RNY3 modulates cell proliferation and IL13 mRNA levels in a T lymphocyte model: a possible new epigenetic mechanism of IL-13 regulation

[EN] llergic asthma is the most common type of asthma. It is characterized by TH2 cell–driven infammation in which interleukin-13 (IL-13) plays a pivotal role. Cytoplasmic RNAs (Y-RNAs), a variety of non-coding RNAs that are dysregulated in many cancer types, are also diferentially expressed in patients with allergic asthma. Their function in the development of the disease is still unknown. We investigated the potential role of RNY3 RNA (hY3) in the TH2 cell infammatory response using the Jurkat cell line as a model. hY3 expression levels were modulated to mimic the upregulation efect in allergic disease. We evaluated the efect of hY3 over cell stimulation and the expression of the TH2 cytokine IL13. Total RNA was isolated and retrotranscribed, and RNA levels were assessed by qPCR. In Jurkat cells, hY3 levels increased upon stimulation with phorbol 12-myristate 13-acetate (PMA) and ionomycin. When transfecting with high levels of hY3 mimic molecules, cell proliferation rate decreased while IL13 mRNA levels increased upon stimulation compared to stimulated control cells. Our results show the efect of increased hY3 levels on cell proliferation and the levels of IL13 mRNA in Jurkat cells. Also, we showed that hY3 could act over other cells via exosomes. This study opens up new ways to study the potential regulatory function of hY3 over IL-13 production and its implications for asthma development.Publicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCLE

Rigid polyurethane foams with infused nanoclays: Relationship between cellular structure and thermal conductivity

Producción CientíficaA water blown rigid polyurethane (PU) formulation has been used to manufacture cellular nanocomposites containing different concentrations of montmorillonite nanoclays. The PU foams have been produced using a low shear mixing technique for dispersing the nanoclays and by reactive foaming to generate the cellular structure. A detailed characterization of the cellular structure has been performed. The effect of the nanoparticles on the reaction kinetics and the state of intercalation of the nanoparticles in the foams has been analyzed. The thermal conductivity and extinction coefficient of the different materials has been measured and the results obtained have been correlated with the materials structure. A strong reduction of cell size and modifications on cell size distribution, anisotropy ratio and fraction of material in the struts has been detected when the clays are added. In addition, a reduction of the thermal conductivity has been observed. Different theoretical models have been employed to explain thermal conductivity changes in terms of structural features. It has been found that, in addition to the modifications in the cellular structure, changes in the extinction coefficient and thermal conductivity of the matrix polymer play an important role on the final values of the thermal conductivity for these materials.We would like to acknowledge to Mr. Vela and Mr. Ferrer, from BASF Española S.L., for supplying the PU formulation employed in this research. The authors are grateful to the Spanish Ministry of Science and Education which supported this work with a FPU Grant Ref-AP-2008-03602 given to Mr. Estravís. In addition, Financial assistance from the Spanish Ministry of Science and Innovation, FEDER program (MAT 2012 – 34901 and MAT2015-69234-R), the Junta de Castile and Leon (VA035U13) and the EU Commission (FP7 program, EC project NanCore number 214148) is acknowledged

Implementación del aprendizaje colaborativo utilizando la herramienta Nearpod en las clases prácticas de Alergología

Memoria ID-144. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2019-2020.[ES]Nearpod es una herramienta digital que permite la interacción profesor-alumno mediante dispositivo móviles, utilizando la conexión a internet, y posibilita la inserción de actividades en las presentaciones de contenidos. El objetivo general es mejorar el proceso de enseñanza aprendizaje en la docencia práctica de la asignatura de Alergologí

La GTPasa Cdec42 regula el tráfico intracelular necesario para el crecimiento polarizado de Schizosaccharomyces pombe

