Selection of Tumor-Specific Cytotoxic T Lymphocytes in Acute Myeloid Leukemia Patients Through the Identification of T-Cells Capable to Establish Stable Interactions With the Leukemic Cells: “Doublet Technology”

The relevance of the immune system in cancer has long been studied. Autologous adoptive T cell therapies, based on the use of tumor infiltrating lymphocytes (TILs), have made great progress in recent years for the treatment of solid tumors, especially melanoma. However, further work is needed to isolate tumor-reactive T cells among patients diagnosed with hematologic malignancies. The dynamics of the interaction between T cells and antigen presenting cells (APC) dictate the quality of the immune responses. While stable joints between target cells and T lymphocytes lead to the induction of T cell activation and immune response, brief contacts contribute to the induction of immune-tolerance. Taking advantage of the strong interaction between target cell and activated T-cells, we show the feasibility to identify and isolate tumor-specific cytotoxic T lymphocytes (CTLs) from acute myeloid leukemia (AML) patients by flow cytometry. Using this technology, CTLs bound through T cell receptor (TCR) to tumor cells can be identified in peripheral blood and bone marrow and subsequently selected and isolated by FACS-based cell sorting. These CTLs display higher percentage of effector cells and marked cytotoxic activity against AML blasts. In conclusion, we have developed a new procedure to identify and select specific cytotoxic T cells in patients diagnosed with acute myeloid leukemia.Instituto de Salud Carlos III PFIS-FI12/00189Instituto de Salud Carlos III ISCIII PI14/02074Instituto de Salud Carlos III PI11/02366Instituto de Salud Carlos III PI17/02177European Union (ERDF/ESF, Investing in your future)CIBER CB16/12/0048

Sensitivity of hematopoietic stem cells to mitochondrial dysfunction by SdhD gene deletion

It is established that hematopoietic stem cells (HSC) in the hypoxic bone marrow have adapted their metabolism to oxygen-limiting conditions. This adaptation includes suppression of mitochondrial activity, induction of anerobic glycolysis, and activation of hypoxia-inducible transcription factor 1α (Hif1α)-dependent gene expression. During progression of hematopoiesis, a metabolic switch towards mitochondrial oxidative phosphorylation is observed, making this organelle essential for determining cell fate choice in bone marrow. However, given that HSC metabolism is essentially oxygen-independent, it is still unclear whether functional mitochondria are absolutely required for their survival. To assess the actual dependency of these undifferentiated cells on mitochondrial function, we have performed an analysis of the hematopoiesis in a mouse mutant, named SDHD-ESR, with inducible deletion of the mitochondrial protein-encoding SdhD gene. This gene encodes one of the subunits of the mitochondrial complex II (MCII). In this study, we demonstrate that, in contrast to what has been previously established, survival of HSC, and also myeloid and B-lymphoid progenitors, depends on proper mitochondrial activity. In addition, gene expression analysis of these hematopoietic lineages in SDHD-ESR mutants calls into question the proposed activation of Hif1α in response to MCII dysfunction.Ministerio de Ciencia e Innovación SAF2009-06970Junta de Andalucía CTS-4589Instituto de Salud Carlos III PI-0355-201

Combined treatment of graft versus host disease using donor regulatory T cells and ruxolitinib

Donor derived regulatory T lymphocytes and the JAK1/2 kinase inhibitor ruxolitinib are currently being evaluated as therapeutic options in the treatment of chronic graft versus host disease (cGvHD). In this work, we aimed to determine if the combined use of both agents can exert a synergistic efect in the treatment of GvHD. For this purpose, we studied the efect of this combination both in vitro and in a GvHD mouse model. Our results show that ruxolitinib favors the ratio of thymic regulatory T cells to conventional T cells in culture, without afecting the suppressive capacity of these Treg. The combination of ruxolitinib with Treg showed a higher efcacy as compared to each single treatment alone in our GvHD mouse model in terms of GvHD incidence, severity and survival without hampering graft versus leukemia efect. This benefcial efect correlated with the detection in the bone marrow of recipient mice of the infused donor allogeneic Treg after the adoptive transfer

