Cellular Senescence, Mitochondrial Dysfunction, and Their Link to Cardiovascular Disease

Cardiovascular diseases (CVDs), a group of disorders affecting the heart or blood vessels, are the primary cause of death worldwide, with an immense impact on patient quality of life and disability. According to the World Health Organization, CVD takes an estimated 17.9 million lives each year, where more than four out of five CVD deaths are due to heart attacks and strokes. In the decades to come, an increased prevalence of age-related CVD, such as atherosclerosis, coronary artery stenosis, myocardial infarction (MI), valvular heart disease, and heart failure (HF) will contribute to an even greater health and economic burden as the global average life expectancy increases and consequently the world’s population continues to age. Considering this, it is important to focus our research efforts on understanding the fundamental mechanisms underlying CVD. In this review, we focus on cellular senescence and mitochondrial dysfunction, which have long been established to contribute to CVD. We also assess the recent advances in targeting mitochondrial dysfunction including energy starvation and oxidative stress, mitochondria dynamics imbalance, cell apoptosis, mitophagy, and senescence with a focus on therapies that influence both and therefore perhaps represent strategies with the most clinical potential, range, and utility

Which older people decline participation in a primary care trial of physical activity and why: insights from a mixed methods approach

This article is available through the Brunel Open Access Publishing Fund. Copyright 2014 Rogers et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Physical activity is of vital importance to older peoples’ health. Physical activity intervention studies with older people often have low recruitment, yet little is known about non-participants. Methods: Patients aged 60–74 years from three UK general practices were invited to participate in a nurse-supported pedometer-based walking intervention. Demographic characteristics of 298 participants and 690 non-participants were compared. Health status and physical activity of 298 participants and 183 non-participants who completed a survey were compared using age, sex adjusted odds ratios (OR) (95% confidence intervals). 15 non-participants were interviewed to explore perceived barriers to participation. Results: Recruitment was 30% (298/988). Participants were more likely than non-participants to be female (54% v 47%; p = 0.04) and to live in affluent postcodes (73% v 62% in top quintile; p < 0.001). Participants were more likely than non-participants who completed the survey to have an occupational pension OR 2.06 (1.35-3.13), a limiting longstanding illness OR 1.72 (1.05-2.79) and less likely to report being active OR 0.55 (0.33-0.93) or walking fast OR 0.56 (0.37-0.84). Interviewees supported general practice-based physical activity studies, particularly walking, but barriers to participation included: already sufficiently active, reluctance to walk alone or at night, physical symptoms, depression, time constraints, trial equipment and duration. Conclusion: Gender and deprivation differences suggest some selection bias. However, trial participants reported more health problems and lower activity than non-participants who completed the survey, suggesting appropriate trial selection in a general practice population. Non-participant interviewees indicated that shorter interventions, addressing physical symptoms and promoting confidence in pursuing physical activity, might increase trial recruitment and uptake of practice-based physical activity endeavours.The National Institute for Health Research (NIHR) under its Research for Patient Benefit Programme (Grant Reference Number PB-PG-0909-20055)

Effects of drying and pretreatment on the nutritional and functional quality of raisins

The close relationship between the consumption of fruits and health status stems from the nutritional and non-nutritional compounds found in fruits which play a key role in the prevention of different diseases. However, fruit processing and storage greatly affect fruit compounds. The aim of the present work was to study the influence of processing on the stability of macro and micronutrients present in grapes, with a view to recommending products that provide the highest nutritional quality and the best health conditions. The study focused on fruit dehydration treatments. Conventional and microwave-assisted air-drying processes were used to obtain raisins. Dehydration caused a decrease of all grape compounds studied excluding total phenols. Moreover, compared to conventional processing, microwave-assisted drying produced greater losses of ascorbic acid in the grape and increased pectin solubilization with a consequent change in texture. However the microwave-dehydrated samples showed higher antioxidant activity. © 2011 The Institution of Chemical Engineers.The translation of this paper was funded by the Universidad Politecnica de Valencia.Carranza Concha, J.; Benlloch Tinoco, M.; Camacho Vidal, MM.; Martínez Navarrete, N. (2012). Effects of drying and pretreatment on the nutritional and functional quality of raisins. Food and Bioproducts Processing. 90(2):243-248. https://doi.org/10.1016/j.fbp.2011.04.002S24324890

Scaling properties of protein family phylogenies

One of the classical questions in evolutionary biology is how evolutionary processes are coupled at the gene and species level. With this motivation, we compare the topological properties (mainly the depth scaling, as a characterization of balance) of a large set of protein phylogenies with a set of species phylogenies. The comparative analysis shows that both sets of phylogenies share remarkably similar scaling behavior, suggesting the universality of branching rules and of the evolutionary processes that drive biological diversification from gene to species level. In order to explain such generality, we propose a simple model which allows us to estimate the proportion of evolvability/robustness needed to approximate the scaling behavior observed in the phylogenies, highlighting the relevance of the robustness of a biological system (species or protein) in the scaling properties of the phylogenetic trees. Thus, the rules that govern the incapability of a biological system to diversify are equally relevant both at the gene and at the species level.Comment: Replaced with final published versio

Unique and conserved MicroRNAs in wheat chromosome 5D revealed by next-generation sequencing

