293 research outputs found

    A case study from the southern Cape linefishery 2: Considering one’s options when the fish leave

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    Fishers in the small-scale, commercial linefishery in the southern Cape, South Africa, are exposed to variability and change in the marine social-ecological system of which they are a part. Faced with multi-scalar changes within this complex system, fishers employ a wide range of strategies in reaction to change. As part of a broader study of stressors that bring about change in these systems, this contribution examines the fishers’ responses to these changes and is based on a participant-led, semi-structured interview process of skippers/boat owners, crew, processors and spouses/partners, in six communities in the southern Cape region, and has been supplemented with appropriate secondary data. The results are discussed using a resilience framework. The data were initially considered thematically by stressor, but results identified that a place-based analysis was equally important. Three major groupings were identified: (1) fishers who adapt and show clear business-orientation, (2) fishers who cope, and (3) fishers who react and are thus caught in a poverty trap. In addition to place-specific history, local feedback loops and indirect effects need to be better accounted for to understand these responses to change at various scales. The results of this study are expected to contribute to the basis of scenario planning in the region

    Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large‐scale deletions or point mutations

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    We designed and engineered mitochondrially targeted obligate heterodimeric zinc finger nucleases (mtZFNs) for site‐specific elimination of pathogenic human mitochondrial DNA (mtDNA). We used mtZFNs to target and cleave mtDNA harbouring the m.8993T>G point mutation associated with neuropathy, ataxia, retinitis pigmentosa (NARP) and the “common deletion” (CD), a 4977‐bp repeat‐flanked deletion associated with adult‐onset chronic progressive external ophthalmoplegia and, less frequently, Kearns‐Sayre and Pearson's marrow pancreas syndromes. Expression of mtZFNs led to a reduction in mutant mtDNA haplotype load, and subsequent repopulation of wild‐type mtDNA restored mitochondrial respiratory function in a CD cybrid cell model. This study constitutes proof‐of‐principle that, through heteroplasmy manipulation, delivery of site‐specific nuclease activity to mitochondria can alleviate a severe biochemical phenotype in primary mitochondrial disease arising from deleted mtDNA species

    Genome editing in mitochondria corrects a pathogenic mtDNA mutation in vivo.

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    Mutations of the mitochondrial genome (mtDNA) underlie a substantial portion of mitochondrial disease burden. These disorders are currently incurable and effectively untreatable, with heterogeneous penetrance, presentation and prognosis. To address the lack of effective treatment for these disorders, we exploited a recently developed mouse model that recapitulates common molecular features of heteroplasmic mtDNA disease in cardiac tissue: the m.5024C>T tRNAAla mouse. Through application of a programmable nuclease therapy approach, using systemically administered, mitochondrially targeted zinc-finger nucleases (mtZFN) delivered by adeno-associated virus, we induced specific elimination of mutant mtDNA across the heart, coupled to a reversion of molecular and biochemical phenotypes. These findings constitute proof of principle that mtDNA heteroplasmy correction using programmable nucleases could provide a therapeutic route for heteroplasmic mitochondrial diseases of diverse genetic origin

    ‘Stepping away from the computer and into the sweats': The construction and negotiation of exercise identities in a Norwegian public company

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    While research has found that a developed exercise identity enables individuals to view exercise participation as self- reinforcing, the social barriers to such exercise identity development and participation have not been fully addressed. The subsequent aim of this study was to explore some of the social complexities at play in terms of how company employees construct and manage their exercise identities within a work place setting. A case-study method was used to address the research issue over a nine-month period. The case to be studied included a sample of 72 employees from a Norwegian public company who participated in an on-going work-based exercise programme called ‘Exercise for all’. The principal means of data collection comprised participant observation, individual interviews and exercise logbooks. The data were subject to inductive analysis. The primary barriers to exercise participation included high levels of social comparison in a competitive working context, particularly in relation to ‘competent colleagues’, and feelings of guilt associated with partaking in ‘recreational’ activities during work hours. Strategies engaged with to overcome and negotiate such obstacles included justifying participation through a health-related discourse, and constructing a more distinct ‘worker-exerciser’ identity
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