Novel mechanisms of tumorigenesis and progression of cutaneous T cell lymphoma: role OF PLCG1-PRKCQ-STAT3 signalling network

RESUMEN: El linfoma cutáneo de células T (LCCT) es un grupo de linfomas no Hodgkin caracterizado por la proliferación clonal de linfocitos T malignos CD4+ en la piel, con un pronóstico desfavorable a estadios avanzados. Estudios previos han identificado múltiples alteraciones moleculares en genes específicos y vías de señalización como PLCG1, PRKCQ y JAK-STAT, revelando su papel potencial en CTCL. En esta tesis, proponemos P-STAT3 como biomarcador de estadios avanzados de la enfermedad. La activación de esta proteína se puede llevar a cabo por múltiples mecanismos como la desregulación de la señalización de JAK, PLCG1 y PRKCQ. Además, revelamos el potencial papel de PRKCQ en la tumorogénesis y progresión de CTCL a través de un modelo in vivo y los posibles genes diana que participan en estos procesos. El uso de inhibidores específicos de estas rutas de señalización, solos o en combinación, podrían mejorar el tratamiento de estos pacientes.ABSTRACT: Cutaneous T Cell Lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphomas characterised by the clonal proliferation of malignant CD4+ T cells in the skin with an unfavourable prognosis at advanced stages. Previous studies have identified multiple molecular alterations in specific genes and signalling pathways including PLCG1, PRKCQ and JAK-STAT revealing a potential role of these pathways in CTCL. In this thesis, P-STAT3 has been proposed as a biomarker of advanced stages of CTCL patients. The activation of this protein may be triggered by multiple mechanisms such as deregulated JAK, PLCG1 and PRKCQ signalling pathways. In addition, we also provide evidence of the potential role of PRKCQ in the tumorigenesis and progression of CTCL in an in vivo model and the target genes that may participate in these processes. The use of specific inhibitors of these pathways, alone or in combination, may provide a rational to improve the treatment of these patients.La financiación necesaria para la realización de esta Tesis Doctoral ha sido aportada por el Instituto Carlos III mediante los proyectos PI16/00156 y PIE15/00081, y por la asociación Luchemos por la Vida mediante los proyectos concedidos en 2016, 2018 y 2019. La autora de esta Tesis ha disfrutado de contrato del Programa de Personal Investigador en formación predoctoral, referencia MPREVAL18/01 concedido por la Universidad de Cantabria, el IDIVAL y la Consejería de Educación del Gobierno de Cantabria

Relación entre la regulación emocional y la autoestima

Introducción: Autoestima y regulación emocional son constructos psicológicos relacionadoscon la salud mental. El presente estudio pretende explorar la relación existenteentre estos dos constructos. Objetivo: Analizar la relación entre la autoestima ydistintas dimensiones de la regulación emocional y conocer cuáles tienen más relacióncon la autoestima. Método: Cien personas, entre 20 y 30 años, de la población generalparticiparon en el estudio (51 mujeres y 49 hombres). Fueron evaluadas a travésdel Cuestionario de Autoestima de Rosenberg (Rosenberg, 1965) y la Escala de Dificultadesen la Regulación Emocional (DERS, Gratz y Roemer, 2004). Resultados: Losresultados muestran una correlación significativa entre la autoestima y las subescalasdel DERS: Atención, Claridad, Aceptación, Funcionamiento y Regulación. El análisisde regresión reveló que las dimensiones más relacionadas con la autoestima fueron laAceptación y la Atención. Conclusión: Es esperable encontrar una relación entre lacapacidad de regular las emociones y un constructo que supone una valoración positivade uno mismo, la autoestima. En concreto, la capacidad de prestar atención a lasemociones y aceptarlas podrían ser aspectos fundamentales en la construcción de unautoconcepto y una valoración de sí mismo positivos. En investigaciones futuras sepropone estudiar en profundidad estas relaciones con el fin de poder realizar recomendacionessobre qué aspectos de la regulación emocional trabajar con el fin de potenciarautoestima y bienestar.Introduction: Self-esteem and emotional regulation are psychological constructs relateto mental health. The current research pretends to explore the relation betweenthese two constructs. Objective: Analyze the relation between self-esteem and differentsdimensions of emotional regulation, and knowing which have more relation withthe self-esteem. Method: one hundred people from the general population participatedin this study (51 women and 49 men), with ages between 20-30 years were evaluatedthrough the Rosenberg self-esteem questionnaire (Rosenberg, 1965) and Scale of difficulty in emotional regulation (DERS, Gratz & Roemer, 2004). Results: The resultsshow a significant correlation between self-esteem and the subscales of the DERS: attention,clarity, acceptance, operation and regulation. Regression analysis revealedthat most related to self-esteem dimensions were acceptance and attention. Conclusion:It is expected to find a relationship between the ability to regulate emotions anda construct that implies a positive evaluation of one’s own, the self-esteem. In particular,the ability to pay attention to emotions and accept could be key aspects in constructinga positive self-concept and self-assessment. In future research it is proposedto study in depth these relationships in order to be able to make recommendationsabout which aspects work in emotional regulation in order to enhance self-esteem andwell-being

