The production of 2-deoxyribonolactones (C1'-oxidation product), C4'-oxidized abasic sites and C5'-carbonyl terminated strand scission products was investigated in complexes of double-stranded DNA with protamine, poly-L-lysine and spermine exposed to X-ray radiation. The lesions were quantified by high-performance liquid chromatography through the release of the corresponding low-molecular-weight products 5-methylenefuran-2(5H)-one, N-(2'-hydroxy-ethyl)-5-methylene-D-pyrrolin-2-one and furfural, respectively. All binders were found to increase the relative yield of C1' oxidation up to 40% of the total 2-deoxyribose damage through the indirect effect versus approximately 18% typically found in homogeneous solutions by the same technique. On the contrary, the yield of C5'-oxidation was found to be suppressed almost completely, while in homogeneous solutions it constituted approximately 14% of the total. The observed change in end product distribution is attributed to free valence transfer to and from the complexing agent, although the mechanisms associated with this process remain unclear.
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http://dx.doi.org/10.1667/RR15396.1 | DOI Listing |
EClinicalMedicine
August 2024
Division of Cancer Prevention and Population Sciences, Department of Health Services Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Background: Lung cancer screening recommendations employ annual frequency for eligible individuals, despite evidence that it may not be universally optimal. The impact of imposing a structure on the screening frequency remains unknown. The ENGAGE framework, a validated framework that offers fully dynamic, analytically optimal, personalised lung cancer screening recommendations, could be used to assess the impact of screening structure on the effectiveness and efficiency of lung cancer screening.
View Article and Find Full Text PDFTo determine if the use of theory, data and end-user perspectives to guide an adaptation of the Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) yields better outcomes and improves the "fit" of TranS-C to community mental health centers (CMHCs), relative to the standard version. Ten counties in California were cluster-randomized by county to Adapted or Standard TranS-C. Within each county, adults who exhibited sleep and circadian dysfunction and serious mental illness (SMI) were randomized to immediate TranS-C or Usual Care followed by Delayed Treatment with TranS-C (UC-DT).
View Article and Find Full Text PDFTyrosine phosphorylation is an important post-translational modification that regulates many biochemical signaling networks in multicellular organisms. To date, 46,000 tyrosines have been observed in human proteins, but relatively little is known about the function and regulation of most of these sites. A major challenge has been producing recombinant phospho-proteins in order to test the effects of phosphorylation.
View Article and Find Full Text PDFWhile the genetic paradigm of cancer etiology has proven powerful, it remains incomplete as evidenced by the widening spectrum of non-cancer cell-autonomous "hallmarks" of cancer. Studies have demonstrated the commonplace presence of high oncogenic mutational burdens in homeostatically-stable epithelia. Hence, the presence of driver mutations alone does not result in cancer.
View Article and Find Full Text PDFOphthalmic Genet
January 2025
Department of Ophthalmology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Introduction: Due to the recent advent of gene-targeted retinal therapies, the clinical value of high-yield genetic testing for inherited retinal dystrophies (IRDs) has increased considerably. However, diagnostic yield is limited by the reported patient populations in allele frequency databases. This study aimed to determine the effect of race and ethnicity on diagnostic yield in IRDs.
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