Genetic studies of the human plasma orosomucoid (alpha-1 acid glycoprotein)

Orosomucoid (ORM) or alpha-1 acid glycoprotein is an acute phase protein of human plasma whose function is suggested to be the competitive inhibition of cellular recognition by infective agents. Isoelectric focusing (IEF) and immunoblotting have been combined and optimum conditions have been determined for reliable classification of different ORM phenotypes. Addition of 6 M urea in an IEF gel revealed additional microheterogeneity in the ORM system which has not been previously reported. 1,667 individuals from different native ethnic groups of North and South America, Africa and New Guinea have been screened to determine the distribution of ORM alleles. Two common alleles, ORM1*1 and ORM1*2 have been observed and their frequencies were determined. Genetically independent variation consistent with expression of the ORM2 locus was observed in American and African blacks but was not observed in other sampled populations. The population allele frequencies for this new locus were 0.958, 0.025, 0.006, 0.011, for alleles ORM2*1, ORM2*2, ORM2*3, ORM2*4, respectively. Family studies confirm the autosomal codominant inheritance of the phenotypes observed at both ORM loci. ^

Genetic epidemiology of childhood brain tumors

A rare familial cancer syndrome involving childhood brain tumors (CBT), breast cancer, sarcomas and an array of other tumors has been described (Li and Fraumeni 1969, 1975, 1982, 1987). A survey of CBT identified through the Connnecticut Tumor Registry in 1984 revealed a high frequency of CBT, leukemia and other childhood cancer in siblings of CBT patients (Farwell and Flannery, 1984). Other syndromes such as neurofibromatosis and nevoid basal cell carcinoma syndrome have also been associated with CBT; however, no systematic family studies have been conducted to determine the extent to which cancer aggregates in family members of CBT patients. This family study was designed to determine the frequency of cancer aggregation overall or at specific sites, to determine the frequency of known or potentially hereditary syndromes in families of CBT patients, and to determine a genetic model to characterize familial cancer syndromes and to identify specific kindreds to which such a model(s) might apply. This study includes 244 confirmed CBT patients referred to the University of Texas M. D. Anderson Cancer Center between the years 1944 and 1983, diagnosed under the age of 15 years and resident in the U.S. or Canada. Family histories were obtained on the proband's first (parents, siblings and offspring) and second degree (proband's aunts, uncles and grandparents) relatives following sequential sampling scheme rules. To determine if cancer aggregates in families, we compared the cancer experience in the population to that expected in the general population using Connecticut Tumor Registry calendar year, age, race and sex-specific rates. The standardized incidence ratio (SIR) for cancer overall was 0.91 (41 observed (O) and 44.94 expected (E); 95% Confidence Interval (CI) = 0.65-1.24). We observed a significant excess of colon cancer among the proband's first degree relatives (O/E = 5/1.64; 95% CI = 1.01-7.65), in particular those under age 45 year. Segregation analysis showed evidence for multifactorial inheritance in the small percentage (N = 5) of the families. ^

A GENETIC MARKER STUDY OF NON - INSULIN DEPENDENT DIABETICS IN THE MEXICAN-AMERICAN COMMUNITY FROM STARR COUNTY, TEXAS (PLASMA GLUCOSE, HEMOGLOBIN ANALYSIS)

Diabetes mellitus occurs in two forms, insulin-dependent (IDDM, formerly called juvenile type) and non-insulin dependent (NIDDM, formerly called adult type). Prevalence figures from around the world for NIDDM, show that all societies and all races are affected; although uncommon in some populations (.4%), it is common (10%) or very common (40%) in others (Tables 1 and 2).^ In Mexican-Americans in particular, the prevalence rates (7-10%) are intermediate to those in Caucasians (1-2%) and Amerindians (35%). Information about the distribution of the disease and identification of high risk groups for developing glucose intolerance or its vascular manifestations by the study of genetic markers will help to clarify and solve some of the problems from the public health and the genetic point of view.^ This research was designed to examine two general areas in relation to NIDDM. The first aims to determine the prevalence of polymorphic genetic markers in two groups distinguished by the presence or absence of diabetes and to observe if there are any genetic marker-disease association (univariate analysis using two by two tables and logistic regression to study the individual and joint effects of the different variables). The second deals with the effect of genetic differences on the variation in fasting plasma glucose and percent glycosylated hemoglobin (HbAl) (analysis of Covariance for each marker, using age and sex as covariates).^ The results from the first analysis were not statistically significant at the corrected p value of 0.003 given the number of tests that were performed. From the analysis of covariance of all the markers studied, only Duffy and Phosphoglucomutase were statistically significant but poor predictors, given that the amount they explain in terms of variation in glycosylated hemoglobin is very small.^ Trying to determine the polygenic component of chronic disease is not an easy task. This study confirms the fact that a larger and random or representative sample is needed to be able to detect differences in the prevalence of a marker for association studies and in the genetic contribution to the variation in glucose and glycosylated hemoglobin. The importance that ethnic homogeneity in the groups studied and standardization in the methodology will have on the results has been stressed. ^

