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.

Orientador : Carmen Silvia Bertuzzo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-02T04:23:22Z (GMT). No. of bitstreams: 1 Santos_Kelly_M.pdf: 15332993 bytes, checksum: 39bff3e0afd6a69cc924f944b9927971 (MD5) Previous issue date: 2002 / Resumo: A Síndrome de Turner (ST), descrita por Henry Turner em 1938, caracteriza-se classicamente por um fenótipo feminino associado à baixa estatura, infantilismo sexual, esterilidade, além de diversas malfonnações. Há evidências de que mutações na enzima metilenotetrahidrofolato redutase (MTHFR), ligada ao metabolismo do ácido fólico, levariam a aberrações cromossômicas devido a fenômenos de hipometilação. No presente estudo nós avaliamos a freqüência das mutações C677T e A1298C no gene da MTHFR em 49 portadoras de ST e em 200 indivíduos controles. O método de análise foi a Reação em Cadeia da Polimerase (PCR) seguida de digestão enzimática específica. Encontramos 26% de pacientes heterozigotas para a mutação C677T, 18% de homozigotas mutantes para a mutação C677T, 22% de pacientes heterozigotas A1298C, 10% de homozigotas mutante 1298C e 14% de heterozigotas para ambas as mutações C677T/A1298C. Nossos resultados indicam uma incidência elevada de indivíduos mutantes C677T (p<0,001) em nossa amostra. Sugerindo que a deficiência da MTHFR pode ser identificada como um fator de risco para nascimentos de crianças com ST / Abstract: Henry Tumer described Turner's syndrome (TS) in 1938 and characterized it as a classicaI female phenotype associated with a short stature, sexual irmnaturity,sterility and other maIformations. Evidences exist that methylenetetrahydrofolate reductase (MTHFR) enzyme mutations related to folic acid metabolism lead to chromosomal aberrations due to the hypomethylation phenomenon. This study evaIuates the frequency of C677T and A1298C mutations of the MTHFR gene among 49 individuais with TS and 200 control individuais. An analysisof the results was obtained using the polymerase chain reaction (PCR), which was followed by specific enzymatic digestion. In this study, 26% of patients were heterozygous for the C677T mutation, 18% were homozygous for the C677T mutation, 22% ofthe patients were heterozygous for the A1298C mutation and 14% were heterozygous for both C677T/A1298C mutations. Our results demonstrated a higher incidence of C677T mutant individuais (p<0.001) in this sample. Suggesting that MTHFR deficiency can be defined as a risk factor for the birth of TS children / Mestrado / Ciencias Biomedicas / Mestre em Ciências Médicas

No description available.

No description available.

Yes / Background: The changes that occur in the microbiome of aging individuals are unclear, especially in light of the imperfect correlation of frailty with age. Studies in older human subjects have reported subtle effects, but these results may be confounded by other variables that often change with age such as diet and place of residence. To test these associations in a more controlled model system, we examined the relationship between age, frailty, and the gut microbiome of female C57BL/6 J mice. Results: The frailty index, which is based on the evaluation of 31 clinical signs of deterioration in mice, showed a near-perfect correlation with age. We observed a statistically significant relationship between age and the taxonomic composition of the corresponding microbiome. Consistent with previous human studies, the Rikenellaceae family, which includes the Alistipes genus, was the most significantly overrepresented taxon within middle-aged and older mice. The functional profile of the mouse gut microbiome also varied with host age and frailty. Bacterial-encoded functions that were underrepresented in older mice included cobalamin (B12) and biotin (B7) biosynthesis, and bacterial SOS genes associated with DNA repair. Conversely, creatine degradation, associated with muscle wasting, was overrepresented within the gut microbiomes of the older mice, as were bacterial-encoded β-glucuronidases, which can influence drug-induced epithelial cell toxicity. Older mice also showed an overabundance of monosaccharide utilization genes relative to di-, oligo-, and polysaccharide utilization genes, which may have a substantial impact on gut homeostasis. Conclusion: We have identified taxonomic and functional patterns that correlate with age and frailty in the mouse microbiome. Differences in functions related to host nutrition and drug pharmacology vary in an age-dependent manner, suggesting that the availability and timing of essential functions may differ significantly with age and frailty. Future work with larger cohorts of mice will aim to separate the effects of age and frailty, and other factors. / This work was supported by the Canadian Institutes of Health Research (CIHR) through an Emerging Team Grant to RGB, CIHR Operating Grants to Langille et al. Microbiome 2014, 2:50 Page 10 of 12 http://www.microbiomejournal.com/content/2/1/50 SEH (MOP 126018) and RAR (MOP 93718), and a CIHR Fellowship to MGIL. Infrastructure was supported by the Canada Foundation for Innovation through a grant to RGB. RGB also acknowledges the support of the Canada Research Chairs program.

