Thesis (Ph. D.)--University of Hong Kong, 1994. / Includes bibliographical references (leaves 90-100).

Thesis (M.S.)--Springfield College, 2002. / Includes bibliographical references.

Tierärztl. Hochsch., Diss., 2004--Hannover.

Tierärztl. Hochsch., Diss., 2004--Hannover.

ix, 46 leaves : ill. ; 29 cm Notes Typescript Thesis (M.S.)--University of Oregon, 1987 Includes vita and abstract Bibliography: leaves 37-46 Another copy on microfilm is located in Archives

Made available in DSpace on 2015-04-09T12:28:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-02-28Bitstream added on 2015-04-09T12:48:02Z : No. of bitstreams: 1 000813816.pdf: 2026611 bytes, checksum: 4bc553c95658091144370545d57b7857 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Avaliou-se a expressão do transportador de monocarboxilato 1 (MCT1) e sua proteína auxiliar CD147 nas hemácias de equinos da raça Brasileiro de Hipismo (BH) e de raças européias selecionadas para as mesmas modalidades. Utilizou-se 29 equinos, 16 da raça BH divididos em dois grupos segundo o histórico de competições em provas da modalidade salto, grupo de desempenho inferior (DI, n=8) e grupo de desempenho superior (DS, n=8) esta divisão foi confirmada pelo calculo do Custo de Frequência Cardíaca (CFC) e Custo de Lactato CLAC) e 13 equinos de origem européia que foram classificados como grupo Elite devido ao histórico de participação em provas com maiores alturas que os BHs. Com os BHs foram realizados dois testes um de velocidades incrementais (TVI) e um teste de saltos incrementais (TSI) onde valores de frequência cardíaca (FC) e lactato foram avaliados antes e após os testes, assim como sangue para a realização do Western Blot, o sangue dos animais Elite foram coletados antes após a Copa São Paulo de hipismo. Houve diferença estatística (p≤0,05) nos CFC e CLAC entre os grupos DI e DS no TSI e o mesmo não encontrado para o TVI. Em relação a expressão do MCT1 e CD147, houve diferença (p≤0,05) nos valores basais entre os BHs e o grupo Elite, não foram encontradas diferenças nas expressões entre os grupos DI e DS em quaisquer períodos de avaliação e o grupo Elite apresentou maior expressão (p≤0,05) de CD147 após a prova de hipismo. Concluiu-se que os BHs possuem maior expressão de MCT1 e CD147 quando comparados com raças européias e que estas expressam mais as proteínas estudadas após uma sessão aguda de esforço / We evaluated the expression of monocarboxylate transporter 1 (MCT1) and its ancillary protein CD147 in equine erythrocytes of Brazilian (BH) and European show jumphorses.We used 29 horses , 16 of BH breed divided into two groups according to his historical show jump competitions, group underperformed (DI, n = 8) and group of superior performance (DS, n = 8) this division was confirmed by calculating the Cost of Heart Rate (CFC) and Cost of Lactate (CLAC) and 13 horses of European origin which were classified as Elite group due to the history of participation in events with greater heights than BHs. The BHs were tested twice, with a incremental speeds test (TVI) and a test of incremental jumps (IST) where values of heart rate (HR) and lactate were evaluated before and after the tests as well as blood for the Western blot, Elite animals blood were collected before and after Copa São Paulo of show jump. There was a statistical difference (p≤ 0.05) in the CFC and CLAC between DI and DS groups in IST, the same was not found for TVI. Regarding the expression of MCT1 and CD147 , significant differences (p ≤ 0.05) at baseline between the BHs and the Elite group, no differences in expression were found between DI and DS groups in any evaluation periods and the Elite group had higher expression (p ≤ 0.05) of CD147 after the show jump competition. It was concluded that BH’s expression of MCT1 and CD147 is higher when compared to European breeds and that they express more CD147 after an acute bout of effort / FAPESP: 11/15804-2

Submitted by WALTER HEINZ FERINGER JUNIOR null (walterferinger@gmail.com) on 2018-03-22T22:47:37Z No. of bitstreams: 1 TESE_WALTER_HEINZ_FERINGER_JUNIOR.pdf: 2433033 bytes, checksum: 618fd780a0ad05e04e544c2769f96c3d (MD5) / Approved for entry into archive by Alexandra Maria Donadon Lusser Segali null (alexmar@fcav.unesp.br) on 2018-03-23T10:43:56Z (GMT) No. of bitstreams: 1 feringerjunior_wh_dr_jabo.pdf: 2433033 bytes, checksum: 618fd780a0ad05e04e544c2769f96c3d (MD5) / Made available in DSpace on 2018-03-23T10:43:56Z (GMT). No. of bitstreams: 1 feringerjunior_wh_dr_jabo.pdf: 2433033 bytes, checksum: 618fd780a0ad05e04e544c2769f96c3d (MD5) Previous issue date: 2017-11-13 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O principal mecanismo de transporte dos íons lactato e H+ em equinos e cães é o complexo transportador formado pelos transportadores de monocarboxilatos, isoformas 1 (MCT1) e 4 (MCT4) juntamente com a proteína auxiliar CD147. Objetivando identificar diferenças entre equinos com desempenho distinto, 16 equinos da raça Brasileiro de Hipismo (BH) foram distribuídos em dois grupos, desempenho inferior (DI, n=8) e desempenho superior (DS, n=8) que foram submetidos a teste de salto incrementai (TSI). Realizou-se biópsia do músculo Gluteus medius para tipificação e análise das expressões das isoformas MCT1, MCT4 e CD147. Amostras sanguíneas foram colhidas para avaliar as expressões MCT1 e CD147 das hemácias. Aplicaram-se testes de normalidade de Shapiro Wilk e homogeneidade de Levene. As medidas morfométricas foram submetidas ao teste de Tukey. Teste “t” de Student não pareado para a comparação das médias dos grupos DI e DS. Aplicou-se correlação de Spearman para as expressões dos transportadores. Para todas as análises utilizou-se p≤0,05. Não houve diferença entre os grupos quanto à frequência de cada tipo de fibra e constatou-se maior quantidade das fibras tipo I em relação às fibras IIA e IIX em todos os equinos avaliados. Não houve diferença entre os pesos moleculares e a expressão das proteínas MCT1, MCT4, e CD147 musculares ou sanguíneas. Houve correlações positivas entre MCT1 vs. CD147 e MCT4 vs. CD147 musculares dos grupos DI e DS. As correlações encontradas foram esperadas uma vez que as isoformas estudadas dependem intimamente da proteína auxiliar CD147 para o transporte. Os equinos BH não apresentaram diferenças nas expressões dos MCT1,4 e CD147, musculares ou sanguíneos, mesmo com níveis de condicionamento diferentes. Com o objetivo de investigar as concentrações de lactato plasmático e das hemácias e avaliar as expressões eritrocitáras do complexo transportador MT1/CD147, 6 cães da raça American Pitbull Terrier (APBT) foram submetidos ao teste de esforço incremental (TEI) em esteira. No final de cada incremento de velocidade foi coletado sangue da veia cefálica. Foram mensuradas concentrações de lactato sanguíneo (LS), plasmático (LP), pH e hematócrito (Ht). A concentração do lactato dentro das hemácias (LH) foi estimada e estabeleceu-se a relação LH:LP. As expressões sanguíneas do complexo MCT1/CD147 foram avaliadas por Western Bloting. Aplicou-se análise de variância de uma via seguido pelo teste de Dunn’s. Para pH e Ht aplicou-se teste t de student para amostras pareadas e a correlação de Pearson foi utilizada para MCT1 e CD147, estabeleceu-se nível de significância P≤0,05. LS, LP e LH e pH não apresentaram diferenças entre si, a relação LH:LP foi próxima de 1 com tendência de aumento. MCT1 e CD147 apresentaram 48 e 59 kDa de peso molecular e 1,27 e 1,05 de unidades ópticas arbitrárias (UOA). Não foram encontradas correlações entre MCT1 e CD147. A grande velocidade de transporte do MCT1/CD147 explica a relação LP:LH próxima de 1, esta velocidade e o mecanismo de arquejo podem explicar os valores de pH constantes. A raça APBT, quando submetidos à atividade física apresentaram tendência de aumento da relação LH:LP e expressam de maneira homogênea o complexo MCT1/CD147. / The central transport mechanism of lactate and H+ ions in horses and dogs is the carrier complex formed by the monocarboxylate, isoform 1 (MCT1) and 4 (MCT4) associated with the ancillary protein CD147. This study aimed to identify possible differences between horses with different performances levels, 16 horses of the Brazilian Sport Horse breed (BH) were distributed in two groups, inferior performance (IP, n = 8) and superior performance (SP, n = 8). A Gluteus medius muscle biopsy was performed for cellular typing and analysis of MCT1, MCT4, and CD147 muscle expressions. By jugular venipuncture, blood samples were collected to evaluate MCT1 and CD147 expressions in the red blood cells (RBC). Normality Shapiro Wilk test and homogeneity of Levene were applied. The morphometric measurements were submitted to the Tukey test, and not paired Student's t-test were applied to compare the mean of the IP and SP groups for all variables and was used Spearman's correlation for isoform expressions, for all analyzes, p≤0.05. There were no differences between the groups regarding the frequency of each type of fiber and a higher number of type I fibers were observed about the IIA and IIX fibers in all groups. There was no difference between molecular weights and expressions of MCT1, MCT4, and CD147 in muscle or blood. There were positive correlations between muscles MCT1 vs CD147 and MCT4 vs CD147 in both groups. The relationships found were expected since the MCT1 and 4 depended on the CD147 ancillary protein for correct functioning. The BH horses do not present differences in the muscle or RBC expressions of MCT1, 4 and CD147, even with different conditioning levels. To investigate plasma and erythrocyte lactate concentrations and to evaluate erythrocyte expression of the MT1/CD147 transporter complex, six dogs of the American Pit Bull Terrier breed (APBT) were submitted to a treadmill incremental effort test (IET). At the end of each increment of speed, blood was collected from the cephalic vein. Concentrations of blood (BL) and plasma lactate (PL), pH and hematocrit (Ht) were measured. The concentration of lactate inside the red blood cells (LC) was estimated and the LC: PL ratio was established, the blood expressions of the MCT1/CD147 transporter complex were evaluated by western blot. Data were submitted to the Shapiro-Wilks normality test, one-way ANOVA and Dunn's test. For pH and Ht, paired Student's t-test was applied, and Pearson's correlation was used for MCT1 and CD147 analysis, for all analyzes, p≤0.05. BL, PL, LC, pH showed no differences, the LC: PL ratio was close to 1 with an increasing tendency. MCT1 and CD147 presented 48 and 59 kDa of molecular weight and 1.27 and 1.05 of arbitrary optical units (AOU). No correlations were found between MCT1 and CD147. The high transport velocity of the MCT1/CD147 could explain the LC: PL ratio close to 1, this velocity plus the grasping mechanism may explain the constant of pH values. The APBT submitted to intense physical activity showed a tendency to increase the LC: PL ratio, and homogeneously express the MCT1/CD147 complex / FAPESP: 11/11080-0

