A genomewide scan for early-onset coronary artery disease in 438 families: the GENECARD Study.

A family history of coronary artery disease (CAD), especially when the disease occurs at a young age, is a potent risk factor for CAD. DNA collection in families in which two or more siblings are affected at an early age allows identification of genetic factors for CAD by linkage analysis. We performed a genomewide scan in 1,168 individuals from 438 families, including 493 affected sibling pairs with documented onset of CAD before 51 years of age in men and before 56 years of age in women. We prospectively defined three phenotypic subsets of families: (1) acute coronary syndrome in two or more siblings; (2) absence of type 2 diabetes in all affected siblings; and (3) atherogenic dyslipidemia in any one sibling. Genotypes were analyzed for 395 microsatellite markers. Regions were defined as providing evidence for linkage if they provided parametric two-point LOD scores >1.5, together with nonparametric multipoint LOD scores >1.0. Regions on chromosomes 3q13 (multipoint LOD = 3.3; empirical P value <.001) and 5q31 (multipoint LOD = 1.4; empirical P value <.081) met these criteria in the entire data set, and regions on chromosomes 1q25, 3q13, 7p14, and 19p13 met these criteria in one or more of the subsets. Two regions, 3q13 and 1q25, met the criteria for genomewide significance. We have identified a region on chromosome 3q13 that is linked to early-onset CAD, as well as additional regions of interest that will require further analysis. These data provide initial areas of the human genome where further investigation may reveal susceptibility genes for early-onset CAD.

Un modelo de producción en gruta: el Alfar de Cabrera D'Anoia, Barcelona

La utilización de grutas y cuevas para llevar a cabo actividades productivas fue un hecho habitual en época medieval. Este trabajo pretende analizar un modelo de producción cerámica que se adapta a un espacio físico considerablemente limitado por las características geológicas del entorno. El alfar de Cabrera d¿Anoia constituye un ejemplo paradigmático de dicho modelo e ilustra un proceso de evolución cronológica y de transformación del entorno para satisfacer las necesidades de la producción cerámica.

La pileta del despoblado medieval de Revenga (Burgos): a propósito del lavado ritual de los difuntos y sus evidencias arqueológicas

Las excavaciones en el yacimiento de Revenga dieron a conocer los testimonios arqueológicos correspondientes a la iglesia de este despoblado, así como su extensa área funeraria. Aquellos trabajos localizaron en el interior del espacio litúrgico una enigmática pileta rupestre a la que se atribuyó inicialmente una función de carácter bautismal. Sin embargo, la revisión de los testimonios arqueológicos, así como el avance de las investigaciones, sugieren que dicha cavidad rupestre se debería relacionar, de forma más plausible, con el lavado de los difuntos, una costumbre funeraria muy arraigada en época medieval que estuvo integrada de forma ordinaria entre los ritos que rodeaban las exequias cristianas.

El despoblado altomedieval de Cuyacabras (Burgos): Realidad, principios y argumentos

The archaeological site of Cuyacabras (Quintanar de la Sierra, Burgos) is one of main early medieval reference settlements in Upper Arlanza basin lands and it attracts a great amount of visitors. The monumental featured half-caved church and the necropolis consisting of several burials dug into the rock present around the whole area are material evidences of an ancient hill town which has remained uninhabited from middle XIIIth century. New fieldworks on this whole site, excavated during the sixties, have been focused on improving the scientific impact of the site and setting up to date the records and information entries for the necropolis. All obtained data emphasize the weakness of several principles used to put in value the settlement, and they also suggest a revision of several-year-old discussions on one hand, and on the other one, they encourage scholars to propound new up to date theories which will fi t better with our knowledge"s current context.

