944 research outputs found

    The neutral amino acid transporter SLC7A10 in adipose tissue, obesity and insulin resistance

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    Obesity, insulin resistance and type 2 diabetes represent major global health challenges, and a better mechanistic understanding of the altered metabolism in these conditions may give improved treatment strategies. SLC7A10, a member of the SLC7 subfamily of solute carriers, also named ASC-1 (alanine, serine, cysteine transporter-1), has recently been implicated as an important modulator of core processes in energy- and lipid metabolism, through its particularly high expression in adipocytes. In human cohorts, adipose SLC7A10 mRNA shows strong inverse correlations with insulin resistance, adipocyte size and components of the metabolic syndrome, strong heritability, and an association with type 2 diabetes risk alleles. SLC7A10 has been proposed as a marker of white as opposed to thermogenic beige and brown adipocytes, supported by increased formation of thermogenic beige adipocytes upon loss of Slc7a10 in mouse white preadipocytes. Overexpression of SLC7A10 in mature white adipocytes was found to lower the generation of reactive oxygen species (ROS) and stimulate mitochondrial respiratory capacity, while SLC7A10 inhibition had the opposite effect, indicating that SLC7A10 supports a beneficial increase in mitochondrial activity in white adipocytes. Consistent with these beneficial effects, inhibition of SLC7A10 was in mouse and human white adipocyte cultures found to increase lipid accumulation, likely explained by lowered serine uptake and glutathione production. Additionally, zebrafish with partial global Slc7a10b loss-of-function were found to have greater diet-induced body weight and larger visceral adipocytes compared to controls. However, challenging that SLC7A10 exerts metabolic benefits only in white adipocytes, suppression of SLC7A10 has been reported to decrease mitochondrial respiration and expression of thermogenic genes also in some beige and brown adipocyte cultures. Taken together, the data point to an important but complex role of SLC7A10 in metabolic regulation across different adipose tissue depots and adipocyte subtypes. Further research into SLC7A10 functions in specific adipocyte subtypes may lead to new precision therapeutics for mitigating the risk of insulin resistance and type 2 diabetes.publishedVersio

    But a walking shadow: designing, performing and learning on the virtual stage

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    Representing elements of reality within a medium, or taking aspects from one medium and placing them in another is an act of remediation. The process of this act, however, is largely taken for granted. Despite the fact that available information enables a qualitative assessment of the history of multimedia and their influences on different fields of knowledge, there are still some areas that require more focused research attention. For example, the relationship between media evolution and new developments in scenographic practice is currently under investigation. This article explores the issue of immediacy as a condition of modern theatre in the context of digital reality. It discusses the opportunities and challenges that recent technologies present to contemporary practitioners and theatre design educators, creating a lot of scope to break with conventions. Here, we present two case studies that look into technology-mediated learning about scenography through the employment of novel computer visualization techniques. The first case study is concerned with new ways of researching and learning about theatre through creative exploration of design artefacts. The second case study investigates the role of the Immersive Virtual World Second Life™ (SL) in effective teaching of scenography, and in creating and experiencing theatrical performances

    Structured evaluation of virtual environments for special-needs education

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    This paper describes the development of a structured approach to evaluate experiential and communication virtual learning environments (VLEs) designed specifically for use in the education of children with severe learning difficulties at the Shepherd special needs school in Nottingham, UK. Constructivist learning theory was used as a basis for the production of an evaluation framework, used to evaluate the design of three VLEs and how they were used by students with respect to this learning theory. From an observational field study of student-teacher pairs using the VLEs, 18 behaviour categories were identified as relevant to five of the seven constructivist principles defined by Jonassen (1994). Analysis of student-teacher behaviour was used to provide support for, or against, the constructivist principles. The results show that the three VLEs meet the constructivist principles in very different ways and recommendations for design modifications are put forward

    Gene expression profile of oral squamous cell carcinomas from Sri Lankan betel quid users