Memoria presentada por Miguel Estravís Sastre para optar al Grado de Doctor en Biología, realizada en el Instituto de Biología Funcional y Genómica, centro mixto de la Universidad de Salamanca (Departamento de Microbiología y Genética) y el Consejo Superior de Investigaciones Científicas.Las GTPasas de la familia Rho son moléculas clave en la regulación de la morfogénesis de la célula. En Schizosaccharomyces pombe, Cdc42, un miembro de la familia Rho, es una proteína que participa en el establecimiento de la polaridad celular y regula la formación de cables de actina. El objetivo de este trabajo de Tesis Doctoral ha sido el estudio de nuevas funciones de la GTPasa Cdc42 en S. pombe. Puesto que Cdc42 es una proteína esencial, el estudio de su función se ha llevado a cabo mediante la generación de mutantes termosensibles, que muestran defectos en las interacciones funcionales de esta GTPasa y otras proteínas, y permiten caracterizar defectos en los procesos en los que interviene Cdc42. De esta forma, en la cepa cdc42-L160S se observan múltiples defectos en procesos relacionados con secreción, tráfico de membranas y formación de vacuolas. Los estudios realizados nos indican que en S. pombe Cdc42 regula varios procesos de tráfico intracelular. Y que, junto con su proteína efectora Pob1, participa en la localización del exocisto y regula la secreción celular. Adicionalmente los resultados obtenidos sugieren que Rho3 y Cdc42 son parcialmente redundantes en la regulación de la exocitosis y del tráfico intracelular y que Cdc42 participa en la fusión vacuolar. Además, la caracterización de los defectos de la cepa mutante cdc42-L160S en el proceso de conjugación permite adjudicar nuevas funciones a la proteína Cdc42 de S. pombe en la regulación de la respuesta a feromonas, en el establecimiento de la polaridad celular en respuesta a estímulos externos y en la fusión celular.Agradezco a la Junta de Castilla y León por la concesión del contrato que me ha permitido desarrollar este trabajo.Peer Reviewe

La GTPASA CDC42 regula el tráfico intracelular necesario para el crecimiento polarizado de SCHIZOSACCHAROMYCES POMBE

[ES] Las GTPasas de la familia Rho son moléculas clave en la regulación de la morfogénesis de la célula. En Schizosaccharomyces pombe, Cdc42, un miembro de la familia Rho, es una proteína que participa en el establecimiento de la polaridad celular y regula la formación de cables de actina. El objetivo de este trabajo de Tesis Doctoral ha sido el estudio de nuevas funciones de la GTPasa Cdc42 en S. pombe. Puesto que Cdc42 es una proteína esencial, el estudio de su función se ha llevado a cabo mediante la generación de mutantes termosensibles, que muestran defectos en las interacciones funcionales de esta GTPasa y otras proteínas, y permiten caracterizar defectos en los procesos en los que interviene Cdc42. De esta forma, en la cepa cdc42-L160S se observan múltiples defectos en procesos relacionados con secreción, tráfico de membranas y formación de vacuolas. Los estudios realizados nos indican que en S. pombe Cdc42 regula varios procesos de tráfico intracelular. Y que, junto con su proteína efectora Pob1, participa en la localización del exocisto y regula la secreción celular. Adicionalmente los resultados obtenidos sugieren que Rho3 y Cdc42 son parcialmente redundantes en la regulación de la exocitosis y del tráfico intracelular y que Cdc42 participa en la fusión vacuolar. Además, la caracterización de los defectos de la cepa mutante cdc42-L160S en el proceso de conjugación permite adjudicar nuevas funciones a la proteína Cdc42 de S. pombe en la regulación de la respuesta a feromonas, en el establecimiento de la polaridad celular en respuesta a estímulos externos y en la fusión celular.[EN] The Rho family GTPases are key molecules in the regulation of cell morphogenesis. In Schizosaccharomyces pombe, Cdc42, a member of the Rho family, is a protein involved in establishing cell polarity and regulates the formation of actin cables. The aim of this PhD Thesis has been the study of new functions of the GTPase Cdc42 in S. pombe. Since it is an essential protein Cdc42, study their function is performed by the generation of temperature-sensitive mutants which show defects in the functional interactions of this GTPase and other proteins, and to characterize defects in processes in which it intervenes Cdc42. Thus, in strain cdc42-L160S multiple defects are observed in processes related to secretion, membrane trafficking and formation of vacuoles. Studies show that in S. pombe Cdc42 regulates several intracellular trafficking processes. And, along with its Pob1 effector protein, is involved in regulating location exocisto and cellular secretion. Additionally, the results obtained suggest that RHO3 and Cdc42 are partially redundant in the regulation of exocytosis of intracellular trafficking and Cdc42 and is involved in vacuolar fusion. Furthermore, the characterization of the mutant strain defective cdc42-L160S in the conjugation process allows new functions to allot Cdc42 protein S. pombe in regulating the response to pheromone, in establishing cell polarity in response to external stimuli and cell fusion