Attitudes About Predictive MEN1 Genetic Testing in Minors

Multiple Endocrine Neoplasia type 1 (MEN1) is a hereditary cancer syndrome characterized by tumors of the endocrine system. Tumors most commonly develop in the parathyroid glands, pituitary gland, and the gastro-entero pancreatic tract. MEN1 is a highly penetrant condition and age of onset is variable. Most patients are diagnosed in early adulthood; however, rare cases of MEN1 present in early childhood. Expert consensus opinion is that predictive genetic testing should be offered at age 5 years, however there are no evidence-based studies that clearly establish that predictive genetic testing at this age would be beneficial since most symptoms do not present until later in life. This study was designed to explore attitudes about the most appropriate age for predictive genetic testing from individuals at risk of having a child with MEN1. Participants who had an MEN1 mutation were invited to complete a survey and were asked to invite their spouses to participate as well. The survey included several validated measures designed to assess participants’ attitudes about predictive testing in minors. Fifty-eight affected participants and twenty-two spouses/partners completed the survey. Most participants felt that MEN1 genetic testing was appropriate in healthy minors. Younger age and increased knowledge of MEN1 genetics and inheritance predicted genetic testing at a younger age. Additionally, participants who saw more positive than negative general outcomes from genetic testing were more likely to favor genetic testing at younger ages. Overall, participants felt genetic testing should be offered at a younger age than most adult onset conditions and most felt the appropriate time for testing was when a child could understand and participate in the testing process. Psychological concerns seemed to be the primary focus of participants who favored later ages for genetic testing, while medical benefits were more commonly cited for younger age. This exploratory study has implications for counseling patients whose children are at risk of developing MEN1 and illustrates issues that are important to patients and their spouses when considering testing in children.

Genetic variants within the Wnt/ B-catenin signaling pathway as indicators of bladder cancer clinical outcomes

The genetic factors that influence bladder cancer clinical outcomes are largely unknown. In this clinical outcomes study, I assessed genetic variations in the Wnt/β-catenin stem-cell pathway genes for association with recurrence and progression. A total of 230 SNPS in 40 genes from the Wnt/β-catenin pathway were genotyped in 419 histologically confirmed non-muscle invasive bladder cancer cases. Several significant associations were observed in the clinical outcomes analysis. Under the dominant model WNT8B: rs4919464 (HR: 1.55, 95% CI: 1.17-2.06, P=2.2x10-3) and WNT8B: rs3793771 (HR: 1.54, 95% CI: 1.09-1.62, P=4.6x10-3 ) were statistically significantly associated with an increase risk of recurrence while two other variants, APC2: rs11668593 (HR: 2.50, 95% CI: 1.43-4.35, P=1.2x10-3) and LRP5 : rs312778 (HR: 1.81, 95% CI: 1.23-2.65, P=2.7x10-3), were significantly associated with recurrence risk under the recessive model of inheritance. Four SNPs in the recessive model were associated with an increased risk of progression (AXIN2: rs1544427, LRP5: rs312778, AXIN1: rs370681, AXIN1: rs2301522). LRP5: rs312778 had the most significant increased risk of progression with a 2.68 (95% CI: 1.52-4.72, P=6.4x10-4)-fold increased risk. Stratification analysis based on treatment regimen (transurethral resection (TUR) and Bacillus Calmette-Guérin (BCG)) was also performed. Individuals with at least one variant in AXIN2: rs2007085 were found to have a 2.09 (95% CI: 1.24-3.52, P=5.4x10-3) -fold increased risk of recurrence in those that received TUR only, and no statistically significant effect was seen in those that received BCG. Individuals who received TUR with at least one variant in LEF1: rs10516550 were found to have a 2.26 (95% CI: 1.22-4.18, P=9.7x10-3)-fold increase risk of recurrence and no statistically significant effect was found in individuals who received BCG. Also, the recessive model of LRP6: rs2302684 in TUR only treatment was shown to have a 1.95 (95%CI: 1.18-3.21, P=8.8x10 -3)-fold increased risk of recurrence, and a suggested protective effect associated with a (HR: 0.83, 95% CI: 0.51-1.37, P=0.468) decreased risk of recurrence. Together, these findings implicate the Wnt/β-catenin stem-cell pathway as playing a role in bladder cancer clinical outcomes and have important implications for personalization of future treatment regimens. ^

