Mechanisms of helicase activated DNA end resection in bacteria

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Mechanics of linear microcracking in trabecular bone

Microcracking in trabecular bone is responsible both for the mechanical degradation and remodeling of the trabecular bone tissue. Recent results on trabecular bone mechanics have demonstrated that bone tissue microarchitecture, tissue elastic heterogeneity and tissue-level mechanical anisotropy all should be considered to obtain detailed information on the mechanical stress state. The present study investigated the influence of tissue microarchitecture, tissue heterogeneity in elasticity and material separation properties and tissue-level anisotropy on the microcrack formation process. Microscale bone models were executed with the extended finite element method. It was demonstrated that anisotropy and heterogeneity of the bone tissue contribute significantly to bone tissue toughness and the resistance of trabecular bone to microcrack formation. The compressive strain to microcrack initiation was computed to increase by a factor of four from an assumed homogeneous isotropic tissue to an assumed anisotropic heterogenous tissue.     

Schizosaccharomyces pombe KAT5 contributes to resection and repair of a DNA double-strand break

Chromatin remodeling is essential for effective repair of a DNA double-strand break (DSB). KAT5 (Schizosaccharomyces pombe Mst1, human TIP60) is a MYST family histone acetyltransferase conserved from yeast to humans that coordinates various DNA damage response activities at a DNA DSB, including histone remodeling and activation of the DNA damage checkpoint. In S. pombe, mutations in mst1⁺ causes sensitivity to DNA damaging drugs. Here we show that Mst1 is recruited to DSBs. Mutation of mst1⁺ disrupts recruitment of repair proteins and delays resection. These defects are partially rescued by deletion of pku70, which has been previously shown to antagonize repair by homologous recombination (HR). These phenotypes of mst1 are similar to pht1-4KR, a nonacetylatable form of histone variant H2A.Z, which has been proposed to affect resection. Our data suggest that Mst1 functions to direct repair of DSBs toward HR pathways by modulating resection at the DSB.     

PARylation of BRCA1 limits DNA break resection through BRCA2 and EXO1

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RNA-DNA hybrids prevent resection at dysfunctional telomeres

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Sequence and chromatin features guide DNA double-strand break resection initiation

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Surgical resection as a predictor of cancer-specific survival by stage at diagnosis and cancer type,United States, 2006–2015

BackgroundWhen solid tumors are amenable to definitive resection, clinical outcomes are generally superior to when those tumors are inoperable. However, the population-level cancer survival benefit of eligibility for surgery by cancer stage has not yet been quantified.MethodsUsing Surveillance, Epidemiology and End Results data allowing us to identify patients who were deemed eligible for and received surgical resection, we examined the stage-specific association of surgical resection with 12-year cancer-specific survival. The 12-year endpoint was selected to maximize follow-up time and thereby minimize the influence of lead time bias.ResultsAcross a variety of solid tumor types, earlier stage at diagnosis allowed for surgical intervention at a much higher rate than later-stage diagnosis. At every stage, surgical intervention was associated with a substantially higher rate of 12-year cancer-specific survival, with absolute differences of up to 51% for stage I, 51% for stage II, and 44% for stage III cancer, and stage-specific mortality relative risks of 3.6, 2.4, and 1.7, respectively.ConclusionsDiagnosis of solid cancers in early stages often enables surgical resection, which reduces the risk of death from cancer. Receipt of surgical resection is an informative endpoint that is strongly associated with long-term cancer-specific survival at every stage.     

Effects of whole-body vibration on bone properties in aged rats

Objective:This study aimed to explore optimal conditions of whole-body vibration (WBV) for improving bone properties in aged rats.Methods:Eighty-week-old rats were divided into baseline control (BC), age-matched control (CON) and experimental groups, which underwent WBV (0.5 g) at various frequencies (15, 30, 45, 60 or 90 Hz) or WBV (45 Hz) with various magnitudes (0.3, 0.5, 0.7 or 1.0 g) for 7 weeks. After interventions, femur bone size, bone mechanical strength and circulating bone formation/resorption markers were measured, and trabecular bone microstructure (TBMS) and cortical bone geometry (CBG) of femurs were analyzed by micro-CT.Results:Several TBMS parameters and trabecular bone mineral content were significantly lower in the 15 Hz WBV (0.5 g) group than in the CON group, suggesting damage to trabecular bone. On the other hand, although frequency/magnitude of WBV did not influence any CBG parameters, the 0.7 g and 1.0 g WBV (45 Hz) group showed an increase in tissue mineral density of cortical bone compared with the BC and CON groups, suggesting the possibility of improving cortical bone properties.Conclusion:Based on these findings, it should be noted that WBV conditions are carefully considered when applied to elderly people.