Combined treatment of graft versus host disease using donor regulatory T cells and ruxolitinib

[EN] Donor derived regulatory T lymphocytes and the JAK1/2 kinase inhibitor ruxolitinib are currently being evaluated as therapeutic options in the treatment of chronic graft versus host disease (cGvHD). In this work, we aimed to determine if the combined use of both agents can exert a synergistic effect in the treatment of GvHD. For this purpose, we studied the effect of this combination both in vitro and in a GvHD mouse model. Our results show that ruxolitinib favors the ratio of thymic regulatory T cells to conventional T cells in culture, without affecting the suppressive capacity of these Treg. The combination of ruxolitinib with Treg showed a higher efficacy as compared to each single treatment alone in our GvHD mouse model in terms of GvHD incidence, severity and survival without hampering graft versus leukemia effect. This beneficial effect correlated with the detection in the bone marrow of recipient mice of the infused donor allogeneic Treg after the adoptive transfer.SITis study is partially funded by NovartisThe authors thank Dr. João Lacerda for critical reading of the manuscript. This work was supported by grants from Novartis and the Andalusian Regional Government (P18-RT-4047, PI-0052-2018). A.R.G. and J.A.P.S. are members of CIBERONC (CB16/12/00480) and TerCel (16/0011/0035). J.V. is member of CIBERNED (CB06/05/0027). A.R.G. is funded by a Grant of the University of Seville (US-1380874) co-funded by the European Regional Development Fund (ERDF)

Hugo Chávez: una década en el poder

Una década de Hugo Chávez Frías y su proyecto político en Venezuela trajo consigo un cambio de paradigmas que llama la atención de la sociedad en general. Este libro es el resultado del esfuerzo conjunto de un grupo de académicos de distintas nacionalidades que desde sus líneas de investigación realizan análisis que le brindan al lector elementos para comprender de manera global lo que significa una década de gobierno del Presidente Chávez en Venezuela.Este libro es el resultado del esfuerzo conjunto de un grupo de académicos de distintas nacionalidades que desde sus líneas de investigación realizan análisis que le brindan al lector elementos para comprender de manera global lo que significa una década de gobierno del Presidente Chávez en Venezuela

INNOVA Research Journal

La clase de matemáticas está en un proceso de evolución, las clases tradicionales centradas en el profesor van perdiendo vigencia en la educación ecuatoriana, dando paso a clases que priorizan al estudiante y sus aprendizajes. Tradicionalmente el docente de matemáticas ha tenido formación profesional en áreas técnicas y poca capacitación en aspectos pedagógicos que le den habilidades para llevar adelante una clase fundada en paradigmas constructivistas del aprendizaje, centrados en el estudiante y la calidad de sus aprendizajes. Una clase constructivista de matemáticas implica tener un estudiante con una visión diferente a su formación tradicional, debe estar motivado por alcanzar aprendizajes significativos, para esto debe ser capaz de investigar, analizar, reflexionar, plantear soluciones creativas, resolver situaciones del contexto, formado en valores y que aporta al crecimiento de la sociedad

INNOVA Research Journal

la Universidad Internacional del Ecuador (Sede Loja) en conjunto con la Fundación de Conservación Jocotoco, desde agosto de 2015, vienen desarrollando actividades de cuidado del tapir de montaña (Tapirus pinchaque) y los hábitats en los que se desarrolla en Los Andes del sur de Ecuador, en ambientes de bosque nublado y páramos de la Reserva Biológica Tapichalaca y zonas colindantes. Para ello se propuso la realización del presente proyecto que busca establecer un sistema de monitoreo e investigación de esta especie bandera con fines ecoturísticos, así como también para apoyar la capacitación en educación ambiental; mediante un diagnóstico preliminar y la implementación de un sistema de investigación y monitoreo de los especímenes mediante cámaras trampa y observación directa, con el fin de generar datos poblacionales e imágenes de esta especie en su hábitat natural e identificar los sitios más idóneos para observar estos animales en actividades de ecoturismo; se busca además crear cartillas y cuentos didácticos que describan los principales aspectos ecológicos del tapir de montaña, sin descuidar el desarrollo de propuestas de conservación, acordes con los objetivos del milenio, las metas estratégicas de los gobiernos autónomos descentralizados parroquiales y provinciales locales y los Planes de Manejo de los Parques Nacionales Podocarpus y Yacuri

