SILAC labeling coupled to shotgun proteomics analysis of membrane proteins of liver stem/hepatocyte allows to candidate the inhibition of TGF-beta pathway as causal to differentiation

Background: Despite extensive research on hepatic cells precursors and their differentiated states, much remains to be learned about the mechanism underlying the self-renewal and differentiation.Results: We apply the SILAC (stable isotope labeling by amino acids in cell culture) approach to quantitatively compare the membrane proteome of the resident liver stem cells (RLSCs) and their progeny spontaneously differentiated into epithelial/hepatocyte (RLSCdH). By means of nanoLC-MALDI-TOF/TOF approach, we identified and quantified 248 membrane proteins and 57 of them were found modulated during hepatocyte differentiation. Functional clustering of differentially expressed proteins by Ingenuity Pathway Analysis revealed that the most of membrane proteins found to be modulated are involved in cell-to-cell signaling/interaction pathways. Moreover, the upstream prediction analysis of proteins involved in cell-to-cell signaling and interaction unveiled that the activation of the mesenchymal to epithelial transition (MET), by the repression of TGFB1/Slug signaling, may be causal to hepatocyte differentiation.Conclusions: Taken together, this study increases the understanding of the underlying mechanisms modulating the complex biological processes of hepatic stem cell proliferation and differentiation. © 2014 Montaldo et al.; licensee BioMed Central Ltd

Prévenir les troubles musculosquelettiques chez les soignants : connaître les expositions et étude des outils d’aide à la manutention

ObjectifsDans le cadre de la Caisse nationale de retaite des agents des collectivités locales (CNRACL), la démarche d’évaluation et de prévention des risques vise à conduire à une démarche spécifique au milieu hospitalier et à construire des outils d’évaluation des risques dans le réseau des CHU français. Les études menées sur la prévention des troubles musculosquelettiques (TMS) associent principalement les compétences en ergonomie, épidémiologie et médecine du travail des CHU d’Angers et de Grenoble. Méthode Une première étude épidémiologique a permis d’identifier les facteurs de risque de TMS et de lombalgie en milieu hospitalier ; une seconde s’est intéressée à l’évaluation des outils d’aide à la manutention des patients en milieu de soins sous un angle ergonomique. Résultats Les salariés du secteur santé sont en moyenne exposés à 2,4 facteurs de risque des 19 répertoriés (3,5 pour le reste du réseau) et ne souffrent pas plus de TMS des membres supérieurs que les autres salariés de la région des Pays-de-la-Loire. En revanche, les expositions aux manutentions manuelles de charges lourdes liées aux soins aux patients sont plus fréquentes. Les aides techniques pour la manutention étudiées ne répondent pas aux critères de dépendance du patient ou aux conditions organisationnelles du service. Du point de vue psychologique, le rapport du patient au matériel ainsi que l’usage du corps du soignant dans la relation aux soins doivent être pris en compte. Conclusion L’approche biomécanique a fait l’objet de cette première investigation. Il s’agit d’une démarche de prévention pluridisciplinaire intégrée dans la politique d’établissement

MiR-675-5p supports hypoxia induced epithelial to mesenchymal transition in colon cancer cells

The survival rates in colon cancer patients are inversely proportional to the number of lymph node metastases. The hypoxia-induced Epithelial to Mesenchymal Transition (EMT), driven by HIF1\uce\ub1, is known to be involved in cancer progression and metastasis. Recently, we have reported that miR-675-5p promotes glioma growth by stabilizing HIF1\uce\ub1 here, by use of the syngeneic cell lines we investigated the role of the miR-675-5p in colon cancer metastasis. Our results show that miR-675-5p, over expressed in metastatic colon cancer cells, participates to tumour progression by regulating HIF1\uce\ub1 induced EMT. MiR-675- 5p increases Snail transcription by a dual strategy: i) stabilizing the activity of the transcription factor HIF1\uce\ub1 and ii) and inhibiting Snail's repressor DDB2 (Damage specific DNA Binding protein 2). Moreover, transcriptional analyses on specimens from colon cancer patients confirmed, in vivo, the correlation between miR-675-5p over-expression and metastasis, thus identifying miR-675-5p as a new marker for colon cancer progression and therefore a putative target for therapeutic strategies

Particle acoustic detection in gravitational wave aluminum resonant antennas

The results on cosmic rays detected by the gravitational antenna NAUTILUS have motivated an experiment (RAP) based on a suspended cylindrical bar, which is made of the same aluminum alloy as NAUTILUS and is exposed to a high energy electron beam. Mechanical vibrations originate from the local thermal expansion caused by warming up due to the energy lost by particles crossing the material. The aim of the experiment is to measure the amplitude of the fundamental longitudinal vibration at different temperatures. We report on the results obtained down to a temperature of about 4 K, which agree at the level of about 10% with the predictions of the model describing the underlying physical process.Comment: RAP experiment, 16 pages, 7 figure

CD90+ liver cancer cells modulate endothelial cell phenotype through the release of exosomes containing H19 lncRNA.

