Using time-varying quantile regression approaches to model the influence of prenatal and infant exposures on childhood growth

<p>For many applications, it is valuable to assess whether the effects of exposures over time vary by quantiles of the outcome. We have previously shown that quantile methods complement the traditional mean-based analyses, and are useful for studies of body size. Here, we extended previous work to time-varying quantile associations. Using data from over 18,000 children in the U.S. Collaborative Perinatal Project, we investigated the impact of maternal pre-pregnancy body mass index (BMI), maternal pregnancy weight gain, placental weight, and birth weight on childhood body size measured 4 times between 3 months and 7 years, using both parametric and non-parametric time-varying quantile regressions. Using our proposed model assessment tool, we found that non-parametric models fit the childhood growth data better than the parametric approaches. We also observed that quantile analysis resulted in difference inferences than the conditional mean models in three of the four constructs (maternal per-pregancy BMI, maternal weight gain, and placental weight). Overall, these results suggest the utility of applying time-varying quantile models for longitudinal outcome data. They also suggest that in the studies of body size, merely modelling the conditional mean may lead to incomplete summary of the data.</p

Image_2_Genomics and transcriptomics reveal new molecular mechanism of vibriosis resistance in fish.jpg

Infectious diseases have caused dramatic production decline and economic loss for fish aquaculture. However, the poor understanding of fish disease resistance severely hampered disease prevention. Chinese tongue sole (Cynoglossus semilaevis) is an important economic flatfish suffering from vibriosis. Here we used genomic, transcriptomic and experimental approaches to investigate the molecular genetic mechanisms underlying fish vibriosis resistance. A genome-wide comparison revealed that the genes under selective sweeps were enriched for glycosaminoglycan (GAG) chondroitin sulfate (CS)/dermatan sulfate (DS) metabolism. Transcriptomic analyses prioritized synergic gene expression patterns in this pathway, which may lead to an increased CS/DS content in the resistant family. Further experimental evidence showed that carbohydrate sulfotransferases 12 (Chst12), a key enzyme for CS/DS biosynthesis, has a direct antibacterial activity. To the best of our knowledge, this is the first report that the chst12 gene has a bactericidal effect. In addition, CS/DS is a major component of the extracellular matrix (ECM) and the selection signatures and fine-tuned gene expressions of ECM-receptor interaction genes indicated a modification in the ECM structure with an enhancement of the barrier function. Furthermore, functional studies conducted on Col6a2, encoding a collagen gene which constitutes the ECM, pointed to that it may act as a cellular receptor for Vibrio pathogens, thus plays an important role for the Vibrio invasion. Taken together, these findings provide new insights into the molecular protective mechanism underlying vibriosis resistance in fish, which offers crucial genomic resources for the resistant germplasm breeding and infectious disease control in fish culturing.</p

β3 integrin receptor medicated OPN induction of CCL20 expressions.

<p>(A) CCL20 gene expressions in isolated CD4+T cells from 8 hCD and 8 uGD in the presence or absence of 1 µg/ml rOPN for 12 h. (B) Expressions of OPN receptors on CD4+ T cells from uGD patients, eGD patients, nGD patients and hCD. (C) β3 integrin receptor antibody blocked induction of CCL20 mRNA and protein levels by OPN. The freshly isolated PBMCs were cultured in the presence or absence of 1 µg/ml rOPN for 12 h. Blocking Abs to integrin β3, or its isotype control mAb (IgG) were added at 5 µg/ml. Supernatants from cultures and CD4+T cells separated from PBMCs were used to analyze the expression levels of CCL20. Shown are representative results from 3 independent experiments with separate specimens. All data were presented as mean±SEM. *, <i>P</i><0.05; ***, <i>P</i><0.001, versus medium control; #, <i>P</i><0.05 versus Ctrl mAb.</p

Effect of OPN on induction of CCL20 expression was mediated by IL-17, NF-κB and MAPK pathways.

<p>(A, B) PBMCs were isolated from normal subjects and treated with rOPN (1 µg/ml) at different time point. The IL-17 mRNA expression in purified CD4+T cells (A) and protein level in culture medium (B) were analyzed. Induction of CCL20 mRNA in CD4+T cells (C) and protein levels in culture medium (D) by OPN was blocked by antibody against IL-17, and inhibitors of IKK and MAPKs. Shown are representative results from 3 independent experiments with separate specimens. All data were presented as mean±SEM. *, <i>P</i><0.05 versus OPN; # <i>P</i><0.05 versus medium control; ns>0.05 versus OPN.</p

Plasma CCL20 and CCL20 mRNA in CD4+T cells from GD patients and normal controls.

<p>(A) Distribution of plasma CCL20 levels in 35 healthy control donors, 50 untreated GD patients, 15 euthyroid GD patients and 12 TRAb-negative GD patients. Median values, interquartile ranges and ranges are denoted by horizontal bars, boxes and vertical bars, respectively. (B) CCL20 mRNA levels in CD4+T cells from healthy controls, uGD, eGD and nGD patients. Data were presented as mean±SEM.*, <i>P</i><0.05; **, <i>P</i><0.01.</p

Pearson’s correlation and multiple stepwise linear regression analysis of CCL20 associated with classic GD diagnostic parameters.

<p><i>r</i>, correlation coefficient; β, Regression coefficient; SE, standard error.</p

Clinical characteristics of the subjects.

a<p><i>P</i><0.001, untreated GD (uGD) compared with healthy Control Donors (hCD).</p>b1<p><i>P</i><0.001,</p>b2<p><i>P</i>>0.05, euthyroid GD (eGD) compared with uGD.</p>c<p><i>P</i><0.001,TRAb-negative GD patients (nGD) compared with uGD. All data were presented as mean±SD.</p

Plasma OPN levels in GD patients and normal controls and the correlation between plasma CCL20 with OPN.

<p>(A) Distribution of plasma OPN levels in 35 healthy control donors, 50 untreated GD patients, 15 euthyroid GD patients and 12 TRAb-negative GD patients. Median values, interquartile ranges and ranges are denoted by horizontal bars, boxes and vertical bars, respectively. (B) Regression scatter plots showing the correlation between logarithm-transformed plasma CCL20 level and logarithm-transformed plasma OPN level. The correlation shown was significant (<i>r</i> = 0.62, <i>P</i><0.001).</p