Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD.

Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.

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.

Amor e Identidad

El presente libro es una celebración. Celebramos que las Jornadas "Amor i identitat en la literatura feta per dones", organizada por el Centro "Dona i Literatura, que tuvieron lugar en la Facultad de Filología de la Universidad de Barcelona en marzo de 1995 y cuyos resultados estan recogidos en este volumen, gozaron de un alto nivel académico y de una gran acogida por parte de profesores, estudiantes y el público en general. Este volumen, el segundo de la colección "Mujeres y Literatura, es un reflejo de nuestra voluntad de continuar colaborando en explorar, dar a conocer y disfrutar la literatura escrita por mujeres en un amplio y muy diverso campo cultural.

Belleza escrita en femenino

La belleza femenina no es simplemente una cusetión estética, sino también política. Históricamente, la mujer ha sido el objeto pasivo de la mirada masculina, el objeto de sueño y de deseo de los hombres. Los cánones estéticos establecidos por pintores, escultures, fotógrafos, poetas -aunque variables según las épocas y la evolución de los gustos- llevaron siempre implícita una visión patriarcal del papel de la mujer en la sociedad y han conformado una imagen de la mujer que ésta ha asumido. Para la ensayista estadounidense Naomi Wolf, el "mito de la belleza" es un arma ideológica que frena el progreso de las mujeres, las aisla y genera hostilidad entre ellas mismas...

Amor e Identidad

El presente libro es una celebración. Celebramos que las Jornadas "Amor i identitat en la literatura feta per dones", organizada por el Centro "Dona i Literatura, que tuvieron lugar en la Facultad de Filología de la Universidad de Barcelona en marzo de 1995 y cuyos resultados estan recogidos en este volumen, gozaron de un alto nivel académico y de una gran acogida por parte de profesores, estudiantes y el público en general. Este volumen, el segundo de la colección "Mujeres y Literatura, es un reflejo de nuestra voluntad de continuar colaborando en explorar, dar a conocer y disfrutar la literatura escrita por mujeres en un amplio y muy diverso campo cultural.

Belleza escrita en femenino

La belleza femenina no es simplemente una cusetión estética, sino también política. Históricamente, la mujer ha sido el objeto pasivo de la mirada masculina, el objeto de sueño y de deseo de los hombres. Los cánones estéticos establecidos por pintores, escultures, fotógrafos, poetas -aunque variables según las épocas y la evolución de los gustos- llevaron siempre implícita una visión patriarcal del papel de la mujer en la sociedad y han conformado una imagen de la mujer que ésta ha asumido. Para la ensayista estadounidense Naomi Wolf, el "mito de la belleza" es un arma ideológica que frena el progreso de las mujeres, las aisla y genera hostilidad entre ellas mismas...

Meta-analysis identifies multiple loci associated with kidney function-related traits in east Asian populations.

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

Role of reactive hyperreninemia in blood pressure changes induced by sodium depletion in patients with refractory hypertension

Sixteen patients with refractory hypertension were submitted to vigorous sodium depletion while cardiovascular homeostasis was monitored with measurements of hormonal and hemodynamic parameters and repeat saralasin tests. This regimen resulted in a negative sodium balance by an average of 300 mEq. The loss of sodium closely correlated to the decrease of body weight (r = 0.70, p less than 0.005). Blood pressure (BP) decreased from 176/166 +/- 8/3 to 155/109 +/-6/3 mm Hg. There was a significant correlation between percent increments in plasma renin activity (PRA) and the rise in plasma norepinephrine (r = 0.68, p less than 0.05) and a close negative correlation between percent increase in PRA and the ratio of fall in mean blood pressure (MAP) per unit of weight loss (r = -0.73, p less than 0.005). Thus, patients with the least percent increase in PRA demonstrated the greatest fall in BP per unit of weight loss, indicating that relative rather than absolute elevation of renin may be the factor limiting antihypertensive efficacy of sodium depletion. Sodium depletion induced increase in peripheral resistance and decrease in cardiac output, both mostly attributable to relative hyperreninemia. Indeed, the adverse hemodynamic changes were reversed by angiotensin inhibition, during which BP normalized. It is concluded that vigorous sodium depletion complemented by angiotensin blockade or suppression with sympatholytic agents improves management of otherwise refractory hypertension.

Revistes del fons americà de la Biblioteca Josep M. Figueras

Revistes del fons americà de la Biblioteca Josep M. Figueras és la catalogació, feta per Sandra Basurre i Fuensanta Marmolejo, de les revistes que, provinentsde diverses donacions, formen part del fons americanista «sens dubte més nodrit i important de l'estat espanyol en el període comprès entre la primeria de segle i els anys quaranta», en paraules de Pere Pi Sunyer. El Centre d'Estudis d'HistòriaContemporània - Biblioteca Josep M. Figueras s'ha dedicat, d'ençà de l'any 1967, en què fou creat, a una tasca de conservació i sistematització dels testimonis documentals de la Guerra Civil i, més en general, de la història contemporània del'estat espanyol, amb especial referència als de tema català. Així, doncs, a més de ser un dels fons més considerables sobre catalanisme, Guerra Civil i política contemporània, la seva riquesa de material historiogràfic és completada per aquest fons americà.

