Decay of linkage disequilibrium within genes across HGDP-CEPH human samples: most population isolates do not show increased LD

Background: It is well known that the pattern of linkage disequilibrium varies between human populations, with remarkable geographical stratification. Indirect association studies routinely exploit linkage disequilibrium around genes, particularly in isolated populations where it is assumed to be higher. Here, we explore both the amount and the decay of linkage disequilibrium with physical distance along 211 gene regions, most of them related to complex diseases, across 39 HGDP-CEPH population samples, focusing particularly on the populations defined as isolates. Within each gene region and population we use r2 between all possible single nucleotide polymorphism (SNP) pairs as a measure of linkage disequilibrium and focus on the proportion of SNP pairs with r2 greater than 0.8.Results: Although the average r2 was found to be significantly different both between and within continental regions, a much higher proportion of r2 variance could be attributed to differences between continental regions (2.8% vs. 0.5%, respectively). Similarly, while the proportion of SNP pairs with r2 > 0.8 was significantly different across continents for all distance classes, it was generally much more homogenous within continents, except in the case of Africa and the Americas. The only isolated populations with consistently higher LD in all distance classes with respect to their continent are the Kalash (Central South Asia) and the Surui (America). Moreover, isolated populations showed only slightly higher proportions of SNP pairs with r2 > 0.8 per gene region than non-isolated populations in the same continent. Thus, the number of SNPs in isolated populations that need to be genotyped may be only slightly less than in non-isolates. Conclusion: The "isolated population" label by itself does not guarantee a greater genotyping efficiency in association studies, and properties other than increased linkage disequilibrium may make these populations interesting in genetic epidemiology.

Genetic origin, admixture, and asymmetry in maternal and paternal human lineages in Cuba

Background: Before the arrival of Europeans to Cuba, the island was inhabited by two Native American groups, the Tainos and the Ciboneys. Most of the present archaeological, linguistic and ancient DNA evidence indicates a South American origin for these populations. In colonial times, Cuban Native American people were replaced by European settlers and slaves from Africa. It is still unknown however, to what extent their genetic pool intermingled with and was 'diluted' by the arrival of newcomers. In order to investigate the demographic processes that gave rise to the current Cuban population, we analyzed the hypervariable region I (HVS-I) and five single nucleotide polymorphisms (SNPs) in the mitochondrial DNA (mtDNA) coding region in 245 individuals, and 40 Y-chromosome SNPs in 132 male individuals. Results: The Native American contribution to present-day Cubans accounted for 33% of the maternal lineages, whereas Africa and Eurasia contributed 45% and 22% of the lineages, respectively. This Native American substrate in Cuba cannot be traced back to a single origin within the American continent, as previously suggested by ancient DNA analyses. Strikingly, no Native American lineages were found for the Y-chromosome, for which the Eurasian and African contributions were around 80% and 20%, respectively. Conclusion: While the ancestral Native American substrate is still appreciable in the maternal lineages, the extensive process of population admixture in Cuba has left no trace of the paternal Native American lineages, mirroring the strong sexual bias in the admixture processes taking place during colonial times.

Synthesis, binding affinity, and molecular docking analysis of new benzofuranone derivative as pontential antipsychotics

The complex etiology of schizophrenia has prompted researchers to develop clozapine-related multitargetstrategies to combat its symptoms. Here we describe a series of new 6-aminomethylbenzofuranones in aneffort to find new chemical structures with balanced affinities for 5-HT2 and dopamine receptors. Throughbiological and computational studies of 5-HT2A and D2 receptors, we identified the receptor serine residuesS3.36 and S5.46 as the molecular keys to explaining the differences in affinity and selectivity betweenthese new compounds for this group of receptors. Specifically, the ability of these compounds to establishone or two H-bonds with these key residues appears to explain their difference in affinity. In addition, wedescribe compound 2 (QF1004B) as a tool to elucidate the role of 5-HT2C receptors in mediating antipsychoticeffects and metabolic adverse events. The compound 16a (QF1018B) showed moderate to high affinitiesfor D2 and 5-HT2A receptors, and a 5-HT2A/D2 ratio was predictive of an atypical antipsychotic profile.

