Effects of deleting cannabinoid receptor-2 on mechanical and material properties of cortical and trabecular bone

Acknowledgements We thank Dr J.S. Gregory for assistance with Image J and Mr K. Mackenzie for assistance with Micro-CT analysis. Funding ABK was funded by a University of Aberdeen, Institute of Medical Sciences studentship and the Overseas Research Students Awards Scheme.Peer reviewedPublisher PD

Mechanical and material properties of cortical and trabecular bone from cannabinoid receptor-1-null (Cnr1-/-) mice

Funding ABK was funded by a studentship from the University of Aberdeen, Institute of Medical Sciences, and the Overseas Research Students Awards Scheme Acknowledgments We are grateful to Dr J.S. Gregory for assistance with Image J and Mr K. Mackenzie for assistance with Micro-CT analysis.Peer reviewedPostprin

Model fidelity and students’ responses to an authenticated unit of Cooperative Learning

A wealth of school-based interventions report on students’ positive responses to the use of models-based practice in physical education. However, research that examines the effectiveness of models-based practice rarely reports on the fidelity of implementation i.e. when all of the characteristics of a model are implemented. The purpose of this study was to explore model fidelity in the use of the Cooperative Learning model. Action research and systematic observation (using the Cooperative Learning Validation Tool which acknowledged the key characteristics of the model) were used to confirm model fidelity. Consequently, the themes of ‘scaffolding student learning', 'working together', and 'deeper learning' could be directly linked to the authentic use of Cooperative Learning context. The paper concludes by arguing that when reporting on findings from empirical research on the use of Cooperative Learning we need to adopt a more robust approach in determining – through rigor and quality of research – the authenticity of implementation

The ITEST learning resource center's online evaluation database; Examples from the collection

