Genetic studies of osteoporosis in Malta : a review

Osteoporosis is a complex metabolic disease with a strong genetic component which results in a decrease in bone mineral density and deterioration in the microarchitecture of bone, leading to an increased risk of fractures. During the last decade, a number of genetic studies of the Maltese population were performed to determine a potential genetic component which increases the individual’s susceptibility to osteoporosis. Both family and population case-control approaches were used. Linkage analysis using large affected families has identified a region on chromosome 11p12, following which functional studies have shown that variations within two genes found in that region namely, TRAF6 and CD44, affect gene expression, and, more specifically, pre-mRNA splicing in the case of CD44. This is the first report of strong suggestive linkage of 11p12 to osteoporosis. Using the candidate gene approach, selected candidate genes, which had been studied in other populations and been found to increase susceptibility to osteoporosis to varying degrees in some of them, included those coding for the vitamin D and oestrogen receptors (VDR & ER1), osteoprotegerin (TNFRSF11B), collagen type 1 (COL1A1), methylenetetrahydrofolate reductase (MTHFR) and lipoprotein receptor related protein (LRP)-5. In the Maltese population, the most significant result showed that a polymorphism in the promoter region of TNFRSF11B, which codes for osteoprotegerin, had a significant effect on bone mineral density, thus increasing the susceptibility to osteoporosis. These studies have shown that variations within three different genes, namely TRAF6, CD44 and TNFRSF11B, all involved in osteoclast biology, might increase the risk of osteoporosis and could therefore serve as targets for novel therapeutic agents.peer-reviewe

Linkage to chromosome 11p12 in two Maltese families with a highly penetrant form of osteoporosis

Osteoporosis is a metabolic bone disease with a strong genetic component. Family-based linkage studies were performed by a number of investigators to try to identify loci that might contain genes responsible for an increased susceptibility to osteoporosis. A whole-genome linkage scan using 400 microsatellite markers was performed in 27 members from two Maltese families with a highly penetrant form of osteoporosis. The phenotype was defined by lumbar and femoral z-scores calculated after measurement of bone mineral density by DEXA. Both males and females were among the affected individuals. Multipoint parametric and non-parametric linkage analyses were performed by EasyLinkage v4.01 using GENEHUNTER v2.1, assuming dominant and recessive modes of inheritance with variable penetrance. Evidence of linkage was observed to a marker at 11p12 where a non-parametric LOD score of 5.77 (P¼0.0006) was obtained. A maximum heterogeneity LOD score of 2.55 for this region was obtained for the dominant mode of inheritance with 90% penetrance and a phenocopy rate of 1%. Following fine mapping, the critical interval was narrowed to a region that is 52.94cM from 11p-telomere. In this region, the gene for tumour necrosis factor receptor-associated factor 6 (TRAF6) is located approximately 1 cM away from the indicated marker. Sequencing of the promoter region and exons of the TRAF6 gene revealed three sequence variants, one of which was found in three affected members within one family.peer-reviewe

Recorrido sobre las lenguas del Chaco y los aportes a la investigación lingüística

El Chaco es una de las regiones más ricas de América del Sur, no sólo desde el punto de vista ecológico, sino en términos de su diversidad etnolingüística. Este artículo ofrece primero un panorama actualizado sobre las lenguas chaqueñas y su clasificación genealógica así como un estado del arte de las obras publicadas sobre las lenguas del Chaco argentino. Después de reseñar los estudios sobre sintaxis en las lenguas chaqueñas anteriores a este volumen de Amerindia, las autoras se centran en los planteos teóricos que emergen del estudio de la cláusula y las relaciones interclausales en esta área lingüística, haciendo hincapié en los sistemas de alineamiento, las clases de palabras, sus límites y superposiciones, la relacionalidad de los sustantivos, los distintos tipos de cláusulas y de predicados, los procesos de combinación de verbos y de enlace entre cláusulas a nivel oracional y discursivo. Por último, pasan revista a los aspectos en los cuales los trabajos compilados contribuyen a la discusión y profundización de todos esos temas.Fil: Golluscio, Lucia Angela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Centro Argentino de Información Científica y Tecnológica; Argentina. Universidad de Buenos Aires. Facultad de Filosofía y Letras; ArgentinaFil: Vidal, Alejandra Silvia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad Nacional de Formosa. Facultad de Humanidades. Instituto de Investigaciones Lingüísticas; Argentin

The Impact of Adopting a Community College Baccalaureate Policy on States' Graduation Rate and Enrollment: A Consideration for All and Latino Students

