Economy of Operon Formation: Cotranscription Minimizes Shortfall in Protein Complexes

Genes of prokaryotes and Archaea are often organized in cotranscribed groups, or operons. In contrast, eukaryotic genes are generally transcribed independently. Here we show that there is a substantial economic gain for the cell to cotranscribe genes encoding protein complexes because it synchronizes the fluctuations, or noise, in the levels of the different components. This correlation substantially reduces the shortfall in production of the complex. This benefit is relatively large in small cells such as bacterial cells, in which there are few mRNAs and proteins per cell, and is diminished in larger cells such as eukaryotic cells

Cohort profile: the avon longitudinal study of parents and children: ALSPAC mothers cohort

The Avon Longitudinal Study of Children and Parents (ALSPAC) was established to understand how genetic and environmental characteristics influence health and development in parents and children. All pregnant women resident in a defined area in the South West of England, with an expected date of delivery between 1st April 1991 and 31st December 1992, were eligible and 13 761 women (contributing 13 867 pregnancies) were recruited. These women have been followed over the last 19–22 years and have completed up to 20 questionnaires, have had detailed data abstracted from their medical records and have information on any cancer diagnoses and deaths through record linkage. A follow-up assessment was completed 17–18 years postnatal at which anthropometry, blood pressure, fat, lean and bone mass and carotid intima media thickness were assessed, and a fasting blood sample taken. The second follow-up clinic, which additionally measures cognitive function, physical capability, physical activity (with accelerometer) and wrist bone architecture, is underway and two further assessments with similar measurements will take place over the next 5 years. There is a detailed biobank that includes DNA, with genome-wide data available on >10 000, stored serum and plasma taken repeatedly since pregnancy and other samples; a wide range of data on completed biospecimen assays are available. Details of how to access these data are provided in this cohort profile

Theory of periodic swarming of bacteria: application to Proteus mirabilis

The periodic swarming of bacteria is one of the simplest examples for pattern formation produced by the self-organized collective behavior of a large number of organisms. In the spectacular colonies of Proteus mirabilis (the most common species exhibiting this type of growth) a series of concentric rings are developed as the bacteria multiply and swarm following a scenario periodically repeating itself. We have developed a theoretical description for this process in order to get a deeper insight into some of the typical processes governing the phenomena in systems of many interacting living units. All of our theoretical results are in excellent quantitative agreement with the complete set of available observations.Comment: 11 pages, 8 figure

Molecular Distributions in Gene Regulatory Dynamics

We show how one may analytically compute the stationary density of the distribution of molecular constituents in populations of cells in the presence of noise arising from either bursting transcription or translation, or noise in degradation rates arising from low numbers of molecules. We have compared our results with an analysis of the same model systems (either inducible or repressible operons) in the absence of any stochastic effects, and shown the correspondence between behaviour in the deterministic system and the stochastic analogs. We have identified key dimensionless parameters that control the appearance of one or two steady states in the deterministic case, or unimodal and bimodal densities in the stochastic systems, and detailed the analytic requirements for the occurrence of different behaviours. This approach provides, in some situations, an alternative to computationally intensive stochastic simulations. Our results indicate that, within the context of the simple models we have examined, bursting and degradation noise cannot be distinguished analytically when present alone.Comment: 14 pages, 12 figures. Conferences: "2010 Annual Meeting of The Society of Mathematical Biology", Rio de Janeiro (Brazil), 24-29/07/2010. "First International workshop on Differential and Integral Equations with Applications in Biology and Medicine", Aegean University, Karlovassi, Samos island (Greece), 6-10/09/201

Changes in ponderal index and body mass index across childhood and their associations with fat mass and cardiovascular risk factors at age 15

