Search results for "PAPER"
showing 10 items of 2166 documents
Role of Gadd45a in Wip1-dependent regulation of intestinal tumorigenesis.
2012
Conversion of intestinal stem cells into tumor-initiating cells is an early step in Apc(Min)-induced polyposis. Wild-type p53-induced phosphatase 1 (Wip1)-dependent activation of a DNA damage response and p53 has a permanent role in suppression of stem cell conversion, and deletion of Wip1 lowers the tumor burden in Apc(Min) mice. Here we show that cyclin-dependent kinase inhibitor 2a, checkpoint kinase 2, and growth arrest and DNA damage gene 45a (Gadd45a) exert critical functions in the tumor-resistant phenotype of Wip1-deficient mice. We further identified Gadd45a as a haploinsufficient gene in the regulation of Wip1-dependent tumor resistance in mice. Gadd45a appears to function through…
D-2-hydroxyglutarate produced by mutant IDH2 causes cardiomyopathy and neurodegeneration in mice.
2014
Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) have been discovered in several cancer types and cause the neurometabolic syndrome D2-hydroxyglutaric aciduria (D2HGA). The mutant enzymes exhibit neomorphic activity resulting in production of D2-hydroxyglutaric acid (D-2HG). To study the pathophysiological consequences of the accumulation of D-2HG, we generated transgenic mice with conditionally activated IDH2R140Q and IDH2R172K alleles. Global induction of mutant IDH2 expression in adults resulted in dilated cardiomyopathy, white matter abnormalities throughout the central nervous system (CNS), and muscular dystrophy. Embryonic activation of mutant IDH2 resulted in more pronounced ph…
Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults
2018
Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health.Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n= 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult s…
The evolution of RNA viruses: A population genetics view.
2000
RNA viruses are excellent experimental models for studying evolution under the theoretical framework of population genetics. For a proper justification of this thesis we have introduced some properties of RNA viruses that are relevant for studying evolution. On the other hand, population genetics is a reductionistic theory of evolution. It does not consider or make simplistic assumptions on the transformation laws within and between genotypic and phenotypic spaces. However, such laws are minimized in the case of RNA viruses because the phenotypic space maps onto the genotypic space in a much more linear way than on higher DNA-based organisms. Under experimental conditions, we have tested th…
Linker histone H1 is essential for Drosophila development, the establishment of pericentric heterochromatin, and a normal polytene chromosome structu…
2009
We generated mutant alleles of Drosophila melanogaster in which expression of the linker histone H1 can be down-regulated over a wide range by RNAi. When the H1 protein level is reduced to ∼20% of the level in wild-type larvae, lethality occurs in the late larval – pupal stages of development. Here we show that H1 has an important function in gene regulation within or near heterochromatin. It is a strong dominant suppressor of position effect variegation (PEV). Similar to other suppressors of PEV, H1 is simultaneously involved in both the repression of euchromatic genes brought to the vicinity of pericentric heterochromatin and the activation of heterochromatic genes that depend on their pe…
Parvovirus B19 Genotype Specific Amino Acid Substitution in NS1 Reduces the Protein's Cytotoxicity in Culture
2010
A clinical association between idiopathic liver disease and parvovirus B19 infection has been observed. Fulminant liver failure, not associated with other liver-tropic viruses, has been attributed to B19 in numerous reports, suggesting a possible role for B19 components in the extensive hepatocyte cytotoxicity observed in this condition. A recent report by Abe and colleagues (Int J Med Sci. 2007;4:105-9) demonstrated a link between persistent parvovirus B19 genotype I and III infection and fulminant liver failure. The genetic analysis of isolates obtained from these patients demonstrated a conservation of key amino acids in the nonstructural protein 1 (NS1) of the disease-associated genotyp…
Cuando se genera una controversia sociocientífica, ¿aumenta su presencia de noticias en prensa local: el caso del agua en Almería
2017
En este trabajo estudiamos qué relación existe entre las noticias controvertidas y su presencia en la prensa, examinando el caso concreto del agua en Almería. A través de una metodología variada realizamos el análisis documental, obteniendo una muestra representativa de un periodo normal y otra de un periodo controvertido que situamos en el periodo de mayor difusión de nuestro tópico. Los resultados muestran una escasa presencia para la muestra en estado normal y un abundante promedio diario para el periodo controvertido. Estos resultados y el diferente tratamiento de consensuado o controvertido nos permiten plantear la elección de dos noticias y una alternativa de uso en el aula diferente …
The uncertainties of climate change in Spanish daily newspapers: Content analysis of press coverage from 2000 to 2010
2014
This paper explores media coverage of climate science through a selection of Spanish newspapers (El País, El Mundo, ABC, Expansión and Levante). We selected a stratified random sample of 363 items to be studied for eleven years (2000-2010). Content analysis allowed us to find out media attention paid to climate science, prevalence of informative tables, evaluation and characterization of news, as well as the presence of questioning or rejection of climate change. According to main results, press coverage of climate science in Spain was mainly focused on the consequences rather than on the causes or natural sources, and media attention paid to it was limited. Overlapping with social and macr…
BIOAVAILABILITY TO JUVENILE RAINBOW TROUT (ONCORYNCHUS MYKISS) OF RETENE AND OTHER MIXED-FUNCTION OXYGENASE-ACTIVE COMPOUNDS FROM SEDIMENTS
2002
Retene (7-isopropyl-1-methylphenanthrene) is a naturally formed polycyclic aromatic hydrocarbon (PAH) that causes teratogenicity in fish larvae and induction of cytochrome P450 (CYP1A) enzymes. Retene occurs at high concentrations (or =3,300 microg/g dry wt) in surface sediments contaminated by resin acids from pulp mill effluents. To assess the environmental risks of retene, it is important to evaluate conditions affecting its bioavailability and accumulation by fish. Fingerling rainbow trout were exposed to retene-spiked or naturally contaminated sediments and sampled after 4 d to determine liver CYP1A activity and concentrations of retene metabolites in bile as indicators of retene accum…