MicroRNAs are a class of short, non-coding, single-stranded RNAs that act as post-transcriptional regulators in gene expression. miRNA analysis of Triticum aestivum chromosome 5D was performed on 454 GS FLX Titanium sequences of flow sorted chromosome 5D with a total of 3,208,630 good quality reads representing 1.34x and 1.61x coverage of the short (5DS) and long (5DL) arms of the chromosome respectively. In silico and structural analyses revealed a total of 55 miRNAs; 48 and 42 miRNAs were found to be present on 5DL and 5DS respectively, of which 35 were common to both chromosome arms, while 13 miRNAs were specific to 5DL and 7 miRNAs were specific to 5DS. In total, 14 of the predicted miRNAs were identified in wheat for the first time. Representation (the copy number of each miRNA) was also found to be higher in 5DL (1,949) compared to 5DS (1,191). Targets were predicted for each miRNA, while expression analysis gave evidence of expression for 6 out of 55 miRNAs. Occurrences of the same miRNAs were also found in Brachypodium distachyon and Oryza sativa genome sequences to identify syntenic miRNA coding sequences. Based on this analysis, two other miRNAs: miR1133 and miR167 were detected in B. distachyon syntenic region of wheat 5DS. Five of the predicted miRNA coding regions (miR6220, miR5070, miR169, miR5085, miR2118) were experimentally verified to be located to the 5D chromosome and three of them : miR2118, miR169 and miR5085, were shown to be 5D specific. Furthermore miR2118 was shown to be expressed in Chinese Spring adult leaves. miRNA genes identified in this study will expand our understanding of gene regulation in bread wheat

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Health status and lifestyle factors as predictors of depression in middle-aged and elderly Japanese adults: a seven-year follow-up of the Komo-Ise cohort study

<p>Abstract</p> <p>Background</p> <p>Depression is a common mental disorder. Several studies suggest that lifestyle and health status are associated with depression. However, only a few large-scale longitudinal studies have been conducted on this topic.</p> <p>Methods</p> <p>The subjects were middle-aged and elderly Japanese adults between the ages of 40 and 69 years. A total of 9,650 respondents completed questionnaires for the baseline survey and participated in the second wave of the survey, which was conducted 7 years later. We excluded those who complained of depressive symptoms in the baseline survey and analyzed data for the remaining 9,201 individuals. In the second-wave survey, the DSM-12D was used to determine depression. We examined the risks associated with health status and lifestyle factors in the baseline survey using a logistic regression model.</p> <p>Results</p> <p>An age-adjusted analysis showed an increased risk of depression in those who had poor perceived health and chronic diseases in both sexes. In men, those who were physically inactive also had an increased risk of depression. In women, the analysis also showed an increased risk of depression those with a BMI of 25 or more, in those sleeping 9 hours a day or more and who were current smokers. A multivariate analysis showed that increased risks of depression still existed in men who had chronic diseases and who were physically inactive, and in women who had poor perceived health and who had a BMI of 25 or more.</p> <p>Conclusions</p> <p>These results suggest that lifestyle and health status are risk factors for depression. Having a chronic disease and physical inactivity were distinctive risk factors for depression in men. On the other hand, poor perceived health and a BMI of 25 or more were distinctive risk factors for depression in women. Preventive measures for depression must therefore take gender into account.</p

Bottom-up assembly of metallic germanium

Extending chip performance beyond current limits of miniaturisation requires new materials and functionalities that integrate well with the silicon platform. Germanium fits these requirements and has been proposed as a high-mobility channel material, a light emitting medium in silicon-integrated lasers, and a plasmonic conductor for bio-sensing. Common to these diverse applications is the need for homogeneous, high electron densities in three-dimensions (3D). Here we use a bottom-up approach to demonstrate the 3D assembly of atomically sharp doping profiles in germanium by a repeated stacking of two-dimensional (2D) high-density phosphorus layers. This produces high-density (1019 to 1020 cm-3) low-resistivity (10-4Ω ∙ cm) metallic germanium of precisely defined thickness, beyond the capabilities of diffusion-based doping technologies. We demonstrate that free electrons from distinct 2D dopant layers coalesce into a homogeneous 3D conductor using anisotropic quantum interference measurements, atom probe tomography, and density functional theory

The association of patient trust and self-care among patients with diabetes mellitus

BACKGROUND: Diabetes requires significant alterations to lifestyle and completion of self management tasks to obtain good control of disease. The objective of this study was to determine if patient trust is associated with reduced difficulty and hassles in altering lifestyle and completing self care tasks. METHODS: A cross-sectional telephone survey and medical record review was performed to measure patient trust and difficulty in completing diabetes tasks among 320 medically underserved patients attending diabetes programs in rural North Carolina, USA. Diabetes tasks were measured three ways: perceived hassles of diabetic care activities, difficulty in completing diabetes-related care activities, and a global assessment of overall ability to complete diabetes care activities. The association of patient trust with self-management was examined after controlling for patient demographics, physical functioning, mental health and co-morbidities. RESULTS: Level of patient trust was high (median 22, possible max 25). Higher trust levels were associated with lower levels of hassles (p = 0.006) and lower difficulty in completing care activities (p = 0.001). Patients with higher trust had better global assessments of overall ability to complete diabetes care activities (p < 0.0001). CONCLUSION: Higher patient trust in physicians is associated with reduced difficulty in completing disease specific tasks by patients. Further studies are needed to determine the causal relationship of this association, the effect of trust on other outcomes, and the potential modifiability of trus