Distinction morale entre animaux sauvages et non‐sauvages : une critique de l’approche contextuelle de Clare Palmer

Dans deux articles récents, Clare Palmer défend la portée morale de la distinction entre animaux non humains domestiqués et animaux non humains sauvages suivant une approche « contextuelle ». Suivant cette approche, Palmer considère que les liens historiques qui unissent les animaux domestiqués aux êtres humains, à l'origine causale d'un état de dépendance et de vulnérabilité subi par les premiers, génèrent des obligations morales spéciales à leur égard (devoir de protection, notamment) non partagées par les animaux non-domestiqués (« sauvages »). Considérant tout d'abord les limites de la distinction sauvage/domestique et de l'approche contextuelle proposées par Palmer, cet article questionne la capacité de l'approche contextuelle de Palmer à pouvoir faire sens néanmoins d'une autre idée de sauvage, à savoir un sauvage « localisé » ou environnemental

Les limites du principe de neutralité libérale en termes de politiques environnementales

Le principe de neutralité libéral (PNL) est l’idée selon laquelle l’autorité publique d’une société libérale doit permettre à tous ses membres politiques de suivre leur conception personnelle, individuelle de la vie bonne. Cet article vise à démontrer la non neutralité morale du PNL et les limites politiques que celle-ci implique – considérée dans le cadre du PNL – au niveau environnemental. Dans cet objectif, les trois aspects de neutralité engagés par le PNL seront exposés, puis critiqués. Cette analyse en trois temps visera à défendre la thèse selon laquelle le PNL ne permet pas au libéralisme politique de mettre en place des politiques environnementales qui seraient satisfaisantes d’un point de vue non- anthropocentré ni pour le moins « viables » écologiquement

Les limites du principe de neutralité libérale en termes de politiques environnementales

Le principe de neutralité libéral (PNL) est l’idée selon laquelle l’autorité publique d’une société libérale doit permettre à tous ses membres politiques de suivre leur conception personnelle, individuelle de la vie bonne. Cet article vise à démontrer la non neutralité morale du PNL et les limites politiques que celle-ci implique – considérée dans le cadre du PNL – au niveau environnemental. Dans cet objectif, les trois aspects de neutralité engagés par le PNL seront exposés, puis critiqués. Cette analyse en trois temps visera à défendre la thèse selon laquelle le PNL ne permet pas au libéralisme politique de mettre en place des politiques environnementales qui seraient satisfaisantes d’un point de vue non- anthropocentré ni pour le moins « viables » écologiquement

Resistance risk assessment of the novel complex II inhibitor pyflubumide in the polyphagous pest Tetranychus urticae

Pyflubumide is a novel selective carboxanilide acaricide that inhibits mitochondrial complex II of spider mite species such as Tetranychus urticae. We explored the baseline toxicity and potential cross-resistance risk of pyflubumide in a reference panel of T. urticae strains resistant to various acaricides with different modes of action. A cyenopyrafen-resistant strain (JPR) was identified as the only strain with low-to-moderate level of cross-resistance to pyflubumide (LC50 = 49.07 mg/L). In a resistance risk assessment approach, JPR was subsequently selected which led to two highly resistant strains JPR-R1 (RR = 466.7) and JPR-R2 (RR = 614.8). Interestingly, compared to adult females, resistance was much less pronounced in adult males and eggs of the two JPR-R strains. In order to elucidate resistance mechanisms, we first sequenced the complex II subunits in susceptible and resistant strains, but target-site insensitivity could not be detected. In contrast, synergism/antagonism experiments strongly suggested that cytochrome P450 monooxygenases are involved in pyflubumide resistance. We therefore conducted genome-wide gene expression experiments to investigate constitutive and induced expression patterns and documented the overexpression of five cytochrome P450 and four carboxyl/choline esterase genes in the JPR-R strains after pyflubumide exposure. Together, we provide a first resistance risk assessment of a novel complex II inhibitor and provide first evidence for metabolic resistance mediated by cytochrome P450s in T. urticae

Drug-bug crosstalk impacts compositional and functional features of in vitro gut microbial ecosystem

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Development of a quality assurance process for the SoLid experiment

The SoLid experiment has been designed to search for an oscillation pattern induced by a light sterile neutrino state, utilising the BR2 reactor of SCK circle CEN, in Belgium. The detector leverages a new hybrid technology, utilising two distinct scintillators in a cubic array, creating a highly segmented detector volume. A combination of 5 cm cubic polyvinyltoluene cells, with (LiF)-Li-6:ZnS(Ag) sheets on two faces of each cube, facilitate reconstruction of the neutrino signals. Whilst the high granularity provides a powerful toolset to discriminate backgrounds; by itself the segmentation also represents a challenge in terms of homogeneity and calibration, for a consistent detector response. The search for this light sterile neutrino implies a sensitivity to distortions of around O(10)% in the energy spectrum of reactor (v) over bare. Hence, a very good neutron detection efficiency, light yield and homogeneous detector response are critical for data validation. The minimal requirements for the SoLid physics program are a light yield and a neutron detection efficiency larger than 40 PA/MeV/cube and 50% respectively. In order to guarantee these minimal requirements, the collaboration developed a rigorous quality assurance process for all 12800 cubic cells of the detector. To carry out the quality assurance process, an automated calibration system called CALIPSO was designed and constructed. CALIPSO provides precise, automatic placement of radioactive sources in front of each cube of a given detector plane (16 x 16 cubes). A combination of Na-22, Cf-252 and AmBe gamma and neutron sources were used by CALIPSO during the quality assurance process. Initially, the scanning identified defective components allowing for repair during initial construction of the SoLid detector. Secondly, a full analysis of the calibration data revealed initial estimations for the light yield of over 60 PA/MeV and neutron reconstruction efficiency of 68%, validating the SoLid physics requirements