Cdc42 regulates polarized growth and cell integrity in fission yeast

Resumen del trabajo presentado al Annual Main Meeting of Society For Experimental Biology(SEB) celebrado en Valencia (España) en julio de 2013.The Rho family of GTPases is a group of proteins conserved among the eukaryotic organisms, which has a central role in regulating actin cytoskeleton organization. Fission yeast Schizosaccharomyces pombe undergoes morphogenetic changes during both vegetative and sexual cell cycles that require asymmetric cell growth and actin cytoskeleton reorganization. Cdc42, an essential member of the Rho proteins, provides the coordinated regulation of actin organization, secretion, and endocytosis required for polarized growth. Active Cdc42 mainly localizes to growth areas of the plasma membrane and regulates For3, the formin responsible for actin cable nucleation during interphase. Additionally, it regulates secretion, membrane traffic, and exocyst localization during vegetative growth. Like other Rho GTPases, Cdc42 is positively regulated by GDP-GTP exchange factors (GEFs) and negatively regulated by GTPase-activating proteins (GAPs) and GDP dissociation inhibitors (GDIs). These regulators play important roles in the specificity of Cdc42 function. Scd1 and Gef1 are the two described Cdc42 GEFs in S. pombe, and Rga4 is the only GAP. We describe here other Rho GAPs that collaborate with Rga4 in the regulation of Cdc42 and the maintenance of cell morphology and polarized growth.Peer Reviewe

Role of the TSLP and its Receptor in the Treatment of Asthma

Thymic stromal lymphopoietin (TSLP) is a crucial cytokine in initiating and regulating immune responses. Various cell types, including epithelial cells, fibroblasts, and dendritic cells, synthesize TSLP. TSLP activates dendritic cells, which subsequently promote the differentiation of T cells into T-helper 2 (TH2) cells, a subset of T cells that produce cytokines involved in allergic responses. Genetic studies have linked TSLP to the development of asthma and other inflammatory disorders, indicating its importance in the pathogenesis of these diseases. Inhibiting the TSLP-TSLR axis has been suggested as a precision medicine strategy for treating several phenotypes and endotypes of asthma. Tezepelumab is a human monoclonal antibody that selectively binds to TSLP, thereby blocking its interaction with its heterodimeric receptor, reducing inflammation in the airways, and improving asthma symptoms

Mathematical modeling of Seppälä Stockmann sales promotion

Bakalaura darba temats ir „Seppälä Stockmann pieprasījuma stimulēšanas matemātiskā modelēšana”. Bakalaura darba mērķis ir izskatīt preču realizācijas stimulēšanas un cenu pazeminājuma (markdown) būtību un svarīgākus matemātiskus modeļus, ka arī aplūkot to pielietojuma iespējas praksē uz veikala Seppälä Stockmann piemēra. Darbs sastāv no trim nodaļām, kurās tiek izskatīta preču realizācijas stimulēšanas un cenu pazeminājuma būtība, pielietojuma iemesli, kritēriji un rezultāti, ka arī tiek pielietoti matemātiskie modeļi izdevīguma analīzei. Darba izstrādes procesā tika secināts, ka efektīvi izmantojot esošo uzņēmuma informāciju par klientu pirktspēju un tendencēm, var noteikt tādu cenu un atlaižu shēmu sezonas laikā, kurš palielinās uzņēmuma ieņēmumus līdz 25%. Darba apjoms ir 70 lappuses. Darbs ir uzrakstīts latviešu valodā, un tajā iekļautas 23 tabulas un 19 attēli. Atslēgvārdi: preču realizācijas stimulēšana, nocenojums, atlaižu shēma, determinēts modelis, stohastiskais modelisThe research topic of bachelor thesis is “Mathematical modeling of Seppälä Stockmann sales promotion”. The aim of the thesis is to explore sales promotion and markdown principles and mathematical models in connection with Seppälä Stockmann pricing strategy. Three chapters include the review of core markdown and sales promotion mathematical models, which would provide basis for analyzing temporal and spatial price patterns of subsequent markdowns, as well as the results of mathematical price and markdown programming for Seppälä Stockmann retailer. The thesis contains 70 pages, 23 tables and 19 pictures. Keywords: sales promotion, markdown, deterministic markdown model, stochastic markdown model, deman

