183 research outputs found

    Impaired perceptual learning in a mouse model of Fragile X syndrome is mediated by parvalbumin neuron dysfunction and is reversible.

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    To uncover the circuit-level alterations that underlie atypical sensory processing associated with autism, we adopted a symptom-to-circuit approach in the Fmr1-knockout (Fmr1-/-) mouse model of Fragile X syndrome. Using a go/no-go task and in vivo two-photon calcium imaging, we find that impaired visual discrimination in Fmr1-/- mice correlates with marked deficits in orientation tuning of principal neurons and with a decrease in the activity of parvalbumin interneurons in primary visual cortex. Restoring visually evoked activity in parvalbumin cells in Fmr1-/- mice with a chemogenetic strategy using designer receptors exclusively activated by designer drugs was sufficient to rescue their behavioral performance. Strikingly, human subjects with Fragile X syndrome exhibit impairments in visual discrimination similar to those in Fmr1-/- mice. These results suggest that manipulating inhibition may help sensory processing in Fragile X syndrome

    A comparative study of approaches towards energy efficiency and renewable energy use at higher education institutions

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    © 2019 Elsevier Ltd The potential for energy efficiency and for the deployment of renewable energy at universities is substantial, and they represent promising ways to meet an institution's energy needs on the one hand, without a large climate burden on the other. However, in order to achieve successful investment and results, it is imperative to understand the level of current commitment to energy actions. Therefore, this paper investigates the level of engagement in energy efficiency measures of a sample of 50 higher education institutions from round the world, and identifies which types of renewable energy are being used to date. Results show that in more than half of the universities only a small portion of energy consumption comes from renewable sources (1%–20%) and solar/photovoltaics is the most used source (70%). Investment in energy efficiency is more common in the sample, with 54% of the universities reporting higher levels of engagement, mainly in buildings (78%) and equipment/machineries (56%). Departing from the assumption that sustainable energy use is a pre-condition for campuses to pursue sustainability, the paper identifies current deficiencies and discusses improvements in this key area, with experiences which may be replicable elsewhere

    Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

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    Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

    Characterization of monoolein-based lipoplexes using fluorescence spectroscopy

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    Lipoplexes are commonly used as delivery systems in vitro and in vivo, the role of a neutral lipid as helper being of extreme importance in these systems. Cationic liposomes composed of dioctadecyldimethylammonium bromide (DODAB) with monoolein (MO) as a helper, at different molar ratios (1:2; 1:1 and 1:0.5) were prepared, and subsequently titrated to DNA. The structural and physicochemical properties of the lipid/DNA complexes were assessed by Ethidium Bromide (EtBr) exclusion, 90º Static Light Scattering (90º SLS) assays and Fluorescence Resonance Energy Transfer (FRET). In EtBr exclusion assays, the steady-state fluorescence spectra of EtBr were decomposed into the sum of two lognormal emissions, emanating from two different environments – H2O and DNA, and the effect of charge ratio (+/-) was observed. 90º SLS assays gave an important contribution, detecting size variations in systems with different MO fractions on the lipoplexes. In FRET assays, 2-(3-(diphenylhexatrienyl)propanoyl)-1-hexadecanoyl-sn-glycero-3-phosphocholine (DPH-HPC) was used as donor and EtBr as acceptor. The DNA component previously calculated by EtBr exclusion, was used to determine the energy transfer efficiency, as an indirect measurement of the lipoplexes structural and physicochemical properties. Our results demonstrate that the inclusion of monoolein in the cationic liposomes formulation significantly modifies the rate of DNA complexation, being DODAB:MO (1:1) the system with higher DNA condensation efficiency.Fundação para a Ciência e a Tecnologia (FCT

    In Vitro Evaluation of a Soluble Leishmania Promastigote Surface Antigen as a Potential Vaccine Candidate against Human Leishmaniasis

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    International audiencePSA (Promastigote Surface Antigen) belongs to a family of membrane-bound and secreted proteins present in severalLeishmania (L.) species. PSA is recognized by human Th1 cells and provides a high degree of protection in vaccinated mice.We evaluated humoral and cellular immune responses induced by a L. amazonensis PSA protein (LaPSA-38S) produced in aL. tarentolae expression system. This was done in individuals cured of cutaneous leishmaniasis due to L. major (CCLm) or L.braziliensis (CCLb) or visceral leishmaniasis due to L. donovani (CVLd) and in healthy individuals. Healthy individuals weresubdivided into immune (HHR-Lm and HHR-Li: Healthy High Responders living in an endemic area for L. major or L. infantuminfection) or non immune/naive individuals (HLR: Healthy Low Responders), depending on whether they produce high orlow levels of IFN-c in response to Leishmania soluble antigen. Low levels of total IgG antibodies to LaPSA-38S were detectedin sera from the studied groups. Interestingly, LaPSA-38S induced specific and significant levels of IFN-c, granzyme B and IL-10 in CCLm, HHR-Lm and HHR-Li groups, with HHR-Li group producing TNF-a in more. No significant cytokine response wasobserved in individuals immune to L. braziliensis or L. donovani infection. Phenotypic analysis showed a significant increasein CD4+ T cells producing IFN-c after LaPSA-38S stimulation, in CCLm. A high positive correlation was observed between thepercentage of IFN-c-producing CD4+ T cells and the released IFN-c. We showed that the LaPSA-38S protein was able toinduce a mixed Th1 and Th2/Treg cytokine response in individuals with immunity to L. major or L. infantum infectionindicating that it may be exploited as a vaccine candidate. We also showed, to our knowledge for the first time, the capacityof Leishmania PSA protein to induce granzyme B production in humans with immunity to L. major and L. infantum infectio
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