Mitogen activated protein kinase (MAPK) signaling consists of a phosphorylation cascade leading to the phosphorylation of an effector that can translocate to the nucleus and regulate transcription. MAPK signaling can be activated by diverse stimuli such as osmotic stress and hormones. Additionally, MAPK signaling can be activated by receptor tyrosine kinase (RTK) signaling in response to a growth factor binding to the RTK. It has been shown that heterodimerization of the RTKs human epidermal growth factor receptor 2 (HER2) with HER3 is highly correlated to tumor growth and metastasis in breast cancer. Previous research showed that in breast cancer cells, Mitogen Three Kinase 1 (MTK1) is a protein kinase that functions in association with the HER3 receptor upon heregulin (HRG) stimulation. Here, MTK1 has been shown to form a complex in breast cancer cells consisting of Grb2, Shc, GIT1 and ERK1/2. Furthermore, MTK1 was shown to induce extracellular acidification due to lactate secretion and cell migration. A shift from aerobic metabolism to glycolysis in cancer cells was first observed by Otto Warburg. Since then, increased glycolysis and the resulting lactate secretion have been described in multiple types of cancers and is recognized as one of the hallmarks of cancer. This dissertation aims to establish the function of MTK1 in HRG induced RTK signaling in breast cancer cells. To accomplish this goal, we identified proteins of known function that interact with MTK1 to infer the role of MTK1. Applying this strategy, we provide evidence for the first time of mitochondrial regulation of oxidative phosphorylation by MTK1, independent of glycolytic regulation. In addition, our results demonstrate that GIT1 regulates glycolysis-mediated lactic acidosis (higher extracellular acidification caused by increased lactic acid efflux) in MCF-7 cells, independent of mitochondrial function. For the first time, our research shows that the glycolytic enzyme phosphoglycerate kinase 1 (PGK1) associates with MTK1 and GIT1 in MCF-7 cells. Furthermore, it is demonstrated that PGK1 is regulated by HRG stimulation through both phosphorylation of PGK1 and its dissociation from the MTK1 complex. The protein complex consisting of MTK1, GIT1, and PGK1 favors the conversion of pyruvate to lactate resulting rather than oxidative phosphorylation of pyruvate inside the mitochondria. The resulting lactate is secreted and drives extracellular acidification, a hallmark of cancer.