This study evaluates the Community College Baccalaureate (CCB) as a regulatory change and its impact on undergraduate six-year graduation rate and enrollment at public four-year institutions for all students and for Latinos specifically. This policy diverges from the standard historical structure of higher education in the United States, which traditionally differentiates the missions of community colleges from those of four-year institutions. Moreover, the adoption of CCBs is an interesting policy experiment in that they appear to offer a solution that reconciles two seemingly conflicting preoccupations of state governments. These concerns include increased educational offerings, reduction of funding for bachelor’s degrees, and improvement in baccalaureate degree completion rates. In this dissertation, I demonstrate how shifting to a CCB policy influences enrollment and graduation rates at pubic four-year institutions. This study found that adopting a CCB policy has a positive effect on undergraduate enrollment for all students in public four-year institutions. It also indicated that the policy has a positive though statistically significant effect on the enrollment of Latinos. This investigation also found that the policy did not have any effect on average six-year graduation rates of Latinos or all other students. This study indicates that CCBs share the same conundrum that has daunted community colleges since their creation. CCBs expand educational access, but they may be playing a role in the growing stratification of higher education by excluding many Latino students from enrolling in four-year programs. Moreover, their impact on graduation rates reinforce the suspicion harbored by scholars about the frailty of community colleges in a political environment that focuses on reducing the cost of higher education. CCBs might be searching for more revenue sources to compensate for the declining support of state governments for higher education. However, as they are able to expand their reach, they are accepting funding at levels below other state universities offering bachelor’s degrees, in this way perpetuating the underfunding problem that they were hoping to alleviate. This study’s results make it -probable that underfunding issues may be affecting the service CCBs provide to baccalaureate-seeking students and ultimately their possibility of graduating.PHDHigher EducationUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/150041/1/avidalr_1.pd

Variants within protectin (CD59) and CD44 genes linked to an inherited haplotype in a family with coeliac disease

Coeliac disease (CD) is an autoimmune disorder characterised by inflammation, villous atrophy and hyperplasia of the small intestinal mucosa that affects genetically susceptible individuals. A genome-wide scan was performed in 17 family members with high incidence of CD. Highest nonparametric linkage (NPL) and logarithm of odds (LOD) scores were of 6.21 (P = 0.0107) and 2.57, respectively, to a region on chromosome 11p13-12. Following fine mapping, NPL and LOD scores did not change, but the linkage interval on chromosome 11 was narrowed to a region that is approximately 50.94 cM from pTer. Two inherited haplotypes on chromosomes 11p13-12 and 9q21 were observed in all affected members but not in the majority of clinically normal individuals. Sequencing of genes at region 11p13-12 showed a number of sequence variants, two of which were linked with the inherited haplotype. One of these variants in the CD59 gene was found at a very low frequency in the population and could possibly affect pre-messenger RNA splicing. This study is of particular importance for the identification of novel genes that might be responsible for CD other than human leukocyte antigen.peer-reviewe

Determinantes del uso del crédito de las microempresas formales del sector comercio en el Perú 2014 -2016

La presente tesis analiza los determinantes del uso del crédito de las microempresas formales del sector comercio en Perú entre los años 2014 y 2016, para lo cual se consideraron variables a nivel de la empresa como tamaño, años de experiencia, recibió capacitación en temas financieros y ubicación geográfica, también variables a nivel del conductor como sexo, edad y nivel educativo, variables que fueron escogidas tras la revisión de literatura. Para esto se trabajó con un pool de datos obtenido uniendo la Encuesta Nacional de Empresas de tres años. Asimismo, se utilizó un modelo logit para estimar el porcentaje en que las características influyen en las probabilidades de usar un crédito. La literatura empírica revisada, a nivel de Latinoamérica y Perú, sugiere que a mayor sea el tamaño de la empresa, mayores sean las probabilidades de hace uso del crédito, así como también que el conductor tenga mayor nivel de estudio o que sea hombre incrementan estas probabilidades. Los resultados obtenidos muestran que las variables propuestas son significativas al 1%, además, estos concuerdan con lo señalado en la literatura empírica. Acerca de las variables del conductor de la microempresa, se obtuvo que cuando el este es hombre tiene más de probabilidades de hacer uso que cuando es mujer. En esta misma línea, cuando el conductor ha concluido sus estudios superiores, tiene más probabilidades que uno que no concluyó su educación básica. Respecto de las variables de las características de la empresa, a medida que se incrementa el nivel de ventas, las empresas harán un menor uso del crédito, asimismo, el historial crediticio influye en que la microempresa pueda hacer uso de uno.This thesis analyzes what are the determinants of the use of credit in commerce formal micro-enterprises in Peru between 2014 and 2016, there have been considered variables at the company level such as size, years of experience, received training in financial topics and geography location, also variables at the driver level such as sex, age and educational level, variables that were chosen after the literature review. For this, I worked with a data pool obtained by appending the National Survey of Enterprise of three years, from 2015 to 2017. Likewise, a logit model was used to estimate the percentage in which the characteristics influence the probabilities of using a loan. The empirical literature reviewed, at the level of Latin America and Peru, suggests that the larger the size of the company, the greater the probabilities of using credit, as well, as that the driver has a higher level of education or that he is a man, these increase probabilities. The results obtained show that the proposed variables are significant at 1%, furthermore, they are consistent to what was indicated in the empirical literature. About the driver variables, it was obtained that when the driver is a man, he is more likely to use credit that when driver is a woman. In addition, when the driver has completed his higher education, he is more likely than one who did not complete his school studies. Regarding the variables of the characteristics of the company, as the level of sales increases, companies will make less use of credit, likewise, credit score influences whether the microenterprise can make use of one

