Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory.

RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory.The authors’ research is funded by the Wellcome Trust (grant number 086871/Z/08/Z), the MRC (G0701500), a joint award from the MRC (G1000183) and Wellcome Trust (093875/Z/10/ Z) in support of the Behavioral and Clinical Neuroscience Institute at Cambridge University, and an MRC strategic award to the Imperial College-Cambridge University-Manchester University (ICCAM) addiction cluster (G1000018).This is the final version of the article. It first appeared from Springer at http://dx.doi.org/10.1007/s00213-016-4405-8

Ultrasound morphology of carotid plaque and its link with lipid: protein content and 3d microstructure of the plaque.

the 22nd Meeting of the European Society of Neurosonology and Cerebral Hemodynamics (ESNCH), 19-21 May 2017. Berlin, Germany, and published in the International Journal of Stroke 12(1S): 57 (Poster 101), May 2017. ISSN: 1747-4930, eISSN: 1747-4949

Combining local model calibration with the emergent constraint approach to reduce uncertainty in the tropical land carbon cycle feedback

The role of the land carbon cycle in climate change remains highly uncertain. A key source of the projection spread is related to the assumed response of photosynthesis to warming, especially in the tropics. The optimum temperature for photosynthesis determines whether warming positively or negatively impacts photosynthesis, thereby amplifying or suppressing CO2 fertilisation of photosynthesis under CO2-induced global warming. Land carbon cycle models have been extensively calibrated against local eddy flux measurements, but this has not previously been clearly translated into a reduced uncertainty in terms of how the tropical land carbon sink will respond to warming. Using a previous parameter perturbation ensemble carried out with version 3 of the Hadley Centre coupled climate–carbon cycle model (HadCM3C), we identify an emergent relationship between the optimal temperature for photosynthesis, which is especially relevant in tropical forests, and the projected amount of atmospheric CO2 at the end of the century. We combine this with a constraint on the optimum temperature for photosynthesis, derived from eddy covariance measurements using the adjoint of the Joint UK Land Environment Simulator (JULES) land surface model. Taken together, the emergent relationship from the coupled model and the constraint on the optimum temperature for photosynthesis define an emergent constraint on future atmospheric CO2 in the HadCM3C coupled climate–carbon cycle under a common emissions scenario (A1B). The emergent constraint sharpens the probability density of simulated CO2 change (2100–1900) and moves its peak to a lower value of 497 ± 91 compared to 607 ± 128 ppmv (parts per million by volume) when using the equal-weight prior. Although this result is likely to be model and scenario dependent, it demonstrates the potential of combining the large-scale emergent constraint approach with a parameter estimation using detailed local measurements.</p

Popular attitudes to memory, the body, and social identity : the rise of external commemoration in Britain, Ireland, and New England

A comparative analysis of samples of external memorials from burial grounds in Britain, Ireland and New England reveals a widespread pattern of change in monument style and content, and exponential growth in the number of permanent memorials from the 18th century onwards. Although manifested in regionally distinctive styles on which most academic attention has so far been directed, the expansion reflects global changes in social relationships and concepts of memory and the body. An archaeological perspective reveals the importance of external memorials in articulating these changing attitudes in a world of increasing material consumption

Dengue outlook for the World Cup in Brazil: an early warning model framework driven by real-time seasonal climate forecasts.

PublishedJournal ArticleResearch Support, Non-U.S. Gov'tBACKGROUND: With more than a million spectators expected to travel among 12 different cities in Brazil during the football World Cup, June 12-July 13, 2014, the risk of the mosquito-transmitted disease dengue fever is a concern. We addressed the potential for a dengue epidemic during the tournament, using a probabilistic forecast of dengue risk for the 553 microregions of Brazil, with risk level warnings for the 12 cities where matches will be played. METHODS: We obtained real-time seasonal climate forecasts from several international sources (European Centre for Medium-Range Weather Forecasts [ECMWF], Met Office, Meteo-France and Centro de Previsão de Tempo e Estudos Climáticos [CPTEC]) and the observed dengue epidemiological situation in Brazil at the forecast issue date as provided by the Ministry of Health. Using this information we devised a spatiotemporal hierarchical Bayesian modelling framework that enabled dengue warnings to be made 3 months ahead. By assessing the past performance of the forecasting system using observed dengue incidence rates for June, 2000-2013, we identified optimum trigger alert thresholds for scenarios of medium-risk and high-risk of dengue. FINDINGS: Our forecasts for June, 2014, showed that dengue risk was likely to be low in the host cities Brasília, Cuiabá, Curitiba, Porto Alegre, and São Paulo. The risk was medium in Rio de Janeiro, Belo Horizonte, Salvador, and Manaus. High-risk alerts were triggered for the northeastern cities of Recife (p(high)=19%), Fortaleza (p(high)=46%), and Natal (p(high)=48%). For these high-risk areas, particularly Natal, the forecasting system did well for previous years (in June, 2000-13). INTERPRETATION: This timely dengue early warning permits the Ministry of Health and local authorities to implement appropriate, city-specific mitigation and control actions ahead of the World Cup. FUNDING: European Commission's Seventh Framework Research Programme projects DENFREE, EUPORIAS, and SPECS; Conselho Nacional de Desenvolvimento Científico e Tecnológico and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro.DENFREE projectEUPORIAS projectSPECS projectEuropean Commission's Seventh Framework Research ProgrammeConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado do Rio de Janeir

A user-centred evaluation framework for the Sealife semantic web browsers

Background: Semantically-enriched browsing has enhanced the browsing experience by providing contextualised dynamically generated Web content, and quicker access to searched-for information. However, adoption of Semantic Web technologies is limited and user perception from the non-IT domain sceptical. Furthermore, little attention has been given to evaluating semantic browsers with real users to demonstrate the enhancements and obtain valuable feedback. The Sealife project investigates semantic browsing and its application to the life science domain. Sealife's main objective is to develop the notion of context-based information integration by extending three existing Semantic Web browsers (SWBs) to link the existing Web to the eScience infrastructure. / Methods: This paper describes a user-centred evaluation framework that was developed to evaluate the Sealife SWBs that elicited feedback on users' perceptions on ease of use and information findability. Three sources of data: i) web server logs; ii) user questionnaires; and iii) semi-structured interviews were analysed and comparisons made between each browser and a control system. / Results: It was found that the evaluation framework used successfully elicited users' perceptions of the three distinct SWBs. The results indicate that the browser with the most mature and polished interface was rated higher for usability, and semantic links were used by the users of all three browsers. / Conclusion: Confirmation or contradiction of our original hypotheses with relation to SWBs is detailed along with observations of implementation issues