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International audience; ROP of bulky functional β-lactones mediated by an achiral diamino-bis(phenolate) yttrium catalyst affords syndio-enriched polyhydroxyalkanoates.

Affinity maturation, the progressive increase in serum antibody affinity after vaccination, is an essential process that contributes to an effective humoral response against vaccines and infections. Germinal centres (GCs) are key for affinity maturation, as they are where B cells undergo somatic hypermutation of their immunoglobulin genes in the dark zone, before going through positive selection in the light zone via interactions with T follicular helper cells and follicular dendritic cells. In aged mice, affinity maturation has been shown to be impaired, but whether B cell-intrinsic factors contribute to this defect remains unclear. In this study, we show that B cells from aged B cell receptor transgenic mice are able to become GC B cells, which are capable of receiving positive selection signals to a similar extent as B cells from young adult mice. Consistent with this, ageing also does not impact the ability of B cells to undergo somatic hypermutation and acquire affinity-enhancing mutations. Together, this shows that there are no B cell-intrinsic defects in affinity maturation with age when the B cell receptor repertoire is constant.

International audience; Enhancing thermal stability of polyhydroxyalkanoates for their closed-loop chemistry

Background Tropical coral reefs cover only ca. 0.1% of the Earth’s surface but harbour exceptional marine biodiversity and provide vital ecosystem services to millions of people living nearby. They are currently threatened by global (e.g. climate change) and local (e.g. chemical pollution) stressors that interact in multiple ways. While global stressors cannot be mitigated by local actions alone, local stressors can be reduced through ecosystem management. Here, we aimed to systematically review experimental studies assessing the toxicity of chemical pollutants to tropical reef-building corals to generate accessible and usable knowledge and data that can be used to calculate measurement endpoints in ecological risk assessment. From the quantitative estimates of effects, we determined toxicity thresholds as the highest exposures tested at which no statistically significant adverse effects were observed, and we compared them to regulatory predicted no effect concentrations for the protection of marine organisms, to assess whether these reference values are indeed protective of corals. Methods The evidence was taken from a systematic map of the impacts of chemicals arising from human activity on tropical reef-building corals published in 2021. All studies in the map database corresponding to the knowledge cluster “Evidence on the ecotoxicological effects of chemicals on corals” were selected. To identify subsequently published literature, the search was updated using a subset of the search string used for the systematic map. Titles, abstracts and full-texts were screened according to the criteria defining the selected cluster of the map. Because the eligibility criteria for the systematic review are narrower than the criteria used to define the cluster in the systematic map, additional screening was performed. Studies included were critically appraised and each study was rated as low, unclear, medium, or high risk of bias. Data were extracted from the studies and synthesised according to a strategy dependent on the type of exposure and outcome. Review findings The systematic review reports the known effects of chemical exposures on corals from 847 studies corresponding to 181 articles. A total of 697 studies (161 articles) were included in the quantitative synthesis and 150 studies (50 articles) in the narrative synthesis of the findings. The quantitative synthesis records the effects of 2706 exposure concentrations-durations of 164 chemicals or mixtures of chemicals, and identifies 105 toxicity thresholds corresponding to 56 chemicals or mixtures of chemicals. When toxicity thresholds were compared to reference values set for the protection of marine organisms by environmental agencies, the reference values appear to be protective of corals for all but three chemicals assessed: the metal copper and the pesticides diuron and irgarol 1051. Conclusions This open-access database of known ecotoxicological effects of chemical exposures on corals can assist managers in the ecological risk assessment of chemicals, by allowing easy determination of various ecotoxicological thresholds. Several limitations of the toxicity tests synthesised here were noted (in particular the lack of measurement of effective concentrations for more than half of the studies). Overall, most of the currently available data on coral toxicity should be replicated independently and extended to corals from less studied geographical regions and functional groups.