Background: Little is known about whether associations between childhood adiposity and later adverse cardiovascular health outcomes are driven by tracking of overweight from childhood to adulthood and/or by vascular and metabolic changes from childhood overweight that persist into adulthood. Our objective is to characterise associations between trajectories of adiposity across childhood and a wide range of cardiovascular risk factors measured in adolescence, and explore the extent to which these are mediated by fat mass at age 15. Methods and Findings: Using data from the Avon Longitudinal Study of Parents and Children, we estimated individual trajectories of ponderal index (PI) from 0-2 years and BMI from 2-10 years using random-effects linear spline models (N = 4601). We explored associations between PI/BMI trajectories and DXA-determined total-body fat-mass and cardiovascular risk factors at 15 years (systolic and diastolic blood pressure, fasting LDL-and HDL-cholesterol, triglycerides, C-reactive protein, glucose, insulin) with and without adjustment for confounders. Changes in PI/BMI during all periods of infancy and childhood were associated with greater DXA-determined fat-mass at age 15. BMI changes in childhood, but not PI changes from 0-2 years, were associated with most cardiovascular risk factors in adolescence; associations tended to be strongest for BMI changes in later childhood (ages 8.5-10), and were largely mediated by fat mass at age 15. Conclusion: Changes in PI/BMI from 0-10 years were associated with greater fat-mass at age 15. Greater increases in BMI from age 8.5-10 years are most strongly associated with cardiovascular risk factors at age 15, with much of these associations mediated by fat-mass at this age. We found little evidence supporting previous reports that rapid PI changes in infancy are associated with future cardiovascular risk. This study suggests that associations between early overweight and subsequent adverse cardiovascular health are largely due to overweight children tending to remain overweight

Cardiovascular biomarkers and vascular function during childhood in the offspring of mothers with hypertensive disorders of pregnancy: findings from the Avon Longitudinal Study of Parents and Children

<p><b>Aims:</b> It is uncertain if the higher blood pressure (BP) observed in the offspring of hypertensive pregnancies is an isolated abnormality or one that is accompanied by impaired vascular function and alterations in lipid and inflammation markers that would be indicative of a more general cardiometabolic disturbance of the type observed in the mother during pre-eclampsia.</p> <p><b>Methods and results:</b> In a large UK cohort of maternal-offspring pairs (n = 3537–4654), assessed at age 9–12 years, we examined the associations of maternal gestational hypertension and pre-eclampsia with offspring BP, endothelial function assessed by brachial artery flow-mediated dilatation; arterial stiffness assessed by carotid to radial pulse wave velocity; brachial artery distensibility and BP (vascular outcomes); as well as markers of inflammation, lipids and apolipoproteins A1 and B. Offspring of women with pre-eclampsia or gestational hypertension had higher systolic blood pressure by 2.04 mmHg (95% CI: 1.33, 2.76) and 1.82 mmHg (95% CI: 0.03, 3.62), respectively, and higher diastolic blood pressure by 1.10 mmHg (95% CI: 0.47, 1.73) and 1.26 mmHg (95% CI: −0.32, 2.85), respectively, in analyses adjusted for maternal and offspring body mass index (BMI), offspring dietary sodium intake and other potential confounders. However, we found no associations of either hypertensive disorder of pregnancy with the other vascular outcomes or with inflammatory markers, lipids, and apolipoproteins.</p> <p><b>Conclusion:</b> Pre-eclampsia and gestational hypertension are associated with higher offspring BP in childhood in the absence of other vascular alterations or metabolic derangements. The findings support the existence of shared mother-offspring risk factors that are specific for higher BP, rather than the additional cardiometabolic abnormalities of hypertensive disorder of pregnancy having long-term consequences for offspring.</p&gt

Cohort profile: the 'Children of the 90s' - the index offspring of the Avon Longitudinal Study of Parents and Children

