Educational Leadership Preparation: What Supervisors, Candidates, And Mentors Said

The findings of this study identified practicum areas that meet the educational demands of candidates while highlighting practicum areas that need improvement. The study contributes to the knowledge base of the field by drawing upon feedback from university supervisors, school mentors and program candidates to evaluate and improve the practicum experience in the educational leadership program. Program candidates are in the best position to discuss their recent experiences of exposure to the real world. Supervisors and mentors can witness from their first hand experience how effective practicum activities work. Responses from supervisors, mentors and candidates regarding leadership practicum experiences are valuable to program developers in their future program redesign effort. Practicum experiences expose candidates to real-world school leadership experiences. Unfortunately, because of all kinds of conditional limitations, such practicum experiences can only be offered in conjunction with candidates' regular work in school. However, leadership practicum experiences can be well planned with a high collaboration of supervisors, mentors and candidates who have an invested interest in school improvement. In this study, what we learn from the differences of perceptions among supervisors, mentors and candidates is a caution to all stakeholders that we need to do a better job to prepare the next generation of school leaders. Supervisors, mentors and candidates need to form a coalition to explore other options, especially out-of-the-box strategies, to deliver a highly effective practicum program for potential educational leaders.&nbsp

Fluorescence correlation spectroscopy, combined with bimolecular fluorescence complementation, reveals the effects of β-arrestin complexes and endocytic targeting on the membrane mobility of neuropeptide Y receptors

Fluorescence correlation spectroscopy (FCS) and photon counting histogram (PCH) analysis are powerful ways to study mobility and stoichiometry of G protein coupled receptor complexes, within microdomains of single living cells. However, relating these properties to molecular mechanisms can be challenging. We investigated the influence of β-arrestin adaptors and endocytosis mechanisms on plasma membrane diffusion and particle brightness of GFP-tagged neuropeptide Y (NPY) receptors. A novel GFP-based bimolecular fluorescence complementation (BiFC) system also identified Y1 receptor-β-arrestin complexes. Diffusion co-efficients (D) for Y1 and Y2-GFP receptors in HEK293 cell plasma membranes were 2.22 and 2.15×10−9 cm2 s−1 respectively. At a concentrationwhich promoted only Y1 receptor endocytosis, NPY treatment reduced Y1-GFPmotility (D 1.48×10−9 cm2 s−1), but did not alter diffusion characteristics of the Y2-GFP receptor. Agonist induced changes in Y1 receptor motility were inhibited by mutations (6A) which prevented β-arrestin recruitment and internalisation; conversely they became apparent in a Y2 receptor mutant with increased β-arrestin affinity. NPY treatment also increased Y1 receptor-GFP particle brightness, changes which indicated receptor clustering, and which were abolished by the 6A mutation. The importance of β-arrestin recruitment for these effects was illustrated by reduced lateral mobility (D 1.20–1.33×10−9 cm2 s−1) of Y1 receptor-β-arrestin BiFC complexes. Thus NPY-induced changes in Y receptormotility and brightness reflect early events surrounding arrestin dependent endocytosis at the plasma membrane, results supported by a novel combined BiFC/FCS approach to detect the underlying receptor-β-arrestin signalling complex

Fluorescence correlation spectroscopy, combined with bimolecular fluorescence complementation, reveals the effects of β-arrestin complexes and endocytic targeting on the membrane mobility of neuropeptide Y receptors

Fluorescence correlation spectroscopy (FCS) and photon counting histogram (PCH) analysis are powerful ways to study mobility and stoichiometry of G protein coupled receptor complexes, within microdomains of single living cells. However, relating these properties to molecular mechanisms can be challenging. We investigated the influence of β-arrestin adaptors and endocytosis mechanisms on plasma membrane diffusion and particle brightness of GFP-tagged neuropeptide Y (NPY) receptors. A novel GFP-based bimolecular fluorescence complementation (BiFC) system also identified Y1 receptor-β-arrestin complexes. Diffusion co-efficients (D) for Y1 and Y2-GFP receptors in HEK293 cell plasma membranes were 2.22 and 2.15×10−9 cm2 s−1 respectively. At a concentrationwhich promoted only Y1 receptor endocytosis, NPY treatment reduced Y1-GFPmotility (D 1.48×10−9 cm2 s−1), but did not alter diffusion characteristics of the Y2-GFP receptor. Agonist induced changes in Y1 receptor motility were inhibited by mutations (6A) which prevented β-arrestin recruitment and internalisation; conversely they became apparent in a Y2 receptor mutant with increased β-arrestin affinity. NPY treatment also increased Y1 receptor-GFP particle brightness, changes which indicated receptor clustering, and which were abolished by the 6A mutation. The importance of β-arrestin recruitment for these effects was illustrated by reduced lateral mobility (D 1.20–1.33×10−9 cm2 s−1) of Y1 receptor-β-arrestin BiFC complexes. Thus NPY-induced changes in Y receptormotility and brightness reflect early events surrounding arrestin dependent endocytosis at the plasma membrane, results supported by a novel combined BiFC/FCS approach to detect the underlying receptor-β-arrestin signalling complex

Sun, sea, sand and silicone: mapping cosmetic surgery tourism

This multi-site, mixed methods project charted the experiences of British, Chinese and Australian patients travelling abroad for cosmetic surgery. Cosmetic surgery tourism is a fast developing industry that incorporates novel forms of labour and organisational structures that cross national boundaries, as well as drawing together pre-existing medical and tourism infrastructure. While medical tourism has often been characterised as wealthy patients from the global south travelling to the global north for high quality medical treatment unavailable at home, cosmetic surgery patients often travel from global north to global south, but these patients are on modest incomes. Despite this they can sometimes access upmarket private hospitals beyond their reach back home, made possible by favourable currency rates, cheap flights and lower labour costs outside the richest countries in the world. UK and Australian patients travelled for surgeries that were popular back home – such as breast augmentation and uplift, ‘tummy tuck’, rhinoplasty and liposuction. Others travel regionally, for example within Europe, often also motivated by cost savings. There are important exceptions to this pattern: Chinese patients travelling to South Korea access more expensive but high quality cosmetic surgery unavailable back home. Here patients from abroad often seek particular types of surgery prevalent amongst South Koreans, for example eye or jawbone surgery, or high tech surgery, such as breast augmentation using the patient’s own fat and stem cells. Patients therefore travel from global north to global south, across regional borders, and many are also ex-patriates. UK patients in Spain were most usually already living in Southern Spain or Gibraltar. Monitoring the movements of cosmetic surgery tourists is important in predicting health tourism in the future. As public healthcare systems are increasingly squeezed, patients become consumers in search of cut price procedures, taking on the risks of the choices they make. This research aimed to broaden understandings of surgical tourist experiences, the organisations involved, and the implications for globalize

MACiE: a database of enzyme reaction mechanisms.

SUMMARY: MACiE (mechanism, annotation and classification in enzymes) is a publicly available web-based database, held in CMLReact (an XML application), that aims to help our understanding of the evolution of enzyme catalytic mechanisms and also to create a classification system which reflects the actual chemical mechanism (catalytic steps) of an enzyme reaction, not only the overall reaction. AVAILABILITY: http://www-mitchell.ch.cam.ac.uk/macie/.EPSRC (G.L.H. and J.B.O.M.), the BBSRC (G.J.B. and J.M.T.—CASE studentship in association with Roche Products Ltd; N.M.O.B. and J.B.O.M.—grant BB/C51320X/1), the Chilean Government’s Ministerio de Planificacio´n y Cooperacio´n and Cambridge Overseas Trust (D.E.A.) for funding and Unilever for supporting the Centre for Molecular Science Informatics.application note restricted to 2 printed pages web site: http://www-mitchell.ch.cam.ac.uk/macie