Autonomous Reef Monitoring Structures (ARMS) are artificial mini-reefs designed for standardized sampling of sessile and small motile cryptobenthic organisms. ARMS are also effective for collecting small cryptobenthic fishes, such as the combtooth blennies of the genus Cirripectes. Recent studies discovered several Cirripectes species endemic to islands or archipelagos, in spite of the generally broad distributions of tropical and subtropical blennies. Thus, to evaluate the diversity and distribution of Cirripectes species in the Mascarene Archipelago, a little-studied region but an important biodiversity hotspot, complete mitochondrial genomes, and nuclear rhodopsin genes were sequenced for 39 specimens collected with ARMS deployed on outer reef slopes at Reunion and Rodrigues islands. Mitochondrial COI sequences were analyzed to integrate these specimens within the largest dataset of publicly available sequences. Three species were found in the Mascarene Archipelago, Cirripectes castaneus, Cirripectes randalli, and Cirripectes stigmaticus. C. castaneus and C. stigmaticus both have an Indo-Pacific distribution with several haplotypes shared among distant localities. In agreement with the literature, C. randalli shows a small-range endemism restricted to the Mascarenes. We confirmed the presence of C. castaneus, C. randalli, and C. stigmaticus in Rodrigues, and the presence of C. stigmaticus in Reunion. This study contributes to filling the gaps in taxonomic and molecular knowledge of the reef cryptobiome in the South-West Indian Ocean, and provides the first complete mitogenomes for the genus, a crucial step for future molecular-based inventories (e.g., eDNA).

International audience; α,ω-Bis(trialkoxysilyl) telechelic polyether/polyolefin copolymers were synthesized and evaluated as monocomponent adhesive precursors. The Ru-catalyzed tandem ring-opening insertion-metathesis polymerization (ROIMP) and cross-metathesis (CM) reactions in the presence of a bis(trialkoxysilyl)alkene as chain-transfer agent (CTA) were first explored toward the synthesis of such silyl-modified polymers (SMPs). The one-pot, two-step ROIMP/CM of cyclooctene (COE) and poly(propyleneglycol) diacrylate (PPG(*)) with {(EtO)3Si(CH2)3NHC(O)OCH2CH═}2 (CTAEt) catalyzed by Grubb’s second generation catalyst (Method II) successfully enables the preparation of α,ω-[(EtO)3Si]2-PCOE/PPG(*) alternated copolymers, isolated in 10–100 g. The polyether/polyolefin copolymers were thoroughly characterized by SEC, 1D and 2D NMR, and FTIR spectroscopies and mass spectrometry analyses. The good thermal stability and rheofluidifying profile of the PCOE/PPG* copolymers are maintained following their catalyzed moisture-curing, as revealed by TGA, DSC, and rheology. The corresponding siloxane cross-linked copolymers then demonstrate strain-at-break, elongation-at-break, and wood-adhesion properties greater than those of the benchmarked SMP reference from Bostik, namely, Polyvest E100 (strain-at-break on wood up to 4.0 vs 2.6 MPa, respectively). These characteristics can be tuned according to the PCOE/PPG* ratio and also revealed significantly better than the ones of our previously reported alike siloxane cross-linked PCOE/PPG* copolymers similarly prepared, yet from a one-pot, one-step ROIMP/CM approach (Method I). Such polyolefin/polyether monocomponent SMPs are thus promising adhesive precursors.

International audience; Polydicyclopentadiene (PDCPD) thermoset, as commonly prepared by ring-opening metathesis polymerization (ROMP), features excellent mechanical, thermal and anti-corrosion properties, but lacks ductility and toughness. In situ addition of 2 to 8 wt% of Styrene-Ethylene-Butylene-Styrene (SEBS) thermoplastic during material preparation slightly alters the stiffness while improving its toughness and ductility. Remarkably, 4wt% SEBS increases PDCPD glass transition temperature T g up to 165 °C (i.e. + 7 °C). Calorimetric analyses suggest that addition of SEBS, acting as a plasticizer during molding, reduces the polymerization time of DCPD. This result offers a simple method to adjust PDCPD impact properties and to increase its T g .

International audience; We report here on the ring-opening polymerization (ROP) of racemic beta-thiobutyrolactone (rac-TBL), as the first chemical synthesis of poly(3-thiobutyrolactone) (P3TB), the thioester analogue of the ubiquitous poly(3-hydroxybutyrate) (P3HB). The ROP reactions proceed very fast (TOF >12 000 h(-1) at r.t.) in the presence of various metal-based catalysts. Remarkably, catalyst systems based on non-chiral yttrium complexes stabilized by tetradentate amino alkoxy- or diamino-bis(phenolate) ligands {ONXOR1,R2}(2-) (X=O, N) provide access to cyclic P3TB with either high isoselectivity (P-m up to 0.90) or high syndiotactic bias (P-r up to 0.70). The stereoselectivity can be controlled by manipulation of the substituents on the ligand platform and adequate choice of the reaction solvent and temperature as well. The cyclic polymer topology is evidenced by MALDI-ToF MS, NMR and TGA. Highly isotactic cyclic P3TB is a semi-crystalline material as revealed by DSC.

