Naturally Occurring Asbestos in France: Geological Mapping, Mineral Characterization and Regulatory Developments

International audienceIn France, the asbestos banning is subject to a national decree (n° 96-1133), published in 1996. The regulatory texts and standards adopted to control this banning concern in particular asbestos-bearing manufactured products, but remain difficult to apply to asbestos-bearing natural materials (ie. rocks, soils). Considering problems related to such asbestos-bearing natural materials, the Ministry of Ecological and Solidary Transition has mandated the French Geological Survey to locate the impacted areas. Mappings were priority carried out in geological domains where NOA was predictable (French Alps, Corsica). These studies integrated field expertise, sampling and laboratory analyses, in order to characterize the potential of geological units to contain NOA. Furthermore, some expertises were carried out on geological formations exploited in France to produce aggregates. These studies concerned the quarries exploiting massive basic or ultrabasic rocks, likely to contain NOA, and quarries exploiting alluvium likely to contain asbestos-bearing rock pebbles. These studies highlight the difficulty of establishing robust diagnoses for natural materials. Indeed, distinction between cleavage fragments resulting from the fragmentation of non-asbestos particles and proper asbestos fibers is particularly problematic for laboratories. Thus, a recent study of the National Agency for Health Safety, Food, Environment and Work (2015) recommends to apply the asbestos regulation for elongated mineral particles (L/D > 3:1, L > 5 μm, D < 3 μm) with chemical composition corresponding to one of the five regulated amphibole species, irrespective of their mode of crystallization (asbestiform or non-asbestiform). The upcoming regulatory changes are part of a decree published in 2017, including the prior identification of asbestos in natural soils or rocks likely to be impacted by the execution of work. Specific protocols will be defined for sampling, analysis and characterization of natural materials that may contain asbestos

Pop-down tectonics, fluid channelling and ore deposits within ancient hot orogens

International audienceMany Archaean and Paleoproterozoic deformation zones, often rich in ore resources, show particular structural patterns in particularmarked by regional vertical stretch. These zones are not restricted to greenstone-bearing Archaean domains that may have suffered gravity-driven sagduction of heavy supra-crustals, as extensively discussed since the last twenties. Structures are actually best explained by pop-down tectonics of upper-crustal unitswithin an underlyingweak crust submitted to horizontal regional shortening.Herewe present three complementary examples fromtwo Archaean greenstone belts (Abitibi sub-Province, Quebec, andMurchison belt, South Africa) and one greenstone-lacking Paleoproterozoic belt (Thompson belt,Manitoba). In the three examples, ore is concentrated along steeply dipping deformation zones, rich in syntectonic deposits and marked by substantial sub-vertical crustal stretch. On the other hand, the three regions show differences in age, in metamorphic grade (from sub-greenschist facies to upper amphibolite facies), in metal contents (gold, antimony, nickel), in metal sources, transfers and concentration histories. Our compared analysis emphasizes that pop-down tectonics associatedwith horizontal shortening of weak lithospheres may account for observed geometric patterns and provide a new and promising frame for the analysis of relationships between structural patterns and ore concentrations within old cratons

Evolution of a Paleoproterozoic “weak type” orogeny in the West African Craton (Ivory Coast).

International audienceThe Paleoproterozoic domain of Ivory Coast lies in the central part of the West African Craton (WAC) and is mainly constituted by TTG, greenstones, supracrustal rocks and leucogranites. A compilation of metamorphic and radiometric data highlights that: i) metamorphic conditions are rather homogeneous through the domain, without important metamorphic jumps, ii) HP-LT assemblages are absent and iii) important volumes of magmas emplaced during the overall Paleoproterozoic orogeny suggesting the occurrence of long-lived rather hot geotherms. Results of the structural analysis, focused on three areas within the Ivory Coast, suggest that the deformation is homogeneous and distributed through the Paleoproterozoic domain. In details, results of this study point out the long-lived character of vertical movements during the Eburnean orogeny with a two folds evolution. The first stage is characterized by the development of “domes and basins” geometries without any boundary tectonic forces and the second stage is marked by coeval diapiric movements and horizontal regional-scale shortening. These features suggest that the crust is affected by vertical movements during the overall orogeny. The Eburnean orogen can then be considered as an example of longlived Paleoproterozoic “weak type” orogen