Minimizing recombinations in consensus networks for phylogeographic studies

Background: We address the problem of studying recombinational variations in (human) populations. In this paper, our focus is on one computational aspect of the general task: Given two networks G1 and G2, with both mutation and recombination events, defined on overlapping sets of extant units the objective is to compute a consensus network G3 with minimum number of additional recombinations. We describe a polynomial time algorithm with a guarantee that the number of computed new recombination events is within ϵ = sz(G1, G2) (function sz is a well-behaved function of the sizes and topologies of G1 and G2) of the optimal number of recombinations. To date, this is the best known result for a network consensus problem.Results: Although the network consensus problem can be applied to a variety of domains, here we focus on structure of human populations. With our preliminary analysis on a segment of the human Chromosome X data we are able to infer ancient recombinations, population-specific recombinations and more, which also support the widely accepted 'Out of Africa' model. These results have been verified independently using traditional manual procedures. To the best of our knowledge, this is the first recombinations-based characterization of human populations. Conclusion: We show that our mathematical model identifies recombination spots in the individual haplotypes; the aggregate of these spots over a set of haplotypes defines a recombinational landscape that has enough signal to detect continental as well as population divide based on a short segment of Chromosome X. In particular, we are able to infer ancient recombinations, population-specific recombinations and more, which also support the widely accepted 'Out of Africa' model. The agreement with mutation-based analysis can be viewed as an indirect validation of our results and the model. Since the model in principle gives us more information embedded in the networks, in our future work, we plan to investigate more non-traditional questions via these structures computed by our methodology.

African signatures of recent positive selection in human FOXI1

Background: The human FOXI1 gene codes for a transcription factor involved in the physiology of the inner ear, testis, and kidney. Using three interspecies comparisons, it has been suggested that this may be a gene underhuman-specific selection. We sought to confirm this finding by using an extended set of orthologous sequences.Additionally, we explored for signals of natural selection within humans by sequencing the gene in 20 Europeans,20 East Asians and 20 Yorubas and by analysing SNP variation in a 2 Mb region centered on FOXI1 in 39worldwide human populations from the HGDP-CEPH diversity panel.Results: The genome sequences recently available from other primate and non-primate species showed that FOXI1divergence patterns are compatible with neutral evolution. Sequence-based neutrality tests were not significant inEuropeans, East Asians or Yorubas. However, the Long Range Haplotype (LRH) test, as well as the iHS and XP-Rsbstatistics revealed significantly extended tracks of homozygosity around FOXI1 in Africa, suggesting a recentepisode of positive selection acting on this gene. A functionally relevant SNP, as well as several SNPs either on theputatively selected core haplotypes or with significant iHS or XP-Rsb values, displayed allele frequencies stronglycorrelated with the absolute geographical latitude of the populations sampled.Conclusions: We present evidence for recent positive selection in the FOXI1 gene region in Africa. Climate mightbe related to this recent adaptive event in humans. Of the multiple functions of FOXI1, its role in kidney-mediatedwater-electrolyte homeostasis is the most obvious candidate for explaining a climate-related adaptation.

Genetic studies of the Roma (Gypsies): a review

Background: Data provided by the social sciences as well as genetic research suggest that the 8-10 million Roma (Gypsies) who live in Europe today are best described as a conglomerate of genetically isolated founder populations. The relationship between the traditional social structure observed by the Roma, where the Group is the primary unit, and the boundaries, demographic history and biological relatedness of the diverse founder populations appears complex and has not been addressed by population genetic studies. Results: Recent medical genetic research has identified a number of novel, or previously known but rare conditions, caused by private founder mutations. A summary of the findings, provided in this review, should assist diagnosis and counselling in affected families, and promote future collaborative research. The available incomplete epidemiological data suggest a non-random distribution of disease-causing mutations among Romani groups.Conclusion: Although far from systematic, the published information indicates that medical genetics has an important role to play in improving the health of this underprivileged and forgotten people of Europe. Reported carrier rates for some Mendelian disorders are in the range of 5 -15%, sufficient to justify newborn screening and early treatment, or community-based education and carrier testing programs for disorders where no therapy is currently available. To be most productive, future studies of the epidemiology of single gene disorders should take social organisation and cultural anthropology into consideration, thus allowing the targeting of public health programs and contributing to the understanding of population structure and demographic history of the Roma.

