1,721,027 research outputs found
Clinical and Molecular Genetic Studies in Mitochondrial Disease
Get PDFUp to a third of adults attending the Queen Square UK NHS Specialised Service for Rare Mitochondrial Disease out-patient clinic remain genetically undetermined. This thesis describes research which aimed to establish the molecular basis of mitochondrial disease in these patients and evaluate genotype/phenotype correlations. Both novel clinical syndromes and molecular causes of disease were identified. Furthermore, new insights into the respiratory chain (RC) protein structure were elucidated. Novel clinical phenotypes: Three previously unrecognised mitochondrial disease phenotypes were characterised. First, m.9185T>C in MT-ATP6, encoding subunit 6 of ATP synthase (complex V), was detected in a pedigree exhibiting matrilineal inheritance. Presentation was with axonal Charcot-Marie-Tooth (CMT2) disease. Further screening of 270 patients with genetically unclassified CMT2 demonstrated three additional families harbouring the same mutation, thus proving a causal link between reduced complex V activity and impaired axonal function. Second, a severe distal myopathy was observed in two unrelated patients with de novo dominant POLG mutations. Finally, COX10 mutations were linked to adult cytochrome c oxidase (COX) deficiency. Despite a complex multisystem phenotype comprising short stature, proximal myopathy, fatigue, sensorineural hearing loss, pigmentary maculopathy, renal Fanconi syndrome and premature ovarian failure, the patient’s clinical severity was considerably milder than fatal COX10-related infantile disease. Nuclear gene mutations: Three major experimental strategies were employed to locate mutations in the nuclear genes of adults with clinically and/or biochemically suspected mitochondrial disease. First, a candidate gene approach identified RRM2B mutations in 2/33 patients with multiple mitochondrial DNA deletions. Second, whole-exome sequencing confirmed COX10 mutations can cause adult mitochondrial disease. Finally, combined homozygosity mapping/whole-exome sequencing in a consanguineous family led to the discovery that NDUFA4 mutations cause COX-deficient Leigh syndrome. This example of ‘back-translation’ led to the discovery that NDUFA4, previously considered to be a complex I subunit, is actually an important component of the COX enzyme complex
Mitochondrial myopathies in adults and children: management and therapy development
No full textPurpose of reviewThe clinical and genetic heterogeneity of mitochondrial myopathies presents considerable diagnostic challenges. In addition, mitochondrial dysfunction seems to contribute to the development and progression of many age-related neurodegenerative diseases. This review presents recently published data concerning prevalence, phenotype, gene discovery, disease mechanisms, diagnostic tools and treatment strategies for mitochondrial diseases, and summarizes current understanding concerning the role mitochondria play in the pathogenesis of other common neurological disorders.Recent findingsHeteroplasmic levels of pathogenic mitochondrial DNA mutations are common amongst the general population, although there is considerable geographic variation. Mitochondrial abnormalities also occur in common neurodegenerative disorders, implying a mechanistic link between mitochondrial dysfunction and development or progression of disease. The phenotypic spectrum associated with well recognized pathogenic variants continues to expand, whereas next-generation sequencing is identifying new disease-causing nuclear genetic mutations. Biomarkers and imaging modalities for diagnosis and disease monitoring are now in place and novel treatment strategies are emerging. Alas, no clinical trial data for treatment in mitochondrial disease have been published in the last 12 months.SummaryDespite rapid advances in gene discovery, details concerning the altered protein products and cellular pathways that result in mitochondrial disease remain elusive. Understanding the consequences of deleterious mutations and the cellular adaptive response is imperative so that therapeutic targets can be identified
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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