312 research outputs found

    The principles and practices of educational neuroscience: commentary on Bowers (2016)

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    In his recent critique of Educational Neuroscience, Bowers argues that neuroscience has no role to play in informing education, which he equates with classroom teaching. Neuroscience, he suggests, adds nothing to what we can learn from psychology. In this commentary, we argue that Bowers’ assertions misrepresent the nature and aims of the work in this new field. We suggest that, by contrast, psychological and neural levels of explanation complement rather than compete with each other. Bowers’ analysis also fails to include a role for educational expertise – a guiding principle of our new field. On this basis, we conclude that his critique is potentially misleading. We set out the well-documented goals of research in Educational Neuroscience, and show how, in collaboration with educators, significant progress has already been achieved, with the prospect of even greater progress in the future

    The Epithelial Sodium Channel (ENaC) Establishes a Trafficking Vesicle Pool Responsible for Its Regulation

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    The epithelial sodium channel (ENaC) is the rate-limiting step for sodium reabsorption across tight epithelia. Cyclic-AMP (cAMP) stimulation promotes ENaC trafficking to the apical surface to increase channel number and transcellular Na+ transport. Removal of corticosteroid supplementation in a cultured cortical collecting duct cell line reduced ENaC expression. Concurrently, the number of vesicles trafficked in response to cAMP stimulation, as measured by a change in membrane capacitance, also decreased. Stimulation with aldosterone restored both the basal and cAMP-stimulated ENaC activity and increased the number of exocytosed vesicles. Knocking down ENaC directly decreased both the cAMP-stimulated short-circuit current and capacitance response in the presence of aldosterone. However, constitutive apical recycling of the Immunoglobulin A receptor was unaffected by alterations in ENaC expression or trafficking. Fischer Rat Thyroid cells, transfected with α,β,γ-mENaC had a significantly greater membrane capacitance response to cAMP stimulation compared to non-ENaC controls. Finally, immunofluorescent labeling and quantitation revealed a smaller number of vesicles in cells where ENaC expression was reduced. These findings indicate that ENaC is not a passive passenger in regulated epithelial vesicle trafficking, but plays a role in establishing and maintaining the pool of vesicles that respond to cAMP stimulation. © 2012 Edinger et al

    Elevated Paracellular Glucose Flux across Cystic Fibrosis Airway Epithelial Monolayers Is an Important Factor for Pseudomonas aeruginosa Growth.

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    People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease

    The Lhx1-Ldb1 complex interacts with Furry to regulate microRNA expression during pronephric kidney development

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    The molecular events driving specification of the kidney have been well characterized. However, how the initial kidney field size is established, patterned, and proportioned is not well characterized. Lhx1 is a transcription factor expressed in pronephric progenitors and is required for specification of the kidney, but few Lhx1 interacting proteins or downstream targets have been identified. By tandem-affinity purification, we isolated FRY like transcriptional coactivator (Fryl), one of two paralogous genes, fryl and furry (fry), have been described in vertebrates. Both proteins were found to interact with the Ldb1-Lhx1 complex, but our studies focused on Lhx1/Fry functional roles, as they are expressed in overlapping domains. We found that Xenopus embryos depleted of fry exhibit loss of pronephric mesoderm, phenocopying the Lhx1-depleted animals. In addition, we demonstrated a synergism between Fry and Lhx1, identified candidate microRNAs regulated by the pair, and confirmed these microRNA clusters influence specification of the kidney. Therefore, our data shows that a constitutively-active Ldb1-Lhx1 complex interacts with a broadly expressed microRNA repressor, Fry, to establish the kidney field.Fil: Espiritu, Eugenel B.. University of Pittsburgh; Estados UnidosFil: Crunk, Amanda E.. University of Pittsburgh; Estados UnidosFil: Bais, Abha. University of Pittsburgh; Estados UnidosFil: Hochbaum, Daniel. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cervino, Ailen Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Phua, Yu Leng. University Of Pittsburgh Medical Center; Estados UnidosFil: Butterworth, Michael B.. University of Pittsburgh; Estados UnidosFil: Goto, Toshiyasu. Tokyo Medical And Dental University; JapónFil: Ho, Jacqueline. University Of Pittsburgh Medical Center; Estados UnidosFil: Hukriede, Neil A.. University of Pittsburgh; Estados UnidosFil: Cirio, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; Argentin

    Observed Reductions in Schistosoma mansoni Transmission from Large-Scale Administration of Praziquantel in Uganda: A Mathematical Modelling Study

