IL28B polymorphisms are markers of therapy response and are influenced by genetic ancestry in chronic hepatitis C patients from an admixed population

Background: IL28B polymorphisms are predictors of therapy response in hepatitis C virus (HCV) patients. We do not know whether they are markers of treatment response in admixed populations or not. Aims: To determine whether IL28B polymorphisms are predictors of therapy response in patients with HCV from an admixed population and are influenced by genetic ancestry. Methods: rs12979860 and rs8099917 were genotyped in 222 HCV patients treated with pegylated interferon and ribavirin. Ancestry was determined using genetic markers. Results: IL28B rs12979860 C/C was associated with sustained virological response (SVR), whereas C/T and T/T were associated with failure to therapy (P = 1.12 x 10(-5)). IL28B rs8099917 T/T was associated with SVR, and G/G and G/T were associated with nonresponse/ relapse (NR/R) (P = 8.00 x 10(-3)). Among HCV genotype 1 patients with C/C genotype, genomic ancestry did not interfere with therapy response. Among patients with rs12979860 T/T genotype, African genetic contribution was greater in the NR/R group (P = 1.51 x 10(-3)), whereas Amerindian and European genetic ancestry contribution were higher in the SVR group (P = 3.77 x 10(-3) and P = 2.16 x 10(-2) respectively). Among HCV type 1 patients with rs8099917 T/T, African genetic contribution was significantly greater in the NR/R group (P = 5.0 x 10(-3)); Amerindian and European ancestry genetic contribution were greater in the SVR group. Conclusion: IL28B rs12979860 and rs8099917 polymorphisms were predictors of therapy response in HCV genotypes 1, 2 and 3 subjects from an admixed population. Genomic ancestry did not interfere with response to therapy in patients with rs12979860 C/C, whereas it interfered in patients with C/T and T/T genotypes. Among HCV genotype 1 rs8099917 T/T patients, genomic ancestry interfered with response to therapy.

CD80 and CD86 polymorphisms in populations of various ancestries: 5 new CD80 promoter alleles

CD80 and CD86 are closely linked genes on chromosome 3 that code for glycoproteins of the immunoglobulin superfamily, expressed on the surface of antigen-presenting cells. These costimulatory molecules play essential roles for stimulation and inhibition of T cells through binding to CD28 and CTLA-4 receptors. In this study, CD80 promoter and CD86 exon 8 polymorphisms were analyzed to investigate the genetic diversity and microevolution of the 2 genes. We genotyped 1,124 individuals, including Brazilians of predominantly European, mixed African and European, and Japanese ancestry, 5 Amerindian populations, and an African sample. All variants were observed in Africans, which suggests their origin in Africa before the human migrations out of that continent. Five new CD80 promoter alleles were identified and confirmed by cloning and sequencing, and promoter 2 is most likely the ancestral allele. Nucleotide -79 is monomorphic in 4 Amerindian populations, where the presence of the -79 G allele is probably the result of gene flow from non-Amerindians. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Scientific concepts and public policies: Semiotic-cultural obstacles concerning intergroup and intercultural relationships

I attempt to articulate Jahoda's (2012) critical reflections regarding definitions of culture in recent cross-cultural studies and Moghaddam's (2012) claims of an omnicultural imperative to guide the elaboration of public policies for managing relationships among human groups from different cultural origins. For this, I will approach some aspects of the socio-historical and ontogenetic roots of the notion of culture. The notion of culture and the consequent public policies involving intercultural managing are being transformed as our global society develops. It has been proposed that some ways of dealing with the culture of the other are crucial to achieve awareness in respect of one's own cultural positioning when making science and attempting social interventions. Finally, the experience of Brazilian psychologists working on challenges faced by Amerindians dealing with the national society they live in will be presented as a pioneering work aiming to interfere in the development of public policies ethically concerned with the assurance of cultural integrity of currently marginalized social groups.

