1,720,973 research outputs found
Hepatic glucocorticoid receptor expression in adult sheep following early gestational and / or postnatal undernutrition
In humans and animals environmental constraints during pre- and postnatal life result in phenotypic changes that can be associated with altered cardiovascular and metabolic disease risk in later life (Barker et al., 2002, Poore et al., 2006). The liver is a key organ in glucose and lipid metabolism and altered maternal diet or body composition are associated with changes in fetal liver blood flow (Haugen et al., 2005). Intrauterine challenges such as hypoxia alter blood flow to left and right lobes of the liver differentially. Maternal gestational low protein diet in rats alters adult hepatic gene expression with different effects between liver lobes (Zhang & Byrne, 2000). The glucocorticoid receptor (GR) is a gene associated with disturbances in cardiovascular and metabolic control. However the interaction between pre- and postnatal environments on hepatic GR is unknown. We investigated the effect of reduced early gestation maternal nutrition and/or early postnatal life undernutrition on the expression of GR in adult sheep liver. Welsh Mountain ewes received 100% (C, n=36) or 50 % of total nutrient requirements (U, n=39) from 1-31 days of gestation, and 100 % thereafter. Offspring were fed ad libitum (CC, n=20; UC, n=19) or to reduce body weight to 85 % of individual target weight from 12 to 25 weeks postnatal age and ad libitum thereafter (CU, n=17; UU, n=21). Each group contained approximately equal numbers of males and females and the ratio of twins to singletons was ~2:1. Offspring were sacrificed at 2.5 years, the livers were harvested and segments from the left and right lobes were frozen in liquid nitrogen. GR mRNA levels were measured by semi quantitative RT-PCR and normalized using the mean of three housekeeping genes (RPL19, ?Actin and GAPDH) selected by use of the geNormTM normalizing kit. All data were analysed by ANOVA. Early life nutrition had no effect on GR mRNA expression. GR mRNA expression was significantly higher in males than females (P<0.001). In both males and females the right liver lobe had higher GR mRNA expression than the left (P<0.001). In females, twins had a higher GR mRNA expression than singletons (P<0.05). We conclude that differences in GR expression between left and right lobes of the liver exist in adult sheep, although early gestation and/or postnatal nutrition did not affect these levels. Our finding of increased GR mRNA expression in males suggests that they may be more sensitive to the adverse effects of excess glucocorticoids
Progesterone inhibits insulin-like growth factor binding protein-1 (IGFBP-1) production by explants of the Fallopian tube
The Fallopian tube provides the environment for early embryo growth, a process which is influenced by insulin-like growth factors (IGFs) in the tubal fluid. Whether the bioavailability of tubal IGFs is modulated by locally produced IGF-binding protein (IGFBP-1) is not clear. An explant culture system from human Fallopian tube mucosa was, therefore, developed enabling the potential for IGFBP-1 production by this tissue to be examined directly. Initial characterization of the system established that the explants maintained responsiveness to steroids. Thus, oviduct-specific glycoprotein production, a major product of the oviduct in vivo, continued to be made via an estrogen-sensitive pathway in the culture. The presence of mRNA for IGFBP-1 was established within the explants by the use of quantitative RT–PCR and IGFBP-1 protein was measured by enzyme-linked immunosorbent assay. Although insulin and estradiol had no consistent effect on IGFBP-1, addition of progesterone had a significant inhibitory effect on IGFBP-1 production, both at the mRNA and protein levels. A dose-range of progesterone revealed an incremental inhibitory effect of progesterone on IGFBP-1 output (maximal effect, 25–50 nmol/l), consistent with physiological inhibition of this process during the luteal phase. We suggest that progesterone might, therefore, play a role in controlling the bioavailability of IGFs to the embryo during early development within the Fallopian tube
Developmental exposure to bisphenol A leads to cardiometabolic dysfunction in adult mouse offspring
Bisphenol A (BPA) is a chemical compound that has adverse health outcomes in adults when exposed during the perinatal period. However, its effect on cardiovascular function remains to be elucidated. In this study, we examined the effects of daily administration of BPA to pregnant mice from gestational days 11 to 19 on cardiometabolic outcomes in the adult offspring. Prenatal BPA exposure resulted in altered growth trajectory and organ size, increase adiposity and impaired glucose homeostasis in male and female offspring. In addition, these BPA offspring exhibited raised systolic blood pressure, and in the males this was accompanied by impaired vascular tone. The aortas in females, but not in males, from the BPA group also showed reduced estrogen receptor gene expression. These results indicate that prenatal exposure to BPA increased susceptibility of the offspring to developing cardiovascular and metabolic dysfunction later in lif
Statin treatment corrects endothelial dysfunction but not markers of inflammation in offspring of protein restricted dams
Progesterone up-regulates WT1 mRNA and protein, and alters the relative expression of WT1 transcripts in cultured endometrial stromal cells
ObjectiveTo determine the change in expression of the Wilms tumor suppressor gene product, WT1, by progesterone alone in endometrial stromal cell culture and to study its relationship with prolactin, a marker of decidualization. In addition, to examine the change in ratio of WT1 isoforms with and without exon 5 message.MethodsEndometrial biopsies were taken from eight patients who had hysterectomy. Stromal cells were isolated and cultured in the presence of progesterone alone (12 days) or progesterone and 8-bromo-cyclic adenosine monophosphate (cAMP) (6 days). RNA was extracted from cells, and reverse transcription, real-time polymerase chain reaction (PCR), and conventional PCR were done to analyze WT1 mRNA expression. Immunocytochemistry was performed on equivalent cells to study WT1 protein expression. Decidualization was identified by increased prolactin concentrations in the media and immunocytochemical markers IGFBP-1 and collagen IV.ResultsReverse transcription and real-time PCR revealed a significant increase in WT1 mRNA with increasing progesterone concentrations when decidualization was occurring (n = 6, P = .002). Increasing progesterone concentrations also increased the proportion of the WT1 transcript containing a 17-amino-acid insert (+ exon 5 expression); changes in WT1 exon 5 expression have been shown to be involved in control of proliferation and differentiation. Significant correlations between WT1 message and prolactin existed at physiologic progesterone concentrations (6.25, 12.5, 25, and 50 nM; P < .05) until prolactin concentrations reached a plateau at 100 nM. At concentrations of progesterone alone (> 25 nM) and progesterone with 8-bromo-cAMP, WT1 protein was localized to the nuclei of many of the decidualized stromal cells.ConclusionThe changing expression of WT1 isoforms in endometrial stromal cells caused by progesterone may be important for differentiation into the decidualized phenotype. <br/
Brain natriuretic peptide expression is significantly elevated during rapid myocardial regeneration in MRL mice undergoing cryo-injury to the heart
Expression of agouti-related peptide, neuropeptide Y, pro-opiomelanocortin and the leptin receptor isoforms in fetal mouse brain from pregnant dams on a protein-restricted diet
Expression of agouti-related peptide, neuropeptide Y, pro-opiomelanocortin and leptin receptor isoforms were found in fetal mouse brain at embryonic day 12 (E12). Levels of expression for these genes were altered in brains of E12 fetuses from pregnant dams on a protein-restricted diet, suggesting that the fetal brain is responsive to changes in maternal nutrition prior to birth
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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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