Orientador: Flávia Lombardi Lopes / Resumo: A meningite se caracteriza pela inflamação da aracnóide, pia-máter e líquor; causando danos às estruturas corticais e subcorticais. As meningites bacterianas estão intimamente relacionadas ao nível de desenvolvimento socioeconômico do país e são consideradas endêmicas no Brasil. Apesar dos esforços para o desenvolvimento de medicamentos e vacinas, a doença ainda possui altos índices de morbidade. Ela ocorre quando bactérias atravessam barreiras de proteção do corpo e alcançam o sistema nervoso central, desencadeando uma resposta imunológica. Sabe-se que durante o curso da doença os níveis de homocisteína do líquor aumentam, promovendo desmielinização e danos neuronais, e que a vitamina B12 é um tratamento utilizado para diminuir danos. Os microRNAs (miRNAs) são instrumentos de resposta fisiológica, tendo sua expressão modificada em diferentes tecidos, em decorrência de diferentes estímulos fisiológicos e patológicos. Estão associados ao controle da expressão de diferentes mediadores inflamatórios e sua ausência é capaz de causar danos severos a resposta imune. Considerando a importância dos miRNAs para regulação de processos imunes o presente estudo visou elucidar os padrões de expressão dos miRNAs durante o processo inflamatório da meningite pneumocócica (MP), bem como observar esses padrões em resposta ao tratamento adjuvante da doença com vitamina B12. Observamos um total de 37 miRNAs diferencialmente expressos, a infecção regulou positivamente 22 deles, e outros 7 negativ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Meningitis is characterized by an arachnoid, pia mater and cerebrospinal fluid inflammation; causing damage to the cortical and subcortical structures. Bacterial meningitis is closely related to the level of socioeconomic development of country and is considered endemic in Brazil. Despite efforts to develop drugs and vaccines, the disease still has high rates of morbidity and mortality. Occurring when bacteria cross body protection barriers and reach the central nervous system, triggering immune response. It is known that during disease course the the levels of homocysteine increase in cerebrospinal fluid, leading to demyelination and neuronal damage, and that vitamin B12 is a treatment used to reduce those damages. MicroRNAs (miRNAs) are instruments of physiological response, having their expression modified in different tissues, due to different physiological and pathological stimuli. They are associated with expression control of different inflammatory mediators and their absence is capable of causing severe damage to the immune response. Considering the importance of miRNAs in regulation of immune processes, the present study aimed to elucidate miRNA expression patterns during the inflammatory process resulting from pneumococcal meningitis (PM), and to observe these patterns in response to adjuvant treatment of vitamin B12 in infected rats. We observed a total of 37 differentially expressed miRNAs; the infection positively regulated 22 and negatively regulated 7 of them, ... (Complete abstract click electronic access below) / Mestre