The effect of CO2-3 on the growth of barite {001} and {210} surfaces: An AFM study

The growth of barite {001} and {210} faces from aqueous solutions moderately supersaturated with respect to barite (βbarite ≈ 12 for experiments on {001} surfaces and βbarite ≈ 7 for experiments on {210} surfaces) and bearing different concentrations of carbonate has been studied in situ using an atomic force microscope (AFM). Nanoscopic observations show that, above a certain carbonate concentration threshold in the aqueous solution, the advancement of monolayers (~3.5Å in height) on barite {001} and {210} surfaces is strongly inhibited. However, inhibition never affects the growth of the first monolayer, whose growth rate increases in the presence of carbonate. In contrast, the second monolayer growth rate decreases as the concentration of carbonate in the solution increases. For high carbonate concentrations in the solution, growth stops after the formation of the first monolayer. While on barite {001} faces, the formation of a second monolayer does not occur for carbonate concentrations higher than 0.2 mM, on barite {210} faces the complete inhibition of the second monolayer is observed for carbonate concentrations higher than 0.05 mM. Once growth on {001} or {210} faces is completely inhibited, i.e. such surfaces are in the ‘‘dead zone’’, growth can be recovered by increasing supersaturation. In order to study the recovery behaviour of barite {001} and {210} faces from the ‘‘dead zone’’, an additional series of AFM experiments have been conducted. In these experiments, carbonate-free aqueous solutions with increasing supersaturations with respect to barite were passed over {001} and {210} surfaces previously ‘‘poisoned’’ with carbonate. Our experimental results show that the recovery of growth on barite {001} faces requires an important increase of the solution supersaturation. In contrast, the recovery of barite {210} surface growth does not require any supersaturation increase, but spontaneously occurs in a few minutes. Our observations of inhibition and growth recovery on barite surfaces at a nano-scale are discussed and compared with the descriptions given by the classical crystal growth inhibition models

A 3D bioprinted hydrogel gut-on-chip with integrated electrodes for transepithelial electrical resistance (TEER) measurements

Conventional gut-on-chip (GOC) models typically represent the epithelial layer of the gut tissue, neglecting other important components such as the stromal compartment and the extracellular matrix (ECM) that play crucial roles in maintaining intestinal barrier integrity and function. These models often employ hard, flat porous membranes for cell culture, thus failing to recapitulate the soft environment and complex 3D architecture of the intestinal mucosa. Alternatively, hydrogels have been recently introduced in GOCs as ECM analogs to support the co-culture of intestinal cells in in vivo-like configurations, and thus opening new opportunities in the organ-on-chip field. In this work, we present an innovative GOC device that includes a 3D bioprinted hydrogel channel replicating the intestinal villi architecture containing both the epithelial and stromal compartments of the gut mucosa. The bioprinted hydrogels successfully support both the encapsulation of fibroblasts and their co-culture with intestinal epithelial cells under physiological flow conditions. Moreover, we successfully integrated electrodes into the microfluidic system to monitor the barrier formation in real time via transepithelial electrical resistance measurements

New Models Used to Determine the Dioxins Total Amount and Toxicity (TEQ) in Atmospheric Emissions from Thermal Processes

In order to reduce the calculation effort during the simulation of the emission of polychlorinated dibenzo-p-dioxins and furans (PCDD/F) during municipal solid waste incineration, minimizing the number of simulated components is mandatory. For this purpose, two new multilinear regression models capable of determining the dioxins total amount and toxicity of an atmospheric emission have been adjusted based on previously published ones. The new source of data used (almost 200 PCDD/F analyses) provides a wider range of application to the models, increasing also the diversity of the emission sources, from industrial and laboratory scale thermal processes. Only three of the 17 toxic congeners (1,2,3,6,7,8-HxCDD, 2,3,7,8-TCDF and OCDF), whose formation was found to be linearly independent, were necessary as inputs for the models. All model parameters have been statistically validated and their confidence intervals have been calculated using the Bootstrap method. The resulting coefficients of determination (R2) for the models are 0.9711 ± 0.0056 and 0.9583 ± 0.0085; its root mean square errors (RMSE) are 0.2115 and 0.2424, and its mean absolute errors (MAE) are 0.1541 and 0.1733 respectively.Juan A. Conesa and Nuria Ortuño acknowledge the support for this work by the CTQ2016-76608-R project from the Ministry of Economy, Industry and Competitiveness (Spain). Damià Palmer thanks IQS—Universitat Ramon Llull for its financial support

