57 research outputs found

    Autophagy plays an important role in protecting Pacific oysters from OsHV-1 and Vibrio aestuarianus infections.

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    Recent mass mortality outbreaks around the world in Pacific oysters, Crassostrea gigas, have seriously affected the aquaculture economy. Although the causes for these mortality outbreaks appear complex, infectious agents are involved. Two pathogens are associated with mass mortality outbreaks, the virus ostreid herpesvirus 1 (OsHV-1) and the bacterium Vibrio aestuarianus. Here we describe the interactions between these 2 pathogens and autophagy, a conserved intracellular pathway playing a key role in innate immunity. We show for the first time that autophagy pathway is present and functional in Pacific oysters and plays an important role to protect animals from infections. This study contributes to better understand the innate immune system of Pacific oysters.This work was partially funded through the EU project Bivalife (FP7 KBBE, contract n 266157), the Poitou Charentes Region and DPMA (Direction des p^eches maritimes et de l’aquaculture, AESTU project). David Rubinsztein is aWellcome Trust Prinicipal Research Fellow.This is the final published version. It first appeared at http://www.tandfonline.com/doi/full/10.1080/15548627.2015.1017188

    Small molecule binding sites on the Ras:SOS complex can be exploited for inhibition of Ras activation.

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    Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. We describe a fragment screening campaign using X-ray crystallography that led to the discovery of three fragment binding sites on the Ras:SOS complex. The identification of tool compounds binding at each of these sites allowed exploration of two new approaches to Ras pathway inhibition by stabilizing or covalently modifying the Ras:SOS complex to prevent the reloading of Ras with GTP. Initially, we identified ligands that bound reversibly to the Ras:SOS complex in two distinct sites, but these compounds were not sufficiently potent inhibitors to validate our stabilization hypothesis. We conclude by demonstrating that covalent modification of Cys118 on Ras leads to a novel mechanism of inhibition of the SOS-mediated interaction between Ras and Raf and is effective at inhibiting the exchange of labeled GDP in both mutant (G12C and G12V) and wild type Ras

    Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

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    Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

    Pseudo-true SDFs in conditional asset pricing models

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    This article is motivated by the need to bridge some gap between modern asset pricing theory and recent developments in econometric methodology. While asset pricing theory enhances the use of conditional pricing models, econometric inference of conditional models can be challenging due to misspecification or weak identification. To tackle the case of misspecification, we utilize the conditional Hansen and Jagannathan (1997) (HJ) distance as studied by Gagliardini and Ronchetti (2016), but we set the focus on interpretation and estimation of the pseudo-true value defined as the argument of the minimum of this distance. While efficient Generalized Method of Moments (GMM) has no meaning for estimation of a pseudo-true value, the HJ-distance not only delivers a meaningful loss function, but also features an additional advantage for the interpretation and estimation of managed portfolios whose exact pricing characterizes the pseudo-true pricing kernel (stochastic discount factor (SDF)). For conditionally affine pricing kernels, we can display some managed portfolios which are well-defined independently of the pseudo-true value of the parameters, although their exact pricing is achieved by the pseudo-true SDF. For the general case of nonlinear SDFs, we propose a smooth minimum distance (SMD) estimator (Lavergne and Patilea, 2013) that avoids a focus on specific directions as in the case of managed portfolios. Albeit based on kernel smoothing, the SMD approach avoids instabilities and the resulting need of trimming strategies displayed by classical local GMM estimators when the density function of the conditioning variables may take arbitrarily small values. In addition, the fact that SMD may allow fixed bandwidth asymptotics is helpful regarding the curse of dimensionality. In contrast with the true unknown value for a well-specified model, the estimated pseudo-true value, albeit defined in a time-invariant (unconditional) way, may actually depend on the choice of the state variables that define fundamental factors and their scaling weights. Therefore, we may not want to be overly parsimonious about the set of explanatory variables. Finally, following Antoine and Lavergne (2014), we show how SMD can be further robustified to deal with weaker identification contexts. Since SMD can be seen as a local extension of the method of jackknife GMM (Newey and Windmeijer, 2009), we characterize the Gaussian asymptotic distribution of the estimator of the pseudo-true value using classical U-statistic theorems

    Rejoinder on : pseudo-true SDFs in conditional asset pricing models

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    We are extremely grateful to the discussants appointed by the co-editors of Journal of Financial Econometrics for their thorough and constructive comments on our paper. Lars P. Hansen has chosen to set the focus on the population analysis while Patrick Gagliardini and Diego Ronchetti have co-authored an impressive contribution mainly devoted to (statistical) comparison of estimators. Furthermore, Sydney Ludvigson, on the one hand, Raymond Kan and Cesare Robotti, on the other, have shared their discussion between the two dual issues of population analysis and inferential methods. We are also grateful to Rachidi Kotchoni for his discussion at the 2018 CIREQ Econometrics Conference on “Recent Advances in the Method of Moments”..

