7,594 research outputs found

    Self-help/mutual aid groups in mental health : ideology, helping mechanisms and empowerment

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    In the last quarter of the twentieth century, self-help/mutual aid groups for mental health issues started to emerge in growing numbers, mainly in Western societies, offering and/or advocating for alternative non-traditional forms of support, and attracted the attention of many researchers and clinicians for their unique characteristics. Among the subjects of interest are typologies of groups, helping mechanisms and benefits from participation. However, there is lack of systematic research in the area and existing studies have been largely confined to the therapeutic value of these groups instead of acknowledging their socio-political meaning and subsequent psychosocial benefits for their members like personal empowerment. The present study was conducted during the transitional years from a Conservative to a newly elected Labour Government (1996 -1998), with subsequent policy shifts taking place in the welfare sector. The purpose of the study was to explore the potential of self-help groups as part of a broader new social movement, the service user movement, focussing on the English scene. It addressed this issue examining the relevance of a group typology based on political ideology and focus of change. To test the validity of this classification for members, a set of individual characteristics and group mechanisms as well as their change through time were examined. The sample consisted of fourteen mental health selfhelp/mutual aid groups from London and South East England, with a variety of structural and organisational features. The methodology used was a combination of both quantitative (self-completion questionnaires) and qualitative techniques (analysis of written material, participant observation and interviews). Measurements were repeated after a one-year interval (Time 1N=67, Time 2 N=56). Findings showed that, indeed, political ideology of self-help/mutual aid groups provided the basis of a meaningful typology and constitutes a comprehensive way of categorising them. Group ideology was related to specific helping mechanisms and aspects of personal empowerment. Specifically, conservative and combined group members reported more expressive group processes like sharing of feelings and self-disclosure, while radical group members were more empowered and optimistic. Group identification was also associated with specific helping activities and aspects of empowerment in the three group categories. The psychosocial character of group types and the beneficial outcomes for members remained stable through time. In general, prolonged participation was reflected in greater member identification with the group and resulted in improved mental wellbeing, increased social support, companionship and optimism for the future

    A Cornish palimpsest : Peter Lanyon and the construction of a new landscape, 1938-1964

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    The thesis examines the emergence of Peter Lanyon as one of the few truly innovative British landscape painters this century. In the Introduction I discuss the problematic nature of landscape art and consider the significance of Lanyon's discovery that direct description and linear perspective can be replaced with allusive representational elements by fusing the emotional and imaginative life of the artist with the physical activity of painting. Chapter One concentrates on the period 1936-8 when Lanyon was taught by Borlase Smart, a key figure in the St Ives art colony between the wars. Chapter Two examines the influence of Adrian Stokes and the links between Lanyon's painting and the theories developed in books such as Colour and Form and The Quattro Cento. Chapter Three analyses the period 1940-45 when Lanyon was directly influenced by the constructivism of Nicholson, Hepworth and Gabo. I look closely at their approaches to abstraction and assess Lanyon's relative position to them. The importance of Neo-Romanticism and the status of St Ives as a perceived avant-garde community is also addressed. In Chapter Four I discuss how Lanyon resolved to achieve a new orientation in his art on his return from wartime service with the RAF by synthesising constructivism, and traditional landscape. The Generation and Surfacing Series demonstrate his preoccupation with a sense of place, a fascination with the relationships between the human body and landscape and his struggle to find a technique and style that was entirely his own. His sense of existential insideness is discussed in Chapter Five through an examination of the work derived from Portreath, St. Just and Porthleven - key places in Lanyon's psychological attachment to the landscape of West Penwith. In Chapter Six I examine Lanyon's attachment to myths and archetypal forms, tracing the influence of Bergson's vitalist philosophy as well as his use of Celtic and classical motifs. Chapter Seven is a discussion of the malaise evident in Lanyon's work by 1955 and the impact of American Abstract Expressionism at the Tate Gallery a year later. In the summer of 1959 Lanyon joined the Cornish Gliding Club and Chapter Eight looks at how this necessitated a dynamic, expanded conception of the landscape and a re-thinking of relations within the picture field. The ability to dissolve boundaries encouraged him to break down distinctions between painting and construction so that abstract sculptural elements were now assembled into independent works of art. Finally, Chapter Nine assesses Lanyon's overall position in relation to his early influences and to St Ives art as a whole, his response to new directions in art coming out of London and NewYork in the early 1960s and the importance of travel as a stimulus for further realignment in his artistic and topographical horizons. His pictorial inventiveness and vitality remained unabated at the time of his death and would undoubtedly have continued to be enriched by travel abroad and contact with new movements in modem art on both sides of the Atlanti

