Cognitive-Experiential Self Theory assumes that reasoning conforms to a parallel dual processing model (comprising rational and experiential systems), through which we make sense of the world. The ...Rational Experiential Inventory was developed to measure an individual’s preference for rational (need for cognition) and experiential (faith in intuition) thinking, with individual differences proposed to influence the respective dominance of each. While small but consistent gender effects have been found previously, age effects have rarely been reported or investigated across the lifespan. We examine both age and gender differences in Rational Experiential Inventory scores, using combined data from five studies involving adult participants (
n
=
520, 61.9% male) with a mean age of 41.45
years (
SD
=
11.73, range 20–74
years). Results suggest a convergence of the rational and experiential systems in adulthood, although the timing may be different for women and men. In later adulthood, the relationship appears to diverge again.
The reproductive performance of 7286 ewes from three Merino genetic resource flocks maintained in the central-western region of New South Wales was used to compare the use of fertility and fecundity ...information and net reproduction information whether recorded early (at 2 and 3 years of age) or later in life (at 4 and 5 years of age) with lifetime performance (at 2–6 years of age) as alternative selection criteria to identify productive older ewes to retain in the breeding flock. While the lifetime net reproduction rate is the best indicator of a ewe’s reproductive performance in later life, producers basing their selection decisions on pregnancy scanning data, which provides information on both fertility and fecundity, can improve the net reproduction rate of their flock by 2% regardless of the base reproduction rate. Despite little difference in likely flock reproduction rates between using early or later life scanning information as the selection criteria, early life performance is the best choice for commercial producers because it provides scope for eliminating twice-dry ewes from the breeding flock early in life, especially when combined with udder examination at marking.
Although transcriptional hierarchies have been extensively studied in invertebrates, their involvement in mammalian cell-type specification is poorly understood. Here we report a hepatocyte ...transcriptional cascade suggested by the expression patterns of hepatic transcription factors in dedifferentiated hepatomas and hepatocyte: fibroblast hybrids in which the liver phenotype was extinguished. These results indicated that the homeoprotein hepatocyte nuclear factor-1 alpha (HNF-1 alpha), and HNF-4, a member of the steroid hormone receptor superfamily, were regulated coordinately or in a hierarchy by a higher-order locus, independently of other hepatic transactivators. HNF-4 was implicated as an essential positive regulator of HNF-1 alpha, as deletion of an HNF-4 binding site in the HNF-1 alpha promoter abolished promoter activity, and HNF-4 potently transactivated the HNF-1 alpha promoter in cotransfection assays. Moreover, genetic complementation of dedifferentiated hepatomas with HNF-4 complementary DNA rescued expression of endogenous HNF-1 alpha messenger RNA and DNA-binding activity. Our studies therefore define an HNF-4---HNF-1 alpha (4---1 alpha) transcriptional hierarchy operative in differentiated hepatocytes but selectively inhibited by an extinguishing locus and somatic mutations which antagonize the liver phenotype.
Hepatocyte nuclear factor 4 alpha (HNF4α), a member of the nuclear receptor superfamily, is essential for liver function and is linked to several diseases including diabetes, hemophilia, ...atherosclerosis, and hepatitis. Although many DNA response elements and target genes have been identified for HNF4α, the complete repertoire of binding sites and target genes in the human genome is unknown. Here, we adapt protein binding microarrays (PBMs) to examine the DNA‐binding characteristics of two HNF4α species (rat and human) and isoforms (HNF4α2 and HNF4α8) in a high‐throughput fashion. We identified ∼1400 new binding sequences and used this dataset to successfully train a Support Vector Machine (SVM) model that predicts an additional ∼10,000 unique HNF4α‐binding sequences; we also identify new rules for HNF4α DNA binding. We performed expression profiling of an HNF4α RNA interference knockdown in HepG2 cells and compared the results to a search of the promoters of all human genes with the PBM and SVM models, as well as published genome‐wide location analysis. Using this integrated approach, we identified ∼240 new direct HNF4α human target genes, including new functional categories of genes not typically associated with HNF4α, such as cell cycle, immune function, apoptosis, stress response, and other cancer‐related genes. Conclusion: We report the first use of PBMs with a full‐length liver‐enriched transcription factor and greatly expand the repertoire of HNF4α‐binding sequences and target genes, thereby identifying new functions for HNF4α. We also establish a web‐based tool, HNF4 Motif Finder, that can be used to identify potential HNF4α‐binding sites in any sequence. (HEPATOLOGY 2009.)
Glucocorticoids stimulate hepatic phosphoenolpyruvate carboxykinase (PEPCK; EC 4.1.1.32) gene expression, thereby increasing the rate of gluconeogenesis. The effect of glucocorticoids on PEPCK gene ...expression is mediated by a set of promoter elements collectively referred to as the glucocorticoid response unit. The response unit spans a 100-bp segment and includes two glucocorticoid receptor binding sites (GR1 and GR2) and two accessory factor binding sites (AF1 and AF2), all of which are required for a maximal glucocorticoid response. The AF1 element also serves as a retinoic acid response element and may be involved in developmental and tissue-specific expression of the gene. In this study we report that COUP-TF and HNF-4, two orphan members of the nuclear receptor superfamily, bind to the AF1 element and function as accessory factors for the glucocorticoid response of the PEPCK gene.
