177,187 research outputs found
Gene Therapy of ABCA4-Associated Diseases.
No full textThe ATP-binding cassette (ABC) transporter gene, ABCA4 (ABCR), was characterized in 1997 as the causal gene for autosomal recessive Stargardt disease (STGD1). Shortly thereafter several other phenotypes were associated with mutations in ABCA4, which now have collectively emerged as the most frequent cause of retinal degeneration phenotypes of Mendelian inheritance. ABCA4 functions as an important transporter (or "flippase") of vitamin A derivatives in the visual cycle. Several ways to alleviate the effects of the defective ABCA4 protein, which cause accumulation of 11-c/s and all-trans-retinal in photoreceptors and lipofuscin in the retinal pigment epithelium, have been proposed. Although ABCA4 has proven to be a difficult research target, substantial progress through genetic, functional, and translational studies has allowed major advances in therapeutic applications for ABCA4-associated pathology, which should be available to patients in the (near) future. Here, we summarize the status of the gene therapy-based treatment options of ABCA4-associated diseases. © 2015 Cold Spring Harbor Laboratory Press; all rights reserved
Molecular pharmacology of receptors. V
No full text• G. Gebers, LH. Allikmets, A. Zharkovsky. Effect of nifedipine on analgesia induced by GАВАA and GABAB receptor agonists in rats
• T. Kivastik, A. Zharkovsky Changes in sensitivity of dopamine autoreceptors after single and chronic morphine administration to rats
• J. Harro, A. Lang, A. Põld, Т. Ööpik, E. Vasar. Cholecystokinin and anxiety: a brief review
• E. Vasar, E. Peuranen, J. Harro, A. Lang, L Oreland, P.T. Männistö. Social isolation modulates the sensitivity of cholecystokinin receptors in the rat brain
• I.A. Fleidervish, A.I. Undrovinas, N.A. Burnashev, J.C. Makielski, A. Paju. Modified gating kinetics of cardiac codium channels as a possible cause of ischemia-induced depolarization
• M. Zilmer, E. Karelson. Plasma membrane receptors as targets for cancerogens
• E. Karelson, M. Zilmer, J. Laasik. Possible mechanismus of galanin neurotropic activity
• R-A. Kiivet, J.O. Svensson, L. Bertilsson, P. Sjoqvist. Frequency of impaired hydroxylation of. mephenytoin and debrisoquine in an Estonian population
• P. Pokk, A. Zharkovsky. The effcct of sleep deprivation on the locomotor activity of mice
• M. Otter, T. Ööpik. Bioperiodical changes of antihypoxic effect of neuroleptic drugs in albino micehttp://tartu.ester.ee/record=b1076444~S1*es
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe 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
"Closing the R&D Gap, Evaluating the Sources of R&D Spending"
No full textBoth spending and tax policies have been implemented in the United States with the goal of stimulating private sector research and development (R&D). Karier questions whether current R&D policy, especially the research and experimentation tax credit, can contribute to closing the gap between nondefense expenditures on R&D in the United States and such expenditures in other countries, such as Japan and Germany. He also explores possible changes to our current R&D policy to make it more effective.
Pseudo-vitelliform macular detachment and cuticular drusen: Exclusion of 6 candidate genes
No full textPurpose: The etiology and genetic cause of pseudo-vitelliform macular detachment with cuticular drusen (PVMD/CD) are unknown; nor is it clear if this phenotype represents a separate disease entity, or is a sub-phenotype of disorders with overlapping clinical presentation. To answer this question, we screened a cohort of patients affected with PVMD/CD for variation in six plausible candidate genes (ABCA4, VMD2, TIMP-3, peripherin/RDS, fibulin 5 (FIBL5) and complement factor H (CFH)) associated with diseases of overlapping phenotypes. Methods: Twenty-eight patients, diagnosed with pseudo-vitelliform macular detachment and cuticular drusen, were evaluated by clinical examination, fundus photography, fluorescein angiography and autofluorescence imaging. DNA from all study subjects were screened for variants in the ABCA4, VMD2, TIMP-3, peripherin/RDS, FIBL5 and CFH genes by a combination of DHPLC, array screening and direct sequencing. Results: All patients presented with cuticular drusen; pseudo-vitelliform detachment was seen in 21 cases, while atrophic changes following regression of the detachment were seen in the remaining 7 subjects. Visual acuity ranged from 20/20 to CF. The screening revealed an I32V mutation in peripherin/RDS in one patient and 2ABCA4 variants, T897I and G1961E, in 2 more patients. No amino acid-altering variants were detected in VMD2, TIMP-3, and FIBL5 genes. The frequency of the CFH Y402H variant in this cohort corresponded to that detected in the general population. Conclusions: Screening of 6 candidate genes detected possibly disease-associated mutations in only 3/28 (10.7%) of patients presenting with PVMD/CD, eliminating these genes as causal for this phenotype. Copyright © Informa Healthcare USA, Inc
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
Clinical expression of cone dystrophy associated with a novel deleterious ABCR (ABCA4) mutation in an italian family
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