BACKGROUND: CD90+ liver cancer cells have been described as cancer stem-cell-like (CSC), displaying aggressive and metastatic phenotype. Using two different in vitro models, already described as CD90+ liver cancer stem cells, our aim was to study their interaction with endothelial cells mediated by the release of exosomes. METHODS: Exosomes were isolated and characterized from both liver CD90+ cells and hepatoma cell lines. Endothelial cells were treated with exosomes, as well as transfected with a plasmid containing the full length sequence of the long non-coding RNA (lncRNA) H19. Molecular and functional analyses were done to characterize the endothelial phenotype after treatments. RESULTS: Exosomes released by CD90+ cancer cells, but not by parental hepatoma cells, modulated endothelial cells, promoting angiogenic phenotype and cell-to-cell adhesion. LncRNA profiling revealed that CD90+ cells were enriched in lncRNA H19, and released this through exosomes. Experiments of gain and loss of function of H19 showed that this LncRNA plays an important role in the exosome-mediated phenotype of endothelial cells. CONCLUSIONS: Our data indicate a new exosome-mediated mechanism by which CSC-like CD90+ cells could influence their tumor microenvironment by promoting angiogenesis. Moreover, we suggest the lncRNA H19 as a putative therapeutic target in hepatocellular carcinoma

The effect of introducing IGRA to screen French healthcare workers for tuberculosis and potential conclusions for the work organisation

INTRODUCTION: In France, pre-employment screening for tuberculosis (TB) is performed for healthcare workers (HCW). Screening is repeated when exposure to TB patients or infectious material occurs. The results of these TB screenings were analysed in a retrospective analysis. METHOD: Tuberculin skin tests (TST) and interferon-gamma release assays (QuantiFERON® Gold In-Tube - QFT) were used to perform the TB screenings. The screening results of 637 HCWs on whom QFT was performed were taken from the records of the University Hospital of Nantes. RESULTS: In three (0.5%) HCW, the QFT was indeterminate. In 22.2%, the QFT was positive. A second QFT was performed in 118 HCWs. The reversion rate was 42% (5 out of 17). The conversion rate was 6% (6 out of 98). A TST was performed on 466 (73.5%) of the HCWs. Results for TST > 10 mm were 77.4%. In those with a TST < 10 mm, QFT was positive in 14% and in those with a TST ≥ 10 mm, QFT was positive in 26.7%. Depending on the definition for conversion in the QFT, the annual attack rate was 4.1% or 7.3%. X-ray and pneumology consultation was based on positive QFT rather than TST alone (52 out of 56). No active TB was detected. CONCLUSION: The TST overestimated the prevalence of LTBI in this cohort. The decision about X-ray and consultation regarding preventive treatment should be based on the QFT rather than the TST results. The high reversion rate should be taken into consideration when consulting with HCWs regarding preventive treatment. The high conversion rate seems to indicate that preventive measures such as wearing masks should be improved

New Perspectives on Quine's Word and Object

[Introduction to Special Issues] Quinean theses marked several fields of philosophy and, since its publication, "Word and Object" has become a landmark in the canon of analytical philosophy. The Quinean contribution is not limited to the philosophy of language. His work sheds light on many important topics in the philosophy of mind and the philosophy of mathematics. He is celebrated for introducing a naturalised conception of epistemology, which emphasised the role of the natural scientific method in determining the processes of knowledge acquisition. On the one hand, this view brought him to embrace behaviourism, the thesis that psychological terms do not refer to inner mental states and instead are to be analysed in terms of speakers’ dispositions to verbal behaviour. On the other hand, he rejected the traditional philosophical study of scientific knowledge and mathematics in particular, because of its failure to reduce mathematics to pure logic

Spike-in SILAC proteomic approach reveals the vitronectin as an early molecular signature of liver fibrosis in hepatitis C infections with hepatic iron overload

Hepatitis C virus (HCV)-induced iron overload has been shown to promote liver fibrosis, steatosis, and hepatocellular carcinoma. The zonal-restricted histological distribution of pathological iron deposits has hampered the attempt to perform large-scale in vivo molecular investigations on the comorbidity between iron and HCV. Diagnostic and prognostic markers are not yet available to assess iron overload-induced liver fibrogenesis and progression in HCV infections. Here, by means of Spike-in SILAC proteomic approach, we first unveiled a specific membrane protein expression signature of HCV cell cultures in the presence of iron overload. Computational analysis of proteomic dataset highlighted the hepatocytic vitronectin expression as the most promising specific biomarker for iron-associated fibrogenesis in HCV infections. Next, the robustness of our in vitro findings was challenged in human liver biopsies by immunohistochemistry and yielded two major results: (i) hepatocytic vitronectin expression is associated to liver fibrogenesis in HCV-infected patients with iron overload; (ii) hepatic vitronectin expression was found to discriminate also the transition between mild to moderate fibrosis in HCV-infected patients without iron overload. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim