Receptor activity-modifying protein-dependent effects of mutations in the calcitonin receptor-like receptor:implications for adrenomedullin and calcitonin gene-related peptide pharmacology

Background and Purpose Receptor activity-modifying proteins (RAMPs) define the pharmacology of the calcitonin receptor-like receptor (CLR). The interactions of the different RAMPs with this class B GPCR yield high-affinity calcitonin gene-related peptide (CGRP) or adrenomedullin (AM) receptors. However, the mechanism for this is unclear. Experimental Approach Guided by receptor models, we mutated residues in the N-terminal helix of CLR, RAMP2 and RAMP3 hypothesized to be involved in peptide interactions. These were assayed for cAMP production with AM, AM2 and CGRP together with their cell surface expression. Binding studies were also conducted for selected mutants. Key Results An important domain for peptide interactions on CLR from I32 to I52 was defined. Although I41 was universally important for binding and receptor function, the role of other residues depended on both ligand and RAMP. Peptide binding to CLR/RAMP3 involved a more restricted range of residues than that to CLR/RAMP1 or CLR/RAMP2. E101 of RAMP2 had a major role in AM interactions, and F111/W84 of RAMP2/3 was important with each peptide. Conclusions and Implications RAMP-dependent effects of CLR mutations suggest that the different RAMPs control accessibility of peptides to binding residues situated on the CLR N-terminus. RAMP3 appears to alter the role of specific residues at the CLR-RAMP interface compared with RAMP1 and RAMP2

A Generic Framework for Criterion-Referenced Assessment of Undergraduate Essays

This paper presents a brief review of the relative merits of norm-referenced and criterion-referenced assessment of undergraduate students' written work. Acknowledging that there are both positive and negative aspects of criterion referencing, a generic framework for such assessment of undergraduate essays is presented. It comprises criteria and standards (organised by `dimensions of achievement', i.e. content, process, affect and skills), proficiency standards for English language and communication competence, and cartographic and graphic skills. Problems of implementation include the size and complexity of the framework and the need to interpret and clarify the criteria and standards for students

Monitoring Cross-Linking, the Evolution of Refractive Index and the Glass Transition Temperature of an Epoxy Resin Using an Optical Fiber Sensor

Hyphenated analytical techniques enable the simultaneous measurement of relevant processing and materials parameters under identical environmental conditions. In the current study, a power-compensated differential scanning calorimeter (DSC) was custom-modified to enable the integration of an optical fibre sensor to monitor in situ the progression of the cross-linking reactions by inferring the evolution of the refractive index. A cleaved optical fibre was used and it served as a Fresnel reflection sensor (FRS). The DSC was calibrated with and without the integrated FRS and it was demonstrated that it did not influence the performance of the DSC. The FRS was calibrated using reference refractive index oils within the DSC. An epoxy/amine resin system was cross-linked at 70 ^oC and the enthalpy of cross-linking and the evolution of the refractive index were monitored simultaneously using the DSC and FRS respectively. After the cross-linking was completed, the DSC was programmed to perform a ramped heating schedule from ambient temperature to 150 ^oC. The FRS was capable of detecting glass transition temperature (Tg) of the cross-linked resin. An excellent correlation was observed for the Tg obtained by the FRS and DSC. The contribution of factors affecting the resolution of the data from the FRS are discussed.</p

Professionalism, Golf Coaching and a Master of Science Degree: A commentary

As a point of reference I congratulate Simon Jenkins on tackling the issue of professionalism in coaching. As he points out coaching is not a profession, but this does not mean that coaching would not benefit from going through a professionalization process. As things stand I find that the stimulus article unpacks some critically important issues of professionalism, broadly within the context of golf coaching. However, I am not sure enough is made of understanding what professional (golf) coaching actually is nor how the development of a professional golf coach can be facilitated by a Master of Science Degree (M.Sc.). I will focus my commentary on these two issues

Treatment-limiting renal tubulopathy in patients treated with tenofovir disoproxil fumarate.

