Siradjouba, laboratoire de la gestion des frontières par le Mali

Le village malien de Siradjouba se situe dans la région historique et culturelle du Wassoulou, à cheval sur le Mali et la Guinée, à environ 250 km au sud de Bamako, au cœur d’une région d’exploitation aurifère et d’orpaillage artisanal. Il a attiré mon attention par la récurrence de litiges l’opposant aux localités voisines de Guinée depuis un siècle. L’objectif ici est de confronter l’administration de cet espace frontalier périphérique aux politiques territoriales menées par le Mali depuis son indépendance. Deux périodes sont privilégiées : les années qui suivent l’indépendance du Mali, temps de construction nationale, et depuis 1995, quand le Mali conçoit et promeut le concept de « pays-frontières ».The Malian village of Siradjouba is located in the historical and cultural region of Wassoulou that is straddling Mali and Guinea, and about 250 km south of Bamako, in the heart of an artisanal gold mining area. What came under my attention is the recurring disputes between Siradjouba and Guinean neighbouring places over the last century. My purpose is to observe the administration of this peripheral borderland in light of the territorial policies conducted by the Malian State since its national independence. My paper will focus on two periods: the years after independence, time of national building, and the period since 1995, when Mali has designed and promoted the concept of “pays-frontières”

Protein folding activity of ribosomal rna is a selective target of two unrelated antiprion drugs

Background: 6-Aminophenanthridine (6AP) and Guanabenz (GA, a drug currently in use for the treatment of hypertension) were isolated as antiprion drugs using a yeast-based assay. These structurally unrelated molecules are also active against mammalian prion in several cell-based assays and in vivo in a mouse model for prion-based diseases.Methodology/Principal Findings: Here we report the identification of cellular targets of these drugs. Using affinity chromatography matrices for both drugs, we demonstrate an RNA-dependent interaction of 6AP and GA with the ribosome. These specific interactions have no effect on the peptidyl transferase activity of the ribosome or on global translation. In contrast, 6AP and GA specifically inhibit the ribosomal RNA-mediated protein folding activity of the ribosome.Conclusion/Significance: 6AP and GA are therefore the first compounds to selectively inhibit the protein folding activity of the ribosome. They thus constitute precious tools to study the yet largely unexplored biological role of this protein folding activity

Protein Folding Activity of Ribosomal RNA Is a Selective Target of Two Unrelated Antiprion Drugs

International audienceBACKGROUND: 6-Aminophenanthridine (6AP) and Guanabenz (GA, a drug currently in use for the treatment of hypertension) were isolated as antiprion drugs using a yeast-based assay. These structurally unrelated molecules are also active against mammalian prion in several cell-based assays and in vivo in a mouse model for prion-based diseases. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the identification of cellular targets of these drugs. Using affinity chromatography matrices for both drugs, we demonstrate an RNA-dependent interaction of 6AP and GA with the ribosome. These specific interactions have no effect on the peptidyl transferase activity of the ribosome or on global translation. In contrast, 6AP and GA specifically inhibit the ribosomal RNA-mediated protein folding activity of the ribosome. CONCLUSION/SIGNIFICANCE: 6AP and GA are therefore the first compounds to selectively inhibit the protein folding activity of the ribosome. They thus constitute precious tools to study the yet largely unexplored biological role of this protein folding activity

Guinée et Soudan français : frontière intra-impériale incertaine ? 1878-1915

Ce travail a pour objectif d'étudier le processus d'élaboration de la frontière actuelle entre le Mali et la Guinée, entre 1878 et 1915. La définition de cette limite intra-impériale est effectuée dans un contexte de conquête, dans un espace fortement maillé sur le plan politique

Preclinical detection of variant CJD and BSE prions in blood

International audienc

The Smallest Infectious Substructure Encoding the Prion Strain Structural Determinant Revealed by Spontaneous Dissociation of Misfolded Prion Protein Assemblies

International audienceIt is commonly accepted that the prion replicative propensity and strain structural determinant (SSD) are encoded in the fold of PrPSc amyloid fibril assemblies. By exploring the quaternary structure dynamicity of several prion strains, we revealed that all mammalian prion assemblies exhibit the generic property of spontaneously generating two sets of discreet infectious tetrameric and dimeric species differing significantly by their specific infectivity. By using perturbation approaches such as dilution and ionic strength variation, we demonstrated that these two oligomeric species were highly dynamic and evolved differently in the presence of chaotropic agents. In general, our observations of seven different prion strains from three distinct species highlight the high dynamicity of PrPSc assemblies as a common and intrinsic property of mammalian prions. The existence of such small infectious PrPSc species harboring the SSD indicates that the prion infectivity and the SSD are not restricted only to the amyloid fold but can also be encoded in other alternative quaternary structures. Such diversity in the quaternary structure of prion assemblies tends to indicate that the structure of PrPSc can be divided into two independent folding domains: a domain encoding the strain structural determinant and a second domain whose fold determines the type of quaternary structure that could adopt PrPSc assemblies

The smallest infectious substructure encoding the prion strain structural determinant revealed by spontaneous dissociation of misfolded prion protein assemblies

Abstract It is commonly accepted that the prion replicative propensity and strain structural determinant (SSD) are encoded in the fold of PrP Sc amyloid fibril assemblies. By exploring the quaternary structure dynamicity of several prion strains, we revealed that all mammalian prion assemblies exhibit the generic property of spontaneously generating two sets of discreet infectious tetrameric and dimeric species differing significantly by their specific infectivity. By using perturbation approaches such as dilution and ionic strength variation, we demonstrated that these two oligomeric species were highly dynamic and evolved differently in the presence of chaotropic agents. In general, our observations of seven different prion strains from three distinct species highlight the high dynamicity of PrP Sc assemblies as a common and intrinsic property of mammalian prions. The existence of such small infectious PrP Sc species harboring the SSD indicates that the prion infectivity and the SSD are not restricted only to the amyloid fold but can also be encoded in other alternative quaternary structures. Such diversity in the quaternary structure of prion assemblies tends to indicate that the structure of PrP Sc can be divided into two independent folding domains: a domain encoding the strain structural determinant and a second domain whose fold determines the type of quaternary structure that could adopt PrP Sc assemblies. Highlights Mammalian prion assemblies are highly dynamic Prion assemblies spontaneously disassemble into two infectious oligomers Prion infectivity is not exclusively encoded in the amyloid fibrils’ structure Two independent folding domains could structure Prion assemblie

Scrapie prions: an etiologic agent of sCJD in human?

International audienc

Evaluation of the infectivity present in white blood cells prepared from scrapie infected sheep by Cerebellar Organotypic Slice Culture Assay.

<p>Immunoblots of PK-treated slice culture homogenates probed with anti-PrP antibody Sha31, showing PrP^res accumulation in slice culture. (A) Cerebellar organotypic slices were prepared from tg338 pups and maintained in culture during 42 days <i>in vitro</i> after exposure to white blood cells prepared from blood collected from five scrapie infected sheep (D1, D2, D3, D4 and D5) at different times: 50 days post inoculation (dpi), 80 dpi, 130 dpi and at the terminal stage (180 dpi). For quantification purposes, slice cultures were also exposed to serial dilutions of PG127 scrapie-infected brain stock prepared from terminally ill tg338 mice, previously used <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0104287#pone.0104287-ArellanoAnaya1" target="_blank">[31]</a>. To visualize low levels of PrP^res, membranes were exposed over-night (B).</p