Defining new criteria for selection of cell-based intestinal models using publicly available databases

The criteria for choosing relevant cell lines among a vast panel of available intestinal-derived lines exhibiting a wide range of functional properties are still ill-defined. The objective of this study was, therefore, to establish objective criteria for choosing relevant cell lines to assess their appropriateness as tumor models as well as for drug absorption studies.

Zoledronic acid efficacy and safety over five years in postmenopausal osteoporosis

In a 5-year study involving 119 postmenopausal women, zoledronic acid 4 mg given once-yearly for 2, 3 or 5 years was well tolerated with no evidence of excessive bone turnover reduction or any safety signals. BMD increased significantly. Bone turnover markers decreased from baseline and were maintained within premenopausal reference ranges. INTRODUCTION: After completion of the core study, two consecutive, 2-year, open-label extensions investigated the efficacy and safety of zoledronic acid 4 mg over 5 years in postmenopausal osteoporosis. METHODS: In the core study, patients received 1 to 4 mg zoledronic acid or placebo. In the first extension, most patients received 4 mg per year and then patients entered the second extension and received 4 mg per year or calcium only. Patients were divided into three subgroups according to years of active treatment received (2, 3 or 5 years). Changes in BMD and bone turnover markers (bone ALP and CTX-I) were assessed. RESULTS: All subgroups showed substantial increases in BMD and decreases in bone markers. By the end of the core study, 37.5% of patients revealed a suboptimal reduction (< 30%) of bone ALP levels. After subsequent study drug administration during the extensions, there was no evidence of progressive reduction of bone turnover markers. Furthermore, increased marker levels after treatment discontinuation demonstrates preservation of bone remodelling capacity. CONCLUSIONS: This study showed that zoledronic acid 4 mg once-yearly was well tolerated and effective in reducing biomarkers over 5 years. Detailed analysis of bone marker changes, however, suggests that this drug regimen causes insufficient reduction of remodelling activity in one third of patients.

Multifactor effects and evidence of potential interaction between complement factor H Y402H and LOC387715 A69S in age-related macular degeneration.

BACKGROUND: Variants in the complement cascade genes and the LOC387715/HTRA1, have been widely reported to associate with age-related macular degeneration (AMD), the most common cause of visual impairment in industrialized countries. METHODS/PRINCIPAL FINDINGS: We investigated the association between the LOC387715 A69S and complement component C3 R102G risk alleles in the Finnish case-control material and found a significant association with both variants (OR 2.98, p = 3.75 x 10(-9); non-AMD controls and OR 2.79, p = 2.78 x 10(-19), blood donor controls and OR 1.83, p = 0.008; non-AMD controls and OR 1.39, p = 0.039; blood donor controls), respectively. Previously, we have shown a strong association between complement factor H (CFH) Y402H and AMD in the Finnish population. A carrier of at least one risk allele in each of the three susceptibility loci (LOC387715, C3, CFH) had an 18-fold risk of AMD when compared to a non-carrier homozygote in all three loci. A tentative gene-gene interaction between the two major AMD-associated loci, LOC387715 and CFH, was found in this study using a multiplicative (logistic regression) model, a synergy index (departure-from-additivity model) and the mutual information method (MI), suggesting that a common causative pathway may exist for these genes. Smoking (ever vs. never) exerted an extra risk for AMD, but somewhat surprisingly, only in connection with other factors such as sex and the C3 genotype. Population attributable risks (PAR) for the CFH, LOC387715 and C3 variants were 58.2%, 51.4% and 5.8%, respectively, the summary PAR for the three variants being 65.4%. CONCLUSIONS/SIGNIFICANCE: Evidence for gene-gene interaction between two major AMD associated loci CFH and LOC387715 was obtained using three methods, logistic regression, a synergy index and the mutual information (MI) index.

VEGF-B-induced vascular growth leads to metabolic reprogramming and ischemia resistance in the heart

Angiogenic growth factors have recently been linked to tissue metabolism. We have used genetic gain- and loss-of function models to elucidate the effects and mechanisms of action of vascular endothelial growth factor-B (VEGF-B) in the heart. A cardiomyocyte-specific VEGF-B transgene induced an expanded coronary arterial tree and reprogramming of cardiomyocyte metabolism. This was associated with protection against myocardial infarction and preservation of mitochondrial complex I function upon ischemia-reperfusion. VEGF-B increased VEGF signals via VEGF receptor-2 to activate Erk1/2, which resulted in vascular growth. Akt and mTORC1 pathways were upregulated and AMPK downregulated, readjusting cardiomyocyte metabolic pathways to favor glucose oxidation and macromolecular biosynthesis. However, contrasting with a previous theory, there was no difference in fatty acid uptake by the heart between the VEGF-B transgenic, gene-targeted or wildtype rats. Importantly, we also show that VEGF-B expression is reduced in human heart disease. Our data indicate that VEGF-B could be used to increase the coronary vasculature and to reprogram myocardial metabolism to improve cardiac function in ischemic heart disease.

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

Report of the Second European Zebrafish Principal Investigator Meeting in Karlsruhe, Germany, March 21-24, 2012.

The second European Zebrafish Principal Investigator (PI) Meeting was held in March, 2012, in Karlsruhe, Germany. It brought together PIs from all over Europe who work with fish models such as zebrafish and medaka to discuss their latest results, as well as to resolve strategic issues faced by this research community. Scientific discussion ranged from the development of new technologies for working with fish models to progress in various fields of research such as injury and repair, disease models, and cell polarity and dynamics. This meeting also marked the establishment of the European Zebrafish Resource Centre (EZRC) at Karlsruhe that in the future will serve as an important focus and community resource for zebrafish- and medaka-based research.

Family Reunification among Two Groups of Runaway Adolescents Utilizing Emergency Shelters

Limited research has addressed reunification of runaway youths with their families following an emergency shelter stay; however, recent studies have shown that those who reunify with their families following a shelter stay have more positive outcomes than those relocated to other residences. This study evaluated differences between two samples of runaway youth utilizing youth emergency shelters in New York (n = 155) and Texas (n = 195) and identified factors associated with reunification among these two groups of adolescents. Less than half (43.7%) of the youths were reunited with their families. Among New York runaway youths, those who had lived primarily with someone other than a parent before shelter admission, were physically abused, or neglected were less likely to return home. Among youths admitted to emergency shelter services in Texas, those with longer shelter stays, living primarily with someone other than a parent before shelter admission, or being pregnant or a parent were less likely to reunify. This study provides valuable information concerning family reunification following shelter service use; however, additional research is needed to delineate youth, family, and shelter system factors that distinguish successful from unsuccessful reunification over an extended period of time.

Rompecabezas : Teoría social, empiria y control social a la luz de Delito y Sociedad, Revista de Ciencias Sociales

La presente investigación tiene como propósito llevar a cabo una aproximación sobre la temática del control social a partir de un estudio exploratorio en cuanto a la utilización del término, razón por la cual no descansa en la intención de reponerlo en la exhaustividad del detalle. En efecto, debido al carácter polisémico que reviste este concepto, en el que subyacen diversas caracterizaciones y valoraciones, estimo que es propicio realizar un aporte por sistematizar su uso en las ciencias sociales en general, y en la sociología, en particular. Asimismo, creo que es relevante desarrollar una investigación alrededor de la temática del control social debido a la centralidad que está adoptando contemporáneamente en nuestro país como problemática social, si se la considera dentro del marco de la denominada seguridad ciudadana y del tratamiento del delito. Ahora bien, el presente trabajo versará sobre los distintos usos y sentidos del concepto control social, y se propone abordarlo tomando como objeto de estudio una serie de artículos publicados en distintos números de ?Delito y Sociedad, Revista de Ciencias Sociales?. En efecto, el objetivo general apuntará a explorar cuáles fueron los usos del concepto de control social a partir de un análisis teórico-metodológico de dichas publicaciones, el cual se encuentra lejos de sostener un binarismo como concepción epistemológica que pretenda disociar la teoría de la práctica

Los ricos, esos sí que son peligrosos : Entrevista a Juan Pegoraro

Fil: Oyhandy, Angela. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

Rompecabezas : Teoría social, empiria y control social a la luz de Delito y Sociedad, Revista de Ciencias Sociales

La presente investigación tiene como propósito llevar a cabo una aproximación sobre la temática del control social a partir de un estudio exploratorio en cuanto a la utilización del término, razón por la cual no descansa en la intención de reponerlo en la exhaustividad del detalle. En efecto, debido al carácter polisémico que reviste este concepto, en el que subyacen diversas caracterizaciones y valoraciones, estimo que es propicio realizar un aporte por sistematizar su uso en las ciencias sociales en general, y en la sociología, en particular. Asimismo, creo que es relevante desarrollar una investigación alrededor de la temática del control social debido a la centralidad que está adoptando contemporáneamente en nuestro país como problemática social, si se la considera dentro del marco de la denominada seguridad ciudadana y del tratamiento del delito. Ahora bien, el presente trabajo versará sobre los distintos usos y sentidos del concepto control social, y se propone abordarlo tomando como objeto de estudio una serie de artículos publicados en distintos números de ?Delito y Sociedad, Revista de Ciencias Sociales?. En efecto, el objetivo general apuntará a explorar cuáles fueron los usos del concepto de control social a partir de un análisis teórico-metodológico de dichas publicaciones, el cual se encuentra lejos de sostener un binarismo como concepción epistemológica que pretenda disociar la teoría de la práctica