Integral field spectroscopy of planetary nebulae: mapping the line diagnostics and hydrogen-poor zones with VLT FLAMES

Results from the first dedicated study of Galactic planetary nebulae (PNe) by means of optical integral field spectroscopy with the Very Large Telescope Fibre Large Array Multi Element Spectrograph Argus integral field unit are presented. Three typical Galactic disc PNe have been mapped with the 11.5 × 7.2-arcsec2 Argus array: 2D spectral maps of the main shell of NGC 5882 and of large areas of NGC 6153 and NGC 7009 with 297 spatial pixels per target were obtained at subarcsec resolutions. A corresponding number of 297 spectra per target were obtained in the 396.4–507.8 nm range. Spatially resolved maps of emission lines and of nebular physical properties such as electron temperatures, densities and ionic abundances were produced. The abundances of helium and of doubly ionized carbon and oxygen, relative to hydrogen, were derived from optical recombination lines (ORLs), while those of O2+ were also derived from the classic collisionally excited lines (CELs). The occurrence of the abundance discrepancy problem, pertaining to oxygen, was investigated by mapping the ratio of ORL/CEL abundances for O2+[the abundance discrepancy factor (ADF)] across the face of the PNe. The ADF varies between targets and also with position within the targets, attaining values of ∼40 in the case of NGC 6153 and ∼30 in the case of NGC 7009. Correlations of the ADF with geometric distance from the central star and plasma surface brightness (for NGC 6153), as well as with [O III] electron temperature, plasma ionization state and other physical properties of the targets are established. Very small values of the temperature fluctuation parameter in the plane of the sky, t2A(O2+), are found in all cases.It is argued that these results provide further evidence for the existence in run-of-the-mill PNe of a distinct nebular component consisting of hydrogen-deficient, super-metal-rich plasma. The zones containing this posited component appear as undulations in the C II and O II ORL abundance diagnostics of about 2 spatial pixels across, and so any associated structures should have physical sizes of less than ∼1000 astronomical units. Regarding the origin of the inferred zones, we propose that circumstellar discs, Abell 30-type knots, or Helix-type cometary globules may be involved. Implications for emission-line studies of nebulae are discussed

Identifying human toxicodynamic variability: a systematic evidence map of the current knowledge

Current chemical risk assessment uses a default uncertainty factor (UF) of 3.16 for toxicodynamic (TD) variability in humans. The objective was to create a systematic evidence map (SEM) of the human variability in TD by identifying and organizing the available empirical data to assess if a further refinement of the default UF of 3.16 for TD can be achieved. PubMed and Web of Science™ were searched from 2004 to 2023. Studies were screened according to the eligibility criteria. Inclusion criteria included studies, where TD could be separated from toxicokinetics (TK) to exclude an impact of TK on TD variability. The literature search retrieved 2408 studies. Manual screening identified 23 in vitro studies assessing human TD variability quantitively, of which only seven in vitro studies provided quantitative estimates of a TD variability factor. No in vivo study met the inclusion criteria. Several studies found TD UF of 3.16 not covering human variability; others did. However, the data were heterogeneous, and variability in Points of Departure (PODs) and methods used to estimate TD variability complicated comparisons across studies. A standardized approach for TDVFs determination is identified. This SEM underscores the scarcity of data assessing human variability in TD, while omitting the influence of TK.Toxicolog

Investigating combined toxicity of binary mixtures in bees: meta-analysis of laboratory tests, modelling, mechanistic basis and implications for risk assessment

Bees are exposed to a wide range of multiple chemicals “chemical mixtures” from anthropogenic (e.g. plant protection products or veterinary products) or natural origin (e.g. mycotoxins, plant toxins). Quantifying the relative impact of multiple chemicals on bee health compared with other environmental stressors (e.g. varroa, viruses, and nutrition) has been identified as a priority to support the development of holistic risk assessment methods. Here, extensive literature searches and data collection of available laboratory studies on combined toxicity data for binary mixtures of pesticides and non-chemical stressors has been performed for honey bees (Apis mellifera), wild bees (Bombus spp.) and solitary bee species (Osmia spp.). From 957 screened publications, 14 publications provided 218 binary mixture toxicity data mostly for acute mortality (lethal dose: LD50) after contact exposure (61%), with fewer studies reporting chronic oral toxicity (20%) and acute oral LC50 values (19%). From the data collection, available dose response data for 92 binary mixtures were modelled using a Toxic Unit (TU) approach and the MIXTOX modelling tool to test assumptions of combined toxicity i.e. concentration addition (CA), and interactions (i.e. synergism, antagonism). The magnitude of interactions was quantified as the Model Deviation Ratio (MDR). The CA model applied to 17% of cases while synergism and antagonism were observed for 72% (MDR > 1.25) and 11% (MDR < 0.83) respectively. Most synergistic effects (55%) were observed as interactions between sterol-biosynthesis-inhibiting (SBI) fungicides and insecticide/acaricide. The mechanisms behind such synergistic effects of binary mixtures in bees are known to involve direct cytochrome P450 (CYP) inhibition, resulting in an increase in internal dose and toxicity of the binary mixture. Moreover, bees are known to have the lowest number of CYP copies and other detoxification enzymes in the insect kingdom. In the light of these findings, occurrence of these binary mixtures in relevant crops (frequency and concentrations) would need to be investigated. Addressing this exposure dimension remains critical to characterise the likelihood and plausibility of such interactions to occur under field realistic conditions. Finally, data gaps and further work for the development of risk assessment methods to assess multiple stressors in bees including chemicals and non-chemical stressors in bees are discussed

Follicle-Stimulating Hormone Receptor: Advances and Remaining Challenges

International audienc

Concentration addition, independent action and generalized concentration addition models for mixture effect prediction of sex hormone synthesis in vitro

Humans are concomitantly exposed to numerous chemicals. An infinite number of combinations and doses thereof can be imagined. For toxicological risk assessment the mathematical prediction of mixture effects, using knowledge on single chemicals, is therefore desirable. We investigated pros and cons of the concentration addition (CA), independent action (IA) and generalized concentration addition (GCA) models. First we measured effects of single chemicals and mixtures thereof on steroid synthesis in H295R cells. Then single chemical data were applied to the models; predictions of mixture effects were calculated and compared to the experimental mixture data. Mixture 1 contained environmental chemicals adjusted in ratio according to human exposure levels. Mixture 2 was a potency adjusted mixture containing five pesticides. Prediction of testosterone effects coincided with the experimental Mixture 1 data. In contrast, antagonism was observed for effects of Mixture 2 on this hormone. The mixtures contained chemicals exerting only limited maximal effects. This hampered prediction by the CA and IA models, whereas the GCA model could be used to predict a full dose response curve. Regarding effects on progesterone and estradiol, some chemicals were having stimulatory effects whereas others had inhibitory effects. The three models were not applicable in this situation and no predictions could be performed. Finally, the expected contributions of single chemicals to the mixture effects were calculated. Prochloraz was the predominant but not sole driver of the mixtures, suggesting that one chemical alone was not responsible for the mixture effects. In conclusion, the GCA model seemed to be superior to the CA and IA models for the prediction of testosterone effects. A situation with chemicals exerting opposing effects, for which the models could not be applied, was identified. In addition, the data indicate that in non-potency adjusted mixtures the effects cannot always be accounted for by single chemicals

Iconographie de la Crucifixion et dévotion laïque : la cathédrale de Fribourg-en-Brisgau dans la première moitié du XIVe siècle

La représentation de la Crucifixion dans de grandes compositions aux tympans des églises est un phénomène tardif dans l’Occident médiéval : elle pose le problème de l’intégration de l’iconographie monumentale dans le contexte religieux et homilétique. Les premiers exemples de la fin du XIe siècle étaient liés aux hérésies cathare et petrobrusienne du sud de la France. Au XIVe siècle, la diffusion du thème rend plus difficile une approche globale de la question. Dans le contexte précis et bien..

Exploration et modélisation structurale d’interactions protéiques guidées par l’information évolutive

Protein complexes are of fundamental importance in most biological processes and mainly carry out their function in networks. The structure of their interface can give us crucial information to understand the mechanisms behind these processes. This thesis focuses on the improvement of the performance of structural prediction methods, in particular by exploiting co-evolutionary information. As part of my PhD project, I participated in major developments in our docking server, InterEvDock2, which suggests 10 interface models for a pair of input proteins using a mix of different scoring properties. InterEvDock2 now also accepts oligomeric structure inputs or sequence inputs, for which it can model monomeric structures, as well as user constraints taken from prior knowledge of the interaction. I validated the performance of InterEvDock2 on a large benchmark of 812 docking cases and found that InterEvDock2 was capable of finding a correct complex structure in as much as 32 % of these cases. My work then focused on finding a more efficient and explicit way of integrating implicitly defined evolutionary information into scoring. I made this information directly compatible with atomic-scale scoring thanks to homologous interface modelling. This strongly increases predictive power, from 32% to 40% on our large benchmark. Moreover, throughout my PhD, I was able to participate in 10 blind-test docking challenges through CAPRI (Critical Assessment of Predicted Interactions). The strategies applied by our team, which enabled us to rank first in the latest CAPRI round for 2016-2019, are described in the last chapter of this manuscript. This work aims at helping biologists study their proteins or biological pathways of interest using well performing prediction methods. It constitutes a step towards the final goal of interactome prediction.Les protéines sont des acteurs centraux du vivant et agissent rarement seules. La structure 3D de leurs interactions aide à mieux comprendre les mécanismes des processus biologiques dans lesquels elles sont impliquées. L’objectif de cette thèse était d’améliorer la performance des méthodes de prédiction structurale, notamment en utilisant l’information de (co-)évolution. J'ai participé à des évolutions majeures de notre serveur de docking, InterEvDock2, qui, à partir de deux protéines, propose 10 modèles d'interface en croisant des scores aux propriétés différentes. Le serveur accepte désormais aussi en entrée des structures oligomériques ou des séquences protéiques, pour lesquelles il modélise la structure monomérique, ainsi que des contraintes connues a priori sur l’interaction. Sur un large ensemble de 812 cas test, InterEvDock2 prédit une structure de complexe correcte dans 32 % des cas. J’ai ensuite recherché un moyen plus explicite d'intégrer dans les fonctions de score l’information évolutive contenue dans les alignements de séquences. J’ai rendu cette information compatible avec l’utilisation de scores atomiques par la modélisation 3D des interfaces homologues. Ceci améliore la performance prédictive de 32 à 40% sur notre large base de test. De plus, durant ma thèse, j'ai pu participer à 10 tests de docking à l’aveugle via CAPRI (Critical Assessment of Predicted Interactions). Les stratégies qui ont permis à notre équipe d’être classée première sur la période 2016-2019 sont décrites dans le dernier chapitre de ce manuscrit. Ce travail vise à aider les biologistes à étudier les protéines ou voies biologiques d'intérêt en utilisant des méthodes de prédiction performantes et constitue un pas en avant dans l'objectif final de la prédiction des interactomes