    Patterns of subspecies diversity in the giraffe, Giraffa camelopardalis (L. 1758): comparison of systematic methods and their implications for conservation policy

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    This thesis examines the subspecific taxonomic status of the giraffe and considers the role of formal taxonomy in the formulation of conservation policy. Where species show consistent. geographically structured phenotypic variation such geographic patterns may indicate selective forces (or other population-level effects) acting. upon local populations. These consistent geographic patterns may be recognised formally as subspecies and may be of interest in single or multi-species biodiversity or biogeography studies for delimiting areas of conservation priority. Subspecies may also be used in the formulation of management policies and legislation. Subspecies are, by definition, allopatric. This thesis explicitly uses methodology of systematic biology and phylogenetic reconstruction to investigate patterns of variation between geographic groups. The taxonomic status of the giraffe is apposite for review. The species provides three independent data sets that may be analysed quantitatively for geographic structure; pelage patterns, morphology and genetics. Museum specimens. grouped according to geographic origin, were favoured for study as more than one type of data was often available for an individual. Population aggregation analysis of forty pelage pattern characters maintained six separate subspecies, while agglomerating some neighbouring populations into a subspecies. A 'traditional' morphometric approach, using multivariate statistical analysis of adult skull measurements, was complemented by a geometric morphometric approach; landmarkrestricted eigenshape analysis. Four morphologically distinct groups were recognised by both morphological analyses. Phylogenetic analysis of mitochondrial DNA control region sequences indicates five major cIades. Nested cIade analysis identifies population fragmentation, range expansion and genetic isolation by distance as contributing to the genetic structure of the giraffe. The results of the analyses show remarkable congruence. These results are discussed in terms of the formulation of conservation policy and the differing requirements of'blological and legal classification systems. The value of a formal taxonomic framework to the recognition, and subsequent conservation, of biodiversity is emphasised

    Investigating interactions between influenza A virus and respiratory syncytial virus during coinfection

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    Respiratory viruses are the cause of significant disease burden and coinfections with more than one virus constitute between 10-30% of viral respiratory infections. Interactions among respiratory viruses are recognised for their importance in influencing viral dynamics, however direct virus-virus interactions are poorly understood. Influenza A virus (IAV) and respiratory syncytial virus (RSV) are important respiratory pathogens that share epidemiological characteristics, including timing of seasonal peaks of infections, and biological characteristics, including cellular tropism within the respiratory tract. To characterise interactions between IAV and RSV during coinfection, we developed an in vitro model in A549 cells, a cell line derived from the human lung. Analysis of viral growth kinetics and viral dynamics by live cell imaging showed that, while IAV replication appears unaffected by coinfection with RSV, RSV replication is significantly decreased in coinfection. Imaging of coinfected cells stained for IAV and RSV nucleoproteins and glycoproteins show that they localise to the same regions of the plasma membrane, suggesting there may be opportunity for viral interactions during viral assembly. To further explore this hypothesis, virus particles budding from coinfected cells were examined using super-resolution confocal microscopy. Filamentous structures extended from coinfected cells, that incorporated glycoproteins from both viruses in distinct patches along the filament. The ultra-structure of these filaments, determined by cryo-electron tomography, revealed the formation of chimeric viral particles (CVPs) that contained genomes and structural features from both IAV and RSV. Additionally, coinfection by IAV and RSV generated pseudotyped RSV filaments that incorporate IAV glycoproteins. Functional assays using a sialidase showed that CVPs can facilitate entry of IAV into cells that were stripped of IAV entry receptors, demonstrating CVPs possess expanded receptor tropism. To determine the likelihood for CVP formation in the airway epithelium, we coinfected primary differentiated human bronchial epithelial cell (hBEC) cultures at air-liquid interface. We observed that IAV and RSV infect ciliated epithelial cells and identified foci of coinfection. IAV and RSV proteins both localised at the apical surface of coinfected cells, providing opportunity for interactions to occur during viral assembly. Additionally, IAV and RSV replication kinetics and cytopathic effect in hBEC cultures reflected trends observed in the in vitro cell model, suggesting that viral interactions may be conserved between simplified and representative airway models. Overall, this project characterises interactions between IAV and RSV during coinfection and we show that coinfection by IAV and RSV results in formation of a novel class of viral particles. By expanding viral tropism, formation of CVPs may alter viral dissemination within the respiratory tract, potentially impacting disease outcomes for a coinfected individual. Further, by defining a previously unknown source of viral interaction with implications on viral structure, we contribute more widely to the understanding of the properties of IAV and RSV, and their infection biology as a whole

    Changing discourses and mediation in the Israeli-Palestinian conflict : towards the Declaration of Principles 1993.