The National Science Foundation-funded ITEST Learning Resource Center at EDC has developed an online database of instruments for ITEST project level evaluators and researchers to use as they develop measures for their projects. This article details the purpose and development of that database and highlights three instruments from it that represent the kind of evaluation tools archived there. Although the ITEST online evaluation instrument database is not publicly accessible, it represents an innovative way to collect, analyze and share evaluation instruments for use by a specific community of practice. The instruments shared in this article are available for public use, with appropriate citation, and represent the quality and aims of tools and instruments housed in the database. Keywords: Database, Teacher professional, development, Secondary school, Digital library collection, For those who evaluate or conduct research on technology integration and innovative Science, Technology, Engineering and Mathematics (STEM) educational programs, finding appropriate, valid and reliable measures of student skills and understanding and teachers' needs can be a challenge. To help address this challenge, the National Science Foundation-funded ITEST Learning Resource Center has developed an online database of instruments for ITEST project level evaluators and researchers to use as they develop measures for their projects. This article details the purpose and development of that database and highlights three instruments in it that represent the kind of evaluation tools archived there. Although the ITEST online evaluation instrument database is not publicly accessible, it represents an innovative way to collect, analyze and share evaluation instruments for use by a specific community of practice. The instruments shared in this article are available for public use, with appropriate citation, and represent the quality and aims of tools and instruments housed in the database. We will first describe the ITEST program and the role of the ITEST Learning Resource center, then detail the purpose and development of the online database, and end by sharing three examples of instruments ITEST 52 from that database that measure student technology skill level, content understanding and teachers' technology needs. ABOUT ITEST The National Science Foundation (NSF) established the Information Technology Experiences for Students and Teachers (ITEST) program in direct response to the looming shortage of information technology workers in the United States. The ITEST program is designed to address this shortage by increasing opportunities for students and teachers to learn about, experience, and use information technologies within the context of science, technology, engineering, and mathematics (STEM), including Information Technology (IT) courses. The ITEST program goals include increased and maintained student interest in IT through the creation of effective student education programs in both school and non-school settings. ITEST projects take two forms: youth-based projects offer exciting, hands-on STEM and IT experiences for students in out-of-school settings, and comprehensive projects provide professional development to teachers so that they can better use IT in their STEM and IT classes. The ITEST program started in 2003, and has funded four cohorts to date, totaling 76 projects. ITEST projects are in 36 states and approximately half of the projects are youth-based and half comprehensive projects. The ITEST program also funds a National Learning Resource Center to support, synthesize and disseminate the learning from the program to a wider audience. The National ITEST Learning Resource Center at Education Development Center (EDC) collaborates with ITEST Projects across the United States to achieve program goals, weave together promising practices and leverage their combined achievements into new knowledge. Activities of the Learning Resource Center (LRC) include: annual allproject meetings, called the ITEST Annual Summit; dissemination of promising practices and cutting edge research; and ongoing technical assistance targeted at content areas such as skills and standards, recruitment and retention of teachers and students, and technical issues such as working with specific types of technology in the classroom. The Learning Resource Center also leads a national research study focused on understanding the factors that contribute to teacher change, the development of student interest and skills and program models. The ITEST LRC collaborates with ITEST projects to design local and regional research studies, gather and analyze data, and report and disseminate findings. Findings from these studies inform and guide formal and informal educators in planning, implementing and evaluating IT-enriched STEM initiatives. ITEST RESEARCH APPROACH The ITEST LRC approach to designing and implementing the ITEST national research agenda is rooted in the principles of collaborative inquiry. Using an adaptation of Lawrenz and Huffman's (2003) multi-site participatory evaluation model, the LRC works with ITEST projects and their evaluators to develop a multi-site, coordinated research program to answer questions of interest to the ITEST community and the field. Through this process, the LRC generates research questions that will inform project practice and development; build on project evaluations and data collection to inform the generation of research areas and questions; leverage local evaluation data collection and analysis to form the base of the larger inquiry; and highlight issues of Equity and Access, and Informal and Formal Learning. ITEST collaborative research activities have included documentation and dissemination of compiled project level evaluation approaches and findings; the International Journal of Technology in Teaching & Learning 53 formation of thematic working groups to investigate research questions; online evaluation peer exchanges; evaluation technical assistance events, such as conference calls presenting strategies for writing strong reports; development and dissemination of literature reviews; and the collection, compilation and analysis of ITEST project evaluation instruments. Through the online evaluation peer exchange and other calls for submission of evaluation instruments, the ITEST LRC collected and categorized more than 90 instruments-42 student instruments and 49 teacher instruments-that measure aspects of ITEST program outcomes such as classroom implementation of IT; pedagogical practice in science and technology; IT skills and proficiencies; attitudes about technology; technology access; technology use; technology confidence; and technology integration. These instruments are housed in a searchable online database, accessible to the ITEST program community through the ITEST Learning Resource Center website. Built using digital library technology, users can search the database with key words that represent the programmatic outcomes included in the instruments. For example, a user could search for teacher instruments that measure technology integration and technology access. This search would yield 60 instruments. A search for student instruments that measure technology skills and proficiency yields 74 instruments. Now, obviously, these numbers are higher than the numbers of instruments referred to above; bugs in the database software cause it to turn up duplicates when searching, so users need to be cautious and look to make sure the instruments it finds are relevant. Overall, this searchable database serves the purpose of offering ITEST project evaluators a resource for instrument development. In the instrument development descriptions below, note that more than one of the evaluators featured in this article consulted other ITEST project evaluators for advice on instrument development. This electronic resource supports the growing network of ITEST principal investigators and evaluators. BACKGROUN

TBC1D1 Regulates Insulin- and Contraction-Induced Glucose Transport in Mouse Skeletal Muscle

