1,720,987 research outputs found
BIOCHEMICAL AND GENETIC APPROACHES TO UNRAVEL MITOCHONDRIAL COMPLEX I DEFICIENCY
Get PDFUsing biochemical and genetic approaches we have been able to identify the genetic defect underlying mitochondrial complex I deficiency in 3 patients out of the 12 patients in the cohort. The patient cohort investigated in this study is genetically heterogeneous, originating from several different geographical areas: England, France, the Middle East, Israel, India and Pakistan. They presented with different clinical phenotypes: Leigh syndrome, congenital lactic acidosis, hypertrophic cardiomyopathy, encephalopathy, developmental delay, Alpers’ disease.
After having excluded the mitochondrial DNA molecule for carrying mutations in muscle (analysis carried out by the diagnostic laboratories’ staff, at the National Hospital for Neurology, Queen Square, London), a biochemical investigation was undertaken in patients’ fibroblasts: the complex I activity defect was confirmed in this tissue as well for all the patients, and Blue Native studies were carried out. Antibodies against several subunits of complex I identified various subassemblies of the ~1MDa holoenzyme in several patients; in some others various degrees of reduction in holo-complex I content were observed. Analysis of the complex I pattern on Blue Native gels led the genetic screening towards a subset of genes, already known to be involved in complex I deficiency.
Two families were also run on the Affymetrix 10K SNP chip array and then a homozygosity mapping approach was undertaken on the assumption that the affected individuals inherited two copies of the same ancestral mutated allele from a common ancestor (autozygosity). A subsequent bioinformatics analysis (also involving the implementation of the Maestro and MitoCarta databases) allowed the selection of a subgroup of genes that could possibly bear the genetic defect; this was done taking into account the Blue Native complex I pattern as well.
Genetic screening identified a novel 8bp frameshift deletion (c.377_384del; Q126fsX2) in the NDUFS4 gene as cause of the disease in a patient from the first pedigree analyzed by homozygosity mapping. Her cousin was heterozygous for the same defect, but no other mutation has been identified, leaving this complex I deficiency case unsolved. In the second pedigree analyzed by homozygosity mapping approach, a homozygous mutation in a novel complex I assembly factor never previously linked to human disease has been identified. The c.1054C>T; R352W mutation in FOXRED1 segregated with disease in the family and was not found in 268 healthy control alleles. Western blot analysis showed a reduced steady-state level of FOXRED1 in patient fibroblasts and restoration of complex I activity after lentiviral transduction of patient fibroblasts with wild-type FOXRED1 cDNA. Finally, by candidate gene sequencing, two novel compound heterozygous mutations in NDUFAF1 were identified in a third patient: c.631C>T; R211C and c.733G>A; G245R.
In summary, this study allowed the identification of mutations in (i) one complex I subunit, NDUFS4, already associated with complex I deficiency; (ii) one novel complex I assembly factor: FOXRED1; (iii) and NDUFAF1, a known complex I assembly factor whose mutations give a similar complex I Blue Native pattern to the one observed in our patient. In conclusion our combined approach proved to be efficient in the identification of the genetic defect in patients affected with complex I deficiency
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
Autosomal Recessive Ala93Thr mutation in caveolin-3 gene : a new family
No full textCaveolin-3 is the muscle-specific protein of the caveolin family. It is expressed both in cardiac and skeletal muscles and it is the principal integral membrane component of caveolae, small vescicular invaginations of the plasma membrane implicated in cell signalling. Mutations in the caveolin-3 gene (CAV3) are associated with four different phenotypes: limb girdle muscular dystrophy 1C (LGMD1C), rippling muscle disease (RMD), distal myopathy and familial iperCKemia. All phenotypes are usually inherited with an autosomal dominant pattern of inheritance. We describe an Italian family which presented an autosomal recessive pattern of inheritance. A 30-year-old man presented with rippling, myotonic discharges at electromyography and elevated serum CK levels. His 34-year-old sister had normal muscular strength but referred rippling after strong exercise. DM1 and DM2 gene analysis was normal. Muscle biopsy was obtained from brachial biceps after written informed consent. Caveolin-3 immunohistochemistry (IHC) analysis and full gene sequencing were ultimately performed. Muscle biopsy showed a mild dystrophic pattern and a partial deficit of caveolin-3 at IHC analysis. Mutation analysis showed the homozygous mutation c.277G>A (Ala93Thr) in the CAV3 gene in both probands. Genetic analysis was extended to parents. They carried the same mutation in heterozygosis, were completely asymptomatic and showed normal cardiac function. The same mutation had been previously described by Kubisch et al. (2005) in homozygosis associated with a severe form of RMD. Our patients did not presented a more severe phenotype that usually seen. We confirmed the presence of intrafamilial variability. So far few missense mutations of the caveolin-3 gene behave as recessive. Genetic confirmation in independent families strengthens the reliability of genetic assessment. The mechanism preserving the integrity of caveolin oligomerisation and sarcolemmal localization in the presence of heterozygous A93T mutant caveolin-3 remains to be understood
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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