53 research outputs found

    Value-based decision-making of cigarette and nondrug rewards in dependent and occasional cigarette smokers:An FMRI study

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    Little is known about the neural functioning that underpins drug valuation and choice in addiction, including nicotine dependence. Following ad libitum smoking, 19 dependent smokers (smoked≥10/day) and 19 occasional smokers (smoked 0.5‐5/week) completed a decision‐making task. First, participants stated how much they were willing‐to‐pay for various amounts of cigarettes and shop vouchers. Second, during functional magnetic resonance imaging, participants decided if they wanted to buy these cigarettes and vouchers for a set amount of money. We examined decision‐making behaviour and brain activity when faced with cigarette and voucher decisions, purchasing (vs not purchasing) cigarettes and vouchers, and “value signals” where brain activity correlated with cigarette and voucher value. Dependent smokers had a higher willingness‐to‐pay for cigarettes and greater activity in the bilateral middle temporal gyrus when faced with cigarette decisions than occasional smokers. Across both groups, the decision to buy cigarettes was associated with activity in the left paracingulate gyrus, right nucleus accumbens, and left amygdala. The decision to buy vouchers was associated with activity in the left superior frontal gyrus, but dependent smokers showed weaker activity in the left posterior cingulate gyrus than occasional smokers. Across both groups, cigarette value signals were observed in the left striatum and ventromedial prefrontal cortex. To summarise, nicotine dependence was associated with greater behavioural valuation of cigarettes and brain activity during cigarette decisions. When purchasing cigarettes and vouchers, reward and decision‐related brain regions were activated in both groups. For the first time, we identified value signals for cigarettes in the brain

    The discovery of a typical radio galaxy at z = 4.88

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    ‘The definitive version is available at www3.interscience.wiley.com '. Copyright Royal Astronomical Society. DOI: 10.1111/j.1745-3933.2009.00715.xIn this Letter, we report the discovery of a z= 4.88 radio galaxy discovered with a new technique which does not rely on pre-selection of a sample based on radio properties such as steep-spectral index or small angular size. This radio galaxy was discovered in the Elais-N2 field and has a spectral index of α= 0.75 , i.e. not ultra-steep spectrum. It also has a luminosity consistent with being drawn from the break of the radio luminosity function and can therefore be considered as a typical radio galaxy. Using the Spitzer Wide-Area Infrared Extragalactic Survey (SWIRE) data over this field, we find that the host galaxy is consistent with being similarly massive to the lower redshift powerful radio galaxies (∼1–3L★) . However, we note that at z= 4.88, the Hα line is redshifted into the IRAC 3.6 μm filter, and some of the flux in this band may be due to this fact rather than the stellar continuum emission. The discovery of such a distant radio source from our initial spectroscopic observations demonstrates the promise of our survey for finding the most distant radio sources.Peer reviewe

    Composition and Acidification of the Culture Medium Influences Chronological Aging Similarly in Vineyard and Laboratory Yeast

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    Chronological aging has been studied extensively in laboratory yeast by culturing cells into stationary phase in synthetic complete medium with 2% glucose as the carbon source. During this process, acidification of the culture medium occurs due to secretion of organic acids, including acetic acid, which limits survival of yeast cells. Dietary restriction or buffering the medium to pH 6 prevents acidification and increases chronological life span. Here we set out to determine whether these effects are specific to laboratory-derived yeast by testing the chronological aging properties of the vineyard yeast strain RM11. Similar to the laboratory strain BY4743 and its haploid derivatives, RM11 and its haploid derivatives displayed increased chronological life span from dietary restriction, buffering the pH of the culture medium, or aging in rich medium. RM11 and BY4743 also displayed generally similar aging and growth characteristics when cultured in a variety of different carbon sources. These data support the idea that mechanisms of chronological aging are similar in both the laboratory and vineyard strains

    Observing Supermassive Black Holes across cosmic time: from phenomenology to physics

