1,720,963 research outputs found
Transcriptional control of Nramp 1: a paradigm for the repressive action of c-Myc
No full textSlc11a1/Nramp1 (solute carrier family 11 member a1/murine natural resistance-associated macrophage protein 1 gene) encodes a divalent cation transporter that resides within lysosomes/late endosomes of macrophages. Nramp1 modulates the cellular distribution of divalent cations in response to cell activation by intracellular pathogens. Nramp1 expression is repressed and activated by the proto-oncogene c-Myc and Miz-1 (c-Myc-interacting zinc finger protein 1) respectively. Here we demonstrate, using a c-Myc mutant (V394D, Val394Asp) that is incapable of binding Miz-1, that c-Myc repression of Nramp1 transcription is dependent on its interaction with Miz-1. An oligo pull-down assay demonstrates specific binding of recombinant Miz-1 to the Nramp1 Miz-1-binding site or initiator element(s), and Miz-1-dependent c-Myc recruitment
Quantitative analysis of the methylation status of the hepatic PPAR-alpha promoter CPG island by pyrosequencing in offspring of rats fed a protein-restricted diet during pregnancy
No full textEffect of reduced maternal protein consumption during pregnancy in the rat on plasma lipid concentrations and expression of peroxisomal proliferator-activated receptors in the liver and adipose tissue of the offspring
No full textThe effect of protein consumption during pregnancy on peroxisomal proliferator-activated receptor (PPAR) expression and plasma lipid concentrations in the offspring were determined in the rat. Rats were fed isocaloric diets containing either 18% (w/w) (control) or 9% (w/w) casein throughout pregnancy, and chow during lactation. Maternal protein intake did not alter fetal hepatic PPAR? and ? expression at 20/21 days gestation (n = 5/group). Liver PPAR? expression was 69% greater (P < 0.0001) in the 9% group, whereas PPAR? was not altered, in the offspring 6 days after weaning (n = 5/group). Adipose PPAR? expression was 59% lower (P < 0.01) in the 9% group after weaning. This was accompanied by an increase (35%, P < 0.02) in plasma triacylglycerol and nonesterified fatty acid concentrations (55%, (P < 0.01) in the 9% group after weaning. These data show that maternal protein intake during pregnancy alters the regulation of PPAR expression, which represents a potential mechanism to explain impaired lipid homeostasis in the offspring
The effect of prenatal under-nutrition on the expression of DNA methyltransferases and methyl CPG binding protein 2 in the liver after weaning
No full textInduction of an altered metabolic phenotype
in the offspring of rats fed a protein-restricted (PR) diet
during pregnancy involves hypomethylation and increased expression of the hepatic glucocorticoid receptor (GR) and
PPARa promoters. To determine the mechanism responsible
for promoter hypomethylation we investigated the effect
of feeding a PR diet to pregnant rats on the expression of
DNA methyltransferase (DMNT)-1 which maintains DNA
methylation during mitosis, DNMT 3a and 3b which catalyse
DNA methylation de novo, the DNA demethylase MBD2 and
the methyl CpG binding protein (MeCP)-2 which recruits
enzymes that regulate covalent histone modifications to
methylated DNA in the liver of the adult offspring.
Methods: Rats were fed either a control or PR diet from
conception to delivery, and chow during lactation. Offspring
were weaned onto chow at postnatal day 28 and
killed at postnatal day 34. mRNA expression was determined
by real-time quantitative RT PCR.
Results: There was no effect of prenatal under-nutrition on
the expression of DNMT 3a or 3b, or on the expression of
MBD2. DNMT1 expression was significantly lower (17%,
p b0.05) and MeCP2 expression was reduced (28.6%,
p b0.05) in the PR offspring vs. controls.
Discussion: These results suggest that prenatal undernutrition
induces hypomethylation of the PPARa and GR
promoters by reducing the capacity of DNMT1 to methylate
hemimethylated DNA during mitosis. Thus induction of an
altered phenotype by prenatal under-nutrition may be the
result of impaired DNMT1 activity. Lower MeCP2 expression,
together with hypomethylation of CpGs, may facilitate
histone acetylation leading to increased transcription.
Disclosure: Was this work supported by industry? No
The effect of prenatal under-nutrition, neonatal leptin exposure, and post-weaning fat intake on the expression of genes associated with lipid-metabolism in adipose tissue in female rats
No full textDietary protein restriction in the pregnant rat induces altered epigenetic regulation of the glucocorticoid receptor and peroxisomal proliferator-activated receptor alpha in the heart of the offspring which is prevented by folic acid.
No full textIn healthy individuals, glucose and fatty acids are substrates for ATP generation in the heart. There is emerging evidence from patients with type 2 diabetes mellitus that preferential use of fatty acid b-oxidation for energy production may be linked to cardiomyopathy (Fink, 2004). PPARa activity is important for regulating fatty acid b-oxidation in the heart and is increased in hearts of rats with experimentally induced diabetes (Fink, 2004). Prenatal undernutrition is related inversely to risk of type 2 diabetes mellitus in man (Poole & Byrne, 2005) and insulin resistance in rats (Bertram & Hanson, 2001). We have shown that maternal dietary protein restriction induces persistent alterations to hepatic and carbohydrate metabolism in the offspring by altering the epigenetic regulation of PPARa and the glucocorticoid receptor(GR) (Lillycrop et al. 2005). Here we have tested the hypothesis that prenatal protein restriction induces hypomethylation of the GR and PPARa promoters in the heart, and that this is prevented by supplementation of the protein-restricted (PR) diet with folic acid
Feeding a protein-restricted diet during pregnancy in the rat induces altered gene promoter methylation in the liver of the F1 and F2 offspring [In special abstracts issue]
No full textBackground: There is evidence in humans and experimental
animals for non-genomic transmission of induced phenotypes
between generations. Induction of an altered phenotype in
the F1 generation by feeding a protein-restricted (PR) diet to
pregnant rats involves altered epigenetic regulation of
specific genes. We investigated whether altered epigenetic
regulation of hepatic PPARa and glucocorticoid receptor (GR)
promoters induced in the F1 generation by prenatal undernutrition
is passed to the F2 offspring.Methods: Rats (F0) were fed a control (18% protein) or PR
(9% protein) diet throughout pregnancy and chow during
lactation. F1 females were mated and fed chow throughout
pregnancy and lactation. F1 and F2 offspring were fed chow.
Male offspring from the F1 and F2 generations (n =6 per F0
dietary group) were killed at day 80. Methylation of the
hepatic PPARa and GR promoters was determined by
methylation-sensitive real-time PCR. mRNA expression was
measured by real-time RT-PCR.Results: Methylation of the hepatic PPARa and GR promoters
was lower (8% to 11%, p b0.05) in the F1 and F2 PR offspring.
There were trends towards higher PPARa and GR expression
in the PR offspring
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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