From pathway to regulon in Arabidopsis

Combined bioinformatic approaches, using genomic and transcriptomic data, are applied to investigate the fatty acid biosynthesis pathway, at the molecular level, and in the context of the system biology of Arabidopsis. Fatty acids are essential components of all known bacterial and eukaryotic cells with critical role in cells as energy reserves and the metabolic precursors for biological membranes. The pathway for fatty acid synthesis seems to be conserved across all living systems. Acetyl-CoA carboxylase, a member of a superfamily of biotin-dependent enzymes, catalyzes the first committed step of the fatty acid biosynthesis pathway. Phylogenetic study exposed complex and intertwined evolutionary histories of this family, with multiple domain fusions and rearrangements. As revealed by meta-analysis of a wide array of Arabidopsis transcriptomic data, fatty acid biosynthesis is transcriptionally regulated, and this regulation not only extends across all pathway reactions, but also some substrate- and cofactor-producing reactions, thus defining a major transcriptionally co-regulated pathway. Meta-analysis of the transcriptome is extended to find groups of coexpressed genes (also called modules, or regulons) in the Arabidopsis genome. Major functionally-coherent gene groups were identified. These comprise development, information processing, defense, and metabolism, as well as tissue- and organelle-specific processes

Regulon organization of Arabidopsis

<p>Abstract</p> <p>Background</p> <p>Despite the mounting research on Arabidopsis transcriptome and the powerful tools to explore biology of this model plant, the organization of expression of Arabidopsis genome is only partially understood. Here, we create a coexpression network from a 22,746 Affymetrix probes dataset derived from 963 microarray chips that query the transcriptome in response to a wide variety of environmentally, genetically, and developmentally induced perturbations.</p> <p>Results</p> <p>Markov chain graph clustering of the coexpression network delineates 998 regulons ranging from one to 1623 genes in size. To assess the significance of the clustering results, the statistical over-representation of GO terms is averaged over this set of regulons and compared to the analogous values for 100 randomly-generated sets of clusters. The set of regulons derived from the experimental data scores significantly better than any of the randomly-generated sets. Most regulons correspond to identifiable biological processes and include a combination of genes encoding related developmental, metabolic pathway, and regulatory functions. In addition, nearly 3000 genes of unknown molecular function or process are assigned to a regulon. Only five regulons contain plastomic genes; four of these are exclusively plastomic. In contrast, expression of the mitochondrial genome is highly integrated with that of nuclear genes; each of the seven regulons containing mitochondrial genes also incorporates nuclear genes. The network of regulons reveals a higher-level organization, with dense local neighborhoods articulated for photosynthetic function, genetic information processing, and stress response.</p> <p>Conclusion</p> <p>This analysis creates a framework for generation of experimentally testable hypotheses, gives insight into the concerted functions of Arabidopsis at the transcript level, and provides a test bed for comparative systems analysis.</p

Wycena europejskich i amerykańskich opcji za pomocą procesów decyzyjnych Markowa

W pracy opisano teoretyczne podstawy procesów decyzyjnych Markowa (MDP), przedstawiono algorytmy wyceny europejskich opcji kupna i sprzedaży oraz amerykańskich opcji kupna wykorzystujące MDP. Wyniki porównano z wycenami uzyskanymi metodą Blacka–Scholesa

Koszty długu publicznego i bankructwa państwa

W pracy zestawiono wyniki badań empirycznych dotyczących wpływu wysokości długu publicznego, deficytu budżetowego i bankructwa państwa na gospodarkę. Otrzymane rezultaty wskazują, że nadmierne zadłużenie jest bardzo szkodliwe dla rozwoju gospodarczego, w przeciwieństwie do ogłoszenia bankructwa, które na ogół uzdrawia gospodarkę i jest początkiem wyjścia z kryzysu

Dissecting the dynamics of dysregulation of cellular processes in mouse mammary gland tumor

<p>Abstract</p> <p>Background</p> <p>Elucidating the sequence of molecular events underlying breast cancer formation is of enormous value for understanding this disease and for design of an effective treatment. Gene expression measurements have enabled the study of transcriptome-wide changes involved in tumorigenesis. This usually occurs through identification of differentially expressed genes or pathways.</p> <p>Results</p> <p>We propose a novel approach that is able to delineate new cancer-related cellular processes and the nature of their involvement in tumorigenesis. First, we define modules as densely interconnected and functionally enriched areas of a Protein Interaction Network. Second, 'differential expression' and 'differential co-expression' analyses are applied to the genes in these network modules, allowing for identification of processes that are up- or down-regulated, as well as processes disrupted (low co-expression) or invoked (high co-expression) in different tumor stages. Finally, we propose a strategy to identify regulatory miRNAs potentially responsible for the observed changes in module activities. We demonstrate the potential of this analysis on expression data from a mouse model of mammary gland tumor, monitored over three stages of tumorigenesis. Network modules enriched in adhesion and metabolic processes were found to be inactivated in tumor cells through the combination of dysregulation and down-regulation, whereas the activation of the integrin complex and immune system response modules is achieved through increased co-regulation and up-regulation. Additionally, we confirmed a known miRNA involved in mammary gland tumorigenesis, and present several new candidates for this function.</p> <p>Conclusions</p> <p>Understanding complex diseases requires studying them by integrative approaches that combine data sources and different analysis methods. The integration of methods and data sources proposed here yields a sensitive tool, able to pinpoint new processes with a role in cancer, dissect modulation of their activity and detect the varying assignments of genes to functional modules over the course of a disease.</p

Fokus på barns egen helse

I denne oppgaven ønsker jeg å belyse et tema som jeg mener er viktig for meg i rollen som kroppsøvingslærer, og som også er viktig i dagens samfunn. Og det er å bevisstgjøre elevene om god og sunn helse. Men hva er sunn helse? Er det å være fysisk aktiv? Er det et sunt kosthold? Og hva er et sunt kosthold? I jungelen av gode råd og anbefalinger er det ikke alltid så lett å vite hva som er ”det rette”. Jeg har nok ikke det ultimate svaret jeg heller, men vil prøve å hjelpe elevene til å se sammenhengen mellom mat, søvn og aktivitet, og at dette kan være med på å gi dem en sunn helse. Jeg arbeider som ”ufaglært” lærer ved en 1-10 skole og tenker at jeg veileder daglig, både faglig og sosialt. Det er mange forskjellige typer veiledning og jeg tror vi lærere veileder mer enn vi selv er klar over. Jeg føler meg bevisst på rollen som veileder, etter studiene i sosialpedagogikk, som har vektlagt både veiledning og kommunikasjon. Jeg vil i denne oppgaven ha fokus på barn og unges helse, og ønsker å øke elevenes kunnskap om sin egen helse. Det jeg legger i begrepet sunn helse, er summen av mat, søvn og aktivitet og jeg vil derfor prøve å veilede en del av mine elever i hva som kan være med på å gi dem sunn helse. I tillegg er dette et aktuelt tema i samfunnet, fordi barn og unge er mer stillesittende i dagens samfunn enn eldre mennesker, noe som kan gi de unge store helseplager senere i livet. Jeg har fått tillatelse fra ledelsen ved skolen til å bruke en aktivitetsdagbok som verktøy i mitt arbeide med å sette fokus på sunn helse. Jeg kommer senere inn på hva en aktivitetsdagbok er. Jeg har ikke vurdert det nødvendig å innhente tillatelse fra foreldre, fordi tema og kunnskap om helse går igjen i læreplanen i fagene kroppsøving og mat og helse. (www.udir.no

Articulation of three core metabolic processes in Arabidopsis: Fatty acid biosynthesis, leucine catabolism and starch metabolism

<p>Abstract</p> <p>Background</p> <p>Elucidating metabolic network structures and functions in multicellular organisms is an emerging goal of functional genomics. We describe the co-expression network of three core metabolic processes in the genetic model plant <it>Arabidopsis thaliana</it>: fatty acid biosynthesis, starch metabolism and amino acid (leucine) catabolism.</p> <p>Results</p> <p>These co-expression networks form modules populated by genes coding for enzymes that represent the reactions generally considered to define each pathway. However, the modules also incorporate a wider set of genes that encode transporters, cofactor biosynthetic enzymes, precursor-producing enzymes, and regulatory molecules. We tested experimentally the hypothesis that one of the genes tightly co-expressed with starch metabolism module, a putative kinase AtPERK10, will have a role in this process. Indeed, knockout lines of AtPERK10 have an altered starch accumulation. In addition, the co-expression data define a novel hierarchical transcript-level structure associated with catabolism, in which genes performing smaller, more specific tasks appear to be recruited into higher-order modules with a broader catabolic function.</p> <p>Conclusion</p> <p>Each of these core metabolic pathways is structured as a module of co-expressed transcripts that co-accumulate over a wide range of environmental and genetic perturbations and developmental stages, and represent an expanded set of macromolecules associated with the common task of supporting the functionality of each metabolic pathway. As experimentally demonstrated, co-expression analysis can provide a rich approach towards understanding gene function.</p