Interethnic diversity of NAT2 polymorphisms in Brazilian admixed populations

Abstract Background N-acetyltransferase type 2 (Nat2) is a phase II drug- metabolizing enzyme that plays a key role in the bioactivation of aromatic and heterocyclic amines. Its relevance in drug metabolism and disease susceptibility remains a central theme for pharmacogenetic research, mainly because of its genetic variability among human populations. In fact, the evolutionary and ethnic-specific SNPs on the NAT2 gene remain a focus for the potential discoveries in personalized drug therapy and genetic markers of diseases. Despite the wide characterization of NAT2 SNPs frequency in established ethnic groups, little data are available for highly admixed populations. In this context, five common NAT2 SNPs (G191A, C481T, G590A, A803G and G857A) were investigated in a highly admixed population comprised of Afro-Brazilians, Whites, and Amerindians in northeastern Brazil. Thus, we sought to determine whether the distribution of NAT2 polymorphism is different among these three ethnic groups. Results Overall, there were no statistically significant differences in the distribution of NAT2 polymorphism when Afro-Brazilian and White groups were compared. Even the allele frequency of 191A, relatively common in African descendents, was not different between the Afro-Brazilian and White groups. However, allele and genotype frequencies of G590A were significantly higher in the Amerindian group than either in the Afro-Brazilian or White groups. Interestingly, a haplotype block between G590A and A803G was verified exclusively among Amerindians. Conclusions Our results indicate that ethnic admixture might contribute to a particular pattern of genetic diversity in the NAT2 gene and also offer new insights for the investigation of possible new NAT2 gene-environment effects in admixed populations.

Impact of diabetes mellitus on arterial stiffness in a representative sample of an urban Brazilian population

Background Independent of other cardiovascular (CV) risk factors, increased arterial stiffness has been established as a predictor of morbidity and mortality. The main aim of this study was to investigate the impact of diabetes on arterial stiffness in a representative sample of an urban Brazilian population plus Amerindians. Methods A total of 1,415 individuals from the general population were randomly selected plus 588 Amerindians from a native community in Brazil. In addition, a sub-sample of 380 individuals from the general population had 5-year follow-up data. Pulse wave velocity (PWV) was measured with a non-invasive automatic device (Complior, Colson; Garges les Gonesses, France) and increased arterial stiffness was defined as PWV ≥ 12 m/s. Results In the overall group, diabetic individuals had higher frequencies of increased arterial stiffness and hypertension. They also had higher values of PWV, body mass index, total cholesterol, triglycerides, systolic and diastolic blood pressures compared to non-diabetic individuals (p < 0.01). In an analysis stratified by hypertension, PWV values and increased arterial stiffness frequency were higher in diabetic individuals in both groups (hypertensive and non-hypertensive) (p < 0.05). Furthermore, higher risk for increased arterial stiffness was observed in the diabetic individuals from the overall group (OR = 2.27; CI = 1.47-3.52, p < 0.001) and from the hypertensive group (OR = 2.70; CI = 1.58-4.75, p < 0.001), adjusted for covariates. Regarding the ethnic stratification, diabetic individuals from Amerindian, White, and Mulatto (mixed-race) groups had higher PWV values and a greater frequency of increased arterial stiffness compared to non-diabetic individuals. Both diabetic and non-diabetic individuals had higher PWV values after 5 years. There was no significant difference in the 5-year PWV progression in diabetic compared to non-diabetic individuals. Conclusions These results confirm, in a sample of Brazilian population, that the presence of diabetes is associated with increased arterial stiffness and it may contribute in part to increased cardiovascular risk in diabetic patients.

Genetic characterization, population history and evolutionary medicine perspective in two native south american populations: Yanesha and Wichi

Two Amerindian populations from the Peruvian Amazon (Yanesha) and from rural lowlands of the Argentinean Gran Chaco (Wichi) were analyzed. They represent two case study of the South American genetic variability. The Yanesha represent a model of population isolated for long-time in the Amazon rainforest, characterized by environmental and altitudinal stratifications. The Wichi represent a model of population living in an area recently colonized by European populations (the Criollos are the population of the admixed descendents), whose aim is to depict the native ancestral gene pool and the degree of admixture, in relation to the very high prevalence of Chagas disease. The methods used for the genotyping are common, concerning the Y chromosome markers (male lineage) and the mitochondrial markers (maternal lineage). The determination of the phylogeographic diagnostic polymorphisms was carried out by the classical techniques of PCR, restriction enzymes, sequencing and specific mini-sequencing. New method for the detection of the protozoa Trypanosoma cruzi was developed by means of the nested PCR. The main results show patterns of genetic stratification in Yanesha forest communities, referable to different migrations at different times, estimated by Bayesian analyses. In particular Yanesha were considered as a population of transition between the Amazon basin and the Andean Cordillera, evaluating the potential migration routes and the separation of clusters of community in relation to different genetic bio-ancestry. As the Wichi, the gene pool analyzed appears clearly differentiated by the admixed sympatric Criollos, due to strict social practices (deeply analyzed with the support of cultural anthropological tools) that have preserved the native identity at a diachronic level. A pattern of distribution of the seropositivity in relation to the different phylogenetic lineages (the adaptation in evolutionary terms) does not appear, neither Amerindian nor European, but in relation to environmental and living conditions of the two distinct subpopulations.