Necropolis rupestres y el poblamiento altomedieval en el Alto Arlanza (Burgos)

El estudio del poblamiento altomedieval en el Alto Arlanza sigue vinculado, casi en exclusiva, al análisis que deriva de una visión difusa de sus necrópolis rupestres. Los problemas de visibilidad que plantean los testimonios materiales de estos asentamientos han provocado, como ha ocurrido en otros territorios, que el análisis arqueológico tradicional se haya focalizado en el estudio exclusivo de los elementos funerarios, por lo que disponemos en realidad de un registro parcial y claramente deficitario de las evidencias aldeanas. Poner de relieve la notable indefinición de estos testimonios y señalar las dificultades cronológicas que afecta a estas evidencias constituye dos elementos de reflexión necesarios para redefinir las nuevas estrategias en la construcción de un registro de calidad que permita adentrarnos con seguridad en la génesis del paisaje medieval y, en particular, en la formación de la red aldeana.

The evolution of unicoloniality in ant societies : recognition, dispersal and population genetic structure

Introduction Societies of ants, bees, wasps and termites dominate many terrestrial ecosystems (Wilson 1971). Their evolutionary and ecological success is based upon the regulation of internal conflicts (e.g. Ratnieks et al. 2006), control of diseases (e.g. Schmid-Hempel 1998) and individual skills and collective intelligence in resource acquisition, nest building and defence (e.g. Camazine 2001). Individuals in social species can pass on their genes not only directly trough their own offspring, but also indirectly by favouring the reproduction of relatives. The inclusive fitness theory of Hamilton (1963; 1964) provides a powerful explanation for the evolution of reproductive altruism and cooperation in groups with related individuals. The same theory also led to the realization that insect societies are subject to internal conflicts over reproduction. Relatedness of less-than-one is not sufficient to eliminate all incentive for individual selfishness. This would indeed require a relatedness of one, as found among cells of an organism (Hardin 1968; Keller 1999). The challenge for evolutionary biology is to understand how groups can prevent or reduce the selfish exploitation of resources by group members, and how societies with low relatedness are maintained. In social insects the evolutionary shift from single- to multiple queens colonies modified the relatedness structure, the dispersal, and the mode of colony founding (e.g. (Crozier & Pamilo 1996). In ants, the most common, and presumably ancestral mode of reproduction is the emission of winged males and females, which found a new colony independently after mating and dispersal flights (Hölldobler & Wilson 1990). The alternative reproductive tactic for ant queens in multiple-queen colonies (polygyne) is to seek to be re-accepted in their natal colonies, where they may remain as additional reproductives or subsequently disperse on foot with part of the colony (budding) (Bourke & Franks 1995; Crozier & Pamilo 1996; Hölldobler & Wilson 1990). Such ant colonies can contain up to several hundred reproductive queens with an even more numerous workforce (Cherix 1980; Cherix 1983). As a consequence in polygynous ants the relatedness among nestmates is very low, and workers raise brood of queens to which they are only distantly related (Crozier & Pamilo 1996; Queller & Strassmann 1998). Therefore workers could increase their inclusive fitness by preferentially caring for their closest relatives and discriminate against less related or foreign individuals (Keller 1997; Queller & Strassmann 2002; Tarpy et al. 2004). However, the bulk of the evidence suggests that social insects do not behave nepotistically, probably because of the costs entailed by decreased colony efficiency or discrimination errors (Keller 1997). Recently, the consensus that nepotistic behaviour does not occur in insect colonies was challenged by a study in the ant Formica fusca (Hannonen & Sundström 2003b) showing that the reproductive share of queens more closely related to workers increases during brood development. However, this pattern can be explained either by nepotism with workers preferentially rearing the brood of more closely related queens or intrinsic differences in the viability of eggs laid by queens. In the first chapter, we designed an experiment to disentangle nepotism and differences in brood viability. We tested if workers prefer to rear their kin when given the choice between highly related and unrelated brood in the ant F. exsecta. We also looked for differences in egg viability among queens and simulated if such differences in egg viability may mistakenly lead to the conclusion that workers