Internalization and desensitization of the human glucose-dependent-insulinotropic receptor is affected by N-terminal acetylation of the agonist

How incretins regulate presence of their receptors at the cell surface and their activity is of paramount importance for the development of therapeutic strategies targeting these receptors. We have studied internalization of the human Glucose-Insulinotropic Polypeptide receptor (GIPR). GIP stimulated rapid robust internalization of the GIPR, the major part being directed to lysosomes. GIPR internalization involved mainly clathrin-coated pits, AP-2 and dynamin. However, neither GIPR C-terminal region nor β-arrestin1/2 was required. Finally, N-acetyl-GIP recognized as a dipeptidyl-IV resistant analogue, fully stimulated cAMP production with a ∼15-fold lower potency than GIP and weakly stimulated GIPR internalization and desensitization of cAMP response. Furthermore, docking N-acetyl-GIP in the binding site of modelled GIPR showed slighter interactions with residues of helices 6 and 7 of GIPR compared to GIP. Therefore, incomplete or partial activity of N-acetyl-GIP on signaling involved in GIPR desensitization and internalization contributes to the enhanced incretin activity of this peptide.

Comparative Study of Different Methods for the Prediction of Drug− Polymer Solubility

In this study, a comparison of different methods to predict drug−polymer solubility was carried out on binary systems consisting of five model drugs (paracetamol, chloramphenicol, celecoxib, indomethacin, and felodipine) and polyvinylpyrrolidone/vinyl acetate copolymers (PVP/VA) of different monomer weight ratios. The drug−polymer solubility at 25 °C was predicted using the Flory−Huggins model, from data obtained at elevated temperature using thermal analysis methods based on the recrystallization of a supersaturated amorphous solid dispersion and two variations of the melting point depression method. These predictions were compared with the solubility in the low molecular weight liquid analogues of the PVP/VA copolymer (N-vinylpyrrolidone and vinyl acetate). The predicted solubilities at 25 °C varied considerably depending on the method used. However, the three thermal analysis methods ranked the predicted solubilities in the same order, except for the felodipine−PVP system. Furthermore, the magnitude of the predicted solubilities from the recrystallization method and melting point depression method correlated well with the estimates based on the solubility in the liquid analogues, which suggests that this method can be used as an initial screening tool if a liquid analogue is available. The learnings of this important comparative study provided general guidance for the selection of the most suitable method(s) for the screening of drug−polymer solubility.

An In-depth Appraisal of Career Termination Experiences in Elite Cricket.

This qualitative study explored the career termination experiences of 9 male, retired professional cricketers, between the ages of 28 to 40 (M = 34, SD = 4.65). The participants took part in retrospective, semi-structured interviews. Data from the interviews were inductively content analysed within three transition phases of the retirement process: reasons for retirement, factors affecting adaptation, and reactions to retirement. The reasons for retirement were multicausal with the majority of the participants highlighting contractual pressures and a lack of communication as important precursors to retirement. Three main themes accounted for the factors affecting adaptation: a limited pursuit of other interests, developmental experiences and coping strategies. In terms of reactions to retirement, all of the participants reflected negatively on the termination of their career, with a sense of loss and resentment characterising the post-retirement period. The findings illustrated the sport-specific nature of career termination in professional cricket, and added further support to the emerging consensus that the distinction between voluntary and involuntary retirement is, at best, unclear.

Enhancing Student Learning Experiences in Sport Psychology Modules Using Practical Activities

The University of Worcester states in its most recent strategic plan (2013 – 2018) a set of enduring values that guide and direct the activities of the institution. The first listed, and perhaps the most important value is the striving to be “an outstanding university at which to be a student”. This is further supplemented by values such as “to inspire our students to reach their full potential through excellent, innovative teaching, scholarship and research” (University of Worcester 2013: p.4). One of the many ways in which the institution strives to provide this outstanding educational experience is through regular engagement, both formal and informal, with students at a number of points in each semester. Regular experiences of collating formal and informal feedback has led to the identification of a common theme amongst Higher National Diploma (HND) students in the Institute of Sport and Exercise Sciences (ISES), where they consistently request ‘more practicals’. The ISES modules however are designed to incorporate a high degree of interaction, practical activities and tasks. This is especially important for those studying at HND level as research suggests differences in learning preferences exist when compared to undergraduate students, the former preferring a more tactile style of learning (Peters et al. 2008). Using an introductory Sport Psychology HND module as an example, practical activities and tasks are fully embedded in the taught sessions to enable contextual links to be made between the learning outcomes and their subsequent use. Examples of these include: a. interviewing athletes to produce a performance profile (Butler & Hardy 1992); b. completing psychometric instruments such as the Competitive State Anxiety Inventory-2 (CSAI-2) to measure competitive anxiety in sport (Martens et al. 1990) and demonstrate data collection and construct measurement; c. performing relaxation interventions on the students to demonstrate how specific techniques (in this instance, decreasing somatic anxiety) might work in practice; d. demonstrating how observational learning facilitates skill acquisition by creating experimental conditions that the students participate in, in teaching a new skill. Nevertheless owing to the students' previously stated on-going requests for more practical activities, it became evident that assumptions about what students consider an effective means of experiential or active learning in the context of sport-related disciplines of study needed to be investigated. This is where the opportunity to undertake an action research project arose, this being a practical method commonly employed in pedagogical enquiry to aid reflection on teaching and assessment practice for the purposes of working towards continuous improvement.

Recensão: Claire Bishop, "Radical Museology: or What’s ‘Contemporary’ In Museums of Contemporary Art?"

Recensão de: Claire Bishop, "Radical Museology: or What’s ‘Contemporary’ In Museums of Contemporary Art?", Londres: Koenig Books, 2013

La Terre sainte, royaume de Marie : journal bi-mensuel / Oeuvre religieuse de l'Orient ; [dir. Claude-Régis Girard]

1875/05/20 (A11,N9)- (A11,N10).

La Terre sainte, royaume de Marie : journal bi-mensuel / Oeuvre religieuse de l'Orient ; [dir. Claude-Régis Girard]

1875/02/20 (A11,N3)- (A11,N4).

La Terre sainte, royaume de Marie : journal bi-mensuel / Oeuvre religieuse de l'Orient ; [dir. Claude-Régis Girard]

1875/04/30 (A11,N7)- (A11,N8).

La Terre sainte, royaume de Marie

Variante(s) de titre : La Terre sainte et les églises orientales

La Terre sainte, royaume de Marie : journal bi-mensuel / Oeuvre religieuse de l'Orient ; [dir. Claude-Régis Girard]

1875/01/26 (A11,N1)- (A11,N2).

La Terre sainte, royaume de Marie : journal bi-mensuel / Oeuvre religieuse de l'Orient ; [dir. Claude-Régis Girard]

1875/03/20 (A11,N5)- (A11,N6).

Magasin des modes nouvelles, françaises et anglaises, décrites d'une manière claire & précise, & représentées par des planches en taille-douce, enluminées

1786-1789.