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    To date schistosomiasis control programmes based on chemotherapy have largely aimed at controlling morbidity in treated individuals rather than at suppressing transmission. In this study, a mathematical modelling approach was used to estimate reductions in the rate of Schistosoma mansoni reinfection following annual mass drug administration (MDA) with praziquantel in Uganda over four years (2003-2006). In doing this we aim to elucidate the benefits of MDA in reducing community transmission.Age-structured models were fitted to a longitudinal cohort followed up across successive rounds of annual treatment for four years (Baseline: 2003, TREATMENT: 2004-2006; n = 1,764). Instead of modelling contamination, infection and immunity processes separately, these functions were combined in order to estimate a composite force of infection (FOI), i.e., the rate of parasite acquisition by hosts.MDA achieved substantial and statistically significant reductions in the FOI following one round of treatment in areas of low baseline infection intensity, and following two rounds in areas with high and medium intensities. In all areas, the FOI remained suppressed following a third round of treatment.This study represents one of the first attempts to monitor reductions in the FOI within a large-scale MDA schistosomiasis morbidity control programme in sub-Saharan Africa. The results indicate that the Schistosomiasis Control Initiative, as a model for other MDA programmes, is likely exerting a significant ancillary impact on reducing transmission within the community, and may provide health benefits to those who do not receive treatment. The results obtained will have implications for evaluating the cost-effectiveness of schistosomiasis control programmes and the design of monitoring and evaluation approaches in general

    Structure of Fat Jets at the Tevatron and Beyond

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    Boosted resonances is a highly probable and enthusiastic scenario in any process probing the electroweak scale. Such objects when decaying into jets can easily blend with the cornucopia of jets from hard relative light QCD states. We review jet observables and algorithms that can contribute to the identification of highly boosted heavy jets and the possible searches that can make use of such substructure information. We also review previous studies by CDF on boosted jets and its measurements on specific jet shapes.Comment: invited review for a special "Top and flavour physics in the LHC era" issue of The European Physical Journal C, we invite comments regarding contents of the review; v2 added references and institutional preprint number

    A powerful intervention: general practitioners' use of sickness certification in depression

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    <b>Background</b> Depression is frequently cited as the reason for sickness absence, and it is estimated that sickness certificates are issued in one third of consultations for depression. Previous research has considered GP views of sickness certification but not specifically in relation to depression. This study aimed to explore GPs views of sickness certification in relation to depression.<p></p> <b>Methods</b> A purposive sample of GP practices across Scotland was selected to reflect variations in levels of incapacity claimants and antidepressant prescribing. Qualitative interviews were carried out between 2008 and 2009.<p></p> <b>Results</b> A total of 30 GPs were interviewed. A number of common themes emerged including the perceived importance of GP advocacy on behalf of their patients, the tensions between stakeholders involved in the sickness certification system, the need to respond flexibly to patients who present with depression and the therapeutic nature of time away from work as well as the benefits of work. GPs reported that most patients with depression returned to work after a short period of absence and that it was often difficult to predict which patients would struggle to return to work.<p></p> <b>Conclusions</b> GPs reported that dealing with sickness certification and depression presents distinct challenges. Sickness certificates are often viewed as powerful interventions, the effectiveness of time away from work for those with depression should be subject to robust enquiry

    How low can SUSY go? Matching, monojets and compressed spectra

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    If supersymmetry (SUSY) has a compressed spectrum then the current mass limits from the LHC can be drastically reduced. We consider a possible 'worst case' scenario where the gluino and/or squarks are degenerate with the lightest SUSY particle (LSP). The most sensitive searches for these compressed spectra are via the final state LSPs recoiling against initial state radiation (ISR). Therefore it is vital that the ISR is understood and possible uncertainties in the predictions are evaluated. We use both MLM (with Pythia 6) and CKKW- L (with Pythia 8) matching and vary matching scales and parton shower properties to accurately determine the theoretical uncertainties in the kinematic distributions. All current LHC SUSY and monojet analyses are employed and we find the most constraining limits come from the CMS Razor and CMS monojet searches. For a scenario of squarks degenerate with the LSP and decoupled gluinos we find Mq~>340M_{\tilde{q}}>340 GeV. For gluinos degenerate with the LSP and decoupled squarks, Mg~>500M_{\tilde{g}}>500 GeV. For equal mass squarks and gluinos degenerate with the LSP, Mq~,g~>650M_{\tilde{q},\tilde{g}}>650 GeV.Comment: References added, version submitted to ep
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