34 resultados para Coen, Enrico: The art of genes: how organisms make themselves
Resumo:
What are the conditions under which some austerity programmes rely on substantial cuts to social spending? More specifically, do the partisan complexion and the type of government condition the extent to which austerity policies imply welfare state retrenchment? This article demonstrates that large budget consolidations tend to be associated with welfare state retrenchment. The findings support a partisan and a politico-institutionalist argument: (i) in periods of fiscal consolidation, welfare state retrenchment tends to be more pronounced under left-wing governments; (ii) since welfare state retrenchment is electorally and politically risky, it also tends to be more pronounced when pursued by a broad pro-reform coalition government. Therefore, the article shows that during budget consolidations implemented by left-wing broad coalition governments, welfare state retrenchment is greatest. Using long-run multipliers from autoregressive distributed lag models on 17 OECD countries during the 1982–2009 period, substantial support is found for these expectations.
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Thin, human-like sculptures by the artist Alberto Giacometti, applied as environmental cues, have been found to facilitate dieting by reducing chocolate intake and promoting healthy snack choices. However, the processes underlying this “Giacometti effect” have been left unexplored so far. The present study therefore first examines the effortlessness of the effect. More specifically, it aims to determine whether the sculptures reduce unhealthy food intake when only few cognitive resources for their influence are available. For this purpose, the participants in a chip tasting were given the cognitive load task of memorizing either 10 or two digits during the tasting. The results indicate that the sculptures reduced participants’ chip intake independent of the cognitive load. Thus, they influenced participants’ eating behavior even when only few cognitive resources were available. The results also indicate that the sculptures reduced chip intake only when the participants liked the chips. The sculptures could thus exert their influence when individuals were motivated to eat and the dieting cues were useful. The finding that the Giacometti sculptures, applied as environmental dieting or health cues, influenced individuals when only few cognitive resources were available, could indicate a crucial advantage for the application of these cues in complex, real-world settings.
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This paper focuses on the normative notion of ‘good death’, its practical relevance as a frame of reference for ‘death work’ procedures in institutional elder care in Switzerland and the ways in which it may be challenged within migrant ‘dying trajectories’. In contemporary palliative care, the concept of ‘good death’ focuses on the ideal of an autonomous dying person, cared for under a specialised biomedical authority. Transferred to the nursing home context, characterised by long-term basic care for the very old under conditions of scarce resources, the notion of ‘good death’ is broken down into ready-to-use, pragmatic elements of daily routines. At the same time, nursing homes are increasingly confronted with socially and culturally diversified populations. Based on ethnographic findings, we give insight into current practices of institutional ‘death work’ and tensions arising between contradicting notions of a ‘good death’, by referring to decision-making, life-prolonging measures, notions on food/feeding and the administration of sedative painkillers.
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BACKGROUND: Hallucinations are perceptions in the absence of a corresponding external sensory stimulus. However, during auditory verbal hallucinations, activation of the primary auditory cortex has been described. AIMS: The objective of this study was to investigate whether this activation of the auditory cortex contributes essentially to the character of hallucinations and attributes them to alien sources, or whether the auditory activation is a sign of increased general auditory attention to external sounds. METHOD: The responsiveness of the auditory cortex was investigated by auditory evoked potentials (N100) during the simultaneous occurrence of hallucinations and external stimuli. Evoked potentials were computed separately for periods with and without hallucinations; N100 power, topography and brain electrical sources were analysed. RESULTS: Hallucinations lowered the N100 amplitudes and changed the topography, presumably due to a reduced left temporal responsivity. CONCLUSIONS: This finding indicates competition between auditory stimuli and hallucinations for physiological resources in the primary auditory cortex. The abnormal activation of the primary auditory cortex may thus be a constituent of auditory hallucinations.
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The expressional profile of mitochondrial transcripts and of genes involved in the mitochondrial biogenesis pathway induced by ALCAR daily supplementation in soleus muscle of control and unloaded 3-month-old rats has been analyzed. It has been found that ALCAR treatment is able to upregulate the expression level of mitochondrial transcripts (COX I, ATP6, ND6, 16 S rRNA) in both control and unloaded animals. Interestingly, ALCAR feeding to unloaded rats resulted in the increase of transcript level for master factors involved in mitochondrial biogenesis (PGC-1alpha, NRF-1, TFAM). It also prevented the unloading-induced downregulation of mRNA levels for kinases able to transduce metabolic (AMPK) and neuronal stimuli (CaMKIIbeta) into mitochondrial biogenesis. No significant effect on the expressional level of such genes was found in control ALCAR-treated rats. In addition, ALCAR feeding was able to prevent the loss of mitochondrial protein content due to unloading condition. Correlation analysis revealed a strong coordination in the expression of genes involved in mitochondrial biogenesis only in ALCAR-treated suspended animals, supporting a differentiated effect of ALCAR treatment in relation to the loading state of the soleus muscle. In conclusions, we demonstrated the ability of ALCAR supplementation to promote only in soleus muscle of hindlimb suspended rats an orchestrated expression of genes involved in mitochondrial biogenesis, which might counteract the unloading-induced metabolic changes, preventing the loss of mitochondrial proteins.
