Thermal energy and the rate of genetic evolution in marine fishes

Slower genetic evolution in microbial thermophiles has been attributed to internal mutation control mechanisms in very high temperatures, whereas the tempo of plant microevolution has been positively correlated to ambient thermal conditions. Here, using a global dataset of 136 teleost fish species, contrasting warm and cool water species, and controlling for any differences between species in mutation control mechanisms, we found mitochondrial genetic evolution was 1.61 times faster in warm water species. These results suggest that temperature-mediated reduction in mutation rate is only important in extreme thermal regimes.     

Quirks of dye nomenclature. 3. Trypan blue

Trypan blue is colorant from the 19^th century that has an association with Africa as a chemotherapeutic agent against protozoan (Trypanosomal) infections, which cause sleeping sickness. The dye still is used for staining biopsies, living cells and organisms, and it also has been used as a colorant for textiles.     

Gestational intake of methyl donors and global LINE-1 DNA methylation in maternal and cord blood: Prospective results from a folate-replete population

Maternal diet affects offspring DNA methylation in animal models, but evidence from humans is limited. We investigated the extent to which gestational intake of methyl donor nutrients affects global DNA methylation in maternal and umbilical cord blood. Among mother-infant pairs in Project Viva, a folate-replete US population, we estimated maternal intakes of vitamin B12, betaine, choline, folate, cadmium, zinc and iron periconceptionally and during the second trimester. We examined associations of these nutrients with DNA methylation, measured as %5-methyl cytosines (%5mC) in Long Interspersed Nuclear Element-1 (LINE-1), in first trimester (n = 830) and second trimester (n = 671) maternal blood and in cord blood at delivery (n = 516). Cord blood methylation was higher for male than female infants {mean [standard deviation (SD)] 84.8 [0.6] vs. 84.4 [0.7]%}. In the multivariable-adjusted model, maternal intake of methyl donor nutrients periconceptionally and during the second trimester of pregnancy was not positively associated with first trimester, second trimester or cord blood LINE-1 methylation. Periconceptional betaine intake was inversely associated with cord blood methylation [regression coefficient = −0.08% (95% confidence interval (CI): −0.14, −0.01)] but this association was attenuated after adjustment for dietary cadmium, which itself was directly associated with first trimester methylation and inversely associated with cord blood methylation. We also found an inverse association between periconceptional choline [−0.10%, 95% CI: −0.17, −0.03 for each SD (∼63 mg/day)] and cord blood methylation in males only. In this folate-replete population, we did not find positive associations between intake of methyl donor nutrients during pregnancy and DNA methylation overall, but among males, higher early pregnancy intakes of choline were associated with lower cord blood methylation.Key words: DNA methylation, pregnancy, cord blood, maternal diet, cadmium     

Prediction and course of symptoms and lung function around an exacerbation in chronic obstructive pulmonary disease

Background

Frequent exacerbations induce a high burden to Chronic Obstructive Pulmonary Disease (COPD). We investigated the course of exacerbations in the published COSMIC study that investigated the effects of 1-year withdrawal of fluticasone after a 3-month run-in treatment period with salmeterol/fluticasone in patients with COPD.

Methods

In 373 patients, we evaluated diary cards for symptoms, Peak Expiratory Flow (PEF), and salbutamol use and assessed their course during exacerbations.

Results

There were 492 exacerbations in 224 patients. The level of symptoms of cough, sputum, dyspnea and nocturnal awakening steadily increased from 2 weeks prior to exacerbation, with a sharp rise during the last week. Symptoms of cough, sputum, and dyspnea reverted to baseline values at different rates (after 4, 4, and 7 weeks respectively), whereas symptoms of nocturnal awakening were still increased after eight weeks. The course of symptoms was similar around a first and second exacerbation. Increases in symptoms and salbutamol use and decreases in PEF were associated with a higher risk to develop an exacerbation, but with moderate predictive values, the areas under the receiver operating curves ranging from 0.63 to 0.70.

Conclusions

Exacerbations of COPD are associated with increased symptoms that persist for weeks and the course is very similar between a first and second exacerbation. COPD exacerbations are preceded by increased symptoms and salbutamol use and lower PEF, yet predictive values are too low to warrant daily use in clinical practice.     

Mechanical ventilation with high tidal volumes attenuates myocardial dysfunction by decreasing cardiac edema in a rat model of LPS-induced peritonitis

Background

Injurious mechanical ventilation (MV) may augment organ injury remote from the lungs. During sepsis, myocardial dysfunction is common and increased endothelial activation and permeability can cause myocardial edema, which may, among other factors, hamper myocardial function. We investigated the effects of MV with injuriously high tidal volumes on the myocardium in an animal model of sepsis.

Methods

Normal rats and intraperitoneal (i.p.) lipopolysaccharide (LPS)-treated rats were ventilated with low (6 ml/kg) and high (19 ml/kg) tidal volumes (Vt) under general anesthesia. Non-ventilated animals served as controls. Mean arterial pressure (MAP), central venous pressure (CVP), cardiac output (CO) and pulmonary plateau pressure (P_plat) were measured. Ex vivo myocardial function was measured in isolated Langendorff-perfused hearts. Cardiac expression of endothelial vascular cell adhesion molecule (VCAM)-1 and edema were measured to evaluate endothelial inflammation and leakage.

Results

MAP decreased after LPS-treatment and Vt-dependently, both independent of each other and with interaction. MV Vt-dependently increased CVP and Pplat and decreased CO. LPS-induced peritonitis decreased myocardial function ex vivo but MV attenuated systolic dysfunction Vt-dependently. Cardiac endothelial VCAM-1 expression was increased by LPS treatment independent of MV. Cardiac edema was lowered Vt-dependently by MV, particularly after LPS, and correlated inversely with systolic myocardial function parameters ex vivo.

