Vers la structuration d’une filière aurifère « durable » ? Etude du cas de la Guyane française

L’objectif de cet article est de se demander si la filière aurifère légale en Guyane française peut servir les objectifs du développement durable. En effet, cette filière est en proie à des difficultés : alors que les cours de l’or sont en constante augmentation, le nombre d’opérateurs miniers diminue constamment, depuis près de sept ans. Ce paradoxe aurifère guyanais trouve ses origines dans la volonté étatique française d'organiser la filière et d'en faire un exemple en matière de « durabilité », volonté clairement exprimée à la suite du Grenelle de l’Environnement. Principalement élaboré à partir d’entretiens semi-directifs et d’archives, l’article a notamment cherché à analyser les principaux éléments de cette structuration, le schéma départemental d’orientation minière (SDOM), en cours d’adoption, et plusieurs initiatives destinées à améliorer les pratiques des opérateurs miniers qui sont majoritairement des artisans. Toutefois, cette évolution révèle des antagonismes entre les parties prenantes (collectivités territoriales, services de l'État, opérateurs miniers et environnementalistes). Ces derniers ont fait surface lors de l’affaire du Camp Caïman, impliquant la multinationale Iamgold, et pendant le processus d’élaboration du SDOM lui-même. Des problématiques connexes telles que les revendications locales de gestion de la ressource aurifère, mais aussi et surtout l’orpaillage illégal, dressent des perspectives d’avenir plutôt incertaines pour la filière aurifère.The aim of this article is to wonder whether the gold mining sector, in French Guiana, can be in line with the objectives of sustainable development. Actually, this sector is in the grip of difficulties: whereas gold rates are in constant increase, the number of mining operators drops constantly, since nearly seven years. This Guianese paradox originates in the will of the French State to make gold sector an example as regards “sustainability”, as clearly expressed in the aftermath of the « Grenelle of the Environment ». Mainly based on semi-directing talks and archives, the article sought to analyze the key elements of this structuring: the project of Departmental Mining Master Plan (SDOM) and several initiatives dedicated to improve the mining operators’ practices. However, this evolution of which pace is variously appreciated, is not done without disagreements, insofar as it puts in relief antagonisms between the stakeholders (mainly territorial collectivities and the central level, operators mining and environmentalists). Indeed, these antagonisms were revealed, on the one hand, during the Camp Caiman case (which involved Iamgold), and on the other hand during the development process of the SDOM itself. Related problems such as local claims of mining governance and the illegal artisanal and small scale gold mining draw up future prospects rather mitigated for the sector

Cell-based strategies for regeneration of salivary glands

Mesenchymale Stammzellen sind durch ihre Eigenschaften der uneingeschränkten Selbsterneuerung und der Fähigkeit in verschiedene Zelllinien zu differenzieren, eine vielversprechende Quelle für die regenerative Medizin. Es besteht ein steigendes Interesse an ihrer Isolierung, Charakterisierung und ihrer Funktion in vivo. Es werden permanent neue Gewebe gesucht, aus denen die Isolierung mesenchymaler Stammzellen möglich ist, da sie nur in geringer Anzahl im Gewebe vorliegen und somit große Mengen an Spendergewebe benötigt wird, um ausreichend Zellen zu erhalten. Zusätzlich gibt es bestimmte pathologische Zustände, bei denen es den Speicheldrüsen nicht mehr möglich ist zu regenerieren. Es kann nicht mehr genügend Speichel gebildet werden und eine Xerostomie entwickelt sich, die die Lebensqualität der betroffenen Patienten massiv einschränkt. Ziel dieser Arbeit war es zu zeigen, dass die Speicheldrüsen eine Quelle für mesenchymale Stammzellen darstellen und außerdem ein klinisch leicht zugängliches Gewebe sind. Sowohl die Glandula parotidea, als auch die Glandula submandubularis erwiesen sich als geeignetes Gewebe für die Isolierung mesenchymaler Stammzellen. Das in dieser Arbeit etablierte Isolierungsprotokoll ermöglichte es zuverlässig größere Mengen MSCs zu erhalten, die in ihrer Morphologie ein homogenes Erscheinungsbild aufwiesen. In der FACS-Analyse der Zellen konnten Marker mesenchymaler Stammzellen detektiert und ein Fehlen hämatopoetischer Marker nachgewiesen werden. Die Zellen scheinen zusätzlich ein gewebespezifisches Expressionsprofil auszuweisen. Die Differenzierung der Zellen in die osteogene, adipogene und chondrogene Zelllinie war für jede Probe möglich, wobei geringfügige Unterschiede bei den Zellen aus den unterschiedlichen Ursprungsgeweben nachzuweisen waren. Die immunophänotypischen Charakteristika humaner primärer mesenchymaler Stammzellen aus der Glandula submandibularis konnten auch für die primären mesenchymalen Stammzellen aus murinem Submandibularisgewebe nachgewiesen werden. Dies waren grundlegende Voraussetzungen für die Etablierung eines radiogen induzierten Xerostomie- Mausmodels.Mesenchymal stem cells are a promising cell source for biomedical applications such as tissue engineering or regenerative medicine, while their specific characteristics involve an unlimited capacity of self-renewal and the ability to differentiate into multiple cell lineages. There is a continuously growing interest in the isolation, characterisation and biology of stem cells. In this context, the isolation of stem cells from novel sources is important as the currently defined donor tissues have specific disadvantages like large donor site morbidity as well as the presence of stem cells in very small amounts requiring large amounts of donor tissue to be harvested. The regeneration of salivary glands is disabled under certain pathological conditions e.g. as a result of radiation therapy for head and neck cancers. In this case saliva production is severely impaired and xerostomia results which massively restricts the quality of life of these patients. Taking into account that salivary glands are a possible valuable and clinically applicable source of stem cells the aim of this study was the isolation, characterisation and differentiation of stem cells from normal adult human parotid and submandubular glands. In this study we established a protocol that makes it possible to isolate a sufficient amount of mesenchymal stem cells from salivary gland tissue. The isolated cells were morphologically homogeneous and the fluorescence activated cell sorting-assays demonstrated mesenchymal stem cell marker and the absence of any hematopoetic marker at all. Additional the mesenchymal stem cells seem to express a tissue specific marker profile. Differentiation into the osteogenic, adipogenic and chondrogenic celline was always possible

Vers la structuration d’une filière aurifère « durable » ? Etude du cas de la Guyane française

The aim of this article is to wonder whether the gold mining sector, in French Guiana, can be in line with the objectives of sustainable development. Actually, this sector is in the grip of difficulties: whereas gold rates are in constant increase, the number of mining operators drops constantly, since nearly seven years. This Guianese paradox originates in the will of the French State to make gold sector an example as regards “sustainability”, as clearly expressed in the aftermath of the « Grenelle of the Environment ». Mainly based on semi-directing talks and archives, the article sought to analyze the key elements of this structuring: the project of Departmental Mining Master Plan (SDOM) and several initiatives dedicated to improve the mining operators’ practices. However, this evolution of which pace is variously appreciated, is not done without disagreements, insofar as it puts in relief antagonisms between the stakeholders (mainly territorial collectivities and the central level, operators mining and environmentalists). Indeed, these antagonisms were revealed, on the one hand, during the Camp Caiman case (which involved Iamgold), and on the other hand during the development process of the SDOM itself. Related problems such as local claims of mining governance and the illegal artisanal and small scale gold mining draw up future prospects rather mitigated for the sector