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    Oral squamous cell carcinoma (OSCC) is one of the major health problems in Sri Lanka and the disease is associated with the habit of Betel Quid (BQ) chewing. Using 35k oligo microarrays, we analyzed the gene expression profile of 15 Sri Lankan patients diagnosed with OSCCs and pair-wised normal controls and correlated the findings with the clinicopathological data. Following the recording of the scanned array images and data analysis, results for selected candidate genes were verified using QRT-PCR. Upon analysis, a total of 263 genes [71 (27%) of unknown functions previously not reported in OSCCs and 192 (73%) of known functions] were found as differentially expressed between tumors and controls. For the genes with known functions, 66 (34%; such as COL4A1, MMP1, MMP3, PLAU, SPARC and KRT19) were previously reported in OSCC and for the remaining 126 (66%; such as CD47, APOL3, RRAGC, BPIL1 and AZGP1) this is the first report in OSCCs. Hierarchical clustering of the differentially expressed 263 genes grouped the samples into several clusters with the larger one being dominated by tumors of stage 3 and 4. Two cases (a verrucous SCC and an advanced SCC), did not cluster with any of the other samples. We found two main biological pathways (cell communication and integrin-mediated cell adhesion) and 5 gene ontology categories (transcription regulator activity, structural molecule activity, intracellular signaling, cytoskeleton and signal transduction) of relevance to the OSCCs examined. Results from the QRT-PCR verified the results from the microarray experiment. This study provides valuable information on gene expression profile of OSCCs of habitual users of BQ from Sri Lanka. Of particular interest were the list of genes of known and unknown functions and the two biological pathways that we suggest as candidate genes in oral cancers associated with BQ chewing in Southeast Asia, in particular Sri Lanka. The suggested candidate genes might be used as molecular biomarkers in the early detection of the alarming problem of OSCCs in Southeast Asia in association with BQ use. These findings provide valuable information that might help in the selection of possible biomarkers that can be used in early detection of the alarming problem of oral cancer in Southeast Asia.publishedVersio

    Financial Time series: motif discovery and analysis using VALMOD

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    Motif discovery and analysis in time series data-sets have a wide-range of applications from genomics to finance. In consequence, development and critical evaluation of these algorithms is required with the focus not just detection but rather evaluation and interpretation of overall significance. Our focus here is the specific algorithm, VALMOD, but algorithms in wide use for motif discovery are summarised and briefly compared, as well as typical evaluation methods with strengths. Additionally, Taxonomy diagrams for motif discovery and evaluation techniques are constructed to illustrate the relationship between different approaches as well as inter-dependencies. Finally evaluation measures based upon results obtained from VALMOD analysis of a GBP-USD foreign exchange (F/X) rate data-set are presented, in illustration

    Submerged in the mainstream? A case study of an immigrant learner in a New Zealand primary classroom

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    Immigrant children from diverse language backgrounds face not only linguistic challenges when enrolled in mainstream English-medium classrooms, but also difficulties adjusting to an unfamiliar learning community. The culture of primary school classrooms in New Zealand typically reflects conventions across three dimensions: interactional, instructional task performance and cognitive-academic development. All three dimensions are underpinned by the culturally specific discourse conventions involved in language socialisation. New learners may be helped by classmates or their teacher to understand and successfully use these conventions, but left on their own they may sink rather than swim. This is a case study of one Taiwanese 11-year old boy, 'John', who entered a New Zealand primary classroom midway through the school year. John's basic conversational ability was sound, but he did not possess the interactive classroom skills needed to operate in the new culture of learning. Selected from a wider study of the classroom, transcript data from audio-recorded excerpts of John's interactions over several months with his teacher and classmates are interpreted from perspectives derived from sociocultural and language socialisation theories. The article concludes with a brief consideration of the extent to which John constructed, or was constrained from constructing meaningful learning experiences, and suggestions for further research and reflection

    Wikis, blogs and podcasts: a new generation of Web-based tools for virtual collaborative clinical practice and education

