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.

Population amalgamation and genetic variation: observations on artificially agglomerated tribal populations of Central and South America.

The interpretation of data on genetic variation with regard to the relative roles of different evolutionary factors that produce and maintain genetic variation depends critically on our assumptions concerning effective population size and the level of migration between neighboring populations. In humans, recent population growth and movements of specific ethnic groups across wide geographic areas mean that any theory based on assumptions of constant population size and absence of substructure is generally untenable. We examine the effects of population subdivision on the pattern of protein genetic variation in a total sample drawn from an artificial agglomerate of 12 tribal populations of Central and South America, analyzing the pooled sample as though it were a single population. Several striking findings emerge. (1) Mean heterozygosity is not sensitive to agglomeration, but the number of different alleles (allele count) is inflated, relative to neutral mutation/drift/equilibrium expectation. (2) The inflation is most serious for rare alleles, especially those which originally occurred as tribally restricted "private" polymorphisms. (3) The degree of inflation is an increasing function of both the number of populations encompassed by the sample and of the genetic divergence among them. (4) Treating an agglomerated population as though it were a panmictic unit of long standing can lead to serious biases in estimates of mutation rates, selection pressures, and effective population sizes. Current DNA studies indicate the presence of numerous genetic variants in human populations. The findings and conclusions of this paper are all fully applicable to the study of genetic variation at the DNA level as well.

Population and molecular evolution studies on the Melanocortin 1 receptor locus implicate its role in human pigmentation variation

Human pigmentation is a complex trait with the observed variation caused by the varied production of eumelanin (brown/black melanins) and phaeomelanin (red/yellow melanins) by the melanocytes. The melanocortin 1 receptor (MC1R), a G protein-coupled receptor expressed in the melanocytes, is a regulator eu- and phaeomelanin synthesis, and MC1R mutations causing skin and coat color changes are known in many mammals. To understand the role of MC1R in human pigmentation variation, I have sequenced the MC1R gene in 121 individuals sampled from world populations. In addition, I have sequenced the MC1R gene in common and pygmy chimpanzees, gorilla, orangutan, and baboon to study the evolution of MC1R and to infer the ancestral human MC1R sequence. The ancestral MC1R sequence is observed in all 25 African individuals studied, but at lower frequencies in the other populations examined, especially in East and Southeast Asians. The Arg163Gln variant is absent in the Africans studied, almost absent in Europeans, and at a low frequency in Indians, but is at an exceptionally high frequency (70%) in East and Southeast Asians. To further evaluate the role of MC1R variants in human pigmentation variation, I have combined these molecular evolution and population studies with functional assays on MC1R variants and primate MC1Rs. ^

New cytochromes P450: Tale of two variants

Cytochrome P450s, a superfamily of heme enzymes found in most living organisms. They are responsible for metabolism of many therapeutic drugs, industrial pollutants, carcinogens, and additives to foodstuffs, as well as some endogenous compounds including fatty acids and steroids. First pass drug metabolism studies represent mainly liver and small intestine elimination, and are viewed as the standard to predict therapeutic outcome. However, drug plasma levels determined after administration do not always correlate with therapeutic efficacy of the drug. Therefore, a possible explanation may come by understanding drug metabolism in extrahepatic tissues and/or at the site of drug action. Identification and characterization of novel tissue specific isoforms of P450 generated by alternative splicing of known P450 genes or as yet unidentified genes is essential to predict pharmacological outcome of drugs or the fate of a carcinogen that act at sites remote from liver. ^ Using RT-PCR, brain-specific cytochrome P450s were detected in samples of human autopsy brain. So far, we have identified two human brain variants including P450 2D7 and P450 1A1. We have shown the presence of the P450 1A1 brain specific splice variant in African Americans, Caucasians and Indians albeit different patterns of liver to brain variant ratio were seen distributed throughout each population. Interestingly, the splice variant was detected only in the brain but not in any other tissues from the same individual. Homology modeling was used to compare the variant 3D structure to the liver form structure and differences in the substrate access channels and substrate binding sites were noticed. Automated computational docking was used to predict the metabolic fate of the potent carcinogenic substrate, benzo[a]pyrene. P450 1A1 brain variant showed no binding orientations that could produce the active metabolite, whereas P450 1A1 liver form did reveal orientations capable of generating active carcinogenic product. In vitro P32 labeling studies verified the docking predictions. Therefore, the data support the hypothesis that P450 brain splice variants mediate the metabolism of xenobiotics by mechanisms distinct from the well-studied liver counterparts. ^

