Análisis molecular y funcional de dachsous durante el desarrollo larvario de Drosophila melanogaster

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 27-06-2014La Polaridad Planar Celular (PPC) es un mecanismo evolutivamente conservado que inicialmente fue caracterizado en Drosophila melanogaster y participa en la organización tridimensional de los tejidos. Las caderinas atípicas son componentes esenciales en este proceso. En esta tesis nos hemos centrado en el estudio de la caderina atípica Dachsous (Ds) de Drosophila que participa en la vía Fat/ Ds de PPC. Además de esta función, Ds participa en otros procesos durante el desarrollo regulando la proliferación celular a través de la vía de Hippo. Durante el desarrollo de esta tesis, se ha llevado a cabo un estudio molecular exhaustivo del locus ds. Utilizando técnicas moleculares como el northern blot y la RT-qPCR se ha podido demostrar la existencia de diferentes isoformas transcripcionales, y conocer la composición exónica de algunas de ellas. Con un nuevo anticuerpo, hemos detectado nuevas proteínas Ds mediante western blot y analizando la localización subcelular de estas en los discos imaginales. También hemos analizado la función de las isoformas solubles DsEx y DsIntra, sin dominio transmembrana y compuestas por la región extracelular y la región citoplasmática respectivamente. El análisis genético de falta de función y/o sobreexpresión de las mencionadas isoformas revelan un papel esencial de la región citoplasmática tanto para la actividad de Ds en PPC como en el control de la proliferación celular. Por último, hemos mostrado por primera vez que el mecanismo de PPC, a través de la proteína Ds, actúa durante el desarrollo del órgano de Jonhston (OJ), el órgano auditivo de Drosophila melanogaster. Estos experimentos preliminares muestran que la PPC, como mecanismo evolutivamente conservado, participa en la formación del sistema auditivo de diferentes organismos. Esto, permitirá utilizar a Drosophila como modelo para identificar nuevos genes relacionados con sorderas hereditarias en humanosThe Planar Cell Polarity (PCP) is an evolutionary conserved mechanism initially characterized in Drosophila melanogaster. PCP is required for the three-dimensional organization of the tissues to form organs and the atypical cadherins play an essential role in this process. In this experimental work I have focused on the study of the Drosophila atypical cadherin Dachsous (Ds). In addition to its role in the Ds/Ft pathway of PPC mechanism, Ds participates in the control of cell proliferation through the modulation of the activity of Hippo pathway. During the course of producing my doctoral thesis, a comprehensive molecular analysis of the ds gene has been carried out using different molecular techniques such as northern blot and RT-qPCR. The results have shown the existence of novel ds transcriptional isoforms. The exonic composition of three of those isoforms named DsEx, Ds1 and DsIntra has been determined. The generation of a new Ds antibody has allowed us to detect by western blot some of those Ds isoforms focusing our interest on their subcellular location in the imaginal epithelial cells. Additionally, we have also addressed the functional relevance of the soluble isoforms DsIntra (cytoplasmic region) and DsEx (extracellular region) without a transmembrane domain to be anchored to the cell membrane. A genetic-molecular analysis using several loss of function conditions as well as the overexpression of different Ds forms has demonstrated an essential role of the cytoplasmic region in the two main developmental functions in which Ds participates: PCP and cell proliferation. Finally, we have shown the first evidence that suggest a role of Ds and therefore the PCP mechanism during the formation of the Drosophila auditory system named the Johnston’s organ. These preliminary results suggest that PCP is an evolutionary mechanism involved in the development of the auditory organ from insect to vertebrates. This indicates that Drosophila might be an interesting animal model to identify novel genes associated with PCP and hereditary hearing-loss diseases in humans

La implantación del Inglés en las aulas de Primaria: ¿Por qué les cuesta aprender Inglés?

Entendemos el bilingüismo como la práctica de al menos dos lenguas por parte de un individuo o un grupo o comunidad de hablantes. En la actualidad, y favorecido por la globalización, el conocimiento de un segundo idioma, y principalmente el inglés, se ha convertido en una necesidad imperante. Actualmente parece que los esfuerzos y las políticas puestas en marcha para potenciar el aprendizaje del inglés son menos exitosos en España que en el resto de países europeos. Como posibles causas, se barajan varias: una incompleta formación del profesorado, las características propias de los programas que se aplican o la falta de recursos fuera del sistema educativo para reforzar lo aprendido. En este estudio nos planteamos conocer los factores que influyen en el fracaso del aprendizaje del inglés en España mediante una investigación cualitativa en la que incluimos a alumnos, profesores y padres.Grado en Educación Primari

