Browsing by Issue Date, starting with "2010-05"
Now showing 1 - 5 of 5
Results Per Page
Sort Options
- Ant colony algorithms for multiple objective combinatorial optimization: applications to the minimum spanning trees problemsPublication . Cardoso, Pedro J. S.The study of meta-heuristic solutions based on the Ant Colony Optimization (ACO) paradigm for the Multiple Objective Minimum Spanning Trees and related combinatorial problems is the main concern of this investigation. In the commonly accepted complexity scale for problems, the Multiple Objective Minimum Spanning Trees is rated as an $\NP$-complete problem. Furthermore, as in the generality of the multiple objective optimization problem, the solution of the Minimum Spanning Trees case is a set of trade-off solutions in the sense that to improve one of the objectives it is necessary to worse at least one of the others, which is a major concern in a practical point of view. In the first part of the investigation, a theoretical analysis of the problem is made to complement the known results. This analysis corroborates the fact that in practice the use of exact methods to solve the Multiple Objective Minimum Spanning Trees problems is only applied in specific circumstances. This implies that to solve the problem an approximation method must be considered as an alternative. In particular, two methods based on the ACO paradigm are proposed: the Multiple Objective Network optimization based on an ACO (MONACO) and the $\epsilon$-Depth ANT Explorer (e-DANTE). The MONACO method uses a set of pheromone trails and specific heuristics to approximate the Pareto set. The e-DANTE method is an improvement of the MONACO method that uses a depth search procedure, based on the best performing solutions, to deeply exploit the search space. The proposed methods are tested with selected multiple objective problems, improving the results previously obtained by other authors. To test the MONACO and e-DANTE algorithms over the Multiple Objective Minimum Spanning Trees problem is proposed a library/repository of multiple objective network problems established over a systematized set of networks generators. The results obtained with MONACO and e-DANTE are then compared with the results obtained with a Brute Force and the Weighted Sum method.
- Plasmodium infection alters Anopheles gambiae detoxification gene expressionPublication . Felix, Rute C.; Mueller, Pie; Ribeiro, Vera; Ranson, Hilary; Silveira, HenriqueBackground: Anopheles gambiae has been shown to change its global gene expression patterns upon Plasmodium infection. While many alterations are directly related to the mosquito's innate immune response, parasite invasion is also expected to generate toxic by-products such as free radicals. The current study aimed at identifying which loci coding for detoxification enzymes are differentially expressed as a function of Plasmodium berghei infection in midgut and fat body tissues. Results: Using a custom-made DNA microarray, transcript levels of 254 loci primarily belonging to three major detoxification enzyme families (glutathione S-transferases, cytochrome P450 monooxygenases and esterases) were compared in infected and uninfected mosquitoes both during ookinete invasion and the release of sporozoites into the hemocoel. The greatest changes in gene expression were observed in the midgut in response to ookinete invasion. Interestingly, many detoxification genes including a large number of P450s were down-regulated at this stage. In the fat body, while less dramatic, gene expression alterations were also observed and occurred during the ookinete invasion and during the release of sporozoites into the hemocoel. While most gene expression changes were tissue-related, CYP6M2, a CYP previously associated with insecticide resistance, was over-expressed both in the midgut and fat body during ookinete invasion. Conclusions: Most toxicity-related reactions occur in the midgut shortly after the ingestion of an infected blood meal. Strong up-regulation of CYP6M2 in the midgut and the fat body as well as its previous association with insecticide resistance shows its broad role in metabolic detoxification.
- Comparison and consolidation of microarray data sets of human tissue expressionPublication . Russ, Jenny; Futschik, Matthias E.Background: Human tissue displays a remarkable diversity in structure and function. To understand how such diversity emerges from the same DNA, systematic measurements of gene expression across different tissues in the human body are essential. Several recent studies addressed this formidable task using microarray technologies. These large tissue expression data sets have provided us an important basis for biomedical research. However, it is well known that microarray data can be compromised by high noise level and various experimental artefacts. Critical comparison of different data sets can help to reveal such errors and to avoid pitfalls in their application. Results: We present here the first comparison and integration of four freely available tissue expression data sets generated using three different microarray platforms and containing a total of 377 microarray hybridizations. When assessing the tissue expression of genes, we found that the results considerably depend on the chosen data set. Nevertheless, the comparison also revealed statistically significant similarity of gene expression profiles across different platforms. This enabled us to construct consolidated lists of platform-independent tissue-specific genes using a set of complementary measures. Follow-up analyses showed that results based on consolidated data tend to be more reliable. Conclusions: Our study strongly indicates that the consolidation of the four different tissue expression data sets can increase data quality and can lead to biologically more meaningful results. The provided compendium of platform-independent gene lists should facilitate the identification of novel tissue-specific marker genes.
- Short RNA half-lives in the slow-growing marine cyanobacterium ProchlorococcusPublication . Steglich, Claudia; Lindell, Debbie; Futschik, Matthias; Rector, Trent; Steen, Robert; Chisholm, Sallie WAbstract Background RNA turnover plays an important role in the gene regulation of microorganisms and influences their speed of acclimation to environmental changes. We investigated whole-genome RNA stability of Prochlorococcus, a relatively slow-growing marine cyanobacterium doubling approximately once a day, which is extremely abundant in the oceans. Results Using a combination of microarrays, quantitative RT-PCR and a new fitting method for determining RNA decay rates, we found a median half-life of 2.4 minutes and a median decay rate of 2.6 minutes for expressed genes - twofold faster than that reported for any organism. The shortest transcript half-life (33 seconds) was for a gene of unknown function, while some of the longest (approximately 18 minutes) were for genes with high transcript levels. Genes organized in operons displayed intriguing mRNA decay patterns, such as increased stability, and delayed onset of decay with greater distance from the transcriptional start site. The same phenomenon was observed on a single probe resolution for genes greater than 2 kb. Conclusions We hypothesize that the fast turnover relative to the slow generation time in Prochlorococcus may enable a swift response to environmental changes through rapid recycling of nucleotides, which could be advantageous in nutrient poor oceans. Our growing understanding of RNA half-lives will help us interpret the growing bank of metatranscriptomic studies of wild populations of Prochlorococcus. The surprisingly complex decay patterns of large transcripts reported here, and the method developed to describe them, will open new avenues for the investigation and understanding of RNA decay for all organisms.
- Analysis of the asymmetrically expressed Ablim1 locus reveals existence of a lateral plate Nodal-independent left sided signal and an early, left-right independent role for nodal flowPublication . Stevens, Jonathan; Ermakov, Alexander; Bragança, José; Hilton, Helen; Underhill, Peter; Bhattacharya, Shoumo; Brown, Nigel A.; Norris, Dominic P.Abstract Background Vertebrates show clear asymmetry in left-right (L-R) patterning of their organs and associated vasculature. During mammalian development a cilia driven leftwards flow of liquid leads to the left-sided expression of Nodal, which in turn activates asymmetric expression of the transcription factor Pitx2. While Pitx2 asymmetry drives many aspects of asymmetric morphogenesis, it is clear from published data that additional asymmetrically expressed loci must exist. Results A L-R expression screen identified the cytoskeletally-associated gene, actin binding lim protein 1 (Ablim1), as asymmetrically expressed in both the node and left lateral plate mesoderm (LPM). LPM expression closely mirrors that of Nodal. Significantly, Ablim1 LPM asymmetry was detected in the absence of detectable Nodal. In the node, Ablim1 was initially expressed symmetrically across the entire structure, resolving to give a peri-nodal ring at the headfold stage in a flow and Pkd2-dependent manner. The peri-nodal ring of Ablim1 expression became asymmetric by the mid-headfold stage, showing stronger right than left-sided expression. Node asymmetry became more apparent as development proceeded; expression retreated in an anticlockwise direction, disappearing first from the left anterior node. Indeed, at early somite stages Ablim1 shows a unique asymmetric expression pattern, in the left lateral plate and to the right side of the node. Conclusion Left LPM Ablim1 is expressed in the absence of detectable LPM Nodal, clearly revealing existence of a Pitx2 and Nodal-independent left-sided signal in mammals. At the node, a previously unrecognised action of early nodal flow and Pkd2 activity, within the pit of the node, influences gene expression in a symmetric manner. Subsequent Ablim1 expression in the peri-nodal ring reveals a very early indication of L-R asymmetry. Ablim1 expression analysis at the node acts as an indicator of nodal flow. Together these results make Ablim1 a candidate for controlling aspects of L-R identity and patterning.