Disclination dipoles are the Holy Grail for high temperature superplasticity in ceramics

A model for high-temperature plasticity of polycrystals controlled by disclination dipoles is proposed that predict a parabolic dependence of the strain rate versus the applied stress. The presence of a precise stationary disclination density explains the origin of plasticity without microstructural invariance, commonly known as superplasticity. The disclination mechanism is universal, although other processes, such as dislocation glide, are superposed to this one in many systems such as metals or metallic alloys. While, in ceramics it is likely to be the only operative mechanism. Activation of disclination dipoles is a necessary condition for plasticity and sufficient one for superplastic yielding.This work was supported by the Ministerio de Economía y Competitividad (Government of Spain) and FEDER Funds under Grants No. MAT2015-71411-R. BMM wants to acknowledge the support of the Spanish MINECO by means of a “Juan de la Cierva-Incorporación” fellowship during her sabbatical stay in Zaragoza and also the funding by the ‘Junta de Andalucía’ Regional Government through the project P18-RTJ-1972.Peer reviewe

Fungos associados a podridao-da-coroa em frutos de banana organica (Musa spp. L.) em Piura, Peru

The department of Piura is the principal banana-producing zone in Peru, sharing 87% of exportations. In this zone, one of the most important postharvest diseases is crown rot. The economic loses attributed to this disease are estimated to be between 25 and 30% of organic bananas exported. The objective of this study was to identify the causal agents associated with this disease. Samples taken refrigerated fruit from the areas of Querecotillo, Salitral and Mallares were taken and selected after the fact. Thielaviopsis paradoxa, Lasiodiplodia theobromae, Colletotrichum musae and Fusarium verticilloides. In order to demonstrate the pathogenicity of the isolated species, inoculations were given in the area of the crown of the fruit on healthy bananas. These fungi caused symptoms of infection in different proportions, concluding that crown rot is a disease with a complex etiology.El departamento de Piura es la principal zona productora de banano orgánico para la exportación en Perú, participando con el 87% del volumen de las exportaciones. En esta zona una de las enfermedades más importantes en postcosecha es la pudrición de la corona del fruto, las pérdidas económicas por esta enfermedad se han estimado entre el 25 y el 30% de la fruta exportada. El objetivo del presente estudio fue identificar los agentes causales asociados a esta enfermedad. Se evaluaron muestras de frutos de las zonas de Querecotillo, Salitral y Mallares empacados en cámaras de refrigeración, posteriormente se seleccionaron muestras con síntomas de pudrición de la corona, realizándose siembras de tejido enfermo en medio PDA+estreptomicina. Se aislaron e identificaron a Thielaviopsis paradoxa, Lasiodiplodia theobromae, Colletotrichum musae y Fusarium verticillioides. Para demostrar la patogenecidad de las especies aisladas, se realizaron inoculaciones sobre la zona de la corona en frutos sanos de banano. Todos estos hongos causaron síntomas de infección en diferentes proporciones, concluyéndose que la pudrición de la corona es una enfermedad de etiología compleja.O departamento de Piura e a principal regiao produtora de banana organica para exportacao no Peru, participando com 87% do volume de exportacoes. Nesta area, uma das mais importantes doencas pos-colheita e a podridao-da-coroa do fruto, as perdas economicas desta doenca sao estimadas entre 25 e 30% dos frutos exportados. O objetivo deste estudo foi identificar os agentes causadores associados a esta doenca. Amostras de frutas foram avaliadas nas areas de Querecotillo, Salitral e Mallares e embaladas em cámaras de refrigeracao, posteriormente foram selecionadas amostras com sintomas de podridao-dacoroa, realizando plantios do tecido doentes em meio PDA+estreptomicina. Foram isolados e identificados Thielaviopsis paradoxa, Lasiodiplodia theobromae, Colletotrichum musae e Fusarium verticillioides. Para demonstrar a patogenicidade das especies isoladas, foram realizadas inoculacoes na coroa de frutos de bananas saudaveis. Todos estes fungos causaram sintomas da infeccao em diferentes proporcoes, concluindo-se que a podridao-da-coroa e uma doenca de etiología complexa

