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  • Proceedings of the National Academy of Sciences  (4)
  • 1
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 30 ( 2015-07-28)
    Abstract: Alcohol abuse is highly prevalent, but little is understood about the molecular causes. Here, we report that Ras suppressor 1 (Rsu1) affects ethanol consumption in flies and humans. Drosophila lacking Rsu1 show reduced sensitivity to ethanol-induced sedation. We show that Rsu1 is required in the adult nervous system for normal sensitivity and that it acts downstream of the integrin cell adhesion molecule and upstream of the Ras-related C3 botulinum toxin substrate 1 (Rac1) GTPase to regulate the actin cytoskeleton. In an ethanol preference assay, global loss of Rsu1 causes high naïve preference. In contrast, flies lacking Rsu1 only in the mushroom bodies of the brain show normal naïve preference but then fail to acquire ethanol preference like normal flies. Rsu1 is, thus, required in distinct neurons to modulate naïve and acquired ethanol preference. In humans, we find that polymorphisms in RSU1 are associated with brain activation in the ventral striatum during reward anticipation in adolescents and alcohol consumption in both adolescents and adults. Together, these data suggest a conserved role for integrin/Rsu1/Rac1/actin signaling in modulating reward-related phenotypes, including ethanol consumption, across phyla.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 2
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2016
    In:  Proceedings of the National Academy of Sciences Vol. 113, No. 14 ( 2016-04-05), p. 3879-3884
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 113, No. 14 ( 2016-04-05), p. 3879-3884
    Abstract: Dysfunctional reward processing is implicated in various mental disorders, including attention deficit hyperactivity disorder (ADHD) and addictions. Such impairments might involve different components of the reward process, including brain activity during reward anticipation. We examined brain nodes engaged by reward anticipation in 1,544 adolescents and identified a network containing a core striatal node and cortical nodes facilitating outcome prediction and response preparation. Distinct nodes and functional connections were preferentially associated with either adolescent hyperactivity or alcohol consumption, thus conveying specificity of reward processing to clinically relevant behavior. We observed associations between the striatal node, hyperactivity, and the vacuolar protein sorting-associated protein 4A ( VPS4A ) gene in humans, and the causal role of Vps4 for hyperactivity was validated in Drosophila . Our data provide a neurobehavioral model explaining the heterogeneity of reward-related behaviors and generate a hypothesis accounting for their enduring nature.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2016
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 3
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2015
    In:  Proceedings of the National Academy of Sciences Vol. 112, No. 41 ( 2015-10-13), p. 12610-12615
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 112, No. 41 ( 2015-10-13), p. 12610-12615
    Abstract: In a changing climate, future inundation of the United States’ Atlantic coast will depend on both storm surges during tropical cyclones and the rising relative sea levels on which those surges occur. However, the observational record of tropical cyclones in the North Atlantic basin is too short (A.D. 1851 to present) to accurately assess long-term trends in storm activity. To overcome this limitation, we use proxy sea level records, and downscale three CMIP5 models to generate large synthetic tropical cyclone data sets for the North Atlantic basin; driving climate conditions span from A.D. 850 to A.D. 2005. We compare pre-anthropogenic era (A.D. 850–1800) and anthropogenic era (A.D.1970–2005) storm surge model results for New York City, exposing links between increased rates of sea level rise and storm flood heights. We find that mean flood heights increased by ∼1.24 m (due mainly to sea level rise) from ∼A.D. 850 to the anthropogenic era, a result that is significant at the 99% confidence level. Additionally, changes in tropical cyclone characteristics have led to increases in the extremes of the types of storms that create the largest storm surges for New York City. As a result, flood risk has greatly increased for the region; for example, the 500-y return period for a ∼2.25-m flood height during the pre-anthropogenic era has decreased to ∼24.4 y in the anthropogenic era. Our results indicate the impacts of climate change on coastal inundation, and call for advanced risk management strategies.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2015
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2017
    In:  Proceedings of the National Academy of Sciences Vol. 114, No. 45 ( 2017-11-07), p. 11861-11866
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 114, No. 45 ( 2017-11-07), p. 11861-11866
    Abstract: The flood hazard in New York City depends on both storm surges and rising sea levels. We combine modeled storm surges with probabilistic sea-level rise projections to assess future coastal inundation in New York City from the preindustrial era through 2300 CE. The storm surges are derived from large sets of synthetic tropical cyclones, downscaled from RCP8.5 simulations from three CMIP5 models. The sea-level rise projections account for potential partial collapse of the Antarctic ice sheet in assessing future coastal inundation. CMIP5 models indicate that there will be minimal change in storm-surge heights from 2010 to 2100 or 2300, because the predicted strengthening of the strongest storms will be compensated by storm tracks moving offshore at the latitude of New York City. However, projected sea-level rise causes overall flood heights associated with tropical cyclones in New York City in coming centuries to increase greatly compared with preindustrial or modern flood heights. For the various sea-level rise scenarios we consider, the 1-in-500-y flood event increases from 3.4 m above mean tidal level during 1970–2005 to 4.0–5.1 m above mean tidal level by 2080–2100 and ranges from 5.0–15.4 m above mean tidal level by 2280–2300. Further, we find that the return period of a 2.25-m flood has decreased from ∼500 y before 1800 to ∼25 y during 1970–2005 and further decreases to ∼5 y by 2030–2045 in 95% of our simulations. The 2.25-m flood height is permanently exceeded by 2280–2300 for scenarios that include Antarctica’s potential partial collapse.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2017
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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