Isolation and Characterization of Ischemia-Derived Astrocytes (IDAs) with Ability to Transactivate Quiescent Astrocytes

Reactive gliosis involving activation and proliferation of astrocytes and microglia, is a widespread but largely complex and graded glial response to brain injury. Astroglial population has a previously underestimated high heterogeneity with cells differing in their morphology, gene expression profile, and response to injury. Here, we identified a subset of reactive astrocytes isolated from brain focal ischemic lesions that show several atypical characteristics. Ischemia-derived astrocytes (IDAs) were isolated from early ischemic penumbra and core. IDA did not originate from myeloid precursors, butrather from pre-existing local progenitors. Isolated IDA markedly differ from primary astrocytes, as they proliferate in vitro with high cell division rate, show increased migratory ability, have reduced replicative senescence and grow in the presence of macrophages within the limits imposed by the glial scar. Remarkably, IDA produce a conditioned medium that strongly induced activation on quiescent primary astrocytes and potentiated the neuronal death triggered by oxygen-glucose deprivation. When re-implanted into normal rat brains, eGFP-IDA migrated around the injection site and induced focal reactive gliosis. Inhibition of gamma secretases or culture on quiescent primary astrocytes monolayers facilitated IDA differentiation to astrocytes. We propose that IDA represent an undifferentiated, pro-inflammatory, highly replicative and migratory astroglial subtype emerging from the ischemic microenvironment that may contribute to the expansion of reactive gliosis.Fil: Villarreal, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Rosciszewski, Gerardo Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Murta, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Cadena, María Vanesa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; ArgentinaFil: Usach, Vanina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Dodes Traian, Martín Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Setton, Clara Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Barbeito, Osvaldo Luis. Instituto Pasteur de Montevideo; UruguayFil: Ramos, Alberto Javier. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentin

Analysis and hydraulic model (2d) hyper concentrated sediment flows in west of the saws Ambato, Catamarca, Argentina

Los flujos de sedimentos hiper concentrados se pueden clasificar en inundaciones de barro, flujos de barro y flujo de escombros. Estos flujos se diferencian por la reología de la mezcla agua-sedimento. En los flujos de barro los esfuerzos que domina el fenómeno son el límite elástico y el esfuerzo viscoso. Un modelo reológico cuadrático permite simular adecuadamente condiciones de flujos que van desde aguas claras hasta flujos hiper concentrados de sedimentos. En este trabajo se analiza un evento hidrológico severo con flujo de barro ocurrido recientemente en Siján, Catamarca, Argentina aplicando el modelo de simulación (FLO-2D) de diferencias finitas.Hyper concentrated sediment flows have been classifield as mudfloods, mudflows and debris flows. Distinct physical processes differentiate these types of hyper concentrations based on the rheology of thewater-sediment mixture. Mudflows are flows with predominant yield and viscous stresses. A quadratic rheological model enables appropiate simulation offlooding conditions ranging from clear water to hyper concentrated sedimentflows.This paper presents a severe hydrological event recently occurred in Siján, Catamarca, Argentina. In this event mud flow was generated. This paper present a simulation model of finite differences (FLO-2D) to simulate the event.Fil: Eder, Matías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Estudios Avanzados en Ingeniería y Tecnología. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Estudios Avanzados en Ingeniería y Tecnología; ArgentinaFil: Barbeito, Osvaldo Luis. Secretaria de Ambiente y Desarrollo Sustentable de la Nación. Instituto Nacional del Agua y del Ambiente (Córdoba); Argentina. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Ambrosino, Silvio Norberto. Secretaria de Ambiente y Desarrollo Sustentable de la Nación. Instituto Nacional del Agua y del Ambiente (Córdoba); Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Hillman, Gerardo Daniel. Universidad Nacional de Córdoba; ArgentinaFil: Moya, Gonzalo. Universidad Nacional de Córdoba; ArgentinaFil: Rodriguez, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Estudios Avanzados en Ingeniería y Tecnología. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto de Estudios Avanzados en Ingeniería y Tecnología; Argentin

El método Jolly Phonics como herramienta para el aprendizaje de la lengua inglesa en Educación Infantil

