Genome-wide association studies and genomic selection assays made in a large sample of cacao (Theobroma cacao L.) germplasm reveal significant marker-trait associations and good predictive value for improving yield potential.

A genome-wide association study (GWAS) was undertaken to unravel marker-trait associations (MTAs) between SNP markers and phenotypic traits. It involved a subset of 421 cacao accessions from the large and diverse collection conserved ex situ at the International Cocoa Genebank Trinidad. A Mixed Linear Model (MLM) in TASSEL was used for the GWAS and followed by confirmatory analyses using GAPIT FarmCPU. An average linkage disequilibrium (r2) of 0.10 at 5.2 Mb was found across several chromosomes. Seventeen significant (P ≤ 8.17 × 10-5 (-log10 (p) = 4.088)) MTAs of interest, including six that pertained to yield-related traits, were identified using TASSEL MLM. The latter accounted for 5 to 17% of the phenotypic variation expressed. The highly significant association (P ≤ 8.17 × 10-5) between seed length to width ratio and TcSNP 733 on chromosome 5 was verified with FarmCPU (P ≤ 1.12 × 10-8). Fourteen MTAs were common to both the TASSEL and FarmCPU models at P ≤ 0.003. The most significant yield-related MTAs involved seed number and seed length on chromosome 7 (P ≤ 1.15 × 10-14 and P ≤ 6.75 × 10-05, respectively) and seed number on chromosome 1 (P ≤ 2.38 × 10-05), based on the TASSEL MLM. It was noteworthy that seed length, seed length to width ratio and seed number were associated with markers at different loci, indicating their polygenic nature. Approximately 40 candidate genes that encode embryo and seed development, protein synthesis, carbohydrate transport and lipid biosynthesis and transport were identified in the flanking regions of the significantly associated SNPs and in linkage disequilibrium with them. A significant association of fruit surface anthocyanin intensity co-localised with MYB-related protein 308 on chromosome 4. Testing of a genomic selection approach revealed good predictive value (genomic estimated breeding values (GEBV)) for economic traits such as seed number (GEBV = 0.611), seed length (0.6199), seed width (0.5435), seed length to width ratio (0.5503), seed/cotyledon mass (0.6014) and ovule number (0.6325). The findings of this study could facilitate genomic selection and marker-assisted breeding of cacao thereby expediting improvement in the yield potential of cacao planting material.

Weight Gain Trajectories from Birth to Adolescence and Cardiometabolic Status in Adolescence.

OBJECTIVE: To assess the influence of the trajectory of weight gain from birth to adolescence on cardiovascular and metabolic risk. We studied childhood body mass index (BMI) trajectories from birth to age 14 years and cardiometabolic risk factors at age 14 years. STUDY DESIGN: In total, 410 children with weight and height measurements were assessed from birth throughout childhood, from the Childhood Asthma Prevention Study, a prospective community-based cohort. BMI trajectory groups were determined by latent basis growth mixture models. Of these subjects, 190 had detailed cardiometabolic risk factors assessed at age 14 years. RESULTS: Three BMI trajectory groups were identified; normal BMI, "early rising" excess BMI from 2 years, and "late rising" excess BMI from 5 years. Differences were found between normal and excess BMI in children at 14 years of age. In addition, children with an early rising BMI trajectory had statistically significantly higher central adiposity and a more atherogenic lipoprotein profile at age 14 years than children with a late rising BMI trajectory (P < .05). No differences between BMI trajectory groups in vascular structure or function was identified at age 14 years. CONCLUSIONS: Earlier onset of an elevated BMI trajectory persisting from birth to age 14 years results in an unfavorable cardiometabolic risk profile at age 14 years, including central adiposity and more atherogenic lipoproteins, independent of achieved BMI.

Asthma and atopy prevalence are not reduced among former tuberculosis patients compared with controls in Lima, Peru.

BACKGROUND: Although there are theoretical reasons for believing that asthma and atopy may be negatively correlated with tuberculosis, epidemiological studies have had conflicting findings. OBJECTIVE: To determine if people with confirmed tuberculosis were less likely to be atopic and less likely to have atopic disease including asthma compared to those with no previous tuberculosis. METHODS: Patients in Lima, Peru with a prior history of tuberculosis were identified from clinic records in this cohort study. A representative sample of individuals without a prior tuberculosis diagnosis was recruited from the same community. Allergen skin prick testing was performed to classify atopic status. Allergic rhinitis was identified by history. Asthma was defined by symptoms and spirometry. Eosinophilic airway inflammation was measured using exhaled nitric oxide levels. RESULTS: We evaluated 177 patients with, and 161 individuals without, previous tuberculosis. There was a lower prevalence of atopy among people with prior tuberculosis on univariate analysis (odds ratio 0.57; 95% confidence interval 0.37-0.88) but, after adjustment for potential confounders, this was no longer statistically significant (aOR 0.64, 95% CI 0.41-1.01). The prevalence of allergic rhinitis (aOR 0.76, 95% CI 0.47 to 1.24 and asthma (aOR 1.18, 95% CI 0.69 to 2.00) did not differ significantly between the two groups. We also found no significant difference in the prevalence of elevated exhaled nitric oxide (aOR 1.30, 95% CI 0.78 to 2.17) or a combined index of atopic disease (aOR 0.86, 95% CI 0.54 to 1.36). CONCLUSION: In this urban environment in a middle-income country, prior tuberculosis may be associated with a reduced risk of atopy but does not protect against asthma and atopic disease.

