Glutamate induces autophagy via the two-pore channels in neural cells

NAADP (nicotinic acid adenine dinucleotide phosphate) has been proposed as a second messenger for glutamate in neuronal and glial cells via the activation of the lysosomal Ca2+ channels TPC1 and TPC2. However, the activities of glutamate that are mediated by NAADP remain unclear. In this study, we evaluated the effect of glutamate on autophagy in astrocytes at physiological, non-toxic concentration. We found that glutamate induces autophagy at similar extent as NAADP. By contrast, the NAADP antagonist NED-19 or SiRNA-mediated inhibition of TPC1/2 decreases autophagy induced by glutamate, confirming a role for NAADP in this pathway. The involvement of TPC1/2 in glutamate-induced autophagy was also confirmed in SHSY5Y neuroblastoma cells. Finally, we show that glutamate leads to a NAADP-dependent activation of AMPK, which is required for autophagy induction, while mTOR activity is not affected by this treatment. Taken together, our results indicate that glutamate stimulates autophagy via NAADP/TPC/AMPK axis, providing new insights of how Ca2+ signalling glutamate-mediated can control the cell metabolism in the central nervous system

The Purinergic System as a Pharmacological Target for the Treatment of Immune-Mediated Inflammatory Diseases

Immune-mediated inflammatory diseases (IMIDs) encompass a wide range of seemingly unrelated conditions, such as multiple sclerosis, rheumatoid arthritis, psoriasis, inflammatory bowel diseases, asthma, chronic obstructive pulmonary disease, and systemic lupus erythematosus. Despite differing etiologies, these diseases share common inflammatory pathways, which lead to damage in primary target organs and frequently to a plethora of systemic effects as well. The purinergic signaling complex comprising extracellular nucleotides and nucleosides and their receptors, the P2 and P1 purinergic receptors, respectively, as well as catabolic enzymes and nucleoside transporters is a major regulatory system in the body. The purinergic signaling complex can regulate the development and course of IMIDs. Here we provide a comprehensive review on the role of purinergic signaling in controlling immunity, inflammation, and organ function in IMIDs. In addition, we discuss the possible therapeutic applications of drugs acting on purinergic pathways, which have been entering clinical development, to manage patients suffering from IMIDs

A Three-Dimensional Code for Muon Propagation through the Rock: MUSIC

We present a new three-dimensional Monte-Carlo code MUSIC (MUon SImulation Code) for muon propagation through the rock. All processes of muon interaction with matter with high energy loss (including the knock-on electron production) are treated as stochastic processes. The angular deviation and lateral displacement of muons due to multiple scattering, as well as bremsstrahlung, pair production and inelastic scattering are taken into account. The code has been applied to obtain the energy distribution and angular and lateral deviations of single muons at different depths underground. The muon multiplicity distributions obtained with MUSIC and CORSIKA (Extensive Air Shower simulation code) are also presented. We discuss the systematic uncertainties of the results due to different muon bremsstrahlung cross-sections.Comment: 24 pages, 11 Postscript figures, LaTeX, to be published in Astroparticle Physic

Física e cultura popular : a poesia do samba na sala de aula

A criatividade é um elemento comum, tanto no trabalho do cientista como do artista e, uma aproximação entre esses dois campos do conhecimento pode facilitar a compreensão da Ciência como lugar de construção de conhecimento que está baseado, dentre outros aspectos, em concepções prévias trazidas por aqueles que participam dessa construção. Este trabalho apresenta parte de uma pesquisa que se baseou na aproximação entre a Física e elementos da cultura popular – a poesia do samba – como mediadora da investigação da origem das concepções alternativas de alunos do ensino médio sobre a reflexão da luz, através de um projeto de parceria entre a universidade e escolas, que envolveu alunos de graduação e ensino médio e que ocorreu no âmbito das escolas, para estudar a origem das concepções alternativas dos alunos, levando-se em conta as concepções de autores de músicas populares

CRIAÇÃO, DESENVOLVIMENTO E CONSOLIDAÇÃO DE UM CURSO SUPERIOR: O CASO DO CURSO DE CIÊNCIAS CONTÁBEIS DA FACULDADE DE AMERICANA.

O presente trabalho é um estudo de caso a respeito da criação, desenvolvimento e consolidação do Curso de Ciências Contábeis da Faculdade de Americana – FAM. Visa entender os procedimentos adotados para que recebesse o reconhecimento do Ministério da Educação e Cultura – MEC e analisar, empiricamente, os resultados alcançados por esse curso, classificando-o entre os melhores do país, segundo o Guia das Melhores Universidades (Guia do Estudante) nas edições de 2009 e 2010. De início, foram analisados o projeto apresentado pela Faculdade de Americana ao MEC, a autorização de funcionamento recebida através da Portaria Ministerial nº 1.575/2001, a Portaria de Reconhecimento nº 217/2006, bem como as exigências, avaliações e sugestões feitas pelo Ministério da Educação durante esse processo. Posteriormente, comparada a progressão da grade curricular do Curso de Ciências Contábeis da FAM com a Proposta Nacional de Conteúdo Para o Curso de Graduação em Ciências Contábeis, verificou-se a aderência desse curso a tal proposta, atendendo aos seus pressupostos teóricos e à realização de atividades práticas pertinentes. Por fim, a partir dos resultados das duas últimas edições do Guia do Estudante, importante meio de divulgação qualitativa dos cursos superiores no Brasil, e observando-se a sua metodologia de avaliação, constatou-se que o Curso de Ciências Contábeis da FAM tem-se consolidado como um dos principais do gênero, especialmente levando-se em consideração as instituições privadas de ensino superior da região metropolitana de Campinas/SP, onde se localiza a Faculdade de Americana