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    In the last decade, a combination of high sensitivity, high spatial resolution observations and of coordinated multi-wavelength surveys has revolutionized our view of extra-galactic black hole (BH) astrophysics. We now know that supermassive black holes reside in the nuclei of almost every galaxy, grow over cosmological times by accreting matter, interact and merge with each other, and in the process liberate enormous amounts of energy that influence dramatically the evolution of the surrounding gas and stars, providing a powerful self-regulatory mechanism for galaxy formation. The different energetic phenomena associated to growing black holes and Active Galactic Nuclei (AGN), their cosmological evolution and the observational techniques used to unveil them, are the subject of this chapter. In particular, I will focus my attention on the connection between the theory of high-energy astrophysical processes giving rise to the observed emission in AGN, the observable imprints they leave at different wavelengths, and the methods used to uncover them in a statistically robust way. I will show how such a combined effort of theorists and observers have led us to unveil most of the SMBH growth over a large fraction of the age of the Universe, but that nagging uncertainties remain, preventing us from fully understating the exact role of black holes in the complex process of galaxy and large-scale structure formation, assembly and evolution.Comment: 46 pages, 21 figures. This review article appears as a chapter in the book: "Astrophysical Black Holes", Haardt, F., Gorini, V., Moschella, U and Treves A. (Eds), 2015, Springer International Publishing AG, Cha

    Informing UK governance of resilience to climate risks: improving the local evidence-base

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    International assessments of evidence on climate change (e.g. Intergovernmental Panel on Climate Change, IPCC) or national climate change risk assessments (e.g. UK Climate Change Risk Assessment, CCRA) do not offer a sufficiently granular perspective on climate impacts to adequately inform governance of resilience to climate risks at the local level. Using an analysis of UK decision-makers managing and responding to heatwaves and flood risks, this paper argues how more robust local evidence is needed to inform decision-making regarding adaptation options for enhancing local resilience. We identify evidence gaps and issues relating to local climate change impacts, including sources and quality of evidence used, adequacy and accessibility of evidence available, ill-communicated evidence and conflicting or misused evidence. A lack of appreciation regarding how scientific evidence and personal judgement can mutually enhance the quality of decision-making underpins all of these gaps. Additionally, we find that the majority of evidence currently used is reductively based upon socio-economic and physical characteristics of climate risks. We argue that a step change is needed in local climate resilience that moves beyond current physical and socio-economic risk characterisation to a more inclusive co-constitution of social and politically defined climate risks at the local scale that are better aligned with the local impacts felt and needs of stakeholders

    The MDT-15 Subunit of Mediator Interacts with Dietary Restriction to Modulate Longevity and Fluoranthene Toxicity in Caenorhabditis elegans

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    Dietary restriction (DR), the limitation of calorie intake while maintaining proper nutrition, has been found to extend life span and delay the onset of age-associated disease in a wide range of species. Previous studies have suggested that DR can reduce the lethality of environmental toxins. To further examine the role of DR in toxin response, we measured life spans of the nematode Caenorhabditis elegans treated with the mutagenic polyaromatic hydrocarbon, fluoranthene (FLA). FLA is a direct byproduct of combustion, and is one of U.S. Environmental Protection Agency's sixteen priority environmental toxins. Treatment with 5 µg/ml FLA shortened the life spans of ad libitum fed nematodes, and DR resulted in increased sensitivity to FLA. To determine the role of detoxifying enzymes in the toxicity of FLA, we tested nematodes with mutations in the gene encoding the MDT-15 subunit of mediator, a transcriptional coactivator that regulates genes involved in fatty acid metabolism and detoxification. Mutation of mdt-15 increased the life span of FLA treated animals compared to wild-type animals with no difference observed between DR and ad libitum fed mdt-15 animals. We also examined mutants with altered insulin-IGF-1-like signaling (IIS), which is known to modulate life span and stress resistance in C. elegans independently of DR. Mutation of the genes coding for the insulin-like receptor DAF-2 or the FOXO-family transcription factor DAF16 did not alter the animals' susceptibility to FLA compared to wild type. Taken together, our results suggest that certain compounds have increased toxicity when combined with a DR regimen through increased metabolic activation. This increased metabolic activation appears to be mediated through the MDT-15 transcription factor and is independent of the IIS pathway

    Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

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    Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

    Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

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