Bifactor model of effortful control and impulsivity and their prospective prediction of ego resiliency.

OBJECTIVE: Children's effortful control and impulsivity are important predictors of the personality trait, ego resiliency (i.e., resiliency). Most researchers have not considered the fact that effortful control and impulsivity share substantial conceptual and empirical overlap, yet they also have been shown to be distinct. We tested a bifactor model of effortful control and impulsivity to characterize their shared and unique variance, the prospective prediction of resiliency by the factors of the bifactor model, and moderation by sex and age. METHOD: In a longitudinal study of children (N = 214; 76.5% non-Hispanic Caucasian, 12.2% Hispanic, 11.3% other race/ethnicity), parent- and teacher-reported effortful control and impulsivity, as well as behavioral measures of effortful control, were assessed on two occasions (T1: 4.5-8 years; T2: 6-10 years). Parent-reported resiliency was used as a covariate (T1) and the outcome (T3: 8-12 years). RESULTS: The bifactor model yielded a common effortful inhibitory control factor, pure attentional control factor, and pure impulsivity factor. Pure impulsivity and pure attentional control positively predicted resiliency, but only for girls. Effortful inhibitory control did not uniquely predict resiliency. CONCLUSION: Disentangling the shared and unique aspects of effortful control and impulsivity could clarify the roles they play in important outcomes, such as resiliency.

Treatment of bowel in experimental gastroschisis with a nitric oxide donor.

OBJECTIVE: To reduce the harmful effect of bowel exposure to amniotic fluid in gastroschisis, we used the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) in an animal model of gastroschisis and assessed the ideal concentration for treatment of changes in bowel. STUDY DESIGN: Gastroschisis was surgically induced in rat fetuses on day 18.5 of gestation. The fetuses were divided into 5 groups (n = 12 animals/group): control (C), gastroschisis (G), gastroschisis + GSNO 5 µmol/L (GNO1), gastroschisis + GSNO 0.5 µmol/L (GNO2), and gastroschisis + GSNO 0.05 µmol/L (GNO3). On day 21.5 of gestation, fetuses were collected by cesarean delivery. Body and intestinal weight were measured and the bowels were either fixed for histometric and immunohistochemical study or frozen for Western blotting. We analyzed bowel morphometry on histological sections and expression of the NO synthase (NOS) enzymes by Western blotting and immunohistochemistry. Data were analyzed by analysis of variance or Kruskal-Wallis test when appropriate. RESULTS: Morphological and histometric measurements of weight, diameter, and thickness of the layers of the intestinal wall decreased with GSNO treatment, especially in the GNO3 group, when compared with the G group (P < .05). The expression of neuronal NOS, endothelial NOS, and inducible NOS decreased mainly in GNO3 group compared to the G group (P < .05), with no difference compared to C group (P > .05). CONCLUSION: Fetal treatment with 0.05 µmol/L GSNO resulted in significant improvement of bowel morphology in gastroschisis.

Antenatal steroid and tracheal occlusion restore vascular endothelial growth factor receptors in congenital diaphragmatic hernia rat model.

OBJECTIVE: Investigate the effects of antenatal steroids and tracheal occlusion on pulmonary expression of vascular endothelial growth factor receptors in rats with nitrofen-induced congenital diaphragmatic hernia. STUDY DESIGN: Fetuses were exposed to nitrofen at embryonic day 9.5. Subgroups received dexamethasone or were operated on for tracheal occlusion, or received combined treatment. Morphologic variables were recorded. To analyze vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 expression, we performed Western blotting and immunohistochemistry. Morphologic variables were analyzed by analysis of variance and immunohistochemistry by Kruskal-Wallis test. RESULTS: Congenital diaphragmatic hernia decreased body weight, total lung weight, and lung-to-body weight ratio. Tracheal occlusion increased total lung weight and lung-to-body weight ratio (P < .05). Fetuses with congenital diaphragmatic hernia had reduced vascular endothelial growth factor receptor 1 and vascular endothelial growth factor receptor 2 expression, whereas steroids and tracheal occlusion increased their expression. Combined treatment increased expression of receptors, but had no additive effect. CONCLUSION: Vascular endothelial growth factor signaling disruption may be associated with pulmonary hypertension in congenital diaphragmatic hernia. Tracheal occlusion and steroids provide a pathway for restoring expression of vascular endothelial growth factor receptors.