The activity of mouse Cerberus like 2 during cardiogenesis - genetic and morphogenetic studies

Cardiogenesis is a delicate and complex process that requires the coordination of an intricate network of pathways and the different cell types. Therefore, understanding heart development at the morphogenetic level is an essential requirement to uncover the causes of congenital heart disease and to provide insight for disease therapies. Mouse Cerberus like 2 (Cerl2) has been defined as a Nodal antagonist in the node with an important role in the Left-Right (L/R) axis establishment, at the early embryonic development. As expected, Cerl2 knockout mice (Cerl2-/-) showed multiple laterality defects with associated cardiac failure. In order to identify the endogenous role of Cerl2 during heart formation independent of its described functions in the node, we accurately analyzed animals where laterality defects were not present. We thereby unravel the consequences of Cerl2 lossof- function in the heart, namely increased left ventricular thickness due to hyperplasia of cardiomyocytes and de-regulated expression of cardiac genes. Furthermore, the Cerl2 mutant neonates present impaired cardiac function. Once that the cardiac expression of Cerl2 is mostly observed in the left ventricle until around midgestration, this result suggest a specific regulatory role of Cerl2 during the formation of the left ventricular myoarchitecture. Here, we present two possible molecular mechanisms underlying the cardiac Cerl2 function, the regulation of Cerl2 antagonist in activation of the TGFßs/Nodal/Activin/Smad2 signaling identified by increased Smad2 phosphorilation in Cerl2-/- hearts and the negative feedback between Cerl2 and Wnt/ß-catenin signaling in heart formation. In this work and since embryonic stem cells derived from 129 mice strain is extensively used to produce targeted mutants, we also present echocardiographic reference values to progressive use of juveniles and young adult 129/Sv strain in cardiac studies. In addition, we investigate the cardiac physiology of the surviving Cerl2 mutants in 129/Sv background over time through a follow-up study using echocardiographic analysis. Our results revealed that Cerl2-/- mice are able to improve and maintain the diastolic and most of systolic cardiac physiologic parameters as analyzed until young adult age. Since Cerl2 is no longer expressed in the postnatal heart, we suggest that an intrinsic and compensatory mechanism of adaptation may be active for recovering the decreased cardiac function found in Cerl2 mutant neonates. Altogether, these data highlight the role of Cerl2 during embryonic heart development in mice. Furthermore, we also suggest that Cerl2-/- may be an interesting model to uncover the molecular, cellular and physiological mechanisms behind the improvement of the cardiac function, contributing to the development of therapeutic approaches to treat heart failures.

Electrical characterization of metal-oxide-polymer devices for non-volatile memory applications

The objective of this thesis is to study the properties of resistive switching effect based on bistable resistive memory which is fabricated in the form of Al2O3/polymer diodes and to contribute to the elucidation of resistive switching mechanisms. Resistive memories were characterized using a variety of electrical techniques, including current-voltage measurements, small-signal impedance, and electrical noise based techniques. All the measurements were carried out over a large temperature range. Fast voltage ramps were used to elucidate the dynamic response of the memory to rapid varying electric fields. The temperature dependence of the current provided insight into the role of trapped charges in resistive switching. The analysis of fast current fluctuations using electric noise techniques contributed to the elucidation of the kinetics involved in filament formation/rupture, the filament size and correspondent current capabilities. The results reported in this thesis provide insight into a number of issues namely: (i) The fundamental limitations on the speed of operation of a bi-layer resistive memory are the time and voltage dependences of the switch-on mechanism. (ii) The results explain the wide spread in switching times reported in the literature and the apparently anomalous behaviour of the high conductance state namely the disappearance of the negative differential resistance region at high voltage scan rates which is commonly attributed to a “dead time” phenomenon which had remained elusive since it was first reported in the ‘60s. (iii) Assuming that the current is filamentary, Comsol simulations were performed and used to explain the observed dynamic properties of the current-voltage characteristics. Furthermore, the simulations suggest that filaments can interact with each other. (iv) The current-voltage characteristics have been studied as a function of temperature. The findings indicate that creation and annihilation of filaments is controlled by filling and neutralizing traps localized at the oxide/polymer interface. (v) Resistive switching was also studied in small-molecule OLEDs. It was shown that the degradation that leads to a loss of light output during operation is caused by the presence of a resistive switching layer. A diagnostic tool that predicts premature failure of OLEDs was devised and proposed. Resistive switching is a property of oxides. These layers can grow in a number of devices including, organic light emitting diodes (OLEDs), spin-valve transistors and photovoltaic devices fabricated in different types of material. Under strong electric fields the oxides can undergo dielectric breakdown and become resistive switching layers. Resistive switching strongly modifies the charge injection causing a number of deleterious effects and eventually device failure. In this respect the findings in this thesis are relevant to understand reliability issues in devices across a very broad field.

Papel das proteínas de choque térmico na apoptose mediada por espécies reativas de oxigénio em culturas celulares

Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

Relações entre capacidades musicais, consciência fonológica e desempenho da leitura em crianças do 1º e 2º ano de escolaridade

Dissertação de mestrado, Neurociências Cognitivas e Neuropsicologia, Faculdade de Ciências Humanas e Sociais, Universidade do Algarve, 2015

Characterization of TRIB2 following PI3K inhibition

Dissertação de mestrado, Oncobiologia,(Mecanismos Moleculares do Cancro), Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

Characterization of pro- and anti-angiogenic factors in models of diabetic retinopathy

Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2015

Estudo do papel de CITED2 na diferenciação das células estaminais embrionárias

Dissertação de mestrado, Biologia Molecular e Microbiana, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Quimioterapia da dengue: fármacos disponíveis e perspectivas de novas terapêuticas

Dissertação de mestrado, Ciências Farmacêuticas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Caracterização de variantes de Grapevine Fanleaf Virus (GFLV), Arabis Mosaic Virus (ARMV) e respectivos RNAS satélites presentes em castas portuguesas de Vitis Vinifera

Dissertação de mestrado, Biologia Molecular e Microbiana, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Route planning in wireless sensor networks for data gathering purposes

Dissertação de Mestrado, Engenharia Informática, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Satisfação marital e stresse parental em mães da população geral: um estudo correlacional

Dissertação de mestrado, Psicologia Clínica e da Saúde, Faculdade de Ciências Humanas e Sociais, Universidade do Algarve, 2015

Abordagens farmacológicas e modelos animais para a Lesão Aguda do Pulmão e Síndrome de Dificuldade Respiratória Aguda

Dissertação de Mestrado, Ciências Farmacêuticas, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

Loss of Par3 leads to aberrant divisions and faster mitotic progression in differentiating primary murine keratinocytes

Dissertação de Mestrado, Oncobiologia: Mecanismos Moleculares do Cancro, Faculdade de Ciências e Tecnologia, Universidade do Algarve, 2015

A pluridocência no 1º Ciclo

Dissertação de mestrado, Ensino do 1º e do 2º Ciclos do Ensino Básico, Escola Superior de Educação e Comunicação, Universidade do Algarve, 2014

Papel do peptídeo natriurético cerebral de tipo B na classificação do tipo de AVC isquémico

Tese de doutoramento, Medicina Clinica (Neurologia), Universidade de Lisboa, Faculdade de Medicina, 2014