148 research outputs found
Increased RPA1 gene dosage affects genomic stability potentially contributing to 17p13.3 duplication syndrome
A novel microduplication syndrome involving various-sized contiguous duplications in 17p13.3 has recently been described, suggesting that increased copy number of genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features including facial dysmorphism, developmental delay, and autism spectrum disorder. We have previously shown that patient-derived cell lines from individuals with haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR-dependent DNA damage response (DDR). Here, we show that cell lines from patients with duplications specifically incorporating RPA1 exhibit a different although characteristic spectrum of DDR defects including abnormal S phase distribution, attenuated DNA double strand break (DSB)-induced RAD51 chromatin retention, elevated genomic instability, and increased sensitivity to DNA damaging agents. Using controlled conditional over-expression of RPA1 in a human model cell system, we also see attenuated DSB-induced RAD51 chromatin retention. Furthermore, we find that transient over-expression of RPA1 can impact on homologous recombination (HR) pathways following DSB formation, favouring engagement in aberrant forms of recombination and repair. Our data identifies unanticipated defects in the DDR associated with duplications in 17p13.3 in humans involving modest RPA1 over-expression
Effect of an aqueous extract of annatto (Bixa orellana) seeds on lipid profile and biochemical markers of renal and hepatic function in hipercholesterolemic rats
Cell density and solvent are critical parameters affecting formazan evaluation in MTT assay
Comparação do autocuidado entre usuários com hipertensão de serviços da atenção à saúde primária e secundária
Exploring new physics frontiers through numerical relativity
The demand to obtain answers to highly complex problems within strong-field gravity has been met with significant progress in the numerical solution of Einstein's equations - along with some spectacular results - in various setups. We review techniques for solving Einstein's equations in generic spacetimes, focusing on fully nonlinear evolutions but also on how to benchmark those results with perturbative approaches. The results address problems in high-energy physics, holography, mathematical physics, fundamental physics, astrophysics and cosmology
Ocorrência de rota vírus e adeno vírus em crianças de até 11 anos de idade sem sintomatologia de diarréia em Goiânia - GO
Quality of primary health care: an analysis of avoidable hospitalizations in a Minas Gerais county, Brazil
Anemia among indigenous women in Brazil: findings from the First National Survey of Indigenous People’s Health and Nutrition
The effectiveness of a rotavirus vaccine in preventing hospitalizations and deaths presumably due to acute infectious diarrhea in Brazilian children: a quasi-experimental study
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