Aprendizaje servicio: diálogo universidad y sociedad

Las prácticas de ApS en las que se dan cita diferentes métodos de aprendizaje activo, como el aprendizaje experiencial, el cooperativo o el constructivismo, se ajustan a los fundamentos pedagógicos demandados en el Espacio Europeo de Educación Superior (EEES). Los proyectos de aprendizaje-servicio permiten desarrollar los contenidos curriculares, es decir, aprendizajes académicos, facilitando la práctica de la planificación, el esfuerzo, la responsabilidad y el compromiso solidario. La metodología práctica de “Aprendizaje-Servicio”, además de lograr mayor formación profesional y personal por parte de nuestros estudiantes, contribuye, a devolver a la sociedad la confianza que ha depositado en nosotros como organización promotora de conocimiento y de compromiso social

Language report for Catalan (English version)

The central objective of the Metanet4u project is to contribute to the establishment of a pan-European digital platform that makes available language resources and services, encompassing both datasets and software tools, for speech and language processing, and supports a new generation of exchange facilities for them.Peer ReviewedPreprin

Herramientas de gestión logística y su impacto sobre el costo de almacenamiento de la empresa Inversiones Micade S.A.C., Trujillo, 2021

El objetivo general de la presente investigación fue utilizar las distintas herramientas de gestión logística con el fin de reducir el costo de almacenamiento de la empresa Inversiones Micade S.A.C. El tipo de investigación fue aplicada y el diseño fue pre experimental; la muestra estuvo conformada por los procesos de la gestión logística de la empresa donde se servicio al cliente; entre las técnicas de recopilación de datos de datos se usaron las siguientes: la observación directa, la encuesta y el análisis documental. Se utilizó herramientas tales como: diagrama de Ishikawa, Pareto, indicadores de gestión (KPI), diagrama de flujo, 5S, Kardex, análisis ABC, SRM y establecimiento de políticas de reposición. Una vez realizado el diagnóstico de la situación actual en la empresa y de haber aplicado las herramientas mencionadas, se evaluó la variación del costo de almacenamiento tanto en el almacén de materias primas como de productos terminados obteniendo una reducción de S/. 5,646.81 y S/. 5,480.00 respectivamente

Advanced lipoprotein parameters could better explain atheromatosis in non-diabetic chronic kidney disease patients

Background: Chronic kidney disease (CKD) patients have a high burden of atheromatous cardiovascular disease (ASCVD) not fully explained by traditional lipid parameters. Lipoprotein composition and subclass particle number information could improve ASCVD risk assessment. The objective of this study is to investigate the association of advanced lipoprotein parameters with the risk of atheromatosis in a subpopulation of the NEFRONA study. Methods: This was a cross-sectional study in 395 non-diabetic individuals (209 CKD and 186 non-diabetic and non-CKD) without statin therapy. Vascular ultrasound examination assessing 10 territories was combined with advanced lipoprotein testing performed by nuclear magnetic resonance spectroscopy. Logistic regression was used to estimate adjusted odds ratios (ORs) per 1 standard deviation increment. Results: Atheromatosis was more prevalent in CKD patients (33.9% versus 64.6%). After adjusting for age, gender, smoking habit and CKD stage, the amount of triglycerides (TGs) within low-density lipoprotein (LDL) lipoproteins was independently and positively associated with atheromatosis [OR 1.33; 95% confidence interval (CI) 1.03–1.74; P = 0.03]. Similarly, total and medium LDL particles (LDL-Ps) showed a positive association (OR 1.29; 95% CI 1.00–1.68; P = 0.05 and OR 1.34; 95% CI 1.04–1.75; P = 0.03, respectively). TG-loaded medium LDL-Ps were higher in CKD patients compared with controls and showed an adjusted OR of 1.40 (95% CI 1.09–1.82; P = 0.01) in non-diabetic patients (CKD and non-CKD individuals). In contrast, non-diabetic CKD patients showed a similar coefficient but the significance was lost (OR 1.2; 95% CI 0.8–1.7; P = 0.359). Conclusions: Non-diabetic CKD patients showed a higher amount of TG-loaded medium LDL-Ps compared with controls. These particles were independently associated with atheromatosis in non-diabetic patients.This work was supported by the intramural program of the IRB Lleida, the Instituto de Salud Carlos III [RETIC RD16/0009/0011, FIS PI18/00610], the Ministerio de Ciencia, Innovación y Universidades [IJC2018-037792-I] and the FEDER funds

