Room to Flourish: Lessons for Canadian Grantmaking Foundations from Sweden, Germany and the Netherlands

While Canada has experienced a long and successful history of encouraging social participation and community activity through its grantmaking foundation sector, this article argues that Canada’s historic and present-day regulatory restrictions have limited the extent to which its foundation sector has been allowed to innovate and flourish. To exemplify the types of tractable regulatory schemes that have allowed grantmaking foundation sectors in comparative contexts to prosper, the evolution of the grantmaking foundation sectors in Sweden, Germany, and the Netherlands is examined within the context of social origins theory. One important contribution of this article is to compare their regulatory frameworks to the Canadian context. It concludes with lessons learned for the Canadian grantmaking foundation sector and for public officials to consider.Bien que le secteur des fondations subventionnaires au Canada ait connu une longue histoire de réussites dans l’encouragement de la participation sociale et de l’activité communautaire, cet article soutient qu’une réglementation restrictive autant dans le passé qu’au présent a limité l’innovation et l’épanouissement dans le secteur. Afin de montrer comment une réglementation plus souple pourrait permettre aux fondations canadiennes de prospérer davantage, cet article recourt à la théorie des origines sociales pour examiner le secteur en Suède, en Allemagne et aux Pays-Bas. Une contribution importante de cet article consiste ainsi à comparer les contextes réglementaires dans ces pays à celui du Canada. En conclusion, il fait des recommandations pour les fondations subventionnaires et le secteur public canadiens

Evaluating and Optimizing Fish Health and Welfare During Experimental Procedures.

This is the final version of the article. It first appeared from Mary Ann Liebert, Inc. via http://dx.doi.org/10.1089/zeb.2015.1165Many facilities house fish in separate static containers post-procedure, for example, while awaiting genotyping results. This ensures fish can be easily identified, but it does not allow for provision of continuous filtered water or diet. At the Wellcome Trust Sanger Institute, concern over the housing conditions led to the development of an individual housing system (GeneS) enabling feeding and water filtration. Trials to compare the water quality measures between the various systems found that fish housed in static containers experienced rapid deterioration in water quality. By day 1, measures of ammonia were outside the Institute's prescribed values and continued to rise until it was 25-fold higher than recommended levels. Nitrite levels were also outside recommended levels for all fish by day 9 and were twofold higher by the end of the trial. The water quality measures for tanks held on the recirculating system were stable even though food was provided. These results indicate that for housing zebrafish, running water or appropriately timed water changes are a critical component to ensure that the ethical obligations are met.We thank the staff from the Sanger Institute's Research Support Facility, Zebrafish Mutation Project, and Jacqui White for their support. This work was supported by the Wellcome Trust grant number 098051

Standardized Welfare Terms for the Zebrafish Community.

This is the final version of the article. It first appeared from Mary Ann Liebert via https://doi.org/10.1089/zeb.2016.1248Managing the welfare of laboratory animals is critical to animal health, vital in the understanding of phenotypes created by treatment or genetic alteration and ensures compliance of regulations. Part of an animal welfare assessment is the requirement to record observations, ensuring all those responsible for the animals are aware of their health status and can act accordingly. Although the use of zebrafish in research continues to increase, guidelines for conducting welfare assessments and the reporting of observations are considered unclear compared to mammalian species. To support the movement of zebrafish between facilities, significant improvement would be achieved through the use of standardized terms to ensure clarity and consistency between facilities. Improving the clarity of terminology around welfare not only addresses our ethical obligation but also supports the research goals and provides a searchable description of the phenotypes. A Collaboration between the Wellcome Trust Sanger Institute and Cambridge University (Department of Medicine-Laboratory of Molecular Biology) has led to the creation of the zebrafish welfare terms from which standardization of terminology can be achieved.This work was supported by the Wellcome Trust (grant no. 098051), the National Institutes of Health Office of Research Infrastructure Programs award (P40OD011021), the National Institutes of Health (grant no. A154503), National Institutes for Health Research to the Biomedical Research Centre (grant no. RG64229), and a Wellcome Trust Personal Research Fellowship (103950/Z/14/Z)

Targeting of Slc25a21 is associated with orofacial defects and otitis media due to disrupted expression of a neighbouring gene.

