Ability of γδ T cells to modulate the Foxp3 T cell response is dependent on adenosine.

Whether γδ T cells inhibit or enhance the Foxp3 T cell response depends upon their activation status. The critical enhancing effector in the supernatant is adenosine. Activated γδ T cells express adenosine receptors at high levels, which enables them to deprive Foxp3+ T cells of adenosine, and to inhibit their expansion. Meanwhile, cell-free supernatants of γδ T cell cultures enhance Foxp3 T cell expansion. Thus, inhibition and enhancement by γδ T cells of Foxp3 T cell response are a reflection of the balance between adenosine production and absorption by γδ T cells. Non-activated γδ T cells produce adenosine but bind little, and thus enhance the Foxp3 T cell response. Activated γδ T cells express high density of adenosine receptors and have a greatly increased ability to bind adenosine. Extracellular adenosine metabolism and expression of adenosine receptor A2ARs by γδ T cells played a major role in the outcome of γδ and Foxp3 T cell interactions. A better understanding of the functional conversion of γδ T cells could lead to γδ T cell-targeted immunotherapies for related diseases

Invariant Distribution of Promoter Activities in Escherichia coli

Cells need to allocate their limited resources to express a wide range of genes. To understand how Escherichia coli partitions its transcriptional resources between its different promoters, we employ a robotic assay using a comprehensive reporter strain library for E. coli to measure promoter activity on a genomic scale at high-temporal resolution and accuracy. This allows continuous tracking of promoter activity as cells change their growth rate from exponential to stationary phase in different media. We find a heavy-tailed distribution of promoter activities, with promoter activities spanning several orders of magnitude. While the shape of the distribution is almost completely independent of the growth conditions, the identity of the promoters expressed at different levels does depend on them. Translation machinery genes, however, keep the same relative expression levels in the distribution across conditions, and their fractional promoter activity tracks growth rate tightly. We present a simple optimization model for resource allocation which suggests that the observed invariant distributions might maximize growth rate. These invariant features of the distribution of promoter activities may suggest design constraints that shape the allocation of transcriptional resources

Asymmetric WIMP dark matter

In existing dark matter models with global symmetries the relic abundance of dark matter is either equal to that of anti-dark matter (thermal WIMP), or vastly larger, with essentially no remaining anti-dark matter (asymmetric dark matter). By exploring the consequences of a primordial asymmetry on the coupled dark matter and anti-dark matter Boltzmann equations we find large regions of parameter space that interpolate between these two extremes. Interestingly, this new asymmetric WIMP framework can accommodate a wide range of dark matter masses and annihilation cross sections. The present-day dark matter population is typically asymmetric, but only weakly so, such that indirect signals of dark matter annihilation are not completely suppressed. We apply our results to existing models, noting that upcoming direct detection experiments will constrain a large region of the relevant parameter space.Comment: 32 pages, 6 figures, updated references, updated XENON100 bounds, typo in figure caption correcte

Evaluation of a standard provision versus an autonomy promotive exercise referral programme: rationale and study design

Background The National Institute of Clinical Excellence in the UK has recommended that the effectiveness of ongoing exercise referral schemes to promote physical activity should be examined in research trials. Recent empirical evidence in health care and physical activity promotion contexts provides a foundation for testing the utility of a Self Determination Theory (SDT) -based exercise referral consultation. Methods/Design Design: An exploratory cluster randomised controlled trial comparing standard provision exercise on prescription with a Self Determination Theory-based (SDT) exercise on prescription intervention. Participants: 347 people referred to the Birmingham Exercise on Prescription scheme between November 2007 and July 2008. The 13 exercise on prescription sites in Birmingham were randomised to current practice (n=7) or to the SDT-based intervention (n=6). Outcomes measured at 3 and 6-months: Minutes of moderate or vigorous physical activity per week assessed using the 7-day Physical Activity Recall; physical health: blood pressure and weight; health status measured using the Dartmouth CO-OP charts; anxiety and depression measured by the Hospital Anxiety and Depression Scale and vitality measured by the subjective vitality score; motivation and processes of change: perceptions of autonomy support from the advisor, satisfaction of the needs for competence, autonomy, and relatedness via physical activity, and motivational regulations for exercise. Discussion This trial will determine whether an exercise referral programme based on Self Determination Theory increases physical activity and other health outcomes compared to a standard programme and will test the underlying SDT-based process model (perceived autonomy support, need satisfaction, motivation regulations, outcomes) via structural equation modelling. Trial registration The trial is registered as Current Controlled trials ISRCTN07682833

Using Management Objectives to Specify Management Information Systems - A Contribution to MIS Success

Data warehouse projects, today, are in an ambivalent situation. On the one hand, data warehouses are critical for a company’s success and various methodological and technological tools are sophisticatedly developed to implement them. On the other hand, a significant amount of data warehouse projects fails due to non-technical reasons such as insufficient management support or in-corporative employees. But management support and user participation can be increased dramatically with specification methods that are understandable to these user groups. This paper aims at overcoming possible non-technical failure reasons by introducing a user-adequate specification approach within the field of management information systems.\u

Epigenetic Regulation of Cytokine Gene Expression in T Lymphocytes

The developmental program of T helper and regulatory T cell lineage commitment is governed by both genetic and epigenetic mechanisms. The principal events, signaling pathways and the lineage determining factors involved have been extensively studied in the past ten years. Recent studies have elucidated the important role of chromatin remodeling and epigenetic changes for proper regulation of gene expression of lineage-specific cytokines. These include DNA methylation and histone modifications in epigenomic reprogramming during T helper cell development and effector T cell functions. This review discusses the basic epigenetic mechanisms and the role of transcription factors for the differential cytokine gene regulation in the T helper lymphocyte subsets

Clinical Features Reflect Exon Sites of EGFR Mutations in Patients with Resected Non-Small-Cell Lung Cancer

The aim of the current study was to determine the clinical significance according to the subtypes of epidermal growth factor receptor (EGFR) mutations and presence of KRAS mutations in operable non-small-cell lung cancer (NSCLC). We sequenced exons 18-21 of the EGFR tyrosine kinase domain and examined mutations in codons 12 and 13 of KRAS in tissues of patients with NSCLC who had undergone surgical resection. EGFR mutations were more frequent in never-smokers than smokers (33% vs. 14%, respectively; p=0.009) and in females than in males (31% vs. 16%, respectively; p=0.036). Mutations in exon 18-19 and 20-21 were found in 10 and 22 patients, respectively. Never-smokers and broncho-alveolar cell carcinoma features were positively associated with a mutation in exon 18-19 (p=0.027 and 0.016, respectively). The five-year survival rate in patients with a mutation in exons 18-19 (100%) was higher than that in patients without such mutation (47%; p=0.021). KRAS mutations were found in 16 patients (12%) and were not related to the overall survival (p=0.742). Patients with an EGFR mutation in exons 18-19 had better survival than patients without such mutation. Subtypes of EGFR mutations may be prognostic factors in patients undergoing curative resection