1,991 research outputs found

    Do Women Need a National Government? Portents and Prospects for Social Policy in a Decentralized Federation

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    This article presents a critique of recent policy discussions about the decentralisation of social programs in Canada, arguing that such discussions neglect the impact of decentralisation on poor women and children in particular. The paper goes on to advocate a form of social corporatism or "social partners"--with women as a key constituency to set standards for federal and provincial programs.Cet article présente une critique des discussions sur les politiques récentes en faveur de la décentralisation des programmes sociaux au Canada, qui soutiennent que ce genre de discussions négligent l’impact que la décentralisation a sur les femmes et sur les enfants pauvres en particulier. Cet exposé se poursuit en recommandant une forme de corporatisme social ou "partenaires sociaux" — avec les femmes comme composantes importantes pour établir des normes des programmes fédéraux et provinciaux

    Uptake of synthetic low density lipoprotein by leukemic stem cells — a potential stem cell targeted drug delivery strategy

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    Chronic Myeloid Leukemia (CML) stem/progenitor cells, which over-express Bcr-Abl, respond to imatinib by a reversible block in proliferation without significant apoptosis. As a result, patients are unlikely to be cured owing to the persistence of leukemic quiescent stem cells (QSC) capable of initiating relapse. Previously, we have reported that intracellular levels of imatinib in primary primitive CML cells (CD34<sup>+</sup>38<sup>lo/−</sup>), are significantly lower than in CML progenitor cells (total CD34<sup>+</sup>) and leukemic cell lines. The aim of this study was to determine if potentially sub-therapeutic intracellular drug concentrations in persistent leukemic QSC may be overcome by targeted drug delivery using synthetic Low Density Lipoprotein (sLDL) particles. As a first step towards this goal, however, the extent of uptake of sLDL by leukemic cell lines and CML patient stem/progenitor cells was investigated. Results with non-drug loaded particles have shown an increased and preferential uptake of sLDL by Bcr-Abl positive cell lines in comparison to Bcr-Abl negative. Furthermore, CML CD34<sup>+</sup> and primitive CD34<sup>+</sup>38<sup>lo/−</sup> cells accumulated significantly higher levels of sLDL when compared with non-CML CD34<sup>+</sup> cells. Thus, drug-loading the sLDL nanoparticles could potentially enhance intracellular drug concentrations in primitive CML cells and thus aid their eradication

    Strategies to Reduce the Harmful Effects of Extreme Heat Events: A Four-City Study

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    Extreme heat events (EHEs) are becoming more intense, more frequent and longer lasting in the 21st century. These events can disproportionately impact the health of low-income, minority, and urban populations. To better understand heat-related intervention strategies used by four U.S. cities, we conducted 73 semi-structured interviews with government and non-governmental organization leaders representing public health, general social services, emergency management, meteorology, and the environmental planning sectors in Detroit, MI; New York City, NY; Philadelphia, PA and Phoenix, AZ—cities selected for their diverse demographics, climates, and climate adaptation strategies. We identified activities these leaders used to reduce the harmful effects of heat for residents in their city, as well as the obstacles they faced and the approaches they used to evaluate these efforts. Local leaders provided a description of how local context (e.g., climate, governance and city structure) impacted heat preparedness. Despite the differences among study cities, political will and resource access were critical to driving heat-health related programming. Upon completion of our interviews, we convened leaders in each city to discuss these findings and their ongoing efforts through day-long workshops. Our findings and the recommendations that emerged from these workshops could inform other local or national efforts towards preventing heat-related morbidity and mortality

    Exotic Corn Lines with Increased Resistant Starch and Impact on Starch Thermal Characteristics

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    Ten parent corn lines, including four mutants (dull sugary2, amyloseextender sugary2, amylose-extender dull, and an amylose-extender with introgressed Guatemalen germplasm [GUAT ae]) and six lines with introgressed exotic germplasm backgrounds, were crossed with each other to create 20 progeny crosses to increase resistant starch (RS) as a dietary fiber in corn starch and to provide materials for thermal evaluation. The resistant starch 2 (RS2) values from the 10 parent lines were 18.3–52.2% and the values from the 20 progeny crosses were 16.6–34.0%. The %RS2 of parents was not additive in the offspring but greater RS2 in parents was correlated to greater RS2 in the progeny crosses (r = 0.63). Differential scanning calorimetry (DSC) measured starch thermal characteristics, revealing positive correlations of peak gelatinization temperature and change in enthalpy with %RS2 (r = 0.65 and r = 0.67, P ≤ 0.05); however, % retrogradation (a measure of RS3) and retrogradation parameters did not correlate with %RS2. The %RS2 and onset temperature increased with the addition of the ae gene, likely because RS delays gelatinization

