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Nowadays, life expectancy is increasing but is not systematically accompanied by a decent quality of life during aging. With the overall aging of the population, it is urgent to highlight strategies to promote the maintenance of autonomy at old age. While the effects of exercise training on limiting the loss of functional autonomy in the elderly are well-established, the molecular mechanisms by which it may slowdown the hallmarks of skeletal muscle aging, notably through the regulation of telomere health and cellular senescence, need to be further investigated. In this thesis, we found that even if endurance training did not effectively reduce senescence, the training status might attenuate the senescence-associated secretory phenotype in human skeletal muscle. Moreover, the age-dependent increase in TERRA expression might represent a novel biological marker of aging which is alleviated by endurance training., (MOTR - Sciences de la motricité) -- UCL, 2022

Learning biology, and in particular systematics, requires learning a substantial amount of specific vocabulary, both for botanical and zoological studies. While crucial, the precise identification of structures serving as evolutionary traits and systematic criteria is not per se a highly motivating task for students. Teaching this in a traditional teaching setting is quite challenging especially with a large crowd of students to be kept engaged. This is even more difficult if, as during the COVID-19 crisis, students are not allowed to access laboratories for hands-on observation on fresh specimens and sometimes restricted to short-range movements outside their home. Here, we present QuoVidi, a new open-source web platform for the organization of large-scale treasure hunts. The platform works as follows: students, organized in teams, receive a list of quests that contain morphologic, ecologic, or systematic terms. They have to first understand the meaning of the quests, then go and find them in the environment. Once they find the organism corresponding to a quest, they upload a geotagged picture of their finding and submit this on the platform. The correctness of each submission is evaluated by the staff. During the COVID-19 lockdown, previously validated pictures were also submitted for evaluation to students that were locked in low-biodiversity areas. From a research perspective, the system enables the creation of large image databases by the students, similar to citizen science projects. Beside the enhanced motivation of students to learn the vocabulary and perform observations on self-found specimens, this system allows instructors to remotely follow and assess the work performed by large numbers of students. The interface is freely available, open-source and customizable. Unlike existing naturalist platforms, allows the educators to fully customize the quests of interest. This enables the creation of multiple teaching scenarios, without being bound to a fixed sc

Limited knowledge of the molecular evolution of deep-sea fish proteomes so far suggests that a few widespread residue substitutions in cytosolic proteins binding hydrophilic ligands contribute to resistance to the effects of high hydrostatic pressure (HP). Structure-function studies with additional protein systems, including membrane bound proteins, are essential to provide a more general picture of adaptation in these extremophiles. We explored molecular features of HP adaptation in proteins binding hydrophobic ligands, either in lipid bilayers (cytochrome P450 1A - CYP1A) or in the cytosol (the aryl hydrocarbon receptor - AHR), and their partners P450 oxidoreductase (POR) and AHR nuclear translocator (ARNT), respectively. Cloning studies identified the full-length coding sequence of AHR, CYP1A and POR, and a partial sequence of ARNT from Coryphaenoides armatus, an abyssal gadiform fish thriving down to 5000m depth. Inferred protein sequences were aligned with many non-deep-sea homologs to identify unique amino acid substitutions of possible relevance in HP adaptation. Positionally unique substitutions of various physicochemical properties were found in all four proteins, usually at sites of strong-to-absolute residue conservation. Some were in domains deemed important for protein-protein interaction or ligand binding. In addition, some involved removal or addition of beta-branched residues; local modifications of beta-branched residue patterns could be important to HP adaptation. In silico predictions further suggested that some unique substitutions might substantially modulate the flexibility of the polypeptide segment in which they are found. Repetitive motifs unique to the abyssal fish AHR were predicted to be rich in glycosylation sites, suggesting that post-translational changes could be involved in adaptation as well. Recombinant CYP1A and AHR showed functional properties (spectral characteristics, catalytic activity and ligand binding) that demonstrate prop

Long chain polyunsaturated fatty acids (LC-PUFAs) such as eicosapentaenoic acid (EPA, 20:5n-3) affect zooplankton fitness and ability to cope with environmental stressors. However, the impact of LC-PUFAs on zooplankton sensitivity to chemical stressors is unknown. Here, we aimed to document the interaction between EPA and cadmium (Cd), as model chemical stressor, in Daphnia magna. A life-history experiment was performed in which daphnid neonates were raised into adulthood on three diets of different lipid composition: (i) algae mix; (ii) algae mix supplemented with control liposomes; (iii) algae mix supplemented with liposomes containing EPA. Juveniles (3rd, 4th and 5th brood) released by daphnids during this life-history experiment were sampled, challenged with Cd during 48 h and their immobility was assessed. At the end of this life-history experiment, another immobilisation test was performed with adults from each treatment. Daphnids absorbed, incorporated and transferred ingested EPA to their offspring. Liposome feeding increased adult tolerance to Cd. The presence of EPA in liposomes did not increase adult tolerance to Cd. Offspring's tolerance to Cd was influenced by the brood number and the maternal diet. It was positively correlated with the PUFA level in body neutral lipids, especially alpha-linolenic acid (ALA, 18:3n-3) and negatively correlated with the saturated fatty acid level in body neutral lipids, especially stearic acid (18:0). Overall, these results emphasize the importance of dietary lipids and maternal transfer of body lipids in D. magna sensitivity to Cd and highlight the need to take into account these parameters in ecotoxicological studies and risk assessment.

Hydrostatic pressure (HP) increases by about 1 atmosphere (0.1 MPa) for each ten-meter depth increasein the water column. This thermodynamical parameter could well influence the response to and effects ofxenobiotics in the deep-sea biota, but this possibility remains largely overlooked. To grasp the extent of HPadaptation in deep-sea fish, comparative studies with living cells of surface species exposed to chemicalsat high HP are required. We initially conducted experiments with precision-cut liver slices of a deep-sea fish (Coryphaenoides rupestris), co-exposed for 15 h to the aryl hydrocarbon receptor (AhR) agonist3-methylcholanthrene at HP levels representative of the surface (0.1 MPa) and deep-sea (5–15 MPa; i.e.,500–1500 m depth) environments. The transcript levels of a suite of stress-responsive genes, such asthe AhR battery CYP1A, were subsequently measured (Lemaire et al., 2012; Environ. Sci. Technol. 46,10310–10316). Strikingly, the AhR agonist-mediated increase of CYP1A mRNA content was pressure-dependently reduced in C. rupestris. Here, the same co-exposure scenario was applied for 6 or 15 h toliver slices of a surface fish, Dicentrarchus labrax, a coastal species presumably not adapted to high HP.Precision-cut liver slices of D. labrax were also used in 1 h co-exposure studies with the pro-oxidant tert-butylhydroperoxide (tBHP) as to investigate the pressure-dependence of the oxidative stress response(i.e., reactive oxygen production, glutathione and lipid peroxidation status). Liver cells remained viable inall experiments (adenosine triphosphate content). High HP precluded the AhR agonist-mediated increaseof CYP1A mRNA expression in D. labrax, as well as that of glutathione peroxidase, and significantly reducedthat of heat shock protein 70. High HP (1 h) also tended per se to increase the level of oxidative stress inliver cells of the surface fish. Trends to an increased resistance to tBHP were also noted. Whether thelatter observation truly reflects a

The polyunsaturated fatty acid (PUFA) composition of fish tissues, which generally reflects that of thediet, affects various cellular properties such as membrane structure and fluidity, energy metabolism andsusceptibility to oxidative stress. Since these cellular parameters can play an important role in the cellularresponse to organic and inorganic pollutants, a variation of the PUFA supply might modify the toxicityinduced by such xenobiotics. In this work, we investigated whether the cellular fatty acid profile has animpact on the in vitro cell sensitivity to two environmental pollutants: methylmercury and cadmium.Firstly, the fatty acid composition of the rainbow trout liver cell line RTL-W1 was modified by enrichingthe growth medium with either alpha-linolenic acid (ALA, 18:3n-3), eicosapentaenoic acid (EPA, 20:5n-3),docosahexaenoic acid (DHA, 22:6n-3), linoleic acid (LA, 18:2n-6), arachidonic acid (AA, 20:4n-6) or docos-apentaenoic acid (DPA, 22:5n-6). These modified cells and their control (no PUFA enrichment) were thenchallenged for 24 h with increasing concentrations of methylmercury or cadmium. We observed that (i)the phospholipid composition of the RTL-W1 cells was profoundly modulated by changing the PUFA con-tent of the growth medium: major modifications were a high incorporation of the supplemented PUFA inthe cellular phospholipids, the appearance of direct elongation and desaturation metabolites in the cellu-lar phospholipids as well as a change in the gross phospholipid composition (PUFA and monounsaturatedfatty acid (MUFA) levels and n-3/n-6 ratio); (ii) ALA, EPA and DPA enrichment significantly protected theRTL-W1 cells against both methylmercury and cadmium; (iv) DHA enrichment significantly protectedthe cells against cadmium but not methylmercury; (v) AA and LA enrichment had no impact on the celltolerance to both methylmercury and cadmium; (vi) the abundance of 20:3n-6, a metabolite of the n-6 biotransformation pathway, in phospholipids was negati

We investigated the changes of vitamins A and E as well as PCBs and DDTs during lactation in northern elephant seal (Mirounga angustirostris) mother-pup pairs. On average, milk vitamin A concentrations were 6 times higher during late lactation than during early lactation, a pattern that differs dramatically from terrestrial mammals. Vitamin A concentrations also significantly increased in the inner blubber throughout lactation, whereas they remained constant in the outer blubber. Similar dynamics were observed for PCBs and DDTs in maternal blubber and milk. Blubber appears to be an important storage site for vitamin A and organochlorines in seals and a direct transfer of those molecules to the mammary gland may occur. The dynamics of vitamin A, PCBs and DDTs differed from those of vitamin E. There was a significant drop in milk vitamin E concentrations between early and late lactation, which is the usual pattern observed in terrestrial mammals. The dynamics of vitamin E in the blubber layers also differed from those of vitamin A, suggesting different mechanisms of mobilization and transfer into the milk.

Arenicola marina lives in marine environments where hydrogen peroxide concentrations reach micromolar levels. The annelid also forms reactive species through metabolic pathways. Its antioxidant systems include a cytosolic peroxiredoxin, peroxiredoxin 6 (AmPrx6 or AmPRDX6) that shows high homology to the mammalian 1-Cys peroxiredoxin. Previous work confirmed the peroxidase activity of AmPrx6 in the presence of dithiotreitol. Herein, we performed an in vitro kinetic characterization of the recombinant enzyme. AmPrx6 reduced hydrogen peroxide and peroxynitrite with rate constants of 1.1 × 107 and 2 × 106 M−1 s−1, respectively, at pH 7.4 and 25 °C. Reduction of tert-butyl hydroperoxide was slower. The pKa of the peroxidatic thiol of AmPrx6 was determined as 5.1 ± 0.2, indicating that it exists as thiolate, the reactive species, at physiological pH. The reductive part of the catalytic cycle was also explored. Hydrogen sulfide, present in millimolar concentrations in marine sediments where the annelid lives and that is able to reduce the mammalian 1-Cys peroxiredoxin, did not support AmPrx6 peroxidase activity. The enzyme was not reduced by other potential physiological reductants tested. Our data indicate that in this annelid, Prx6 could contribute to peroxide detoxification in the presence of a so far unidentified reducing counterpart.

Deep-sea fish are highly contaminated with organochlorine compounds(OCs), which are persistent man-made chemicals. Because it is very difficult to maintain these fish alive for toxicological experiments, the real impact of such contamination remains unknown. By analysing liver samples of the deep-sea grenadier Coryphaenoides rupestris (200 - 2600 meter depth), we first observed signs of an oxidative impact linked to OCs' metabolism. The activity of the phase 1 detoxification cytochrome P4501A (CYP1A) enzyme was positively correlated to OCs loads and antioxidant enzymes activities (catalase, superoxide dismutase). Still, the magnitude of CYP1A induction was fairly low compared to the huge contamination. We then developed the precision-cut liver slices (PCLS) technology to study more in-depth the oxidative impact of OCs' metabolism on living liver cells of C. rupestris. Two shallow fish (Salmo salar, Dicentrarchus labrax) were also chosen as basis for comparison. Hyperbaric cylinders were used to investigate in this comparative study the effects of the high hydrostatic pressure (typical of the deep-sea) on the response of liver cells of these fish to contaminants, their pro- and anti-oxidant status and that of heat shock proteins (also known to participate in a general stress response to toxicants). Apart from the obtention of the first-ever data on living deep-sea fish liver cells, we found a striking pressure-dependent reduction of CYP1A induction in each species, suggesting that deep-sea fish might be less prone to the oxidative impact of OCs metabolism in their environment (a feature that might explain their high OCs loads)., (BIOL 3) -- UCL, 2011

Based on the imidazo-[1,2-a]-pyrazin-3-(7H)-one scaffold, a dual action prodrug has been designed for combining antioxidant and anti-inflammatory activities, possibly unmasked upon oxidation. The construction of the target-molecule requires two building blocks, namely a 2-amino-1,4-pyrazine and a 2-ketoaldehyde. Attempts to synthesize the 2-ketoaldehyde (5a) derived from ibuprofen failed, but led to the corresponding 2-ketoaldoxime (7a) which could not be condensed with the pyrazine synthons. However, a model compound, i.e. phenylglyoxal aldoxime, reacted well under microwave activation to furnish novel imidazo[1,2-a]-pyrazine-3-(7H)-imine derivatives (18a,b). These heterobicycles behave as antioxidants by inhibiting the lipid peroxidation, and one compound (18b) is endowed with a significant anti-inflammatory effect in a cellular test. Unexpectedly, all the synthetic intermediates derived from ibuprofen are good inhibitors of FAAH, the most active compound (4a) featuring the 1,3-dithian-2-yl motif.