1,720,965 research outputs found

    British Society for Matrix Biology Autumn Meeting 2022: "Matrix in Development"

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    Introduction: In postnatal development, chondro-osseous transitions such as endochondral ossification (EO) are regulated by rapid matrix turnover, mineralisation and chondro-osseous transdifferentiation, all disrupted in osteoarthritis (OA). We are exploring how force governs these transitions of cartilage to bone; previous studies from our group indicate cartilage matrix and chondrocyte phenotypic plasticity in the growth plate, and stability in articular cartilage, is mechanoregulated. Here, we describe exploitation of a human ‘developmental biology-inspired platform’ alongside in vivo studies, to study cartilage mineralisation.Materials and Methods: In vivo studies reveal chondro-osseous transitions are inhibited by forces. We synthesise GelMA using click chemistry to generate hydrogels with compressive moduli of 3–5 kPa. Buoyancy-driven gradients of BMP-2 within hydrogels seeded with hMSCs were cultured for 28 days. qPCR, histology and immunohistochemistry assessed, cartilage, hypertrophic and bone markers. Uniaxial cyclic compression (0.5 Hz, 10% strain) was applied using Electroforce5500. Cells from Confetti-UBCre mice are being used for lineage tracing studies.Results: MSC-laden GelMA constructs showed differential gene expression across the gradient, indicating tri-phasic osteochondral tissue formation within 28 days. Runx2/Sox9 immunostaining confirmed osteochondral differentiation, increased expression of SPP1, SP7, Runx2, Col1 indicated osteogenesis at one end, while distinct expression of Col10 and Runx2 in the central region marked cellular hypertrophy. The effects of cyclic loading on cell signalling, hyaline cartilage formation and thickness, calcification and phenotypic plasticity/stability are being assessed and compared with in vivo findings.Discussion: These data validate the formation of a humanised osteochondral gradient recapitulating developmental processes, in vitro. It is hypothesised that the generated osteochondral tissues will reflect the results of phenotypic changes in cells and ECM regulation, under physiological and pathological loads. The model will be integrated with snRNA sequencing and lineage tracing, to study trans-differentiation. This approach provides an experimentally tractable mechanobiology model and clinically conformant osteochondral tissue development model enabling fundamental biology and disease modelling across scales

    Engineering growth factor gradients to drive spatiotemporal tissue patterning in organ-on-a-chip systems

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    Spatial heterogeneity plays a key role in the development and function of human tissues and therefore needs to be incorporated within in vitro models to maximise physiological relevance and predictive power. Here, we developed and optimised methods to generate spatial heterogeneity of hydrogel-embedded bioactive signalling molecules within organ-on-a-chip (OOAC) systems, to drive spatiotemporal tissue patterning through controlled stem cell differentiation. As an exemplar application, we spatially patterned bone morphogenetic protein-2 (BMP-2) in both closed-channel and open-chamber OOAC formats. The resulting BMP-2 gradient in 3D heparin methacryloyl/gelatin methacryloyl, successfully drove spatially divergent differentiation of human bone marrow-derived stem cells into bone-like and cartilage-like regions, mimicking the process of endochondral ossification in the growth plate. The application of hydrogel-embedded morphogens to drive spatial tissue patterning within OOAC systems represents a significant technological advancement and has broad-ranging applicability for a diverse range of tissues and organs, and a wide variety of OOAC platforms

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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