Hemoglobinuria paroxística nocturna: estudio de la enfermedad y sus tratamientos

Paroxysmal nocturnal hemoglobinuria (PNH), term established by Enneking in 1925, is a rare, clonal, and acquired disease of the hematopoietic stem cells. Generally, it starts with a mutation in the PIG -A gene, causing a deficiency of membrane proteins, such as CD55 and CD59. However, recent studies treveal that the clonal architecture of the disease is far more complex. Due to the deficiency of these proteins, there is an uncontrolled activation of the complement, which is associated with hemolysis and other clinical manifestations very variable among patients. PNH is also associated with aplastic anemia, in fact, it has been observed that both diseases are closely related, being able to derive one from the other over time. Because of the great variability of symptoms, the diagnosis of the disease has always been an arduous task. But this paper study a recent technique that has facilitated this work: flow cytometry. Until recently, there were only two main therapies for patients with PNH; allogeneic bone marrow transplantation and supportive treatment against symptoms. But at the beginning of the millennium, Eculizumab, marketed as Soliris®, a huma nized anti -C5 monoclonal antibody, protein of the complement system, was introduced, which has been a major advance in the treatment of the disease. As a result of its discovery, new strategies of complement inhibition have been investigated. Due to the hi gh morbimortality and the great impact on patients with PNH, the latest advances in research during the last decade could not be more encouragingLa Hemoglobinuria Paroxística N octurna (HPN), término establecido en 1925 por Enneking, es una enfermedad rara, clonal y adquirida de las células madr e hematopoyéticas. Generalmente se inicia con una mutación en el gen PIG -A, causando una deficiencia de proteínas membranales, como CD55 y CD59. Sin embargo, estudios más recientes ponen de manifiesto que la arquitectura clonal de la enfermedad es bastante más compleja. Debido a la deficiencia de dichas proteínas, se produce una activación descontrolada del complement o, que se asocia a hemó lisis y a otras manifestaciones clínicas muy variables entre pacientes. La HPN también se asocia a la anemia aplásica, de hecho, se ha observado que ambas enfermedades están estrechamente relacionadas, pudiendo derivar una en la otra con el tiempo. A causa de la gran variabilidad de síntomas, el diagnóstico de la enfermedad ha sido siempre una ardua tarea. En este ensayo se estudia una técnica recien te que ha facilitado esta labor, la citometría de flujo. Hasta hace poco, solo existí an dos terapias principales para los pacientes con HPN; el trasplante alogénico de médula ósea y el tratamiento de apoyo contra los síntomas. Pero a principios del milenio, se introdujo en el esquema terapéutico el Eculizumab, comercializado como Soliris®, un anticuerpo monoclonal humanizado anti -C5, proteína del sistema del complemento. Ha constituido un avance primordial para el tratamiento de la enfermedad, a raíz de su descubrimiento, se ha comenzado a investigar nuevas estrategias de inhibición del complemento. Debido a la alta morbimortalidad y el gran impacto que supone la HPN en quien la padece, que se esté avanzando tanto en la última década resulta alentadorUniversidad de Sevilla. Grado en Farmaci

Epidemiological modeling of Trypanosoma cruzi: Low stercorarian transmission and failure of host adaptive immunity explain the frequency of mixed infections in humans

People living in areas with active vector-borne transmission of Chagas disease have multiple contacts with its causative agent, Trypanosoma cruzi. Reinfections by T. cruzi are possible at least in animal models leading to lower or even hardly detectable parasitaemia. In humans, although reinfections are thought to have major public health implications by increasing the risk of chronic manifestations of the disease, there is little quantitative knowledge about their frequency and the timing of parasite re-inoculation in the course of the disease. Here, we implemented stochastic agent-based models i) to estimate the rate of re-inoculation in humans and ii) to assess how frequent are reinfections during the acute and chronic stages of the disease according to alternative hypotheses on the adaptive immune response following a primary infection. By using a hybrid genetic algorithm, the models were fitted to epidemiological data of Argentinean rural villages where mixed infections by different genotypes of T. cruzi reach 56% in humans. To explain this percentage, the best model predicted 0.032 (0.008–0.042) annual reinfections per individual with 98.4% of them occurring in the chronic phase. In addition, the parasite escapes to the adaptive immune response mounted after the primary infection in at least 20% of the events of re-inoculation. With these low annual rates, the risks of reinfection during the typically long chronic stage of the disease stand around 14% (4%-18%) and 60% (21%-70%) after 5 and 30 years, with most individuals being re-infected 1–3 times overall. These low rates are better explained by the weak efficiency of the stercorarian mode of transmission than a highly efficient adaptive immune response. Those estimates are of particular interest for vaccine development and for our understanding of the higher risk of chronic disease manifestations suffered by infected people living in endemic areas.Fil: Tomasini, Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Ragone, Paula Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Gourbière, Sébastien. Université de Perpignan Via Domitia; FranciaFil: Aparicio, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Investigaciones en Energia No Convencional. Universidad Nacional de Salta. Facultad de Ciencias Exactas. Departamento de Física. Instituto de Investigaciones en Energia No Convencional; ArgentinaFil: Diosque, Patricio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; Argentin

Chiral nanotubes self-assembled from discrete non-covalent macrocycles

Many strategies have been used to construct supramolecular hollow tubes, including helical folding of oligomers, bundling of rod-like structures, rolling-up of sheets and stacking of covalent cycles. On the other hand, controlling chirality at the supramolecular level continues attracting much interest because of its implications in future applications of porous systems. This review article covers the main examples in the literature that use simple molecular structures as chiral units for precise assembly into discrete non-covalent cyclic structures that are able to form chiral supramolecular tubular system

