Carboxylesterases (CEs) are nonspecific hydrolytic enzymes and responsible for the metabolism of xenobiotics and endobiotics that contain ester bonds. There are two human CE isoforms found in liver, CES1 and CES2. In this study it is shown that the mere abundance of CES1 protein expression in human liver does not predict its biochemical activity. The human interindividual variation in CES1 activities may attribute to several mechanisms. One possibility is the presence of endogenous inhibitors in liver, arachidonic acid (AA) and 27-hydroxycholesterol (27-HC). CES1 is also expressed in human monocytes/macrophages and is proposed to catalyze the rate-limiting step of cholesterol ester mobilization in macrophages. It is of interest to determine whether CES1 can degrade the lipid mediators, 2-arachidonoylglycerol (2-AG), prostaglandin E2-1-glyceryl ester (PGE2-G), and prostaglandin F2α-1-glyceryl ester (PGF2α-G), in monocytes/macrophages and to determine if this metabolism is inhibited by organophosphate pesticide exposure.

Recent retrospectives of classic psychology articles by Meehl (1978) and Wachtel (1980), concerning problems with psychology’s research paradigm, have been viewed by commentators, on the whole, as germane as when first published. However, no similar examination of Lykken’s (1991) classic criticisms of psychology’s dominant research tradition has been undertaken. Twenty years on, this thesis investigates whether Lykken’s criticisms and conclusions are still valid via an exposition of three contentious issues in psychological science: the measurement problem, null hypothesis significance testing, and the granularity of research methods. Though finding that little progress has been made, Observation Oriented Modelling is advanced as a promising methodological solution for improving psychological research.

<p>This investigation focused on the mRNA expression of drug metabolising Cytochromes P-450 (CYP) and UDP-glucuronosyltransferases (UGT) and the transport protein P-glycoprotein (Pgp) in the small intestine of humans and rats.</p><p>The mRNA expression of the investigated genes in the human small intestine (duodenum) varies between individuals giving each one of us personal profile. In general, the most dominant forms are Pgp, CYPs 2C9, 2D6, 3A4, and UGTs 1A1, 1A10, 2B7. However, which of these is the highest expressed one varies between individuals.</p><p>The correlation in expression between some CYP forms and UGT forms respectively is relatively high, which indicates that they have some regulatory mechanisms in common. It was also shown that the mRNA expression of both CYPs and UGTs may be affected by endogenous and exogenous factors. Sex and ethnic background, affected the mRNA expression of CYP2A6 and 2E1 respectively. Commonly used drugs such as acetylsalicylicacid (ASA) and omeprazole (omep) affect CYP2A6, CYP2E1 (ASA) and CYP3A4, UGT1A4 (omep). The expression of UGT1A4 is also affected by smoking. All these factors are commonly used and can therefore lead to important drug-drug interactions.</p><p>It was also shown that the human small intestinal CYP mRNA expression pattern differs from that found in the rat. The rat CYP expression is rather constant between the different individuals, and the main rat intestinal forms are CYP1A1, CYP2C, CYP2D6 and CYP3A1. The expression is the same for females and males and no difference can be seen between the different segments of the rat small intestine. As metabolic studies have often been done with rat liver we compared the mRNA expression in the two organs. We found that the mRNA expression of 1A1 was absent in the liver and that the CYP2B1, CYP2Cs, CYP2D1 and Pgp all had a stronger mRNA expression in the small intestine compared to the liver. It is therefore important to realise that results from metabolic studies on liver may not be directly extrapolated to the small intestine.</p><p>Artemisinin is an orally used drug in multidrug treatment of malaria in Southeast Asia. It has been suggested that artemisinin can induce drug metabolism and therefore be involved in drug-drug interactions. This study shows that artemisinin induces mainly the CYP2B via nuclear receptor CAR.</p>

This investigation focused on the mRNA expression of drug metabolising Cytochromes P-450 (CYP) and UDP-glucuronosyltransferases (UGT) and the transport protein P-glycoprotein (Pgp) in the small intestine of humans and rats. The mRNA expression of the investigated genes in the human small intestine (duodenum) varies between individuals giving each one of us personal profile. In general, the most dominant forms are Pgp, CYPs 2C9, 2D6, 3A4, and UGTs 1A1, 1A10, 2B7. However, which of these is the highest expressed one varies between individuals. The correlation in expression between some CYP forms and UGT forms respectively is relatively high, which indicates that they have some regulatory mechanisms in common. It was also shown that the mRNA expression of both CYPs and UGTs may be affected by endogenous and exogenous factors. Sex and ethnic background, affected the mRNA expression of CYP2A6 and 2E1 respectively. Commonly used drugs such as acetylsalicylicacid (ASA) and omeprazole (omep) affect CYP2A6, CYP2E1 (ASA) and CYP3A4, UGT1A4 (omep). The expression of UGT1A4 is also affected by smoking. All these factors are commonly used and can therefore lead to important drug-drug interactions. It was also shown that the human small intestinal CYP mRNA expression pattern differs from that found in the rat. The rat CYP expression is rather constant between the different individuals, and the main rat intestinal forms are CYP1A1, CYP2C, CYP2D6 and CYP3A1. The expression is the same for females and males and no difference can be seen between the different segments of the rat small intestine. As metabolic studies have often been done with rat liver we compared the mRNA expression in the two organs. We found that the mRNA expression of 1A1 was absent in the liver and that the CYP2B1, CYP2Cs, CYP2D1 and Pgp all had a stronger mRNA expression in the small intestine compared to the liver. It is therefore important to realise that results from metabolic studies on liver may not be directly extrapolated to the small intestine. Artemisinin is an orally used drug in multidrug treatment of malaria in Southeast Asia. It has been suggested that artemisinin can induce drug metabolism and therefore be involved in drug-drug interactions. This study shows that artemisinin induces mainly the CYP2B via nuclear receptor CAR.