Internal arsenite bioassay calibration using multiple reporter cell lines

Bioassays with bioreporter bacteria are usually calibrated with analyte solutions of known concentrations that are analysed along with the samples of interest. This is done as bioreporter output (the intensity of light, fluorescence or colour) does not only depend on the target concentration, but also on the incubation time and physiological activity of the cells in the assay. Comparing the bioreporter output with standardized colour tables in the field seems rather difficult and error-prone. A new approach to control assay variations and improve application ease could be an internal calibration based on the use of multiple bioreporter cell lines with drastically different reporter protein outputs at a given analyte concentration. To test this concept, different Escherichia coli-based bioreporter strains expressing either cytochrome c peroxidase (CCP, or CCP mutants) or β-galactosidase upon induction with arsenite were constructed. The reporter strains differed either in the catalytic activity of the reporter protein (for CCP) or in the rates of reporter protein synthesis (for β-galactosidase), which, indeed, resulted in output signals with different intensities at the same arsenite concentration. Hence, it was possible to use combinations of these cell lines to define arsenite concentration ranges at which none, one or more cell lines gave qualitative (yes/no) visible signals that were relatively independent of incubation time or bioreporter activity. The discriminated concentration ranges would fit very well with the current permissive (e.g. World Health Organization) levels of arsenite in drinking water (10 µg l−1).

Transcription factor PROX1 induces colon cancer progression by promoting the transition from benign to highly dysplastic phenotype.

The Drosophila transcription factor Prospero functions as a tumor suppressor, and it has been suggested that the human counterpart of Prospero, PROX1, acts similarly in human cancers. However, we show here that PROX1 promotes dysplasia in colonic adenomas and colorectal cancer progression. PROX1 expression marks the transition from benign colon adenoma to carcinoma in situ, and its loss inhibits growth of human colorectal tumor xenografts and intestinal adenomas in Apc(min/+) mice, while its transgenic overexpression promotes colorectal tumorigenesis. Furthermore, in intestinal tumors PROX1 is a direct and dose-dependent target of the beta-catenin/TCF signaling pathway, responsible for the neoplastic transformation. Our data underscore the complexity of cancer pathogenesis and implicate PROX1 in malignant tumor progression through the regulation of cell polarity and adhesion.

Schizotypal perceptual aberrations of time: correlation between score, behavior and brain activity.

A fundamental trait of the human self is its continuum experience of space and time. Perceptual aberrations of this spatial and temporal continuity is a major characteristic of schizophrenia spectrum disturbances--including schizophrenia, schizotypal personality disorder and schizotypy. We have previously found the classical Perceptual Aberration Scale (PAS) scores, related to body and space, to be positively correlated with both behavior and temporo-parietal activation in healthy participants performing a task involving self-projection in space. However, not much is known about the relationship between temporal perceptual aberration, behavior and brain activity. To this aim, we composed a temporal Perceptual Aberration Scale (tPAS) similar to the traditional PAS. Testing on 170 participants suggested similar performance for PAS and tPAS. We then correlated tPAS and PAS scores to participants' performance and neural activity in a task of self-projection in time. tPAS scores correlated positively with reaction times across task conditions, as did PAS scores. Evoked potential mapping and electrical neuroimaging showed self-projection in time to recruit a network of brain regions at the left anterior temporal cortex, right temporo-parietal junction, and occipito-temporal cortex, and duration of activation in this network positively correlated with tPAS and PAS scores. These data demonstrate that schizotypal perceptual aberrations of both time and space, as reflected by tPAS and PAS scores, are positively correlated with performance and brain activation during self-projection in time in healthy individuals along the schizophrenia spectrum.

Cannabinoid 1 receptor promotes cardiac dysfunction, oxidative stress, inflammation, and fibrosis in diabetic cardiomyopathy.

Endocannabinoids and cannabinoid 1 (CB(1)) receptors have been implicated in cardiac dysfunction, inflammation, and cell death associated with various forms of shock, heart failure, and atherosclerosis, in addition to their recognized role in the development of various cardiovascular risk factors in obesity/metabolic syndrome and diabetes. In this study, we explored the role of CB(1) receptors in myocardial dysfunction, inflammation, oxidative/nitrative stress, cell death, and interrelated signaling pathways, using a mouse model of type 1 diabetic cardiomyopathy. Diabetic cardiomyopathy was characterized by increased myocardial endocannabinoid anandamide levels, oxidative/nitrative stress, activation of p38/Jun NH(2)-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs), enhanced inflammation (tumor necrosis factor-α, interleukin-1β, cyclooxygenase 2, intracellular adhesion molecule 1, and vascular cell adhesion molecule 1), increased expression of CB(1), advanced glycation end product (AGE) and angiotensin II type 1 receptors (receptor for advanced glycation end product [RAGE], angiotensin II receptor type 1 [AT(1)R]), p47(phox) NADPH oxidase subunit, β-myosin heavy chain isozyme switch, accumulation of AGE, fibrosis, and decreased expression of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA2a). Pharmacological inhibition or genetic deletion of CB(1) receptors attenuated the diabetes-induced cardiac dysfunction and the above-mentioned pathological alterations. Activation of CB(1) receptors by endocannabinoids may play an important role in the pathogenesis of diabetic cardiomyopathy by facilitating MAPK activation, AT(1)R expression/signaling, AGE accumulation, oxidative/nitrative stress, inflammation, and fibrosis. Conversely, CB(1) receptor inhibition may be beneficial in the treatment of diabetic cardiovascular complications.