Differences in nutritional status between rural and urban Yucatec Maya children: The importance of early life conditions

Early-life conditions shape childhood growth and are affected by urbanization and the nutritional transition. To investigate how early-life conditions (across the “first” and “second” 1000 days) are associated with rural and urban children's nutritional status, we analyzed anthropometric data from Maya children in Yucatan, Mexico. We collected weight, height and triceps skinfold measures, then computed body mass and fat mass indices (BMI/FMI), in a cross-sectional sample of 6-year-olds (urban n = 72, rural n = 66). Demographic, socioeconomic and early-life variables (birthweight/mode, rural/urban residence, household crowding) were collected by maternal interview. We statistically analyzed rural-urban differences in demographic, socioeconomic, early-life, and anthropometric variables, then created linear mixed models to evaluate associations between early-life variables and child anthropometric outcomes. Two-way interactions were tested between early-life variables and child sex, and between early-life variables and rural-urban residence. Results showed that rural children were shorter-statured, with lower overweight/obesity and cesarean delivery rates, compared to urban children. Household crowding was a negative predictor of anthropometric outcomes; the strongest effect was in boys and in urban children. Birthweight positively predicted anthropometric outcomes, especially weight/BMI. Birth mode was positively (not statistically) associated with any anthropometric outcome. Cesarean delivery was more common in boys than in girls, and predicted increased height in urban boys. In conclusion, urbanization and household crowding were the most powerful predictors of Maya 6-year-old anthropometry. The negative effects of crowding may disproportionately affect Maya boys versus girls and urban versus rural children. Early-life conditions shape Maya children's nutritional status both in the “first” and “second” 1000 days.     

AP-1 activation through endogenous H(2)O(2) generation by alveolar macrophages

Reactive oxygen species released during the respiratory burst are known to participate in cell signaling. Here we demonstrate that hydrogen peroxide produced by the respiratory burst activates AP-1 binding. Stimulation of the macrophage cell line NR8383 with respiratory burst agonists ADP and C5a increased AP-1 binding activity. Importantly, this increase in binding was blocked by catalase, confirming mediation by endogenous H₂O₂. Moreover, exogenously added H₂O₂ mimicked the agonists, and also activated AP-1. Antibodies revealed that the activated AP-1 complex is composed predominantly of c-Fos/c-Jun heterodimers. Treatment of the cells with ADP, C5a and H₂O₂ (100 μM) all increased the phosphorylation of c-Jun. c-Fos protein was increased in cells treated with C5a or high dose (200 μM) H₂O₂, but not in cells treated with ADP. The MEK inhibitor, PD98059, partially blocked the C5a-mediated increase in AP-1 binding. A novel membrane-permeable peptide inhibitor of JNK, JNKi, also inhibited AP-1 activation. Together these data suggest that C5a-mediated AP-1 activation requires both the activation of the ERK and JNK pathways, whereas activation of the JNK pathway is sufficient to increase AP-1 binding with ADP. Thus, AP-1 activation joins the list of pathways for which the respiratory burst signals downstream events in the macrophage.     

Cardiovascular Patterning as Determined by Hemodynamic Forces and Blood Vessel Genetics

Background

Vascular patterning depends on coordinated timing of arteriovenous specification of endothelial cells and the concomitant hemodynamic forces supplied by the onset of cardiac function. Using a combination of 3D imaging by OPT and embryo registration techniques, we sought to identify structural differences between three different mouse models of cardiovascular perturbation.

Results

Endoglin mutant mice shared a high degree of similarity to Mlc2a mutant mice, which have been shown to have a primary developmental heart defect causing secondary vessel remodeling failures. Dll4 mutant mice, which have well-characterized arterial blood vessel specification defects, showed distinct differences in vascular patterning when compared to the disruptions seen in Mlc2a ^-/- and Eng ^-/- models. While Mlc2a ^-/- and Eng ^-/- embryos exhibited significantly larger atria than wild-type, Dll4 ^-/- embryos had significantly smaller hearts than wild-type, but this quantitative volume decrease was not limited to the developing atrium. Dll4 ^-/- embryos also had atretic dorsal aortae and smaller trunks, suggesting that the cardiac abnormalities were secondary to primary arterial blood vessel specification defects.

Conclusions

The similarities in Eng ^-/- and Mlc2a ^-/- embryos suggest that Eng ^-/- mice may suffer from a primary heart developmental defect and secondary defects in vessel patterning, while defects in Dll4 ^-/- embryos are consistent with primary defects in vessel patterning.     

Thyme travels: 15N isoscapes of Thymus vulgaris L. invasion in lightly grazed pastoral communities

Alterations to ecosystem nitrogen (N) cycling by introduced plant species may increase the invasibility of habitat providing a positive feedback for the introduced species to become invasive. Spatial patterns of foliar and soil δ¹⁵N ratios reflect variation in rates and process of N‐cycling across invaded landscapes and provide insight into N‐source uptake and utilization strategies of invasive plant species. To evaluate invasion‐associated changes in soil and foliar δ¹⁵N at different scales: regional (among different sites), local (between north‐ and south‐facing aspect at the same site), and microsite (within populations in the same community), we measured foliar and soil δ¹⁵ N, animal faeces cover (as a proxy for grazing intensity) and N₂‐fixing species cover from inside to outside Thymus vulgaris L. (thyme)‐invaded lightly grazed pastoral communities in Central Otago, southern South Island, New Zealand. Mean thyme foliar δ¹⁵N were near‐zero across the invaded landscape, and did not change across the advancing edge of invasion or with aspect. There was no evidence that associations with N₂‐fixing species provide a potential N source. Soil δ¹⁵N was lower inside of thyme compared to at the edge or outside of thyme and was varied between aspects at some sites. Animal faeces cover as a proxy for grazing intensity explained only 23% of this observed variation of soil δ¹⁵N. Thyme invasion may result in lowered soil δ¹⁵N reflecting alterations to N dynamics. Associated invasion‐related impacts of animal grazing may also impact soil δ¹⁵N. Further studies are required to distinguish the underlying mechanism responsible for the observed patterns of foliar and soil δ¹⁵N values across thyme‐invaded Central Otago landscapes.     