OBJECTIVE: TBC1D1 is a member of the TBC1 Rab-GTPase family of proteins and is highly expressed in skeletal muscle. Insulin and contraction increase TBC1D1 phosphorylation on phospho-Akt substrate motifs (PASs), but the function of TBC1D1 in muscle is not known. Genetic linkage analyses show a TBC1D1 R125W missense variant confers risk for severe obesity in humans. The objective of this study was to determine whether TBC1D1 regulates glucose transport in skeletal muscle. RESEARCH DESIGN AND METHODS: In vivo gene injection and electroporation were used to overexpress wild-type and several mutant TBC1D1 proteins in mouse tibialis anterior muscles, and glucose transport was measured in vivo. RESULTS: Expression of the obesity-associated R125W mutant significantly decreased insulin-stimulated glucose transport in the absence of changes in TBC1D1 PAS phosphorylation. Simultaneous expression of an inactive Rab-GTPase (GAP) domain of TBC1D1 in the R125W mutant reversed this decrease in glucose transport caused by the R125W mutant. Surprisingly, expression of TBC1D1 mutated to Ala on four conserved Akt and/or AMP-activated protein kinase predicted phosphorylation sites (4P) had no effect on insulin-stimulated glucose transport. In contrast, expression of the TBC1D1 4P mutant decreased contraction-stimulated glucose transport, an effect prevented by concomitant disruption of TBC1D1 Rab-GAP activity. There was no effect of the R125W mutation on contraction-stimulated glucose transport. CONCLUSIONS: TBC1D1 regulates both insulin- and contraction-stimulated glucose transport, and this occurs via distinct mechanisms. The R125W mutation of TBC1D1 impairs skeletal muscle glucose transport, which could be a mechanism for the obesity associated with this mutation

Proteinase-activated receptor 2 modulates OA-related pain, cartilage and bone pathology

Objective Proteinase-activated receptor 2 (PAR2) deficiency protects against cartilage degradation in experimental osteoarthritis (OA). The wider impact of this pathway upon OA-associated pathologies such as osteophyte formation and pain is unknown. Herein, we investigated early temporal bone and cartilage changes in experimental OA in order to further elucidate the role of PAR2 in OA pathogenesis. Methods OA was induced in wild-type (WT) and PAR2-deficient (PAR2−/−) mice by destabilisation of the medial meniscus (DMM). Inflammation, cartilage degradation and bone changes were monitored using histology and microCT. In gene rescue experiments, PAR2−/− mice were intra-articularly injected with human PAR2 (hPAR2)-expressing adenovirus. Dynamic weight bearing was used as a surrogate of OA-related pain. Results Osteophytes formed within 7 days post-DMM in WT mice but osteosclerosis was only evident from 14 days post induction. Importantly, PAR2 was expressed in the proliferative/hypertrophic chondrocytes present within osteophytes. In PAR2−/− mice, osteophytes developed significantly less frequently but, when present, were smaller and of greater density; no osteosclerosis was observed in these mice up to day 28. The pattern of weight bearing was altered in PAR2−/− mice, suggesting reduced pain perception. The expression of hPAR2 in PAR2−/− mice recapitulated osteophyte formation and cartilage damage similar to that observed in WT mice. However, osteosclerosis was absent, consistent with lack of hPAR2 expression in subchondral bone. Conclusions This study clearly demonstrates PAR2 plays a critical role, via chondrocytes, in osteophyte development and subchondral bone changes, which occur prior to PAR2-mediated cartilage damage. The latter likely occurs independently of OA-related bone changes