An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells

Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown. The A-kinase anchoring protein, AKAP-Lbc, possesses GEF activity, specifically activates RhoA, and is expressed in primary renal inner medullary collecting duct principal (IMCD) cells. Through screening of 18,431 small molecules and synthesis of a focused library around one of the hits, we identified an inhibitor of the interaction of AKAP-Lbc and RhoA. This molecule, Scaff10-8, bound to RhoA, inhibited the AKAP-Lbc-mediated RhoA activation but did not interfere with RhoA activation through other GEFs or activities of other members of the Rho family of small GTPases, Rac1 and Cdc42. Scaff10-8 promoted the redistribution of AQP2 from intracellular vesicles to the periphery of IMCD cells. Thus, our data demonstrate an involvement of AKAP-Lbc-mediated RhoA activation in the control of AQP2 trafficking

Scaff10-8 does not promote the insertion of AQP2 into the plasma membrane of IMCD cerlls.

<p>(A) IMCD cells were treated with either compound (30 μM) or DMSO for 1 or 24 h. Membrane proteins were biotinylated followed by precipitation with streptavidin agarose beads. Pulldown (PD) and supernatant fractions were separated by 12% SDS-PAGE. Pan-Cadherin was used as a loading control for the PD fraction, Hsp90 for the supernatants. A representative Western blot is shown. (B) Signals from A were quantified by densitometric analysis. The amount of AQP2 in the PD fractions were related to Pan-Cadherin. MW = molecular weight. M = molecular weight standard. cg = complex glycosylated; hm = high mannose glycosylated; ng = non-glycosylated. 10–8 = Scaff10-8. n = 3. Mean ± SEM is plotted.</p

Scaff10-8 promotes the redistribution of AQP2 to the plasma membrane of primary IMCD cells, which is independent of cAMP elevation and associated with depolymerization of F-actin.

<p>(A) Upper panel. IMCD cells were treated with DMSO (1%; control), the solvent of Scaff10-8, or forskolin (10 μM, 30 min) to stimulate cAMP synthesis. Lower panels: The cells were treated for 1 hour with Scaff10-8 (30 μM) alone (control) or with Scaff10-8 and forskolin. Forskolin (10 μM) was added for the final 30 min of Scaff10-8 incubation. AQP2 (green) was detected with specific primary and Cy3-coupled secondary antibodies, F-actin (red) with Alexa Fluor 647-Phalloidin and nuclei with DAPI (blue). Signals were visualized using a laser scanning microscope. Representative images are shown. n = 3. The magnified views were derived from the indicated boxes. (B) The signal intensities arising from intracellular and plasma membrane AQP2 were recorded, related to nuclear signal intensities, and the ratios of plasma membrane to intracellular fluorescence signal intensities were calculated (n = 30 cells per condition). Ratios > 1 indicate a predominant localization of AQP2 at the plasma membrane. Statistically significant differences were calculated using one-way ANOVA with posthoc Bonferroni. Mean ± SEM; *, p ≤ 0.05; *** p ≤ 0.001.</p

Scaff10-8 inhibits activation of RhoA in primary IMCD cells.

<p>IMCD cells were incubated with Scaff10-8 (30 μM, 1 h). DMSO (1%), the solvent of Scaff10-8, served as a control. The cells were lysed, (A) active RhoA was precipitated with the RhoA binding domain of Rhotekin coupled to sepharose beads, (B) active Cdc42 and Rac1 were precipitated with with GST fused to the (p21) binding domain (PBD) of p21 activated kinase 1 protein (PAK-1) coupled to sepharose beads. Inputs and pulldown fractions were separated by SDS-PAGE. Hsp90 or GAPDH were used as loading controls. Representative Western blots from 3–5 independent experiments are shown. Signals were semiquantitatively analyzed by densitometry. The amount of active RhoA was related to normalized RhoA (total RhoA to Hsp90 (Input)). Accordingly, active Cdc42 and Rac1 were related to normalized Cdc42 and Rac1, respectively (total RhoA to GAPDH (Input)). PD, Pulldown. n = 3–5. Statistically significant differences were determined using one-way ANOVA with posthoc Bonferroni. Mean ± SEM is plotted. *, p ≤ 0.05; **, p ≤ 0.01; *** p ≤ 0.001.</p