CDC42 regulates different steps of fission yeast mating

Resumen del póster presentado a la EMBO Conference on Fission Yeast: Pombe 2013; 7th International Fission Yeast Meeting celebrada en Londres (UK) del 24 al 29 de junio de 2013.Fission yeast conjugation takes place in conditions of starvation and involves morphological changes that, in response to external signaling, lead to the formation of “shmoos”, cell fusion, and formation of zygotes. Schizosaccharomyces pombe Cdc42 GTPase is a key regulator of cell morphogenesis during vegetative growth and also has functions during mating in the pheromone signal transduction and the establishment of the growth pattern that leads to the “shmoo” formation. Here we analyze the role of Cdc42 in cell fusion during mating using the cdc42-L160S thermosensitive mutant strain. While most cdc42 related mutant strains are sterile, cdc42-L160S cells can activate the pheromone pathway and mate at low efficiency. Nuclear accumulation of Ste11 transcription factor is low, cells have defects in polarity establishment, and mating-specific cell adhesion is impaired. Besides these defects, which may be related to an impaired pheromone signal transduction, cdc42-L160S mutant strain also shows cell fusion defects after the mating partners contact, as well as defects in the widening of the conjugation bridge once the cell fusion occurs. These late defects are not caused by mislocalization of the exocyst, Fus1 formin or Dni1, a tetraspan protein required for correct membrane organization and cell wall remodelling during mating. By contrast, the septin ring appears disorganized and that might cause the lack of expansion of the conjugation bridge.This suggests for the first time in fission yeast that septins are regulated by Cdc42 in a critical manner to allow proper accomplishment of the mating process.Peer Reviewe

Cdc42 Regulates Multiple Membrane Traffic Events in Fission Yeast

Fission yeast Cdc42 regulates polarized growth and is involved in For3 formin activation and actin cable assembly. We show here that a thermosensitive strain carrying the cdc42L160S allele has membrane traffic defects independent of the actin cable defects. This strain has decreased acid phosphatase (AP) secretion, intracellular accumulation of vesicles and fragmentation of vacuoles. In addition, the exocyst is not localized to the tips of these cells. Overproduction of the scaffold protein Pob1 suppressed cdc42L160S thermosensitive growth and restored exocyst localization and AP secretion. The GTPase Rho3 also suppressed cdc42L160S thermosensitivity, restored exocyst localization and AP secretion. However, Rho3 did not restore the actin cables in these cells as Pob1 does. Similarly, overexpression of psy1+, coding a syntaxin (t-SNARE) homolog, or of ypt2+, coding an SEC4 homolog in fission yeast, rescued growth at high temperature but did not restore actin cables, nor the exocyst-polarized localization. cdc42L160S cells also have defects in vacuole formation that were rescued by Pob1, Rho3 and Psy1. All together, we propose that Cdc42 and the scaffold Pob1 are required for membrane trafficking and fusion, contributing to polarized secretion, endosome recycling, vacuole formation and growth.This work was supported by grants BFU2007-60675 and BFU2010-15641 from the Dirección General de Investigación, MICINN, Spain, and grant GR231 from Junta de Castilla y León.Peer Reviewe