Prediction of enzyme function by combining sequence similarity and protein interactions

Background: A number of studies have used protein interaction data alone for protein function prediction. Here, we introduce a computational approach for annotation of enzymes, based on the observation that similar protein sequences are more likely to perform the same function if they share similar interacting partners. Results: The method has been tested against the PSI-BLAST program using a set of 3,890 protein sequences from which interaction data was available. For protein sequences that align with at least 40% sequence identity to a known enzyme, the specificity of our method in predicting the first three EC digits increased from 80% to 90% at 80% coverage when compared to PSI-BLAST. Conclusion: Our method can also be used in proteins for which homologous sequences with known interacting partners can be detected. Thus, our method could increase 10% the specificity of genome-wide enzyme predictions based on sequence matching by PSI-BLAST alone.

Discovering the campus together: a mobile and computer-based learning experience

One of the most relevant difficulties faced by first-year undergraduate students is to settle into the educational environment of universities. This paper presents a case study that proposes a computer-assisted collaborative experience designed to help students in their transition from high school to university. This is done by facilitating their first contact with the campus and its services, the university community, methodologies and activities. The experience combines individual and collaborative activities, conducted in and out of the classroom, structured following the Jigsaw Collaborative Learning Flow Pattern. A specific environment including portable technologies with network and computer applications has been developed to support and facilitate the orchestration of a flow of learning activities into a single integrated learning setting. The result is a Computer-Supported Collaborative Blended Learning scenario, which has been evaluated with first-year university students of the degrees of Software and Audiovisual Engineering within the subject Introduction to Information and Communications Technologies. The findings reveal that the scenario improves significantly students’ interest in their studies and their understanding about the campus and services provided. The environment is also an innovative approach to successfully support the heterogeneous activities conducted by both teachers and students during the scenario. This paper introduces the goals and context of the case study, describes how the technology was employed to conduct the learning scenario, the evaluation methods and the main results of the experience.

Recursos sobre protección de los derechos de la mujer en Internet

Con el objetivo de contribuir a salvaguardar los derechos fundamentales de las mujeres, hemos realizado este trabajo en el que intentamos recoger de la manera más exhaustiva que permita un medio tan voluble y cambiantecomo internet, los recursos existentes en la red sobre la Protección de los Derechos de la Mujer, y de esta manera facilitar el acceso a los mismos. La intención que ha guiado desde un principio a la elaboración de estaobra ha sido proporcionar un recurso de información práctica a aquellos profesionalesque desarrollan tareas relacionadas con la protección de los derechos de la mujer, así como a cualquier otra persona interesada o que necesite estar informada sobre esta temática. Así pues, el objetivo que nos hemos marcado no ha sido otro que el dedesarrollar una guía que permita a sus usuarios/as encontrar en internet aquellas direcciones sobre Derechos de la Mujer que facilitan un contenido sustancial e interesante.

Girona, capital jurisdiccional de la Catalunya convulsa dels anys 1630

El treball té per marc precís els anys 1635-37. El seu objecteés la transferència de Barcelona a Girona de la plana major deles institucions virregnals de Catalunya (la Reial Audiència, laBatllia General, l’ofici del mestre racional...) i el seu personal.

L'equilibri en la força

Aquesta unitat didàctica desenvolupada durant el Màster de Professorat de Secundària està pensada per ser impartida a l’assignatura Física i Química de 4t d’ESO, més concretament a la part de física, com introducció a la Dinàmica. Es parteix de les idees prèvies de l’alumnat sobre situacions quotidianes on hi actuen forces. Es contrasten aquestes amb una posada en comú i amb l’explicació del professor, que va introduint progressivament conceptes nous com l’equilibri o els vectors, a mesura que es fan necessaris. En les sessions posteriors s’insisteix en el caràcter vectorial de les forces i es centra l’atenció en dos casos particulars: la força de fregament i la força elàstica. Sobre aquestes dues es treballa resolent un cas i fent una experiència pràctica, fomentant la competència comunicativa. La finalitat de la metodologia és acabar construint les Lleis de Newton, les quals hauran d’exposar en una presentació al final de la unitat.