behave nepotistically. The acceptance of queens in polygnous ants raises the question whether the varying degree of relatedness affects their share in reproduction. In such colonies workers should favour nestmate queens over foreign queens. Numerous studies have investigated reproductive skew and partitioning of reproduction among queens (Bourke et al. 1997; Fournier et al. 2004; Fournier & Keller 2001; Hammond et al. 2006; Hannonen & Sundström 2003a; Heinze et al. 2001; Kümmerli & Keller 2007; Langer et al. 2004; Pamilo & Seppä 1994; Ross 1988; Ross 1993; Rüppell et al. 2002), yet almost no information is available on whether differences among queens in their relatedness to other colony members affects their share in reproduction. Such data are necessary to compare the relative reproductive success of dispersing and non-dispersing individuals. Moreover, information on whether there is a difference in reproductive success between resident and dispersing queens is also important for our understanding of the genetic structure of ant colonies and the dynamics of within group conflicts. In chapter two, we created single-queen colonies and then introduced a foreign queens originating from another colony kept under similar conditions in order to estimate the rate of queen acceptance into foreign established colonies, and to quantify the reproductive share of resident and introduced queens. An increasing number of studies have investigated the discrimination ability between ant workers (e.g. Holzer et al. 2006; Pedersen et al. 2006), but few have addressed the recognition and discrimination behaviour of workers towards reproductive individuals entering colonies (Bennett 1988; Brown et al. 2003; Evans 1996; Fortelius et al. 1993; Kikuchi et al. 2007; Rosengren & Pamilo 1986; Stuart et al. 1993; Sundström 1997; Vásquez & Silverman in press). These studies are important, because accepting new queens will generally have a large impact on colony kin structure and inclusive fitness of workers (Heinze & Keller 2000). In chapter three, we examined whether resident workers reject young foreign queens that enter into their nest. We introduced mated queens into their natal nest, a foreign-female producing nest, or a foreign male-producing nest and measured their survival. In addition, we also introduced young virgin and mated queens into their natal nest to examine whether the mating status of the queens influences their survival and acceptance by workers. On top of polgyny, some ant species have evolved an extraordinary social organization called 'unicoloniality' (Hölldobler & Wilson 1977; Pedersen et al. 2006). In unicolonial ants, intercolony borders are absent and workers and queens mix among the physically separated nests, such that nests form one large supercolony. Super-colonies can become very large, so that direct cooperative interactions are impossible between individuals of distant nests. Unicoloniality is an evolutionary paradox and a potential problem for kin selection theory because the mixing of queens and workers between nests leads to extremely low relatedness among nestmates (Bourke & Franks 1995; Crozier & Pamilo 1996; Keller 1995). A better understanding of the evolution and maintenance of unicoloniality requests detailed information on the discrimination behavior, dispersal, population structure, and the scale of competition. Cryptic genetic population structure may provide important information on the relevant scale to be considered when measuring relatedness and the role of kin selection. Theoretical studies have shown that relatedness should be measured at the level of the `economic neighborhood', which is the scale at which intraspecific competition generally takes place (Griffin & West 2002; Kelly 1994; Queller 1994; Taylor 1992). In chapter four, we conducted alarge-scale study to determine whether the unicolonial ant Formica paralugubris forms populations that are organised in discrete supercolonies or whether there is a continuous gradation in the level of aggression that may correlate with genetic isolation by distance and/or spatial distance between nests. In chapter five, we investigated the fine-scale population structure in three populations of F. paralugubris. We have developed mitochondria) markers, which together with the nuclear markers allowed us to detect cryptic genetic clusters of nests, to obtain more precise information on the genetic differentiation within populations, and to separate male and female gene flow. These new data provide important information on the scale to be considered when measuring relatedness in native unicolonial populations.

A prospective molecular surveillance study evaluating the clinical impact of community-acquired respiratory viruses in lung transplant recipients.