Baire and automata

In his thesis Baire defined functions of Baire class 1. A function f is of Baire class 1 if it is the pointwise limit of a sequence of continuous functions. Baire proves the following theorem. A function f is not of class 1 if and only if there exists a closed nonempty set F such that the restriction of f to F has no point of continuity. We prove the automaton version of this theorem. An ω-rational function is not of class 1 if and only if there exists a closed nonempty set F recognized by a Büchi automaton such that the restriction of f to F has no point of continuity. This gives us the opportunity for a discussion on Hausdorff's analysis of Δ°2, ordinals, transfinite induction and some applications of computer science

Deep reflection seismic imaging of the internal zone of the South Armorican Hercynian belt (western France) (ARMOR 2/Géofrance 3D Program) Imagerie sismique de la zone interne de la chaîne hercynienne sud-armoricaine (projet Armor 2/programme Géofrance 3D)

International audienceWe present results and interpretation of a 72 km long deep seismic reflection profile acquired across the internal zone of the Hercynian belt of South Brittany. The profile is of excellent quality, most of the crust being highly reflective. The “ARMOR 2 South” profile, is correlated with the “ARMOR 2 North” profile that was published in 2003. Correlation of the main subsurface reflections with surface geological and structural data provides important information about the crustal structure that resulted from thickening during Late Devonian and regional-scale extension during Late Carboniferous. In particular, seismics image shows a very high reflectivity zone, lying flat over more than 40 km at about 10–12 km depth. This zone is interpreted as a major zone of ductile crustal thinning. Nous présentons les résultats et l'interprétation d'un profil de sismique réflexion en écoute longue, de 72 km de long à travers les zones internes de la chaîne hercynienne sud-armoricaine. Le profil est d'excellente qualité, avec une forte réflectivité à travers toute la croûte. Le profil, « ARMOR 2 Sud », est corrélé avec le profil « ARMOR 2 Nord » publié en 2003. Les corrélations des réflexions les plus superficielles avec les données géologiques et structurales de surface fournissent d'importantes informations sur la structure crustale qui résulte d'un épaississement débutant au Dévonien supérieur et d'une extension régionale au Carbonifère supérieur. En particulier, la sismique met en évidence une zone sub-horizontale à très forte réflectivité, de plus de 40 km de long à environ 10–12 km de profondeur. Cette zone est interprétée comme une zone d'amincissement crustal majeur

Ttc7a regulates hematopoietic stem cell functions while controlling the stress-induced response

The molecular machinery that regulates the balance between self-renewal and differentiation properties of hematopoietic stem cells (HSC) has yet to be characterized in detail. Here we found that the tetratricopeptide repeat domain 7 A (Ttc7a) protein, a putative scaffold protein expressed by HSC, acts as an intrinsic regulator of the proliferative response and the self-renewal potential of murine HSC in vivo. Loss of Ttc7a consistently enhanced the competitive repopulating ability of HSC and their intrinsic capacity to replenish the hematopoietic system after serial cell transplantations, relative to wildtype cells. Ttc7a-deficient HSC exhibit a different transcriptomic profile for a set of genes controlling the cellular response to stress, which was associated with increased proliferation in response to chemically induced stress in vitro and myeloablative stress in vivo. Our results therefore revealed a previously unrecognized role of Ttc7a as a critical regulator of HSC stemness. This role is related, at least in part, to regulation of the endoplasmic reticulum stress response.</p