Estudi d’un pretractament aerobi per a la degradació de compostos lignocel·lulòsics involucrats en la digestió anaeròbica dels residus municipals

Treballs Finals de Grau d'Enginyeria Química, Facultat de Química, Universitat de Barcelona, Curs: 2013-2014, Tutor: Joan Mata ÁlvarezThe introduction of anaerobic digestion (AD) for the treatment of the organic matter, such as the organic fraction of municipal solid waste (OFMSW), nowadays is getting more interesting. The main difficulty in the treatment of this waste fraction is the hydrolysis step because of the complexity of organic matter. To avoid these problems, many pretreatments are used in order to increase the solubilization by breaking complex molecules into simple monomers, and to improve the efficiency of AD due to increase the hydrolysis, which is the rate-limiting step. In this project, a biological pretreatment is used to increase the hydrolytic step by using mature compost. The compost fermentative bacteria may break the complex molecules and/or the lignocellulosic materials by means of a fast organic matter solubilization of OFMSW and of bagasse. The results from precomposting the OFMSW indicate that the best conditions of organic matter solubilization were 10% compost and 1 day. Increments of biomethane production of approximately 30% can be achieved in these conditions. A preliminary study of the economic viability of the process shows that these results can be carried out the precomposting on an industrial scale. In the case of bagasse, precomposting mean a decrease in the results so, for this kind of materials with a high soluble fraction composed by very degradable compounds, such as sugars, this pretreatment is not a good option

Heregulin Activity Assays for Residual Testing of Cell Therapy Products

Background: Heregulin is a ligand for the protooncogene product ErbB/HER that acts as a key mitogenic factor for human Schwann cells (hSCs). Heregulin is required for sustained hSC growth in vitro but must be thoroughly removed before cell collection for transplantation due to potential safety concerns. The goal of this study was to develop simple cell-based assays to assess the effectiveness of heregulin addition to and removal from aliquots of hSC culture medium. These bioassays were based on the capacity of a β1-heregulin peptide to elicit ErbB/HER receptor signaling in adherent ErbB2+/ErbB3+ cells. Results: Western blotting was used to measure the activity of three different β1-heregulin/ErbB-activated kinases (ErbB3/HER3, ERK/MAPK and Akt/PKB) using phospho-specific antibodies against key activating residues. The duration, dose-dependency and specificity of β1-heregulin-initiated kinase phosphorylation were investigated, and controls were implemented for assay optimization and reproducibility to detect β1-heregulin activity in the nanomolar range. Results from these assays showed that the culture medium from transplantable hSCs elicited no detectable activation of the aforementioned kinases in independent rounds of testing, indicating that the implemented measures can ensure that the final hSC product is devoid of bioactive β1-heregulin molecules prior to transplantation. Conclusions: These assays may be valuable to detect impurities such as undefined soluble factors or factors for which other biochemical or biological assays are not yet available. Our workflow can be modified as necessary to determine the presence of ErbB/HER, ERK, and Akt activators other than β1-heregulin using native samples, such as fresh isolates from cell- or tissue extracts in addition to culture medium.Fil: Monje, Paula. Indiana University. School Of Medicine.; Estados UnidosFil: Bacallao, Ketty. Miami University. School Of Medicine; Estados UnidosFil: Aparicio, Gabriela Inés. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Biotecnológicas; Argentina. Indiana University. School Of Medicine.; Estados UnidosFil: Lalwani, Anil. Cell and Gene Therapy CMC and Regulatory Advisor; Estados Unido

Twisting the Baum-Connes morphism by a non-unitary representation

Let G be a locally compact group and rho a non-unitary finite dimensional representation of G. We consider tensor products of rho by some unitary representations of G in order to define two Banach algebras analogous to the group C*-algebras, C*(G) and C*_r(G). We calculate the K-theory of such algebras for a large class of groups satisfying the Baum-Connes conjecture.Comment: 40 pages, in frenc

Escuela de Liderazgo Joven en Tuluá Valle

No aplicaLa innovación social, nace de la necesidad de mejorar las condiciones sociales o a partir de las problemáticas de un grupo. La relación entre estas, es también mejorar la forma de hacer las cosas, que sea sostenible y que en sí genere un beneficio para las comunidades, lo que ha dado lugar para crear, innovar y enfrentar problemáticas. Es con base a la perspectiva propia y social de la fundación, fomentar la creación de nuevas formas de generar bienestar; además, de reinventar la gestión pública de manera que las metodologías generen alcances, capacidades de sostenimiento y mejoramiento para un bien común. Enfocada en esta ocasión desde la psicología del liderazgo y como proyecto esencial de la organización; Fundación ONG la Red, permite la apertura de un trabajo de articulación en temas de fortalecimiento de la participación juvenil en el centro del Valle del Cauca y fomentando los gobiernos escolares; por medio de dinámicas culturales y sociales, que permiten ampliar el conocimiento y la intervención de estos jóvenes en políticas públicas.Social innovation arises from the need to improve social conditions or from the problems of a group. The relationship between these is also to improve the way of doing things, which is sustainable and which in itself generates a benefit for the communities, which has given rise to creating, innovating and facing problems. It is based on the foundation's own and social perspective, to promote the creation of new ways to generate well-being; In addition, to reinvent public management so that methodologies generate scope, sustainment capabilities and improvement for a common good. Focused on this occasion from the psychology of leadership and as an essential project of the organization, Fundación NGO la Red, allows the opening of articulation work on issues of strengthening youth participation in the center of Valle del Cauca and promoting school governments ; through cultural and social dynamics, which allow expanding the knowledge and intervention of these young people in public policies