Originalmente, a teoria de nicho ecológico fundamenta-se em indivíduos de uma espécie sendo ecologicamente equivalentes por utilizarem os recursos de forma similar. Portanto, o nicho de uma espécie é definido em termos do uso médio de recursos. Porém, a qualidade e abundância de recursos consumidos, sexo, idade ou morfotipo do consumidor influenciam o comportamento alimentar individual. Estudos recentes sobre forrageamento ótimo tem foco de interesse na variação interindividual no uso de recursos. Ao longo da sua área de distribuição são reconhecidas populações da toninha Pontoporia blainvillei (Cetacea) e no litoral paulista, possivelmente hajam três subpopulações dessa espécie: norte, centro e sul. Meu primeiro objetivo foi investigar se há variação na dieta entre essas três subpopulações de toninha. Adicionalmente, investiguei quais fatores entre sazonalidade, sexo e idade dos indivíduos poderiam estruturar a dieta em uma dessas subpopulações (central). Utilizei 58 indivíduos provenientes de captura acidental no litoral paulista, com representantes das regiões norte, centro e sul. A amostra incluiu juvenis e adultos de ambos os sexos, capturados em todas as estações do ano. Identifiquei as espécies nos conteúdos estomacais usando os otólitos de peixes e os bicos de lulas. Estimei o tamanho das presas utilizando regressões com as medidas dessas estruturas e investiguei a estruturação da dieta usando um índice de variação da dieta. Houve uma clara variação na dieta ente as subpopulações paulistas, possivelmente devido à diferença espacial na disponibilidade de presas. Para a subpopulação central não houve variação na dieta decorrente da sazonalidade ou do sexo. A ausência de variação sazonal pode ser devido à pouca alteração na abundância da principal presa, P. harroweri, no ambiente ao longo do ano. A ausência de variação decorrente do sexo pode ser devido a seleção de presa estar mais relacionada a características de corpo mole e fácil digestão e não ao tamanho da presa, sendo essa seleção comum para ambos os sexos. Indivíduos de idades diferentes possuem dietas distintas, com juvenis consumindo mais espécies que os adultos. Essa mudança de nicho alimentar pode ser devida ao período de aprendizado. Finalmente, mesmo descontando os efeitos da disponibilidade temporal e espacial de presas, do sexo e da idade, houve variação interindividual da dieta na subpopulação central. Somente estudos com marcadores isotópicos poderão investigar se essa variação é devida à especialização individual em toninhas / Ecological niche theory is originally based on the assumption that individuals of a species use similar resources and therefore are ecologically equivalents. Under this framework, the niche of the species can be defined in terms of average resource use. However, factors such as quality and quantity of prey resources in the environment, consumer gender, age or morphotype may influence the individual feeding behavior. Considering that possible interindividual variation, recently studies under optimal foraging theory have variation among individuals as a focus of interest. The species P. blainvillei is partionated in populations along its range and probably, subpopulations can be found in the Sao Paulo state coast: northern, central and southern. Hence, my first goal was to investigate if there is diet variation among the three franciscana subpopulations from Sao Paulo coast. Additionally, I searched for which factors would be the diet structure defined within one of the subpopulations (the central one). I have considered the seasonality, individual gender and sex as possible factors influencing the diet structure within the central subpopulation. I had 58 franciscana specimens obtained from bycatch in the Sao Paulo coast, being them from northern, central and southern regions. They were juveniles and adults of both genders and bycaught in all the seasons. I identified the prey species from the gut contents with fish otholits and squid beaks. I estimated prey length and weight using regressions with that structures measures and I investigated the diet structure using a diet variation index. Within the central subpopulation I found no diet variation based on seasonality or individual gender, instead I found diet variation for individuals from different ages. Probably, most of the diet variation among subpopulations is due to prey availability spatial difference. The lack of diet variation based on seasonality may be due to little seasonal variation in the abundance of the main prey, P. harroweri. The lack of variation due to gender is probably related to the prey selection on soft body and easy digestion instead of prey size, being this type of selection common for both genders. Juveniles franciscana preyed on more species than the adults and that niche shift as an age effect can be consequence of forraging skills development. Enclosing, even discarding the effects of the spacial and temporal prey availability, individual gender and age, I found interindividual-level diet variation within the central subpopulation, which can points out to franciscana individual specialization, but isotopic studies are required to infer that specialization

Originalmente, a teoria de nicho ecológico fundamenta-se em indivíduos de uma espécie sendo ecologicamente equivalentes por utilizarem os recursos de forma similar. Portanto, o nicho de uma espécie é definido em termos do uso médio de recursos. Porém, a qualidade e abundância de recursos consumidos, sexo, idade ou morfotipo do consumidor influenciam o comportamento alimentar individual. Estudos recentes sobre forrageamento ótimo tem foco de interesse na variação interindividual no uso de recursos. Ao longo da sua área de distribuição são reconhecidas populações da toninha Pontoporia blainvillei (Cetacea) e no litoral paulista, possivelmente hajam três subpopulações dessa espécie: norte, centro e sul. Meu primeiro objetivo foi investigar se há variação na dieta entre essas três subpopulações de toninha. Adicionalmente, investiguei quais fatores entre sazonalidade, sexo e idade dos indivíduos poderiam estruturar a dieta em uma dessas subpopulações (central). Utilizei 58 indivíduos provenientes de captura acidental no litoral paulista, com representantes das regiões norte, centro e sul. A amostra incluiu juvenis e adultos de ambos os sexos, capturados em todas as estações do ano. Identifiquei as espécies nos conteúdos estomacais usando os otólitos de peixes e os bicos de lulas. Estimei o tamanho das presas utilizando regressões com as medidas dessas estruturas e investiguei a estruturação da dieta usando um índice de variação da dieta. Houve uma clara variação na dieta ente as subpopulações paulistas, possivelmente devido à diferença espacial na disponibilidade de presas. Para a subpopulação central não houve variação na dieta decorrente da sazonalidade ou do sexo. A ausência de variação sazonal pode ser devido à pouca alteração na abundância da principal presa, P. harroweri, no ambiente ao longo do ano. A ausência de variação decorrente do sexo pode ser devido a seleção de presa estar mais relacionada a características de corpo mole e fácil digestão e não ao tamanho da presa, sendo essa seleção comum para ambos os sexos. Indivíduos de idades diferentes possuem dietas distintas, com juvenis consumindo mais espécies que os adultos. Essa mudança de nicho alimentar pode ser devida ao período de aprendizado. Finalmente, mesmo descontando os efeitos da disponibilidade temporal e espacial de presas, do sexo e da idade, houve variação interindividual da dieta na subpopulação central. Somente estudos com marcadores isotópicos poderão investigar se essa variação é devida à especialização individual em toninhas / Ecological niche theory is originally based on the assumption that individuals of a species use similar resources and therefore are ecologically equivalents. Under this framework, the niche of the species can be defined in terms of average resource use. However, factors such as quality and quantity of prey resources in the environment, consumer gender, age or morphotype may influence the individual feeding behavior. Considering that possible interindividual variation, recently studies under optimal foraging theory have variation among individuals as a focus of interest. The species P. blainvillei is partionated in populations along its range and probably, subpopulations can be found in the Sao Paulo state coast: northern, central and southern. Hence, my first goal was to investigate if there is diet variation among the three franciscana subpopulations from Sao Paulo coast. Additionally, I searched for which factors would be the diet structure defined within one of the subpopulations (the central one). I have considered the seasonality, individual gender and sex as possible factors influencing the diet structure within the central subpopulation. I had 58 franciscana specimens obtained from bycatch in the Sao Paulo coast, being them from northern, central and southern regions. They were juveniles and adults of both genders and bycaught in all the seasons. I identified the prey species from the gut contents with fish otholits and squid beaks. I estimated prey length and weight using regressions with that structures measures and I investigated the diet structure using a diet variation index. Within the central subpopulation I found no diet variation based on seasonality or individual gender, instead I found diet variation for individuals from different ages. Probably, most of the diet variation among subpopulations is due to prey availability spatial difference. The lack of diet variation based on seasonality may be due to little seasonal variation in the abundance of the main prey, P. harroweri. The lack of variation due to gender is probably related to the prey selection on soft body and easy digestion instead of prey size, being this type of selection common for both genders. Juveniles franciscana preyed on more species than the adults and that niche shift as an age effect can be consequence of forraging skills development. Enclosing, even discarding the effects of the spacial and temporal prey availability, individual gender and age, I found interindividual-level diet variation within the central subpopulation, which can points out to franciscana individual specialization, but isotopic studies are required to infer that specialization