Thesis (Ph.D.) - University of Queensland, 2002. / Includes bibliography.

Microalgae have a profound effect on the world due to their large contribution to net carbon fixation. Although they are phototrophic, more than 50% of microalgae are thought to depend on external supply of metabolites such as B-vitamins. In oceans, algae are therefore often found together with a community of bacteria and form intricate networks where metabolites are exchanged. Currently, only a fraction of the related mechanisms and metabolite exchanges between algae and bacteria have been uncovered and many more are likely to exist. The work presented in this thesis is based on a model system for algae-bacterial interactions made up of the green alga, Lobomonas rostrata and the alpha-proteobacterium Mesorhizobium loti. In the model system, it is known that the bacterium provides vitamin B12 to the alga and itself, whilst the alga provides fixed carbon. I have applied methods from the field of computational biology to study the interactions between these organisms and other similar partnerships, with the aim of uncovering new insights. The thesis is made up of three research chapters, each focused on using a specific method to study algae-bacterial interactions. I developed a genome scale metabolic model of metabolism of M. loti that enabled simulation of growth. The model simulates 1908 enzymatic reactions and takes 1804 metabolites into account. Using the model, I simulated growth of the bacterium on 1018 different substrates with the aim of identifying substrates supplied by L. rostrata when the two organisms are co-cultured. In addition, I carried out a set of simulations studying the bacterium’s ability to produce B12 from 1368 different substrates. The modelling efforts in this project was successful in enabling simulations, but it was not possible to validate the simulations with experimental data. A transcriptomics experiment was undertaken with the aim of identifying genes related to the interaction between L. rostrata and M. loti. In the experiment, the partners from the model system was grown in axenic and co-culture conditions and RNA samples were taken from each state. Using RNA-seq, the RNA samples were sequenced and from this a candidate transcriptome was created. The expression of each putative gene was then quantified and differentially expressed genes were identified. Based on sequence similarity, candidate functions were assigned where possible. In the analysis of differentially expressed genes, it was found that there appears to be an increased expression of a transporter responsible for uptake of the plant hormone, auxin. Currently, only a small fraction of all bacteria has been shown to produce B12 and it is not clear in which phylogenetic groups this is a common trait. I therefore applied methods from comparative genomics to study the synthesis of this metabolite in more than 8000 bacterial species. This involved developing a computational framework that allowed me to search for the presence of more than 50 genes in more than 8000 genomes in a rapid manner. I found that 37.2% of bacteria can synthesis B12 and that this capability is very common in some phylogenetic groups such as Cyanobacteria, but extremely rare in others such as Lactobacillus. I was also able to confirm that cyanobacteria are not able to make cobalamin, a variant of B12 used by eukaryotic algae, and thus they are unlikely to support algal growth in the photic zone. In the final section of the thesis, I discuss the application of computational biology methods in this field and summarise my experience from applying genome scale modelling, comparative genomics and transcriptomics to study algae-bacterial interactions.

Thesis (MTech (Medical Technology))--Cape Technikon, 1992. / As early as 1822 it was discovered that treating a patient, who had a macrocytic anaemia, with a diet containing liver, a rich source of folic acid (folacin), brought about an excellent haematological response. extract, a source of The same happened in 1851 when a yeast vitamin B12 (cobalamine), corrected a megaloblastic anaemia. It is well known that a lack of either one or both of these vitamins is responsible for a megaloblastic anemia which has been shown to be hematologically indistinguishable yet requires different treatment to correct. It is therefore important to make a correct diagnosis as to the cause of the illness in a megaloblastic anaemia by the measurement of vitamin B12 and folate levels. Various laboratory test methods were developed over the past 20 to 30 years and through constant improvement culminated in the current radio immune assay (RIA) technique used for the measurement of vitamin B12 and folate values. This method has many advantages over the microbiological method that preceeded it, but is still dependent on normal values or reference ranges. These reference ranges, supplied with each test kit, are obtained from a white American population and are probably only applicable to the white South African population.