Conclusion

MV attenuated LPS-induced systolic myocardial dysfunction in a Vt-dependent manner. This was associated with a reduction in cardiac edema following a lower transmural coronary venous outflow pressure during LPS-induced coronary inflammation.     

Similarity of the CDC and WHO weight-for-length growth charts in predicting risk of obesity at age 5 years

The World Health Organization (WHO) 2006 weight-for-length (WFL) or BMI growth charts are now recommended as the new standard for children under 24 months. The objective of this study was to examine associations of ever being overweight during 1-24 months, based on the older Centers for Disease Control and Prevention (CDC) and WHO cutpoints, with risk of obesity at age 5 years. From well-child visits to a Massachusetts multi-site group practice during 1980-2008, we studied 15,488 children with length/height and weight measurements at 1, 6, 12, 18, and 24 months, and at 5 years. The main exposures were ever being overweight during 1-24 months using each of three cutpoints: CDC WFL ≥ 95th percentile, WHO WFL or BMI ≥ 97.7th percentile. The main outcome was obesity at 5 years (CDC BMI ≥ 95th percentile). We calculated multivariable odds ratios (ORs), adjusted for age, sex, race/ethnicity, and year. At 5 years, 10.8% of participants were obese. During 1-24 months, 21.3, 18.3, and 20.2% were ever overweight using CDC WFL, WHO WFL, and WHO BMI cutpoints, respectively. ORs (95% confidence interval (CI)) for associations of ever being overweight during 1-24 months with obesity at 5 years were 6.0 (5.4, 6.6), 6.3 (5.7, 7.0), and 6.0 (5.4, 6.7), respectively. Ever being overweight in the first 2 years of life is a strong predictor of obesity at 5 years. CDC WFL, WHO WFL, and WHO BMI cutpoints for overweight in early childhood provided similar estimates of later obesity risk.     

Developmental origins of childhood overweight: potential public health impact

Several modifiable pre- and postnatal determinants of childhood overweight are known, but no one has examined how they influence risk of overweight in combination. We estimated the risk of overweight at age 3 years according to levels of maternal smoking during pregnancy, gestational weight gain, breastfeeding duration, and infant sleep duration. We studied 1,110 mother-child pairs in Project Viva, a prospective prebirth cohort study. The main outcome measure was child overweight (BMI for age and sex >or=95th percentile) at age 3. We ran logistic regression models with all four modifiable risk factors as well as the covariates maternal BMI and education, child race/ethnicity, and household income. From the model, we obtained the estimated probability of overweight for each of the 16 combinations of the four risk factors. During pregnancy, 9.8% of mothers smoked and 50% gained excessive weight. In infancy, 73% mother-child pairs breastfed for <12 m, and 31% of infants slept <12 h/day. Among the 3-year-old children in the cohort, 9.5% were overweight. In the prediction model, the estimated probability of overweight ranged from 0.06 among children exposed to favorable levels of all four risk factors, to 0.29 with adverse levels of all four. Healthful levels of four behaviors during early development predicted much lower probability of overweight at age 3 than adverse levels. Interventions to modify several factors during pregnancy and infancy could have substantial impact on prevention of childhood overweight.     

Response of forest tree seedlings to simulated litterfall damage.

Litterfall is an important cause of seedling mortality in many forests ranging from wet tropical to boreal. However, there is a lack of studies that investigate differences between species in seedling resilience to litterfall damage. We selected seedling pairs of seven tree species and simulated litterfall damage by pinning one of each pair to the ground. The mortality and growth rates varied significantly between species for pinned individuals, but were similar for unpinned seedlings. The mortality of pinned Nestegis cunninghamii and Prumnopitys ferruginea was significantly greater than that of unpinned individuals (P < 0.05). However, contrary to expectations, the growth rates of pinned Hedycarya arborea and Nothofagus menziesii were much greater than for those left unpinned (P < 0.05). In general, seedling resilience to the bending damage differed substantially between species. N. cunninghamii and P. ferruginea suffered high mortalities and did not increase growth rates in response to damage, whereas, H. arborea and N. menziesii suffered few mortalities and regained height quickly. Other study species demonstrated intermediate resilience. This study demonstrates that some species are more likely to survive in high-risk litterfall regimes than are others. Given that litterfall risk can vary greatly between microsites, these results suggest that litterfall can contribute to regeneration niche differentiation. This revised version was published online in August 2006 with corrections to the Cover Date.     

A covariotide model explains apparent phylogenetic structure of oxygenic photosynthetic lineages

The aims of the work were (1) to develop statistical tests to identify whether substitution takes place under a covariotide model in sequences used for phylogenetic inference and (2) to determine the influence of covariotide substitution on phylogenetic trees inferred for photosynthetic and other organisms. (Covariotide and covarion models are ones in which sites that are variable in some parts of the underlying tree are invariable in others and vice versa.) Two tests were developed. The first was a contingency test, and the second was an inequality test comparing the expected number of variable sites in two groups with the observed number. Application of these tests to 16S rDNA and tufA sequences from a range of nonphotosynthetic prokaryotes and oxygenic photosynthetic prokaryotes and eukaryotes suggests the occurrence of a covariotide mechanism. The degree of support for partitioning of taxa in reconstructed trees involving these organisms was determined in the presence or absence of sites showing particular substitution patterns. This analysis showed that the support for splits between (1) photosynthetic eukaryotes and prokaryotes and (2) photosynthetic and nonphotosynthetic organisms could be accounted for by patterns arising from covariotide substitution. We show that the additional problem of compositional bias in sequence data needs to be considered in the context of patterns of covariotide/covarion substitution. We argue that while covariotide or covarion substitution may give rise to phylogenetically informative patterns in sequence data, this may not always be so.