Dinámica de HMGB1 durante la formación de trampas extracelulares de neutrófilos inducida con suero de pacientes con artritis reumatoide

La artritis reumatoide (AR) es una enfermedad crónica, inflamatoria sistémica que afecta principalmente a las articulaciones sinoviales periféricas que conduce a la destrucción del cartílago, erosión ósea y deformidad articular. La inflamación sinovial se caracteriza por infiltración leucocitaria, los más abundantes son los neutrófilos, durante su activación incrementan la producción de especies reactivas de oxígeno, con ello se libera el calcio intracelular, se activan enzimas que finalmente conducen a la formación de trampas extracelulares de neutrófilos (NET´s). Durante la liberación de NETs se liberan patrones moleculares asociados a daño, entre ellos HMGB1 (High mobility group box 1). Una proteína nuclear que en el espacio nuclear actúa como alarmina incrementando la respuesta inflamatoria. Evaluamos la dinámica de HMGB1 durante la formación de trampas extracelulares de neutrófilos inducida con suero de pacientes con AR y evaluar su relación con diversos marcadores de actividad de la enfermedad característicos del proceso inflamatorio en artritis reumatoide. Demostramos que HMGB1 es liberada al espacio extracelular durante la inducción de NETs con suero de pacientes con AR, los pacientes con AR presentan incremento en la expresión relativa de HMGB1 y se encuentra asociada a las características clínicas de los pacientes con AR

Dinámica de HMGB1 durante la formación de trampas extracelulares de neutrófilos inducida con suero de pacientes con artritis reumatoide

La artritis reumatoide (AR) es una enfermedad crónica, inflamatoria sistémica que afecta principalmente a las articulaciones sinoviales periféricas que conduce a la destrucción del cartílago, erosión ósea y deformidad articular. La inflamación sinovial se caracteriza por infiltración leucocitaria, los más abundantes son los neutrófilos, durante su activación incrementan la producción de especies reactivas de oxígeno, con ello se libera el calcio intracelular, se activan enzimas que finalmente conducen a la formación de trampas extracelulares de neutrófilos (NET´s). Durante la liberación de NETs se liberan patrones moleculares asociados a daño, entre ellos HMGB1 (High mobility group box 1). Una proteína nuclear que en el espacio nuclear actúa como alarmina incrementando la respuesta inflamatoria. Evaluamos la dinámica de HMGB1 durante la formación de trampas extracelulares de neutrófilos inducida con suero de pacientes con AR y evaluar su relación con diversos marcadores de actividad de la enfermedad característicos del proceso inflamatorio en artritis reumatoide. Demostramos que HMGB1 es liberada al espacio extracelular durante la inducción de NETs con suero de pacientes con AR, los pacientes con AR presentan incremento en la expresión relativa de HMGB1 y se encuentra asociada a las características clínicas de los pacientes con AR

Evaluation of chromosome organization and microtubule arrangement in goat (capra aegragrus) oocytes after vitrification, in vitro maturation and fertilization, and early embryo development

Objective: Evaluate the use of Ethylene Glycol (EG), Dimethyl Sulfoxide (DMSO), Sucrose and Fetal Bovine Serum (FBS) as cryoprotectants and their effect on the organization of chromosomes and the arrangement of microtubules, during the vitrification process in goat oocytes matured in vitro and in the development of preimplantation embryos produced in vitro. Design/methodology/approach: In vitro matured oocytes were divided into 3 groups (control group, cryoprotectant exposed group, vitrified group). A mixture of 15% EG, 15% DMSO, 0.4 M sucrose and 20% FBS was used for the vitrification using the Cryotop device. In vitro matured oocytes were warmed and afterwards each group was divided into two more groups. Both groups were subjected to immunofluorescence, the first group to observe the damage produced to the chromosomes and microtubules and the second group to observe the effect on the in vitro embryo development. Results: The combined use of 15% EG, 15% DMSO, 0.4 M Sucrose and 20% FBS during vitrification did not prevent cryoinjuries in goat oocytes and in vitro produced embryos, since embryo development was disrupted before the blastocyst stage by stopping cleavage at the morula stage. This disruption was associated with chromosome decondensation and the absence of a microtubule network, thereby hindering chromosomal segregation. Limitations on study/implications: The effect of conventional cryoprotectants on chromosomes and microtubules arrangement on vitrified goat oocytes and in vitro embryo production. Findings/conclusions: The combined use of 15% EG, 15% DMSO, 0.4 M sucrose and 20% FBS as vitrification cryoprotectants did not prevent cryoinjuries in caprine oocytes and did not improve caprine embryo development in vitro

Innate Immunity Alterations in Type 2 Diabetes Mellitus: Understanding Infection Susceptibility

Diabetes is a chronic disease characterized by marked alterations in the metabolism of glucose and by high concentrations of glucose in the blood due to a decreased insulin production or resistance to the action of this hormone in peripheral tissues. The International Diabetes Federation estimates a global incidence of diabetes of about 10% in the adult population (20 - 79 years old), some 430 million cases reported worldwide in 2018. It is well documented that people with diabetes have a higher susceptibility to infectious diseases and therefore show higher morbidity and mortality compared to the non-diabetic population. Given that the innate immune response plays a fundamental role in protecting against invading pathogens through a myriad of humoral and cellular mechanisms, the present work makes a comprehensive review of the innate immune alterations in patients with type 2 diabetes mellitus (T2D) as well as a brief description of the molecular events leading or associated to such conditions. We show that in these patients a compromised innate immune response increases susceptibility to infections