Abstract
Soybean oil consumption has increased greatly in the past half-century and is linked to obesity and diabetes. To test the hypothesis that soybean oil diet alters hypothalamic gene expression ...in conjunction with metabolic phenotype, we performed RNA sequencing analysis using male mice fed isocaloric, high-fat diets based on conventional soybean oil (high in linoleic acid, LA), a genetically modified, low-LA soybean oil (Plenish), and coconut oil (high in saturated fat, containing no LA). The 2 soybean oil diets had similar but nonidentical effects on the hypothalamic transcriptome, whereas the coconut oil diet had a negligible effect compared to a low-fat control diet. Dysregulated genes were associated with inflammation, neuroendocrine, neurochemical, and insulin signaling. Oxt was the only gene with metabolic, inflammation, and neurological relevance upregulated by both soybean oil diets compared to both control diets. Oxytocin immunoreactivity in the supraoptic and paraventricular nuclei of the hypothalamus was reduced, whereas plasma oxytocin and hypothalamic Oxt were increased. These central and peripheral effects of soybean oil diets were correlated with glucose intolerance but not body weight. Alterations in hypothalamic Oxt and plasma oxytocin were not observed in the coconut oil diet enriched in stigmasterol, a phytosterol found in soybean oil. We postulate that neither stigmasterol nor LA is responsible for effects of soybean oil diets on oxytocin and that Oxt messenger RNA levels could be associated with the diabetic state. Given the ubiquitous presence of soybean oil in the American diet, its observed effects on hypothalamic gene expression could have important public health ramifications.
Abstract The master circadian clock located in the suprachiasmatic nuclei (SCN) is dominantly entrained by external light/dark cycle to run with a period of a solar day, that is, 24 h, and ...synchronizes various peripheral clocks located in the body's cells and tissues accordingly. A daily restricted normocaloric feeding regime synchronizes the peripheral clocks but has no effect on SCN rhythmicity. The aim of this study was to elucidate whether feeding regime may affect the molecular mechanism generating SCN rhythmicity under conditions in which the rhythmicity is disturbed, as occurs under constant light. The rats were maintained under constant light for 30 days and were either fed ad libitum during the whole period, or their access to food was restricted to only 6 h a day during the last 2 weeks in constant light. Locomotor activity was monitored during the whole experiment. On the last day in constant light, daily expression profiles of the clock genes Per1 , Per2 , Bmal1 , and Rev-erbα were determined in the SCN of both groups by in situ hybridization. Due to their exposure to constant light, the rats fed ad libitum became completely arrhythmic, while those exposed to the restricted feeding were active mostly during the time of food availability. In the SCN of behaviorally arrhythmic rats, no oscillations in Rev-erbα and Bmal1 gene expression were detected, but very low amplitude, borderline significant, oscillations in Per1 and Per2 persisted. Restricted feeding induced significant circadian rhythms in Rev-erbα and Bmal1 gene expression, but did not affect the low amplitude oscillations of Per1 and Per2 expression. These findings demonstrate that, under specific conditions, when the rhythmicity of the SCN is disturbed and other temporal entraining cues are lacking, the SCN molecular clockwork may likely sense temporal signals from changes in metabolic state delivered by normocaloric food.
Palliative care is an increasingly important area of clinical practice and health service delivery. The heterogeneity of the patient population and the multidisciplinary nature of care draw on ...knowledge from many fields of clinical practice and academic enquiry. This has implications for the retrieval of evidence and literature and the spread of new knowledge in palliative care. This study shows that the CINAHL, Embase and PsycINFO bibliographic databases hold sizeable repositories of palliative care articles not indexed on Medline. It also highlights the number and range of journals publishing palliative care content. In 2005 alone, 1985 journals published 6983 items. These findings show the challenges for palliative care professionals in managing the complex evidence base for this diverse field of care and the importance of mechanisms that facilitate the identification of palliative care information. Dissemination strategies that ensure that new knowledge reaches the many audiences implicit in the range of journals publishing palliative care are also critical in supporting improvements in clinical practice and service delivery.
Medical student selection and assessment share an underlying high stakes context with the need for valid and reliable tools. This study examined the predictive validity of three tools commonly used ...in Australia: previous academic performance (Grade Point Average (GPA)), cognitive aptitude (a national admissions test), and non-academic qualities of prospective medical students (interview).
A four year retrospective cohort study was conducted at Flinders University Australia involving 382 graduate entry medical students first enrolled between 2006 and 2009. The main outcomes were academic and clinical performance measures and an indicator of unimpeded progress across the four years of the course.
A combination of the selection criteria explained between 7.1 and 29.1 % of variance in performance depending on the outcome measure. Weighted GPA consistently predicted performance across all years of the course. The national admissions test was associated with performance in Years 1 and 2 (pre-clinical) and the interview with performance in Years 3 and 4 (clinical). Those students with higher GPAs were more likely to have unimpeded progress across the entire course (OR = 2.29, 95 % CI 1.57, 3.33).
The continued use of multiple selection criteria to graduate entry medical courses is supported, with GPA remaining the single most consistent predictor of performance across all years of the course. The national admissions test is more valuable in the pre-clinical years, and the interview in the clinical years. Future selections research should develop the fledgling research base regarding the predictive validity of the Graduate Australian Medical School Admissions Test (GAMSAT), the algorithms for how individual tools are combined in selection, and further explore the usefulness of the unimpeded progress index.
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