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    This thesis focuses on the role of mediators in the process of discursively constructing the dominant narrative erecting the Israeli-Palestinian conflict. In seeking to concentrate on specific mediation processes in the conflict, culminating in the Declaration of Principles, research reveals the highly interactive nature of changing discourses, underpinned by a complex, political process of textual interweaving and overlap that defines the conflict. Much of the literature addressing mediation theory builds on a positivist epistemology which separates fact from value and unquestioningly proceeds from the premise that words mirror the world they describe. Within such a context, mediators remain external to the conflict either arbitrating or facilitating negotiations between the protagonists, but never becoming part of it, contributing to its construction. The application of discourse analysis to the study of mediation challenges this core premise, arguing that any intervention necessarily involves a process of reinterpretation or re- definition of the conflict, engendered by the mediator him or herself. Underpinned by a process of change, the conflict is impinged upon by a plethora of external as well as internal parties to the conflict. These interventions generate a new discourse which interacts with other narratives within the same discursive realm or domain. In this thesis, the term `discourses' refers to those narrative structures in place which enable or constrain political movement in a particular direction at a particular moment in time. Identifying a highly interactive discursive process removes the spotlight away from a narrow and exclusionist conceptualisation of mediation as pertaining to the immediate forum in which negotiations between protagonists and a third party unfold, towards a broader, more inclusive understanding of what the process entails

    Foot and Ankle Impairments Affecting Mobility in Stroke

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    Introduction: Altered foot characteristics are common in people with stroke, with a third presenting with abnormal foot posture which is associated with ambulatory difficulties. Understanding the relationship between measures of foot and ankle impairment and their association with mobility and balance outcomes is therefore important; however, poor clinimetric properties of foot and ankle measures after stroke precludes evaluation of these relationships. Therefore, this research, undertaken as part of a multicentred research project, had the following aims: Study 1: To evaluate the clinimetric properties (feasibility, test–retest reliability, and clinical relevance) of measures of foot and ankle impairments, for application in people with stroke. Study 2: To examine how these measures differ between people with stroke and normal controls; and whether they are associated with mobility and balance outcomes. Methods: In Study 1, community-dwelling people with stroke, able to walk 10 m (metres), attended two testing sessions to evaluate the clinimetric properties of different foot and ankle measures. These included: static foot posture and dynamic foot loading (peak plantar pressure, PPP, contact area, CA and centre of pressure, CP) using a plantar pressure mat; isometric muscle strength using a hand-held dynamometer (HHD); peak ankle and hallux dorsiflexion and stiffness using bespoke rigs; and ankle plantarflexion spasticity using the Tardieu scale. Statistical analysis used intraclass correlation coefficients (ICCs₍₃,₁₎), standard error of measurement (SEM) and Bland–Altman plots. In Study 2, measures identified as reliable from Study 1 were incorporated in a cross-sectional study design. Participants were recruited from acute and community neurological services in East London and North Devon. Statistical analysis tested the differences between groups and between affected limbs in people with stroke. Impairment measures were evaluated using multivariate regression analysis for their association with functional outcomes: walking speed (over 10 m); Timed Up and Go (TUAG), Forward Functional Reach Test (FFRT) and presence of falls (> 1 in the last 3 months). Results: In Study 1, 21 people with stroke tested the measures. These were found to be feasible and easy to administer, although loss of data (up to 33%) was observed. All measures had moderate to excellent test–retest reliability (coefficients 0.50‒0.98), except ankle plantarflexion stiffness (ICCs₍₃,₁₎ = 0.00‒0.11). In Study 2, there were significant differences in all measures between people with stroke (n = 180) and controls (n = 46), apart from static foot posture (p = 0.670), toe deformity (p = 0.782) and peak hallux dorsiflexion (p = 0.320). Between limb differences were identified for all measures except foot posture (p = 0.489) and foot CA (p > 0.05). Multicollinearity analysis found 10 measures appropriate for multivariate regression which identified the following R² and variance explained: 59% walking speed (R² = 0.543); 49% TUAG (R² = 0.435); 36% FFRT (R² = 0.285) and 26% for Falls Presence. Conclusion: The study demonstrated that seven foot and ankle measures of impairment after stroke were clinically feasible, reliable and associated with mobility and balance outcomes. The measures were ankle and foot isometric muscle strength, sway velocity, PPP (RFT and FFT), CA (MFT and FFT) and peak ankle dorsiflexion. These measures can now be incorporated into research to examine methods to improve the treatment of foot and ankle after stroke