Genetics and epidemiology of gallbladder disease in New World native peoples.

Native peoples of the New World, including Amerindians and admixed Latin Americans such as Mexican-Americans, are highly susceptible to diseases of the gallbladder. These include cholesterol cholelithiasis (gallstones) and its complications, as well as cancer of the gallbladder. Although there is clearly some necessary dietary or other environmental risk factor involved, the pattern of disease prevalence is geographically associated with the distribution of genes of aboriginal Amerindian origin, and levels of risk generally correspond to the degree of Amerindian admixture. This pattern differs from that generally associated with Westernization, which suggests a gene-environment interaction, and that within an admixed population there is a subset whose risk is underestimated when admixture is ignored. The risk that an individual of a susceptible New World genotype will undergo a cholecystectomy by age 85 can approach 40% in Mexican-American females, and their risk of gallbladder cancer can reach several percent. These are heretofore unrecognized levels of risk, especially of the latter, because previous studies have not accounted for admixture or for the loss of at-risk individuals due to cholecystectomy. A genetic susceptibility may, thus, be as "carcinogenic" in New World peoples as any known major environmental exposure; yet, while the risk has a genetic basis, its expression as gallbladder cancer is so delayed as to lead only very rarely to multiply-affected families. Estimates in this paper are derived in part from two studies of Mexican-Americans in Starr County and Laredo, Texas.

Word Formation in South American Languages

This volume focuses on word formation processes in smaller and so far underrepresented indigenous languages of South America. The data for the analyses have been mainly collected in the field by the authors. The several language families described here, among them Arawakan, Takanan, and Guaycuruan, as well as language isolates, such as Yurakaré and Cholón, reflect the linguistic diversity of South America. Equally diverse are the topics addressed, relating to word formation processes like reduplication, nominal and verbal compounding, clitic compounding, and incorporation. The traditional notions of the processes are discussed critically with respect to their implementation in minor indigenous languages. The book is therefore not only of interest to readers with an Amerindian background but also to typologists and historical linguists, and it is a supplement to more theory-driven approaches to language and linguistics.

Different population dynamics of human T cell lymphotropic virus type II in intravenous drug users compared with endemically infected tribes

The phylogeny of human T cell lymphotropic virus type II (HTLV-II) was investigated by using strains isolated from Amerindian and Pygmy tribes, in which the virus is maintained primarily through mother-to-child transmission via breast-feeding, and strains from intravenous drug users (IDUs), in which spread is mainly blood-borne via needle sharing. Molecular clock analysis showed that HTLV-II has two different evolutionary rates with the molecular clock for the virus in IDUs ticking 150–350 times faster than the one in endemically infected tribes: 2.7 × 10−4 compared with 1.71/7.31 × 10−7 nucleotide substitutions per site per year in the long terminal repeat region. This dramatic acceleration of the evolutionary rate seems to be related with the mode of transmission. Mathematical models showed the correlation of these two molecular clocks with an endemic spread of HTLV-II in infected tribes compared with the epidemic spread in IDUs. We also noted a sharp increase in the population size of the virus among IDUs during the last decades probably caused by the worldwide increase in intravenous drug use.