    Synthetic routes to novel fluorogenic pyronins and silicon analogs with far-red spectral properties and enhanced aqueous stability

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    International audienceFluorogenic detection of reactive (bio)analytes is often achieved with "smart" probes, whose activation mechanism causes the release of aniline-based fluorophores. Indeed, the protection-deprotection of their primary amino is the simplest way to induce dramatic and valuable changes in spectral features of the fluorogenic reporter. In this context, and due to their small size and intrinsic hydrophilicity, we focused on pyronin dyes and related heteroatom analogs (i.e., formal derivatives of 3-imino-3H-xanthen-6-amine and its silicon analog) for their use as optically tunable aniline-based fluorophores. To overcome some severe limitations associated with the use of such fluorogenic scaffolds (i.e., poor aqueous stability and spectral features only in the green-yellow spectral range), the synthesis of novel unsymmetrical derivatives of (Si)-pyronins bearing a single bulky tertiary aniline (i.e., N-methylindoline and julolidine) was explored and presented in this Article. This structural alteration has been found to be beneficial to dramatically lower electrophilicity of the meso-position and to reach attractive fluorescence properties within the far-red spectral region. † These authors contributed equally to this work

    Aquatic and terrestrial morphotypes of the aquatic invasive plant, Ludwigia grandiflora, show distinct morphological and metabolomic responses

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    International audienceIn the context of expansion of invasive species, survival of invasive plants is conditioned by their ability to adapt. In France, the water primrose , an aquatic invasive species, invades yet wet meadows, leading to a depreciation of their fodder value. Understanding its potential adaption is necessary to its management, strong differences between both morphotypes were expected. So morphological and metabolic responses to terrestrial environment were analyzed for aquatic and terrestrial morphotypes. All morphological and biomass variables were greater in the terrestrial morphotype than the aquatic morphotype, independent of conditions. In terrestrial condition, both morphotypes showed a high production of sugars in root tissues, especially in the terrestrial morphotype and both morphotypes produced a low level of amino acids in shoot tissues. All results demonstrate that the terrestrial condition seems a stressful situation for both morphotypes, which activates glycolysis and fermentation pathways to improve their survival under hypoxic stress. But, only the terrestrial morphotype has been able to adjust its metabolism and maintain efficient growth. In the future, a differential transcriptomic analysis will be carried out to confirm this result

    Saline stress tolerance partly matches with habitat preference in ground-living wolf spiders

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    International audienceSalinity interacts with many physiological functions and therefore probably influences the distribution of terrestrial fauna in tidal flooded salt marshes. The present study tests the hypothesis that the physiological tolerance of stenotopic wolf spiders for saline conditions at least partially determines their occurrence throughout salt-marsh and nonsaline habitats. The duration of survival of three stenotopic wolf spider species (Araneae: Lycosidae) with different habitat preferences is compared in a controlled laboratory experiment. The forest-dwelling Pardosa saltans, the salt-marsh resident Pardosa purbeckensis and its sister species the inlandliving Pardosa agrestis are exposed to experimental conditions with different levels of salinity. Individuals (45 males and 20-45 females per treatment) are placed in individual air-tight boxes filled with water-saturated sand. Three levels of salinity are tested: nonsaline (0‰), medium saline (33-35‰) and highly saline (66-70‰). Contents of carbon, hydrogen and nitrogen and the molar ration carbon/nitrogen remain constant over time and do not differ among salinity treatments, indicating that starvation effects on survival, if any, are similar for all treatments. Conversely, body water significantly decreases over time and differs among salinity treatments, in accordance with patterns of survival. Conforming to their habitat preference, the survival of P. saltans and P. agrestis decreases quickly under highly saline conditions. Pardosa purbeckensis, however, has a high survival under both saline and nonsaline conditions. The duration of survival of females is significantly lower than that of males of P. saltans and P. purbeckensis. Durations of survival of ground-living wolf spiders exposed to salinity partly match their habitat distribution but do not explain the restriction of salt-marsh species to saline habitats
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