Differences in small-for-gestational-age and preterm birth among Asian subgroups in relation to nativity status

This retrospective cohort study examined the association between nativity status and very preterm birth, preterm birth, and small-for-gestational-age (SGA) among Asian subgroups using Texas birth certificate data with no personal identifiers. A total of 877,322 birth certificates of Asian and US-born white women with a singleton birth in Texas from 2001-2004 were analyzed. Birth certificate records of US-born white, Chinese, Japanese, Korean, Vietnamese, Filipino, and Asian Indian women with a singleton birth were included in the analysis. Logistic regressions models were used to explore and understand the differences of the effect of nativity status on birth outcomes in Asian subgroups with US-born whites as the reference group. Most of the Asian subgroups had a lower risk of preterm births compared with US born whites, with reductions in risk ranging from 19% to 49% and the lowest risk of preterm birth observed among foreign-born Chinese mothers. Only Filipino mothers had a higher risk of preterm birth compared to US-born whites. Overall, foreign-born Asians had lower risks for very preterm birth and preterm birth than US-born Asians and US-born whites. US-born Asians were at higher risk for preterm birth than US-born whites. For SGA, all Asian subgroups and Asian subgroups by nativity status were at higher risk of SGA than US-born whites. Asian Indians and Japanese were at highest risk for SGA infants with 2.5 to 3 times the risk of SGA present in US-born whites. Foreign-born Asian women were at higher risk for SGA than their US-born counterparts. This study showed that health disparities among Asian subgroups are hidden by classifying Asians into a single group. By examining Asian subgroups separately and looking at nativity status, the differences in risk of SGA and preterm birth can be revealed so prevention efforts can focus on high risk groups. ^

A study of factors influencing high school students' attitudes and opinions about violence

Tenth grade students in a lower income neighborhood Houston school were surveyed on violence related beliefs, attitudes, and coping ability. Self-administered questionnaires were used to collect information for scale scores for statistical analysis.^ One hundred twenty six students participated of which 60% were Hispanic, 18% Black, 18% White, 2 American Indians, and 3 Asian/Pacific persons. There were 60 males, mean age 16.03, and 66 females, mean age 15.49. One-half of the sample reported repeating a grade, 53.4% of males, and 47% of females. Females' self-reported grades were slightly higher than males.^ Measures of student acceptance of violence and ability to handle conflict peacefully were studied in relation to student responses to questions about five areas: parental monitoring of the student, parent type of punishment, optimism about future prospects, frustration tolerance, and perceived peer group attitudes and practices.^ Significant gender differences included males having higher violence acceptance scores and females higher on coping with conflict peacefully. No significant race differences or gender interactions were found.^ Females' scores on future orientation were inversely related to their scores on the measure of acceptance of violence. For males, parents' punishment and perceived peer attitudes were positively related to their acceptance of violence, p $<$.0083.^ Female handling of conflict was significantly related to frustration tolerance and optimism; not significant were perceived peer attitudes, parent monitoring or punishment method. For males significantly related to handling conflict were perceived peer attitudes, parental monitoring, and severity of punishment, with the last two terms having a significant interaction effect, and inversely correlated (less monitoring, harsher punishment explained lower ability to handle conflict). ^

ISOELECTRIC FOCUSING STUDIES OF STEROID BINDING PROTEINS

Steroid binding proteins are an obvious choice in the search for genetic factors in plasma that might predispose to upper body obesity, a risk factor for non-insulin dependent diabetes and cardiovascular disease. The two steroid binding proteins studied by isoelectric focusing were sex hormone binding globulin (SHBG), the transport protein for sex hormones and corticosteroid binding globulin (CBG), the transport protein for corticosteroids. Auto-radiography and immunoblotting on polyacrylamide gels were used to detect polymorphism in SHBG. Immunoblotting on agarose gels was used to visualize corticosteroid binding globulin. SHBG showed similar structural variation in American Caucasians, American Blacks and Canadian Indians. Two alleles (1, 2) were hypothesized with highly polymorphic frequencies in all three ethnic groups. CBG was not found to be polymorphic, but two variants were found in Caucasian male twins and in a Black individual. The finding of a good assay and a polymorphic system for SHBG are the first steps for additional studies into disease associations. ^

HEMATOCRIT AND HEMOGLOBIN, ATP AND DPG CONCENTRATIONS IN ANDEAN MAN: VARIABILITY BY SEX, AGE, VILLAGE, ALTITUDE, WEIGHT, SMOKING HABITS AND GENETIC CONSTITUTION

