A Food Security Indicator Framework for British Columbia, Canada.

Food security is a determinant of health and increasingly recognized as a focus for health promotion. Led by the Population and Public Health Program, British Columbia Centre for Disease Control, this article outlines the process of development and the evidence-based conceptual framework that guides the systematic selection of food security indicators in the Province. A phased, iterative approach to develop the food security framework was adopted.

Examining school-level implementation of British Columbia, Canada's school food and beverage sales policy: a realist evaluation.

Objective: To identify key school-level contexts and mechanisms associated with implementing a provincial school food and beverage policy.

Design: Realist evaluation. Data collection included semi-structured interviews (n 23), structured questionnaires (n 62), participant observation at public events (n 3) and scans of school, school district and health authority websites (n 67).

District-level implementation of British Columbia's school food and beverage sales policy: a realist evaluation exploring intervention mechanisms in urban and rural contexts.

Intervention: British Columbia's (BC) provincial school food and beverage sales policy.

Research Question: What are the processes associated with district-level implementation of BC's school food and beverage sales policy?

Methods: We adopted a realist approach and a qualitative, multiple case study design that included three urban and two rural BC school districts. Data collection involved semi-structured interviews and questionnaires with health, education, and industry stakeholders, observations, document analysis and website scans.

GPR108, an NF-κB activator suppressed by TIRAP, negatively regulates TLR-triggered immune responses.

Higher vertebrates have evolved innate and adaptive immune systems to defend against foreign substances and pathogens. Sophisticated regulatory circuits are needed to avoid inappropriate immune responses and inflammation. GPR108 is a seven-transmembrane family protein that activates NF-κB strongly when overexpressed.

It's just the right thing to do: Conceptualizing a theory of change for a school food and beverage sales environment interv ention and implications for implementation evaluation.

School food environments are the target of nutrition interventions and evaluations across the globe. Yet little work to-date has articulated the importance of developing a theory of change upon which to base evaluation of both implementation and outcomes. This paper undertakes an interpretive approach to develop a retrospective theory of change for an implementation evaluation of British Columbia's school food and beverage sales Guidelines.

Influence of multiplicative stochastic variation on translational elongation rates.

Experimental data indicate that stochastic effects exerted at the level of translation contribute substantially to the variation in abundance of proteins expressed at moderate to high levels. This study analyzes the theoretical consequences of fluctuations in residue-specific elongation rates during translation. A simple analytical framework shows that rate variation during elongation gives rise to protein production rates that consist of sums of products of random variables.

The Csk-Associated Adaptor PAG Inhibits Effector T Cell Activation in Cooperation with Phosphatase PTPN22 and Dok Adaptors.

The transmembrane adaptor PAG (Cbp) has been proposed to mediate membrane recruitment of Csk, a cytoplasmic protein tyrosine kinase playing a critical inhibitory role during T cell activation, by inactivating membrane-associated Src kinases. However, this model has not been validated by genetic evidence. Here, we demonstrate that PAG-deficient mice display enhanced T cell activation responses in effector, but not in naive, T cells.

Mouse embryonic fibroblasts exhibit extensive developmental and phenotypic diversity.

Analysis of embryonic fibroblasts from GFP reporter mice indicates that the fibroblast cell type harbors a large collection of developmentally and phenotypically heterogeneous subtypes. Some of these cells exhibit multipotency, whereas others do not. Multiparameter flow cytometry analysis shows that a large number of distinct populations of fibroblast-like cells can be found in cultures initiated from different embryonic organs, and cells sorted according to their surface phenotype typically retain their characteristics on continued propagation in culture.

Exploring Public Health's roles and limitations in advancing food security in British Columbia.

Objectives: This research analyzes the roles and limitations of Public Health in British Columbia in advancing food security through the integration of food security initiatives into its policies and programs. It asks the question, can Public Health advance food security? If so, how, and what are its limitations?