Homozygosity for Slc25a21(tm1a(KOMP)Wtsi) results in mice exhibiting orofacial abnormalities, alterations in carpal and rugae structures, hearing impairment and inflammation in the middle ear. In humans it has been hypothesised that the 2-oxoadipate mitochondrial carrier coded by SLC25A21 may be involved in the disease 2-oxoadipate acidaemia. Unexpectedly, no 2-oxoadipate acidaemia-like symptoms were observed in animals homozygous for Slc25a21(tm1a(KOMP)Wtsi) despite confirmation that this allele reduces Slc25a21 expression by 71.3%. To study the complete knockout, an allelic series was generated using the loxP and FRT sites typical of a Knockout Mouse Project allele. After removal of the critical exon and neomycin selection cassette, Slc25a21 knockout mice homozygous for the Slc25a21(tm1b(KOMP)Wtsi) and Slc25a21(tm1d(KOMP)Wtsi) alleles were phenotypically indistinguishable from wild-type. This led us to explore the genomic environment of Slc25a21 and to discover that expression of Pax9, located 3' of the target gene, was reduced in homozygous Slc25a21(tm1a(KOMP)Wtsi) mice. We hypothesize that the presence of the selection cassette is the cause of the down regulation of Pax9 observed. The phenotypes we observed in homozygous Slc25a21(tm1a(KOMP)Wtsi) mice were broadly consistent with a hypomorphic Pax9 allele with the exception of otitis media and hearing impairment which may be a novel consequence of Pax9 down regulation. We explore the ramifications associated with this particular targeted mutation and emphasise the need to interpret phenotypes taking into consideration all potential underlying genetic mechanisms

UC pursues rooted research with a nonprofit, links the many benefits of community gardens

The informal economy, healthy food options and alternative urban food systems are interconnected in important ways. To better understand these connections, and explore a rooted university approach to working with communities, we collaborated with the San Diego Community Garden Network to analyze the production, distribution and consumption of produce from eight community gardens in San Diego County. The project engaged UC San Diego researchers and students with county residents and community-based organizations to develop a survey together. Interviews with the gardeners and data from the completed survey document the ways in which community gardens contribute to individual and household health, well-being and community development. They suggest that despite perceptions that community gardens have marginal commercial capacity, they have the potential to contribute in meaningful ways to community development, particularly in low-income neighborhoods

Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes.

Mutations in whole organisms are powerful ways of interrogating gene function in a realistic context. We describe a program, the Sanger Institute Mouse Genetics Project, that provides a step toward the aim of knocking out all genes and screening each line for a broad range of traits. We found that hitherto unpublished genes were as likely to reveal phenotypes as known genes, suggesting that novel genes represent a rich resource for investigating the molecular basis of disease. We found many unexpected phenotypes detected only because we screened for them, emphasizing the value of screening all mutants for a wide range of traits. Haploinsufficiency and pleiotropy were both surprisingly common. Forty-two percent of genes were essential for viability, and these were less likely to have a paralog and more likely to contribute to a protein complex than other genes. Phenotypic data and more than 900 mutants are openly available for further analysis. PAPERCLIP

Mouse large-scale phenotyping initiatives: overview of the European Mouse Disease Clinic (EUMODIC) and of the Wellcome Trust Sanger Institute Mouse Genetics Project.