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is widely used in the treatment or prevention of HIV and hepatitis B infection. TDF may cause renal tubulopathy in a small proportion of recipients. We aimed to study the risk factors for developing severe renal tubulopathy. METHODS: We conducted an observational cohort study with retrospective identification of cases of treatment-limiting tubulopathy during TDF exposure. We used multivariate Poisson regression analysis to identify risk factors for tubulopathy, and mixed effects models to analyse adjusted estimated glomerular filtration rate (eGFR) slopes. RESULTS: Between October 2002 and June 2013, 60 (0.4%) of 15,983 patients who had received TDF developed tubulopathy after a median exposure of 44.1 (IQR 20.4, 64.4) months. Tubulopathy cases were predominantly male (92%), of white ethnicity (93%), and exposed to antiretroviral regimens that contained boosted protease inhibitors (PI, 90%). In multivariate analysis, age, ethnicity, CD4 cell count and use of didanosine or PI were significantly associated with tubulopathy. Tubulopathy cases experienced significantly greater eGFR decline while receiving TDF than the comparator group (-6.60 [-7.70, -5.50] vs. -0.34 [-0.43, -0.26] mL/min/1.73 m2/year, p < 0.0001). CONCLUSIONS: Older age, white ethnicity, immunodeficiency and co-administration of ddI and PI were risk factors for tubulopathy in patients who received TDF-containing antiretroviral therapy. The presence of rapid eGFR decline identified TDF recipients at increased risk of tubulopathy

State of the field: What can political ethnography tell us about anti-politics and democratic disaffection?

This article adopts and reinvents the ethnographic approach to uncover what governing elites do, and how they respond to public disaffection. Although there is significant work on the citizens’ attitudes to the governing elite (the demand side) there is little work on how elites interpret and respond to public disaffection (the supply side). We argue that ethnography is the best available research method for collecting data on the supply side. In doing so, we tackle long-standing stereotypes in political science about the ethnographic method and what it is good for. We highlight how the innovative and varied practices of contemporary ethnography are ideally suited to shedding light into the ‘black box’ of elite politics. We demonstrate the potential pay-off with reference to important examples of elite ethnography from the margins of political science scholarship. The implications from these rich studies, we argue, suggest a reorientation of how we understand the drivers of public disaffection and the role that political elites play in exacerbating cynicism and disappointment. We conclude by pointing to the benefits to the discipline in embracing elite ethnography both to diversify the methodological toolkit in explaining the complex dynamics of disaffection,and to better enable engagement in renewed public debate about the political establishment

Nail lacquer films’ surface energies and in vitro water-resistance and adhesion do not predict their in vivo residence

The in vivo residence of nail lacquers (which are ideal topical drug carriers for the treatment of nail diseases) determines their frequency of application, and is thereby expected to influence patient adherence and success of treatment. Thus in vitro measurements to indicate lacquers’ in vivo residence are routinely conducted during formulation development. However the literature on in vitro-in vivo correlations is severely limited. Thus, the aim of the work discussed in this paper was to investigate correlations between in vivo residence and in vitro film resistance to water, in vitro film adhesion and surface energy of lacquer films. In vivo measurements were conducted on fingernails in six volunteers. Seven commercially available nail lacquers were tested in commonly-used measurements. Correlations between in vivo residence and in vitro water resistance and adhesion were found to be extremely poor. The surface energies of the lacquer films (which were between 33 and 39 mJ/m2) were also not predictive of in vivo residence. High density polyethylene (HDPE) sheet – whose surface energy was determined to be similar to that of the human nailplate – was found to be a suitable model for the nailplate (when investigating surface energy) and was used in a number of experiments

Outbreak of Tinea capitis by Trichophyton tonsurans and Microsporum canis in Niterói, RJ, Brazil

18 girls from an orphanage (Orfanato Santo Antônio) in Niterói presented tinea capitis due to Trichophyton tonsurans (15 cases - 83.3%) and Microsporum canis (3 cases - 26.7%). Comments are made about clinical, mycological and therapeutic aspects of this microepidem