Comparación de los niveles séricos y de expresión génica de citocinas pro-inflamatorias y anti-inflamatorias en ratones infectados experimentalmente con dos cepas de Trypanosoma cruzi

Trypanosoma cruzi, el agente etiológico de la enfermedad de Chagas, presenta gran variabilidad genética ocasionando diferencias en la respuesta inmune y en el desarrollo de esta afección, que afecta aproximadamente a diez millones de personas a nivel mundial, principalmente en veintiún países endémicos de América Latina incluido Perú. La presente investigación en el modelo experimental de ratón C57BL/6 para la enfermedad de Chagas tuvo como objetivo determinar la parasitemia y carga parasitaria en tejido cardíaco, así como también los niveles séricos y la expresión génica en tejido cardíaco de citocinas proinflamatorias (INF-γ, IL-12 y TNF-α) y antiinflamatorias (IL-10 e IL-4), comparando la infección por la cepa Arequipa (Tc I), originaria de Perú, y la cepa CL Brener (Tc VI), originaria de Brasil. Los resultados de parasitemia mostraron niveles significativamente menores para la cepa Arequipa solo a los 5 días posinfección y la carga parasitaria en tejido cardíaco tuvieron niveles significativamente menores para la cepa Arequipa durante todos los días evaluados. Los resultados de citocinas fueron muy variables y no se detectaron diferencias significativas en los niveles séricos; sin embargo, resalta la sobre expresión génica en tejido cardíaco donde INF-γ fue significativamente menor a los 15, 30 y 60 días posinfección, IL-12 a los 30 días y TNF-α e IL-10 a los 30 y 60 días posinfección en los ratones C57BL/6 infectados con T. cruzi cepa Arequipa en comparación con los infectados por la cepa CL Brener. En conjunto, todo esto parece indicar que la presencia de T. cruzi cepa peruana genera variables reacciones inflamatorias en el hospedero, con menor intensidad solo en ciertos días posinfección que la cepa CL Brener

On the 60th Anniversary of the Hart-Fuller Debate

On the 60th Anniversary of the storied Hart-Fuller Debate, we would like to briefly revisit it to highlight some of its concerns and discussions in order to demonstrate how vivid they still are and may serve as a path to the Rule of Law, concluding on the importance of promoting fruitful argumentation on essential issues in Jurisprudence to enlighten the practice of Law

A moralidade do direito como condição de liberdade em Lon Fuller

O presente trabalho tem como finalidade procurar demonstrar que a moralidade do Direito pode favorecer a liberdade, e, consequentemente, a comunicação social, a partir da proposta de Lon Fuller. Para tal, optamos primeiramente, por dá-lo a conhecer, através de sua biografia e escritos, pois, além de tratar-se de um autor ainda pouco divulgado em nosso país, esse passo pareceu-nos facilitar a compreensão de sua teoria. Em seguida, definimos antropologicamente os conceitos de moralidade e liberdade a partir do realismo jurídico, que entendemos servir de base filosófica para o autor. Após delinear sua postura com relação ao Direito, entramos no cerne da questão a ser confirmada a partir de seus escritos: se há um vínculo entre moralidade e Direito; se promovê-lo favorece a liberdade ou a limita, e se contribui efetivamente para a ordenação social fundamentada na comunicação, a partir de relações livres. Por fim, concluimos com uma breve avaliação crítica e uma sugestão prática para a formação dos estudantes de Direito, de forma a tornar efetiva sua teoria, já que esta sempre foi uma preocupação majoritária para o autor.The present work has the purpose of demonstrating that the morality of Law can favour freedom, and, consequently, the social communication, in the studies of Lon Fuller. For this target, we opted to show him off through a brief biography and writings, because this step seemed to us a way of making his comprehension easier, and also because the author is still not much known in our country. Following, we bring up the antropological concepts of morality and freedom from the juridical realism, for it seems to be the author ́s philosophical basis. After outlining his concept of Law, we get to the central point of the question to be confirmed through his writings: if there is any link between morality and Law; if promoting this link help freedom or constraint it, and if it really contributes to a social order based on communication, departing from free relations. Ending, we conclude with a brief critical valuation and a practical suggestion for the education of Law’s students, which has always been a major concern for the author