NMDA receptors are the most studied receptors in the field of neuroscience and are known to play an important role in development and plasticity. These receptors exhibit different kinetics depending on their subunit composition. NR2A and NR2B are the predominating NMDAR subunits in the brain. These receptors localize to synapses where they interact with other proteins including CaMKIIα, an abundant kinase which plays an important role in synaptic plasticity. Although CaMKIIα is known to bind to all types of NMDARs, it exhibits a higher affinity to NR2B compared to NR2A subunits. Studies have shown that lactate acts as a signaling molecule promoting the expression of genes related to synaptic plasticity via NMDARs activation. However, the mechanism describing how lactate exerts these effects is not well understood. We hypothesize that the redox state change, resulting from the metabolic conversion of lactate to pyruvate, may promote the interaction between CaMKIIα and NMDARs, thereby potentiating NMDARs activity. To tackle this question, we used a pharmacogenetics model consisting of NMDARs expressing HEK293 cells in the presence or absence of CaMKIIα. To monitor NMDARs activity, we use the ratio-metric calcium dye Fura-2 in calcium imaging experiments. We report that L-lactate decreases the peak responses of the NR2A and NR2B NMDARs in the absence of CaMKII expression. Upon CaMKII presence, we found that lactate prolongs the activation period of GluN2B as observed during the washout period and modestly increase the peak response of GluN2A NMDARs. Interestingly, we confirm that expressing CaMKIIα in control (no lactate) HEK cells significantly augmented NR2B but not NR2A NMDARs. We also report that pyruvate was able to increase peak responses of both NR2A and NR2B NMDARs in the absence of CaMKII, while it only increased the NR2A-NMDAR peak responses in the presence of CaMKII. These results suggest that lactate exerts a neuroprotective effect in the absence of CaMKII and it slightly boosts NR2B NMDARs activity when CaMKII is expressed, possibly favoring plasticity. Moreover, data obtained with pyruvate indicates that in our HEK cell model pyruvate affects the NMDARs in a manner independent of the presence of CaMKII through an alternative mechanism.

Title:
 Comparsion of the blood lactate level of an elite judokas during training and competition loads Objectives: The aim of this study was to compare the lactate level of an elite judokas during training and competition loads and to identify potential relationships with other entering variabilities. Methods: The chosen method was empirical, ie collecting data from its own research and statistical representation of the data and linked to the context with other studies. Results: It was found that lactate levels during competition load increases dramatically over training load and pulse rate has no statistical significance as an indicator of the accumulation of lactate. Key words:
 Judo, lactate, training, competition.