Two large-scale phenotyping efforts, the European Mouse Disease Clinic (EUMODIC) and the Wellcome Trust Sanger Institute Mouse Genetics Project (SANGER-MGP), started during the late 2000s with the aim to deliver a comprehensive assessment of phenotypes or to screen for robust indicators of diseases in mouse mutants. They both took advantage of available mouse mutant lines but predominantly of the embryonic stem (ES) cells resources derived from the European Conditional Mouse Mutagenesis programme (EUCOMM) and the Knockout Mouse Project (KOMP) to produce and study 799 mouse models that were systematically analysed with a comprehensive set of physiological and behavioural paradigms. They captured more than 400 variables and an additional panel of metadata describing the conditions of the tests. All the data are now available through EuroPhenome database (www.europhenome.org) and the WTSI mouse portal (http://www.sanger.ac.uk/mouseportal/), and the corresponding mouse lines are available through the European Mouse Mutant Archive (EMMA), the International Knockout Mouse Consortium (IKMC), or the Knockout Mouse Project (KOMP) Repository. Overall conclusions from both studies converged, with at least one phenotype scored in at least 80% of the mutant lines. In addition, 57% of the lines were viable, 13% subviable, 30% embryonic lethal, and 7% displayed fertility impairments. These efforts provide an important underpinning for a future global programme that will undertake the complete functional annotation of the mammalian genome in the mouse model

Diversity Arrays Technology (DArT) for Pan-Genomic Evolutionary Studies of Non-Model Organisms

Background: High-throughput tools for pan-genomic study, especially the DNA microarray platform, have sparked a remarkable increase in data production and enabled a shift in the scale at which biological investigation is possible. The use of microarrays to examine evolutionary relationships and processes, however, is predominantly restricted to model or near-model organisms. Methodology/Principal Findings: This study explores the utility of Diversity Arrays Technology (DArT) in evolutionary studies of non-model organisms. DArT is a hybridization-based genotyping method that uses microarray technology to identify and type DNA polymorphism. Theoretically applicable to any organism (even one for which no prior genetic data are available), DArT has not yet been explored in exclusively wild sample sets, nor extensively examined in a phylogenetic framework. DArT recovered 1349 markers of largely low copy-number loci in two lineages of seed-free land plants: the diploid fern Asplenium viride and the haploid moss Garovaglia elegans. Direct sequencing of 148 of these DArT markers identified 30 putative loci including four routinely sequenced for evolutionary studies in plants. Phylogenetic analyses of DArT genotypes reveal phylogeographic and substrate specificity patterns in A. viride, a lack of phylogeographic pattern in Australian G. elegans, and additive variation in hybrid or mixed samples. Conclusions/Significance: These results enable methodological recommendations including procedures for detecting and analysing DArT markers tailored specifically to evolutionary investigations and practical factors informing the decision to use DArT, and raise evolutionary hypotheses concerning substrate specificity and biogeographic patterns. Thus DArT is a demonstrably valuable addition to the set of existing molecular approaches used to infer biological phenomena such as adaptive radiations, population dynamics, hybridization, introgression, ecological differentiation and phylogeography

Mouse models of rhinovirus-induced disease and exacerbation of allergic airway inflammation

Rhinoviruses cause serious morbidity and mortality as the major etiological agents of asthma exacerbations and the common cold. A major obstacle to understanding disease pathogenesis and to the development of effective therapies has been the lack of a small-animal model for rhinovirus infection. Of the 100 known rhinovirus serotypes, 90% (the major group) use human intercellular adhesion molecule-1 (ICAM-1) as their cellular receptor and do not bind mouse ICAM-1; the remaining 10% (the minor group) use a member of the low-density lipoprotein receptor family and can bind the mouse counterpart. Here we describe three novel mouse models of rhinovirus infection: minor-group rhinovirus infection of BALB/c mice, major-group rhinovirus infection of transgenic BALB/c mice expressing a mouse-human ICAM-1 chimera and rhinovirus-induced exacerbation of allergic airway inflammation. These models have features similar to those observed in rhinovirus infection in humans, including augmentation of allergic airway inflammation, and will be useful in the development of future therapies for colds and asthma exacerbations