Influenza infection imparts an age-related increase in mortality and morbidity. The most effective countermeasure is vaccination; however, vaccines offer modest protection in older adults. To investigate how aging impacts the memory B cell response, we track hemagglutinin-specific B cells by indexed flow sorting and single-cell RNA sequencing (scRNA-seq) in 20 healthy adults that were administered the trivalent influenza vaccine. We demonstrate age-related skewing in the memory B cell compartment 6 weeks after vaccination, with younger adults developing hemagglutinin-specific memory B cells with an FcRL5+ “atypical” phenotype, showing evidence of somatic hypermutation and positive selection, which happened to a lesser extent in older persons. We use publicly available scRNA-seq from paired human lymph node and blood samples to corroborate that FcRL5+ atypical memory B cells can derive from germinal center (GC) precursors. Together, this study shows that the aged human GC reaction and memory B cell response following vaccination is defective.

International audience; Polyhydroxyalkanoates (PHAs) are biodegradable and biocompatible polyesters with a wide range of applications; in particular, they currently stand as promising alternatives to conventional polyolefin-based "plastics". The introduction of sulfur atoms within the PHAs backbone can endow the resulting polythioesters (PTEs) with differentiated, sometimes enhanced thermal, optical and mechanical properties, thereby widening their versatility and use. Hence, PTEs have been gaining increasing attention over the past half-decade. This review highlights recent advances towards the synthesis of well-defined PTEs by ring-opening polymerization (ROP) of cyclic thioesters - namely thiolactones - as well as of S-carboxyanhydrides and thionolactones; it also covers the ring-opening copolymerization (ROCOP) of cyclic thioanhydrides or thiolactones with epoxides or episulfides. Most of the ROP reactions described are of anionic type, mediated by inorganic, organic or organometallic initiators/catalysts, along with a few enzymatic reactions as well. Emphasis is placed on the reactivity of the thio monomers, in relation to their ring-size ranging from 4- to 5-, 6- and 7-membered cycles, the nature of the catalyst/initiating systems implemented and their efficiency in terms of activity and control over the PTE molar mass, dispersity, topology, and microstructure.

International audience; Background. Tropical coral reefs cover only ca. 0.1% of the Earth’s surface but host an outstanding biodiversity and provide important ecosystem services to millions of people living nearby. They are currently threatened by global (e.g., climate change) and local (e.g., chemical pollution) stressors that interact in different ways. While global stressors cannot be mitigated by local actions alone, local stressors can be reduced through ecosystem management. A systematic map on the impacts of chemicals arising from anthropogenic activities on tropical reef-building corals, which are the main engineer species of reef ecosystems, was published in 2021. This systematic map gathered an abundant literature (908 articles corresponding to 7937 studies), and identified four well-represented subtopics, amenable to relevant full syntheses. Here, we focused on one of the four subtopics: we aimed to systematically review the evidence on the ecotoxicological effects of chemicals on tropical reef-building corals.Methods. The evidence will be identified from the recent systematic map on the impacts of chemicals arising from anthropogenic activities on tropical reef-building corals. Especially, all studies in the map database corresponding to the knowledge cluster “evidence on the ecotoxicological effects of chemicals on corals” will be selected. To identify the evidence produced since then, a search update will be performed using a subset of the search string used for the systematic map, and titles, abstracts and full-texts will be screened according to the criteria defining the selected cluster of the map. In addition, as the eligibility criteria for the systematic review are narrower than those used to define the cluster in the systematic map, additional screening will be carried out. The included studies will then be critically appraised and a low, medium, or high risk of bias will be assigned to each study. Data will be extracted from studies and synthesised according to a strategy depending on the type of exposure and outcome. Synthesis will be mainly quantitative but also narrative, aiming to identify toxicity thresholds of chemicals for corals.

