Espace géographique, spatialisation et modélisation en dynamique des systèmes

International audienceCette contribution présente le rôle dévolu à l'espace en Dynamique des Systèmes. Les propriétés systémiques de l'espace géographique sont tout d'abord énoncées, puis sont examinées les principale manières d'introduire l'espace dans la modélisation en Dynamique des Systèmes. Les difficultés rencontrées pour rendre compte de la complexité spatiale sont également soulignées. Enfin, deux exemples d'études démontrent l'apport du raisonnement spatial à la compréhension des dynamiques régionales. / This paper focuses upon the role of space in System Dynamics. In a first stage, systemic properties of geographical space are set out. Then the main methods and studies incorporating spatial elements are reviewed. Difficulties in taking into account spatial complexity in modeling processes are also outlined. In a second stage, two examples of studies enhance how the behaviour of regional dynamics is better understood by integrating a spatial thought into system dynamics modeling

Interaction between methionine synthase isoforms and MMACHC: characterization in cblG-variant, cblG and cblC inherited causes of megaloblastic anaemia

The cblG and cblC disorders of cobalamin (Cbl) metabolism are two inherited causes of megaloblastic anaemia. In cblG, mutations in methionine synthase (MTR) decrease conversion of hydroxocobalamin (HOCbl) to methylcobalamin, while in cblC, mutations in MMACHC disrupt formation of cob(II)alamin (detected as HOCbl). Cases with undetectable methionine synthase (MS) activity are extremely rare and classified as ‘cblG-variant'. In four ‘cblG-variant' cases, we observed a decreased conversion of cyanocobalamin to HOCbl that is also seen in cblC cases. To explore this observation, we studied the gene defects, splicing products and expression of MS, as well as MS/MMACHC protein interactions in cblG-variant, cblG, cblC and control fibroblasts. We observed a full-size MS encoded by MTR-001 and a 124 kDa truncated MS encoded by MTR-201 in cblG, cblC, control fibroblasts and HEK cells, but only the MTR-201 transcript and inactive truncated MS in cblG-variant cells. Co-immunoprecipitation and proximity ligation assay showed interaction between truncated MS and MMACHC in cblG-variant cells. This interaction decreased 2.2, 1.5 and 5.0-fold in the proximity ligation assay of cblC cells with p.R161Q and p.R206W mutations, and HEK cells with knock down expression of MS by siRNA, respectively, when compared with control cells. In 3D modelling and docking analysis, both truncated and full-size MS provide a loop anchored to MMACHC, which makes contacts with R-161 and R-206 residues. Our data suggest that the interaction of MS with MMACHC may play a role in the regulation of the cellular processing of Cbls that is required for Cbl cofactor synthesi

Publisher Correction: A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients

The original version of this Article contained an error in the title, which was incorrectly given as 'APRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients'. This has now been corrected in both the PDF and HTML versions of the Article to read 'A PRDX1 mutant allele causes a MMACHC secondary epimutation in cblC patients'