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"Milsom, Anna"
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Picturing voices, writing thickness: a multimodal approach to translating the afro-cuban tales of lydia cabrera
Lydia Cabrera's career spans much of the twentieth century and her many books provide a unique insight into Afro-Cuban religions, customs, and folktales. Her work crosses the boundaries between ethnography, linguistics and fiction and her texts are inscribed with the dual strands of the African and Iberian cultures that fuse together to form the Cuban. Nonetheless, Cabrera's oeuvre remains relatively unknown outside Spanish-speaking academic circles and to date very little of it has been translated. This research project aims to address Cabrera's unwarranted obscurity by presenting English translations of twelve of her Afro-Cuban tales alongside hitherto unpublished archival material. Polyvocality is identified as a key feature of her work and ways in which 'voice' operates in her four collections of short stories are analysed. It is considered important that all the participants in the story-telling chain be 'heard' in any new presentation of Cabrera's work. This means paying attention to Cabrera as author of the published texts, but also to the informants who were her oral sources, to the translator, and to the reader of the new English versions. The fact that Cabrera's tales often encompass both the scientific (ethnographic) and the artistic (literary), makes the process of translating them a rich and complex endeavour. In formulating a creative response to this complexity, insights are drawn from visual art, concrete poetry, and ethnography. The notion of 'thick translation' (Appiah 1993/2000) provides the theoretical underpinning for the multimodal artefact which is developed. This PhD therefore also crosses disciplines - translation studies and interactive media - and comprises two parts; a written thesis and a DVD-Rom. Ultimately, it is suggested that one future direction for translation is to take a 'visual turn' towards a practice which does more than offer one written text in the place of another.
Dissertation
Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells
Here, DNA damage is shown to occur as a direct consequence of inducing haematopoietic stem cells to exit quiescence in response to conditions of stress; in mice with mutations modelling those seen in Fanconi anaemia, this leads to a complete collapse of the haematopoietic system.
Stress-linked HSC DNA damage
The accumulation of DNA damage as haematopoietic stem cells (HSCs) age is thought to contribute to age-related degeneration, an idea that is supported by the fact that accelerated ageing syndrome caused by defects in DNA repair, such as Fanconi anaemia syndrome, is associated with bone marrow failure. Michael Milsom and colleagues show here that DNA damage is a direct outcome of forcing HSCs to exit quiescence in response to a wide range of stimuli that mimic conditions of stress. In mice with mutations modelling those seen in Fanconi anaemia, this leads to a complete collapse of the haematopoietic system. These findings highlight the possible role of stress-induced HSC DNA damage in diseases that that have a pro-inflammatory component, as well as in normal ageing.
Haematopoietic stem cells (HSCs) are responsible for the lifelong production of blood cells. The accumulation of DNA damage in HSCs is a hallmark of ageing and is probably a major contributing factor in age-related tissue degeneration and malignant transformation
1
. A number of accelerated ageing syndromes are associated with defective DNA repair and genomic instability, including the most common inherited bone marrow failure syndrome, Fanconi anaemia
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,
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. However, the physiological source of DNA damage in HSCs from both normal and diseased individuals remains unclear. Here we show in mice that DNA damage is a direct consequence of inducing HSCs to exit their homeostatic quiescent state in response to conditions that model physiological stress, such as infection or chronic blood loss. Repeated activation of HSCs out of their dormant state provoked the attrition of normal HSCs and, in the case of mice with a non-functional Fanconi anaemia DNA repair pathway, led to a complete collapse of the haematopoietic system, which phenocopied the highly penetrant bone marrow failure seen in Fanconi anaemia patients. Our findings establish a novel link between physiological stress and DNA damage in normal HSCs and provide a mechanistic explanation for the universal accumulation of DNA damage in HSCs during ageing and the accelerated failure of the haematopoietic system in Fanconi anaemia patients.
Journal Article
Exit fromdormancy provokes DNA-damage-induced attrition in haematopoietic stem cells
Haematopoietic stem cells (HSCs) are responsible for the lifelong production of blood cells. The accumulation of DNA damage in HSCs is a hallmark of ageing and is probably a major contributing factor in age-related tissue degeneration and malignant transformation. A number of accelerated ageing syndromes are associated with defective DNA repair and genomic instability, including the most common inherited bone marrow failure syndrome, Fanconi anaemia. However, the physiological source of DNA damage in HSCs from both normal and diseased individuals remains unclear. Here we show in mice that DNA damage is a direct consequence of inducing HSCs to exit their homeostatic quiescent state in response to conditions that model physiological stress, such as infection or chronic blood loss. Repeated activation of HSCs out of their dormant state provoked the attrition of normal HSCs and, in the case of mice with a non-functional Fanconi anaemia DNA repair pathway, led to a complete collapse of the haematopoietic system,which phenocopied the highly penetrant bone marrow failure seen in Fanconi anaemia patients. Our findings establish a novel link between physiological stress and DNA damage in normal HSCs and provide a mechanistic explanation for the universal accumulation of DNA damage in HSCs during ageing and the accelerated failure of the haematopoietic system in Fanconi anaemia patients.
Journal Article
A kinetics-based model of hematopoiesis reveals extrinsic regulation of skewed lineage output from stem cells
Residing at the top of the hematopoietic hierarchy, long-term hematopoietic stem cells (HSCs) are capable of self-renewal and sustained blood cell regeneration. Over the past decades, single-cell and clonal analyses have revealed substantial functional and molecular heterogeneity within this compartment, challenging the notion that self-renewal is inherently tied to balanced, multi-lineage blood production. However, a cohesive model that explains the relationships among these diverse HSC states remains elusive. Here, we combined single-cell transplantations of over 1,000 highly purified murine long-term HSCs with in-depth phenotyping of their clonal progeny to achieve a detailed, time-resolved understanding of heterogeneous reconstitution outcomes. We identified reconstitution kinetics as an overall unifying metric of HSC functional potency, with the most potent HSCs displaying the greatest delay in hematopoietic reconstitution. Importantly, a progressive acceleration in reconstitution kinetics was also associated with a gradual shift in mature cell production from platelet and erythro-myeloid bias to balanced, and eventually lymphoid bias. Serial single-cell transplantations of HSCs revealed a unidirectional acceleration in reconstitution kinetics accompanied by a gradual decline in functional potency of daughter HSCs, aligning diverse phenotypes along a linear hierarchical trajectory. Mathematical modeling, together with experimental modulation of lineage-biased blood production, demonstrated that apparent lineage biases actually arise from cell-extrinsic feedback regulation and clonal competition between slow- and fast-engrafting clones to occupy the limited compartment sizes of mature lineages. Our study reconciles multiple layers of HSC heterogeneity into a unifying framework, prompting a reevaluation of the meaning of lineage biases in both normal and diseased hematopoiesis, with broad implications for other regenerating tissues during development, homeostasis, and repair.Competing Interest StatementThe authors have declared no competing interest.
Paper