Perturbation-Theory and Machine Learning (PTML). Model for High-Throughput Screening of Parham Reactions: Experimental and Theoretical Studies

Machine Learning (ML) algorithms are gaining importance in the processing of chemical information and modelling of chemical reactivity problems. In this work, we have developed a PTML model combining Perturbation-Theory (PT) and ML algorithms for predicting the yield of a given reaction. For this purpose, we have selected Parham cyclization, which is a general and powerful tool for the synthesis of heterocyclic and carbocyclic compounds. This reaction has both structural (substitution pattern on the substrate, internal electrophile, ring size, etc.) and operational variables (organolithium reagent, solvent, temperature, time, etc.), so predicting the effect of changes on substrate design (internal elelctrophile, halide, etc.) or reaction conditions on the yield is an important task that could help to optimize the reaction design. The PTML model developed uses PT operators to account for perturbations in experimental conditions and/or structural variables of all the molecules involved in a query reaction compared to a reaction of reference. Thus, a dataset of >100 reactions has been collected for different substrates and internal electrophiles, under different reaction conditions, with a wide range of yields (0 – 98%). The best PTML model found using General Linear Regression (GLR) has R = 0.88 in training and R = 0.83 in external validation series for 10000 pairs of query and reference reactions. The PTML model has a final R = 0.95 for all reactions using multiple reactions of reference. We also report a comparative study of linear vs. non-linear PTML models based on Artificial Neural Networks (ANN) algorithms. PTML-ANN models (LNN, MLP, RBF) with R ≈ 0.1 - 0.8 do not outperform the first PMTL model. This result confirms the validity of the linearity of the model. Next, we carried out an experimental and theoretical study of non-reported Parham reactions to illustrate the practical use of the PTML model. A 500000-point simulation and a Hammett analysis of the reactivity space of Parham reactions are also reportedMinisterio de Economía y Competitividad (CTQ2016-74881-P) / Ministerio de Economía y Competitividad (CTQ2013-41229-P) / Gobierno Vasco (IT1045-16

New concepts and objectives for protein-amino acid nutrition in rabbits: a review

In the European context, the new legislation to avoid mineral contamination and the ban on antibiotics as growth promoters has led to the definition of new objectives in respect of nitrogen supply. The present study summarizes the state of nitrogen nutrition in rabbits and reviews the role of protein and amino acids in rabbit health and the new nitrogen value of protein sources based on true ileal digestibility (TID) for future recommendations. The main sources of nitrogen for microbial growth are ammonia, urea and protein (endogenous and dietary). The surplus of nitrogen flow to the caecum increases mortality rates during fattening by favouring the growth of potential pathogenic bacteria. Accordingly, feeding strategies to reduce ileal nitrogen flow have been reviewed. A large reduction of dietary protein level might have negative consequences on growth performances and mortality. In order to formulate balanced low protein diets, data on ileal and faecal amino acid digestibility of 14 raw materials is summarized. The use of this different unit for amino acid digestibility is also discussed

Uso de Google Calendar para la coordinación entre asignaturas del Grado en Ingeniería Química

Uno de los aspectos peor valorados por los estudiantes de las nuevas titulaciones de grado es la coordinación entre asignaturas del mismo curso en cuanto a la distribución de controles y otro tipo de pruebas objetivas a lo largo del cuatrimestre, que afecta a la carga de trabajo no presencial en determinados momentos. En la guía docente de cada asignatura aparece la información sobre las pruebas a realizar dentro de un cronograma aproximado por semanas, y está disponible antes del comienzo del curso. Sin embargo, esa distribución puede variar ligeramente una vez empezado el curso debido a diversos motivos, y no se dispone de la información para todas las asignaturas del cuatrimestre en un mismo documento, lo que facilitaría su visualización. En este trabajo se propone el uso de la herramienta Google Calendar con el objetivo de tener un mayor control de este aspecto y poder detectar y corregir conflictos que puedan surgir, aplicándolo al Grado en Ingeniería Química