Hypertension in children and adolescents: epidemiology and natural history

Primary hypertension is detectable in children and adolescents and, as in adults, is associated with a positive family history of hypertension, obesity, and life-style factors. Owing to the well-established childhood obesity epidemic, the population prevalence of high blood pressure (BP) in the young is increasing. Hypertension in childhood is commonly associated with other cardiovascular risk factors as well as obesity. Although death and cardiovascular disability do not occur in hypertensive children, intermediate markers of target organ damage, such as left ventricular hypertrophy, thickening of the carotid vessel wall, retinal vascular changes, and even subtle cognitive changes, are detectable in children and adolescents with high BP. Considering the rates of verified hypertension (>3%) and pre-hypertension (>3%) in asymptomatic children and adolescents, high BP should be considered a common long-term health problem in childhood

Skeletal growth in class II malocclusion from childhood to adolescence: does the profile straighten?

BACKGROUND There is relatively little appreciation of the changes in maxillary-mandibular relationships occurring during adolescence among subjects with normal and increased overjet. The aim of this study was to assess differences in changes in maxillo-mandibular relationships during the adolescent growth period based on the presence of a normal ( 4 mm) overjet in childhood. Our hypothesis was that there is no difference in the change of the A point, nasion, B point (ANB) angle during growth between these two overjet groups. Lateral cephalograms were obtained from 65 subjects taken from the American Association of Orthodontists Foundation (AAOF) Craniofacial Growth Legacy Collections Project. Cephalograms were obtained at ages 7-10 (T0) and 14-17 (T1) with allocation into two groups based on baseline overjet (> 4 mm: group 1, 2-4 mm: group 2). Random effects linear regression was used to account for multiple within -patient measurements with dependent variables including antero-posterior skeletal pattern (based on sella, nasion, A point (SNA); sella, nasion, B point (SNB); and ANB angles). RESULTS We included a similar number of males (n = 34; 52.3%) and females (n = 31; 47.7%). The mean ANB was higher at baseline in group 1 (5.42, SD 2.16°) than in group 2 (3.08, SD 1.91°). The hypothesis was rejected as the ANB angle reduced by 1.92° more in the larger overjet group with the association being statistically significant after accounting for age and gender (P  4 mm overjet group compared to the 2-4 mm group (0.857°, P = 0.271; 95% CI - 0.669 to 2.383). The SNB angle increased by 1.15° more in the higher overjet group but there was only weak evidence of an association (P = 0.086; 95% CI - 2.464 to 0.164). CONCLUSIONS A slight straightening of the facial profile was observed in both groups with a statistically significant greater reduction in ANB arising in the group with larger baseline overjet. This translated into a marginal reduction in the overjet in this group

Distributions of epistasis in microbes fit predictions from a fitness landscape model.

How do the fitness effects of several mutations combine? Despite its simplicity, this question is central to the understanding of multilocus evolution. Epistasis (the interaction between alleles at different loci), especially epistasis for fitness traits such as reproduction and survival, influences evolutionary predictions "almost whenever multilocus genetics matters". Yet very few models have sought to predict epistasis, and none has been empirically tested. Here we show that the distribution of epistasis can be predicted from the distribution of single mutation effects, based on a simple fitness landscape model. We show that this prediction closely matches the empirical measures of epistasis that have been obtained for Escherichia coli and the RNA virus vesicular stomatitis virus. Our results suggest that a simple fitness landscape model may be sufficient to quantitatively capture the complex nature of gene interactions. This model may offer a simple and widely applicable alternative to complex metabolic network models, in particular for making evolutionary predictions

Mycoplasma hyorhinis-contaminated cell lines activate primary innate immune cells via a protease-sensitive factor

Mycoplasma are a frequent and occult contaminant of cell cultures, whereby these prokaryotic organisms can modify many aspects of cell physiology, rendering experiments that are conducted with such contaminated cells problematic. Chronic Mycoplasma contamination in human monocytic cells lines has been associated with suppressed Toll-like receptor (TLR) function. In contrast, we show here that components derived from a Mycoplasma hyorhinis-infected cell line can activate innate immunity in non-infected primary immune cells. Release of pro-inflammatory cytokines such as IL-6 by dendritic cells in response to Mycoplasma hyorhinis-infected cell components was critically dependent on the adapter protein MyD88 but only partially on TLR2. Unlike canonical TLR2 signaling that is triggered in response to the detection of Mycoplasma infection, innate immune activation by components of Mycoplasma-infected cells was inhibited by chloroquine treatment and sensitive to protease treatment. We further show that in plasmacytoid dendritic cells, soluble factors from Mycoplasma hyorhinis-infected cells induce the production of large amounts of IFN-α. We conclude that Mycoplasma hyorhinis-infected cell lines release protein factors that can potently activate co-cultured innate immune cells via a previously unrecognized mechanism, thus limiting the validity of such co-culture experiments

