For MutY, It's All about the OG

MutY and its human ortholog, MUTYH, repair a specific form of DNA damage: adenine mis-paired with the oxidatively modified form of deoxyguanosine, 8-oxo-7,8-dihydro-2′-deoxyguanosine. In a recent issue of Chemistry & Biology, Brinkmeyer et al. utilized mutant forms of MutY to reveal the critical residues in MutY that are required for this selectivity and specificity

Sexual and Psychoemotional Disorders in Male Patients Treated for Prostate Carcinoma

The prostate carcinoma affect the quality of life of most male patients, including in particular their sexual and emotional life. The aim of study was to assess sexual and psychoemotional disorders in male patients diagnosed with prostate carcinoma and receiving cancer treatment. The study’s patients were recruited at the Oncological Hospital in Wieliszew, Poland, between September 2016 and December 2017. The study was performed in 166 male patients diagnosed with prostate cancer. Two standardized questionnaires were used in the study, EORTC QLQ-C30 and QLQ-PR25, for patients with prostate cancer, developed by the European Quality of Life Group. The type and stage of cancer treatments were a significant contributor to feeling tense, worried, depressed, and irritable among the study patients. The stage of treatment, however, caused a negative effect on these parameters. Pretreatment patients declared high or very high satisfaction with their sexual life, while posttreatment patients and those on cancer treatment indicated low sexual satisfaction. However, a feeling of embarrassment during intimate contact as well as erectile disorders correlated both with the type and stage of cancer treatment. Our results show that affected male patients should be offered continuous psychological care, especially those waiting for treatment and those on treatment

XRCC1 and base excision repair balance in response to nitric oxide

Inflammation associated reactive oxygen and nitrogen species (RONs), including peroxynitrite (ONOO−) and nitric oxide (NOradical dot), create base lesions that potentially play a role in the toxicity and large genomic rearrangements associated with many malignancies. Little is known about the role of base excision repair (BER) in removing these endogenous DNA lesions. Here, we explore the role of X-ray repair cross-complementing group 1 (XRCC1) in attenuating RONs-induced genotoxicity. XRCC1 is a scaffold protein critical for BER for which polymorphisms modulate the risk of cancer. We exploited CHO and human glioblastoma cell lines engineered to express varied levels of BER proteins to study XRCC1. Cytotoxicity and the levels of DNA repair intermediates (single-strand breaks; SSB) were evaluated following exposure of the cells to the ONOO− donor, SIN-1, and to gaseous NOradical dot. XRCC1 null cells were slightly more sensitive to SIN-1 than wild-type cells. We used small-scale bioreactors to expose cells to NOradical dot and found that XRCC1-deficient CHO cells were not sensitive. However, using a molecular beacon assay to test lesion removal in vitro, we found that XRCC1 facilitates AAG-initiated excision of two key NOradical dot-induced DNA lesions: 1,N[superscript 6]-ethenoadenine and hypoxanthine. Furthermore, overexpression of AAG rendered XRCC1-deficient cells sensitive to NOradical dot-induced DNA damage. These results show that AAG is a key glycosylase for BER of NOradical dot-induced DNA damage and that XRCC1's role in modulating sensitivity to RONs is dependent upon the cellular level of AAG. This demonstrates the importance of considering the expression of other components of the BER pathway when evaluating the impact of XRCC1 polymorphisms on cancer risk.Massachusetts Institute of Technology. Center for Environmental Health Sciences (NIEHS P30-ES002109)National Institutes of Health (U.S.) (NIH grant P01-CA026731)National Institutes of Health (U.S.) (NIH grant 2-R01-CA079827-05A1)National Institutes of Health (U.S.) (NIH Grant U01-ES016045)National Institutes of Health (U.S.) (NIH Grant GM087798)National Institutes of Health (U.S.) (NIH Grant CA148629)National Institutes of Health (U.S.) (NIH Grant ES019498)National Institutes of Health (U.S.) (Cancer Center Support Grant P30 CA047904

Co-creation and engagement in a DNA integrity cohort study

Abstract Introduction: The partnership between a research community engagement team (CE Team) and a community advisory board (CAB) formed the basis for bidirectional communication in developing resources for participant recruitment in a DNA integrity study. Engaging with a minoritized community, this partnership focused on respect, accessibility, and expanded engagement. Methods: A ten-member CAB, working in two groups defined by meeting time convenience, provided insight and feedback to the CE Team in the creation of recruitment and consent materials, via an iterative design process in which one CAB group reviewed and enhanced materials, and the second group tested and refined them further. The continuous analysis of CE Team notes from CAB meetings captured information needed both for materials refinement and implementation of CAB-suggested activities. Results: The partnership resulted in the co-creation of recruitment and consent materials that facilitated the enrollment of 191 individuals into the study. The CAB encouraged and assisted in expanded engagement inclusive of community leaders. This broader engagement provided information about the DNA integrity study to community decision-makers as well as responded to questions and concerns about the research. The bidirectional communication between the CAB and the CE Team encouraged the researchers to consider topics and research interests related to the current study but also responsive to community concerns. Conclusions: The CAB helped the CE Team develop a better understanding of the language of partnership and respect. In this way, the partnership opened doors for expanded community engagement and effective communication with potential study participants

Input variable selection in time-critical knowledge integration applications: A review, analysis, and recommendation paper

This is the post-print version of the final paper published in Advanced Engineering Informatics. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2013 Elsevier B.V.The purpose of this research is twofold: first, to undertake a thorough appraisal of existing Input Variable Selection (IVS) methods within the context of time-critical and computation resource-limited dimensionality reduction problems; second, to demonstrate improvements to, and the application of, a recently proposed time-critical sensitivity analysis method called EventTracker to an environment science industrial use-case, i.e., sub-surface drilling. Producing time-critical accurate knowledge about the state of a system (effect) under computational and data acquisition (cause) constraints is a major challenge, especially if the knowledge required is critical to the system operation where the safety of operators or integrity of costly equipment is at stake. Understanding and interpreting, a chain of interrelated events, predicted or unpredicted, that may or may not result in a specific state of the system, is the core challenge of this research. The main objective is then to identify which set of input data signals has a significant impact on the set of system state information (i.e. output). Through a cause-effect analysis technique, the proposed technique supports the filtering of unsolicited data that can otherwise clog up the communication and computational capabilities of a standard supervisory control and data acquisition system. The paper analyzes the performance of input variable selection techniques from a series of perspectives. It then expands the categorization and assessment of sensitivity analysis methods in a structured framework that takes into account the relationship between inputs and outputs, the nature of their time series, and the computational effort required. The outcome of this analysis is that established methods have a limited suitability for use by time-critical variable selection applications. By way of a geological drilling monitoring scenario, the suitability of the proposed EventTracker Sensitivity Analysis method for use in high volume and time critical input variable selection problems is demonstrated.E

Open multistate Majorana model

The multistate Majorana model in the presence of dissipation and dephasing is considered. It is proven that increasing the Hilbert space dimension the system becomes more and more fragile to quantum noise. The impossibility to recast the problem in the form of a set of independent spin-$1/2$ problems because of the presence of the noise is pointed out

Gastrointestinal Hyperplasia with Altered Expression of DNA Polymerase β

Background: Altered expression of DNA polymerase β (Pol β) has been documented in a large percentage of human tumors. However, tumor prevalence or predisposition resulting from Pol β over-expression has not yet been evaluated in a mouse model. Methodology/Principal Findings: We have recently developed a novel transgenic mouse model that over-expresses Pol β. These mice present with an elevated incidence of spontaneous histologic lesions, including cataracts, hyperplasia of Brunner's gland and mucosal hyperplasia in the duodenum. In addition, osteogenic tumors in mice tails, such as osteoma and osteosarcoma were detected. This is the first report of elevated tumor incidence in a mouse model of Pol β over-expression. These findings prompted an evaluation of human gastrointestinal tumors with regard to Pol β expression. We observed elevated expression of Pol β in stomach adenomas and thyroid follicular carcinomas, but reduced Pol β expression in esophageal adenocarcinomas and squamous carcinomas. Conclusions/Significance: These data support the hypothesis that balanced and proficient base excision repair protein expression and base excision repair capacity is required for genome stability and protection from hyperplasia and tumor formation