192 research outputs found

    Disability's Encounter with Legislation and Governance: Long-Term Care Homes in Ontario

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    This dissertation is a comprehensive study of the new legal framework for the long-term care (LTC) sector (also known as nursing homes) in Ontario, Canada. The research sought to answer the following question: What are the potential implications for persons with disabilities of the changes made by the Government of Ontario between 2004 and 2018 to the legislation and governance of treatment, care and living circumstances within LTC homes? LTC is where many older women with disabilities and serious illnesses experience care. This study brings a gendered disability perspective to a public policy issue that is usually singularly associated with aging. To theorize the regulation and provision of care in LTC, the author situates LTC research within debates about care in disability scholarship. The concept of caring relationships is used to draw out tensions inherent in receiving and delivering care. Caring relationships are shaped by, among other political and market forces, the legal and administrative structure of a benefit scheme or a regulatory regime. The New Governance literature is employed to describe and examine new processes and procedures that shape caring relationships in LTC. To create a more comprehensive account of the changes, the research methods used were document review, legal analysis and key informant interviews. The feminist political economy literature was relied upon to draw out critical insights about the LTC sector. The majority of changes identified in the review were the creation of new or the strengthening of existing processes. The few substantive changes can be described as fragmented efforts to reduce risks to the safety, physical survival and security of individual residents. These changes if properly understood and implemented are significant in that they afford more procedural protections to residents in caring relationships and allow residents to make claims for inclusion and participation in making care decisions and in influencing conditions within the home. However, the mechanisms were designed without careful consideration of how the actual circumstances of residents, connected to the intermeshing of disability, gender and age, will impact their proper implementation. Consequently, some LTC applicants and residents cannot benefit from the protections offered by the law

    Disability\u27s Encounter with Legislation and Governance: Long-Term Care Homes in Ontario

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    This dissertation is a comprehensive study of the new legal framework for the long-term care (LTC) sector (also known as nursing homes) in Ontario, Canada. The research sought to answer the following question: What are the potential implications for persons with disabilities of the changes made by the Government of Ontario between 2004 and 2018 to the legislation and governance of treatment, care and living circumstances within LTC homes? LTC is where many older women with disabilities and serious illnesses experience care. This study brings a gendered disability perspective to a public policy issue that is usually singularly associated with aging. To theorize the regulation and provision of care in LTC, the author situates LTC research within debates about care in disability scholarship. The concept of caring relationships is used to draw out tensions inherent in receiving and delivering care. Caring relationships are shaped by, among other political and market forces, the legal and administrative structure of a benefit scheme or a regulatory regime. The New Governance literature is employed to describe and examine new processes and procedures that shape caring relationships in LTC. To create a more comprehensive account of the changes, the research methods used were document review, legal analysis and key informant interviews. The feminist political economy literature was relied upon to draw out critical insights about the LTC sector. The majority of changes identified in the review were the creation of new or the strengthening of existing processes. The few substantive changes can be described as fragmented efforts to reduce risks to the safety, physical survival and security of individual residents. These changes if properly understood and implemented are significant in that they afford more procedural protections to residents in caring relationships and allow residents to make claims for inclusion and participation in making care decisions and in influencing conditions within the home. However, the mechanisms were designed without careful consideration of how the actual circumstances of residents, connected to the intermeshing of disability, gender and age, will impact their proper implementation. Consequently, some LTC applicants and residents cannot benefit from the protections offered by the law

    MicroRNA-34a Modulates c-Myc Transcriptional Complexes to Suppress Malignancy in Human Prostate Cancer Cells

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    MicroRNA-34a (miR-34a), a potent mediator of tumor suppressor p53, has been reported to function as a tumor suppressor and miR-34a was found to be downregulated in prostate cancer tissues. We studied the functional effects of miR-34a on c-Myc transcriptional complexes in PC-3 prostate cancer cells. Transfection of miR-34a into PC-3 cells strongly inhibited in vitro cell proliferation, cell invasion and promoted apoptosis. Transfection of miR-34a into PC-3 cells also significantly inhibited in vivo xenograft tumor growth in nude mice. miR-34a downregulated expression of c-Myc oncogene by targeting its 3′ UTR as shown by luciferase reporter assays. miR-34a was found to repress RhoA, a regulator of cell migration and invasion, by suppressing c-Myc–Skp2–Miz1 transcriptional complex that activates RhoA. Overexpression of c-Myc reversed miR-34a suppression of RhoA expression, suggesting that miR-34a inhibits invasion by suppressing RhoA through c-Myc. miR-34a was also found to repress c-Myc-pTEFB transcription elongation complex, indicating one of the mechanisms by which miR-34a has profound effects on cellular function. This is the first report to document that miR-34a suppresses assembly and function of the c-Myc–Skp2–Miz1 complex that activates RhoA and the c-Myc-pTEFB complex that elongates transcription of various genes, suggesting a novel role of miR-34a in the regulation of transcription by c-Myc complex

