Fouilles à Marseille

Les objets du quotidien, devenus mobilier archéologique du fait de leur enfouissement dans les couches sédimentaires ou de leur insertion dans des maçonneries, font partie intégrante des données que les archéologues utilisent pour la compréhension d’un site archéologique. Ajoutés les uns aux autres et au fil du temps, ces objets de la vie quotidienne forment des masses parfois imposantes à récolter pendant le chantier, à gérer et à traiter pour les conserver dignement et à étudier. Mais ils témoignent d’une façon particulièrement concrète de la façon dont les Marseillais ont vécu tout au long du Moyen Âge et de l’époque moderne. On trouvera dans cet ouvrage une étude la plus large possible de catégories variées de ces objets du quotidien. En premier lieu la céramique, retrouvée en contexte « de consommation », renseignant sur les approvisionnements d’une ville portuaire et sur les usages quotidiens de ceux qui y vivaient. Au côté des monnaies, peu nombreuses, des pipes ou du mobilier en verre, qui témoigne d’une évolution des goûts de la table, les objets métalliques et en matière dure animale sont autant de traces d’une matérialité de la vie quotidienne qui vient égayer des vestiges archéologiques parfois un peu arides tant ils ont été détruits au fil des siècles. Cet ouvrage vient ainsi compléter le premier volume paru sur Marseille médiévale et moderne (BiAMA 7), qui avait présenté le cadre général de la cité et le détail des fouilles récentes portant sur ces périodes. Le spécialiste, comme le grand public, y trouvera largement la matière d’une connaissance renouvelée sur ce sujet

Mesothelioma response to carbon nanotubes is associated with an early and selective accumulation of immunosuppressive monocytic cells

BACKGROUND: The asbestos-like toxicity of some engineered carbon nanotubes (CNT), notably their capacity to induce mesothelioma, is a serious cause of concern for public health. Here we show that carcinogenic CNT induce an early and sustained immunosuppressive response characterized by the accumulation of monocytic Myeloid Derived Suppressor Cells (M-MDSC) that counteract effective immune surveillance of tumor cells. METHODS: Wistar rats and C57BL/6 mice were intraperitoneally injected with carcinogenic multi-walled Mitsui-7 CNT (CNT-7) or crocidolite asbestos. Peritoneal mesothelioma development and immune cell accumulation were assessed until 12 months. Leukocyte sub-populations were identified by recording expression of CD11b/c and His48 by flow cytometry. The immunosuppressive activity on T lymphocytes of purified peritoneal leukocytes was assessed in a co-culture assay with activated spleen cells. RESULTS: We demonstrate that long and short mesotheliomagenic CNT-7 injected in the peritoneal cavity of rats induced, like asbestos, an early and selective accumulation of monocytic cells (CD11b/c(int) and His48(hi)) which possess the ability to suppress polyclonal activation of T lymphocytes and correspond to M-MDSC. Peritoneal M-MDSC persisted during the development of peritoneal mesothelioma in CNT-7-treated rats but were only transiently recruited after non-carcinogenic CNT (CNT-M, CNT-T) injection. Peritoneal M-MDSC did not accumulate in mice which are resistant to mesothelioma development. CONCLUSIONS: Our data provide new insights into the initial pathogenic events induced by CNT, adding a new component to the adverse outcome pathway leading to mesothelioma development. The specificity of the M-MDSC response after carcinogenic CNT exposure highlights the interest of this response for detecting the ability of new nanomaterials to cause cancer

Early and sustained immunosuppressive macrophage responses to carcinogenic carbon nanotubes in a rat mesothelioma bioassay.