Atmospheric MUons from PArametric formulas: a fast GEnerator for neutrino telescopes (MUPAGE)

Neutrino telescopes will open, in the next years, new opportunities in observational high energy astrophysics. For these experiments, atmospheric muons from primary cosmic ray interactions in the atmosphere play an important role, because they provide the most abundant source of events for calibration and test. On the other side, they represent the major background source. In this paper a fast Monte Carlo generator (called MUPAGE) of bundles of atmospheric muons for underwater/ice neutrino telescopes is presented. MUPAGE is based on parametric formulas [APP25(2006)1] obtained from a full Monte Carlo simulation of cosmic ray showers generating muons in bundle, which are propagated down to 5 km w.e. It produces the event kinematics on the surface of a user-defined virtual cylinder, surrounding the detector. The multiplicity of the muons in the bundle, the muon spatial distribution and energy spectrum are simulated according to a specific model of primary cosmic ray flux, with constraints from measurements of the muon flux with underground experiments. As an example of the application, the result of the generation of events on a cylindrical surface of 3 km^2 at a depth of 2450 m of water is presented.Comment: 20 pages, 4 figure

Preparation and Properties of PTFE-PMMA Core-Shell Nanoparticles and Nanocomposites

he preparation of polytetrafluoroethylene-poly(methyl methacrylate) (PTFE-PMMA) core-shell particles was described, featuring controlled size and narrow size distribution over a wide compositional range, through a seeded emulsion polymerization starting from a PTFE seed of 26 nanometers. Over the entire MMA/PTFE range, the particle size increases as the MMA/PTFE ratio increases. A very precise control over the particle size can be exerted by properly adjusting the ratio between the monomer and the PTFE seed. Particles in the 80240 nm range can be prepared with uniformity indexes suited to build 2D and 3D colloidal crystals. These core-shell particles were employed to prepare nanocomposites with different compositions, through an annealing procedure at a temperature higher than the glass transition temperature of the shell forming polymer. A perfect dispersion of the PTFE particles within the PMMA matrix was obtained and optically transparent nanocomposites were prepared containing a very high PTFE amount

New evidence of mis 3 relative sea level changes from the messina strait, Calabria (Italy)

none12Investigation of sea-level positions during the highly-dynamic Marine Isotope Stage 3 (MIS 3: 29–61 kyrs BP) proves difficult because: (i) in stable and subsiding areas, coeval coastal sediments are currently submerged at depths of few to several tens of meters below the present sea level; (ii) in uplifting areas, the preservation of geomorphic features and sedimentary records is limited due to the erosion occurred during the Last Glacial Maximum (LGM) with sea level at a depth of −130 m, followed by marine transgression that determined the development of ravinement surfaces. This study discusses previous research in the Mediterranean and elsewhere, and describes new fossiliferous marine deposits overlaying the metamorphic bedrock at Cannitello (Calabria, Italy). Radiocarbon ages of marine shells (about 43 kyrs cal BP) indicate that these deposits, presently between 28 and 30 m above sea level, formed during MIS 3.1. Elevation correction of the Cannitello outcrops (considered in an intermediate-to-far-field position with respect to the ice sheet) with the local vertical tectonic rate and Glacial Isostatic Adjustment (GIA) rate allows the proposal of a revision of the eustatic depth for this highstand. Our results are consistent with recently proposed estimates based on a novel ice sheet modelling technique.openAntonioli F.; Calcagnile L.; Ferranti L.; Mastronuzzi G.; Monaco C.; Orru P.; Quarta G.; Pepe F.; Scardino G.; Scicchitano G.; Stocchi P.; Taviani M.Antonioli, F.; Calcagnile, L.; Ferranti, L.; Mastronuzzi, G.; Monaco, C.; Orru, P.; Quarta, G.; Pepe, F.; Scardino, G.; Scicchitano, G.; Stocchi, P.; Taviani, M

A 2-year point-prevalence surveillance of healthcare-associated infections and antimicrobial use in Ferrara University Hospital, Italy

Background: Healthcare-Associated Infections (HAIs) represent one of the leading issues to patient safety as well as a significant economic burden. Similarly, Antimicrobial Use (AMU) and Resistance (AMR) represent a growing threat to global public health and the sustainability of healthcare services. Methods: A Point Prevalence Survey (PPS) following the 2016 ECDC protocol for HAI prevalence and AMU was conducted at Ferrara University Hospital (FUH). Data were collected by a team of trained independent surveyors in 2016 and 2018. Risk factors independently associated with HAI were assessed by a multivariate logistic regression model. Results: Of the 1102 patients surveyed, 115 (10.4%) had an active HAI and 487 (44.2%) were on at least 1 systemic antimicrobial agent. Factors independently associated with increased HAI risk were a "Rapidly Fatal" McCabe score (expected fatal outcome within 1 year), presence of medical devices (PVC, CVC, indwelling urinary catheter or mechanically assisted ventilation) and a length of hospital stay of at least 1 week. The most frequent types of HAI were pneumonia, bloodstream infections, and urinary tract infections. Antimicrobial resistance to third-generation cephalosporins was observed in about 60% of Enterobacteriaceae. Conclusions: The survey reports a high prevalence of HAI and AMU in FUH. Repeated PPSs are useful to control HAIs and AMU in large acute-care hospitals, highlighting the main problematic factors and allowing planning for improvement actions