A whole system approach to increasing children's physical activity in a multi-ethnic UK city: a process evaluation protocol

Background Engaging in regular physical activity requires continued complex decision-making in varied and dynamic individual, social and structural contexts. Widespread shortfalls of physical activity interventions suggests the complex underlying mechanisms of change are not yet fully understood. More insightful process evaluations are needed to design and implement more effective approaches. This paper describes the protocol for a process evaluation of the JU:MP programme, a whole systems approach to increasing physical activity in children and young people aged 5–14 years in North Bradford, UK. Methods This process evaluation, underpinned by realist philosophy, aims to understand the development and implementation of the JU:MP programme and the mechanisms by which JU:MP influences physical activity in children and young people. It also aims to explore behaviour change across wider policy, strategy and neighbourhood systems. A mixed method data collection approach will include semi-structured interview, observation, documentary analysis, surveys, and participatory evaluation methods including reflections and ripple effect mapping. Discussion This protocol offers an innovative approach on the use of process evaluation feeding into an iterative programme intended to generate evidence-based practice and deliver practice-based evidence. This paper advances knowledge regarding the development of process evaluations for evaluating systems interventions, and emphasises the importance of process evaluation

Correction to: A whole system approach to increasing children's physical activity in a multi-ethnic UK city: a process evaluation protocol

Background Engaging in regular physical activity requires continued complex decision-making in varied and dynamic individual, social and structural contexts. Widespread shortfalls of physical activity interventions suggests the complex underlying mechanisms of change are not yet fully understood. More insightful process evaluations are needed to design and implement more effective approaches. This paper describes the protocol for a process evaluation of the JU:MP programme, a whole systems approach to increasing physical activity in children and young people aged 5–14 years in North Bradford, UK. Methods This process evaluation, underpinned by realist philosophy, aims to understand the development and implementation of the JU:MP programme and the mechanisms by which JU:MP influences physical activity in children and young people. It also aims to explore behaviour change across wider policy, strategy and neighbourhood systems. A mixed method data collection approach will include semi-structured interview, observation, documentary analysis, surveys, and participatory evaluation methods including reflections and ripple effect mapping. Discussion This protocol offers an innovative approach on the use of process evaluation feeding into an iterative programme intended to generate evidence-based practice and deliver practice-based evidence. This paper advances knowledge regarding the development of process evaluations for evaluating systems interventions, and emphasises the importance of process evaluation

Membrane Surface Nanostructures and Adhesion Property of T Lymphocytes Exploited by AFM

The activation of T lymphocytes plays a very important role in T-cell-mediated immune response. Though there are many related literatures, the changes of membrane surface nanostructures and adhesion property of T lymphocytes at different activation stages have not been reported yet. However, these investigations will help us further understand the biophysical and immunologic function of T lymphocytes in the context of activation. In the present study, the membrane architectures of peripheral blood T lymphocytes were obtained by AFM, and adhesion force of the cell membrane were measured by acquiring force–distance curves. The results indicated that the cell volume increased with the increases of activation time, whereas membrane surface adhesion force decreased, even though the local stiffness for resting and activated cells is similar. The results provided complementary and important data to further understand the variation of biophysical properties of T lymphocytes in the context of in vitro activation

Id4, a New Candidate Gene for Senile Osteoporosis, Acts as a Molecular Switch Promoting Osteoblast Differentiation

Excessive accumulation of bone marrow adipocytes observed in senile osteoporosis or age-related osteopenia is caused by the unbalanced differentiation of MSCs into bone marrow adipocytes or osteoblasts. Several transcription factors are known to regulate the balance between adipocyte and osteoblast differentiation. However, the molecular mechanisms that regulate the balance between adipocyte and osteoblast differentiation in the bone marrow have yet to be elucidated. To identify candidate genes associated with senile osteoporosis, we performed genome-wide expression analyses of differentiating osteoblasts and adipocytes. Among transcription factors that were enriched in the early phase of differentiation, Id4 was identified as a key molecule affecting the differentiation of both cell types. Experiments using bone marrow-derived stromal cell line ST2 and Id4-deficient mice showed that lack of Id4 drastically reduces osteoblast differentiation and drives differentiation toward adipocytes. On the other hand knockdown of Id4 in adipogenic-induced ST2 cells increased the expression of Pparγ2, a master regulator of adipocyte differentiation. Similar results were observed in bone marrow cells of femur and tibia of Id4-deficient mice. However the effect of Id4 on Pparγ2 and adipocyte differentiation is unlikely to be of direct nature. The mechanism of Id4 promoting osteoblast differentiation is associated with the Id4-mediated release of Hes1 from Hes1-Hey2 complexes. Hes1 increases the stability and transcriptional activity of Runx2, a key molecule of osteoblast differentiation, which results in an enhanced osteoblast-specific gene expression. The new role of Id4 in promoting osteoblast differentiation renders it a target for preventing the onset of senile osteoporosis

The binding of Varp to VAMP7 traps VAMP7 in a closed, fusogenically inactive conformation.

SNAREs provide energy and specificity to membrane fusion events. Fusogenic trans-SNARE complexes are assembled from glutamine-contributing SNAREs (Q-SNAREs) embedded in one membrane and an arginine-contributing SNARE (R-SNARE) embedded in the other. Regulation of membrane fusion events is crucial for intracellular trafficking. We identify the endosomal protein Varp as an R-SNARE-binding regulator of SNARE complex formation. Varp colocalizes with and binds to VAMP7, an R-SNARE that is involved in both endocytic and secretory pathways. We present the structure of the second ankyrin repeat domain of mammalian Varp in complex with the cytosolic portion of VAMP7. The VAMP7-SNARE motif is trapped between Varp and the VAMP7 longin domain, and hence Varp kinetically inhibits the ability of VAMP7 to form SNARE complexes. This inhibition will be increased when Varp can also bind to other proteins present on the same membrane as VAMP7, such as Rab32-GTP

An early history of T cell-mediated cytotoxicity.

After 60 years of intense fundamental research into T cell-mediated cytotoxicity, we have gained a detailed knowledge of the cells involved, specific recognition mechanisms and post-recognition perforin-granzyme-based and FAS-based molecular mechanisms. What could not be anticipated at the outset was how discovery of the mechanisms regulating the activation and function of cytotoxic T cells would lead to new developments in cancer immunotherapy. Given the profound recent interest in therapeutic manipulation of cytotoxic T cell responses, it is an opportune time to look back on the early history of the field. This Timeline describes how the early findings occurred and eventually led to current therapeutic applications