Quality control of substrate conformation in the Escherichia coli Twin Arginine protein-targeting pathway

In Escherichia coli, the twin arginine translocase (Tat) is one of the major protein translocation mechanisms. The Tat system has the ability to transport folded proteins across the inner membrane. Therefore, it has the ability to discriminate between folding states. However, it is not well understood how the Tat system senses the folding state of a substrate. In this study we probed the Tat proofreading mechanism and we investigated whether Tat substrates in E. coli are translocated by the Tat system due to their rapid folding kinetics. We demonstrate that the E. coli Tat machinery can process a de-novo designed substrate (BT6 maquette). Moreover the Tat proofreading mechanism can discriminated between different folding states of this substrate. This data and the fact that this simple four helix artificial substrate offers a lot of engineering freedom, suggests that BT6 is an ideal candidate to study the Tat proofreading mechanism (chapter 3). In chapter 4, we focussed on the Tat system’s proofreading ability by substituting substrate surfaces of BT6 maquette. Mutants with substituted surface properties were expressed in order to understand what Tat senses as folded. Expression assays showed whether the mutants were accepted or rejected by Tat. We propose that the proofreading system does not sense a global unfolded state of the substrate but has the ability to sense localised unfolded regions. Finally, we tested whether Tat substrates fold co- or post-translationally to determine the speed of the folding kinetics by using an arrest peptide-mediated force measurements assay (chapter 5). This study was to increase our understanding about the rationale for using the Tat system

Fitness costs of key point mutations that underlie acaricide target-site resistance in the two-spotted spider mite Tetranychus urticae

The frequency of insecticide/acaricide target-site resistance is increasing in arthropod pest populations and is typically underpinned by single point mutations that affect the binding strength between the insecticide/acaricide and its target-site. Theory predicts that although resistance mutations clearly have advantageous effects under the selection pressure of the insecticide/acaricide, they might convey negative pleiotropic effects on other aspects of fitness. If such fitness costs are in place, target-site resistance is thus likely to disappear in the absence of insecticide/acaricide treatment, a process that would counteract the spread of resistance in agricultural crops. Hence, there is a great need to reliably quantify the various potential pleiotropic effects of target-site resistance point mutations on arthropod fitness. Here, we used near-isogenic lines of the spider mite pest Tetranychus urticae that carry well-characterized acaricide target-site resistance mutations to quantify potential fitness costs. Specifically, we analyzed P262T in the mitochondrial cytochrome b, the combined G314D and G326E substitutions in the glutamate-gated chloride channels, L1024V in the voltage-gated sodium channel, and I1017F in chitin synthase 1. Five fertility life table parameters and nine single-generation life-history traits were quantified and compared across a total of 15 mite lines. In addition, we monitored the temporal resistance level dynamics of populations with different starting frequency levels of the chitin synthase resistant allele to further support our findings. Three target-site resistance mutations, I1017F and the co-occurring G314D and G326E mutations, were shown to significantly and consistently alter certain fitness parameters in T. urticae. The other two mutations (P262T and L1024V) did not result in any consistent change in a fitness parameter analyzed in our study. Our findings are discussed in the context of the global spread of T. urticae pesticide resistance and integrated pest management

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS AS THERAPEUTIC ALLIES OF THE GUT MICROBIOME ON CHRONIC INFLAMMATION

Our gut harbours around 1014 bacteria of more than 1000 species, accounting for approximately 2 kg of biomass. The gut microbiome plays several vital functions in processes such as the development of the immune system, food digestion and protection against pathogens. For these functions to be beneficial for both host and microbiome, interactions are tightly regulated. Gut and immune cells continuously interact to distinguish among commensal microbiota, harmless foodstuff, and pathogens. A fine balance between inflammatory and anti-inflammatory state is fundamental to protect intestinal homeostasis. Nonsteroidal anti-inflammatories (NSAIDs) are a class of drugs used for management of pain and inflammation. These compounds have heterologous structures but similar therapeutic activities. The target of all NSAIDs are the isoforms of cyclooxygenase enzymes (COX): the primarily constitutive form COX-1, and the inducible from COX-2. Both isoforms catalyse the conversion of arachidonic acid to PGH2, the immediate substrate for specific prostaglandin and thromboxane synthesis. The gut microbiota plays a role in drug metabolism,  resulting in altered bioavailability of these compounds. Additionally, complex host-microbiome interactions lead to modified xenobiotic metabolism and altered expression of genes involved in drug metabolism. These effects can be at gut tissue-level, or distant, including in the liver. Besides the gut microbiome influencing drug metabolism, drugs also impact the microbial communities in the gut. As different drugs exert selective pressures on the gut microbiome,  understanding this bidirectional relationship is crucial for developing effective therapies for managing chronic inflammation