Methods: This policy analysis merges findings from 38 key informant interviews conducted with government and civil society stakeholders involved in the development of food security initiatives, along with an examination of relevant documents. The Population Health Template is used to delineate and analyze Public Health roles in food security.

Sustainability in the Qatar national dietary guidelines, among the first to incorporate sustainability principles.

Objective: To present one of the first national dietary guidelines that incorporates food sustainability principles into its public health recommendations.

Design: The paper outlines recommendations and utilizes an ecological framework of policy analysis to examine context, drivers, consequences and future suggestions in establishing and maintaining sustainability principles within the Qatar Dietary Guidelines.

Setting: Qatar.

Transmembrane adaptor protein PAG/CBP is involved in both positive and negative regulation of mast cell signaling.

The transmembrane adaptor protein PAG/CBP (here, PAG) is expressed in multiple cell types. Tyrosine-phosphorylated PAG serves as an anchor for C-terminal SRC kinase, an inhibitor of SRC-family kinases. The role of PAG as a negative regulator of immunoreceptor signaling has been examined in several model systems, but no functions in vivo have been determined.

Application of Gaussia luciferase in bicistronic and non-conventional secretion reporter constructs.

Background: Secreted luciferases are highly useful bioluminescent reporters for cell-based assays and drug discovery. A variety of secreted luciferases from marine organisms have been described that harbor an N-terminal signal peptide for release along the classical secretory pathway. Here, we have characterized the secretion of Gaussia luciferase in more detail.

Deficits in receptor-mediated endocytosis and recycling in cells from mice with Gpr107 locus disruption.

GPR107 is a type III integral membrane protein that was initially predicted to be a member of the family of G-protein-coupled receptors. This report shows that deletion of Gpr107 leads to an embryonic lethal phenotype that is characterized by a reduction in cubilin transcript abundance and a decrease in the representation of multiple genes implicated in the cubilin-megalin endocytic receptor complex (megalin is also known as LRP2). Gpr107-null fibroblast cells exhibit reduced transferrin internalization, decreased uptake of low-density lipoprotein (LDL) receptor-related protein-1 (LRP1) cargo and resistance to toxins.

Deletion of the murine cytochrome P450 Cyp2j locus by fused BAC-mediated recombination identifies a role for Cyp2j in the pulmonary vascular response to hypoxia.

Epoxyeicosatrienoic acids (EETs) confer vasoactive and cardioprotective functions. Genetic analysis of the contributions of these short-lived mediators to pathophysiology has been confounded to date by the allelic expansion in rodents of the portion of the genome syntenic to human CYP2J2, a gene encoding one of the principle cytochrome P450 epoxygenases responsible for the formation of EETs in humans. Mice have eight potentially functional genes that could direct the synthesis of epoxygenases with properties similar to those of CYP2J2.

Integrating food security into public health and provincial government departments in British Columbia, Canada.

Food security policy, programs, and infrastructure have been incorporated into Public Health and other areas of the Provincial Government in British Columbia, including the adoption of food security as a Public Health Core Program. A policy analysis of the integration into Public Health is completed by merging findings from 48 key informant interviews conducted with government, civil society, and food supply chain representatives involved in the initiatives along with relevant documents and participant/direct observations. The paper then examines the results within the context of historic and international trends and theoretical models of food policy, community food security, and applied policy research.

A high-content imaging workflow to study Grb2 signaling complexes by expression cloning.

Signal transduction by growth factor receptors is essential for cells to maintain proliferation and differentiation and requires tight control. Signal transduction is initiated by binding of an external ligand to a transmembrane receptor and activation of downstream signaling cascades. A key regulator of mitogenic signaling is Grb2, a modular protein composed of an internal SH2 (Src Homology 2) domain flanked by two SH3 domains that lacks enzymatic activity.

Enhanced Tim3 activity improves survival after influenza infection.

Influenza is a major cause of morbidity and mortality in the United States. Studies have shown that excessive T cell activity can mediate pneumonitis in the setting of influenza infection, and data from the 2009 H1N1 pandemic indicate that critical illness and respiratory failure postinfection were associated with greater infiltration of the lungs with CD8+ T cells. T cell Ig and mucin domain 3 (Tim3) is a negative regulator of Th1/Tc1-type immune responses.