Actualmente, es muy importante tener un dominio de una lengua extranjera y, más concretamente, de la lengua inglesa, considerada un idioma global con el cual puedes comunicarte en cualquier lugar. Para la ciudadanía es muy importante poder adquirir este idioma, pero no siempre es fácil. No obstante, varios estudios han demostrado la eficacia del método Jolly Phonics para los aprendices de menor edad, mostrándose especialmente útil para aquellos con dificultades en el proceso de lecto–escritura. Este trabajo pretende abarcar una profunda revisión teórica acerca de este método que, si bien tiene su origen en la enseñanza del inglés como lengua materna, se ha aplicado en numerosos países, como España, fundamentalmente en la etapa de Educación Infantil. Esta revisión se vertebrará a través de un recorrido por la historia y los principios del método y el análisis y la comparativa de datos y resultados de diferentes investigaciones.<br /

A silviculture-oriented spatio-temporal model for germination in Pinus pinea L. in the Spanish Northern Plateau based on a direct seeding experiment

Natural regeneration in Pinus pinea stands commonly fails throughout the Spanish Northern Plateau under current intensive regeneration treatments. As a result, extensive direct seeding is commonly conducted to guarantee regeneration occurrence. In a period of rationalization of the resources devoted to forest management, this kind of techniques may become unaffordable. Given that the climatic and stand factors driving germination remain unknown, tools are required to understand the process and temper the use of direct seeding. In this study, the spatio-temporal pattern of germination of P. pinea was modelled with those purposes. The resulting findings will allow us to (1) determine the main ecological variables involved in germination in the species and (2) infer adequate silvicultural alternatives. The modelling approach focuses on covariates which are readily available to forest managers. A two-step nonlinear mixed model was fitted to predict germination occurrence and abundance in P. pinea under varying climatic, environmental and stand conditions, based on a germination data set covering a 5-year period. The results obtained reveal that the process is primarily driven by climate variables. Favourable conditions for germination commonly occur in fall although the optimum window is often narrow and may not occur at all in some years. At spatial level, it would appear that germination is facilitated by high stand densities, suggesting that current felling intensity should be reduced. In accordance with other studies on P. pinea dispersal, it seems that denser stands during the regeneration period will reduce the present dependence on direct seeding

A comparative pattern of lectin-binding in the endometrial glands of the uterus and placenta of healthy buffaloes and bovines at early gestation

Water buffalo (Bubalus bubalis) and domestic cattle (Bos taurus) are closely related species. However, embryo transfer interspecies has been attempted without any success. The failure in hybrid embryo-implantation is associated with the glycocode in the maternal-fetal interface. Glycosylation patterns have been studied in different species of ruminants; however, in B. bubalis, only the binucleated cells (BNC) have been analyzed. This glycocode is essential for a successful embryo-implantation and can be defined by Lectin-Histochemistry (LHC). The aim of this study is to compare the glycosylation pattern of placenta and uterus in water buffaloes and cattle by LHC. Tissue samples of placenta and uterus from pregnant Mediterranean female water buffaloes (Buf1) and Angus cows (Bov1) were analyzed. All animals were euthanized at 98 days of gestation. LHC was carried out using twelve lectins (Con A, LCA, PSA, sWGA, PHA-e, SBA, UEA-1, WGA, RCA-1, PNA, DBA, BSA-1). The intensity of lectin binding was semiquantitatively scored using a scale of 0 (negative) to 3 (strongly positive). Difference between species was found in trophoblast layer by PSA, SWGA, PNA and BSA-1, in BNC, and in the mononuclear cells by LCA, PSA, PHA-e, DBA, BSA-1, PNA. In utero, differences in the apical cellular membrane and the secretion of glands were identified by DBA and RCA-1, and in the cytoplasm of those glandular epithelial cells by PHA-e, BSA-1, WGA, and SBA. In both species, BNC presented a strong positive reaction with DBA and SBA, a moderate response by LCA, PHA-e, BSA-1 and PNA lectin, and a low reaction by PSA, UEA-1, SWGA, WGA, Con A and RCA-1. The results found in this study suggest that although both species are closely related, glycosylation patterns in the placenta and uterus are different, thus providing a possible reason for embryo transfer not being possible between these species.EEA MercedesFil: Caspe, Sergio Gaston. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mercedes; ArgentinaFil: Konrad, Jose Luis. Universidad Nacional del Nordeste. Facultad de Ciencias Veterinarias; ArgentinaFil: Moore, Prando Dadin. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Sala, Juan Manuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Mercedes; ArgentinaFil: Lischinsky, Lilian Haydee. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Campero, Carlos Manuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Barbeito, Claudio G. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina

Oral microbiome and systemic antineoplastics in cancer treatment:a systematic review

Oral mucositis is one of the most common side effects in cancer patients receiving systemic antineoplastics. However, the underlying biological mechanisms leading to this condition are still unclear. For this reason, it has been hypothesised that systemic antineoplastics may cause an imbalance on the oral microbiota that subsequently triggers oral mucosa damage. A systematic review was performed following the PRISMA protocol and the PICO question established was: patients diagnosed with cancer, who are candidates for receiving systemic antineoplastics (P=Patients), that undergo oral microbiome determinations (I=Intervention), before and after systemic antineoplastics administration (C=Comparison), to analyse changes in the oral microbiome composition (O=Outcome). The bibliographic search was carried out in PubMed and other scientific repositories. Out of 166 obtained articles, only 5 met eligibility criteria. Acute myeloid leukaemia (AML) was the most frequent type of cancer (40 %) among the participants. Only one of the studies included a control group of healthy subjects. Heterogeneity in the protocols and approaches of the included studies hindered a detailed comparison of the outcomes. However, it was stated that a decrease in bacteria ? diversity is often associated with oral mucositis. On the other hand, fungal diversity was not associated with oral mucositis although ? diversity was lower at baseline on patients developing oral candidiasis. There is insufficient scientific evidence of oral microbiological changes in patients undergoing systemic antineoplastics. Further investigations ought to be carried out to identify microorganisms that might play a key role in the pathogenesis of oral mucosa damage in patients undergoing systemic antineoplastics

Nitric oxide-mediated oxidative damage and the progressive demise of motor neurons in ALS

Oxidative damage is a common and early feature of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Dr. Mark Smith and his colleagues have built the case for oxidative stress being a primary progenitor rather than a secondary end-stage epiphenomenon of neurodegeneration. They proposed that reactive oxygen species contribute to the “age-related cascade of neurodegeneration” whereby accumulative oxidative damage with age promotes other characteristic pathological changes in afflicted brain regions, including protein aggregation, metabolic deficiencies, and inflammation. Nitric oxide (NO) likely plays a critical role in this age-related cascade. NO is a major signaling molecule produced in the central nervous system (CNS) to modulate neurological activity through stimulating cyclic GMP synthesis. However, the same physiological concentrations of NO relevant in cellular signaling may also initiate and amplify oxidative damage by diffusion-limited reactions with superoxide (O₂[superscript •−]) to produce peroxynitrite (ONOO⁻). This is perhaps best illustrated in ALS where physiological levels of NO promote survival of motor neurons, but the same concentrations can stimulate motor neuron apoptosis and glial cell activation under pathological conditions. While these changes represent a complex mechanism involving multiple cell types in the pathogenesis of ALS, they also reveal general processes underlying neurodegeneration.Keywords: peroxynitrite, protein nitration, amyotrophic lateral sclerosis, nitric oxide, neurodegenerationKeywords: peroxynitrite, protein nitration, amyotrophic lateral sclerosis, nitric oxide, neurodegeneratio

The pathogenic role of c‑Kit+ mast cells in the spinal motor neuron‑vascular niche in ALS