    Using Evolutionary Conserved Modules in Gene Networks as a Strategy to Leverage High Throughput Gene Expression Queries

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    Background: Large-scale gene expression studies have not yielded the expected insight into genetic networks that control complex processes. These anticipated discoveries have been limited not by technology, but by a lack of effective strategies to investigate the data in a manageable and meaningful way. Previous work suggests that using a pre-determined seednetwork of gene relationships to query large-scale expression datasets is an effective way to generate candidate genes for further study and network expansion or enrichment. Based on the evolutionary conservation of gene relationships, we test the hypothesis that a seed network derived from studies of retinal cell determination in the fly, Drosophila melanogaster, will be an effective way to identify novel candidate genes for their role in mouse retinal development. Methodology/Principal Findings: Our results demonstrate that a number of gene relationships regulating retinal cell differentiation in the fly are identifiable as pairwise correlations between genes from developing mouse retina. In addition, we demonstrate that our extracted seed-network of correlated mouse genes is an effective tool for querying datasets and provides a context to generate hypotheses. Our query identified 46 genes correlated with our extracted seed-network members. Approximately 54% of these candidates had been previously linked to the developing brain and 33% had been previously linked to the developing retina. Five of six candidate genes investigated further were validated by experiments examining spatial and temporal protein expression in the developing retina. Conclusions/Significance: We present an effective strategy for pursuing a systems biology approach that utilizes an evolutionary comparative framework between two model organisms, fly and mouse. Future implementation of this strategy will be useful to determine the extent of network conservation, not just gene conservation, between species and will facilitate the use of prior biological knowledge to develop rational systems-based hypotheses

    Deinococcus geothermalis: The Pool of Extreme Radiation Resistance Genes Shrinks

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    Bacteria of the genus Deinococcus are extremely resistant to ionizing radiation (IR), ultraviolet light (UV) and desiccation. The mesophile Deinococcus radiodurans was the first member of this group whose genome was completely sequenced. Analysis of the genome sequence of D. radiodurans, however, failed to identify unique DNA repair systems. To further delineate the genes underlying the resistance phenotypes, we report the whole-genome sequence of a second Deinococcus species, the thermophile Deinococcus geothermalis, which at its optimal growth temperature is as resistant to IR, UV and desiccation as D. radiodurans, and a comparative analysis of the two Deinococcus genomes. Many D. radiodurans genes previously implicated in resistance, but for which no sensitive phenotype was observed upon disruption, are absent in D. geothermalis. In contrast, most D. radiodurans genes whose mutants displayed a radiation-sensitive phenotype in D. radiodurans are conserved in D. geothermalis. Supporting the existence of a Deinococcus radiation response regulon, a common palindromic DNA motif was identified in a conserved set of genes associated with resistance, and a dedicated transcriptional regulator was predicted. We present the case that these two species evolved essentially the same diverse set of gene families, and that the extreme stress-resistance phenotypes of the Deinococcus lineage emerged progressively by amassing cell-cleaning systems from different sources, but not by acquisition of novel DNA repair systems. Our reconstruction of the genomic evolution of the Deinococcus-Thermus phylum indicates that the corresponding set of enzymes proliferated mainly in the common ancestor of Deinococcus. Results of the comparative analysis weaken the arguments for a role of higher-order chromosome alignment structures in resistance; more clearly define and substantially revise downward the number of uncharacterized genes that might participate in DNA repair and contribute to resistance; and strengthen the case for a role in survival of systems involved in manganese and iron homeostasis

    Risk to human health related to the presence of perfluoroalkyl substances in food

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    Acknowledgements: The Panel wishes to thank the following for their support provided to this scientific output as Hearing experts: Klaus Abraham, Esben Budtz-Jørgensen, Tony Fletcher, Philippe Grandjean, Hans Mielke and Hans Rumke and EFSA staff members: Davide Arcella, Marco Binaglia, Petra Gergelova, Elena Rovesti and Marijke Schutte. The Panel wishes to acknowledge all European competent institutions, Member State bodies and other organisations that provided data for this scientific output. The Panel would also like to thank the following authors and co-authors for providing additional information in relation to their respective studies: Berit Granum, Margie M Peden-Adams, Thomas Webster.Peer reviewedPublisher PD

    Mitochondrial physiology

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    As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

    Mitochondrial physiology

    Get PDF
    As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery
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