AN ASSESSMENT OF KNOWLEDGE AND ATTITUDES OF GENETIC COUNSELING SERVICES IN U.S. HTCs

Hemophilia is a hereditary bleeding disorder which requires lifelong specialized care. A network of Hemophilia Treatment Centers (HTCs) exists to meet the medical needs of patients affected by hemophilia. Genetic counseling services are an integral part of the HTC model of care; however, many HTCs do not have genetic counselors on staff. As a result, the duty to provide these services must fall to other healthcare providers within the HTC. To assess the knowledge and attitudes of these providers we developed a 49 question survey that was distributed electronically to hematologists and nurses at U.S. HTCs. The survey consisted of a three sections: demographic information, knowledge of hemophilia genetics, and attitudes towards genetic services. A total of 111 complete responses were received and analyzed. The average knowledge score among all participants was 74.8% with a total of 81 participants receiving a passing score of 70% or above. Thirty participants scored below 70% in the knowledge section. In general, attitude scores were high indicating that the majority of hematologists and nurses in HTCs feel confident in their ability to provide genetic counseling services. Over 90% of participants reported that they have some form of access to genetic counseling services at their center. Hematologists and nurses practicing in U.S. HTCs demonstrate sufficient knowledge of the genetics of hemophilia, and they generally feel confident in their ability to provide genetic counseling services to their patients. While their knowledge is sufficient, the average knowledge score was lower than 75%. Certain questions covering new genetic technologies and testing practices were more commonly missed than questions asking about more basic aspects of hemophilia genetics, such as inheritance and carrier testing. Finally, many clinics report having access to a counselor, but it is oftentimes a hematologist or nurse who is providing genetic counseling services to patients. Given the inconsistency in knowledge among providers coupled with the high confidence in one’s ability to counsel patients, it leaves room to question whether information about the genetics of hemophilia is being communicated to patients in the most appropriate and accurate manner.

Zircons, isotope ratios and element analyses from tonalite and oxide gabbro of the mid-ocean ridge from ODP Hole 176-735B

A limiting factor in the accuracy and precision of U/Pb zircon dates is accurate correction for initial disequilibrium in the 238U and 235U decay chains. The longest-lived-and therefore most abundant-intermediate daughter product in the 235U isotopic decay chain is 231Pa (T1/2 = 32.71 ka), and the partitioning behavior of Pa in zircon is not well constrained. Here we report high-precision thermal ionization mass spectrometry (TIMS) U-Pb zircon data from two samples from Ocean Drilling Program (ODP) Hole 735B, which show evidence for incorporation of excess 231Pa during zircon crystallization. The most precise analyses from the two samples have consistent Th-corrected 206Pb/238U dates with weighted means of 11.9325 ± 0.0039 Ma (n = 9) and 11.920 ± 0.011 Ma (n = 4), but distinctly older 207Pb/235U dates that vary from 12.330 ± 0.048 Ma to 12.140 ± 0.044 Ma and 12.03 ± 0.24 to 12.40 ± 0.27 Ma, respectively. If the excess 207Pb is due to variable initial excess 231Pa, calculated initial (231Pa)/(235U) activity ratios for the two samples range from 5.6 ± 1.0 to 9.6 ± 1.1 and 3.5 ± 5.2 to 11.4 ± 5.8. The data from the more precisely dated sample yields estimated DPazircon/DUzircon from 2.2-3.8 and 5.6-9.6, assuming (231Pa)/(235U) of the melt equal to the global average of recently erupted mid-ocean ridge basaltic glasses or secular equilibrium, respectively. High precision ID-TIMS analyses from nine additional samples from Hole 735B and nearby Hole 1105A suggest similar partitioning. The lower range of DPazircon/DUzircon is consistent with ion microprobe measurements of 231Pa in zircons from Holocene and Pleistocene rhyolitic eruptions (Schmitt (2007; doi:10.2138/am.2007.2449) and Schmitt (2011; doi:10.1146/annurev-earth-040610-133330)). The data suggest that 231Pa is preferentially incorporated during zircon crystallization over a range of magmatic compositions, and excess initial 231Pa may be more common in zircons than acknowledged. The degree of initial disequilibrium in the 235U decay chain suggested by the data from this study, and other recent high precision datasets, leads to resolvable discordance in high precision dates of Cenozoic to Mesozoic zircons. Minor discordance in zircons of this age may therefore reflect initial excess 231Pa and does not require either inheritance or Pb loss.