    A single codon insertion in PICALM is associated with development of familial subvalvular aortic stenosis in Newfoundland dogs

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    Familial subvalvular aortic stenosis (SAS) is one of the most common congenital heart defects in dogs and is an inherited defect of Newfoundlands, golden retrievers and human children. Although SAS is known to be inherited, specific genes involved in Newfoundlands with SAS have not been defined. We hypothesized that SAS in Newfoundlands is inherited in an autosomal dominant pattern and caused by a single genetic variant. We studied 93 prospectively recruited Newfoundland dogs, and 180 control dogs of 30 breeds. By providing cardiac screening evaluations for Newfoundlands we conducted a pedigree evaluation, genome-wide association study and RNA sequence analysis to identify a proposed pattern of inheritance and genetic loci associated with the development of SAS. We identified a three-nucleotide exonic insertion in phosphatidylinositol-binding clathrin assembly protein (PICALM) that is associated with the development of SAS in Newfoundlands. Pedigree evaluation best supported an autosomal dominant pattern of inheritance and provided evidence that equivocally affected individuals may pass on SAS in their progeny. Immunohistochemistry demonstrated the presence of PICALM in the canine myocardium and area of the subvalvular ridge. Additionally, small molecule inhibition of clathrin-mediated endocytosis resulted in developmental abnormalities within the outflow tract (OFT) of Xenopus laevis embryos. The ability to test for presence of this PICALM insertion may impact dog-breeding decisions and facilitate reduction of SAS disease prevalence in Newfoundland dogs. Understanding the role of PICALM in OFT development may aid in future molecular and genetic investigations into other congenital heart defects of various species

    Resistant Starch and Starch Thermal Characteristics in Exotic Corn Lines Grown in Temperate and Tropical Environments

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    Corn as a food that is heated and cooled to allow starch retrogradation has higher levels of resistant starch (RS). Increasing the amount of RS can make corn an even healthier food and may be accomplished by breeding and selection, especially by using exotic germplasm. Sixty breeding lines of introgressed exotic germplasm backgrounds, selected for high yield, were grown in three tropical and temperate locations and analyzed for starch thermal characteristics and RS levels. Although actual values for all starch characteristics were within normal levels, most characteristics had significant genotypic effects, and all had significant location effects. Thermal properties of retrograded starch were more influenced by the environment than the thermal properties of raw starch, making retrograded starch traits more heritable than raw starch traits. This suggests that a breeding strategy based on retrograded starch traits will have a better chance of success than a breeding strategy based on raw starch traits. A significant genotype effect for RS levels indicates that genotypic selection to raise the level of RS and increase the healthful aspects of corn food should be successful. Significant location effects indicate that breeders using winter nurseries to accelerate their breeding progress need to be careful when making selections using RS data collected on seed grown in the tropics. A small but highly significant correlation between RS and some thermal characteristics, especially percentage of retrogradation, indicates that we may be able to select promising genotypes for RS selection based on our extensive database of thermal characteristics collected on a wide number of diverse corn lines

    From Cosmetic to Metabolized Change: Promoting Paradigm Shifts in a Dominant Culture University

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    The authors provide three case examples modeling the implementation of the Diversity agenda in a school of education within a private Christian university. The second article in a series, the case studies demonstrate contextual application of confronting privilege as it manifests itself in a seemingly homogeneous environment. As the authors document programmatic, personal, and pedagogical methods informed by principles of social justice and equity, the intent is to move beyond cosmetic compliance with accreditation obligations towards a metabolized second order change within students and faculty

    Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration

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    Acknowledgements We are indebted to Jim Humphries, JennyCorrigan, LizDarley, Elizabeth Joynson, Natalie Walters, Sara Wells and the whole necropsy, histology, genotyping and MLC ward 6 teams at MRC Harwell for excellent technical assistance. We thank the staff of the WTSI Illumina Bespoke Team for the RNA-seq data, the Sanger Mouse Genetics Project for the initial mouse characterization and Dr David Adams for critical reading of the manuscript. We also thank KOMP for the mouse embryonic stem cells carrying the knockout first promoter-less allele (tm1a(KOMP)Wtsi) within Zfp016. Conflict of Interest statement. None declared. Funding This work was funded by the UK Medical Research Council (MRC) to A.A.-A. and a Motor Neurone Disease Association (MNDA) project grant to A.A.-A. and EMCF. D.L.H.B. is a Wellcome Trust Senior Clinical Scientist Fellow and P.F. is a MRC/MNDA Lady Edith Wolfson Clinician Scientist Fellow. Funding to pay the Open Access publication charges for this article was provided by the MRC grant number: MC_UP_A390_1106.Peer reviewedPublisher PD
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