Thesis (M.Sc. (Nutrition))--Mahidol University, 1979.

京都大学 / 新制・課程博士 / 博士(人間・環境学) / 甲第23272号 / 人博第987号 / 新制||人||233(附属図書館) / 2020||人博||987(吉田南総合図書館) / 京都大学大学院人間・環境学研究科共生人間学専攻 / (主査)教授 林 達也, 教授 船曳 康子, 教授 久代 恵介, 教授 森谷 敏夫 / 学位規則第4条第1項該当 / Doctor of Human and Environmental Studies / Kyoto University / DGAM

Malaria is caused by the parasite Plasmodium falciparum and still plagues many parts of the world. To date, efforts to control the spread of the parasites have been largely ineffective. Due to development of resistance by the parasites to current therapeutics there is an urgent need for new classes of therapeutics. The vitamin B6 biosynthetic pathway consists of a PLP synthase which produces pyridoxal 5'-phosphate (PLP) within the parasite. The absence of this pathway in humans makes it attractive for selective targeting using small chemical molecules. The PLP synthase condenses D-ribose 5-phosphate (R5P) and DL-glyceraldehyde 3-phosphate (G3P) with ammonia to form PLP. Two proteins make up this PLP synthase – PfPdx1 and PfPdx2. Computational modelling of Pf Pdx1, and mapping of the R5P-binding site pharmacophore facilitated the identification of several ligands with predicted favourable binding interactions. Confirmatory testing of these on the purified Pf Pdx1 in vitro revealed D-erythrose 4-phosphate (E4P) and an analogue 4-phospho-D-erythronhydrazide (4PEHz) were capable of dose-dependently inhibiting the enzyme. The acyclic tetrose scaffold of E4P, with both aldehyde and phosphate group moieties, was thought to affect R5P imine bond formation in Pf Pdx1, possibly allowing the molecule to enter the R5P-binding site of Pf Pdx1. This hypothesis was supported by molecular docking simulations, and suggested that 4PEHz could similarly enter the R5P-binding site. 4PEHz was detrimental to the proliferation of cultured P. falciparum intraerythrocytic parasites and had an inhibitory concentration (IC50) of 10 µM. The selectivity of 4PEHz in targeting Pf Pdx1 was investigated using transgenic cell lines over-expressing Pf Pdx1 and Pf Pdx2, revealing that complementation of PLP biosynthesis rescued the parasites from the detrimental effects of 4PEHz. Functional transcriptomic and proteomic characterisation of 4PEHz-treated parasites revealed that the expression of Pf Pdx2 increased during 4PEHz treatment, moreover showed that other PLP-related processes were affected. These results supported that Pf Pdx1 is targeted by 4PEHz, and affected PLP biosynthesis de novo. Results from this study allude to alternative regulation of de novo PLP biosynthesis within the parasites by E4P. Moreover, contributions from this work showed that the de novo vitamin B6 pathway of P. falciparum is chemically targetable, and a potential strategy for the development of newer antimalarials. / Thesis (PhD)--University of Pretoria, 2013. / gm2013 / Biochemistry / Unrestricted

Thesis (M.C.P.)--Massachusetts Institute of Technology, Dept. of City and Regional Planning, 1961. / Includes bibliographical references (leaves 171-178). / In examining the present status of water resource planning in the Pacific Northwest, numerous critical inadequacies become readily apparent. One method of minimizing some of these inadequacies is through administrative reorganization. Realizing this there have been many different reorganization proposals put forth. Along with these proposals has come much propaganda. In order to obtain a clearer picture comparative criteria were established. Upon doing this it was decided to limit the analysis to the compact, the authority and the inter-agency approaches. Upon applying the criteria to these three structures, the following conclusions were reached: 1) the compact would probably be worse than the existing setup, 2) the inter-agency committee has some value and not too many dangers, 3) the authority fulfills by far the most criteria but because of certain possible dangers should not be strived for, 4) that the criteria are useful in discovering which structures may be unacceptable but they do not tell which is the optimum one. Much is dependent upon the type of planners the structures attract. / by James Myron Bowers. / M.C.P.

京都大学 / 0048 / 新制・課程博士 / 博士(農学) / 甲第18599号 / 農博第2086号 / 新制||農||1027(附属図書館) / 学位論文||H26||N4874(農学部図書室) / 31499 / 京都大学大学院農学研究科応用生命科学専攻 / (主査)教授 三上 文三, 教授 植田 充美, 教授 栗原 達夫 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

No description available.

The vitamin B-6 content of three foods, roast top round of beef in au jus, canned green beans in pot liquor, and whole baked potatoes was measured. These foods are typically served together as choices on the six week cycle menu at three dining halls on the University campus. Random samples were taken when the foods were raw, just cooked, and held for one, two, and three hours. Two additional samples of roast beef were selected as the beef received more cooking and holding treatments. Saccharomyces uvarum was the test organism used in the A.O.A.C. microbiological analyses for vitamin B-6 quantitation. Total vitamin B-6 was measured, not the individual vitamers. Roast beef lost total vitamin B-6, sometimes in significant quantities at every sample time. Green beans followed the same pattern of loss with cooking and increased holding times. Some of the vitamin was leached into the au jus and pot liquor as they were held with the beef and beans, respectively. Whole baked potatoes also lost in vitamin B-6 content with each sample time; however, this loss was not always significant. Institutional cooking and holding procedures utilized for these selected foods had adverse effects on their vitamin B-6 content. / M.S.