    Context-aware software

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    With the advent of PDAs (Personal Digital Assistants), smart phones, and other forms of mobile and ubiquitous computers, our computing resources are increasingly moving off of our desktops and into our everyday lives. However, the software and user interfaces for these devices are generally very similar to that of their desktop counterparts, despite the radically different and dynamic environments that they face. We propose that to better assist their users, such devices should be able to sense, react to, and utilise, the user's current environment or context. That is, they should become context-aware. In this thesis we investigate context-awareness at three levels: user interfaces, applications, and supporting architectures/frameworks. To promote the use of context-awareness, and to aid its deployment in software, we have developed two supporting frameworks. The first is an application-oriented framework called stick-e notes. Based on an electronic version of the common Post-It Note, stick-e notes enable the attachment of any electronic resource (e.g. a text file, movie, Java program, etc.) to any type of context (e.g. location, temperature, time, etc.). The second framework we devised seeks to provide a more universal support for the capture, manipulation, and representation of context information. We call it the Context Information Service (CIS). It fills a similar role in context-aware software development as GUI libraries do in user interface development. Our applications research explored how context-awareness can be exploited in real environments with real users. In particular, we developed a suite of PDA-based context-aware tools for fieldworkers. These were used extensively by a group of ecologists in Africa to record observations of giraffe and rhinos in a remote Kenyan game reserve. These tools also provided the foundations for our HCI work, in which we developed the concept of the Minimal Attention User Interface (MAUI). The aim of the MAUI is to reduce the attention required by the user in operating a device by carefully selecting input/output modes that are harmonious to their tasks and environment. To evaluate our ideas and applications a field study was conducted in which over forty volunteers used our system for data collection activities over the course of a summer season at the Kenyan game reserve. The PDA-based tools were unanimously preferred to the paper-based alternatives, and the context-aware features were cited as particular reasons for preferring them. In summary, this thesis presents two frameworks to support context-aware software, a set of applications demonstrating how context-awareness can be utilised in the ''real world'', and a set of HCI guidelines and principles that help in creating user interfaces that fit to their context of use

    Comparative effectiveness of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on cardiovascular disease prevention