Selected anthropometric variables and aerobic fitness as predictors of cardiovascular disease risk in children

The aim of this study was to assess the suitability of body mass index, waist circumference, waist-to-height ratio and aerobic fitness as predictors of cardiovascular risk factor clustering in children. A cross-sectional study was conducted with 290 school boys and girls from 6 to 10 years old, randomly selected. Blood was collected after a 12-hour fasting period. Blood pressure, waist circumference (WC), height and weight were evaluated according to international standards. Aerobic fitness (AF) was assessed by the 20-metre shuttle-run test. Clustering was considered when three of these factors were present: high systolic or diastolic blood pressure, high low-density lipoprotein (LDL) cholesterol, high triglycerides, high plasma glucose, high insulin concentrations and low high-density lipoprotein (HDL) cholesterol. A ROC curve identified the cut-off points of body mass index (BMI), WC, waist-to-height ratio (WHtR) and AF as predictors of risk factor clustering. BMI, WC and WHR resulted in significant areas under the ROC curves, which was not observed for AF. The anthropometric variables were good predictors of cardiovascular risk factor clustering in both sexes, whereas aerobic fitness should not be used to identify cardiovascular risk factor clustering in these children.     

A study of the oxidation of butan-1-ol and propan-2-ol by nicotinamide-adenine dinucleotide catalysed by yeast alcohol dehydrogenase.

1. The kinetics of oxidation of butan-1-ol and propan-2-ol by NAD+, catalysed by yeast alcohol dehydrogenase, were studied at 25 degrees C from pH 5.5 to 10, and at pH 7.05 from 14 degrees to 44 degrees C, 2. Under all conditions studied the results are consistent with a mechanism whereby some dissociation of coenzyme from the active enzyme-NAD+-alcohol ternary complexes occurs, and the mechanism is therefore not strictly compulsory order. 3. A primary 2H isotopic effect on the maximum rates of oxidation of [1-2H2]butan-1-ol and [2H7]propan-2-ol was found at 25 degrees C over the pH range 5.5-10. Further, in stopped-flow experiments at pH 7.05 and 25 degrees C, there was no transient formation of NADH in the oxidation of butan-1-ol and propan-2-ol. The principal rate-limiting step in the oxidation of dependence on pH of the maximum rates of oxidation of butan-1-ol and propan-2-ol is consisten with the possibility that histidine and cysteine residues may affect or control catalysis.     

Determinants of the anesthetic sensitivity of two-pore domain acid-sensitive potassium channels: molecular cloning of an anesthetic-activated potassium channel from Lymnaea stagnalis

Certain two-pore domain K(+) channels are plausible targets for volatile general anesthetics, yet little is known at the molecular level about how these simple agents cause channel activation. The first anesthetic-activated K(+) current I(K(An)) that was characterized was discovered in the mollusk Lymnaea stagnalis and is remarkable for both its sensitivity to general anesthetics and its stereoselective responses to anesthetic enantiomers (Franks, N. P., and Lieb, W. R. (1988) Nature 333, 662-664 and Franks, N. P., and Lieb, W. R. (1991) Science 254, 427-430). Here we report the molecular cloning of a two-pore domain K(+) channel LyTASK from L. stagnalis and show that, when expressed in HEK-293 cells, it displays the same biophysical characteristics as the anesthetic-activated K(+) current I(K(An)). Sequence analysis and functional properties show it to be a member of the TASK family of channels with approximately 47% identity at the amino acid level when compared with human TASK-1 and TASK-3. By using chimeric channel constructs and site-directed mutagenesis we have identified the specific amino acid 159 to be a critical determinant of anesthetic sensitivity, which, when mutated to alanine, essentially eliminates anesthetic activation in the human channels and greatly reduces activation in LyTASK. The L159A mutation in LyTASK disrupts the stereoselective response to isoflurane while having no effect on the pH sensitivity of the channel, suggesting this critical amino acid may form part of an anesthetic binding site.     

The advantages of dense marker sets for linkage analysis with very large families

Dense sets of hundreds of thousands of markers have been developed for genome-wide association studies. These marker sets are also beneficial for linkage analysis of large, deep pedigrees containing distantly related cases. It is impossible to analyse jointly all genotypes in large pedigrees using the Lander–Green Algorithm, however, as marker density increases it becomes less crucial to analyse all individuals’ genotypes simultaneously. In this report, an approximate multipoint non-parametric technique is described, where large pedigrees are split into many small pedigrees, each containing just two cases. This technique is demonstrated, using phased data from the International Hapmap Project to simulate sets of 10,000, 50,000 and 250,000 markers, showing that it becomes increasingly accurate as more markers are genotyped. This method allows routine linkage analysis of large families with dense marker sets and represents a more easily applied alternative to Monte Carlo Markov Chain methods.