The Departmento de Arica in northern Chile was chosen as the investigation site for a study of the role of certain hematologic and glycolytic variables in the physiological and genetic adaptation to hypoxia.^ The population studied comprised 876 individuals, residents of seven villages at three altitudes: coast (0-500m), sierra (2,500-3,500m) and altiplano (> 4,000m). There was an equal number of males and females ranging in ages from six to 90 years. Although predominantly Aymara, those of mixed or Spanish origin were also examined. The specimens were collected in heparinized vacutainers precipitated with cold trichloroacetic acid (TCA) and immediately frozen to -196(DEGREES)C. Six variables were measured. Three were hematologic: hemoglobin, hematocrit and mean cell hemoglobin concentration. The three others were glycolytic: erythrocyte 2,3-diphosphoglycerate (DPG), adenosine triphosphate (ATP) and the percentage of phosphates (DPG + ATP) in the form of DPG.^ Hemoglobin and hematocrit were measured on site. The DPG and ATP content was assayed in specimens which had been frozen at -196(DEGREES)C and transported to Houston. Structured interviews on site provided information as to lifestyle and family pedigrees.^ The following results were obtained: (1) The actual village, rather than the altitude, of examination accounted for the greatest proportion of the variance in all variables. In the coast, a large difference in levels of ionic lithium in the drinking water exists. The chemical environment of food and drink is postulated to account, in part, for the importance of geographic location in explaining the observed variance. (2) Measurements of individuals from the two extreme altitudes, coast and altiplano, did not exhibit the same relationship with age and body mass. The hematologic variables were significantly related to both age and body build in the coast. The glycolytic variables were significantly related to age and body mass in the altiplano. (3) The environment modified male values more than female values in all variables. The two sexes responded quite differently to age and changes in body mass as well. The question of differing adaptability of the two sexes is discussed. (4) Environmental factors explained a significantly higher proportion of total variability in the altiplano than in the coast for hemoglobin, hematocrit and DPG. Most of the ATP variability at both altitudes is explained by genetic factors. ^

Fray Alonso de la Veracruz : ensayo de síntesis

El artículo presenta una síntesis de la obra escrita de Veracruz y, en parte, también de su acción. De tal modo, se exponen sus escritos filosóficos, en materia de lógica (Recognitio Summularum y Dialectica Resolutio) y de filosofía natural (Physica Speculatio), y las relecciones en las que se ocupó de los títulos de la conquista y la condición de los indios (De dominio infidelium y De decimis). También es propósito del trabajo proporcionar, a quien quiera continuar con el tema, una guía de buena parte de la abundante literatura secundaria que se ha ocupado de Fray Alonso de la Veracruz. Veracruz es un importante representante de la escolástica novohispana del siglo XVI, y simboliza el comienzo del trasplante filosófico que bajo el signo de la escolástica se extendería en Iberoamérica hasta el siglo XVIII y parte del XIX.

La visión y la vocación del excautivo Santiago Avendaño acerca de la cuestión del indio

Santiago Avendaño, cautivo de los indios ranqueles desde los siete hasta los catorce años de edad, dedicó su vida y su obra a la defensa de los derechos de los indios en territorio argentino, a mediar entre las comunidades aborígenes y la sociedad blanca como intérprete, militar, funcionario del gobierno y escritor. Su manuscrito se conservó oculto en la colección de Estanislao Zeballos por ciento cuarenta años y fue precariamente editado en dos tomos (1999 y 2000) por el sacerdote Meinrado Hux. Se ha hallado, además, material epistolar de pluma y letra del excautivo, en parte aún inédito, interpolado en el manuscrito original, de gran importancia para el estudio de la cuestión del indio durante el siglo XIX y para la revisión de las políticas y acciones pasadas implementadas por los gobiernos, porque documenta las ideas de un hombre que llegó a conocer al indio en su medio y a formar parte de su comunidad, sin dejar de pertenecer a la propia. Se analiza la visión y la vocación de Avendaño a través de la reconstrucción de su vida y su accionar en los conflictos de frontera, así como su pensamiento, a la luz de sus escritos.

Política y poesía en Juan Cruz Varela

Juan Cruz Varela es el poeta argentino más importante de la primera generación revolucionaria. Su abundante producción tiene como eje principal el tópico de defender la libertad, en contra de toda tiranía. Sin embargo, y de acuerdo con la política del momento, ese reclamo de libertad no beneficia a todos los habitantes de la pampa. Varela elogia tanto las medidas de Bernardino Rivadavia sobre la cuestión india, como al brazo ejecutor, el coronel Federico Rauch, a través de un comentario periodístico y de un poema, textos de 1827 cuya estructura semántica es casi idéntica. Sin embargo, la posterior corrección del poema (1831) permite apreciar que la conciencia poética de Varela se impone sobre la circunstancia política eventual. Este artículo se complementa con la edición crítica de “En el regreso de la expedición contra los indios bárbaros, mandada por el Coronel D. Federico Rauch", incluida en la sección “Documentos" de esta misma revista.

