Developing Single-Molecule TPM Experiments for Direct Observation of Successful RecA-Mediated Strand Exchange Reaction

RecA recombinases play a central role in homologous recombination. Once assembled on single-stranded (ss) DNA, RecA nucleoprotein filaments mediate the pairing of homologous DNA sequences and strand exchange processes. We have designed two experiments based on tethered particle motion (TPM) to investigate the fates of the invading and the outgoing strands during E. coli RecA-mediated pairing and strand exchange at the single-molecule level in the absence of force. TPM experiments measure the tethered bead Brownian motion indicative of the DNA tether length change resulting from RecA binding and dissociation. Experiments with beads labeled on either the invading strand or the outgoing strand showed that DNA pairing and strand exchange occurs successfully in the presence of either ATP or its non-hydrolyzable analog, ATPγS. The strand exchange rates and efficiencies are similar under both ATP and ATPγS conditions. In addition, the Brownian motion time-courses suggest that the strand exchange process progresses uni-directionally in the 5′-to-3′ fashion, using a synapse segment with a wide and continuous size distribution

Computational Modelling of Genome-Side Transcription Assembly Networks Using a Fluidics Analogy

Understanding how a myriad of transcription regulators work to modulate mRNA output at thousands of genes remains a fundamental challenge in molecular biology. Here we develop a computational tool to aid in assessing the plausibility of gene regulatory models derived from genome-wide expression profiling of cells mutant for transcription regulators. mRNA output is modelled as fluid flow in a pipe lattice, with assembly of the transcription machinery represented by the effect of valves. Transcriptional regulators are represented as external pressure heads that determine flow rate. Modelling mutations in regulatory proteins is achieved by adjusting valves' on/off settings. The topology of the lattice is designed by the experimentalist to resemble the expected interconnection between the modelled agents and their influence on mRNA expression. Users can compare multiple lattice configurations so as to find the one that minimizes the error with experimental data. This computational model provides a means to test the plausibility of transcription regulation models derived from large genomic data sets

Impact of statins and ACE inhibitors on mortality after COPD exacerbations

<p>Abstract</p> <p>Background</p> <p>The purpose of our study was to examine the association of prior outpatient use of statins and angiotensin converting enzyme (ACE) inhibitors on mortality for subjects ≥ 65 years of age hospitalized with acute COPD exacerbations.</p> <p>Methods</p> <p>We conducted a retrospective national cohort study using Veterans Affairs administrative data including subjects ≥65 years of age hospitalized with a COPD exacerbation. Our primary analysis was a multilevel model with the dependent variable of 90-day mortality and hospital as a random effect, controlling for preexisting comorbid conditions, demographics, and other medications prescribed.</p> <p>Results</p> <p>We identified 11,212 subjects with a mean age of 74.0 years, 98% were male, and 12.4% of subjects died within 90-days of hospital presentation. In this cohort, 20.3% of subjects were using statins, 32.0% were using ACE inhibitors or angiotensin II receptor blockers (ARB). After adjusting for potential confounders, current statin use (odds ratio 0.51, 95% confidence interval 0.40–0.64) and ACE inhibitor/ARB use (0.55, 0.46–0.66) were significantly associated with decreased 90-day mortality.</p> <p>Conclusion</p> <p>Use of statins and ACE inhibitors prior to admission is associated with decreased mortality in subjects hospitalized with a COPD exacerbation. Randomized controlled trials are needed to examine whether the use of these medications are protective for those patients with COPD exacerbations.</p

Development of a biomechanical energy harvester

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Assessing Quality of Care of Elderly Patients Using the ACOVE Quality Indicator Set: A Systematic Review

Background: Care of the elderly is recognized as an increasingly important segment of health care. The Assessing Care Of Vulnerable Elderly (ACOVE) quality indicators (QIs) were developed to assess and improve the care of elderly patients. Objectives: The purpose of this review is to summarize studies that assess the quality of care using QIs from or based on ACOVE, in order to evaluate the state of quality of care for the reported conditions. Methods: We systematically searched MEDLINE, EMBASE and CINAHL for English-language studies indexed by February 2010. Articles were included if they used any ACOVE QIs, or adaptations thereof, for assessing the quality of care. Included studies were analyzed and relevant information was extracted. We summarized the results of these studies, and when possible generated an overall conclusion about the quality of care as measured by ACOVE for each condition, in various settings, and for each QI. Results: Seventeen studies were included with 278 QIs (original, adapted or newly developed). The quality scores showed large variation between and within conditions. Only a few conditions showed a stable pass rate range over multiple studies. Overall, pass rates for dementia (interquartile range (IQR): 11%-35%), depression (IQR: 27%-41%), osteoporosis (IQR: 34%-43%) and osteoarthritis (IQR: 29-41%) were notably low. Medication management and use (range: 81%-90%), hearing loss (77%-79%) and continuity of care (76%-80%) scored higher than other conditions. Out of the 278 QIs, 141 (50%) had mean pass rates below 50% and 121 QIs (44%) had pass rates above 50%. Twenty-three percent of the QIs scored above 75%, and 16% scored below 25%. Conclusions: Quality of care per condition varies markedly across studies. Although there has been much effort in improving the care for elderly patients in the last years, the reported quality of care according to the ACOVE indicators is still relatively lo

The Association between ATM IVS 22-77 T>C and Cancer Risk: A Meta-Analysis

BACKGROUND AND OBJECTIVES: It has become increasingly clear that ATM (ataxia-telangiectasia-mutated) safeguards genome stability, which is a cornerstone of cellular homeostasis, and ATM IVS 22-77 T>C affects the normal activity of ATM proteins. However, the association between the ATM IVS 22-77 T>C genetic variant and cancer risk is controversial. Therefore, we conducted a systematic meta-analysis to estimate the overall cancer risk associated with the polymorphism and to quantify any potential between-study heterogeneity. METHODS: A total of nine studies including 4,470 cases and 4,862 controls were analyzed for ATM IVS 22-77 T>C association with cancer risk in this meta-analysis. Heterogeneity among articles and their publication bias were also tested. RESULTS: Our results showed that no association reached the level of statistical significance in the overall risk. Interestingly, in the stratified analyses, we observed an inverse relationship in lung and breast cancer. CONCLUSION: Further functional research on the ATM mechanism should be performed to explain the inconsistent results in different cancer types