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    Background: The renin–angiotensin–aldosterone system (RAAS) plays a crucial role in the development of hypertension, and in the pathogenesis and progression of atherosclerosis, leading to cardiovascular diseases (CVD). ACEIs and ARBs inhibit the RAAS at different targets and achieve comparable BP reductions. Of the two groups, ARBs have a superior safety and tolerability profile. However, there are reports of divergent effects from ACEI and ARBs based on the meta-analyses of clinical trials. ACEIs reduce the risk of MI, cardiovascular (CV) mortality and allcause mortality, whereas ARBs do not. Clinical practice guidelines consider ACEIs and ARBs equivalent, and a comprehensive and up to date assessment of the ‘ARB paradox’ is important to inform future guidelines and ensure safe clinical practice. Objectives: The main objectives of the current thesis are: 1) to investigate the comparative effectiveness of ACEIs and ARBs for preventing CV morbidity and mortality in patients with or at high-risk of CVDs; and 2) to assess the relative contribution of BP-dependent and independent mechanisms on reducing the risk of CV morbidity and mortality, as achieved by ACEIs and ARBs. Methodologies for answering the research questions: A systematic review and meta-analysis of randomized-control trials (RCTs), was performed in addition to a random-effects meta-regression analysis. Pre-specified outcomes, including, myocardial infarction (MI), angina pectoris, stroke, heart failure (HF), all-cause mortality, and CV death were assessed. In addition, specific pre-specified subgroups of patients, including drug subclasses, comparator drugs, population clinical setting, and mean age (years), were evaluated to demonstrate the differential benefits when comparing ACEIs and ARBs. Results: The results for the meta-analysis and meta-regression analysis are divided here into four chapters (4 to 7) according to the CV outcomes for ACEIs and ARBs. In total, 97 RCTs, with 317,984 participants with or at high-risk of CVDs were included in this systematic review, over an average duration of 3.03 years. ACEIs and ARBs with risk of coronary artery disease events: The pooled data shows that there was a significant 16% (RR, 0.84; 95% CI 0.79–0.90; p<0.00001) reduction in the risk of incident MI in relation to ACEI therapy compared control group with no evidence of statistical heterogeneity among the trials (I2=0%.). In contrast, there was no overall benefit identified from ARB therapy (RR, 0.97; 95% CI 0.89-1.06; p= 0.55; I2=30%). The evidence from the direct comparison trials showed no distinction between ACEIs and ARBs in terms of MI risk (RR 1.02; 95% CI 0.95–1.09; p=0.64; I2=0%)). Furthermore, I have shown through a meta-regression analysis that nearly half (9% relative risk reduction) of the protective effect of ACEI on MI risk occurs independently of any BP lowering effect. Both ACEI and ARB therapies have no impact in terms of their capacity to reduce the risk of angina pectoris. Considerable heterogeneity was observed among the effect estimates for ACEIs and ARBs (I 2 : 58% and 61% respectively), which limits the author’s capacity to formulate definitive conclusions. ACEIs and ARBs in preventing stroke: According to this systematic review, the analyses reveal that both ACEIs and ARBs provide a reduction in stroke risk compared with placebo; by 14% (RR, 0.86; 95% CI 0.76-0.98; p=0.02; I2=26%) and 9% (RR, 0.91; 95% CI 0.85-1.00; p=0.05; I2=0%) respectively. Based on direct comparison trials, there appear to be a 4% lesser stroke lowering affect from ARB therapy than noted for ACEI (RR, 0.96; 95% CI 0.87-1.06; p=0.42; I 2=0%), but this finding did not achieve statistical significance. In the meta-regression analysis, both ACEI and ARB therapies have respective risk ratios for stroke reduction that are significantly related to the magnitude of the BP reduction. ACEIs versus ARBs for HF prevention: This overview suggests that ACEIs showed a 20% lower HF risk compared with placebo (RR, 0.80; 95% CI 0.74, 0.87; P= 0.00001). Similarly, ARBs had a 14% lower HF risk compared with placebo (RR, 0.86; 95% CI 0.80–0.92; p< 0.00001). This comparable finding was confirmed in direct comparison trials (RR,1.03; 95% CI 0.97–1.09; p=0.37; I2=0%). However, when analyzing trials with active therapy as the comparator group, ARB appeared to be beneficial, with a 13% significant reduction of HF risk, and no added benefit emerging for ACEIs. BP reduction was a major determinant of the risk reduction achieved by ACEIs, while the ARB effect occurred independently of BP reduction. ACEIs versus ARBs with risk of CV and all-cause mortality: ACEIs are associated with a 9% (RR, 0.91; 95% CI 0.86- 0.97; P=0.002) and 5% (RR, 0.95; 95% CI 0.91- 0.98; p=0.003) relative risk reduction in CV and all-cause mortality respectively. No statistical variation was apparent across the studies (I2=0%). Meanwhile, no such benefit was seen with ARB-based therapy. Direct comparison trials showed that both ACEIs and ARBs were equivalent in terms of the CV (RR, 1.04; 95% CI 0.98-1.10; p=0.16; I2=0%) and all mortality risk (RR, 1.03; 95% CI 0.98-1.08; p=0.20; I 2=0%). The magnitude of the observed risk-reduction seen with ACEIs could be attributed to the magnitude of the BP reduction. Consistent findings involving a series of sensitivity analyses were expected to support the strength of this association. Conclusions: In summary, this study used data from 317,984 participants with or at high-risk of CVDs, suggesting that ARBs are as effective as ACEIs at mitigating potential risk from CV events and mortality. The finding from the direct comparison trials also supports the view that ARBs may be slightly more protective than ACEIs against risk of stroke. The reduction in stroke risk brought about by ACEI and ARB is largely attributable to BP reduction. The magnitude of the risk reduction for HF, CV and all-mortality by ACEIs appear to have largely been driven by the magnitude of the BP reduction. The beneficial effect independent of BP reduction of ACEI on MI risk and ARB on HF risk warrants further study

    Pathophysiology of Primary Coenzyme Q10 Deficiencies. Molecular Characterisation of COQ4 gene.

