Cytochrome c oxidase (COX) represents the terminal enzyme complex of respiratory chain metabolic pathway and it occurs as monomer, dimer or as a part of respiratory supercomplexes in the inner mitochondrial membrane. COX assembly process is complicated, highly regulated and depends on many ancillary proteins. Mutations in COX subunits, which are encoded by mitochondrial and nuclear DNA, or in genes encoding its assembly proteins are frequent cause of very severe mitochondrial disorders. SURF1 assembly protein participates in the first steps of COX assembly, but its exact function is not yet clarified. In humans, mutations of SURF1 gene lead to severe COX defect and fatal neurodegenerative disorder, Leigh syndrome. Knockout of SURF1 gene in mouse causes isolated COX defect as well, but less pronounced and without involvement of CNS. The aim of the thesis was detailed analysis of disturbed COX biogenesis in a condition of SURF1 gene mutations or SURF1 gene knockout, from assembly of COX monomer to interaction of COX into supercomplexes, and to the impact of isolated COX defect on other OXPHOS complexes. Mutations of SURF1 gene in patient's fibroblasts led to marked accumulation of COX assembly intermediates and to a defect in formation of functional COX monomer, which was preferentially built into an...

Cytochrome c oxidase (COX) represents the terminal enzyme complex of respiratory chain metabolic pathway and it occurs as monomer, dimer or as a part of respiratory supercomplexes in the inner mitochondrial membrane. COX assembly process is complicated, highly regulated and depends on many ancillary proteins. Mutations in COX subunits, which are encoded by mitochondrial and nuclear DNA, or in genes encoding its assembly proteins are frequent cause of very severe mitochondrial disorders. SURF1 assembly protein participates in the first steps of COX assembly, but its exact function is not yet clarified. In humans, mutations of SURF1 gene lead to severe COX defect and fatal neurodegenerative disorder, Leigh syndrome. Knockout of SURF1 gene in mouse causes isolated COX defect as well, but less pronounced and without involvement of CNS. The aim of the thesis was detailed analysis of disturbed COX biogenesis in a condition of SURF1 gene mutations or SURF1 gene knockout, from assembly of COX monomer to interaction of COX into supercomplexes, and to the impact of isolated COX defect on other OXPHOS complexes. Mutations of SURF1 gene in patient's fibroblasts led to marked accumulation of COX assembly intermediates and to a defect in formation of functional COX monomer, which was preferentially built into an...

Fingers should demonstrate my filmmaking ability and encourage future employers to hire me to direct a project. This paper will explore in details what methods were used during the production with focus on working within the means of the budget. In the following chapters, I will discuss Fingers, including the writing, preproduction, directing, cinematography, editing, and the final product.

BACKGROUND: Mitochondrial complex I deficiency often leads to a devastating neurodegenerative disorder of childhood. In most cases, the underlying genetic defect is unknown. Recessive nuclear gene mutations, rather than mitochondrial DNA mutations, account for the majority of cases. AIM: Our aim was to identify the genetic basis of complex I deficiency in 34 patients with isolated complex I deficiency, by studying six of the 39 nuclear encoded complex I subunit genes (NDUFV1, NDUFS1, NDUFS2, NDUFS4, NDUFS7 and NDUFS8). These genes have been conserved throughout evolution and carry out essential aspects of complex I function. METHODS: RNA was extracted from patient fibroblasts and cDNA made by reverse transcription. Overlapping amplicons that together spanned the entire coding area of each gene were amplified by PCR. The genes were screened for mutations using denaturing High Performance Liquid Chromatography (dHPLC). Patient samples with abnormal dHPLC profiles underwent direct DNA sequencing. RESULTS: Novel mutations were identified in six of 34 (18%) patients with isolated complex I deficiency. Five patients had two mutations identified and one patient had a single mutation in NDUFS4 identified. All patients with mutations had a progressive encephalopathy and five out of six had Leigh syndrome or Leigh like syndrome. Mutations were found in three nuclear encoded subunit genes, NDUFV1, NDUFS2 and NDUFS4. Three novel NDUFV1 mutations were identified (R386H, K111E and P252R). The R386H mutation was found in two apparently unrelated patients. Four novel NDUFS2 mutations were identified (R221X, M292T, R333Q and IVS9+4A&ltG). The novel NDUFS4 mutation c.221delC was found in two patients - one in homozygous form and the other heterozygous. Specific genotype and phenotype correlations were not identified. CONCLUSIONS: Nuclear encoded complex I subunit gene mutations are an important contributor to the aetiology of isolated complex I deficiency in childhood. Screening of these genes is an essential part of the investigation of complex I deficiency.