Submitted by Maria Beatriz Vieira (mbeatriz.vieira@gmail.com) on 2017-08-25T16:39:37Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) dissertacao_marcelo_moreira_antunes.pdf: 492507 bytes, checksum: 41f643876649cd9c16f704b84a4e0fae (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2017-08-28T20:59:07Z (GMT) No. of bitstreams: 2 dissertacao_marcelo_moreira_antunes.pdf: 492507 bytes, checksum: 41f643876649cd9c16f704b84a4e0fae (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Aline Batista (alinehb.ufpel@gmail.com) on 2017-08-28T20:59:16Z (GMT) No. of bitstreams: 2 dissertacao_marcelo_moreira_antunes.pdf: 492507 bytes, checksum: 41f643876649cd9c16f704b84a4e0fae (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-08-28T20:59:24Z (GMT). No. of bitstreams: 2 dissertacao_marcelo_moreira_antunes.pdf: 492507 bytes, checksum: 41f643876649cd9c16f704b84a4e0fae (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2015-03-27 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / O objetivo deste estudo foi avaliar os efeitos da aplicação de fósforo orgânico (butafosfan) e vitamina B12 (cianocobalamina) sobre marcadores do metabolismo energético, mineral e inflamatório, produção de leite e sobre o índice de funcionalidade hepática de vacas leiteiras primíparas. Vinte e três vacas da raça Holandês foram aleatoriamente separadas em três grupos experimentais: Catosal (CAT, n = 8), que receberam total de 100 mL de Catosal®; Butafosfan (BUT, n = 8), que receberam total de 100 mL de solução aquosa de Butafosfan; e Controle (CTL, n = 7), que receberam total de 100 mL de solução fisiológica 0,9%. Todos os animais receberam os 100 mL divididos em 5 aplicações de 20 mL, em intervalos de 24 horas, por via subcutânea, iniciando logo após o parto. Os animais do grupo BUT apresentaram menores concentrações (P<0,05) de beta hidroxibutirato que os animais do grupo CTL. Os demais parâmetros metabólicos, o escore de condição corporal e a produção de leite não foram influenciados pelos tratamentos (P>0,05). O índice de funcionalidade hepática não foi influenciado pelos tratamentos (P>0,05). Após a separação dos animais em grupos de alto e baixo índice de função hepática, os animais do grupo com melhor função hepática (alto) apresentaram menores concentrações de beta hidroxibutirato (P<0,05) e tendência de menores concentrações de ácidos graxos não esterificados (P<0,10), enquanto que os animais com pior função hepática (baixo) apresentaram tendência de menores concentrações de albumina (P<0,10). Em conclusão, neste estudo o índice de funcionalidade hepática não foi influenciado pelos tratamentos. / The objective of this study was to evaluate the effects of organic phosphorus (butafosfan) and vitamin B12 (cyanocobalamin) on markers of energy, mineral and inflammatory metabolism, milk production and the liver functionality index of primiparous dairy cows. Twenty-three Holstein dairy cows were randomly allocated into three groups: Catosal (CAT, n = 8), receiving total of 100 mL of Catosal®; Butafosfan (BUT, n = 8) that received a total of 100 mL of aqueous Butafosfan; and Control (CTL, n = 7), receiving total of 100 mL of 0.9% saline. All the animals received the 100 mL divided in five 20 mL applications at 24-hour intervals, subcutaneously, beginning soon after birth. The animals in the group BUT showed lower beta-hydroxybutyrate concentrations (P<0.05) than animals in the CTL group. The other metabolic parameters, body condition score and milk production were not affected by treatments (P>0.05). The liver functionality index was not affected by treatments (P> 0.05). After the separation of the animals in groups of high and low index of liver function, the animals of the group with better liver function (high) had lower concentrations of beta-hydroxybutyrate (P<0.05) and a trend of lower concentrations of non-esterified fatty acids (P<0.10), whereas the animals with poor liver function (low) showed a tendency to have lower concentrations of albumin (P <0.10). In conclusion, in this study the liver functionality index was not affected by treatments.

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.