Quantifying Rates of Evolutionary Adaptation in Response to Ocean Acidification

The global acidification of the earth's oceans is predicted to impact biodiversity via physiological effects impacting growth, survival, reproduction, and immunology, leading to changes in species abundances and global distributions. However, the degree to which these changes will play out critically depends on the evolutionary rate at which populations will respond to natural selection imposed by ocean acidification, which remains largely unquantified. Here we measure the potential for an evolutionary response to ocean acidification in larval development rate in two coastal invertebrates using a full-factorial breeding design. We show that the sea urchin species Strongylocentrotus franciscanus has vastly greater levels of phenotypic and genetic variation for larval size in future CO2 conditions compared to the mussel species Mytilus trossulus. Using these measures we demonstrate that S. franciscanus may have faster evolutionary responses within 50 years of the onset of predicted year-2100 CO2 conditions despite having lower population turnover rates. Our comparisons suggest that information on genetic variation, phenotypic variation, and key demographic parameters, may lend valuable insight into relative evolutionary potentials across a large number of species

Cis-regulatory evolution spotlights species differences in the adaptive potential of gene expression plasticity

Plasticity allows organisms to respond to environmental change. Here the authors compare the distribution of cis-regulatory variants in the transcriptomes of Arabidopsis lyrata and A. halleriafter exposure to stress, to trace the role of polygenic selection in the evolution of gene expression plasticity

The effects of low-impact mutations in digital organisms

<p>Abstract</p> <p>Background</p> <p>Avida is a computer program that performs evolution experiments with digital organisms. Previous work has used the program to study the evolutionary origin of complex features, namely logic operations, but has consistently used extremely large mutational fitness effects. The present study uses Avida to better understand the role of low-impact mutations in evolution.</p> <p>Results</p> <p>When mutational fitness effects were approximately 0.075 or less, no new logic operations evolved, and those that had previously evolved were lost. When fitness effects were approximately 0.2, only half of the operations evolved, reflecting a threshold for selection breakdown. In contrast, when Avida's default fitness effects were used, all operations routinely evolved to high frequencies and fitness increased by an average of 20 million in only 10,000 generations.</p> <p>Conclusions</p> <p>Avidian organisms evolve new logic operations only when mutations producing them are assigned high-impact fitness effects. Furthermore, purifying selection cannot protect operations with low-impact benefits from mutational deterioration. These results suggest that selection breaks down for low-impact mutations below a certain fitness effect, the <it>selection threshold</it>. Experiments using biologically relevant parameter settings show the tendency for increasing genetic load to lead to loss of biological functionality. An understanding of such genetic deterioration is relevant to human disease, and may be applicable to the control of pathogens by use of lethal mutagenesis.</p

Evolution of sex-specific pace-of-life syndromes: genetic architecture and physiological mechanisms

Sex differences in life history, physiology, and behavior are nearly ubiquitous across taxa, owing to sex-specific selection that arises from different reproductive strategies of the sexes. The pace-of-life syndrome (POLS) hypothesis predicts that most variation in such traits among individuals, populations, and species falls along a slow-fast pace-of-life continuum. As a result of their different reproductive roles and environment, the sexes also commonly differ in pace-of-life, with important consequences for the evolution of POLS. Here, we outline mechanisms for how males and females can evolve differences in POLS traits and in how such traits can covary differently despite constraints resulting from a shared genome. We review the current knowledge of the genetic basis of POLS traits and suggest candidate genes and pathways for future studies. Pleiotropic effects may govern many of the genetic correlations, but little is still known about the mechanisms involved in trade-offs between current and future reproduction and their integration with behavioral variation. We highlight the importance of metabolic and hormonal pathways in mediating sex differences in POLS traits; however, there is still a shortage of studies that test for sex specificity in molecular effects and their evolutionary causes. Considering whether and how sexual dimorphism evolves in POLS traits provides a more holistic framework to understand how behavioral variation is integrated with life histories and physiology, and we call for studies that focus on examining the sex-specific genetic architecture of this integration

Pattern recognition receptors in immune disorders affecting the skin.

Contains fulltext : 109004.pdf (publisher's version ) (Open Access)Pattern recognition receptors (PRRs) evolved to protect organisms against pathogens, but excessive signaling can induce immune responses that are harmful to the host. Putative PRR dysfunction is associated with numerous immune disorders that affect the skin, such as systemic lupus erythematosus, cryopyrin-associated periodic syndrome, and primary inflammatory skin diseases including psoriasis and atopic dermatitis. As yet, the evidence is often confined to genetic association studies without additional proof of a causal relationship. However, insight into the role of PRRs in the pathophysiology of some disorders has already resulted in new therapeutic approaches based on immunomodulation of PRRs