Stony Brook University

About: Stony Brook University is a education organization based out in Stony Brook, New York, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 32534 authors who have published 68218 publications receiving 3035131 citations. The organization is also known as: State University of New York at Stony Brook & SUNY Stony Brook.

Identification of Cd36 ( Fat ) as an insulin-resistance gene causing defective fatty acid and glucose metabolism in hypertensive rats

Abstract: The human insulin-resistance syndromes, type 2 diabetes, obesity, combined hyperlipidaemia and essential hypertension, are complex disorders whose genetic basis is unknown. The spontaneously hypertensive rat (SHR) is insulin resistant and a model of these human syndromes. Quantitative trait loci (QTLs) for SHR defects in glucose and fatty acid metabolism, hypertriglyceridaemia and hypertension map to a single locus on rat chromosome 4. Here we combine use of cDNA microarrays, congenic mapping and radiation hybrid (RH) mapping to identify a defective SHR gene, Cd36 (also known as Fat, as it encodes fatty acid translocase), at the peak of linkage to these QTLs. SHR Cd36 cDNA contains multiple sequence variants, caused by unequal genomic recombination of a duplicated ancestral gene. The encoded protein product is undetectable in SHR adipocyte plasma membrane. Transgenic mice overexpressing Cd36 have reduced blood lipids. We conclude that Cd36 deficiency underlies insulin resistance, defective fatty acid metabolism and hypertriglyceridaemia in SHR and may be important in the pathogenesis of human insulin-resistance syndromes.

Risk factors for open-angle glaucoma. The Barbados Eye Study.

Abstract: Objective: To evaluate risk factors for open-angle glaucoma among black participants in the Barbados Eye Study. Design: Population-based study of demographic, medical, ocular, familial, and other factors possibly related to open-angle glaucoma. Setting and Participants: The Barbados Eye Study included 4709 Barbados residents identified by a simple random sample of Barbadian-born citizens, 40 to 84 years of age; participation was 84%. This report is based on the 4314 black participants examined at the study site; 302 (7%) met the Barbados Eye Study criteria for open-angle glaucoma. Data Collection: A standardized protocol included applanation tonometry, Humphrey perimetry, fundus photography, blood pressure, anthropometry, and an interview. An ophthalmologic examination was performed for participants who met specific criteria. Main Outcome Measures: Open-angle glaucoma was defined by the presence of both characteristic visual field defects and optic disc damage. Association of open-angle glaucoma with specific factors was evaluated in logistic regression analyses. Results: Age, male gender, high intraocular pressure, and family history of open-angle glaucoma were major risk factors; the latter association was stronger in men than women. Lean body mass and cataract history were the only other factors related to open-angle glaucoma. Although hypertension and diabetes were common in Barbados Eye Study participants, they were unrelated to the prevalence of open-angle glaucoma. However, associations were found with low diastolic blood pressure-intraocular pressure differences and low systolic and diastolic blood pressure/intraocular pressure ratios. Conclusions: In the Barbados Eye Study black population, persons most likely to have open-angle glaucoma were older men and had a family history of open-angle glaucoma, high intraocular pressure, lean body mass, and cataract history. These results suggest the importance of possible genetic or familial factors in open-angle glaucoma. The role of vascular risk factors is consistent with our finding of low blood pressure to intraocular pressure relationships, but the results could be explained by the high intraocular pressure in open-angle glaucoma.

DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1

Abstract: A single double-strand break (DSB) induced by HO endonuclease triggers both repair by homologous recombination and activation of the Mec1-dependent DNA damage checkpoint in budding yeast. Here we report that DNA damage checkpoint activation by a DSB requires the cyclin-dependent kinase CDK1 (Cdc28) in budding yeast. CDK1 is also required for DSB-induced homologous recombination at any cell cycle stage. Inhibition of homologous recombination by using an analogue-sensitive CDK1 protein results in a compensatory increase in non-homologous end joining. CDK1 is required for efficient 5' to 3' resection of DSB ends and for the recruitment of both the single-stranded DNA-binding complex, RPA, and the Rad51 recombination protein. In contrast, Mre11 protein, part of the MRX complex, accumulates at unresected DSB ends. CDK1 is not required when the DNA damage checkpoint is initiated by lesions that are processed by nucleotide excision repair. Maintenance of the DSB-induced checkpoint requires continuing CDK1 activity that ensures continuing end resection. CDK1 is also important for a later step in homologous recombination, after strand invasion and before the initiation of new DNA synthesis.