Paleoclimate and Amerindians: Evidence from stable isotopes and atmospheric circulation

Two Amerindian demographic shifts are attributed to climate change in the northwest plains of North America: at ≈11,000 calendar years before present (yr BP), Amerindian culture apparently split into foothills–mountains vs. plains biomes; and from 8,000–5,000 yr BP, scarce archaeological sites on the open plains suggest emigration during xeric “Altithermal” conditions. We reconstructed paleoclimates from stable isotopes in prehistoric bison bone and relations between weather and fractions of C4 plants in forage. Further, we developed a climate-change model that synthesized stable isotope, existing qualitative evidence (e.g., palynological, erosional), and global climate mechanisms affecting this midlatitude region. Our isotope data indicate significant warming from ≈12,400 to 11,900 yr BP, supporting climate-driven cultural separation. However, isotope evidence of apparently wet, warm conditions at 7,300 yr BP refutes emigration to avoid xeric conditions. Scarcity of archaeological sites is best explained by rapid climate fluctuations after catastrophic draining of the Laurentide Lakes, which disrupted North Atlantic Deep Water production and subsequently altered monsoonal inputs to the open plains.

La actividad lingüística y traductora de fray Bernardo de Lugo

La labor lingüística y traductora de fray Bernardo de Lugo está enmarcada en la misión evangelizadora de la época colonial. Este fraile dominico pasó a la historia de la filología amerindia por haber compuesto la primera gramática de la lengua muisca. La obra, con sus aciertos y defectos, constituye aún hoy una de las principales fuentes de conocimiento del muisca y ha inspirado los trabajos lingüísticos que posteriormente se han realizado sobre esta lengua, extinta desde el siglo XVIII. La presente contribución introduce y contextualiza de forma somera la actividad intelectual de este fraile, recopilando las claves que permiten trazar su perfil como misionero lingüista y poner en valor su aportación a los estudios indigenistas.

The ethical paradigm of Jose Marti's writings beyond Modernity

This dissertation explores the nature of Jose Marti's ethical ideas in relation to the rise of late Nineteenth Century Modernity and in tandem with the deconstruction and subversion of the principal constituencies of colonial and aesthetic discourses. Marti proposes a new paradigm that question the insatiable pursuit of novelty, the hostility towards tradition, the historical perspectivism and a critical stance with regard to social aesthetic Modernity. He also questions the cult of reason, the linear historicism, and the teleological progress framed in philosophical utilitarian pragmatism of bourgeois Modernity. His radical criticism of the structures and institutions of the hegemonic power of the modern state override the ontological and epistemological foundations of Modernity. Marti's deconstruction of the fundamental discourses of euro-centristic Occidental culture leads him, through his ethical writings, to an arqueology of Native American civilizations, thus reinserting, within the false premises of European universalism, his counter-discourse of tradition and the voice of the Other.

RELIGIÃO, COLONIALISMO E ALTERIDADE EM ROGER WILLIAMS

Esta dissertação de mestrado apresenta os resultados da pesquisa sobre Roger Williams – pastor puritano, de origem inglesa, que migrou para a América a fim de participar da constituição da colônia de Massachusetts, no ano de 1631. Pergunta-se, nesta pesquisa, sobre os motivos que levaram Roger Williams a questionar o pensamento dominante, relativo à natureza do ameríndio e à legitimidade da ocupação de suas terras. Parte-se da tese de que a partir das experiências de Roger Williams, primeiro, com o sofrimento dos pobres e com perseguição religiosa na Inglaterra, segundo, suas próprias experiências na América, ele pôde contemplar os ameríndios como vítimas do sistema colonial inglês-puritano. Seu posicionamento seria, portanto, uma abertura à alteridade desses povos. Com isso, o objetivo determinado foi o de analisar a crítica de Roger Williams ao colonialismo inglês e sua defesa aos ameríndios, buscando compreendê-lo frente à alteridade dos ameríndios. Trata-se de uma bibliográfica das obras do autor e também de outros autores que tratam do tema. Como referência teórica, remetemo-nos ao pensamento de Enrique Dussel, principalmente, por meio de algumas categorias da Filosofia da Libertação, como Totalidade, Exterioridade, Alteridade, Alienação, Dominação e Libertação, que possibilitaram pensar o sistema colonial em sua incapacidade de contemplar a exterioridade ameríndia. Também, de Dussel, aplicou-se a reflexão sobre a crítica ética desde a negatividade das vítimas, para poder-se analisar o comportamento do personagem diante da violência colonial. E para a discussão sobre a sujeiticidade de Roger Williams, buscou-se o aporte de Franz J. Hinkelammert quanto à teoria do sujeito. Como resultado, os três capítulos da dissertação apresentam, respectivamente, uma síntese biográfica e contextual do personagem, seguida por uma exposição do debate sobre a humanidade e a civilidade dos ameríndios e sobre a questão da terra e, no terceiro capítulo, uma discussão sobre Roger Williams e a alteridade. Detectou-se, na trajetória do personagem, uma sensibilidade ética que o conduziu à defesa de grupos marginalizados socialmente, primeiro na Inglaterra e depois nas colônias. E diante disso, concluiu-se que a defesa dos ameríndios seguiu esse mesmo critério, possibilitando a Williams distanciar-se das pressuposições europeias quanto à sua superioridade para buscar novos paradigmas que orientassem as relações entre colonos e nativos. Espera-se que este trabalho possa contribuir para as reflexões críticas sobre a gênese do colonialismo e sobre os primeiros sinais de um pensamento crítico no interior do sistema colonial.

Perspectivismo y crítica social. De Nietzsche a la Teoría Crítica

El presente artículo se confronta con una problemática que ha focalizado los debates teóricos en torno a los fundamentos normativos de la crítica en las últimas décadas. La cuestión es si, en un marco social escindido como el nuestro, la crítica tiene que asumir su carácter perspectivista, es decir, su estar ubicada en una de las perspectivas que se enfrentan en el escenario social. Si ello es así, el problema que se abre es el de la posibilidad o no de legitimar racional, moral y políticamente una crítica que asume su estar ya siempre situada en uno de los horizontes normativos que coexisten en el marco social. Este trabajo afronta este problema poniendo en diálogo motivos de la hermenéutica y de la teoría crítica: con ello pretende realizar una aportación a lo que podríamos llamar una reflexión hermenéutica de la crítica, que logre articular carácter perspectivo y pretensión de normatividad de la misma.

Pre-colonial institutions and long-run development in Latin America

The present doctoral thesis studies the association between pre-colonial institutions and long-run development in Latin America. The thesis is organised as follows: Chapter 1 places the motivation of the thesis by underlying relevant contributions in the literature on long-run development. I then set out the main objective of the thesis, followed by a brief outline of it. In Chapter 2, I study the effects of pre-colonial institutions on present-day socioeconomic outcomes for Latin America. The main thesis of this chapter is that more advanced pre-colonial institutions relate to better socioeconomic outcomes today - principally, but not only, through their effects on the Amerindian population. I test such hypothesis with a dataset of 324 sub-national administrative units covering all mainland Latin American countries. The extensive range of controls covers factors such as climate, location, natural resources, colonial activities and pre-colonial characteristics - plus country fixed effects. Results strongly support the main thesis. In Chapter 3, I further analyse the association between pre-colonial institutions and present-day economic development in Latin America by using the historical ethnic homelands as my main unit of analysis. The main hypothesis is that ethnic homelands inhabited by more advanced ethnic groups -as measured by their levels of institutional complexity- relate to better economic development today. To track these long-run effects, I construct a new dataset by digitising historiographical maps allowing me to pinpoint the geospatial location of ethnic homelands as of the XVI century. As a result, 375 ethnic homelands are created. I then capture the levels of economic development at the ethnic homeland level by making use of alternative economic measures --satellite light density data. After controlling for country-specific characteristics and applying a large battery of geographical, locational, and historical factors, I found that the effects of pre-colonial institutions relate to a higher light density --as a proxy for economic activity- in ethnic homelands where more advanced ethnic groups lived. In Chapter 4, I explore a mechanism linking the persistence of pre-colonial institutions in Latin America over the long-run: Colonial and post-colonial strategies along with the ethnic political capacity worked in tandem allowing larger Amerindian groups to "support" the new political systems in ways that would benefit their respective ethnic groups as well as the population at large. This mechanism may have allowed the effects of pre-colonial institutions to influence socioeconomic development outcomes up to today. To shed lights on this mechanism, I combine the index of pre-colonial institutions prepared for the second chapter of the present thesis with individual-level survey data on people's attitudes. By controlling for key observable and unobservable country-specific characteristics, the main empirical results show that areas with a history of more advanced pre-colonial institutions increase the probability of individuals supporting present-day political institutions. Finally, in Chapter 5, I summarise the main findings of the thesis, and emphasise the key weaknesses of the study as well as potential avenues for future research.