Los retos presentes y futuros de las agencias de medios en España

La revolución tecnológica en la que estamos inmersos está afectando a los consumidores, a las marcas y muy especialmente a los medios de comunicación, lo que obliga a las agencias de medios a reformular tanto susestructuras organizativas como los servicios que ofrecen a los anunciantes. En un momento además caracterizado por una grave crisis económica que hace que las inversiones publicitarias de hoy en día estén retrocediendo hasta niveles de hace cinco años atrás.En esta investigación realizaré un análisis retrospectivo de este tipo de agencias desde los años 70 hasta nuestros días, analizando los factores que han impulsado a que las agencias de medios estén cambiando, continuando de este modo con la línea de investigación abierta por el Dr. Francisco Javier Pérez-Latre de la Universidad de Navarra y autor de la tesis “Centrales deCompra de Medios”.

Figures i mirades salvatges en el cinema de Werner Herzog

Aquest treball de recerca vol explorar com el concepte del salvatge europeu es plasmaen l'obra del cineasta alemany Werner Herzog. Aquesta plasmació es produeix tant anivell figuratiu i narratiu com a nivell estètic. Per una banda, en aquests films hi ha un treball del cos i de com aquest es sotmet a diverses regles socials i de representació, que el salvatge contestarà amb un rebuig de l'ordre establert, sovint concretat en la idea de fuga cap a la natura. Per altra banda, l'estètica dels films de Herzog respon al que denominem una mirada salvatge: la representació d'una societat teatral que s'enfonsa, per una banda, i l'ús de recursos formals per a reproduir una mirada primigènia sobre les imatges, per l'altra. En tots els casos, la dinàmica d'alliberament de les forces civilitzadores constitueix el fonament de la narració i l'estètica del cineasta alemany.

El ciclo del fantástico en M. Night Shyamalan

El objeto de esta investigación es detectar la idiosincrasia del fantástico en M. Night Shyamalan. Es decir, qué manifestaciones de modo y estilo ofrecen sus películas, y si existe un elemento que constituya la forma causal y determinadora de su ciclo del fantástico. Para ello se ha partido de unadoble perspectiva. La primera es un estudio de género. A partir de las constantes del fantástico literario y cinematográfico, destacadas por diversos autores, se llega a la modalización del discurso fantástico de Shyamalan. La segunda es un estudio estilístico. El Estilo Trascendental, definido por Paul Schrader, es la base, junto a otras clasificaciones análogas, para averiguar si el estilo del director encaja en las coordenadas de lo que sería el Fantástico Trascendental. Finalmente, elanálisis se completa con las características expresivas de Shyamalan que, integradas en lo anterior, conducen a la pausa como forma del Fantástico Trascendental de este director.

Visions postapocalíptiques: la ruïna i el cos en el cinema de Ciprì i Maresco

Aquest treball de recerca traça, mitjançant una metodologia transversal i comparativa, un recorregut per dos dels pilars fonamentals en la producció videocinematogràfica del duet de directors sicilians Daniele Ciprì i Franco Maresco: el cos i la ruïna. Considerada la seva obra com una visió radical del cinema i la televisió com a mitjà expressiu, al mateix temps que es treuen a la llum les principals motivacions que els han dut a seguir aquesta via al marge dels convencionalismes, s’aborden i analitzen alguns dels conceptes i motius visuals que es troben en ella: el cinisme, el sublim, el grotesc, el context postapocalíptic... Defugint tot propòsit d’establir una cronologia de fets, es destaquen i examinen posteriorment els aspectes més rellevants de la geografia dels espais que filmen i de l’anatomia dels personatges que els habiten, tot desglossant un seguit de subtemes per facilitar l’anàlisi i demostrar que la conjunció de cos i ruïna confecciona una atmosfera expressiva portada al límit de la representació