http://hdl.handle.net/10362/3667 2013-06-08T10:52:22Z http://hdl.handle.net/10362/8589 Title: Intron evolution in primates Authors: Fernando, Olga Description: Dissertation presented to obtain a Ph.D degree in Evolutionary Biology 2011-09-01T00:00:00Z http://hdl.handle.net/10362/8588 Title: Regulation of autoimmune neuroinflammation by stress-responsive genes Authors: Cunha, Andreia Abstract: Inflammation is a protective response generated by innate immune cells, upon infection and/or tissue injury, and aims at clearing the source of infection or noxious stimuli. It is required for activation of adaptive immunity. Inflammation has several layers of regulation in order to minimize the degree of tissue damage. Antigen-presenting cells (APC) constitute one layer of regulation as they initiate the activation of T helper (TH) cells, bridging innate and adaptive immunity. The TH cell response generated is usually protective, although in certain circumstances, that are not completely understood, can also become pathological, as occurs in multiple sclerosis (MS) and in its mouse model, experimental autoimmune encephalomyelitis (EAE). Thus, mechanisms restraining TH cell activation and/or reactivation should prevent the pathogenesis of autoimmune neuroinflammation. In this Thesis we describe two of such mechanisms: one controlled by the transcription factor NF-E2-related factor 2 (Nrf2) and another controlled by one of its downstream genes Heme oxygenase-1 (Hmox1), which encodes the enzyme HO-1. Nrf2 is a transcription factor that regulates cellular responses to oxidative stress, while HO-1 catabolizes heme into carbon monoxide (CO), iron, and biliverdin. Both, Nrf2 and HO-1 have been implicated in dampening inflammatory reactions, including autoimmune neuroinflammation. The aim of this Thesis was to understand the role(s) of Nrf2, and its downstream gene Hmox1, in the regulation of autoimmune neuroinflammation. For this, we studied the role of Nrf2 and Hmox1 expression in the pathogenesis of EAE. Further, we investigated the impact of pharmacological induction of HO-1 expression and exogenous CO administration from a therapeutic point of view. (...) Description: Dissertation presented to obtain the Ph.D degree in Biology 2012-03-01T00:00:00Z http://hdl.handle.net/10362/8585 Title: Insights into the biological significance of alternative splicing in Arabidopsis: functional characterization of a dual-targeted E3 ligase and the SCL30a SR protein Authors: Carvalho, Sofia Domingues de Abstract: RNA splicing is an essential step in eukaryotic gene expression during which introns are precisely removed from the precursor-mRNA (pre-mRNA) and exons joined together to form the mature mRNA molecule. The presence of numerous exons per gene enables the splicing machinery to process the same premRNA differently by selectively removing different intronic sequences, thus generating multiple transcripts, and eventually more than one protein, from a single gene. Such alternative splicing pathways have emerged as a key mechanism for generating proteome diversity and functional complexity. The prevalence of alternative splicing in many genomes, including those of higher plants, suggests that this mechanism plays crucial roles in biological processes. To adapt to an environment in constant change, plants, as sessile organisms, have evolved high degrees of both developmental plasticity and stress tolerance, which are ultimately regulated at the genome level. The exceptional versatility associated with gene regulation by alternative splicing is likely to play a prominent role in plant responses to environmental cues, but the biological significance of this posttranscriptional regulatory mechanism in plants remains poorly understood.(...) Description: Dissertation presented to obtain the Ph.D degree in Molecular Biology 2012-05-01T00:00:00Z http://hdl.handle.net/10362/8576 Title: Chromosomal structure: a selectable trait for evolution Authors: Avelar, Ana Teresa Abstract: Evolution is driven by biological diversity, which is displayed by different phenotypes. These phenotypes arise as a coordinated response to the genetic composition of each organism. Chromosomal rearrangements (CRs), such as inversions and translocations, are a type of mutation contributing both to be-tween and within species phenotypic variation. Additionally, they are a promi-nent feature of several types of cancer, in particular lymphomas. However, unlike other types of mutations, the effects of inversions and translocations have not yet been directly quantified. The objective of this thesis is to quantify the mitotic and meiotic effects of CRs and to understand if chromosomal di-versity is an important macromutation for the generation of biological diversity. Initially, we asked whether chromosomal rearrangements are a poly-morphic mutation in the fission yeast Schizosaccharomyces pombe. We found, like others, that karyotype differences are very common in S. pombe isolates in spite of nucleotide diversity of the order observed within species diversity. This fact led us to test the genetic isolation between the natural iso-lates by scoring hybrid viabilities in pairwise crosses. We found that in some cases hybrid viability was severely impaired. These results prompted us to measure the meiotic and mitotic effects of single CRs in an otherwise isogenic background.(...) Description: Dissertation presented to obtain the Ph.D degree in Evolutionary Biology 2012-11-01T00:00:00Z