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    Programa de Doctorado en Biotecnología, Ingeniería y Tecnología QuímicaLínea de Investigación: Experimentación en Enfermedades RarasClave Programa: DBICódigo Línea: 14Las deficiencias primarias de coenzima Q10 (CoQ10) son un grupo de enfermedades raras genéticas causadas por mutaciones bialélicas recesivas en uno de los genes COQ requeridos en la ruta de biosíntesis de CoQ10, a nivel enzimático o regulador. Las manifestaciones clínicas asociadas son muy heterogéneas y afectan principalmente al sistema nervioso central y periférico, a los riñones, al músculo esquelético y al corazón. La primera parte de esta tesis se centra en el estudio del síndrome de la deficiencia primaria en CoQ10. En primer lugar, hemos realizado una revisión actualizada y exhaustiva de todas las manifestaciones clínicas asociadas a cada una de las variantes patogénicas en los genes COQ descritas en la literatura. En ella, describimos patrones de síntomas relacionados con la edad de aparición de la enfermedad para cada gen COQ e incluso, para cada mutación, cuando es posible. Con estos patrones, hemos intentado establecer correlaciones genotipo-fenotipo para la deficiencia primaria en CoQ10. En segundo lugar, hemos descrito nuevos casos de deficiencia primaria de CoQ10 debido a mutaciones en los genes COQ4 y COQ7, ampliando los fenotipos y genotipos asociados a estos trastornos. Hemos trabajado con diferentes modelos celulares in vitro con mutaciones en COQ4, COQ6 y COQ7, que acumulan intermediarios diagnósticos, específicos para cada defecto COQ. Además, demostramos que el tratamiento con análogos del 4-hidroxibenzoato (4-HB) es eficaz para mejorar la deficiencia de CoQ10 y el defecto respiratorio en nuestros modelos celulares humanos: el ácido 2,4-dihidroxibenzoico (2,4-dHB) para la deficiencia en COQ7 y el ácido vainillínico (VA) para los defectos en COQ6. En la segunda parte de la tesis, nos hemos centrado en la proteína COQ4 humana, que tiene un papel esencial en la biosíntesis de CoQ10. En nuestro trabajo, demostramos que la proteína COQ4 humana es esencial para la biosíntesis de CoQ10 en las células. Hemos generado una línea celular humana KO en COQ4, que tiene una gran deficiencia en CoQ10 y en la respiración mitocondrial. Estos defectos son rescatados con un tratamiento con CoQ10 o con la expresión del gen COQ4 WT. Además, la falta de proteína COQ4 produce la acumulación de un intermediario específico de la ruta de síntesis. También encontramos que la mayoría de las mutaciones descritas en pacientes son hipomórficas, capaces de recuperar completamente la biosíntesis de CoQ10 en las células COQ4 KO cuando son sobreexpresadas. Con estudios de proteómica, hemos podido identificar todas las proteínas COQ (excepto COQ8A) copurificando con COQ4, lo que es una evidencia más de la existencia del complejo de síntesis de CoQ en mamíferos. Además, observamos que la falta de proteínas COQ4 o COQ6 altera los niveles de otras proteínas COQs, probablemente modificando la estabilidad del complejo biosintético. Se ha descrito que las enzimas modificadoras de la cabeza de CoQ en levadura resuelven en loci discretos, denominados dominios CoQ, que se encuentran adyacentes a los sitios de contacto entre el retículo endoplásmico (ER) y las mitocondrias 1,2. Además, el mantenimiento y la distribución del ADN mitocondrial (mtDNA) depende de estos contactos ER-mitocondria 3, y los niveles de colesterol en estos sitios parecen ser clave para ello 4. En la última parte de la tesis, hemos explorado estas relaciones en nuestro modelo COQ4 KO. La falta de COQ4 produce una ligera disminución del número de copias de mtDNA, sin efecto sobre la transcripción de mtDNA y un efecto muy sutil sobre la traducción de proteínas codificadas por el mtDNA. Con respecto a la replicación del mtDNA, la falta de COQ4 o COQ6 induce una tasa de recuperación más rápida del mtDNA después de una depleción inducida. Para encontrar el mecanismo molecular de este sorprendente fenotipo, hemos estudiado el contenido de colesterol y la distribución de proteínas de los nucleoides en gradientes de densidad. Los niveles de colesterol total parecen no estar alterados en las mitocondrias de las células COQ4 KO. Sin embargo, hemos encontrado diferencias sutiles entre COQ4 KO y las células control en la distribución de proteínas de los nucleoides (TFAM y ATAD3) en estos gradientes. Este hecho podría estar detrás de la rápida recuperación del mtDNA después de la depleción inducida. Sin embargo, todavía queda mucho trabajo por hacer para comprender mejor la relación entre la biosíntesis de CoQ y el metabolismo del mtDNA.Universidad Pablo de Olavide de Sevilla. Departamento de Fisiología, Anatomía y Biología Celula
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