Degeneration of motor neurons, glial cell reactivity, and vascular alterations in the CNS are important neuropathological features of amyotrophic lateral sclerosis (ALS). Immune cells trafficking from the blood also infiltrate the affected CNS parenchyma and contribute to neuroinflammation. Mast cells (MCs) are hematopoietic-derived immune cells whose precursors differentiate upon migration into tissues. Upon activation, MCs undergo degranulation with the ability to increase vascular permeability, orchestrate neuroinflammation and modulate the neuroimmune response. However, the prevalence, pathological significance, and pharmacology of MCs in the CNS of ALS patients remain largely unknown. In autopsy ALS spinal cords, we identified for the first time that MCs express c-Kit together with chymase, tryptase, and Cox-2 and display granular or degranulating morphology, as compared with scarce MCs in control cords. In ALS, MCs were mainly found in the niche between spinal motor neuron somas and nearby microvascular elements, and they displayed remarkable pathological abnormalities. Similarly, MCs accumulated in the motor neuron-vascular niche of ALS murine models, in the vicinity of astrocytes and motor neurons expressing the c-Kit ligand stem cell factor (SCF), suggesting an SCF/c-Kit-dependent mechanism of MC differentiation from precursors. Mechanistically, we provide evidence that fully differentiated MCs in cell cultures can be generated from the murine ALS spinal cord tissue, further supporting the presence of c-Kit+ MC precursors. Moreover, intravenous administration of bone marrow-derived c-Kit+ MC precursors infiltrated the spinal cord in ALS mice but not in controls, consistent with aberrant trafficking through a defective microvasculature. Pharmacological inhibition of c-Kit with masitinib in ALS mice reduced the MC number and the influx of MC precursors from the periphery. Our results suggest a previously unknown pathogenic mechanism triggered by MCs in the ALS motor neuron-vascular niche that might be targeted pharmacologically

Mai més i enlloc! Guia per treballar l'impacte de la Guerra Civil

Aquest document és el resultat de dos anys de col·laboració entre el Memorial Democràtic, el Museu d'Història de la ciutat de Barcelona, l'Escola de Cultura de Pau, els Centres de Recursos Pedagògics de Sants i de Ciutat Vella de Barcelona, professors i professores de centres de primària i de secundària de diverses ciutats catalanes, i del Grup d'Educació per la pau. A través del projecte "Mai més i enlloc", tots aquests actors han col·laborat per a que alumnes de primària i de secundària s'apropin a la realitat de la guerra civil, a través de l'equipament cultural del Refugi 307 del barri de Poble Sec a Barcelona

Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis

Background: In the SOD1G93A mutant rat model of amyotrophic lateral sclerosis (ALS), neuronal death and rapid paralysis progression are associated with the emergence of activated aberrant glial cells that proliferate in the degenerating spinal cord. Whether pharmacological downregulation of such aberrant glial cells will decrease motor neuron death and prolong survival is unknown. We hypothesized that proliferation of aberrant glial cells is dependent on kinase receptor activation, and therefore, the tyrosine kinase inhibitor masitinib (AB1010) could potentially control neuroinflammation in the rat model of ALS. Methods: The cellular effects of pharmacological inhibition of tyrosine kinases with masitinib were analyzed in cell cultures of microglia isolated from aged symptomatic SOD1G93A rats. To determine whether masitinib prevented the appearance of aberrant glial cells or modified post-paralysis survival, the drug was orally administered at 30 mg/kg/day starting after paralysis onset. Results: We found that masitinib selectively inhibited the tyrosine kinase receptor colony-stimulating factor 1R (CSF-1R) at nanomolar concentrations. In microglia cultures from symptomatic SOD1G93A spinal cords, masitinib prevented CSF-induced proliferation, cell migration, and the expression of inflammatory mediators. Oral administration of masitinib to SOD1G93A rats starting after paralysis onset decreased the number of aberrant glial cells, microgliosis, and motor neuron pathology in the degenerating spinal cord, relative to vehicle-treated rats. Masitinib treatment initiated 7 days after paralysis onset prolonged post-paralysis survival by 40 %. Conclusions: These data show that masitinib is capable of controlling microgliosis and the emergence/expansion of aberrant glial cells, thus providing a strong biological rationale for its use to control neuroinflammation in ALS. Remarkably, masitinib significantly prolonged survival when delivered after paralysis onset, an unprecedented effect in preclinical models of ALS, and therefore appears well-suited for treating ALS.Agencia Nacional de Investigación e Innovació