Impact of interstitial lung disease on the survival of systemic sclerosis with pulmonary arterial hypertension

Respiratory tract diseases; Systemic sclerosisMalalties del tracte respiratori; Esclerosi sistèmicaEnfermedades del tracto respiratorio; Esclerosis sistémicaTo assess severity markers and outcomes of patients with systemic sclerosis (SSc) with or without pulmonary arterial hypertension (PAH-SSc/non-PAH-SSc), and the impact of interstitial lung disease (ILD) on PAH-SSc. Non-PAH-SSc patients from the Spanish SSc registry and PAH-SSc patients from the Spanish PAH registry were included. A total of 364 PAH-SSc and 1589 non-PAH-SSc patients were included. PAH-SSc patients had worse NYHA-functional class (NYHA-FC), worse forced vital capacity (FVC) (81.2 ± 20.6% vs 93.6 ± 20.6%, P < 0.001), worse tricuspid annular plane systolic excursion (TAPSE) (17.4 ± 5.2 mm vs 19.9 ± 6.7 mm, P < 0.001), higher incidence of pericardial effusion (30% vs 5.2%, P < 0.001) and similar prevalence of ILD (41.8% vs. 44.9%). In individuals with PAH-SSc, ILD was associated with worse hemodynamics and pulmonary function tests (PFT). Up-front combination therapy was used in 59.8% and 61.7% of patients with and without ILD, respectively. Five-year transplant-free survival rate was 41.1% in PAH-SSc patients and 93.9% in non-PAH-SSc patients (P < 0.001). Global survival of PAH-SSc patients was not affected by ILD regardless its severity. The multivariate survival analysis in PAH-SSc patients confirmed age at diagnosis, worse NYHA-FC, increased PVR, reduced DLCO, and lower management with up-front combination therapy as major risk factors. In conclusion, in PAH-SSc cohort risk of death was greatly increased by clinical, PFT, and hemodynamic factors, whereas it was decreased by up-front combination therapy. Concomitant ILD worsened hemodynamics and PFT in PAH-SSc but not survival regardless of FVC impairment

Accumulation of northern krill (Meganyctiphanes norvegica) in a convergence zone at the Cap Breton Canyon (southern Bay of Biscay)

Publicado

Language report for Catalan (Catalan version)

The central objective of the Metanet4u project is to contribute to the establishment of a pan-European digital platform that makes available language resources and services, encompassing both datasets and software tools, for speech and language processing, and supports a new generation of exchange facilities for them.Peer ReviewedPreprin

Histamine signaling and metabolism identify potential biomarkers and therapies for lymphangioleiomyomatosis

Biomarcador; Histamina; LimfangioleiomiomatosiBiomarcador; Histamina; LinfangioleiomiomatosisBiomarker; Histamine; LymphangioleiomyomatosisInhibition of mTOR is the standard of care for lymphangioleiomyomatosis (LAM). However, this therapy has variable tolerability and some patients show progressive decline of lung function despite treatment. LAM diagnosis and monitoring can also be challenging due to the heterogeneity of symptoms and insufficiency of non-invasive tests. Here, we propose monoamine-derived biomarkers that provide preclinical evidence for novel therapeutic approaches. The major histamine-derived metabolite methylimidazoleacetic acid (MIAA) is relatively more abundant in LAM plasma, and MIAA values are independent of VEGF-D. Higher levels of histamine are associated with poorer lung function and greater disease burden. Molecular and cellular analyses, and metabolic profiling confirmed active histamine signaling and metabolism. LAM tumorigenesis is reduced using approved drugs targeting monoamine oxidases A/B (clorgyline and rasagiline) or histamine H1 receptor (loratadine), and loratadine synergizes with rapamycin. Depletion of Maoa or Hrh1 expression, and administration of an L-histidine analog, or a low L-histidine diet, also reduce LAM tumorigenesis. These findings extend our knowledge of LAM biology and suggest possible ways of improving disease management.This research was supported by AELAM, The LAM Foundation (Seed Grant 2019), Instituto de Salud Carlos III grants PI15/00854, PI18/01029, and ICI19/00047 (co-funded by European Regional Development Fund (ERDF), a way to build Europe), Generalitat de Catalunya SGR grants 2014-364 and 2017-449, the CERCA Program, and ZonMW-TopZorg grant 842002003. C.L.M. acknowledges the financial support (PRA-2017-51 project) of the University of Pisa. A.U.K. is supported by Nottingham Trent University’s Independent Fellowship Scheme