Ischemia/reperfusion increases the oxidized state of specific cys residues in proteins from mitochondrial supopulation from rat miocardium that are protected by ischemia preconditioning

Comunicaciones a congreso

Consultoría Financiera para PYMES en Costa Rica.

Proyecto de graduación (Licenciatura en Administración de Empresas. Enfasis en Finanzas) Instituto Tecnológico de Costa Rica, Escuela de Administración de Empresas, 2012.El objetivo general de esta investigación es determinar si estos servicios de Consultoría Financiera satisfacen los requerimientos de capacitación y asesoría que tienen actualmente las PYMES en Costa Rica. Para recabar la información en este proyecto se utilizaron las técnicas de entrevista y cuestionario. Se realizó una entrevista a 12 Empresas Consultoras con el fin de conocer con amplitud el servicio que brinda la Consultoría Financiera a las PYMES de Costa Rica. Adicionalmente, se realizaron 111 cuestionarios a PYMES del Área Metropolitana para obtener información y lograr determinar las principales necesidades que poseen, evaluar el grado de aceptación con respecto a los servicios de las Consultorías Financieras y analizar los efectos de la Consultoría Financiera en las PYMES que han contratado estos servicios. Una vez procesada la información y realizado el análisis, la investigación revela que existe una buena percepción de las PYMES hacia la Consultoría Financiera y su conciencia de las ventajas que ésta podría ofrecerle. No obstante, la gran cantidad de PYMES que no ha contratado Consultoría Financiera, ven en su limitado presupuesto y el desconocimiento del servicio, dos grandes obstáculos para agregar ésta herramienta a su operativa

Role of alkali-cyano group interaction in g-C3N4 based catalysts for hydrogen photo-production

Carbon nitride based materials incorporating K and Na alkali ions were used as support(s) to deposit platinum. The systems were tested in the photo-production of hydrogen using methanol as a sacrificial molecule. Tests under UV and sunlight-type illumination conditions showed an important promoting effect of the alkali ions irrespective of the illumination source characteristics. The measurement of the quantum efficiency was used to quantitatively assess the performance of the catalysts. Outstanding results were obtained, particularly under sunlight illumination. A complete characterization study of the materials was carried out to establish a structure-activity link. This link correlates catalytic activity with the capture of charge carrier species by surface cyano groups directly associated with the presence of alkali ions at the carbon nitride componen

Transgene codon usage drives viral fitness and therapeutic efficacy in oncolytic adenoviruses.

Arming oncolytic adenoviruses with therapeutic transgenes is a well-established strategy for multimodal tumour attack. However, this strategy sometimes leads to unexpected attenuated viral replication and a loss of oncolytic effects, preventing these viruses from reaching the clinic. Previous work has shown that altering codon usage in viral genes can hamper viral fitness. Here, we have analysed how transgene codon usage impacts viral replication and oncolytic activity. We observe that, although transgenes with optimized codons show high expression levels at the first round of infection, they impair viral fitness and are therefore not expressed in a sustained manner. Conversely, transgenes encoded by suboptimal codons do not compromise viral replication and are thus stably expressed over time, allowing a greater oncolytic activity both in vitro and in vivo. Altogether, our work shows that fine-tuning codon usage leads to a concerted optimization of transgene expression and viral replication paving the way for the rational design of more efficacious oncolytic therapies

Stereotactic Body Radiotherapy: is less fractionation more effective in adrenal and renal malignant lesions?

Purpose: Stereotactic body radiotherapy (SBRT) has become an excellent non-invasive alternative for many patients with primary renal cell carcinoma (RCC) and adrenal malignancies (AM). The aims of this study were to analyse how tumor-, patient- and treatment-related factors may influence the outcomes and side effects of SBRT and to assess its benefits as an alternative to surgery. Methods: This retrospective, multicenter study included 25 lesions in 23 patients treated with SBRT using different devices (LINAC, CyberKnife® and Tomotherapy®). A multivariate linear regression was used for the statistical study. Results: Local control time was higher than six months in more than 87% of patients and treatment response was complete for 73.68%. There was an overall 2-year survival of 40% and none of the deaths were secondary to renal or adrenal local progression. Patients treated with lower total radiation dose (mean [m] = 55 Gy) but less fractions with more dose per fraction (> 8.5 Gy) showed better outcome. Patients with previous chemotherapy and surgery treatments also showed higher complete response and disease-free survival (> 6 months). Conclusions: This study highlights the importance of ultra-hypofractionated regimens with higher doses per session. Thus, the referral of patients with RCC and AM to Radiotherapy and Oncology departments should be encouraged supporting the role of SBRT as a minimally invasive and outpatient treatment

Ischemic preconditioning and ischaemia-reperfusion: key role of connexin43 and mitochondrial complexes

