High-throughput genome processing, sophisticated protein sequence analysis, programming, and information management were used to achieve two major advances in the comparative genomics of microbial signal transduction. First, an integrated and flexible bioinformatics platform and the Microbial Signal Transduction database (MiST) were developed, which facilitated the genome-wide analysis of bacterial signal transduction. This platform was used successfully for the high-throughput identification and classification of signal transduction proteins in more than 300 archaeal and bacterial organisms. Second, analysis of information encoded in prokaryotic genomes revealed that the majority of signal transduction systems consist of one-component systems a single protein containing both input and output domains but lacking phosphotransfer domains typical of two-component systems. The prevalence of one-component systems is a paradigm-shifting discovery because two-component systems are currently viewed as the primary mode of signal transduction in prokaryotes. One-component systems are more widely distributed among bacteria and archaea and display a greater diversity of domains than two-component systems. Additionally, in-depth bioinformatic analyses were performed that further characterized the function of two, input, signaling domains. In summary, this systematic, high-throughput delineation of microbial signal transduction is another step forward in our understanding of the genomic basis of life.

TTL3 gene was identified by forward screening of genes involved in lateral root development in Arabidopsis thaliana based on its expression pattern. TTL3 belongs to the TTL (TETRATRICOPEPTIDE-REPEAT THIOREDOXIN-LIKE) gene family. The diploma thesis is aimed on characterisation of changes in TTL1, TTL3 a TTL4 promotor activities in response to external conditions (availability of nitrogen or phosphorus) that affect root growth. Obtained data should elucidate possible relation among TTL gene expression activities, root growth rate, and apical meristem activity. Nitrogen or phosphorus deficiency triggered changes in root growth and root system morphology of experimental plants. Short-term nitrogen deficiency stimulated root growth. Short-term phosphorus deficiency induced gradual growth cessation in main root and long laterals. Long-term deficiency reduced root growth of both N-deficient and P-deficient plants compared to control. The root system size of N-deficient and P-deficient plant was almost similar. Determination of promotor activity using β-glucuronidase reporter gene showed changes in expression activity and its localization in response to root growth intensity. TTL4 gene promotor activity was the most responsive. Its activity was generally higher in slowly growing roots, particularly under...

This work presents a methodology to describe the dynamics and topology of biological regulatory networks through the application of graph theory. We model these networks using Boolean rules and simulations performed with algorithms implemented in MATHEMATICA 7.0. Through this methodology, we characterize the regulatory network of opening and closing of the stomata of a plant by abscisic acid (ABA), including the relationships between the network s elements during the dynamics and the description of the state-space by comparing each one of its elements. For the state of cellular replicative senescence in humans, the goal is to describe a regulatory network of proteins involving the mechanisms of Shelterin complex, DNA double-strand break signaling, and the cell cycle arrest in G1 phase. The network topology must involve a combination of pathways and modules to ensure the stability of the signal and the permanent cell-cycle arrest. The state senescent is also characterized by establishing a secretory phenotype (SASP) with both beneficial and harmful effects for the organism. Different pathways are identified along with the activation of NF-kB in the regulation of these phenotypes and in this sense, a regulatory network to regulate the SASP in replicative senescence is proposed and the main consequences of the SASP for human colon are identified via analysis of microarray data related to normal colon, inflamed colon, colonic adenoma and carcinoma of the colon. / Este trabalho apresenta uma metodologia para descrever a dinâmica e a topologia de redes biológicas regulatórias através da aplicação da teoria de grafos, da modelagem de redes a partir de regras booleanas e através do uso de simulações baseadas em algoritmos implementados no software MATHEMATICA 7.0. Por meio desta metodologia procurou-se caracterizar a rede de regulação de abertura e fechamento dos estômatos de uma planta pelo ácido abscísico (ABA), incluindo a relação entre os elementos da rede durante a dinâmica e a descrição do espaço de estados. No estudo do estado celular de senescência replicativa em humanos, o objetivo é descrever uma rede regulatória de proteínas envolvendo os mecanismos do complexo de Shelterin com a sinalização de duplas quebras no DNA e a sinalização da parada do ciclo celular na fase G1. Por meio desta rede, a topologia deve envolver a combinação de vias e módulos para garantir a estabilidade da sinalização e a parada permanente da célula no estado senescente. O estado senescente também é caracterizado pelo estabelecimento de um fenótipo secretor (SASP) com efeitos tanto benéficos quanto prejudiciais para o organismo. Diferentes vias estão identificadas juntamente com a ativação de NF-kB na regulação deste fenótipo e nesse sentido, uma rede regulatória do SASP em senescência replicativa é proposta e as principais consequências do SASP para o cólon humano são identificadas através da análise de dados de microarranjos que relacionam cólon normal, cólon inflamado, adenoma de cólon e carcinoma de cólon.

In this review, we focused on putatively interesting biomarkers of interstitial cystitis/bladder pain syndrome (IC/BPS) in relation to the etiopathology of this disease. Since its etiopathology is still under discussion, the development of novel biomarkers is critical for the correct classification of the patients in order to open personalized treatment options, on the one hand, and to separate true IC/BPS from the numerous confusable diseases with comparable symptom spectra on the other hand. There is growing evidence supporting the notion that the classical or Hunner-type IC (HIC) and the non-Hunner-type IC (NHIC) are different diseases with different etiopathologies and different pathophysiology at the full-blown state. While genetic alterations indicate close relationship to allergic and autoimmune diseases, at present, the genetic origin of IC/BPS could be identified. Disturbed angiogenesis and impairment of the microvessels could be linked to altered humoral signaling cascades leading to enhanced VEGF levels which in turn could enhance leucocyte and mast cell invasion. Recurrent or chronic urinary tract infection has been speculated to promote IC/BPS. New findings show that occult virus infections occurred in most IC/BPS patients and that the urinary microbiome was altered, supporting the hypothesis of infections as major players in IC/BPS. Environmental and nutritional factors may also influence IC/BPS, at least at a late state (e.g., cigarette smoking can enhance IC/BPS symptoms). The damage of the urothelial barrier could possibly be the result of many different causality chains and mark the final state of IC/BPS, the causes of this development having been introduced years ago. We conclude that the etiopathology of IC/BPS is complex, involving regulatory mechanisms at various levels. However, using novel molecular biologic techniques promise more sophisticated analysis of this pathophysiological network, resulting in a constantly improvement of our understanding of IC/BPS and related diseases.