten Fallen wurden die Beziehungen Quotient/Alter der aspartischen Sàure durch Radiokarbondatierungen gestùtzt. Die D/L Anteile der aspartischen Sàure variierten von ungefâhr 0.07 fur moderne Proben bis ungefâhr 0.45 in Proben, die > 40,000 Jahre ait sind

Fourier Transform Scanning Tunneling Spectroscopy: the possibility to obtain constant energy maps and the band dispersion using a local measurement

We present here an overview of the Fourier Transform Scanning Tunneling spectroscopy technique (FT-STS). This technique allows one to probe the electronic properties of a two-dimensional system by analyzing the standing waves formed in the vicinity of defects. We review both the experimental and theoretical aspects of this approach, basing our analysis on some of our previous results, as well as on other results described in the literature. We explain how the topology of the constant energy maps can be deduced from the FT of dI/dV map images which exhibit standing waves patterns. We show that not only the position of the features observed in the FT maps, but also their shape can be explained using different theoretical models of different levels of approximation. Thus, starting with the classical and well known expression of the Lindhard susceptibility which describes the screening of electron in a free electron gas, we show that from the momentum dependence of the susceptibility we can deduce the topology of the constant energy maps in a joint density of states approximation (JDOS). We describe how some of the specific features predicted by the JDOS are (or are not) observed experimentally in the FT maps. The role of the phase factors which are neglected in the rough JDOS approximation is described using the stationary phase conditions. We present also the technique of the T-matrix approximation, which takes into account accurately these phase factors. This technique has been successfully applied to normal metals, as well as to systems with more complicated constant energy contours. We present results recently obtained on graphene systems which demonstrate the power of this technique, and the usefulness of local measurements for determining the band structure, the map of the Fermi energy and the constant-energy maps.Comment: 33 pages, 15 figures; invited review article, to appear in Journal of Physics D: Applied Physic

Pathways to economic well-being among teenage mothers in Great Britain

The present study examines pathways to independence from social welfare among 738 teenage mothers, participants of the 1970 British Cohort Study, who were followed up at age 30 years. Using a longitudinal design, a pathway model is tested, examining linkages between family social background, cognitive ability, school motivation, and individual investments in education, as well as work- and family-related roles. The most important factors associated with financial independence by age 30 are continued attachment to the labor market as well as a stable relationship with a partner (not necessarily the father of the child). Pathways to financial independence, in turn, are predicted through own cognitive resources, school motivation, and family cohesion. Implications of findings for policy making are discussed.© 2010 Hogrefe Publishing