Children's Hospital Oakland Research Institute

About: Children's Hospital Oakland Research Institute is a based out in . It is known for research contribution in the topics: Population & Human leukocyte antigen. The organization has 1568 authors who have published 2480 publications receiving 203418 citations.

Environmental and genetic contributors to hypospadias: a review of the epidemiologic evidence.

Abstract: This review evaluates current knowledge related to trends in the prevalence of hypospadias, the association of hypospadias with endocrine-disrupting exposures, and the potential contribution of genetic susceptibility to its etiology. The review focuses on epidemiologic evidence. Increasing prevalence of hypospadias has been observed, but such increases tend to be localized to specific regions or time periods. Thus, generalized statements that hypospadias is increasing are unsupported. Owing to the limitations of study designs and inconsistent results, firm conclusions cannot be made regarding the association of endocrine-disrupting exposures with hypospadias. Studies with more rigorous study designs (e.g., larger and more detailed phenotypes) and exposure assessment that encompasses more breadth and depth (e.g., specific endocrine-related chemicals) will be critical to make better inferences about these important environmental exposures. Many candidate genes for hypospadias have been identified, but few of them have been examined to an extent that enables solid conclusions. Further study is needed that includes larger sample sizes, comparison groups that are more representative of the populations from which the cases were derived, phenotype-specific analyses, and more extensive exploration of variants. In conclusion, examining the associations of environmental and genetic factors with hypospadias remain important areas of inquiry, although our actual understanding of their contribution to hypospadias risk in humans is currently limited.

Effect of Zinc Supplementation on Pregnancy and Infant Outcomes: A Systematic Review

Abstract: Poor maternal zinc status has been associated with foetal loss, congenital malformations, intra-uterine growth retardation, reduced birth weight, prolonged labour and preterm or post-term deliveries. A meta-analysis completed in 2007 showed that maternal zinc supplementation resulted in a small but significant reduction in preterm birth. The purposes of this analysis are to update that previous review and expand the scope of assessment to include maternal, infant and child health outcomes. Electronic searches were carried out to identify peer-reviewed, randomised controlled trials where daily zinc supplementation was given for at least one trimester of pregnancy. The co-authors applied the study selection criteria, assessed trial quality and abstracted data. A total of 20 independent intervention trials involving more than 11,000 births were identified. The 20 trials took place across five continents between 1977 and 2008. Most studies assessed the zinc effect against a background of other micronutrient supplements, but five were placebo-controlled trials of zinc alone. The provided dose of supplemental zinc ranged from 5 to 50 mg/day. Only the risk of preterm birth reached statistical significance (summary relative risk 0.86 [95% confidence interval 0.75, 0.99]). There was no evidence that supplemental zinc affected any parameter of foetal growth (risk of low birth weight, birth weight, length at birth or head circumference at birth). Six of the 20 trials were graded as high quality. The evidence that maternal zinc supplementation lowers the risk of preterm birth was graded low; evidence for a positive effect on other foetal outcomes was graded as very low. The effect of zinc supplementation on preterm birth, if causal, might reflect a reduction in maternal infection, a primary cause of prematurity. While further study would be needed to explore this possibility in detail, the overall public health benefit of zinc supplementation in pregnancy appears limited.

Structural basis for the conformational adaptability of apolipophorin III, a helix-bundle exchangeable apolipoprotein.

Abstract: The high-resolution NMR structure of apolipophorin III from the sphinx moth, Manduca sexta, has been determined in the lipid-free state. We show that lipid-free apolipophorin III adopts a unique helix-bundle topology that has several characteristic structural features. These include a marginally stable, up-and-down helix bundle that allows for concerted opening of the bundle about “hinged” loops upon lipid interaction and buried polar/ionizable residues and buried interhelical H-bonds located in the otherwise hydrophobic interior of the bundle that adjust protein stability and facilitate lipid-induced conformational opening. We suggest that these structural features modulate the conformational adaptability of the lipid-free helix bundle upon lipid binding and control return of the open conformation to the original lipid-free helix-bundle state. Taken together, these data provide a structural rationale for the ability of exchangeable apolipoproteins to reversibly interact with circulating lipoprotein particles.

Accumulation of Phosphorylated Sphingoid Long Chain Bases Results in Cell Growth Inhibition in Saccharomyces cerevisiae

Abstract: Sphingolipid metabolites in mammals can function as signaling molecules with cell-specific functions. In Saccharomyces cerevisiae, phosphorylated long chain bases, such as dihydrosphingosine 1-phosphate and phytosphingosine 1-phosphate, have also been implicated in stress responses. To further explore the biological roles of these molecules, we created disruption mutants for LCB4, LCB5, DPL1, YSR2, YSR3, and SUR2. LCB4 and LCB5 encode kinases that phosphorylate long chain bases. DPL1 and YSR2/YSR3 are involved in degradation of the phosphorylated long chain bases. SUR2 catalyzes conversion of dihydrosphingosine to phytosphingosine. We adapted an HPLC method to measure intracellular concentrations of the phosphorylated long chain bases. Double mutants of dpl1 and ysr2 were inviable, whereas dpl1 ysr2 lcb4 triple mutants were viable. Further, growth inhibition associated with accumulated phosphorylated long chain bases was observed in the triple mutant dpl1 ysr2 lcb4 overexpressing LCB4 or LCB5. These results indicate that phosphorylated long chain bases can inhibit cell growth. Mutants defective in both YSR2 and SUR2, which accumulated dihydrosphingosine 1-phosphate only, grew poorly. The phenotypes of the ysr2 sur2 mutants were suppressed by overexpression of DPL1. Our results clearly show that elevated levels of phosphorylated long chain bases have an antiproliferative effect in yeast.