MM is a rare cancer caused by asbestos exposure affecting the serous membrane of pleural and peritoneal cavities. MM remains a highly refractory cancer to existing therapeutic strategies. The asbestos-like toxicity of engineered carbon nanotubes (CNT), notably their capacity to induce malignant mesothelioma (MM), is a serious cause of concern for public health. Intensive research efforts are therefore needed to better understand the pathomechanisms of CNT-induced MM. The present project deals with immunosuppression during the mesothelial response to CNT in rats. There is growing evidence that tumors harbor immunosuppressive cells that inhibit both innate and adaptive immunity, subverting immune surveillance and preventing efficient natural or therapeutic anti-tumor immune responses. We aim to determine if the carcinogenic response to Mitsui-7 CNT (CNT-7) is associated with the accumulation of immunosuppressive macrophages. We used a Wistar rat peritoneum model which allows directly exposing mesothelial cells to CNT or asbestos, and easily sampling the mesothelial cavity for monitoring macrophage responses during the carcinogenic process. We show that FACS-sorted CD11b/chigh and His48int macrophages present in CNT-7-induced mesothelioma microenvironment suppress polyclonal activation of T lymphocytes in vitro. These inhibitory macrophages are already present during the early response to carcinogenic CNT or asbestos (day 1 to 30), well before the establishment of mesothelioma (6 months). Immunosuppressive peritoneal macrophages were not observed in mice, which are resistant to mesothelioma development upon CNT-7. RTqPCR revealed that peritoneal macrophages purified from CNT-treated rats (day 1-30) highly expressed the immunosuppressive mediators IL-10 and Arginase-1 in comparison to naive peritoneal macrophages or macrophages obtained after silica, a particle that does not induce mesothelioma. Altogether, our data demonstrate that carcinogenic CNT possess the intrinsic capacity to induce a preferential, rapid and sustained accumulation of immunosuppressive macrophages before mesothelioma is established. These data provide new insight into the possible contribution of immunosuppression in the early pathogenic processes of CNT-induced mesothelioma

YAP and TAZ are essential for basal and squamous cell carcinoma initiation.

YAP and TAZ are key downstream regulators of the Hippo pathway, regulating cell proliferation and differentiation. YAP and TAZ activation has been reported in different cancer types. However, it remains unclear whether they are required for the initiation of major skin malignancies like basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Here, we analyze the expression of YAP and TAZ in these skin cancers and evaluate cancer initiation in knockout mouse models. We show that YAP and TAZ are nuclear and highly expressed in different BCC types in both human and mice. Further, we find that cells with nuclear YAP and TAZ localize to the invasive front in well-differentiated SCC, whereas nuclear YAP is homogeneously expressed in spindle cell carcinoma undergoing EMT We also show that mouse BCC and SCC are enriched for YAP gene signatures. Finally, we find that the conditional deletion of YAP and TAZ in mouse models of BCC and SCC prevents tumor formation. Thus, YAP and TAZ are key determinants of skin cancer initiation, suggesting that targeting the YAP and TAZ signaling pathway might be beneficial for the treatment of skin cancers.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

RHOJ controls EMT-associated resistance to chemotherapy.

The resistance of cancer cells to therapy is responsible for the death of most patients with cancer1. Epithelial-to-mesenchymal transition (EMT) has been associated with resistance to therapy in different cancer cells2,3. However, the mechanisms by which EMT mediates resistance to therapy remain poorly understood. Here, using a mouse model of skin squamous cell carcinoma undergoing spontaneous EMT during tumorigenesis, we found that EMT tumour cells are highly resistant to a wide range of anti-cancer therapies both in vivo and in vitro. Using gain and loss of function studies in vitro and in vivo, we found that RHOJ-a small GTPase that is preferentially expressed in EMT cancer cells-controls resistance to therapy. Using genome-wide transcriptomic and proteomic profiling, we found that RHOJ regulates EMT-associated resistance to chemotherapy by enhancing the response to replicative stress and activating the DNA-damage response, enabling tumour cells to rapidly repair DNA lesions induced by chemotherapy. RHOJ interacts with proteins that regulate nuclear actin, and inhibition of actin polymerization sensitizes EMT tumour cells to chemotherapy-induced cell death in a RHOJ-dependent manner. Together, our study uncovers the role and the mechanisms through which RHOJ acts as a key regulator of EMT-associated resistance to chemotherapy.info:eu-repo/semantics/publishe

Low incidence of SARS-CoV-2, risk factors of mortality and the course of illness in the French national cohort of dialysis patients

International audienceThe aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially