Intrinsic uncoupling of cytochrome c oxidase may cause the maternally inherited mitochondrial diseases MELAS and LHON

AbstractMutations in the human mtDNA gene encoding subunit III of cytochrome c oxidase (CO) have been reported to cause MELAS and LHON. Paracoccus denitrificans cells expressing substitutions homologous to these MELAS- and LHON-causing mutations had lower growth yield than wild type cells and lower efficiency of proton pumping by CO (e.g. lower H+/e− ratio and lower ΔΨ), but had similar CO activity. These results indicate that both substitutions (F263L>A212T) cause intrinsic uncoupling, which may be the direct cause of the diseases. These results also suggest that subunit III is involved in proton pumping

A Cross-Country Analysis of Household Response to Adult Mortality in Rural Sub-Saharan Africa: Implications for HIV/AIDS Mitigation and Rural Development Policies

Community/Rural/Urban Development, Consumer/Household Economics, Downloads November 2008 - July 2007: 6,

A Cross-Country Analysis of Household Responses to Adult Mortality in Rural Sub-Saharan Africa: Implications For HIV/AIDS Mitigation And Rural Development Policies.

This paper summarizes and synthesizes across the results of a set of country studies on the effects of prime-age adult mortality on rural households in Kenya, Malawi, Mozambique, Rwanda, and Zambia. Each study is based on large representative rural household surveys. These findings have implications for the design of efforts to mitigate some of the most important effects of rural adult mortality, and for key development policies and priorities.HIV/AIDS, sub-Saharan Africa, mortality, Community/Rural/Urban Development, Health Economics and Policy, Downloads July 2008 - July 2009: 21, I11,

Simulated 50 % radiation dose reduction in coronary CT angiography using adaptive iterative dose reduction in three-dimensions (AIDR3D)

To compare the image quality of coronary CT angiography (CTA) studies between standard filtered back projection (FBP) and adaptive iterative dose reduction in three-dimensions (AIDR3D) reconstruction using CT noise additional software to simulate reduced radiation exposure. Images from 93 consecutive clinical coronary CTA studies were processed utilizing standard FBP, FBP with 50 % simulated dose reduction (FBP50 %), and AIDR3D with simulated 50 % dose reduction (AIDR50 %). Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured within 5 regions-of-interest, and image quality for each reconstruction strategy was assessed by two independent readers using a 4-point scale. Compared to FBP, the SNR measured from the AIDR50 % images was similar or higher (airway: 38.3 ± 12.7 vs. 38.5 ± 14.5, p = 0.81, fat: 5.5 ± 1.9 vs. 5.4 ± 2.0, p = 0.20, muscle: 3.2 ± 1.2 vs. 3.1 ± 1.3, p = 0.38, aorta: 22.6 ± 9.4 vs. 20.2 ± 9.7, p < 0.0001, liver: 2.7 ± 1.0 vs. 2.3 ± 1.1, p < 0.0001), while the SNR of the FBP50 % images were all lower (p values < 0.0001). The CNR measured from AIDR50 % images was also higher than that from the FBP images for the aorta relative to muscle (20.5 ± 9.0 vs. 18.3 ± 9.2, p < 0.0001). The interobserver agreement in the image quality score was excellent (κ = 0.82). The quality score was significantly higher for the AIDR50 % images compared to the FBP images (3.6 ± 0.6 vs. 3.3 ± 0.7, p = 0.004). Simulated radiation dose reduction applied to clinical coronary CTA images suggests that a 50 % reduction in radiation dose can be achieved with adaptive iterative dose reduction software with image quality that is at least comparable to images acquired at standard radiation exposure and reconstructed with filtered back projection

Is telomere length socially patterned? Evidence from the West of Scotland Twenty-07 study

Lower socioeconomic status (SES) is strongly associated with an increased risk of morbidity and premature mortality, but it is not known if the same is true for telomere length, a marker often used to assess biological ageing. The West of Scotland Twenty-07 Study was used to investigate this and consists of three cohorts aged approximately 35 (N = 775), 55 (N = 866) and 75 years (N = 544) at the time of telomere length measurement. Four sets of measurements of SES were investigated: those collected contemporaneously with telomere length assessment, educational markers, SES in childhood and SES over the preceding twenty years. We found mixed evidence for an association between SES and telomere length. In 35-year-olds, many of the education and childhood SES measures were associated with telomere length, i.e. those in poorer circumstances had shorter telomeres, as was intergenerational social mobility, but not accumulated disadvantage. A crude estimate showed that, at the same chronological age, social renters, for example, were nine years (biologically) older than home owners. No consistent associations were apparent in those aged 55 or 75. There is evidence of an association between SES and telomere length, but only in younger adults and most strongly using education and childhood SES measures. These results may reflect that childhood is a sensitive period for telomere attrition. The cohort differences are possibly the result of survival bias suppressing the SES-telomere association; cohort effects with regard different experiences of SES; or telomere possibly being a less effective marker of biological ageing at older ages

Measuring and Understanding the Universe

Revolutionary advances in both theory and technology have launched cosmology into its most exciting period of discovery yet. Unanticipated components of the universe have been identified, promising ideas for understanding the basic features of the universe are being tested, and deep connections between physics on the smallest scales and on the largest scales are being revealed.Comment: 39 pages, 11 figures, 1 table, accepted for publication in Reviews of Modern Physics Colloqui

Excess Mucin Impairs Subglottic Epithelial Host Defense in Mechanically Ventilated Patients

Rationale: Aspiration of infective subglottic secretions causes ventilator-associated pneumonia (VAP) in mechanically ventilated patients. Mechanisms underlying subglottic colonization in critical illness have not been defined, limiting strategies for targeted prevention of VAP. Objectives: To characterize subglottic host defense dysfunction in mechanically ventilated patients in the intensive care unit (ICU). To determine whether subglottic mucin contributes to neutrophil phagocytic impairment and bacterial growth. Methods: Prospective subglottic sampling in mechanically ventilated patients (intubated for four or more days), and newly intubated control patients (intubated for less than 30 minutes). Isolation and culture of primary subglottic epithelial cells from controls. Laboratory analysis of host innate immune defenses. Measurements and Main Results: Twenty-four patients in the ICU and 27 newly intubated control patients were studied. Subglottic ICU samples had significantly reduced microbiological diversity and contained potential respiratory pathogens. The subglottic microenvironment in ICU was characterized by neutrophilic inflammation, significantly increased pro-inflammatory cytokines and neutrophil proteases, and altered physical properties of subglottic secretions, including accumulation of mucins. Subglottic mucin from ICU patients impaired the capacity of neutrophils to phagocytose and kill bacteria. Phagocytic function was reversible upon treatment with a mucolytic agent. Subglottic mucus promoted growth and invasion of bacterial pathogens in a novel air-liquid interface model of primary human subglottic epithelium. Conclusions: Mechanical ventilation in ICU is characterized by substantial mucin secretion and neutrophilic inflammation. Mucin impairs neutrophil dysfunction and promotes bacterial growth. Mucolytic agents reverse mucin-mediated neutrophil dysfunction. Enhanced mucus disruption and removal has potential to augment preventive benefits of subglottic drainage