The Avon Longitudinal Study of Parents and Children (ALSPAC) is a transgenerational prospective observational study investigating influences on health and development across the life course. It considers multiple genetic, epigenetic, biological, psychological, social and other environmental exposures in relation to a similarly diverse range of health, social and developmental outcomes. Recruitment sought to enroll pregnant women in the Bristol area of the UK during 1990-92; this was extended to include additional children eligible using the original enrollment definition up to the age of 18 years. The children from 14541 pregnancies were recruited in 1990-92, increasing to 15247 pregnancies by the age of 18 years. This cohort profile describes the index children of these pregnancies. Follow-up includes 59 questionnaires (4 weeks-18 years of age) and 9 clinical assessment visits (7-17 years of age). The resource comprises a wide range of phenotypic and environmental measures in addition to biological samples, genetic (DNA on 11343 children, genome-wide data on 8365 children, complete genome sequencing on 2000 children) and epigenetic (methylation sampling on 1000 children) information and linkage to health and administrative records. Data access is described in this article and is currently set up as a supported access resource. To date, over 700 peer-reviewed articles have been published using ALSPAC data.Andy Boyd, Jean Golding, John Macleod, Debbie A Lawlor, Abigail Fraser, John Henderson, Lynn Molloy, Andy Ness, Susan Ring and George Davey Smit

Geometry-controlled kinetics

It has long been appreciated that transport properties can control reaction kinetics. This effect can be characterized by the time it takes a diffusing molecule to reach a target -- the first-passage time (FPT). Although essential to quantify the kinetics of reactions on all time scales, determining the FPT distribution was deemed so far intractable. Here, we calculate analytically this FPT distribution and show that transport processes as various as regular diffusion, anomalous diffusion, diffusion in disordered media and in fractals fall into the same universality classes. Beyond this theoretical aspect, this result changes the views on standard reaction kinetics. More precisely, we argue that geometry can become a key parameter so far ignored in this context, and introduce the concept of "geometry-controlled kinetics". These findings could help understand the crucial role of spatial organization of genes in transcription kinetics, and more generally the impact of geometry on diffusion-limited reactions.Comment: Submitted versio

Bone Mineral Density Is Positively Related to Carotid Intima-Media Thickness:Findings From a Population-Based Study in Adolescents and Premenopausal Women

Osteoporosis and cardiovascular disease (CVD) are both common causes of morbidity and mortality. Previous studies, mainly of people older than 60 years, suggest a relationship between these conditions. Our aim was to determine the association between bone characteristics and CVD markers in younger and middle‐aged individuals. Women (n = 3366) and their adolescent offspring (n = 4368) from the UK population‐based cohort study, Avon Longitudinal Study of Parents and Children (ALSPAC), were investigated. We measured total body (TB) and hip bone mineral density (BMD), TB bone area (BA) and bone mineral content (BMC) by dual‐energy X‐ray absorptiometry (DXA), and carotid intima‐media thickness (cIMT) by high‐resolution ultrasound. Arterial distensibility was calculated as the difference between systolic and diastolic arterial diameters. Linear regression determined associations between bone exposures and cIMT (in adolescents) and both cIMT and arterial distensibility (in women), generating partial correlation coefficients. Mean (SD) age of women was 48 (4.2) years, body mass index (BMI) was 26.2 (5.0) kg/m(2), and 71% were premenopausal. In confounder‐adjusted analyses (age, height, lean mass, fat mass, menopause, smoking, estrogen replacement, calcium/vitamin D supplementation, and education) TB and hip BMD were both positively associated with cIMT (0.071 [0.030, 0.112], p = 0.001; 0.063 [0.025, 0.101], p = 0.001, respectively). Femoral neck BMD and TB BMD, BMC, and BA were positively associated with arterial distensibility. Mean (SD) age of adolescents was 17 (0.4) years, BMI was 23 (4.1) kg/m(2), and 44.5% were male. Total hip and TB measurements were positively associated with cIMT, with similar magnitudes of association to those found in their mothers. In contrast to most published findings, we identified weak positive associations between BMD and cIMT in predominantly premenopausal women and their adolescent offspring. We found greater femoral neck BMD and TB DXA measurements to be associated with reduced arterial stiffness. Rather than a relationship with preclinical atherosclerosis, in these relatively young populations, we speculate our associations between BMD, cIMT, and arterial distensibility may reflect a shared relationship between bone and vascular growth and development. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research