The histone demethylase JMJD2A/KDM4A links ribosomal RNA transcription to nutrients and growth factors availability

The interplay between methylation and demethylation of histone lysine residues is an essential component of gene expression regulation and there is considerable interest in elucidating the roles of proteins involved. Here we report that histone demethylase KDM4A/JMJD2A, which is involved in the regulation of cell proliferation and is overexpressed in some cancers, interacts with RNA Polymerase I, associates with active ribosomal RNA genes and is required for serum-induced activation of rDNA transcription. We propose that KDM4A controls the initial stages of transition from 'poised', non-transcribed rDNA chromatin into its active form. We show that PI3K, a major signalling transducer central for cell proliferation and survival, controls cellular localization of KDM4A and consequently its association with ribosomal DNA through the SGK1 downstream kinase. We propose that the interplay between PI3K/SGK1 signalling cascade and KDM4A constitutes a mechanism by which cells adapt ribosome biogenesis level to the availability of growth factors and nutrients.

Time-dependent electron interference prior to ionization in the hydrogen atom and hydrogen molecular ion

We investigate electron dynamics in the hydrogen atom and the hydrogen molecular ion when exposed to long wavelength laser pulses yet having intensity insufficient to ionize the system. We find that the field is still able to drive the electron, leading to time-dependent interference effects.

Interference cancellation for distributed wireless systems

O tema principal desta tese é o problema de cancelamento de interferência para sistemas multi-utilizador, com antenas distribuídas. Como tal, ao iniciar, uma visão geral das principais propriedades de um sistema de antenas distribuídas é apresentada. Esta descrição inclui o estudo analítico do impacto da ligação, dos utilizadores do sistema, a mais antenas distribuídas. Durante essa análise é demonstrado que a propriedade mais importante do sistema para obtenção do ganho máximo, através da ligação de mais antenas de transmissão, é a simetria espacial e que os utilizadores nas fronteiras das células são os mais bene ciados. Tais resultados são comprovados através de simulação. O problema de cancelamento de interferência multi-utilizador é considerado tanto para o caso unidimensional (i.e. sem codi cação) como para o multidimensional (i.e. com codi cação). Para o caso unidimensional um algoritmo de pré-codi cação não-linear é proposto e avaliado, tendo como objectivo a minimização da taxa de erro de bit. Tanto o caso de portadora única como o de multipla-portadora são abordados, bem como o cenário de antenas colocadas e distribuidas. É demonstrado que o esquema proposto pode ser visto como uma extensão do bem conhecido esquema de zeros forçados, cuja desempenho é provado ser um limite inferior para o esquema generalizado. O algoritmo é avaliado, para diferentes cenários, através de simulação, a qual indica desempenho perto do óptimo, com baixa complexidade. Para o caso multi-dimensional um esquema para efectuar "dirty paper coding" binário, tendo como base códigos de dupla camada é proposto. No desenvolvimento deste esquema, a compressão com perdas de informação, é considerada como um subproblema. Resultados de simulação indicam transmissão dedigna proxima do limite de Shannon.

Analysis of RNA-seq data from the interaction of Coffea spp. - Colletotrichum kahawae

Tese de mestrado em Bioinformática e Biologia Computacional (Bioinformática), apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2014

A low complexity cross-correlation interference mitigation technique for GNSS

The finite length Gold codes used in satellite navigation systems limit their dynamic range, resulting in the introduction of unwanted peaks that can mask out signals of interest. In this paper, a novel cross-correlation interference mitigation technique dealing with this issue is introduced. A brief overview of the multiple access interference problem inherent in satellite navigation systems using the code division multiple access technique is followed by the details of the proposed method. Simulation case studies and analyses of the results detailing weak signal scenarios, carried out entirely using the Global Navigation System Scope, are presented. A comparison of the results is given in the conclusions section along with remarks on the performance of the proposed method and future work to be carried out.

RT-Bst: an integrated approach for reverse transcription and enrichment of cDNA from viral RNA

The synthesis of cDNA from RNA is challenging due to the inefficiency of reverse transcription (RT). In order to address this, a method was developed known as RT-Bst for sequential RT of RNA and Bst DNA polymerase amplification for enrichment of cDNA in a single tube reaction. Using genomic RNA from bacteriophage MS2, the yield of cDNA produced by RT alone and RT-Bst were compared by analysis of PCR-amplified products. Using random primers a superior performance was observed when amplifying MS2 RNA following RT-Bst compared to RT alone, indicating that greater quantities of cDNA were present after RT-Bst. RT-Bst was also compared with RT alone for their relative ability to produce sufficient cDNA to amplify 8 target regions spanning the respiratory syncytial virus (RSV) genome. Six out of 8 targets were amplified consistently by PCR subsequent to RT-Bst amplification whereas only 3 out of 8 targets could be amplified after RT alone. RSV sequences were selectively amplified using RSV specific primers from a mixed template containing an excess of MS2 RNA in a RT-Bst reaction without amplifying MS2 sequences. This suggests that RT-Bst can be used to amplify RNA sequences non-specifically using random primers and specifically using sequence specific primers and enhances the yield of cDNA when compared to RT alone.

Post-Transcriptional Regulation of BCL2 mRNA by the RNA-Binding Protein ZFP36L1 in Malignant B Cells

The human ZFP36 zinc finger protein family consists of ZFP36, ZFP36L1, and ZFP36L2. These proteins regulate various cellular processes, including cell apoptosis, by binding to adenine uridine rich elements in the 3′ untranslated regions of sets of target mRNAs to promote their degradation. The pro-apoptotic and other functions of ZFP36 family members have been implicated in the pathogenesis of lymphoid malignancies. To identify candidate mRNAs that are targeted in the pro-apoptotic response by ZFP36L1, we reverse-engineered a gene regulatory network for all three ZFP36 family members using the ‘maximum information coefficient’ (MIC) for target gene inference on a large microarray gene expression dataset representing cells of diverse histological origin. Of the three inferred ZFP36L1 mRNA targets that were identified, we focussed on experimental validation of mRNA for the pro-survival protein, BCL2, as a target for ZFP36L1. RNA electrophoretic mobility shift assay experiments revealed that ZFP36L1 interacted with the BCL2 adenine uridine rich element. In murine BCL1 leukemia cells stably transduced with a ZFP36L1 ShRNA lentiviral construct, BCL2 mRNA degradation was significantly delayed compared to control lentiviral expressing cells and ZFP36L1 knockdown in different cell types (BCL1, ACHN, Ramos), resulted in increased levels of BCL2 mRNA levels compared to control cells. 3′ untranslated region luciferase reporter assays in HEK293T cells showed that wild type but not zinc finger mutant ZFP36L1 protein was able to downregulate a BCL2 construct containing the BCL2 adenine uridine rich element and removal of the adenine uridine rich core from the BCL2 3′ untranslated region in the reporter construct significantly reduced the ability of ZFP36L1 to mediate this effect. Taken together, our data are consistent with ZFP36L1 interacting with and mediating degradation of BCL2 mRNA as an important target through which ZFP36L1 mediates its pro-apoptotic effects in malignant B-cells.