1,720,956 research outputs found
The mouse model for ocular albinisin type 1 (OA1) as a tool to study Oa1 function in RPE development
No full textPurpose: Ocular Albinism type 1 (OA1) is an X-linked form of albinism isolated to the eye. The disease causes a severe visual handicap in affected males, manifesting foveal hypoplasia, horizontal and rotatory nystagmus, strabismus, photophobia and lack of stereoscopic vision. Histological analysis of patient melanocytes from the RPE and the skin reveals giant melanosomes (macromelanosomes). Mutations causing this disease were identified in OA1 gene. OA1 is specifically expressed in the retinal pigment epithelium (RPE) and in skin melanocytes . The protein is localized on the melanosomal membrane and displays characteristics typical of the seven transmembrane G protein coupled receptors. In order to understand the biological function of OA1, we generated a mouse model for the disease.
Methods: To generate Oa1 null mice, we deleted the first exon of Oa1 by homologous recombination in ES cells. Histological studies were performed on RPE of wild-type and mutant mice. Interactions of Oa1 with other melanosomal proteins was investigated by mating Oa1 null mice with p and c mice. Ultrastructural and biochemical analyses were conducted in double mutant mice.
Results: Histological analysis of the eyes in Oa1 mutants showed that the RPE was more lightly pigmented. Abnormally large melanosomes (macromelanosomes) could be identified by electron microscopy within the RPE. Interestingly, macromelanosomes could be seen just after birth in mutant mice. Oa1 knock-out mice display a misrouting of the optic fibers as in OA1 patients. A significant decrease of ipsilateral optic fibers could be measured in Oa1 knock-out mice as found in other albino mice. To investigate the function of Oa1 on the melanosomal membrane and its interaction with other genes causing different forms of albinism, we mated Oa1 null mice with p and c mice. Ultrastructural and biochemical analyses were performed in double mutant mice, finding a correlation of the macromelanosomal phenotype and level of pigmentation. We have also studied genes regulating Oa1 expression during development (e.i. Mitf) and we have started experiments aimed to the identification of genes downstream to it.
Conclusion: We developed a mouse model for OA1. Our data demonstrate that the Oa1 knock-out mouse is indeed a good model for the study of OA1 pathology. Furthermore the mouse model will be valuable for the identification of factors mediating RPE influence on retinal development
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
Aberrant splicing in the ocular albinism type 1 gene (OA1/GPR143) is corrected in vitro by morpholino antisense oligonucleotides
No full textAn intronic point mutation was identified in the ocular albinism type 1 (OA1) gene (HUGO symbol, GPR143) in a family with the X-linked form of ocular albinism. Interestingly, the mutation creates a new acceptor splice site in intron 7 of the OA1 gene. In addition to low levels of normally spliced mRNA product of the OA1 gene, the patient samples contained also an aberrantly spliced mRNA with a 165 bp fragment of intron 7 (from position +750 to +914) inserted between exons 7 and 8. The abnormal transcript contained a premature stop codon and was unstable, as revealed by Northern blot analysis. We defined that mutation NC_000023.8:g.25288G > A generated a consensus binding motif for the splicing factor enhancer ASF/SF2, which most likely favored transcription of the aberrant mRNA. Furthermore, it activated a cryptic donor-splice site causing the inclusion between exons 7 and 8 of the 165 bp intronic fragment. Thus, the aberrant splicing is most likely explained by the generation of a de novo splicing enhancer motif. Finally, to rescue OA1 expression in the patient's melanocytes, we designed an antisense morpholino modified oligonucleotide complementary to the mutant sequence. The morpholino, oligonucleotide (MO) was able to rescue OA1 expression and restore the OA1 protein level in the patient's melanocytes through skipping of the aberrant inclusion. The use of MO demonstrated that the lack of OA1 was caused by the generation of a new splice site. Furthermore, this technique will lead to new approaches to correct splice site mutations that cause human diseases
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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