International audience; Background: Tropical coral reefs cover ca. 0.1% of the Earth's surface but host an outstanding biodiversity and provide important ecosystem services to millions of people living nearby. They are currently threatened by local stressors (e.g. nutrient enrichment and chemical pollution arising from poor land management, sewage effluents, agriculture, industry) and global stressors (mainly seawater warming and acidification, i.e. climate change). Global and local stressors interact in different ways, but the presence of one stressor often reduces the tolerance to additional stress. While global stressors cannot be mitigated solely by local actions, local stressors can be reduced through ecosystem management, therefore minimizing the impact of climate change on coral reefs. We systematically mapped the evidence of impacts of chemicals arising from anthropogenic activities on tropical reef-building corals, which are the main engineer species of reef ecosystems, to inform decision-makers on the available evidence on this topic.Methods: We searched the relevant literature using English terms combined in a tested search string in two publication databases (Scopus and Web Of Science Core Collection). The search string combined terms describing the population (tropical reef-building corals) and the exposure (chemicals). We searched for additional literature through three search engines, three dissertations repositories, 11 specialist websites, and through a call to local stakeholders. Titles, abstracts, and full-texts were successively screened using pre-defned eligibility criteria. A database of all studies included in the map with coded metadata was produced. The evidence was described and knowledge clusters and gaps were identifed through the distribution and frequency of studies into types of exposure and/or types of outcomes and/or types of study.Review findings: The initial searches identifed 23,403 articles which resulted in 15,177 articles after duplicate removal. Among them, 908 articles were retained after screening process, corresponding to 7937 studies (a study being the combination of a taxon, an exposure, and an outcome). Among these studies, 30.5% dealt with the impact of nutrient enrichment on corals while 25% concerned the impact of human activities without referenceto a chemical. The most measured outcomes were those related to the chemical concentration in corals (bioaccumulation, 25.8%), to coral physiology (16.9%), cover (14%), and mortality (9%). Half of the studies (48.4%) were experimental—the exposure was controlled by the researchers—and were conducted in laboratory conditions (39.4%) and in situ (9%). The most studied taxa, exposure, and outcomes were diferent between experimental andobservational studies.Conclusions: We identifed four well-represented subtopics that may be amenable to relevant full syntheses via systematic reviews: (1) evidence on bioaccumulation of chemicals by corals; (2) evidence on the efects of nutrient enrichment on corals; (3) evidence on the efects of human activities on corals; and (4) evidence on the ecotoxicological efects of chemicals on corals (except nutrient enrichment). The systematic map shows that corals in their natural environment can be exposed to many categories of chemicals, and that there is a complete gap in experimental research on the combined efects of more than two categories of chemicals. We therefore encourage research on this topic.

Pelvic fractures in children are rare and often the result of high-energy trauma. The possibility of associated lesions cannot be ignored. Treatment at a specialized children's hospital is a must. The multidisciplinary care team must include a paediatric orthopaedic surgeon. In the emergency room, the surgeon contributes to haemodynamic stabilization of the child by reducing and stabilizing posterior arch fractures and restoring the skeletal cohesion to make it easier to move the child and allow other examinations to be performed. Imaging modalities are used to determine the stability of the pelvic ring fracture, the risk of epiphysiodesis of an acetabulum fracture if the triradiate cartilage is open and the joint congruency if the triradiate cartilage is closed. Internal fixation can be used if surgery is being performed for associated non-orthopaedic injuries. Most vertically stable fractures are treated non-surgically. Fractures that are unstable vertically will require surgical treatment. Treatment of acetabulum fractures depends on the status of the triradiate cartilage. In older children, it is similar to the treatments used in adults. In children with open growth plates, the goal is to make sure the acetabulum continues growing. In all cases, the patients must be instructed to start physical therapy as soon as possible. Full recovery can be expected after stable pelvic fractures. Unstable pelvic fractures can lead to sequelae, the severity of which depend on the residual pelvic displacement and involvement of the growth plates that can cause epiphysiodesis. Surgery to correct these deformities is challenging. The most serious occur when the vertical displacement of the hemipelvis must be corrected. After an acetabulum fracture, removal of the growth blocker can be done in children under 10 years of age. In older children, acetabular dysplasia requires periacetabular osteotomy.