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    BACKGROUND: We have witnessed a rapid increase in the use of Web-based 'collaborationware' in recent years. These Web 2.0 applications, particularly wikis, blogs and podcasts, have been increasingly adopted by many online health-related professional and educational services. Because of their ease of use and rapidity of deployment, they offer the opportunity for powerful information sharing and ease of collaboration. Wikis are Web sites that can be edited by anyone who has access to them. The word 'blog' is a contraction of 'Web Log' – an online Web journal that can offer a resource rich multimedia environment. Podcasts are repositories of audio and video materials that can be "pushed" to subscribers, even without user intervention. These audio and video files can be downloaded to portable media players that can be taken anywhere, providing the potential for "anytime, anywhere" learning experiences (mobile learning). DISCUSSION: Wikis, blogs and podcasts are all relatively easy to use, which partly accounts for their proliferation. The fact that there are many free and Open Source versions of these tools may also be responsible for their explosive growth. Thus it would be relatively easy to implement any or all within a Health Professions' Educational Environment. Paradoxically, some of their disadvantages also relate to their openness and ease of use. With virtually anybody able to alter, edit or otherwise contribute to the collaborative Web pages, it can be problematic to gauge the reliability and accuracy of such resources. While arguably, the very process of collaboration leads to a Darwinian type 'survival of the fittest' content within a Web page, the veracity of these resources can be assured through careful monitoring, moderation, and operation of the collaborationware in a closed and secure digital environment. Empirical research is still needed to build our pedagogic evidence base about the different aspects of these tools in the context of medical/health education. SUMMARY AND CONCLUSION: If effectively deployed, wikis, blogs and podcasts could offer a way to enhance students', clinicians' and patients' learning experiences, and deepen levels of learners' engagement and collaboration within digital learning environments. Therefore, research should be conducted to determine the best ways to integrate these tools into existing e-Learning programmes for students, health professionals and patients, taking into account the different, but also overlapping, needs of these three audience classes and the opportunities of virtual collaboration between them. Of particular importance is research into novel integrative applications, to serve as the "glue" to bind the different forms of Web-based collaborationware synergistically in order to provide a coherent wholesome learning experience

    Designing electronic collaborative learning environments

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    Electronic collaborative learning environments for learning and working are in vogue. Designers design them according to their own constructivist interpretations of what collaborative learning is and what it should achieve. Educators employ them with different educational approaches and in diverse situations to achieve different ends. Students use them, sometimes very enthusiastically, but often in a perfunctory way. Finally, researchers study them and—as is usually the case when apples and oranges are compared—find no conclusive evidence as to whether or not they work, where they do or do not work, when they do or do not work and, most importantly, why, they do or do not work. This contribution presents an affordance framework for such collaborative learning environments; an interaction design procedure for designing, developing, and implementing them; and an educational affordance approach to the use of tasks in those environments. It also presents the results of three projects dealing with these three issues

    MetaMine – A tool to detect and analyse gene patterns in their environmental context

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    Background Modern sequencing technologies allow rapid sequencing and bioinformatic analysis of genomes and metagenomes. With every new sequencing project a vast number of new proteins become available with many genes remaining functionally unclassified based on evidences from sequence similarities alone. Extending similarity searches with gene pattern approaches, defined as genes sharing a distinct genomic neighbourhood, have shown to significantly improve the number of functional assignments. Further functional evidences can be gained by correlating these gene patterns with prevailing environmental parameters. MetaMine was developed to approach the large pool of unclassified proteins by searching for recurrent gene patterns across habitats based on key genes. Results MetaMine is an interactive data mining tool which enables the detection of gene patterns in an environmental context. The gene pattern search starts with a user defined environmentally interesting key gene. With this gene a BLAST search is carried out against the Microbial Ecological Genomics DataBase (MEGDB) containing marine genomic and metagenomic sequences. This is followed by the determination of all neighbouring genes within a given distance and a search for functionally equivalent genes. In the final step a set of common genes present in a defined number of distinct genomes is determined. The gene patterns found are associated with their individual pattern instances describing gene order and directions. They are presented together with information about the sample and the habitat. MetaMine is implemented in Java and provided as a client/server application with a user-friendly graphical user interface. The system was evaluated with environmentally relevant genes related to the methane-cycle and carbon monoxide oxidation. Conclusion MetaMine offers a targeted, semi-automatic search for gene patterns based on expert input. The graphical user interface of MetaMine provides a user-friendly overview of the computed gene patterns for further inspection in an ecological context. Prevailing biological processes associated with a key gene can be used to infer new annotations and shape hypotheses to guide further analyses. The use-cases demonstrate that meaningful gene patterns can be quickly detected using MetaMine
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