Comunicaciones a congreso

HDAC6 regulates the dynamics of lytic granules in cytotoxic T lymphocytes

Journal of Cell Science.HDAC6 is a tubulin deacetylase involved in many cellular functions related to cytoskeleton dynamics, including cell migration and autophagy. In addition, HDAC6 affects antigen-dependent CD4+ T cell activation. In this study,we show that HDAC6 contributes to the cytotoxic function of CD8+ T cells. Immunization studies revealed defective cytotoxic activity in vivo in the absence of HDAC6. Adoptive transfer of wild-type or Hdac6-/- CD8+ T cells to Rag1-/- mice demonstrated specific impairment inCD8+ T cell responses against vaccinia infection. Mechanistically, HDAC6-deficient cytotoxic T lymphocytes (CTLs) showed defective in vitro cytolytic activity related to altered dynamics of lytic granules, inhibited kinesin-1-dynactin-mediated terminal transport of lytic granules to the immune synapse and deficient exocytosis, but not to target cell recognition, T cell receptor (TCR) activation or interferon (IFN)γ production. Our results establish HDAC6 as an effectorof theimmune cytotoxic response that acts byaffecting the dynamics, transport and secretion of lytic granules by CTLs.This work was supported by the Ministerio de Economı́a y competitividad (MINECO) [grant number SAF2014-55579-R]; Comunidad Autónoma de Madrid (CAM) [grant number INDISNET01592006]; Instituto de Salud Carlos III y Fondo Europeo de Desarrollo Regional (FEDER) [grant numbers BIOMID-PIE13/041 and RD12/0042/0056]; European Research Council (ERC) [grant number ERC-2011-AdG 294340- GENTRIS

A data mining based clinical decision support system for survival in lung cancer

Background: A clinical decision support system (CDSS) has been designed to predict the outcome (overall survival) by extracting and analyzing information from routine clinical activity as a complement to clinical guidelines in lung cancer patients. Materials and methods: Prospective multicenter data from 543 consecutive (2013–2017) lung cancer patients with 1167 variables were used for development of the CDSS. Data Mining analyses were based on the XGBoost and Generalized Linear Models algorithms. The predictions from guidelines and the CDSS proposed were compared. Results: Overall, the highest (> 0.90) areas under the receiver-operating characteristics curve AUCs for predicting survival were obtained for small cell lung cancer patients. The AUCs for predicting survival using basic items included in the guidelines were mostly below 0.70 while those obtained using the CDSS were mostly above 0.70. The vast majority of comparisons between the guideline and CDSS AUCs were statistically significant (p < 0.05). For instance, using the guidelines, the AUC for predicting survival was 0.60 while the predictive power of the CDSS enhanced the AUC up to 0.84 (p = 0.0009). In terms of histology, there was only a statistically significant difference when comparing the AUCs of small cell lung cancer patients (0.96) and all lung cancer patients with longer (≥ 18 months) follow up (0.80; p < 0.001). Conclusions: The CDSS successfully showed potential for enhancing prediction of survival. The CDSS could assist physicians in formulating evidence-based management advice in patients with lung cancer, guiding an individualized discussion according to prognosis.Instituto de Salud Carlos III PI16/02104Junta de Andalucía PIN-0476-2017Ministerio de Economía y Competitividad FPAP13-1E-242

Creación de Itinerarios virtuales para interpretar el paisaje II

El proyecto pretende diseñar itinerarios virtuales que permitan interpretar el paisaje desde un punto de vista transversal y multidisciplinar. Además se elaborará una guía docente con la que los estudiantes creen otros itinerarios fuera del aula

Transgenic Mouse Models of Alzheimer’s Disease: An Integrative Analysis

Alzheimer’s disease (AD) constitutes the most prominent form of dementia among elderly individuals worldwide. Disease modeling using murine transgenic mice was first initiated thanks to the discovery of heritable mutations in amyloid precursor protein (APP) and presenilins (PS) genes. However, due to the repeated failure of translational applications from animal models to human patients, along with the recent advances in genetic susceptibility and our current understanding on disease biology, these models have evolved over time in an attempt to better reproduce the complexity of this devastating disease and improve their applicability. In this review, we provide a comprehensive overview about the major pathological elements of human AD (plaques, tauopathy, synaptic damage, neuronal death, neuroinflammation and glial dysfunction), discussing the knowledge that available mouse models have provided about the mechanisms underlying human disease. Moreover, we highlight the pros and cons of current models, and the revolution offered by the concomitant use of transgenic mice and omics technologies that may lead to a more rapid improvement of the present modeling batterThis research was funded by INSTITUTO DE SALUD CARLOS III (ISCiii) of Spain, cofinanced by FEDER funds from European Union, through grants PI21/00915 (to AG) and PI21/00914 (to JV); by JUNTA DE ANDALUCIA CONSEJERÍA DE ECONOMÍA Y CONOCIMIENTO through grants UMA18-FEDERJA-211 (to AG), UMA20-FEDERJA-104 (to IMG), P18-RT-2233 (to AG) and US-1262734 (to JV) co-financed by Programa Operativo FEDER 2014–2020 and CONSEJERIA DE SALUD grant PI-0276-2018 (to JAGL); by SPANISH MINISTER OF SCIENCE AND INNOVATION grant PID2019-108911RA-100 (to DBV), BEATRIZ GALINDO PROGRAM BAGAL18/00052 (to DBV), Alzheimer Association AARG-22-928219 (to DBV), grant PID2019-107090RA-100 (to IMG) and RAMON Y CAJAL PROGRAM RYC-2017-21879 (to IMG); and by MALAGA UNIVERSITY grant B1-2019_07 (to ESM), grant B1-2020_04 (to JAGL), grant B1-2019_06 (to IMG) and NASARD grant 27565 2018 (to IMG). M.M.-O. held a predoctoral contract from Malaga University, J.J.F.-V. held a postdoctoral contract from Malaga University, and E.S.-M. a postdoctoral contract (DOC_00251) from Junta de Andalucia. Partial funding for open access charge: Universidad de Málaga