Encuentro con Carlos Alonso : el artista y el hombre : un acto de transmisión

Este artículo propone un encuentro con el artista plástico Carlos Alonso, su vida y su obra, como un acto de transmisión. A través de una entrevista en profundidad y de un trabajo previo con su historia, se produce un encuentro intergeneracional que transmite una forma de ser y de hacer plasmada en su arte. El legado de una historia de vida profundamente enraizada con la historia del siglo XX en Argentina, de la relación con sus maestros y con el arte como concepto universal, resignificado desde su subjetividad y desde su práctica social. En este marco, se recorren algunos modos en que esta transmisión se manifiesta: transmisión y herencia; transmisión como imaginario de futuro; transmisión como manifestación del deseo. La transmisión se ha constituido en uno de los temas de la agenda de la pedagogía actual. Pensar nuestras prácticas pedagógicas en clave de transmisión conlleva un desafío y una necesidad. Un desafío en términos de intencionalidad, del acento que ponemos en la direccionalidad de las mismas. Y una necesidad en términos de compromiso con los niños, los jóvenes y con las generaciones futuras. Compromiso que conlleva el intento de humanización, de que el otro se constituya como sujeto de una cultura, y que no podemos abandonar porque dejaríamos a los que vienen siendo nadie.

La invisibilidad neoliberal y la identidad de los territorios costeros : El caso de las transformaciones de la costa vitivinícola de Berisso

En el presente trabajo se propone la lectura de una nueva racionalidad productiva en la que se observa una relación de poder, no ligada a la localización de las fuerzas de decisiones del mundo global, sino a una forma espacial-territorial en la que dominan sus territorios, a partir de la apropiación y la influencia del mismo a escala local. Se plantea cómo estos territorios que surgen desde el interior de la costa vitivinícola de Berisso presentan una importante identidad cultural, con un pasado tan fuerte como el presente y valorando sus herencias territoriales para lograr una transformación silenciosa.

La propiedad de Ramon Urquiola, desde su constitución hasta el fraccionamiento en la provincia de Buenos Aires, entre los siglos XIX y XX

Este trabajo de investigación está centrado en los siguientes temas: el proceso de adquisición de una gran extensión de tierra en Lobos, provincia de Buenos Aires, a comienzos del siglo XIX; la inserción social y económica del adquirente y la inserción social y política de sus hijos; el cambio de modalidad cultural y de explotación de la tierra a través de dos generaciones; el cambio social y cultural representado por quienes continúan como propietarios al producirse el fraccionamiento debido a las sucesiones hereditarias; el proceso de ventas que lleva a la total enajenación de la tierra en poco más de un siglo; la discusión sobre los factores que llevan a este desenlace.

La agriculturización en el contexto de una nueva ruralidad : Nuevos actores pluriactivos en el departamento Río Primero de la provincia de Córdoba

Desde las últimas décadas, Argentina ha evidenciado un fuerte proceso de agriculturización. El departamento Río Primero, de la provincia de Córdoba, participa de la dinámica visible en gran parte de la región pampeana, y el área de estudio presenta profundas transformaciones productivas, económicas y sociales. En este contexto, los más vulnerables del entramado quedan fuera del sistema productivo. Sin embargo, recientemente, y en forma aparentemente contradictoria, aparecen en escena pequeños productores de origen urbano que comienzan a completar sus ingresos urbanos con los provenientes de actividades agrarias.Abordamos en este trabajo el ingreso a la actividad agraria de nuevos actores pluriactivos de origen urbano, los motivos del mismo, sus modalida desde producción y estrategias de adaptación, sus trayectorias de vida y la conexión con lo rural en sus historias familiares, ponderando de qué manera incide la herencia y/o cesión de tierras en dicho ingreso.