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This dissertation critically examines why mid-Victorian fiction often dismisses or complicates monetary transactions and monetary charity, even as it negatively portrays differences in social status and wealth. I argue that the novel uses representations of failed charity to reconstruct, however briefly, a non- monetary and non-economic source of value. Further, I examine how the novel uses techniques of both genre and style to predict, form, and critique alternate, non-economic, social models. While tension surrounding the practice of charity arises in the late eighteenth century, the increasing dominance of political economy in public discourse forced Victorian literature to take a strong stance, for reasons of both ethics and genre. This stance is complicated by the eighteenth-century legacy that sees charity as a kind of luxury. If giving to the poor makes us feel good, this logic suggests, surely it isn’t moral. Thus, while much eighteenth- and nineteenth-century literature remains dedicated to the ethics of charity, the practice becomes immensely complex. By discussing the works of Tobias Smollett, Charles Dickens, Elizabeth Barrett Browning, and George Eliot, this project exposes a wide variety of responses to this deep cultural anxiety. These authors are, ultimately, strongly invested in redefining the meaning of benevolence as a valid form of social action by moving that benevolence away from monetary gifts and toward abstractly correct moral feelings, though their individual solutions vary widely. / text

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The aim of this thesis was to assess the influence of canistherapeutic intervention on the level of fine motor skills in patients with rare diseases, namely mitochondrial encephalocardiomyopathy caused by TMEM70 gene mutation and Leigh syndrome. Canistherapeutic intervention in these patients is based on activation of motoric functions during programme reasonably designed according to the needs of specific patients. The assistance of the dog is used to achieve this activation. The dog acts as an important motivational factor and the direct contact with it contributes to development of sensomotoric skills of these patients. The thesis summarizes general information about rare diseases and focuses on one of the subgroups of mitochondrial disorders. It presents knowledge about the Leigh syndrome and mitochondrial encephalocardiomyopathy caused by TMEM70 gene mutation. Subsequently the thesis presents information about canistherapy and fine motor skills. The thesis further contains case reports of patients, data from research units and their evaluation. The aim of the thesis was to find out whether patients with mitochondrial disease show improvement of quality and effectivity of selected grasp forms and thus faster and more precise execution assigned tasks focusing on object manipulations. Partial...

This study investigates the challenges facing screenwriters in Australia who set out to represent the Japanese on screen. The study is presented in two parts; an exegesis and a creative practice component consisting of two full length feature film screenplays. The exegesis explores how certain screenwriting conventions have constrained recent screen images of the Japanese within the bounds of the cliched and stereotypical, and argues for a greater resistance to these conventions in the future. The two screenplays experiment with new ways of representing the Japanese in mainstream Australian film and aim to expand the repertoire of Asian images in the national film culture.

"Endymion" è il traît d'union tra i juvenilia di Keats ("Poems", 1817) e i suoi lavori più conosciuti ("Lamia, Isabella ... and other Poems"). Per sua natura, è un'opera di transizione e quindi concede allo studioso un punto di vista privilegiato sullo sviluppo della poetica e della lingua di Keats. Inoltre, l'"Endymion" è l'opera keatsiana più aspramente contestata dalla critica romantica. Gli studiosi moderni hanno analizzato il problema alla luce di considerazioni socio-politiche, il mio lavoro mira invece ad un'analisi più strettamente linguistica. Ricostruisco il contesto linguistico del diciottesimo e diciannovesimo secolo al fine di spiegare il disagio dei recensori nei confronti di "Endymion". Sostengo che il prescrittivismo del Settecento nasce da una profonda ansia relativa alla lingua, causata dalle teorie di Locke. L'atteggiamento prescrittivista influenza la critica romantica e i critici di Keats in particolare, più di quanto potessero fare considerazioni di natura politica. Analizzo le peculiarità linguistiche e strutturali di "Endymion" al fine di provare che Keats elabora una 'poetica dell'incontrollabilità', una serie di strategie stilistiche e testuali, che violano le convenzioni linguistiche e narrative e che vengono quindi percepite come destabilizzanti e stranianti. / "Endymion" is the traît d’union between Keats’s juvenilia ("Poems", 1817)and his better known, and, conventionally, ’mature’ works ("Lamia, Is- abella ... and other Poems", 1820). By its nature, it is a transitional work, and thus gives the scholar special insight into the development of Keats’s poetics and idiom. Moreover, "Endymion" is the Keatsian work which most irritated and provoked contemporary critics; the two pieces of venomous invective it received in the periodical press of the time have become the stuff of scholarly legend. Recent scholarly work has analysed the language of "Endymion" in socio-political terms; my work focuses on more strictly linguistic concerns. I reconstruct the linguistic context of the eighteenth and early nineteenth centuries in order to explain the reviewers’ unease with regard to "Endymion". I maintain that eighteenth-century prescriptivism arose from a deep-seated anxiety regarding language, Lockian in origin, and that the ensuing desire to stabilize and therefore control language informed Romantic criticism in general, and the criticism of Keats’s work in particular, more fundamentally than politics could or did. I analyse the imaginative and linguistic markers of "Endymion" in order to prove that Keats had elaborated a “poetics of uncontrollability”, a series of textual and stylistic strategies, which violated linguistic and narrative standards and were therefore perceived as unsettling.