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Includes bibliographical references (leaves 202-21). / 2 v. (xxiv, 409 leaves) : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Experiments were designed for the early detection of vitamin B12 deficiency in sheep and cattle. Metabolic indicators were examined in animals where deficiency was induced with either nitrous oxide (N2O) or by feeding diets of low cobalt content. Results showed that vitamin B12 dependent enzymes in the liver of ruminants appeared to be affected only at a late stage of deficiency. However changes in concentrations of metabolites of these pathways occured earlier. / Thesis (Ph.D.)--University of Adelaide, Dept. of Animal Sciences, 1994

Tez (Tıpta Uzmanlık) - Süleyman Demirel Üniversitesi, Tıp Fakültesi, İç Hastalıkları ve Doğum Anabilim Dalı, 2006. / Bibliyografya var.

Bakgrund: Alzheimers sjukdom (AD) utgör vanligaste formen av demenssjukdomar i Sverige. Alzheimers sjukdom klassas som en neurodegenerativ sjukdom och karaktäriseras av proteininlagringar samt av hjärnatrofi. Ungefär 150 000 personer i Sverige lever idag med demenssjukdomar, varav 90 000 lider av AD och varje år insjuknar ytterligare 20 000 i demens. Vitamin B12 och folat anses utgöra en viktig del med avseende på hjärnans kognitiva funktioner. Låga nivåer av vitamin B12 och/eller folatbrist medför en höjning av Homocystein (Hcy) i blodet. Syfte: Syftet med examensarbetet var att undersöka det eventuella sambandet mellan nivåerna av vitamin B12, folat respektive Hcy och risken för att drabbas av Alzheimers sjukdom. Utifrån syftet ställdes 2 frågeställningar upp. Frågeställning 1: Finns det en risk att utveckla AD vid förändrade nivåer av folat, vitamin B12 och Hcy. Frågeställning 2: Finns det ett samband mellan förändrade nivåer av folat, vitamin B12 och Hcy vid diagnosticerad AD. Metod: Detta arbete är en litteraturstudie baserat på 7 vetenskapliga artiklar. Resultat: Samtliga fem studier utifrån frågeställning 2 visade att AD-patienter hade höga nivåer av Hcy än kontrollpatienterna. Två av dessa studier visade även att AD-patienterna hade lägre nivåer av både vitamin B12 och folat än kontrollindividerna. Två ytterligare studier av de fem samtliga visade också lägre nivåer av folat än kontrollgruppen.  Totalt 4 av 5 studier visade lägre nivåer av folat. Utifrån frågeställning 1 visade studie 1 att det var enbart de låga nivåerna av folat från baslinjen som förespråkade till insjuknande i AD. Studie 2 indikerade att individer med låga nivåer av vitamin B12 och folat har 2 gånger högre risk för att insjukna i AD. Slutsats: Det är fortfarande oklart idag huruvida nivåerna av vitamin B12, folat och Hcy påverkar riskerna för att utveckla AD. Studierna visar att det finns ett samband mellan markörerna kopplat till AD. Det krävs mer forskning för att fastställa det eventuella sambandet mellan vitamin B12, folat och Hcy. Fler patienter måste undersökas och flera studier bör utföras för att kunna fastställa associationerna av dessa ämnen med AD. Studierna visar att det finns ett samband mellan markörerna kopplat till AD. Fler studier som tar hänsyn till inklusionskriterierna med avseende på nutritionsstatus bör göras.  Detta eftersom lågt BMI (Body Mass Index) kan vara av betydelse för uppkomsten samt riskerna för att insjukna i AD. / Background: Alzheimer's disease (AD) is the most common form of dementia in Sweden. Alzheimer's disease is classified as a neurodegenerative disease and is characterized by protein deposits in certain parts of the brain accompanied with brain atrophy. 150 000 people in Sweden today suffer from dementia, of whom 90 000 suffer from AD and every year another 20 000 dementia cases reside. The highest risk factor of developing AD is old age. After the age of 65, the risk is considerably higher for developing AD. Vitamin B12 and folate is considered to be an important part with respect to the brain's cognitive functions. Folate acts as a donor of the methyl groups in a reaction catalysed by methionine synthase, which produce methyl cobalamin which needs to be metabolised to methionine from Homocystein (Hcy). Low levels of vitamin B12 and/or folate deficiency leads to an increase of Hcy in the blood. Objective: The aim of this study was to investigate the possible link between low levels of vitamin B12, folate and Hcy and the risk of developing Alzheimer's disease. Two question based on the objective of the study were set. Question 1: Is there any risk of developing AD with altered levels of folate, vitamin B12 and Hcy? Question 2: Is there a relationship between altered levels of folate, vitamin B12 and Hcy in diagnosed AD? Methods: This work is a literature study based on 7 scientific articles. Results: All five studies from question 2 showed that AD patients had high levels of Hcy compared to control patients. Two of these studies also revealed that AD patients had lower levels of both vitamin B12 and folate than control individuals. Furthermore 2 out of the 5 studies also displayed lower levels of folate compared to the control group, resulting in a total of 4 out of 5 studies showing lower levels of folate. Based on question 1, study 1 presented that only low levels of folate at baseline correlated with developing AD. Study 2 indicated that individuals with low levels of vitamin B12 and folate had twice times higher risk of developing AD. Conclusion: It is still unclear whether the levels of vitamin B12, folate and Hcy affect AD. The studies investigated show that there is a correlation between the investigated markers linked to AD. However, more research is needed to be able to determine the possible link between vitamin B12, folate and Hcy. More patients must be investigated and several studies should be performed to determine the associations of these subjects with AD.  More studies that take in consideration of nutritional status must be carried out, due to the fact that low BMI (Body Mass Index) may be of importance for the risk of developing AD.