Susceptibility locus on chromosome 1q23-25 for a schizophrenia subtype resembling deficit schizophrenia identified by latent class analysis

Context: Identifying susceptibility genes for schizophrenia may be complicated by phenotypic heterogeneity, with some evidence suggesting that phenotypic heterogeneity reflects genetic heterogeneity. Objective: To evaluate the heritability and conduct genetic linkage analyses of empirically derived, clinically homogeneous schizophrenia subtypes. Design: Latent class and linkage analysis. Setting: Taiwanese field research centers. Participants: The latent class analysis included 1236 Han Chinese individuals with DSM-IV schizophrenia. These individuals were members of a large affected-sibling-pair sample of schizophrenia (606 ascertained families), original linkage analyses of which detected a maximum logarithm of odds (LOD) of 1.8 (z = 2.88) on chromosome 10q22.3. Main Outcome Measures: Multipoint exponential LOD scores by latent class assignment and parametric heterogeneity LOD scores. Results: Latent class analyses identified 4 classes, with 2 demonstrating familial aggregation. The first (LC2) described a group with severe negative symptoms, disorganization, and pronounced functional impairment, resembling "deficit schizophrenia." The second (LC3) described a group with minimal functional impairment, mild or absent negative symptoms, and low disorganization. Using the negative/deficit subtype, we detected genome-wide significant linkage to 1q23-25 (LOD = 3.78, empiric genome-wide P = .01). This region was not detected using the DSM-IV schizophrenia diagnosis, but has been strongly implicated in schizophrenia pathogenesis by previous linkage and association studies.Variants in the 1q region may specifically increase risk for a negative/deficit schizophrenia subtype. Alternatively, these results may reflect increased familiality/heritability of the negative class, the presence of multiple 1q schizophrenia risk genes, or a pleiotropic 1q risk locus or loci, with stronger genotype-phenotype correlation with negative/deficit symptoms. Using the second familial latent class, we identified nominally significant linkage to the original 10q peak region. Conclusion: Genetic analyses of heritable, homogeneous phenotypes may improve the power of linkage and association studies of schizophrenia and thus have relevance to the design and analysis of genome-wide association studies

Comparison of maximum common subgraph isomorphism algorithms for the alignment of 2D chemical structures

The identification of the largest substructure in common when two (or more) molecules are overlaid is important for several applications in chemoinformatics, and can be implemented using a maximum common subgraph (MCS) algorithm. Many such algorithms have been reported, and it is important to know which are likely to be the useful in operation. A detailed comparison was hence conducted of the efficiency (in terms of CPU time) and the effectiveness (in terms of the size of the MCS identified) of eleven MCS algorithms, some of which were exact and some of which were approximate in character. The algorithms were used to identify both connected and disconnected MCSs on a range of pairs of molecules. The fastest exact algorithms for the connected and disconnected problems were found to be the fMCS and MaxCliqueSeq algorithms, respectively, while the ChemAxon_MCS algorithm was the fastest approximate algorithm for both types of problem

Discovery of TUG-770: a highly potent free fatty acid receptor 1 (FFA1/GPR40) agonist for treatment of type 2 diabetes

Free fatty acid receptor 1 (FFA1 or GPR40) enhances glucose-stimulated insulin secretion from pancreatic β-cells and currently attracts high interest as a new target for the treatment of type 2 diabetes. We here report the discovery of a highly potent FFA1 agonist with favorable physicochemical and pharmacokinetic properties. The compound efficiently normalizes glucose tolerance in diet-induced obese mice, an effect that is fully sustained after 29 days of chronic dosing

Rapid Quantification of Molecular Diversity for Selective Database Acquisition

There is an increasing need to expand the structural diversity of the molecules investigated in lead-discovery programs. One way in which this can be achieved is by acquiring external datasets that will enhance an existing database. This paper describes a rapid procedure for the selection of external datasets using a measure of structural diversity that is calculated from sums of pairwise intermolecular structural similarities