The SLC30A2 zinc transporter has been investigated due to its important role in zinc secretion into human milk. SLC30A2 is expressed in mammary epithelial cells, and the presence of genetic variations in this transporter could cause low zinc transport into the milk, leading to Transient Neonatal Zinc Deficiency (TNZD) in newborns. Through bioinformatics analysis 22 SNPs were identified. Therefore, we aim to identify the functional changes caused by 4 SNPs. By subcloning the SLC30A2 open reading frames into the Gateway expression plasmid tagged with red and green fluorescent proteins (mCherry, tGFP). Four SNPs were introduced by mutagenesis and tagged with mCherry. We transfected individual plasmids into mammary epithelial cells (HC11) and observed cellular targeting using epifluorescent imaging. The most common variants located to secreting endosomes and membrane in HC11 cells. Incorrect targeting of SLC30A2 causes mislocalization. It may be possible to identify mothers carrying risk genotypes for infant zinc deficiency.

Prolidase deficiency (MIM 26413), an autosomal recessive phenotype, is caused by rare alleles at a locus on chromosome 19cent.-q13.2. The clinical phenotype is pleiotropic (affecting skin, brain, etc.) and of variable expressivity (benign to early death). I established skin fibroblast cultures from 6 homozygous probands and 6 obligate heterozygotes, purified prolidase (E.C. 3.4.13.9, a homodimer) from normal human fibroblasts, raised a monospecific rabbit antiserum to the subunit, and studied its biosynthesis. Pulse-chase immunoprecipitation experiments showed that the subunit is synthesized in the cytosol as a 58 KDa. polypeptide and not processed further. Homozygous prolidase-deficient cell strains expressed 3 classes of mutant alleles which by complementation analysis mapped to one locus. The alleles were designated CRM$-$ (nul), CRM+ activity/size variant, and CRM+ activity variant. Heterozygotes carrying CRM$-$ alleles have heat stable prolidase (50$ sp circ$C, 1hr); heterozygotes carrying CRM+ variant alleles have heat labile enzyme. The finding implies that variant CRM+ allele(s) can confer negative allelic complementation on the dimeric enzyme (dominant relative phenotype). CRM$-$ homozygous cells contain varying amounts of an alternative imidodipeptidase-like activity. The variant prolidase allele (major gene) and amount of alternative "prolidase" activity (modifier gene) are apparently both determinants of the associated clinical phenotype in prolidase deficiency. I obtained and sequenced a tryptic peptide from human kidney prolidase for synthesis of oligonucleotide probes in the future.

Marginal zinc deficiency (MZD) exists in children of industrialized societies and can impair growth and development. Presently there are no data available on its global prevalence. It is believed that MZD is one of the most common hidden deficiencies throughout the world. This is partly because of the lack of sensitivity and specificity of serum zinc, the most commonly used biomarker of zinc status, to detect MZD . This deficiency in children is always accompanied by a decrease in hair zinc . Although in research settings hair zinc is a recognized biomarker of MZD in children, health practitioners do not presently use it. These cross-sectional studies were designed to examine the hair zinc status of preschoolers in Vancouver . They also aimed at exploring some dietary and non-dietary factors associated with hair zinc status in an attempt to construct and validate a screening tool for detection of MZD. Our first study indicated a mean hair zinc of 75±30 μg/g, with 46% below the cutoff (<70μg/g) for a group (n=87) of low-income preschoolers (Chapter II). Among these children we observed negative associations between the hair zinc and consumption of dairy (R² =0.09, P=0 .01) and milk (R² =0.08, P=0.01), being described as "often sick" (R² =0.55, P=0 .00) and "eating unhealthy" (R² =0.16 P=0.00), and prolonged breastfeeding (R² =0.11, P=0.01). Our citywide survey (n=719) indicated a mean hair zinc of 116±43 μg/g with 17% below the cutoff (Chapter III). Logistic regression analysis indicated sex, age, maternal education, the number of adults at home, consumption frequency of milk, "scores of activity level", "being described as frequently sick" and "taking supplements containing iron" as the significant predictors of hair zinc status . However, the final model had 16% sensitivity while having 98 .3% specificity, indicating its lack of usefulness as a screening tool. Our study provides important information on the hair zinc status of Vancouver preschoolers. Although we did not accomplish our primary goal of constructing and validating a screening tool, we did identify some factors in children and their environment associated with hair zinc, which may help in better understanding of hair zinc as a biomarker of MZD .

Papua New Guinea has been classified by the World Health Organisation as an area where clinical vitamin A deficiency (VAD) exists. This is at variance with the experience of the local physicians who do not encounter classical VAD in clinical practice. This pilot study was carried out to resolve this contradiction, since many suggestions have been made to fortify foods with Vitamin A. If done in the absence of concrete data to back up this classification, it could take the focus away from the real problem as well as potentially create problems of Vitamin A toxicity. Therefore, answers from this study could have far reaching implications in a country such as PNG, which has high childhood mortality and limited financial and manpower resources. The objective of this study was to determine the vitamin A status and identify risk factors of VAD in children aged 6 months to 6 years in a rural area of Papua New Guinea. The survey was carried out in the Ramu region of Madang province. Households and children were randomly selected and standard questionnaires were used to collect information about diet, previous illnesses and night blindness. The weight and height of all children was recorded and an ocular and physical examination carried out by trained personnel. In addition, haemoglobin estimation and examination of blood films for malaria parasites was carried out in all the children. In a randomly selected number of children, estimations of serum retinol and other micronutrient levels were carried out. Results: A total of 609 children were enrolled in the study. Biochemical parameters were studied in 106 of them .The mean age of the children was 35 months. Possible night blindness was reported in 4 children. No xerophthalmia was seen. The prevalence of serum retinol levels ( 0.7 (mol/L (WHO suggested cut off values for subclinical VAD) was 10.3%. Anthropometric indicators indicated a high proportion of the children had stunting and wasting or both. Analysis of dietary patterns, maternal literacy, food availability and other surrogate indicators indicated that the population is at mild-moderate risk of developing VAD. In conclusion, no evidence of clinical vitamin A deficiency was found. Subclinical vitamin A deficiency seemed to occur in this population at a level of mild-moderate public health importance. Further studies need to be carried out to assess the situation in different areas in PNG before policy decisions can be made with regards to mass vitamin A supplementation.

Diss. (sammanfattning) Umeå : Univ., 2005. / Härtill 5 uppsatser + appendix.

Thesis (Ph. D.)--University of Adelaide, Dept. of Plant Science, 1998. / Includes bibliographical references (leaves 218-233).

Thesis (M.Ag.Sc.) - Dept. of Agronomy, University of Adelaide, 1983. / Typescript (photocopy).

Thesis (D.Sc.) --University of Adelaide, 1958.

Thesis (Ph.D.)--University of Missouri-Columbia, 2006. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file (viewed on April 27, 2009) Vita. Includes bibliographical references.

Thesis (DR. P.H.)--University of Michigan.