3,713 research outputs found

    Hippocampal Regulation of Postsynaptic Density Homer1 by Associative Learning

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    Genes involved in synaptic plasticity, particularly genes encoding postsynaptic density proteins, have been recurrently linked to psychiatric disorders including schizophrenia and autism. Postsynaptic density Homer1 proteins contribute to synaptic plasticity through the competing actions of short and long isoforms. The activity-induced expression of shortHomer1isoforms,Homer1aandAnia-3, is thought to be related to processes of learning and memory. However, the precise regulation ofHomer1aandAnia-3with different components of learning has not been investigated. Here, we used in situ hybridization to quantify short and longHomer1expression in the hippocampus following consolidation, retrieval, and extinction of associative fear memory, using contextual fear conditioning in rats.Homer1aandAnia-3, but not longHomer1, were regulated by contextual fear learning or novelty detection, although their precise patterns of expression in hippocampal subregions were dependent on the isoform. We also show for the first time that the two short Homer1 isoforms are regulated after the retrieval and extinction of contextual fear memory, albeit with distinct temporal and spatial profiles. These findings support a role of activity-induced Homer1 isoforms in learning and memory processes in discrete hippocampal subregions and suggest that Homer1a and Ania-3 may play separable roles in synaptic plasticity.</jats:p

    Spatio-temporal analysis of the role of climate in inter-annual variation of malaria incidence in Zimbabwe

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    BACKGROUND: On the fringes of endemic zones climate is a major determinant of inter-annual variation in malaria incidence. Quantitative description of the space-time effect of this association has practical implications for the development of operational malaria early warning system (MEWS) and malaria control. We used Bayesian negative binomial models for spatio-temporal analysis of the relationship between annual malaria incidence and selected climatic covariates at a district level in Zimbabwe from 1988–1999. RESULTS: Considerable inter-annual variations were observed in the timing and intensity of malaria incidence. Annual mean values of average temperature, rainfall and vapour pressure were strong positive predictors of increased annual incidence whereas maximum and minimum temperature had the opposite effects. Our modelling approach adjusted for unmeasured space-time varying risk factors and showed that while year to year variation in malaria incidence is driven mainly by climate, the resultant spatial risk pattern may to large extent be influenced by other risk factors except during high and low risk years following the occurrence of extremely wet and dry conditions, respectively. CONCLUSION: Our model revealed a spatially varying risk pattern that is not attributable only to climate. We postulate that only years characterized by extreme climatic conditions may be important for developing climate based MEWS and for delineating areas prone to climate driven epidemics. However, the predictive value of climatic risk factors identified in this study still needs to be evaluated

    Measurement of Permanent Electric Dipole Moments of Charged Hadrons in Storage Rings

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    Permanent Electric Dipole Moments (EDMs) of elementary particles violate two fundamental symmetries: time reversal invariance (T) and parity (P). Assuming the CPT theorem this implies CP-violation. The CP-violation of the Standard Model is orders of magnitude too small to be observed experimentally in EDMs in the foreseeable future. It is also way too small to explain the asymmetry in abundance of matter and anti-matter in our universe. Hence, other mechanisms of CP violation outside the realm of the Standard Model are searched for and could result in measurable EDMs. Up to now most of the EDM measurements were done with neutral particles. With new techniques it is now possible to perform dedicated EDM experiments with charged hadrons at storage rings where polarized particles are exposed to an electric field. If an EDM exists the spin vector will experience a torque resulting in change of the original spin direction which can be determined with the help of a polarimeter. Although the principle of the measurement is simple, the smallness of the expected effect makes this a challenging experiment requiring new developments in various experimental areas. Complementary efforts to measure EDMs of proton, deuteron and light nuclei are pursued at Brookhaven National Laboratory and at Forschungszentrum Juelich with an ultimate goal to reach a sensitivity of 10^{-29} e cm.Comment: 8 pages, 2 figure

    Point-Coupling Models from Mesonic Hypermassive Limit and Mean-Field Approaches

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    In this work we show how nonlinear point-coupling models, described by a Lagrangian density that presents only terms up to fourth order in the fermion condensate (ψˉψ)(\bar{\psi}\psi), are derived from a modified meson-exchange nonlinear Walecka model. The derivation can be done through two distinct methods, namely, the hypermassive meson limit within a functional integral approach, and the mean-field approximation in which equations of state at zero temperature of the nonlinear point-coupling models are directly obtained.Comment: 18 pages. Accepted for publication in Braz. J. Phy

    Low rate of rhesus immunization from rh- incompatible blood transfusions during liver and heart transplant surgery

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    Transfusion of one unit or more of Rh-positive red blood cells normally causes circulating anti-D antibody to appear 2-6 months later in 80-95% of Rh persons. We asked whether transplant immunosuppression with cyclosporine and corticosteroids affects Rh immuniza¬tion. Nineteen Rh" liver, heart, and heart-lung transplant recipients received 3—153 (median: 10) units of Rh+ RBCs at surgery and were tested for anti-D >2 months later. Three patients developed anti-D at 11—15 days; one may have had an unusually rapid primary immune response and two were secondary to previous exposure by pregnancy. None of the other 16 patients had anti-D when tested 2.5-51 months later (13 patients, >11.5 months). This low rate of Rhesus immunization in association with cyclosporine immunosuppression allows greater flexibility in meeting the transfusion needs of Rh- liver and heart transplant patients. Caution is still advised in young females and in patients who may have been previously exposed to Rh+ RBCs by transfusion or by pregnancy prior to the availability of perinatal Rh immune globulin twenty years ago. Other humoral immune responses to some vaccines or infectious agents may also be impaired in transplant patients© 1989 by The Williams and Wilkins Co

    SITC/iSBTc Cancer Immunotherapy Biomarkers Resource Document: Online resources and useful tools - a compass in the land of biomarker discovery

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    Recent positive clinical results in cancer immunotherapy point to the potential of immune-based strategies to provide effective treatment of a variety of cancers. In some patients, the responses to cancer immunotherapy are durable, dramatically extending survival. Extensive research efforts are being made to identify and validate biomarkers that can help identify subsets of cancer patients that will benefit most from these novel immunotherapies. In addition to the clear advantage of such predictive biomarkers, immune biomarkers are playing an important role in the development, clinical evaluation and monitoring of cancer immunotherapies. This Cancer Immunotherapy Resource Document, prepared by the Society for Immunotherapy of Cancer (SITC, formerly the International Society for Biological Therapy of Cancer, iSBTc), provides key references and online resources relevant to the discovery, evaluation and clinical application of immune biomarkers. These key resources were identified by experts in the field who are actively pursuing research in biomarker identification and validation. This organized collection of the most useful references, online resources and tools serves as a compass to guide discovery of biomarkers essential to advancing novel cancer immunotherapies
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