Dementia is prevalent among elderly people. As the world population ages, it is projected that the number of people affected by dementia may triple in the next 50 years. Over the last two decades, research has focused on identifying potentially modifiable risk factors in development and progression of dementia, such as vitamin B12 and folate. Results concerning the effects of low folate and vitamin B12 on cognitive performance are mixed. The main objective of the present study was to investigate the effects of vitamin deficiency on cognitive functioning in a clinical sample of elderly individuals with cognitive problems using a comprehensive neuropsychological assessment. A retrospective chart-review was performed on the 102 records of patients from the Geriatrics Clinic at the University of North Texas Health Science Center who presented with cognitive deficits. Charts were reviewed to obtain data on vitamin supplementation, vitamin status, history of chronic conditions and other biochemical data. The available database was used to obtain data on neuropsychological assessment. The study demonstrated mild association between vitamin B12 and folate status and cognitive deficits. There appeared to be a higher cut-off level that is above the traditionally used levels for vitamin B12 and folate deficiency concentrations at which cognitive deficits became more pronounced. Clinical applications, limitations and suggestions for future research were discussed.

Background: Folate and cobalamin are essential cofactors for homocysteine (HCY) metabolism. Hyperhomocysteinemia, a multifactorial condition, may reflect B vitamin deficiency and is associated with increased risk of cardiovascular disease, thrombosis, and neurodegenerative and chronic gastrointestinal diseases in humans. Hyperhomocysteinemia has been reported in Greyhounds with suspected chronic enteropathy. Objectives: To evaluate the frequencies of and the association between hypofolatemia and hyperhomocysteinemia in Greyhounds. Animals: Data and serum samples from 559 Greyhounds. Methods: Nested case-control study. The frequency of hypofolatemia in Greyhounds was determined by a laboratory database search. The relationship between hyperhomocysteinemia (measured by gas chromatography-mass spectrometry) and hypocobalaminemia and hypofolatemia was evaluated, and its frequency compared between healthy Greyhounds and Greyhounds with thrombosis or chronic diarrhea. Results: Hypofolatemia was identified in 172 of 423 (41%) Greyhounds and was more common in hypo- than in normocobalaminemic dogs (49% vs. 35%; P = .0064). Hyperhomocysteinemia was detected in 53 of 78 (68%) of Greyhounds, being more common in hypo- than in normofolatemic dogs (88% vs. 59%; P = .0175). All healthy Greyhounds, 21 of 30 (70%) of dogs with chronic diarrhea and 6 of 8 (75%) of those with thrombosis, were hyperhomocysteinemic. Serum HCY concentrations were inversely correlated with serum folate concentration (q = -0.28; P = .0386) and were positively associated with serum albumin concentration (q = 0.66; P = .0022). Conclusions and Clinical Relevance: Hyperhomocysteinemia occurs frequently in the Greyhound population. Its association with hypofolatemia suggests decreased intracellular availability of B vitamins, but the functional implications warrant further investigation. Hyperhomocysteinemia in Greyhounds potentially may serve as a spontaneous canine model to further investigate hyperhomocysteinemia in humans.