International audience; The organocatalyzed ring-opening polymerization (ROP) of various 4-alkoxymethylene-beta-propiolactones (BPL(OR)s; R = CH2CH=H-2 (All), CH2Ph (Bn), (CH2)(3)CH3 (Bu-n), (SiMe2Bu)-Bu-t (TBDMS)) towards the formation of the corresponding poly(hydroxyalkanoate)s (PHAs; poly(BPLOR)s (PBPL(OR)s)) is investigated under mild operating conditions (neat, 60 degrees C), simply using basic organocatalysts of the guanidine (1,5,7-triazabicyclo [4.4.0]dec-5-ene, TBD), amidine (1,8-diazabicyclo[5.4.0]-undec-7-ene, DBU) or phosphazene (2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2diazaphosphorine, BEMP) type. The polymerization proceeds basically at the same rate as the alike organocatalyzed ROP of related beta-lactones (especially the ubiquitous beta-butyrolactone (BL) and alkyl beta-malolactonates (MLA(R)s)), with BEMP being significantly more active than TBD and DBU. Insights into the polymerization mechanisms are gained through detailed 1D/2D NMR spectroscopy and MALDI-ToF mass spectrometry analyses of the resulting PBPL(OR)s and in particular through the identification of the nature of the end-capping groups. Each of the three organobases promotes the polymerization in its own way, as dictated by either its basic, nucleophilic or dual behavior.

International audience; Polyhydroxyalkanoates (PHAs) are a unique class of polyesters especially due to their chemical diversity imparted by their side-chain substituent that provides a handle to tune their properties, such as their thermal, mechanical and (bio)degradability signature. Here, we report that some functional PHAs, namely PBPLFGs (FG = functional group), were synthesized by the controlled stereoselective ring-opening polymerization (ROP) of racemic 4-substituted-β-propiolactones, namely rac-BPLCH2ZPhs with Z = O, S, CH2OCH2, catalyzed by diamino- or amino-alkoxy-bis(phenolate) yttrium amido complexes (1a–1g) in the presence of isopropanol. Unprecedented syndio-enriched (Pr up to 0.87) PBPLCH2ZPhs of high molar mass (Mn,NMR up to 86 400 g mol−1, ĐM < 1.23) were thus typically prepared under mild operating conditions (toluene, 20 °C). Catalyst systems with smaller “uncrowded” Me or Cl ortho-substituents installed on the yttrium phenolate ligands (1a–1c) typically revealed less active than those with larger bulkier tBu or CMe2Ph groups (1d–1g), regardless of the monomer (TOF1a–1c = 0.48–15 h−1, TOF1d–1g = 450–1840 h−1). Irrespective of the catalyst system, exchanging oxygen with sulphur in BPLCH2ZPhs, with Z = O, S, did not affect the stereochemistry, always affording syndiotactic PBPLCH2ZPhs. On the other hand, either atactic or syndiotactic PBPLCH2CH2OCH2Phs were formed upon tuning the catalyst from 1a–1c or 1d–1g, respectively. The intimate relationship, through “non-covalent” interactions, between the chemical nature of the exocyclic functional side-group on the β-lactone and the stereoelectronic tuning arising from the phenolate ligand ortho-substituents within the yttrium coordination sphere, modulated the stereocontrol of the ROP. The thermal behavior of these original functional PHAs depended closely on their side-chain substituent (Tonsetd = 226 to 272 °C; Tg = −15 to +40 °C).

Mathematical modeling has been an important tool in pharmaceutical research for 50 + years and there is increased emphasis over the last decade on using modeling to improve the efficiency and effectiveness of drug development. In an earlier commentary, we applied a multiscale model linking 6 scales (whole body, tumor, vasculature, cell, spatial location, time), together with literature data on nanoparticle and tumor properties, to demonstrate the effects of nanoparticle particles on systemic disposition. The current commentary used a 4-scale model (cell membrane, intracellular organelles, spatial location, time) together with literature data on the intracellular processing of membrane receptors and transporters to demonstrate disruption of transporter homeostasis can lead to drug-drug interaction (DDI) between victim drug (VD) and perpetrator drug (PD), including changes in the area-under-concentration-time-curve of VD in cells that are considered significant by the US Food and Drug Administration (FDA). The model comprised 3 computational components: (a) intracellular transporter homeostasis, (b) pharmacokinetics of extracellular and intracellular VD/PD concentrations, and (c) pharmacodynamics of PD-induced stimulation or inhibition of an intracellular kinetic process. Model-based simulations showed that (a) among the five major endocytic processes, perturbation of transporter internalization or recycling led to the highest incidence and most extensive DDI, with minor DDI for perturbing transporter synthesis and early-to-late endosome and no DDI for perturbing transporter degradation and (b) three experimental conditions (spatial transporter distribution in cells, VD/PD co-incubation time, extracellular PD concentrations) were determinants of DDI detection. We propose modeling is a useful tool for hypothesis generation and for designing experiments to identify potential DDI; its application further aligns with the model-informed drug development paradigm advocated by FDA.