A functional platform for the selection of pathogenic variants of PMM2 amenable to rescue via the use of pharmacological chaperones

Different strategies are being investigated for treating PMM2-CDG, the most common congenital disorder of glycosylation. The use of pharmacochaperones (PCs) is one of the most promising. The present work characterizes the expression, stability, and enzymatic properties of 15 previously described clinical variants of the PMM2 protein, four novel variants, the Pmm2 mouse variant p.Phe115Leu, and its p.Phe119Leu human counterpart, with the aim of extending the potential use of pharmacochaperoning treatment. PMM2 variants were purified as stable homodimers, except for p.Asp65Gly, p.Ile120Thr, and p.Thr237Lys (no expression detected), p.Thr226Ser and p.Val231Met (aggregates), and p.Glu93Ala, p.Phe119Leu, and p.Phe115Leu (partial dissociated). Enzyme activity analyses identified severe variants and milder ones. Pure dimeric mutant proteins showed a reduction in thermal stability except for p.Asn216Asp. The thermal stability of all the unstable mutants was recovered in the presence of the PC compound VIII. This study adds to the list of destabilizing human variants amenable to rescue by small chemical compounds that increase the stability/activity of PMM2. The proposed platform can be reliably used for assessing the disease-causing effects of PMM2 missense variants, for assessing the correlation between genotype and phenotype, for confirming new clinical defects, and for identifying destabilizing mutations amenable to rescue by PCsInstituto de Salud Carlos III; Consejería de Educación, Juventud y Deporte, Comunidad de Madrid; Fundación Isabel Gemio‐La Caixa; Fundación Ramón Areces; Australian Government's Medical Research Future Fun

Chipless RFID tag implementation and machine-learning workflow for robust identification

In this work, we describe a complete step-by-step workflow to apply machine-learning (ML) classification for chipless radio-frequency identification (RFID) tag identification, covering: 1) the tag implementation criteria for circular ring resonator (CRR) and square ring resonator (SRR) arrays for ML interoperability; 2) the data collection procedure to get a sufficiently representative dataset of real measurements; 3) the ML techniques to visualize the data and reduce its dimensionality; 4) the evaluation of the ML classifier to ensure high-accuracy predictions on new measurements; and 5) a thresholding scheme to increase the certainty of the predictions. The differences in the tags' frequency responses are maximized by optimizing the Hamming distance between the tag identifiers (IDs) and by controlling each resonator array's radar cross section (RCS) level. We show that the proposed workflow achieves perfect accuracy for the identification of four tags at a fixed distance of 160 cm. We also evaluate the performance of the proposed workflow to identify up to 16 tags within a flexible range (up to 140 cm), showcasing the tradeoff between the number of tags that can be correctly classified based on the reading range

Kynurenine and Hemoglobin as Sex-Specific Variables in COVID-19 Patients: A Machine Learning and Genetic Algorithms Approach

Differences in clinical manifestations, immune response, metabolic alterations, and outcomes (including disease severity and mortality) between men and women with COVID-19 have been reported since the pandemic outbreak, making it necessary to implement sex-specific biomarkers for disease diagnosis and treatment. This study aimed to identify sex-associated differences in COVID-19 patients by means of a genetic algorithm (GALGO) and machine learning, employing support vector machine (SVM) and logistic regression (LR) for the data analysis. Both algorithms identified kynurenine and hemoglobin as the most important variables to distinguish between men and women with COVID-19. LR and SVM identified C10:1, cough, and lysoPC a 14:0 to discriminate between men with COVID-19 from men without, with LR being the best model. In the case of women with COVID-19 vs. women without, SVM had a higher performance, and both models identified a higher number of variables, including 10:2, lysoPC a C26:0, lysoPC a C28:0, alpha-ketoglutaric acid, lactic acid, cough, fever, anosmia, and dysgeusia. Our results demonstrate that differences in sexes have implications in the diagnosis and outcome of the disease. Further, genetic and machine learning algorithms are useful tools to predict sex-associated differences in COVID-19

Métodos de innovación docente aplicados a los estudios de Ciencias de la Comunicación

Se analiza el fenómeno de la implantación del Espacio Europeo de Educación Superior (EEES) a los estudios de Ciencias de la Comunicación, desde el punto de vista del profesorado. En este sentido se analizan experiencias educativas como: cuadernos de visionado para la iniciación de los alumnos en el comentario fílmico; la utilización didáctica de recursos audiovisuales; el uso de películas como herramientas en la educación de estudiantes; el uso de la televisión informativa; y la aplicación de técnicas de aprendizaje colaborativo entre otras propuestas. Asimismo, se estudia el estado de implantación del EEES en España y se describen propuestas de aplicación del mismo a diferentes áreas de los estudios de Ciencias de la Comunicación. También se dedican estudios a la descripción de nuevas estrategias docentes en el marco del EEES y se proponen fórmulas de evaluación de los aprendizajes. Por último se presta atención a la aplicación de las Tecnologías de la Información y la Comunicación a los citados estudios y se definen nuevas herramientas para apoyar a los estudiantes en su labor.MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer

International audienc