Hongos asociados a la pudrición de la corona en frutos de banano orgánico (Musa spp. L.) en Piura, Perú

The department of Piura is the principal banana-producing zone in Peru, sharing 87% of exportations. In this zone, one of the most important postharvest diseases is crown rot. The economic loses attributed to this disease are estimated to be between 25 and 30% of organic bananas exported. The objective of this study was to identify the causal agents associated with this disease. Samples taken refrigerated fruit from the areas of Querecotillo, Salitral and Mallares were taken and selected after the fact. Thielaviopsis paradoxa, Lasiodiplodia theobromae, Colletotrichum musae and Fusarium verticilloides. In order to demonstrate the pathogenicity of the isolated species, inoculations were given in the area of the crown of the fruit on healthy bananas. These fungi caused symptoms of infection in different proportions, concluding that crown rot is a disease with a complex etiology.O departamento de Piura e a principal regiao produtora de banana organica para exportacao no Peru, participando com 87% do volume de exportacoes. Nesta area, uma das mais importantes doencas pos-colheita e a podridao-da-coroa do fruto, as perdas economicas desta doenca sao estimadas entre 25 e 30% dos frutos exportados. O objetivo deste estudo foi identificar os agentes causadores associados a esta doenca. Amostras de frutas foram avaliadas nas areas de Querecotillo, Salitral e Mallares e embaladas em cámaras de refrigeracao, posteriormente foram selecionadas amostras com sintomas de podridao-dacoroa, realizando plantios do tecido doentes em meio PDA+estreptomicina. Foram isolados e identificados Thielaviopsis paradoxa, Lasiodiplodia theobromae, Colletotrichum musae e Fusarium verticillioides. Para demonstrar a patogenicidade das especies isoladas, foram realizadas inoculacoes na coroa de frutos de bananas saudaveis. Todos estes fungos causaram sintomas da infeccao em diferentes proporcoes, concluindo-se que a podridao-da-coroa e uma doenca de etiología complexa.El departamento de Piura es la principal zona productora de banano orgánico para la exportación en Perú, participando con el 87% del volumen de las exportaciones. En esta zona una de las enfermedades más importantes en postcosecha es la pudrición de la corona del fruto, las pérdidas económicas por esta enfermedad se han estimado entre el 25 y el 30% de la fruta exportada. El objetivo del presente estudio fue identificar los agentes causales asociados a esta enfermedad. Se evaluaron muestras de frutos de las zonas de Querecotillo, Salitral y Mallares empacados en cámaras de refrigeración, posteriormente se seleccionaron muestras con síntomas de pudrición de la corona, realizándose siembras de tejido enfermo en medio PDA+estreptomicina. Se aislaron e identificaron a Thielaviopsis paradoxa, Lasiodiplodia theobromae, Colletotrichum musae y Fusarium verticillioides. Para demostrar la patogenecidad de las especies aisladas, se realizaron inoculaciones sobre la zona de la corona en frutos sanos de banano. Todos estos hongos causaron síntomas de infección en diferentes proporciones, concluyéndose que la pudrición de la corona es una enfermedad de etiología compleja