Se nas pedras faz feguras parecer... Consideraciones sobre iconografía mariana y figuras poéticas en las Cantigas de Santa María de Alfonso X

La iconografía mariana ha quedado reflejada en la poesía hispánica medieval de muchas maneras: desde versos que describen a la Virgen y sus atributos hasta conceptos teológicos y mariológicos expresados plásticamente mediante formas retóricas. Por ejemplo, el jardín y las flores como ornamentos y símbolos personales de Santa María, o bien la imagen de la luz a través de un cristal o una ventana de vidrio en escenas de la Anunciación -con abundantes testimonios pictóricos en el arte medieval-, se encuentran en la poesía en forma de descripciones simbólicas de diversa extensión y género y, por otro lado, de advocaciones marianas o tópicos mariológicos (Ave/Eva, Flos, Hortus, Radix-Virga, Regina, Stella). Este artículo propone, pues, un estudio de conjunto y comparativo de algunos de estos procedimientos, concentrándose en las Cantigas de Santa María del rey Alfonso X. En este sentido, las figuras retóricas, como herramientas que tienden un puente entre lo pictórico y lo poético, dirigen necesariamente la lectura hacia una interpretación simbólica proporcionada por la figuración o typologia, tal como la ha postulado Erich Auerbach para la textualidad medieval. En última instancia, el valor sagrado de la imagen mariana (una herencia del arte icónico bizantino) se representa también en los milagros de las Cantigas de Santa María, obra maestra que evidencia una fuerte influencia de la doctrina iconodúlica.

Mujeres y hombres en el mundo agrario del sur santafecino. Desigualdades y dinámicas sociales en comunidades agrícolas a comienzos del siglo XXI

El desarrollo del capitalismo en el agro ha dado lugar a numerosas transformaciones y a diversos trabajos que reflexionan en torno a este suceso social. En el marco de una nueva ruralidad asociada a una agricultura en transformación y altamente tecnologizada, el presente estudio se construye en base a un análisis acerca de las relaciones que se establecen entre hombres y mujeres en tres comunas del sur de la Provincia de Santa Fe, zona núcleo de la Región Pampeana. Para llevar adelante dicho objetivo hemos escogido, como dimensiones de aproximación principales del análisis: los niveles de educación formal, los espacios de sociabilidad, la economía del hogar, el acceso a la tierra y las prácticas sucesorias. Una muestra estadísticamente representativa de 1.082 casos, junto a observaciones, entrevistas desestructuradas y registros etnográficos, han sido los insumos principales para un abordaje cuali-cuantitativo de los asuntos en cuestión.

Estrategias matrimoniales y patrimonio rural en la frontera : Chascomús (provincia de Buenos Aires-Argentina), 1780-1880

En este trabajo confluyen parte de los resultados de las investigaciones individuales que cada uno de los autores vienen desarrollando sobre el partido de Chascomús (provincia de Buenos Aires, Argentina) para el período 1780-1880. Estudiamos la relación entre la conservación del patrimonio rural y las estrategias matrimoniales dentro del grupo de los primeros pobladores del partido, abarcando las últimas décadas del período colonial y el período independiente hasta la consolidación del Estado Argentino. Proponemos establecer que si bien existieron notables ejemplos de que la vigencia de algunas familias en el partido a lo largo de toda la época se relaciona a la conservación de sus propiedades y a las ventajas derivadas de los matrimonios realizados dentro del grupo de propietarios, existieron diversas estrategias que le permitieron aún a las familias que no poseyeron tierras consolidarse en el mismo partido ya sea como productores independientes, como artesanos, o como mano de obra rural

Patrimonio geológico. Identificación, valoración y gestión de sitios de interés geológico

En las investigaciones en Ciencias Geológicas, en nuestro país y en especial en la Provincia de Buenos Aires, ha sido escaso el desarrollo relacionado con los sitios que requieran una preservación y protección especial. Sin embargo, son abundantes los sitios conocidos y nombrados en la bibliografía geológica que es necesario valorar y preservar como Patrimonio Geológico. El Patrimonio Geológico es un elemento más del patrimonio natural y constituye una parte importante de nuestra herencia natural. En la Conferencia de París auspiciada por la UNESCO en 1972 sobre la protección del patrimonio mundial, cultural y natural, algunos países pusieron en marcha investigaciones dirigidas hacia el conocimiento, su protección y la puesta en valor, lo cual resulta un recurso de indudable significación y una pieza clave para el desarrollo turístico de un territorio. Para conocer en forma exhaustiva el patrimonio geológico de un área es indispensable realizar inventarios, archivar la información necesaria para su descripción y poder recoger datos de interés para mantener actualizados los inventarios. Los diseños de las fichas presentan inconvenientes que se relacionan, en algunos casos, con que son muy sintéticas y demasiado subjetivas, y en otros, muy detalladas y rigurosas.