Metabolic Pathway Analysis: from small to genome-scale networks

The need for mathematical modelling of biological processes has grown alongside with the achievements in the experimental field leading to the appearance and development of new fields like systems biology. Systems biology aims at generating new knowledge through modelling and integration of experimental data in order to develop a holistic understanding of organisms. In the first part of my PhD thesis, I compare two different levels of abstraction used for computing metabolic pathways, constraint-based and graph theoretical methods. I show that the current representations of metabolism as a simple graph correspond to wrong mathematical descriptions of metabolic pathways. On the other hand, the use of stoichiometric information and convex analysis as modelling framework like in elementary flux mode analysis, allows to correctly predict metabolic pathways. In the second part of the thesis, I present two of the first methods, based on elementary flux mode analysis, that can compute metabolic pathways in such large metabolic networks: the K-shortest EFMs method and the EFMEvolver method. These methods contribute to an enrichment of the mathematical tools available to model cell biology and more precisely, metabolism. The application of these new methods to biotechnological problems is also explored in this part. In the last part of my thesis, I give an overview of recent achievements in metabolic network reconstruction and constraint-based modelling as well as open issues. Moreover, I discuss possible strategies for integrating experimental data with elementary flux mode analysis. Further improvements in elementary flux mode computation on that direction are put forward

Portuguese guide lines for the use of biological agents in rheumatoid arthritis - october 2011 update

The authors present the revised version of the Portuguese Society of Rheumatology (SPR) guidelines for the treatment of Rheumatoid Arthritis (RA) with biological therapies. In these guidelines the criteria for introduction and maintenance of biological agents are discussed as well as the contraindications and procedures in the case of non-responders. Biological treatment (with a tumour necrosis factor antagonist, abatacept or tocilizumab) should be considered in RA patients with a disease activity score 28 (DAS 28) equal to or greater than 3.2 des pite treatment with at least 20mg-weekly-dose of methotrexate (MTX) for at least 3 months or, if such treatment is not possible, after 3 months of other conventional disease modifying drug or combination therapy. A DAS 28 score between 2.6 and 3.2 with a significant functional or radiological deterioration under treatment with conventional regi -mens could also constitute an indication for biological treatment. The treatment goal should be remission or, if that is not achievable, at least a low disease activity, defined by a DAS28 lower than 3.2,without significative functional or radiological worsening. The response criteria, at the end of the first 3 months of treatment, are a decrease of at least 0.6 in the DAS28 score. After 6 months of treatment res ponse criteria is defined as a decrease greater than 1.2 in the DAS28 score. Non-responders, in accordance to the Rheumatologist's clinical opi -nion, should try a switch to another biological agent (tumour necrosis factor antagonist, abatacept, rituxi mab or tocilizumab).publishersversionpublishe

Characterisation of microbial attack on archaeological bone

As part of an EU funded project to investigate the factors influencing bone preservation in the archaeological record, more than 250 bones from 41 archaeological sites in five countries spanning four climatic regions were studied for diagenetic alteration. Sites were selected to cover a range of environmental conditions and archaeological contexts. Microscopic and physical (mercury intrusion porosimetry) analyses of these bones revealed that the majority (68%) had suffered microbial attack. Furthermore, significant differences were found between animal and human bone in both the state of preservation and the type of microbial attack present. These differences in preservation might result from differences in early taphonomy of the bones. © 2003 Elsevier Science Ltd. All rights reserved