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Androgens are essential for sexual development and reproduction. However, androgen regulation in health and disease is poorly understood. We showed that human adrenocortical H295R cells grown under starvation conditions acquire a hyperandrogenic steroid profile with changes in steroid metabolizing enzymes HSD3B2 and CYP17A1 essential for androgen production. Here we studied the regulatory mechanisms underlying androgen production in starved H295R cells. Microarray expression profiling of normal versus starved H295R cells revealed fourteen differentially expressed genes; HSD3B2, HSD3B1, CYP21A2, RARB, ASS1, CFI, ASCL1 and ENC1 play a role in steroid and energy metabolism and ANGPTL1, PLK2, DUSP6, DUSP10 and FREM2 are involved in signal transduction. We discovered two new gene networks around RARB and ANGPTL1, and show how they regulate androgen biosynthesis. Transcription factor RARB stimulated the promoters of genes involved in androgen production (StAR, CYP17A1 and HSD3B2) and enhanced androstenedione production. For HSD3B2 regulation RARB worked in cooperation with Nur77. Secretory protein ANGPTL1 modulated CYP17A1 and DUSP6 expression by inducing ERK1/2 phosphorylation. By contrast, our studies revealed no evidence for hormones or cell cycle involvement in regulating androgen biosynthesis. In summary, these studies establish a firm role for RARB and ANGPTL1 in the regulation of androgen production in H295R cells.
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BACKGROUND: Cancer initiation and progression might be driven by small populations of cells endowed with stem cell-like properties. Here we comparatively addressed the expression of genes encoding putative stemness regulators including c-Myc, Klf4, Nanog, Oct4A and Sox2 genes in benign prostatic hyperplasia (BPH) and prostate cancer (PCA). METHODS: Fifty-eight PCA and thirty-nine BPH tissues samples were used for gene expression analysis, as evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of specific Klf4 isoforms was tested by conventional PCR. Klf4 specific antibodies were used for protein detection in a tissue microarray including 404 prostate samples. RESULTS: Nanog, Oct4A and Sox2 genes were comparably expressed in BPH and PCA samples, whereas c-Myc and Klf4 genes were expressed to significantly higher extents in PCA than in BPH specimens. Immunohistochemical studies revealed that Klf4 protein is detectable in a large majority of epithelial prostatic cells, irrespective of malignant transformation. However, in PCA, a predominantly cytoplasmic location was observed, consistent with the expression of a differentially spliced Klf4α isoform. CONCLUSION: Klf4 is highly expressed at gene and protein level in BPH and PCA tissues but a cytoplasmic location of the specific gene product is predominantly detectable in malignant cells. Klf4 location might be of critical relevance to steer its functions during oncogenesis.
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Detailed studies of pharmacodynamic principles relevant to the therapy of bacterial meningitis are difficult to perform in man, while the rabbit model of bacterial meningitis has proved to be extremely valuable and has led to insights that appear relevant for the treatment of humans. Most importantly in the light of the restricted penetration of antibiotics into the CSF, animal studies have shown that in meningitis there is a dose-response curve between the CSF concentrations achieved by antibiotics and their bactericidal activity. This appears to be true for all classes of antibiotics thus far examined, including the beta-lactams, which do not show such a dose-response behaviour in other infections. Only CSF concentrations that exceed the MBC of the infecting organism by at least 10-30-fold achieve consistent and rapid bactericidal activity. Such rapid bactericidal activity is a requirement for successful therapy with beta-lactams and can be impaired with certain antibiotics by the specific conditions in infected CSF (protein content; acidic pH; slow-growing bacteria). However, rapid antibiotic killing of the infecting organisms may not be without adverse effects either. Some antibiotics, particularly beta-lactams lead to the brisk liberation of bacterial cell wall components (e.g. endotoxin, in the case of Gram-negative organisms) which have an inflammatory effect on the host and can lead to a temporary deterioration of the disease. Dexamethasone, when administered with the antibiotic, can prevent some of the adverse effects of rapid bacterial lysis.