A high performance liquid chromatographic (HPLC) system consisting of a binary mobile phase, a µBondapak C₁₈ column, and a fluorescence detector was used to separate the B-6 vitamers pyridoxal (PL), pyridoxine CPN), and pyridoxamine (PM) as well as the internal standard deoxypyridoxine. An extraction procedure, compatible with the HPLC system, was developed to isolate the B-6 vitamers from rat livers, kidneys, and brains. PL values were derived from the sum of tissue PL and pyridoxal phosphate (PLP), the latter having been dephosphorylated to PL. Similarly, PN values were the sum of tissue PN and pyridoxine phosphate (PNP) and PM data the sum of PM and pyridoxamine phosphate (PMP). Separation and quantitation of tissue vitamers were successful and reflected significant relationships between rat vitamin B-6 intakes and tissue concentrations of the B-6 vitamers PL and PM as well as total B-6 vitamer concentration. PM was found to be the major vitamer in all tissues. The HPLC data were compared to values obtained by the AOAC microbiological (MB) assay performed on the same samples. Significant correlations (r) ranging from 0.31 - 0.73 for PL, 0.30 - 0.47 for PM, and 0.48 - 0.55 for total B-6 vitamer concentration were observed between values obtained via the methods. Both HPLC and MB vitamer data approximated reported values. The HPLC method offered the advantages of relative speed and simplicity. / M.S.

The vitamin B-6 status of seemingly healthy adolescent girls was determined using several accepted and proposed parameters in an effort to establish guidelines for status evaluation. HPLC-derived plasma B-6 vitamer [pyridoxal phosphate (PLP), pyridoxine phosphate (PNP), pyridoxamine phosphate (PMP), pyridoxal (PL), pyridoxine (PN), and pyridoxamine (PM)] and 4-pyridoxic acid (4-PA) concentrations and urinary 4-PA levels of 28 white adolescent females, 12-15 years, having radiomonitored plasma PLP concentrations and coenzyme stimulation of erythrocyte alanine aminotransferase activities indicative of adequate status were determined. Mean daily vitamin B-6 and protein intakes of the subjects were 1.48 mg and 78.3 g, respectively. The ranges for plasma B-6 vitamer and 4-PA concentrations for these subjects which had seemingly adequate vitamin B-6 status were as follows: (nmol/L) PLP, 40.9-122.2; PNP, 0-16.1; PMP, 0-8.1; PL, 0- 15.0; PN, 0-21.9; PM, 0-17.8; and 4-PA, 0-55.7. PLP was the predominant plasma B-6 vitamer as well as being the only vitamer found in plasma of all subjects. Urinary 4-PA concentrations of the girls ranged from 0.11-2.50 pmol/mmol creatinine. The B-6 vitamer values of these white adolescent girls should be of use in the establishment of normal ranges for vitamin B-6 status parameters. HPLC methodologies seem to be advantageous for the rapid and accurate assessment of vitamin B-6 status. / Ph. D.

As vitaminas do complexo B e o ferro estão presentes em farinhas de cereais, alimentos amplamente consumidos pela população brasileira. O teor natural desses compostos em farinhas de cereais pode ser significativo no cálculo de uma dieta bem balanceada e o consumo de produtos industrializados enriquecidos com vitaminas do complexo B e ferro ajuda a contribuir na ingestão diária recomendada desses micronutrientes. Tabelas Mundiais de Composição de Alimentos apresentam dados incompletos das vitaminas do complexo B e do ferro em farinhas de cereais. No Brasil, a adição de ácido fólico e ferro em farinhas de milho e trigo produzidas para fins industriais é obrigatória desde 2002. Deste modo, para a adequação dos teores de rotulagem de produtos enriquecidos com vitaminas e ferro se fazem necessários o desenvolvimento e a validação de metodologias analíticas confiáveis e sensíveis para análise de vitaminas do complexo B e ferro em alimentos que apresentam tais micronutrientes em quantidades baixas, porém significativas, que correspondem aos teores naturalmente presentes. O objetivo do presente trabalho é a avaliação dos teores de sete vitaminas do complexo B (B1, B2, B6, ácido pantotênico, ácido fólico, niacina e biotina) e ferro em cinco farinhas de cereais (aveia, arroz, cevada, milho e trigo) utilizadas como matéria prima de produtos enriquecidos na indústria alimentícia, utilizando métodos validados. / Complex B vitamins and iron are present in some cereal foods, a kind of food largely consumed by Brazilian people. The total of these micronutrients can be significant at the dairy ingestion portion and in the consume of industrialized products enriched with complex B vitamins and iron contribute in the recommended dietary intake of these micronutrients. Table of food composition do not report complete data of complex B vitamins and iron in cereal flours. In Brazil, since 2002 the addition of folic acid and iron in com and wheat flours is compulsory. Therefore, to adapt the label of some products enriched with vitamins and iron, there is necessary the development and validation of analytical methods. These methods must be reliable and with enough sensitivity to analyse complex B vitamins and iron, in low concentration, wich are natural content in food. The purpose of this work is the evaluation, with validated methods, of the content of seven complex B vitamíns (B1, B2, B6, niacin, folic acid, pantothenic acid and biotin) and iron in five kinds of cereal flours (oat, rice, barley, com and wheat). These raw materiais are used in food industry in order to enrich the industrialized products.