CTLA-4 +49A/G and CT60 gene polymorphisms in primary Sjögren syndrome

CTLA-4 encodes cytotoxic T lymphocyte-associated antigen-4, a cell-surface molecule providing a negative signal for T-cell activation. CTLA-4 gene polymorphisms have been widely studied in connection with genetic susceptibility to various autoimmune diseases, but studies have led to contradictory results in different populations. This case-control study sought to investigate whether CTLA-4 CT60 and/or +49A/G polymorphisms were involved in the genetic predisposition to primary Sjögren syndrome (pSS). We analysed CTLA-4 CT60 and +49A/G polymorphisms in a first cohort of 142 patients with pSS (cohort 1) and 241 controls, all of Caucasian origin. A replication study was performed on a second cohort of 139 patients with pSS (cohort 2). In cohort 1, the CTLA-4 +49A/G*A allele was found on 73% of chromosomes in patients with pSS, compared with 66% in controls (p = 0.036; odds ratio (OR) 1.41, 95% confidence interval (CI) 1.02 to 1.95). No difference in CTLA-4 CT60 allelic or genotypic distribution was observed between patients (n = 142) and controls (n = 241). In the replication cohort, the CTLA-4 +49A/G*A allele was found on 62% of chromosomes in patients with pSS, compared with 66% in controls (p = 0.30; OR 0.85, 95% CI 0.63 to 1.16). Thus, the CTLA-4 +49A/G*A allele excess among patients from cohort 1 was counterbalanced by its under-representation in cohort 2. When the results from the patients in both cohorts were pooled (n = 281), there was no difference in CTLA-4 +49A/G allelic or genotypic distribution in comparison with controls. Our results demonstrate a lack of association between CTLA-4 CT60 or +49A/G polymorphisms and pSS. Premature conclusions might have been made if a replication study had not been performed. These results illustrate the importance of case-control studies performed on a large number of patients. In fact, sampling bias may account for some contradictory results previously reported for CTLA-4 association studies in autoimmune diseases

AK2 deficiency compromises the mitochondrial energy metabolism required for differentiation of human neutrophil and lymphoid lineages

Reticular dysgenesis is a human severe combined immunodeficiency that is primarily characterized by profound neutropenia and lymphopenia. The condition is caused by mutations in the adenylate kinase 2 (AK2) gene, resulting in the loss of mitochondrial AK2 protein expression. AK2 regulates the homeostasis of mitochondrial adenine nucleotides (ADP, ATP and AMP) by catalyzing the transfer of high-energy phosphate. Our present results demonstrate that AK2-knocked-down progenitor cells have poor proliferative and survival capacities and are blocked in their differentiation toward lymphoid and granulocyte lineages. We also observed that AK2 deficiency impaired mitochondrial function in general and oxidative phosphorylation in particular - showing that AK2 is critical in the control of energy metabolism. Loss of AK2 disrupts this regulation and leads to a profound block in lymphoid and myeloid cell differentiation

B cell depletion in immune thrombocytopenia reveals splenic long-lived plasma cells.

International audiencePrimary immune thrombocytopenia (ITP) is a disorder caused by autoantibody-mediated platelet destruction and decreased platelet production. Rituximab, a B cell-depleting agent, has become the first-line treatment for ITP; however, patients with refractory disease usually require splenectomy. We identified antibody-secreting cells as the major splenic B cell population that is resistant to rituximab. The phenotype, antibody specificity, and gene expression profile of these cells were characterized and compared to those of antibody-secreting cells from untreated ITP spleens and from healthy tissues. Antiplatelet-specific plasma cells (PC) were detected in the spleens of patients with ITP up to 6 months after rituximab treatment, and the PC population displayed a long-lived program similar to the one of bone marrow PC, thus explaining for most of these patients the absence of response to rituximab and the response to splenectomy. When analyzed by multiplex PCR at the single-cell level, normal splenic PC showed a markedly different gene expression profile, with an intermediate signature, including genes characteristic of both long-lived PC and proliferating plasmablasts. Surprisingly, long-lived PC were not detected in untreated ITP spleens. These results suggest that the milieu generated by B cell depletion promotes the differentiation and settlement of long-lived PC in the spleen

Tetratricopeptide repeat domain 7A is a nuclear factor that modulates transcription and chromatin structure

A loss-of-function mutation in tetratricopeptide repeat domain 7A (TTC7A) is a recently identified cause of human intestinal and immune disorders. However, clues to related underlying molecular dysfunctions remain elusive. It is now shown based on the study of TTC7A-deficient and wild-type cells that TTC7A is an essential nuclear protein. It binds to chromatin, preferentially at actively transcribed regions. Its depletion results in broad range of epigenomic changes at proximal and distal transcriptional regulatory elements and in altered control of the transcriptional program. Loss of WT_TTC7A induces general decrease in chromatin compaction, unbalanced cellular distribution of histones, higher nucleosome accessibility to nuclease digestion along with genome instability, and reduced cell viability. Our observations characterize for the first time unreported functions for TTC7A in the nucleus that exert a critical role in chromatin organization and gene regulation to safeguard healthy immune and intestinal status.</p