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The genes for the dopamine transporter (DAT) and the D-Amino acid oxidase activator (DAOA or G72) have been independently implicated in the risk for schizophrenia and in bipolar disorder and/or their related intermediate phenotypes. DAT and G72 respectively modulate central dopamine and glutamate transmission, the two systems most robustly implicated in these disorders. Contemporary studies have demonstrated that elevated dopamine function is associated with glutamatergic dysfunction in psychotic disorders. Using functional magnetic resonance imaging we examined whether there was an interaction between the effects of genes that influence dopamine and glutamate transmission (DAT and G72) on regional brain activation during verbal fluency, which is known to be abnormal in psychosis, in 80 healthy volunteers. Significant interactions between the effects of G72 and DAT polymorphisms on activation were evident in the striatum, parahippocampal gyrus, and supramarginal/angular gyri bilaterally, the right insula, in the right pre-/postcentral and the left posterior cingulate/retrosplenial gyri (P < 0.05, FDR-corrected across the whole brain). This provides evidence that interactions between the dopamine and the glutamate system, thought to be altered in psychosis, have an impact in executive processing which can be modulated by common genetic variation.
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The Antihydrogen Experiment: Gravity, Interferometry, Spectroscopy (AEgIS) experiment is conducted by an international collaboration based at CERN whose aim is to perform the first direct measurement of the gravitational acceleration of antihydrogen in the local field of the Earth, with Δg/g = 1% precision as a first achievement. The idea is to produce cold (100 mK) antihydrogen ( ¯H) through a pulsed charge exchange reaction by overlapping clouds of antiprotons, from the Antiproton Decelerator (AD) and positronium atoms inside a Penning trap. The antihydrogen has to be produced in an excited Rydberg state to be subsequently accelerated to form a beam. The deflection of the antihydrogen beam can then be measured by using a moir´e deflectometer coupled to a position sensitive detector to register the impact point of the anti-atoms through the vertex reconstruction of their annihilation products. After being approved in late 2008, AEgIS started taking data in a commissioning phase in 2012. This paper presents an outline of the experiment with a brief overview of its physics motivation and of the state-of-the-art of the g measurement on antimatter. Particular attention is given to the current status of the emulsion-based position detector needed to measure the ¯H sag in AEgIS.
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Transcatheter mitral interventions has been developed to address an unmet clinical need and may be an alternative therapeutic option to surgery with the intent to provide symptomatic and prognostic benefit. Beyond MitraClip therapy, alternative repair technologies are being developed to expand the transcatheter intervention armamentarium. Recently, the feasibility of transcatheter mitral valve implantation in native non-calcified valves has been reported in very high-risk patients. Acknowledging the lack of scientific evidence to date, it is difficult to predict what the ultimate future role of transcatheter mitral valve interventions will be. The purpose of the present report is to review the current state-of-the-art of mitral valve intervention, and to identify the potential future scenarios, which might benefit most from the transcatheter repair and replacement devices under development.
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Positron emission tomography-computed tomography (PET-CT) has gained widespread acceptance as a staging investigation in the diagnostic workup of malignant tumours and may be used to visualize metabolic changes before the evolution of morphological changes. To make histology of PET findings without distinctive structural changes available for treatment decisions, we developed a protocol for multimodal image-guided interventions using an integrated PET-CT machine. We report our first experience in 12 patients admitted for staging and restaging of breast cancer, non-small cell lung cancer, cervical cancer, soft tissue sarcoma, and osteosarcoma. Patients were repositioned according to the findings in PET-CT and intervention was planned based on a subsequent single-bed PET-CT acquisition of the region concerned. The needle was introduced under CT guidance in a step-by-step technique and correct needle position in the centre of the FDG avid lesion was assured by repetition of a single-bed PET-CT acquisition before sampling. The metabolically active part of lesions was accurately targeted in all patients and representative samples were obtained in 92%. No major adverse effects occurred. We conclude that PET-CT guidance for interventions is feasible and may be promising to optimize the diagnostic yield of CT-guided interventions and to make metabolically active lesions without morphological correlate accessible to percutaneous interventions.
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This article analyses the reporting of evidence in Swiss direct-democratic campaigns in the health policy sector, assuming that an informed public helps democracy function successfully. A content analysis of the media’s news reporting shows that of 5030 media items retrieved, a reference to evidence is found in 6.8%. The voter receives evidence in the form of substantiating arguments, equally distributed among proponents and opponents. Experts have the highest chance of providing evidence, but appear most rarely. Integrating more evidence might provide voters with the diversity of arguments needed to make a truly informed decision.