STAT6 phosphorylation inhibitors block eotaxin-3 secretion in bronchial epithelial cells.

The STAT6 (signal transducer and activator of transcription 6) protein facilitates T-helper cell 2 (Th2) mediated responses that control IgE-mediated atopic diseases such as asthma. We have identified compounds that bind to STAT6 and inhibit STAT6 tyrosine phosphorylation induced by IL-4. In the bronchial epithelial cell line BEAS-2B, compound (R)-84 inhibits the secretion of eotaxin-3, a chemokine eliciting eosinophil infiltration.

PrimerBank: a PCR primer database for quantitative gene expression analysis, 2012 update.

Optimization of primer sequences for polymerase chain reaction (PCR) and quantitative PCR (qPCR) and reaction conditions remains an experimental challenge. We have developed a resource, PrimerBank, which contains primers that can be used for PCR and qPCR under stringent and allele-invariant amplification conditions. A distinguishing feature of PrimerBank is the experimental validation of primer pairs covering most known mouse genes.

Phosphoprotein associated with glycosphingolipid-enriched microdomains differentially modulates SRC kinase activity in brain maturation.

Src family kinases (SFK) control multiple processes during brain development and function. We show here that the phosphoprotein associated with glycosphigolipid-enriched microdomains (PAG)/Csk binding protein (Cbp) modulates SFK activity in the brain. The timing and localization of PAG expression overlap with Fyn and Src, both of which we find associated to PAG.

C-aryl glucosides substituted at the 4'-position as potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors for the treatment of type 2 diabetes.

A series of C-aryl glucosides with various substituents at the 4'-position of the distal aryl ring have been synthesized and evaluated for inhibition of hSGLT1 and hSGLT2. Introduction of alkyl or alkoxy substituents at the 4'-position was found to improve SGLT2 potency, whereas introduction of a hydrophilic group at this position was deleterious. Compounds with alkoxy-, cycloalkoxy- or cycloalkenyloxy-ethoxy scaffolds exhibited good inhibitory activity and high selectivity toward SGLT2.

EGT1442, a potent and selective SGLT2 inhibitor, attenuates blood glucose and HbA(1c) levels in db/db mice and prolongs the survival of stroke-prone rats.

Sodium glucose co-transporter 2 (SGLT2) is a renal type III integral membrane protein that co-transports sodium and glucose from filtrate to epithelium in the proximal tubule. Human subjects with homozygous or compound heterozygous mutations in SLC5A2 exhibit glucosuria without hypoglycemia or other obvious morbidity, suggesting that blockade of SGLT2 has the potential to promote normalization of blood glucose without hypoglycemia in the setting of type 2 diabetes. This report presents the in vitro and in vivo pharmacological activities of EGT1442, a recently discovered SGLT2 inhibitor in the C-aryl glucoside class.

The transcription factor MafB antagonizes antiviral responses by blocking recruitment of coactivators to the transcription factor IRF3.

Viral infection induces type I interferons (IFN-alpha and IFN-beta) that recruit unexposed cells in a self-amplifying response. We report that the transcription factor MafB thwarts auto-amplification by a metastable switch activity. MafB acted as a weak positive basal regulator of transcription at the IFNB1 promoter through activity at transcription factor AP-1-like sites.

ortho-Substituted C-aryl glucosides as highly potent and selective renal sodium-dependent glucose co-transporter 2 (SGLT2) inhibitors.

A series of 2-substituted C-aryl glucosides have been synthesized and evaluated for inhibition of hSGLT1 and hSGLT2. Introduction of an appropriate ortho substituent at the proximal phenyl ring adjacent to the glycosidic bond was found to improve SGLT2 inhibitory activity and dramatically increase selectivity for hSGLT2 over hSGLT1. Selected compounds were investigated for in vivo efficacy.