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.

Stunting Prevalence, Plasma Zinc Concentrations, and Dietary Zinc Intakes in a Nationally Representative Sample Suggest a High Risk of Zinc Deficiency Among Women and Young Children in Cameroon

Abstract: Before initiating a mass zinc fortification program, this study assessed the prevalence of and risk factors for low zinc status among Cameroonian women and children. In a nationally representative survey, we randomly selected 30 clusters in each of 3 strata (North, South, and Yaounde/Douala) and 10 households per cluster, each with a woman aged 15-49 y and a child aged 12-59 mo (n = 1002 households). Twenty-four-hour dietary recalls (with duplicates in a subset) and anthropometric measurements were conducted, and non-fasting blood was collected to measure plasma zinc concentration (PZC) and markers of inflammation. PZC was adjusted for methodologic factors (time of collection and processing, and presence of inflammation). The prevalence of stunting was 33% (32% South; 46% North; 13% Yaounde/Douala). Among women, 82% had low adjusted PZC (<50 μg/dL for pregnant women; <66 μg/dL for others; 79% South, 89% North, 76% Yaounde/Douala). Among children, 83% had low adjusted PZC (<65 μg/dL; 80% South, 92% North, 74% Yaounde/Douala). Risk factors for low PZC among women and children and for low height-for-age Z-score among children were similar and included residence in the North region and rural areas and households with low socioeconomic status. Using estimated average requirement values from the International Zinc Nutrition Consultative Group (IZiNCG), 29 and 41% of women had inadequate zinc intakes, assuming moderate and low bioavailability, respectively, but only 8% of children had inadequate zinc intake. Depending on the estimated physiologic zinc requirement applied, 17% (IZiNCG) and 92% (Institute of Medicine) of women had inadequate absorbable zinc intakes. Total zinc intakes were greatest in the North region, possibly because of different dietary patterns in this area. Zinc deficiency is a public health problem among women and children in Cameroon, although PZC and dietary zinc yield different estimates of the prevalence of deficiency. Large-scale programs to improve zinc nutrition, including food fortification, are needed.

Sphingosine-1-phosphate metabolism and intestinal tumorigenesis: lipid signaling strikes again.

Abstract: Sphingolipids are an evolutionary conserved class of membrane lipids synthesized by all eukaryotic cells. The biological functions of sphingolipids are diverse, encompassing structural roles through their participation in membrane lipid rafts, and informational roles via the involvement of their metabolites in signal transduction pathways. An important sphingolipid metabolite is sphingosine-1-phosphate (S1P), which acts through G protein-coupled receptors present on mammalian cells, thereby stimulating cell proliferation, angiogenesis and inhibiting apoptosis. The main enzyme responsible for S1P synthesis, sphingosine kinase 1 (Sphk1), behaves as an oncogene in experimental systems and is required for polyp enlargement in the Min mouse model of intestinal tumorigenesis. S1P is irreversibly degraded by S1P lyase (SPL), an enzyme that is highly expressed in enterocytes, where it is involved in metabolism of dietary sphingolipids. Forced expression of SPL sensitizes human cells to various stressful stimuli and enhances apoptotic cell death. SPL expression is induced in response to DNA damaging agents in a time- and concentration-dependent manner. On the other hand, SPL is downregulated in human colon cancers and in Min mouse adenomas compared to adjacent uninvolved tissues. These observations suggest that SPL, like Sphk1, may play a role in tumorigenesis. Added support for this notion comes from the fact that S1P-specific antibodies slow tumor progression and angiogenesis in murine xenograft and allograft models. Together, these recent studies have established a link between S1P signaling, metabolism and carcinogenesis that may have implications regarding colon cancer screening, dietary chemoprevention and therapeutics.

Increased High-Density Lipoprotein Cholesterol Levels in Mice With XX Versus XY Sex Chromosomes

Abstract: Objective— The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels. Approach and Results— We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the four core genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male–female gonadal sex and XX–XY chromosome complement. Gonadectomy of adult mice revealed that the male–female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male–female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared with a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an X and Y chromosome. By generating mice with XX, XY, and XXY chromosome complements, we determined that the presence of 2 X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration. Conclusions— We demonstrate that having 2 X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels.