HAL Université de Toulouse, et Toulouse INP
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Liver X receptors and the hallmarks of aging: From molecular mechanisms to therapeutic opportunities
No full textInternational audienceAging is the primary risk factor for cardiovascular disease, cancer, neurodegeneration, and other chronic disorders. Therefore, targeting the hallmarks of aging has emerged as a promising strategy to extend healthspan. Liver X receptors (LXRs) are ligand-dependent nuclear receptors that are activated by specific oxysterols and cholesterol derivatives. They are traditionally known as key regulators of cholesterol homeostasis. However, recent evidence reveals that LXRs also influence autophagy, mitochondrial function, epigenetics, senescence, stem cell dynamics, and intercellular communication. This positions LXRs at the crossroads of multiple hallmarks of aging. This review synthesizes current knowledge on endogenous and synthetic LXR ligands, their transcriptional mechanisms, and their effects on the aforementioned hallmarks and age-related pathophysiology. The clinical development of pan-LXR agonists for atherosclerosis has been hindered by side effects, notably hepatic steatosis. Emerging strategies, including LXRβ-selective ligands, selective LXR modulators (SLiMs), and biased agonists such as dendrogenin A, offer ways to separate the protective vascular, metabolic, and neuroprotective effects from adverse outcomes. Additionally, we explore how LXR signaling intersects with the hallmarks of aging and how it can be leveraged to intervene in atherosclerosis, diabetes, cancer, osteoporosis, age-related macular degeneration, and neurodegenerative diseases. Positioning LXRs within the geroscience framework suggests that LXRs may serve as pharmacological hubs to delay aging and its comorbidities. Future work should prioritize isoform-and tissue-selective approaches, metabolite-inspired ligand design, and integration with the hallmarks of aging to unlock the full therapeutic potential of LXRs.</div
Oral indomethacin modifies small intestine biofilms and host-microbe interaction mediators
No full textInternational audienceBackground and aims: Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause small intestinal injury and dysbiosis. Although NSAID-induced dysbiosis is well-characterized and contributes to enteropathy, the changes in host-bacterial interactions during enteropathy remain largely unexplored. Here we assessed the expression pattern of six toll-like receptors (TLRs) and three antimicrobial peptides (AMPs) over the course of indomethacin (IND)-induced enteropathy in rats, and evaluated their correlations with inflammation and dysbiosis. In addition, we assessed for the first time the effect of IND on small intestinal mucosal biofilm structure.Materials and methods: Mucosal injury, inflammation and expression of TLR and AMP genes were evaluated at five time points following IND administration. Gut microbiota composition was determined by 16S rRNA gene sequencing. Small intestinal mucosal biofilms were visualized using fluorescent in situ hybridisation.Key findings: We found that TLR1, TLR2 and cathelicidin were upregulated, TLR5 was downregulated, whereas TLR6 and TLR9 were not altered in enteropathy. TLR4 expression showed only subtle differences, but correlated with α-defensin 5 and β-defensin 2 levels. We found several correlations between TLRs, AMPs, inflammation and gut bacteria in severe enteropathy, but in early disease stage TLR1, TLR2, TLR5 and cathelicidin expression were more strongly associated with inflammation, whereas TLR4 and defensins were more dependent on gut dysbiosis. IND treatment also caused mild damage to the mucosal microbiota biofilm.Significance: This is the first comprehensive characterization of the time-dependent changes in TLRs, AMPs and mucosal biofilm in NSAID-treated rats, which may help to identify new strategies for the treatment of enteropathy
From innovation to exnovation: insights from post-growth food enterprises in Australia
No full textInternational audienceThis study explores systemic barriers and enablers of post-growth food enterprises in Australia. We analyse three different case studies that offer alternative models of entrepreneurial approaches for achieving sustainability outcomes as a higher priority than economic growth. We identified three post-growth food enterprises that operate at different stages of the food supply chain. We found that these enterprises work towards various, interconnected, sustainability goals by embedding diverse principles into their organisational structure and operations. Their not-for-profit structure enables them to avoid trade-offs between financial extractivism and socio-ecological well-being goals. Additionally, we explored the systemic barriers faced by these enterprises, recognising that they are embedded in an economic system that favours and rewards the pursuit of economic growth. To navigate these barriers, the cases analysed adopted various innovative approaches, such as fostering alternative funding schemes, ways to acquire farmland and technology. While their bottom-up approaches are important, the inertia of dominant food systems impedes transitions to alternatives. We suggest that exnovation - the process of deliberately phasing out unsustainable practices - warrants more attention. For example, exnovating goals, policies, and performance metrics that prioritise economic growth at the expense of sustainability could play a crucial role in unlocking post-growth models. This study provides an orientation for further theoretical and empirical research about post-growth food systems transitions and stresses the value of engaging more with the wider political, economic, and legal foundations of transitions
Strategies to advance the agroecological transition: Insights from a case study of sheep–crop integration in southwestern France
No full textInternational audienceContext: Mediterranean areas face multiple challenges, including biodiversity loss, soil degradation, and vulnerability to climate change. In southern France's Languedoc region, vineyard monoculture dominates, and livestock systems are rare. Agroecological transitions, especially crop-livestock integration, offer opportunities to diversify systems, recycle nutrients, enhance biodiversity, and reduce fire risks. However, such integration is difficult due to climatic constraints, land accessibility, and the current disconnection between crop and livestock systems.Objective: This study aimed to explore how crop-livestock integration practices in the Minervois territory could be expanded to support agroecological transitions. It focused on identifying synergies that address forage needs for local flocks and create benefits for vineyard and cereal farmers.Methods: As part of a larger participatory and locally grounded approach, we designed agroecological scenarios based on integration of sheep farming system with various crop and semi-natural areas. We assessed the potential to reintroduce livestock in an area where few systems have existed recently. The process identified both the biotechnical and coordination conditions required to sustain livestock with local forage throughout the year and to organize exchanges among stakeholders.Results and conclusions: Except under dry conditions, a flock of 1200 ewes could be sustained year-round through a diversified landscape combining cereal crops, vineyard inter-rows, local rangelands, and transhumance (i.e., moving the flock from one territory to another to graze available forage resources). This diversity enhances agroecological performance through crop-livestock complementarities by exploiting synergies between animal and plant species, over time and space. The method used can be adapted to other territories, and stakeholder involvement is essential for developing understanding and implementing feasible scenariosSignificance: The results support future studies aiming to link forage availability with organizational strategies to identify grazing areas and develop concrete implementation plans
The role of hydrogen sulfide and trisulfur radical ion in molybdenum transport by hydrothermal fluids: implications for porphyry-epithermal Cu-Au-Mo deposits
No full textInternational audienceKnowledge of the chemical speciation of molybdenum in fluids under hydrothermal conditions is key to understanding the formation of porphyry Cu-Au-Mo deposits, which are the primary economic source of copper, molybdenum and rhenium. However, the chemical identity and thermodynamic stability of aqueous complexes of molybdenum and the role of different ligands on Mo metal transport yet remain inconsistent and incomplete, in particular for sulfur-bearing fluids typical of such environments. We have experimentally studied the role of hydrogen sulfide (H 2 S and HS -) and the trisulfur radical ion (S 3 •-) in the transport of molybdenum by hydrothermal fluids at 300 °C and 500 bar as a function of pH, redox conditions as well as sulfur speciation and concentration. We combined solubility measurements of molybdenite in hydrothermal reactors using fluid quenching or sampling, with in situ synchrotron X-ray absorption spectroscopy experiments and thermodynamic and molecular modeling. Our solubility and spectroscopic dataset is consistent with the formation of the tetrathiomolybdate complex, MoS 4 2-, in reduced, H 2 S/HS --dominated fluids of neutralto-alkaline pH. In contrast, a mixed-ligand complex with three sulfide ions and one trisulfur radical ion, MoS 3 (S 3 ) -, prevails in more oxidized and more acidic fluids at the sulfide-sulfate transition where S 3 •-is far more abundant. In both complexes, Mo is nominally hexavalent and in a first-shell tetrahedral coordination with sulfur atoms. The derived equilibrium constants of the formal solubility reactions (log 10 K):MoS 2(s) + 2 H 2 S 0 (aq) + 0.5 O 2(g) = MoS 4 2-+ 2 H + + H 2 O (liq) and MoS 2(s) + H 2 S 0 (aq) + S 3 •-+ 0.5 O 2(g) = MoS 3 (S 3 ) -+ H 2 O (liq) , at 300 °C and 500 bar are 0.5±0.4 and 14.6±0.4, respectively. The solubility of MoS 2(s) predicted using these constants aligns well with Mo concentrations measured in natural fluid inclusions in quartz that record S-rich fluids from porphyry-epithermal systems. In contrast, other types of Mo complexes invoked so far (molybdates, alkali ion pairs, oxy-chlorides or oxysulfides) are negligible at such conditions. Thus, trisulfur radical ion complexes may be important carriers of Mo in hydrothermal fluids and would require further systematic investigation across a wide range of temperature and pressure.</p
Quel avenir pour les politiques publiques en faveur de la démocratie alimentaire ?
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Effect of particle size on bioleaching of chalcopyrite at moderate temperature
No full textInternational audienceSeveral methods have been studied to overcome chalcopyrite passivation during bioleaching at atmospheric pressure. One such method is to reduce particle size to increase the reactive surface area of the mineral. However, little is known about the effect of fine particles on the performance of chalcopyrite bioleaching in terms of bacterial growth and activity. In this study, two size fractions were prepared by sieving a raw chalcopyrite concentrate to produce particles between 20 and 100 µm and particles below 20 µm. These three materials were used in batch bioleaching tests performed in 2 L stirred reactors at 42 • C, with a solid concentration of 10 %w/w and the BRGM-KCC microbial consortium. Redox potential and iron and copper concentrations were monitored over time to characterize the reaction progress. With the coarser materials, the redox potential increased to above 750 mV vs. SHE within a day, whereas particles below 20 µm took an additional day to reach this potential. This lag phase permitted faster copper dissolution, resulting in a yield of 35 % after two days. In contrast, a yield of 10-20 % copper was achieved in 15 days using coarser materials. In contrast to previous assumptions, fine particles did not hinder bacterial growth and activity. Rather, they promoted them by increasing the availability of substrates generated by greater sulfide oxidation. Bioleaching chalcopyrite particles < 20 µm produced higher copper yields thanks not only to their larger reactive surface, but also to the delayed increase in redox potential and subsequent chalcopyrite passivation
Quantitative analysis of supercritical CO 2 jet structure from Schlieren imaging in free and impinged configurations
No full textInternational audienceIn recent years supercritical carbon dioxide (sCO) has emerged as a promising technology for machining assistance. Its contribution to the tool lifetime relies on both tribological and thermal actions on the control of the cutting zone. The present contribution proposes an experimental investigation of the flow features of a sCO jet. It intends to address primary data regarding the influence of the operating parameters on the shock structures and the flow characteristic (laminar–turbulent). It also intends to provide some explanations for the thermal behavior of such flow already observed in other published papers. This work addresses both free and impinged jets and investigates the influence of the impingement on the nature of the flow through Schlieren imaging and flow velocity estimation
Direct numerical simulation of bubble cavitation at a wall in micro-gravity
No full textInternational audienceCryogenic tanks used in space applications face challenges due to propellant management, among which is phase change induced by a depressurization. Pool cavitation at the wall in pure methane under micro-gravity conditions is investigated, analyzing its impact on vapor creation and wall heat transfer. A compressible two-phase flow solver, including phase change and conjugate heat transfer, is used. After a validation with available experimental data for single bubble cavitation at the wall in micro-gravity, numerical simulations varying the depressurization amplitude and rate are carried out. Three distinct growth phases are put into evidence: an expansion-controlled phase, occurring within the depressurization time frame, and a transition phase leading to a diffusion-controlled growth where the bubble behaves as in a superheated liquid at constant pressure. Results allow to show the impact that compressible effects have on the phenomenon, and to demonstrate the importance of accounting for a nano-region at the contact line, strongly affecting the wall heat transfer