La inserción social del indígena en las urbes y campañas del territorio bonaerense y su relación con la justicia criminal hispanocriolla durante el período independiente temprano (1810-1835)

La sociedad bonaerense del período independiente temprano, no sólo se caracterizó por estar fuertementejerarquizada desde el punto de vista socioeconómico, sinoademás por ser legalmente desigual y altamente punitiva. Los hechos asentados en los expedientes judiciales correspondientes a causas criminales y correccionales presentadas ante el Juzgado del Crimen, muestran claramente -entre otros aspectos- las características de la justicia criminal hispanocriolla: cómo operaba y se administraba la ley vigente, frente a la cual, los sectores bajos de la pirámide social y en particular, los individuos de casta (indios, negros, morenos, etc.), resultaban ser los más desprotegidos y vulnerables. Por lo tanto, en el presente proyecto, nos interesa abordar la inserción social del indígena en las urbes y campañas, y su integración en el mercado laboral de la época, y a partir de este marco y desde esa sociedad que lo incluía, se pretende indagar alindígena frente al delito y dentro de la dinámica del campo judicial, articulando las dimensiones social, económica y jurídica. De esta manera, combinando las fuentes judiciales de 1810 a 1835 con otros documentos del período, se intenta dar cuenta no sólo de los aspectos sociales y económicos de la vida personal y cotidiana del indígena sino además de las particularidades del proceso de juzgamiento y penalización de sus acciones durante el incipiente período independentista.

Bajo los adoquines está la Pachamama : Territorialidad andina en el Gran La Plata [2008-2011]

Desde hace aproximadamente 20 años, se está viviendo un resurgimiento del movimiento indígena a nivel mundial y continental. El territorio juega un papel esencial para las numerosas organizaciones y comunidades que lo componen, en tanto articula el accionar de estos sujetos al espacio en un sentido procesual y relacional, a través de una concepción en la que la tríada territorio-territorialidad-territorialización, niega la dualidad cartesiana entre materia y espíritu y afirma que toda apropiación material es a la vez simbólica. Según la Encuesta Complementaria de Pueblos Indígenas 2004-2005, complementaria del Censo Nacional de Población, Hogares y Viviendas 2001 del INdEC, el 54 de las 600.329 personas que se autoreconocen como parte de alguno de los más de treinta pueblos aborígenes que habitan en Argentina, se encuentra en áreas urbanas. El interés de este trabajo es el entender cuáles son las modalidades de apropiación material y simbólica del espacio que llevan adelante la Organización Quechua-Aymara Hijos del Cóndor [Kunthurpa Churinkuna] en conjunto con la Academia Mayor de la Lengua Quechua de Cusco-Filial Regional Internacional "Berisso" [Qheswasimi Jamutána Kuraq Suntur Qosqo-Perusuyu], y la Comunidad Qolla Gran La Plata, todas pertenecientes al universo cultural andino, y activas en el ámbito de la capital bonaerense. Es decir, qué territorialidad específica construyen en el espacio urbano, en función de la recreación de su cultura ancestral [analizada a través del enfoque del control cultural], y atendiendo a su relación con sus estrategias políticas y sus condiciones socioeconómicas, que se ponen en juego en la configuración de determinados espacios de socialización. Se trata de una investigación que emplea el método etnográfico, con técnicas tales como la observación participante y la entrevista en profundidad

La palabra de los "naturales" en la justicia : Posibilidades y limitaciones en el análisis de la documentación judicial referida a indígenas (Jujuy, siglo XVII)

El presente artículo se propone establecer variables de análisis en lo que respecta al rol de los indígenas en la documentación judicial colonial. En ese sentido, el corpus principal de análisis lo constituye el Pleito de los indios de Paipaya contra Francisco Salas Valdez (1671) a través del cual vislumbraremos las condiciones de producción del documento, el rol de los mediadores, la distancia cultural o la influencia de las condiciones de subordinación actuantes en el mismo. Consideramos al presente trabajo una aproximación que no pretende ser definitiva, si no abrir un panorama a la reflexión sobre la temática ya que este extenso documento nos brindará elementos de reflexión metodológica y heurística con que abordar el estudio de los indígenas a través de la fuente judicial