The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15

Sound and acceleration are detected by hair bundles, mechanosensory structures located at the apical pole of hair cells in the inner ear. The different elements of the hair bundle, the stereocilia and a kinocilium, are interconnected by a variety of link types. One of these links, the tip link, connects the top of a shorter stereocilium with the lateral membrane of an adjacent taller stereocilium and may gate the mechanotransducer channel of the hair cell. Mass spectrometric and Western blot analyses identify the tip-link antigen, a hitherto unidentified antigen specifically associated with the tip and kinocilial links of sensory hair bundles in the inner ear and the ciliary calyx of photoreceptors in the eye, as an avian ortholog of human protocadherin-15, a product of the gene for the deaf/blindness Usher syndrome type 1F/DFNB23 locus. Multiple protocadherin-15 transcripts are shown to be expressed in the mouse inner ear, and these define four major isoform classes, two with entirely novel, previously unidentified cytoplasmic domains. Antibodies to the three cytoplasmic domain-containing isoform classes reveal that each has a different spatiotemporal expression pattern in the developing and mature inner ear. Two isoforms are distributed in a manner compatible for association with the tip-link complex. An isoform located at the tips of stereocilia is sensitive to calcium chelation and proteolysis with subtilisin and reappears at the tips of stereocilia as transduction recovers after the removal of calcium chelators. Protocadherin-15 is therefore associated with the tip-link complex and may be an integral component of this structure and/or required for its formatio

Longitudinal decrease in blood oxygenation level dependent response in cerebral amyloid angiopathy

AbstractLower blood oxygenation level dependent (BOLD) signal changes in response to a visual stimulus in functional magnetic resonance imaging (fMRI) have been observed in cross-sectional studies of cerebral amyloid angiopathy (CAA), and are presumed to reflect impaired vascular reactivity. We used fMRI to detect a longitudinal change in BOLD responses to a visual stimulus in CAA, and to determine any correlations between these changes and other established biomarkers of CAA progression. Data were acquired from 22 patients diagnosed with probable CAA (using the Boston Criteria) and 16 healthy controls at baseline and one year. BOLD data were generated from the 200 most active voxels of the primary visual cortex during the fMRI visual stimulus (passively viewing an alternating checkerboard pattern). In general, BOLD amplitudes were lower at one year compared to baseline in patients with CAA (p=0.01) but were unchanged in controls (p=0.18). The longitudinal difference in BOLD amplitudes was significantly lower in CAA compared to controls (p<0.001). White matter hyperintensity (WMH) volumes and number of cerebral microbleeds, both presumed to reflect CAA-mediated vascular injury, increased over time in CAA (p=0.007 and p=0.001, respectively). Longitudinal increases in WMH (rs=0.04, p=0.86) or cerebral microbleeds (rs=−0.18, p=0.45) were not associated with the longitudinal decrease in BOLD amplitudes

Testing for haemoglobinopathies in Johannesburg, South Africa: A 30-year review

Background. Haemoglobinopathies are seen mostly in regions where malaria occurs or has occurred, but population migration has resulted in affected individuals being identified in many countries globally. The first molecular genetics services for diagnostic testing and prenatal diagnosis were established, both worldwide and in South Africa (SA), for haemoglobinopathies.Objective. To analyse the diagnostic service offered by the Division of Human Genetics, National Health Laboratory Service and University of the Witwatersrand, from 1983 to 2012. Methods. A retrospective file analysis (N=1 249) was performed for all individuals who had molecular genetic testing for α-thalassaemia, β-thalassaemia and sickle cell anaemia to examine indications for testing, population origins of patients and molecular genetics findings. Results. The α-thalassaemia testing was requested predominantly to explain microcytic hypochromic haematological indices. Five α-globin deletions were identified, the most common being the -α3.7, in individuals of different ethnicities. For β-thalassaemia and sickle cell anaemia, most testing was performed for prenatal diagnosis purposes. For sickle cell anaemia, most prenatal tests were requested by African families. The β-thalassaemia families were mostly of Indian or Mediterranean origin. The most common mutation identified in all Indian groups was IVS1 nt5 (G&gt;C) (c.92+5G&gt;C) and in individuals from the Mediterranean, IVS1 nt110 (G&gt;A) (c.93-21G&gt;A). Conclusion. The molecular genetics service for haemoglobinopathies in SA is comprehensive and specific to the needs of local ethnic groups. Clinically significant haemoglobinopathies occur at significant frequencies in specific high-risk ethnic groups. Appropriate screening programmes should be initiated so that genetic counselling and reproductive options can be offered.