BACKGROUND: Community-acquired respiratory viral infections (RVIs) are common in lung transplant patients and may be associated with acute rejection and bronchiolitis obliterans syndrome (BOS). The use of sensitive molecular methods that can simultaneously detect a large panel of respiratory viruses may help better define their effects. METHODS: Lung transplant recipients undergoing serial surveillance and diagnostic bronchoalveolar lavages (BALs) during a period of 3 years were enrolled. BAL samples underwent multiplex testing for a panel of 19 respiratory viral types/subtypes using the Luminex xTAG respiratory virus panel assay. RESULTS: Demographics, symptoms, and forced expiratory volume in 1 sec were prospectively collected for 93 lung transplant recipients enrolled. Mean number of BAL samples was 6.2+/-3.1 per patient. A respiratory virus was isolated in 48 of 93 (51.6%) patients on at least one BAL sample. Of 81 positive samples, the viruses isolated included rhinovirus (n=46), parainfluenza 1 to 4 (n=17), coronavirus (n=11), influenza (n=4), metapneumovirus (n=4), and respiratory syncytial virus (n=2). Biopsy-proven acute rejection (> or =grade 2) or decline in forced expiratory volume in 1 sec > or =20% occurred in 16 of 48 (33.3%) patients within 3 months of RVI when compared with 3 of 45 (6.7%) RVI-negative patients within a comparable time frame (P=0.001). No significant difference was seen in incidence of acute rejection between symptomatic and asymptomatic patients. Biopsy-proven obliterative bronchiolitis or BOS was diagnosed in 10 of 16 (62.5%) patients within 1 year of infection. CONCLUSION: Community-acquired RVIs are frequently detected in BAL samples from lung transplant patients. In a significant percentage of patients, symptomatic or asymptomatic viral infection is a trigger for acute rejection and obliterative bronchiolitis/BOS.

Reduction of choroidal neovascularization in mice by adeno-associated virus-delivered anti-vascular endothelial growth factor short hairpin RNA.

BACKGROUND: Strategies leading to the long-term suppression of inappropriate ocular angiogenesis are required to avoid the need for repetitive monthly injections for treatment of diseases of the eye, such as age-related macular degeneration (AMD). The present study aimed to develop a strategy for the sustained repression of vascular endothelial growth factor (VEGF), which is identified as the key player in exudative AMD. METHODS: We have employed short hairpin (sh)RNAs combined with adeno-associated virus (AAV) delivery to obtain the targeted expression of potent gene-regulatory molecules. Anti-VEGF shRNAs were analyzed in human retinal pigment epithelial (RPE) cells using Renilla luciferase screening. For in vivo delivery of the most potent shRNA, self-complementary AAV vectors were packaged in serotype 8 capsids (scAAV2/8-hU6-sh9). In vivo efficacy was evaluated either by injection of scAAV2/8-hU6-sh9 into murine hind limb muscles or in a laser-induced murine model of choroidal neovascularization (CNV) following scAAV2/8-hU6-sh9 subretinal delivery. RESULTS: Plasmids encoding anti-VEGF shRNAs showed efficient knockdown of human VEGF in RPEs. Intramuscular administration led to localized expression and 91% knockdown of endogenous murine (m)VEGF. Subsequently, the ability of AAV2/8-encoded shRNAs to impair vessel formation was evaluated in the murine model of CNV. In this model, the sizes of the CNV were significantly reduced (up to 48%) following scAAV2/8-hU6-sh9 subretinal delivery. CONCLUSIONS: Using anti-VEGF vectors, we have demonstrated efficient silencing of endogenous mVEGF and showed that subretinal administration of scAAV2/8-hU6-sh9 has the ability to impair vessel formation in an AMD animal model. Thus, AAV-encoded shRNA can be used for the inhibition of neovascularization, leading to the development of sustained anti-VEGF therapy. Copyright © 2012 John Wiley & Sons, Ltd.

El paper del joc en el desenvolupament d'infants amb TEA

Jugar no és només un sinònim de diversió, sinó que darrera d’aquesta acció s’amaguen molts elements que són imprescindible per al desenvolupament infantil, ja que l’afavoreix en tots els àmbits de la seva vida. Un nen amb Necessitats Educatives Especial té el mateix dret de gaudir d’una estona de joc, i desenvolupar-­‐se com a persona. De fet, el joc és considerat una eina d’aprenentatge a l’edat infantil. Per això, el present treball de grau té com objectiu principal analitzar la importància del joc com a eina educativa amb infants amb un Trastorn de l’Espectre Autista. S’utilitza una metodologia qualitativa, i a través de l’observació, s’analitza com el joc ajuda a un infant amb Trastorn de l’Espectre Autista a adquirir determinades habilitats i capacitats que li permeten tenir certa autonomia. Els resultats obtinguts, permeten afirmar que la Unitat de Suport a l’Educació Especial utilitza el joc com un recurs didàctic per a treballar amb infants amb Autisme. Per això, es planteja una proposta d’intervenció dins d’aquesta unitat.

