Ultrastructure of the Interlamellar Membranes of the Nacre of the Bivalve Pteria hirundo, Determined by Immunolabelling

The current model for the ultrastructure of the interlamellar membranes of molluscan nacre imply that they consist of a core of aligned chitin fibers surrounded on both sides by acidic proteins. This model was based on observations taken on previously demineralized shells, where the original structure had disappeared. Despite other earlier claims, no direct observations exist in which the different components can be unequivocally discriminated. We have applied different labeling protocols on non-demineralized nacreous shells of the bivalve Pteria. With this method, we have revealed the disposition and nature of the different fibers of the interlamellar membranes that can be observed on the surface of the nacreous shell of the bivalve Pteria hirundo by high resolution scanning electron microscopy (SEM). The minor chitin component consists of very thin fibers with a high aspect ratio and which are seemingly disoriented. Each fiber has a protein coat, which probably forms a complex with the chitin. The chitin-protein-complex fibers are embedded in an additional proteinaceous matrix. This is the first time in which the sizes, positions and distribution of the chitin fibers have been observed in situ.AJOM was financed by a PhD Grant of the FPI program from the Spanish Ministerio de Ciencia e Innovación; TCB's PhD Grant belonged to the FPU Program of the same Ministry. AJOM and AGC were supported by Projects CGL2010-20748-C02-01 and CGL2013-48247-P of the mentioned Ministry, and RNM6433 of the Consejería de Economía, Innovación y Ciencia of the Junta de Andalucía. The European COST Action TD0903 contributed via two Short Term Scientific Missions to AJOM in FM's lab in Dijon

Dendritic Cell-Mediated-Immunization with Xenogenic PrP and Adenoviral Vectors Breaks Tolerance and Prolongs Mice Survival against Experimental Scrapie

In prion diseases, PrPc, a widely expressed protein, is transformed into a pathogenic form called PrPSc, which is in itself infectious. Antibodies directed against PrPc have been shown to inhibit PrPc to PrPSc conversion in vitro and protect in vivo from disease. Other effectors with potential to eliminate PrPSc-producing cells are cytotoxic T cells directed against PrP-derived peptides but their ability to protect or to induce deleterious autoimmune reactions is not known. The natural tolerance to PrPc makes difficult to raise efficient adaptive responses. To break tolerance, adenovirus (Ad) encoding human PrP (hPrP) or control Ad were administered to wild-type mice by direct injection or by transfer of Ad-transduced dendritic cells (DCs). Control Ad-transduced DCs from Tg650 mice overexpressing hPrP were also used for immunization. DC-mediated but not direct administration of AdhPrP elicited antibodies that bound to murine native PrPc. Frequencies of PrP-specific IFNγ-secreting T cells were low and in vivo lytic activity only targeted cells strongly expressing hPrP. Immunohistochemical analysis revealed that CD3+ T cell infiltration was similar in the brain of vaccinated and unvaccinated 139A-infected mice suggesting the absence of autoimmune reactions. Early splenic PrPSc replication was strongly inhibited ten weeks post infection and mean survival time prolonged from 209 days in untreated 139A-infected mice to 246 days in mice vaccinated with DCs expressing the hPrP. The efficacy appeared to be associated with antibody but not with cytotoxic cell-mediated PrP-specific responses

IRGM Is a Common Target of RNA Viruses that Subvert the Autophagy Network

Autophagy is a conserved degradative pathway used as a host defense mechanism against intracellular pathogens. However, several viruses can evade or subvert autophagy to insure their own replication. Nevertheless, the molecular details of viral interaction with autophagy remain largely unknown. We have determined the ability of 83 proteins of several families of RNA viruses (Paramyxoviridae, Flaviviridae, Orthomyxoviridae, Retroviridae and Togaviridae), to interact with 44 human autophagy-associated proteins using yeast two-hybrid and bioinformatic analysis. We found that the autophagy network is highly targeted by RNA viruses. Although central to autophagy, targeted proteins have also a high number of connections with proteins of other cellular functions. Interestingly, immunity-associated GTPase family M (IRGM), the most targeted protein, was found to interact with the autophagy-associated proteins ATG5, ATG10, MAP1CL3C and SH3GLB1. Strikingly, reduction of IRGM expression using small interfering RNA impairs both Measles virus (MeV), Hepatitis C virus (HCV) and human immunodeficiency virus-1 (HIV-1)-induced autophagy and viral particle production. Moreover we found that the expression of IRGM-interacting MeV-C, HCV-NS3 or HIV-NEF proteins per se is sufficient to induce autophagy, through an IRGM dependent pathway. Our work reveals an unexpected role of IRGM in virus-induced autophagy and suggests that several different families of RNA viruses may use common strategies to manipulate autophagy to improve viral infectivity

Barcoding T Cell Calcium Response Diversity with Methods for Automated and Accurate Analysis of Cell Signals (MAAACS)

International audienceWe introduce a series of experimental procedures enabling sensitive calcium monitoring in T cell populations by confocal video-microscopy. Tracking and post-acquisition analysis was performed using Methods for Automated and Accurate Analysis of Cell Signals (MAAACS), a fully customized program that associates a high throughput tracking algorithm, an intuitive reconnection routine and a statistical platform to provide, at a glance, the calcium barcode of a population of individual T-cells. Combined with a sensitive calcium probe, this method allowed us to unravel the heterogeneity in shape and intensity of the calcium response in T cell populations and especially in naive T cells, which display intracellular calcium oscillations upon stimulation by antigen presenting cells

An Extended Model of Moral Outrage at Corporate Social Irresponsibility

The final publication is available at Springer via http://dx.doi.org/ 10.1007/s10551-014-2487-

Search for new physics with a monojet and missing transverse energy in pp collisions at √s=7 TeV

This is the pre-print version of the Published Article which can be accessed at the link below.A study of events with missing transverse energy and an energetic jet is performed using pp collision data at a center-of-mass energy of 7 TeV. The data were collected by the CMS detector at the LHC, and correspond to an integrated luminosity of 36  pb-1. An excess of these events over standard model contributions is a signature of new physics such as large extra dimensions and unparticles. The number of observed events is in good agreement with the prediction of the standard model, and significant extension of the current limits on parameters of new physics benchmark models is achieved

Search for the standard model Higgs boson in the decay channel H→ZZ→4l in pp collisions at √s=7TeV

A search for a Higgs boson in the four-lepton decay channel H→ZZ, with each Z boson decaying to an electron or muon pair, is reported. The search covers Higgs boson mass hypotheses in the range of 110100GeV (with 13 below 160GeV), while 67.1±6.0 (9.5±1.3) events are expected from background. The four-lepton mass distribution is consistent with the expectation of standard model background production of ZZ pairs. Upper limits at 95% confidence level exclude the standard model Higgs boson in the ranges of 134-158GeV, 180-305GeV, and 340-465GeV. Small excesses of events are observed around masses of 119, 126, and 320GeV, making the observed limits weaker than expected in the absence of a signal. © 2012 CERN

Copernicus Marine Service ocean state report, issue 4

This is the final version. Available from Taylor & Francis via the DOI in this record. FCT/MCTE