Meta-analysis of the population and phenotypic expression of CYP2C9/2C19 polymorphism on drug metabolism in different ethnicities

The term "pharmacogenetics" has been defined as the scientific study of inherited factors that affect the human drug response. Many pharmacogenetie studies have been published since 1995 and have focussed on the principal enzyme family involved in drug metabolism, the cytochrome P450 family, particularly cytochrome P4502C9 and 2C19. In order to investigate the pharmacogenetic aspect of pharmacotherapy, the relevant studies describing the association of pharmacogenetic factor(s) in drug responses must be retrieved from existing literature using a systematic review approach. In addition, the estimation of variant allele prevalence for the gene under study between different ethnic populations is important for pharmacogenetic studies. In this thesis, the prevalence of CYP2C9/2C19 alleles between different ethnicities has been estimated through meta-analysis and the population genetic principle. The clinical outcome of CYP2C9/2C19 allelic variation on the pharmacotherapy of epilepsy has been investigated; although many new antiepileptic drugs have been launched into the market, carbamazepine, phenobarbital and phenytoin are still the major agents in the pharmacotherapy of epilepsy. Therefore, phenytoin was chosen as a model AED and the effect of CYP2C9/2C19 genetic polymorphism on phenytoin metabolism was further examined.An estimation of the allele prevalence was undertaken for three CYP2C9/2C19 alleles respectively using a meta-analysis of studies that fit the Hardy-Weinberg equilibrium. The prevalence of CYP2C9*1 is approximately 81%, 96%, 97% and 94% in Caucasian, Chinese, Japanese, African populations respectively; the pooled prevalence of CYP2C19*1 is about 86%, 57%, 58% and 85% in these ethnic populations respectively. However, the studies of association between CYP2C9/2C19 polymorphism and phenytoin metabolism failed to achieve any qualitative or quantitative conclusion. Therefore, mephenytoin metabolism was examined as a probe drug for association between CYP2C19 polymorphism and mephenytoin metabolic ratio. Similarly, analysis of association between CYP2C9 polymorphism and warfarin dose requirement was undertaken.It was confirmed that subjects carrying two mutated CYP2C19 alleles have higher S/R mephenytoin ratio due to deficient CYP2C19 enzyme activity. The studies of warfarin and CYP2C9 polymorphism did not provide a conclusive result due to poor comparability between studies.The genetic polymorphism of drug metabolism enzymes has been studied extensively, however other genetic factors, such as multiple drug resistance genes (MDR) and genes encoding ion channels, which may contribute to variability in function of drug transporters and targets, require more attention in future pharmacogenetic studies of antiepileptic drugs.

Designing Lifestyle-specific Food Policies Based on Nutritional Requirements and Ecological Footprints.

Expanded understanding of the trends and determinants of food consumption is needed to reduce the ecological impacts of the contemporary agro-food system while also being attentive to broader issues pertaining to health and the environment. Incorporating these additional aspects and formulating meaningful dietary recommendations is a major challenge. This article seeks to highlight differences in ecological footprint (EF) by activity level for various so-cial groups to meet suggested physiological requirements by nutritionists versus actual food consumption. The study is based on a combination of healthy diet requirements (as expressed by national guidelines) and a survey of a repre-sentative sample of 1,013 Hungarian adults using a bottom-up approach for calculating EFs. Students and women with small children have a higher than average food-related EF due to their higher nutritional needs. At the same time, the elderly are characterized by lower footprints. Perhaps most interesting is our finding that people with seden-tary forms of employment have higher food footprints than those with jobs that require physical labor. We offer rec-ommendations for food-policy planning based on encouraging dietary changes for individuals, differentiated by the nature of their work. The research suggests that dietary policy that improves health often has environmental benefits.

Minsk and Budapest, the two capital cities. Selected studies of post-socialist urban geography and ecological problems of urban areas

The official cooperation between the Hungarian and the Belarusian geography began to be outlined in a sunny afternoon of June 2010 in the Minsk building of the Geographic Faculty of the Belarusian State University, four years ago. Then we reviewed the potential frames of cooperation with Professor Ekaterina Antipova. It was supported by the academican Károly Kocsis, member of the Hungarian Academy of Sciences, director of the Geographical Research Institute, and we could also win the support of the dean Ivan Pirozhnik and the academician Vladimir Loginov from the Belarusian State University and the National Academy of Sciences of Belarus, respectively. This informal cooperation became official in the autumn of 2010 in the frame of the Academic Mobility Agreement Project between the Hungarian and the Belarusian academies of sciences. Since then several publications have appeared about Hungary and Belarus in the geographic journals of both countries, however, this is the first, long awaited, significant common publication. Besides the project-based co-operations like e. g. the EastMig (www.eastmig.mtafki.hu) and the ReSEP-CEE (www.mtafki.hu/ReSEP_CEE_Be.html) supported by the Visegrad Fund, a vivid student exchange program was also launched from the autumn of 2010 between the Geographic Research Institute of the Hungarian Academy of Sciences, and the Geographic Faculty of the Belarusian State University with the scholarship program of the Visegrad Fund. Later the Department of Economic Geography of the Corvinus University of Budapest, headed by István Tózsa became also an active partner of the cooperation. The publishing expenses of this book are also fully financed by the Department of Economic Geography.

Phylogenetic and ecological significance in the evolution of Cetacean tonal sounds

Cetaceans are aquatic mammals that rely primarily on sound for most daily tasks. A compendium of sounds is emitted for orientation, prey detection, and predator avoidance, and to communicate. Communicative sounds are among the most studied Cetacean signals, particularly those referred to as tonal sounds. Because tonal sounds have been studied especially well in social dolphins, it has been assumed these sounds evolved as a social adaptation. However, whistles have been reported in ‘solitary’ species and have been secondarily lost three times in social lineages. Clearly, therefore, it is necessary to examine closely the association, if any, between whistles and sociality instead of merely assuming it. Several hypotheses have been proposed to explain the evolutionary history of Cetacean tonal sounds. The main goal of this dissertation is to cast light on the evolutionary history of tonal sounds by testing these hypotheses by combining comparative phylogenetic and field methods. This dissertation provides the first species-level phylogeny of Cetacea and phylogenetic tests of evolutionary hypotheses of cetacean communicative signals. Tonal sounds evolution is complex in that has likely been shaped by a combination of factors that may influence different aspects of their acoustical structure. At the inter-specific level, these results suggest that only tonal sound minimum frequency is constrained by body size. Group size also influences tonal sound minimum frequency. Species that live in large groups tend to produce higher frequency tonal sounds. The evolutionary history of tonal sounds and sociality may be intertwined, but in a complex manner rejecting simplistic views such as the hypothesis that tonal sounds evolved ‘for’ social communication in dolphins. Levels of social and tonal sound complexity nevertheless correlate indicating the importance of tonal sounds in social communication. At the intraspecific level, tonal sound variation in frequency and temporal parameters may be product of genetic isolation and local levels of underwater noise. This dissertation provides one of the first insights into the evolution of Cetacean tonal sounds in a phylogenetic context, and points out key species where future studies would be valuable to enrich our understanding of other factors also playing a role in tonal sound evolution. ^

A relationship between the Florida Comprehensive Assessment Test 2.0 mathematics scores and racial and ethnic concentration when considering socio-economic status, ESOL student population, and school climate

From the moment children are born, they begin a lifetime journey of learning about themselves and their surroundings. With the establishment of the No Child Left Behind Act of 2001, it mandates that all children receive a high-quality education in a positive school climate. Regardless of the school the child attends or the neighborhood in which the child lives, proper and quality education and resources must be provided and made available in order for the child to be academically successful. The purpose of this ex post facto study was to investigate the relationship between the FCAT 2.0 mathematics scores of public middle school students in Miami-Dade County, Florida and the concentrations of a school's racial and ethnic make-up (Whites, Blacks, and Hispanics), English for Speakers of other Languages (ESOL) population, socio-economic status (SES), and school climate. The research question of this study was: Is there a significant relationship between the FCAT 2.0 Mathematics scores and racial and ethnic concentration of public middle school students in Miami-Dade County when controlling SES, ESOL student population, and school climate for the 2010-2011 school year? The instruments used to collect the data were the FCAT 2.0 and Miami-Dade County Public Schools (M-DCPS) School Climate Survey. The study found that Economically Disadvantaged (SES) students socio-economic status had the strongest correlation with the FCAT 2.0 mathematics scores (r = -.830). The next strongest correlation was with the number of students who agreed that their school climate was positive and helped them learn (r = .741) and the third strongest correlation was a school percentage of White students (r = .668). The study concluded that the FCAT 2.0 mathematics scores of M-DCPS middle school students have a significant relationship with socio-economic status, school climate, and racial concentration.

Phylogenetic and Ecological Significance in the Evolution of Cetacean Tonal Sounds

Cetaceans are aquatic mammals that rely primarily on sound for most daily tasks. A compendium of sounds is emitted for orientation, prey detection, and predator avoidance, and to communicate. Communicative sounds are among the most studied Cetacean signals, particularly those referred to as tonal sounds. Because tonal sounds have been studied especially well in social dolphins, it has been assumed these sounds evolved as a social adaptation. However, whistles have been reported in ‘solitary’ species and have been secondarily lost three times in social lineages. Clearly, therefore, it is necessary to examine closely the association, if any, between whistles and sociality instead of merely assuming it. Several hypotheses have been proposed to explain the evolutionary history of Cetacean tonal sounds. The main goal of this dissertation is to cast light on the evolutionary history of tonal sounds by testing these hypotheses by combining comparative phylogenetic and field methods. This dissertation provides the first species-level phylogeny of Cetacea and phylogenetic tests of evolutionary hypotheses of cetacean communicative signals. Tonal sounds evolution is complex in that has likely been shaped by a combination of factors that may influence different aspects of their acoustical structure. At the inter-specific level, these results suggest that only tonal sound minimum frequency is constrained by body size. Group size also influences tonal sound minimum frequency. Species that live in large groups tend to produce higher frequency tonal sounds. The evolutionary history of tonal sounds and sociality may be intertwined, but in a complex manner rejecting simplistic views such as the hypothesis that tonal sounds evolved ‘for’ social communication in dolphins. Levels of social and tonal sound complexity nevertheless correlate indicating the importance of tonal sounds in social communication. At the intraspecific level, tonal sound variation in frequency and temporal parameters may be product of genetic isolation and local levels of underwater noise. This dissertation provides one of the first insights into the evolution of Cetacean tonal sounds in a phylogenetic context, and points out key species where future studies would be valuable to enrich our understanding of other factors also playing a role in tonal sound evolution.

Population and life-stage specific sensitivities to temperature and salinity stress in barnacles

Temperature and salinity shape the distribution and genetic structure of marine communities. Future warming and freshening will exert an additional stress to coastal marine systems. The extent to which organisms respond to these shifts will, however, be mediated by the tolerances of all life-stages and populations of species and their potential to adapt. We investigated nauplius and cypris larvae of the barnacle Balanus (Amphibalanus) improvisus from the Swedish west coast with respect to temperature (12, 20, and 28 °C) and salinity (5, 15, and 30) tolerances. Warming accelerated larval development and increased overall survival and subsequent settlement success. Nauplii developed and metamorphosed best at intermediate salinity. This was also observed in cypris larvae when the preceding nauplii stages had been reared at a salinity of 30. Direct comparisons of the present findings with those on a population from the more brackish Baltic Sea demonstrate contrasting patterns. We conclude that i) B. improvisus larvae within the Baltic region will be favoured by near-future seawater warming and freshening, that ii) salinity tolerances of larvae from the two different populations reflect salinities in their native habitats, but are nonetheless suboptimal and that iii) this species is generally highly plastic with regard to salinity.

Physiological and ecological variables measured at the high and low pCO2 reef sections

Experiments have shown that ocean acidification due to rising atmospheric carbon dioxide concentrations has deleterious effects on the performance of many marine organisms. However, few empirical or modelling studies have addressed the long-term consequences of ocean acidification for marine ecosystems. Here we show that as pH declines from 8.1 to 7.8 (the change expected if atmospheric carbon dioxide concentrations increase from 390 to 750 ppm, consistent with some scenarios for the end of this century) some organisms benefit, but many more lose out. We investigated coral reefs, seagrasses and sediments that are acclimatized to low pH at three cool and shallow volcanic carbon dioxide seeps in Papua New Guinea. At reduced pH, we observed reductions in coral diversity, recruitment and abundances of structurally complex framework builders, and shifts in competitive interactions between taxa. However, coral cover remained constant between pH 8.1 and ~7.8, because massive Porites corals established dominance over structural corals, despite low rates of calcification. Reef development ceased below pH 7.7. Our empirical data from this unique field setting confirm model predictions that ocean acidification, together with temperature stress, will probably lead to severely reduced diversity, structural complexity and resilience of Indo-Pacific coral reefs within this century.

Population and Government in Colonial Buenos Aires. An Approach to the Study of the Tensions Generated by Demographic Growth in the City (1740-1776)

The relationship between population and government in the City of Buenos Aires is analyzed, focusing on the tensions generated by the arrival of new individuals, a local elite with great interests in commerce and in charge of community affairs, and Spanish functionaries that progressively adopted the ideals of the Bourbon Dynasty, despite also being implicated in local logics. It interests us to observe the governors’ perspectives with respect to everyday developments in the city, their preoccupations and interests, and how they would vary the mechanisms to which they resorted in order to organize daily life, in the period defined between 1740 and 1776.

Directional genetic differentiation and relative migration

Understanding the population structure and patterns of gene flow within species is of fundamental importance to the study of evolution. In the fields of population and evolutionary genetics, measures of genetic differentiation are commonly used to gather this information. One potential caveat is that these measures assume gene flow to be symmetric. However, asymmetric gene flow is common in nature, especially in systems driven by physical processes such as wind or water currents. As information about levels of asymmetric gene flow among populations is essential for the correct interpretation of the distribution of contemporary genetic diversity within species, this should not be overlooked. To obtain information on asymmetric migration patterns from genetic data, complex models based on maximum-likelihood or Bayesian approaches generally need to be employed, often at great computational cost. Here, a new simpler and more efficient approach for understanding gene flow patterns is presented. This approach allows the estimation of directional components of genetic divergence between pairs of populations at low computational effort, using any of the classical or modern measures of genetic differentiation. These directional measures of genetic differentiation can further be used to calculate directional relative migration and to detect asymmetries in gene flow patterns. This can be done in a user-friendly web application called divMigrate-online introduced in this study. Using simulated data sets with known gene flow regimes, we demonstrate that the method is capable of resolving complex migration patterns under a range of study designs.

A roadmap to Sierra Leone English: a sociohistorical and ecological perstective

Programa de doctorado: Traducción, comunicación y cultura