Nuevas técnicas de estadística espacial para la detección de clusters residenciales de población inmigrante

La estadística aplicada a la geografía ha experimentado un avance espectacular en las últimas dos décadas introduciéndose el espacio como eje fundamental del análisis. Este avance se ha visto acompañado por un rápido desarrollo de aplicaciones estadísticas integradas en los sistemas de información geográfica, constituyéndose de esta forma en un conjunto de herramientas imprescindibles en la planificación territorial. Por otro lado, en España, el incremento de población inmigrada en un corto intervalo de tiempo ha hecho necesario analizar su distribución espacial en las áreas urbanas. Los índices de autocorrelación espacial, tanto global como local, y su representación cartográfica constituyen una técnica adecuada para la detección de clusters y patrones espaciales y abre la posibilidad de plantear diferentes modelos econométricos. A partir del caso de la ciudad de Barcelona se aplican las técnicas descritas y se observan los diferentes comportamientos según el grupo de población estudiado.

Distribució espacial de la població immigrant a Osona. Una aproximació quantitativa

Un fet clau pel coneixement de la població immigrant i el disseny de polítiques d’acollida és la seva distribució territorial. Els indicadors de segregació residencial són una eina molt útil. En aquest article es proposen mesures contrastades internacionalment i s’apliquen al cas osonenc considerant Osona com a conjunt i també estudiant per separat el casos de Vic i Manlleu. Tot i ser una comarca amb un percentatge rellevant de població immigrant no es donen situacions segregatives que sí es troben en l’àmbit metropolità.

Indicadores cuantitativos de segregación residencial. El caso de la población inmigrante en Barcelona

La segregación residencial en una ciudad indica el nivel de desigualdad de la distribución de la población entre las diferentes zonas. Es interesante obtener una visión cuantitativa de la segregación residencial para prever y actuar sobre los territorios más afectados por este proceso. En este artículo se propone medir la segregación de los colectivos de inmigrantes desde diferentes ópticas, utilizando la estadística espacial y los sistemas de información geográfica. Con estas herramientas se realiza un estudio sobre la distribución de la población inmigrante para la ciudad de Barcelona. Los resultados apuntan a una disminución en la segregación entre 1996 y 2001. Aunque se aprecian diferencias significativas según la procedencia de cada grupo estudiado.

Población inmigrante y espacio urbano. Indicadores de segregación y pautas de localización

Given the importance of immigrant population growth in Spain, it would be interesting to study its distribution throughout the urban area. The field of statistics suggests different indicators that have a long tradition and permit the quantification of segregation of minority population groups. Through the application of these tools in the Metropolitan Region of Barcelona, this paper demonstrates the utility of analyzing segregation patterns within a city and detecting local patterns of this phenomenon. A new perspective of segregation can be obtained with the use of indicators designed for spatial statistics. The combination of these measures represents a useful procedure for the analysis of the distribution of the immigrant population in urban areas and its extension to different areas such as sociology, economics, urban studies, and housing policy.

No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels.

Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (β = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were associated with 2-h glucose (β = 0.06-0.12 mmol/allele, P ≤ 1.53 × 10(-7)), but no significant interactions were found with PA (P > 0.18) or BMI (P ≥ 0.04). In this large study of gene-lifestyle interaction, we observed no interactions between genetic and lifestyle factors, both of which were associated with 2-h glucose. It is perhaps unlikely that top loci from genome-wide association studies will exhibit strong subgroup-specific effects, and may not, therefore, make the best candidates for the study of interactions.