Biomedical subjects
Publications and source records attributed to Yuval Cohen.
The mutational landscape of an individual's cancer can inform on its molecular state and be used as prognostic and therapeutic markers. The study by Barbour et al.1 analyzes mutational patterns in bladder cancer samples to uncover new biological insights into the ERCC2 gene function and develop new predictive prognostic tools.
Phospholipase-A2 (PLA2) enzymes hydrolyze cell membrane phospholipids to produce arachidonic acid (AA) and lyso-phospholipids (LysoPL), playing a key role in the production of inflammatory lipid mediators, mainly eicosanoids. They are therefore considered pro-inflammatory enzymes and their inhibition has long been recognized as a desirable therapeutic target. However, attempts to develop suitable PLA2 inhibitors for the treatment of inflammatory diseases have yet to succeed. This is due to their functional and structural diversity, and their homeostatic and even anti-inflammatory roles in certain circumstances. In the present review we outline the diversity and functions of PLA2 isoforms, and their interplay in the induction and inhibition of inflammatory processes, with emphasis on discussing approaches for therapeutic manipulation of PLA2 activities.
PURPOSE: To report the morphologic data of adult-onset foveomacular vitelliform dystrophy (AFVD) provided by third-generation optical coherence tomography (OCT 3). DESIGN: Observational case report. METHODS: An 85-year-old woman presenting with AFVD underwent fundus biomicroscopy, fluorescein angiography, and OCT examination. RESULTS: Fundus examination disclosed a round, elevated yellowish lesion, centered by a pigmented spot, in the macula of the left eye. Examination with OCT disclosed an area of hyperreflectivity located between the retinal pigment epithelium layer and the photoreceptor layer, compatible in size with the yellowish elevated lesion. The hyperreflective line corresponding to the photoreceptor layer was elevated by the material and separated from the retinal pigment epithelium layer. CONCLUSIONS: In AFVD, examination with OCT 3 demonstrates elevation of the photoreceptor layer by the material and supports the previous hypothesis that the material is located between the photoreceptor and the retinal pigment epithelium layer.
It is estimated that between 35% and 74% of all human genes can undergo alternative splicing. Currently, the most efficient methods for large-scale detection of alternative splicing use expressed sequence tags (ESTs) or microarray analysis. As these methods merely sample the transcriptome, splice variants that do not appear in deeply sampled tissues have a low probability of being detected. We present a new method by which we can predict that an internal exon is skipped (namely whether it is a cassette-exon) merely based on its naked genomic sequence and on the sequence of its mouse ortholog. No other data, such as ESTs, are required for the prediction. Using our method, which was experimentally validated, we detected hundreds of novel splice variants that were not detectable using ESTs. We show that a substantial fraction of the splice variants in the human genome could not be identified through current human EST or cDNA data.
We have determined the kinetics of up-regulation of the homologous recombination gene RAD51, one of the genes induced following DNA damage in isogenic haploid DNA repair-deficient mutants of Saccharomyces cerevisiae, using treatment with the DNA crosslinking agent 8-methoxypsoralen. We show that RAD51 is up-regulated concomitantly, although independently, with a shift from the G1 cell cycle phase to G2/M arrest. This up-regulation is absent in homologous recombination repair-deficient mutants and increased in mutants deficient in nucleotide excision repair and pol(zeta)-dependent translesion synthesis. We demonstrate that the Rad53-dependent DNA damage signal transduction cascade is active in RAD51 non-inducing mutants. However, when independently eliminated, it too abolishes RAD51 up-regulation. We present a model in which RAD51 up-regulation requires two signals: one depending on the Rad53-dependent DNA damage signal transduction cascade and the other on homologous recombination repair.