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Couplage croisé de Suzuki-Miyaura simple et rapide assisté par micro-ondes dans un solvant eutectique naturel à base de bétaïne/glycérol
No full textInternational audienceIn a context of reducing the environmental impact of chemical processes, the use of petrochemical solvents entails risks for health and the environment, as they are mostly toxic, not very biodegradable and polluting. Green chemistry proposes replacing them with safer alternatives, such as natural deep eutectic solvents (NaDES). Combined with eco-compatible heating techniques (microwaves, ultrasound, mechanochemistry), they can optimize organic synthesis by reducing reaction times and energy consumption. This work aims to combine NaDES as solvent and microwave heating to develop a sustainable and efficient Suzuki-Miyaura coupling method, in line with the principles of green chemistry
Tridimensional interactive plots improve the visualization of global data structure in complex scRNA-seq datasets
No full textInternational audienceSingle-cell RNA sequencing (scRNA-seq) assays generate gene expression data for the individual cells that compose complex and heterogeneous tissues. It is noteworthy, however, that scRNA-seq data are inherently high-dimensional, meaning that each cell is represented as a point in an Euclidean space with as many dimensions as the features (genes) in the dataset. To visualize and explore those datasets in the pursuit of the biologically meaningful pattern emerging from them it is usual to employ non-linear dimensional reduction techniques such as tSNE and UMAP. The vast majority of scRNA-seq scientific publications rely on two-dimensional (2D) plots for the visualization of cell clusters. While 2D projections are generally effective and informative, they may overlook some important global structures or subtle inter-cluster relationships due to the loss of information that inevitably occurs when collapsing highdimensional data into just two dimensions. To address this limitation, we investigated if interactive threedimensional (3D) plots provide additional interpretative value beyond standard 2D representations using scRNA-seq data from zebrafish testes. Fish testes are filled with highly heterogeneous cell populations in dynamic states that are the result of a continual differentiation process that drives the production of millions of spermatozoa from a restricted pool of undifferentiated spermatogonia
Investigating Human-Wildlife Spatio-Temporal Interactions to Support Sustainable Outdoor Recreation
No full textInternational audienceIn recent years, outdoor recreation has gained growing popularity, with a notable rise in new group-based outdoor activities. These opportunities allow people to explore and engage with nature, contributing to the economic development of local communities and, more broadly, to tourism. However, this expansion of outdoor activities raises concerns about potential negative impacts on biodiversity conservation. Scientific ecologists have introduced the concept of the “landscape of fear” to describe how wildlife, such as chamois, may be disturbed by human presence, potentially leading to altered behavior or even loss of plant and animal diversity.At the same time, outdoor practitioners increasingly record their routes using GNSS devices, with trajectories shared as open-source data on different websites. Similarly, ecologists studying the effects of human activity on wildlife collected GNSS trajectories representing animal movement by using GPS collars. These parallel datasets open new opportunities to study spatio-temporal interactions between humans and animals.In this presentation we will first present an overview of our research on how to study these human-animals interactions and propose solutions for sustainable outdoor recreation. Our research focuses on analyzing both human and animal trajectories to identify hotspots and coldspots which are respectively areas of frequent and less frequent co-occurrence. These identified zones first enhance human movement trajectories with ecologic data (e.g., chamois presence from April to June), and then it enriches a mobility network itself through map-matching techniques and attribute transfer, contributing thus to a trajectory-road network loop. Once the loop is finalized, the goal is to propose an algorithm that is able to suggest resilient routes which are routes that avoid temporal hotspots of human-wildlife interaction offering alternative paths that are less crowded and more environmentally sustainable.Second, we present the first results obtained in mountain areas located in the French Alps. While our study area is currently focused on mountain environments, we argue that this approach is transferable to urban contexts, where it can support the development of sustainable alternatives in densely visited touristic areas. For example, this tool can be used by urban planners and mobility services providers to redirect tourist flows to avoid overcrowded landmarks or ecologically fragile zones, thereby reducing pressure on urban green spaces while enhancing visitor experience.This work is part of the IntForOut research project, which aims to develop methods and tools to better quantify human pressure from sports and recreational activities on alpine ecosystems and to suggest alternative solutions for sustainable tourism and mobility
Mn <sup>2+</sup> Complex of a Fluorinated CDTA‐Derivative: Stability, Inertness, and Paramagnetic <sup>1</sup> H, <sup>17</sup> O, and <sup>19</sup> F Relaxation Properties
No full textInternational audienceL2 is a bisamide derivative of cyclohexyl-diamine tetraacetate (CDTA) containing one trifluoromethyl-piperidine- and one dimethyl-amide. While the amide functions are stable at pH 7, at pH 4.35 hydrolysis occurs after 1 day, and it is faster for the amide involving the piperidine. pH potentiometry showed lower basicity for L2 than for CDTA, and similar stability for the two complexes (pMn = 8.28 vs. 8.68 for MnL2 and MnCDTA, respectively). The replacement of carboxylates by amides results in two orders of magnitude higher kinetic inertness for MnL2 (t1/2 = 1134 hours vs. 12 hours; pH 7.4). 17O NMR confirmed one inner sphere water in MnL2 and fast exchange (kex298 = 2.8 × 107 s−1). Its proton relaxivity is remarkable for a small Mn2+ chelate (r1 = 4.59 mM−1s−1, 25 °C, 20 MHz). In the complex, 19F relaxation is strongly accelerated with respect to free L2, with more important effect on longitudinal (130-fold), than on transverse relaxation (25–70-fold). A Mn─F distance of ∼8 Å was estimated from the 19F relaxation rates. MnL2 provides good signal-to-noise ratios on 19F phantom UTE MR images. These data show that fluorinated, monohydrated Mn2+ complexes can offer both 1H and 19F MRI detection
Expanding the Family of Monosubstituted 15-Membered Pyridine-Based Macrocyclic Ligands for Mn(II) Complexation in the Context of MRI
No full textInternational audienceAs Mn(II) complexes attract continuous interest as alternatives to Gd-based contrast agents (CAs) in clinical magnetic resonance imaging (MRI), we synthesized two monosubstituted derivatives of the 15-membered pyridine-based macrocycle 15-pyN3O2 bearing either a 2-pyridylmethyl (L2) or a 2-benzimidazolylmethyl pendant arm (L3) and characterized their Mn(II) complexes MnL2 and MnL3 in the context of MRI contrast agent development. Their X-ray molecular structures confirmed a coordination number of seven and a pentagonal bipyramidal geometry with one coordination site available for inner-sphere water. Protonation constants of L2 and L3, and stability constants with selected divalent metal ions were determined using potentiometry. MnL2 and MnL3 complexes are fully formed at pH 7.4; however, they both display low kinetic inertness due to a significant spontaneous dissociation of the nonprotonated complex. The presence of one inner-sphere water molecule in the Mn(II) complexes was confirmed by 17O NMR and 1H NMRD measurements. The water exchange rate constants are very low (kex298 = 0.46 × 107 and 0.23 × 107 s–1 for MnL2 and MnL3, respectively), but typical for Mn(II) complexes of 15-pyN3O2 derivatives. The relaxivities are in good agreement with monohydrated small-molecular-weight Mn(II) chelates (r1 = 2.49 and 2.77 mM–1 s–1 at 20 MHz, 25 °C, for MnL2 and MnL3, respectively)
Decoupling individual host response and immune cell engager cytotoxic potency
No full textInternational audienceImmune cell engagers are molecular agents, usually antibody-based constructs, engineered to recruit immune cells against cancer cells and kill them. They represent a versatile and powerful tool for cancer immunotherapy. Despite the multiplication of new engagers tested and accepted in the clinics, how molecular and cellular parameters influence their action is poorly understood. In particular, disentangling the respective role of host immune cells and engager biophysical characteristics is needed to improve their design and efficiency. Focusing here on harnessing antibody dependent Natural Killer cell cytotoxicity, we measure the efficiency of 6 original bispecific antibodies (bsAb), associating an anti-HER2 nanobody and an anti-CD16 nanobody. In vitro cytotoxicity data using primary human NK cells on different target cell lines exposing different antigen densities were collected, exhibiting a wide range of bsAb dose response. In order to rationalize our observations, we introduce a simple multiscale model, postulating that the density of bsAb bridging the two cells is the main parameter triggering the cytotoxic response. We introduce two new microscopic parameters: the surface cooperativity describing bsAb affinity at the bridging step and the threshold of bridge density determining the donor-dependent response. Both parameters permit to rank Abs and donors and to predict bsAb potency as a function of antibodies bulk affinities and receptor surface densities on cells. Our approach thus provides a general way to decouple donor response from immune engagers characteristics, rationalizing the landscape of molecule design
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Discovery and chemical biology of CDK8 inhibitors reveals insights for kinase inhibitor development
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