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ImportanceBefore surgery, the best strategy for managing patients who are taking renin-angiotensin system inhibitors (RASIs) (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) is unknown. The lack of evidence leads to conflicting guidelines.ObjectiveTo evaluate whether a continuation strategy vs a discontinuation strategy of RASIs before major noncardiac surgery results in decreased complications at 28 days after surgery.Design, setting, and participantsRandomized clinical trial that included patients who were being treated with a RASI for at least 3 months and were scheduled to undergo a major noncardiac surgery between January 2018 and April 2023 at 40 hospitals in France.InterventionPatients were randomized to continue use of RASIs (n = 1107) until the day of surgery or to discontinue use of RASIs 48 hours prior to surgery (ie, they would take the last dose 3 days before surgery) (n = 1115).Main outcomes and measuresThe primary outcome was a composite of all-cause mortality and major postoperative complications within 28 days after surgery. The key secondary outcomes were episodes of hypotension during surgery, acute kidney injury, postoperative organ failure, and length of stay in the hospital and intensive care unit during the 28 days after surgery.ResultsOf the 2222 patients (mean age, 67 years [SD, 10 years]; 65% were male), 46% were being treated with angiotensin-converting enzyme inhibitors at baseline and 54% were being treated with angiotensin receptor blockers. The rate of all-cause mortality and major postoperative complications was 22% (245 of 1115 patients) in the RASI discontinuation group and 22% (247 of 1107 patients) in the RASI continuation group (risk ratio, 1.02 [95% CI, 0.87-1.19]; P = .85). Episodes of hypotension during surgery occurred in 41% of the patients in the RASI discontinuation group and in 54% of the patients in the RASI continuation group (risk ratio, 1.31 [95% CI, 1.19-1.44]). There were no other differences in the trial outcomes.Conclusions and relevanceAmong patients who underwent major noncardiac surgery, a continuation strategy of RASIs before surgery was not associated with a higher rate of postoperative complications than a discontinuation strategy.Trial registrationClinicalTrials.gov Identifier: NCT03374449.

Qualitative secondary analysis has generated heated debate regarding the epistemology of qualitative research. We argue that shifting to an abductive approach provides a fruitful avenue for qualitative secondary analysts who are oriented towards theory-building. However, the concrete implementation of abduction remains underdeveloped--especially for coding. We address this key gap by outlining a set of tactics for abductive analysis that can be applied for qualitative analysis. Our approach applies Timmermans and Tavory's (Timmermans and Tavory 2012; Tavory and Timmermans 2014) three stages of abduction in three steps for qualitative (secondary) analysis: Generating an Abductive Codebook, Abductive Data Reduction through Code Equations, and In-Depth Abductive Qualitative Analysis. A key contribution of our article is the development of "code equations"--defined as the combination of codes to operationalize phenomena that span individual codes. Code equations are an important resource for abduction and other qualitative approaches that leverage qualitative data to build theory.

The use of alkylzinc bromides in the multicomponent Mannich reaction is described. Heteroleptic organozinc compounds were obtained in THF or 2-MeTHF by direct insertion of zinc dust into the C–Br bond of alkyl bromides. It was found that the presence of a stoichiometric amount of LiCl was essential for the efficiency of the subsequent three-component coupling with aldehydes and amines. A variety of primary, secondary, and tertiary organozinc reagents as well as secondary amines and aromatic aldehydes could be used for the straightforward preparation of α-branched amines. Interestingly, whereas previously reported work describing the preparation and reaction of organozinc iodides in acetonitrile showed higher reactivity of secondary organozinc reagents over primary ones, reactions in THF in the presence of LiCl led to opposite results, with higher reactivity of primary organozinc reagents.

Abstract Background Objective Structured Clinical Examinations (OSCEs) aim to assess medical students’ clinical skills rather than just their theoretical knowledge. We propose a study between the learning style of second-cycle medical students and their performance in OSCEs. Methods During their internship at our hospital, students were invited to complete the LSQ-Fa, a questionnaire designed to identify their preferences among 4 learning styles: active, reflective, theoretical, and pragmatic. In parallel, an evaluation of their clinical skills was conducted through OSCEs. We then performed an analysis to establish a correlation between learning styles and OSCE performance, to better understand how learning preferences influence academic outcomes. Results Between April 2021 and January 2023, 55 students were evaluated by OSCEs and had completed the LSQ-Fa. The average OSCE score was 14.8/20. The theoretical learning style was predominant in 47.3% of students, followed by active (27.3%), reflective (14.6%), and pragmatic (5.4%), with 3 cases of mixed active and theoretical styles (5.4%). No significant correlation was observed between learning style and OSCE performance (p = 0.28), although students with a pragmatic style recorded a slightly higher average. Conclusion This study highlights the importance of considering diverse learning styles in the design of medical education programs.

Saturn’s moon Iapetus, which is in synchronous rotation, is covered by an optically dark material mainly on its leading side, while its trailing side is significantly brighter. Because longer wavelengths probe deeper into the subsurface, observing both sides at a variety of wavelengths brings to light possible changes in thermal, compositional, and physical properties with depth. We have observed Iapetus’s leading and trailing hemispheres at 1.2 and 2.0 mm, using the NIKA2 camera mounted on the IRAM 30-m telescope, and compared our observations to others performed at mm to cm wavelengths. We calibrate our observations on Titan, which is simultaneously observed within the field of view. Due to the proximity of Saturn, it is sometimes difficult to separate Iapetus’s and Titan’s flux from that of Saturn, detected in the telescope’s side lobes. Preliminary results show that the trailing hemisphere brightness temperatures at the two wavelengths are equal within error bars, unlike the prediction made by Ries (2012)[1]. On the leading side, we report a steep spectral slope of increasing brightness temperature (by 10 K) from 1.2 to 2.0 mm, which may indicate rapidly varying emissivities within the top few centimeters of the surface. Comparison to a diffuse scattering model and a thermal model will be necessary to further constrain the thermophysical properties of the subsurface of Iapetus’s two faces.

Abstract Current evidence suggests that macroalgal-dominated habitats are important contributors to the oceanic carbon cycle, though the role of those formed by calcifiers remains controversial. Globally distributed coralline algal beds, built by pink coloured rhodoliths and maerl, cover extensive coastal shelf areas of the planet, but scarce information on their productivity, net carbon flux dynamics and carbonate deposits hampers assessing their contribution to the overall oceanic carbon cycle. Here, our data, covering large bathymetrical (2–51 m) and geographical ranges (53°N–27°S), show that coralline algal beds are highly productive habitats that can express substantial carbon uptake rates (28–1347 g C m−2 day−1), which vary in function of light availability and species composition and exceed reported estimates for other major macroalgal habitats. This high productivity, together with their substantial carbonate deposits (0.4–38 kilotons), renders coralline algal beds as highly relevant contributors to the present and future oceanic carbon cycle.

Abstract Background Awareness-raising and education have been identified as strategies to counter the taboo surrounding death and dying. As the favoured venue for youth education, schools have an essential role to play in informing future decision-makers. However, school workers are not comfortable addressing the subjects of death and dying, which, unlike other social issues, have no guidelines to influence awareness of these subjects in youth. Objectives To systematically explore the knowledge and practices on raising awareness about death and dying in schools, the viewpoints of the people involved (young people, school workers; parents), and the factors that either promote or hinder awareness practices. Method The scoping review method of Levac and Colquhoun (Implement Sci 5(1):69, 2010) will be used. Using a combination of keywords and descriptors, a body of literature will be identified through 15 databases and through grey literature searches, manual searches, consultation of key collaborators, and the list of relevant literature. Publications since 2009 will be selected if they relate directly to awareness-raising about death and dying in schools. Writings will be selected and extracted by two independent people, and conflicts resolved by consensus. The extracted data will be synthesized using a thematic analysis method. Experts from a variety of disciplines (health sciences, humanities, social sciences, and education) will be consulted to enhance the interpretation of the preliminary results. Results will be presented in narrative form and will include tables and diagrams. Conclusion The results of this scoping review will contribute to the development of educational practices adapted to young people and to the identification of future avenues of research on awareness of death and dying.

Abstract Pre-hospital end-tidal carbon dioxide (EtCO2) monitoring and arterial to end-tidal carbon dioxide gradient (Pa-EtCO2) have been associated with mortality in patients with traumatic brain injury. Our study aimed to analyze the association between alveolar EtCO2 or Pa-EtCO2 and mortality in patients admitted in intensive care unit (ICU) with neurological injuries. In our retrospective analysis from using large de-identified ICU databases (MIMIC-III and -IV and eICU databases), we included 2872 ICU patients with neurological injuries, identified according to the International Classification of Diseases (ICD-9 and -10), who underwent EtCO2 monitoring. We performed logistic regression and extended Cox regression to assess the association between mortality and candidate covariates, including EtCO2 and Pa-EtCO2. In-hospital mortality was 26% (n = 747). In univariate analysis, both the Pa-EtCO2 gradient and EtCO2 levels during the first 24 h were significantly associated with mortality (for a 1 mmHg increase: OR = 1.03 [CI95 1.016–1.035] and OR = 0.94 [CI95 0.923–0.953]; p

Abstract Psoriasis is a multifactorial, chronic inflammatory skin disease with unresolved questions on its primary events. Iron overload has been described in the epidermis of psoriasis patients, but its relevance remains unknown. We found that the key iron regulatory hormone hepcidin was highly expressed in the epidermis of psoriasis patients, especially the pustular variants resistant to treatments. In a murine model of acute skin inflammation, keratinocyte-derived hepcidin was required for iron retention in keratinocytes, leading to hyperproliferation of the epidermal layer and neutrophil recruitment, two main features of psoriatic skin lesions. Keratinocytes overexpressing hepcidin were sufficient to elicit these psoriasiform features in a transgenic mouse model. Furthermore, transcriptome analysis of these keratinocytes revealed canonical pathways found in human psoriasis, pointing to a causal role for hepcidin in the pathogenesis of the disease. Altogether, our data suggest that hepcidin could be an actionable target for skin psoriasis treatment, in addition to current therapeutics, or targeted as maintenance therapy during remission to prevent recurrence.

Abstract We have recently identified the uncharacterized ZNF555 protein as a component of a productive complex involved in the morbid function of the 4qA locus in facioscapulohumeral dystrophy. Subsequently named DiPRO1 (Death, Differentiation, and PROliferation related PROtein 1), our study provides substantial evidence of its role in the differentiation and proliferation of human myoblasts. DiPRO1 operates through the regulatory binding regions of SIX1, a master regulator of myogenesis. Its relevance extends to mesenchymal tumors, such as rhabdomyosarcoma (RMS) and Ewing sarcoma, where DiPRO1 acts as a repressor via the epigenetic regulators TIF1B and UHRF1, maintaining methylation of cis-regulatory elements and gene promoters. Loss of DiPRO1 mimics the host defense response to virus, awakening retrotransposable repeats and the ZNF/KZFP gene family. This enables the eradication of cancer cells, reprogramming the cellular decision balance towards inflammation and/or apoptosis by controlling TNF-α via NF-kappaB signaling. Finally, our results highlight the vulnerability of mesenchymal cancer tumors to si/shDiPRO1-based nanomedicines, positioning DiPRO1 as a potential therapeutic target.

Abstract Incidental capture of non-target species poses a pervasive threat to many marine species, with sometimes devastating consequences for both fisheries and conservation efforts. Because of the well-known importance of vocalizations in cetaceans, acoustic deterrents have been extensively used for these species. In contrast, acoustic communication for sea turtles has been considered negligible, and this question has been largely unexplored. Addressing this challenge therefore requires a comprehensive understanding of sea turtles’ responses to sensory signals. In this study, we scrutinized the avenue of auditory cues, specifically the natural sounds produced by green turtles (Chelonia mydas) in Martinique, as a potential tool to reduce bycatch. We recorded 10 sounds produced by green turtles and identified those that appear to correspond to alerts, flight or social contact between individuals. Subsequently, these turtle sounds—as well synthetic and natural (earthquake) sounds—were presented to turtles in known foraging areas to assess the behavioral response of green turtles to these sounds. Our data highlighted that the playback of sounds produced by sea turtles was associated with alert or increased the vigilance of individuals. This therefore suggests novel opportunities for using sea turtle sounds to deter them from fishing gear or other potentially harmful areas, and highlights the potential of our research to improve sea turtles populations’ conservation.

Therapeutic efficacy with durable responses has been demonstrated with several antibody drugs that block key immune checkpoint receptors, including PD-1, PD-L1, and CTLA-4. Despite the success of these drugs, a substantial proportion of patients do not benefit. Targeting multiple inhibitory pathways simultaneously to augment anti-tumor immunity has proven to be a promising approach. The emergence of Repulsive Guidance Molecule b (RGMb), a ligand for PD-L2, as a novel co-inhibitory pathway in T cells, together with its regulation by the gut microbiome, encouraged the discovery and development of fully human anti-RGMb antibodies. Here, we describe phage display-derived monoclonal antibodies (mAbs) 2C11 and 5C10 that bind human RGMb with high affinities of 1.4 nM and 0.72 nM, respectively. Both mAbs 2C11 and 5C10 potently inhibited RGMb interaction with PD-L2. MAb 2C11 effectively inhibited RGMb interaction with bone morphogenetic proteins 2 and 4 (BMP2–4), while leaving RGMb interaction with Neogenin 1 (Neo1) unaffected. Conversely, mAb 5C10 disrupted RGMb interaction with Neo1 while maintaining RGMb binding to BMP2–4. These findings map the 2C11 epitope at the membrane-distal N-terminal region of RGMb, which coincides with both PD-L2- and BMP2–4-binding sites. The PD-L2 binding interface is likely positioned between RGMb’s N-terminal BMP-binding and C-terminal Neo1-binding regions. The in vivo activity of mAb 2C11 in combination with anti-PD-1 or anti-PD-L1 was tested in MC38 and B16-OVA cancer models and demonstrated synergistic effects by significantly enhancing anti-tumor responses. These properties make mAb 2C11 a promising candidate for therapeutic use to overcome immune checkpoint inhibitor resistances, warranting further exploration in clinical settings.

The gut microbiota-brain axis has been associated with the pathogenesis of numerous disorders, but the mechanism(s) underlying these links are generally poorly understood. Accumulating evidence indicates the involvement of gut microbe-derived metabolites. Circulating levels of the gut microbe/host co-metabolite p-cresol sulfate (pCS) correlate with cerebrovascular event risk in individuals with chronic kidney disease (CKD), but whether this relationship is mechanistic is unclear. We hypothesized that pCS would impair the function of the blood–brain barrier (BBB), the primary brain vasculature interface. We report that pCS exposure impairs BBB integrity in human cells in vitro and both acutely (≤6 hours) and chronically (28 days) in mice, enhancing tracer extravasation, disrupting barrier-regulating tight junction components and ultimately exerting a suppressive effect upon whole-brain transcriptomic activity. In vitro and in vivo mechanistic studies showed that pCS activated epidermal growth factor receptor (EGFR) signaling, sequentially activating the intracellular signaling proteins annexin A1 and STAT3 to induce mobilization of matrix metalloproteinase MMP-2/9 and disruption to the integrity of the BBB. This effect was confirmed as specific to the EGFR through the use of both pharmacological and RNA interference approaches. Confirming the translational relevance of this work, exposure of the cerebromicrovascular endothelia to serum from hemodialysis patients in vitro led to a significant increase in paracellular permeability, with the magnitude of permeabilization closely correlating with serum pCS, but not most other uremic toxin, content. Notably, this damaging effect of hemodialysis patient serum was prevented by pharmacological blockade of the EGFR. Our results define a pathway linking the co-metabolite pCS with BBB damage and suggest that targeting the EGFR may mitigate against cerebrovascular damage in CKD. This work further provides mechanistic evidence indicating the role of gut microbe-derived metabolites in human disease.

Metabolic syndrome (MetS) is a cluster of several human conditions including abdominal obesity, hypertension, dyslipidemia, and hyperglycemia, all of which are risk factors of type 2 diabetes, cardiovascular disease, and metabolic dysfunction-associated steatotic liver disease (MASLD). Dietary pattern is a well-recognized MetS risk factor, but additional changes related to the modern Western life-style may also contribute to MetS. Here we hypothesize that the disappearance of amoebas in the gut plays a role in the emergence of MetS in association with dietary changes. Four groups of C57B/6J mice fed with a high-fat diet (HFD) or a normal diet (ND) were colonized or not with Entamoeba muris, a commensal amoeba. Seventy days after inoculation, cecal microbiota, and bile acid compositions were analyzed by high-throughput sequencing of 16S rDNA and mass spectrometry, respectively. Cytokine concentrations were measured in the gut, liver, and mesenteric fat looking for low-grade inflammation. The impact of HFD on liver metabolic dysfunction was explored by Oil Red O staining, triglycerides, cholesterol concentrations, and the expression of genes involved in β-oxidation and lipogenesis. Colonization with E. muris had a beneficial impact, with a reduction in dysbiosis, lower levels of fecal secondary bile acids, and an improvement in hepatic steatosis, arguing for a protective role of commensal amoebas in MetS and more specifically HFD-associated MASLD.

The Mediterranean diet (MD) and its bioactive constituents have been advocated for their neuroprotective properties along with their capacity to affect gut microbiota speciation and metabolism. Mediated through the gut brain axis, this modulation of the microbiota may partly contribute to the neuroprotective properties of the MD. To explore this potential interaction, we evaluated the neuroprotective properties of a novel bioactive blend (Neurosyn240) resembling the Mediterranean diet in a rodent model of chronic low-grade inflammation. Behavioral tests of cognition, brain proteomic analysis, 16S rRNA sequencing, and 1H NMR metabolomic analyses were employed to develop an understanding of the gut-brain axis interactions involved. Recognition memory, as assessed by the novel object recognition task (NOR), decreased in response to LPS insult and was restored with Neurosyn240 supplementation. Although the open field task performance did not reach significance, it correlated with NOR performance indicating an element of anxiety related to this cognitive change. Behavioral changes associated with Neurosyn240 were accompanied by a shift in the microbiota composition which included the restoration of the Firmicutes: Bacteroidota ratio and an increase in Muribaculum, Rikenellaceae Alloprevotella, and most notably Akkermansia which significantly correlated with NOR performance. Akkermansia also correlated with the metabolites 5-aminovalerate, threonine, valine, uridine monophosphate, and adenosine monophosphate, which in turn significantly correlated with NOR performance. The proteomic profile within the brain was dramatically influenced by both interventions, with KEGG analysis highlighting oxidative phosphorylation and neurodegenerative disease-related pathways to be modulated. Intriguingly, a subset of these proteomic changes simultaneously correlated with Akkermansia abundance and predominantly related to oxidative phosphorylation, perhaps alluding to a protective gut-brain axis interaction. Collectively, our results suggest that the bioactive blend Neurosyn240 conferred cognitive and microbiota resilience in response to the deleterious effects of low-grade inflammation.

ABSTRACTThis 1:30,000 scale geological map describes Oxia Planum, Mars, the landing site for the ExoMars Rosalind Franklin rover mission. The map represents our current understanding of bedrock units and their relationships prior to Rosalind Franklin’s exploration of this location. The map details 15 bedrock units organised into 6 groups and 7 textural and surficial units. The bedrock units were identified using visible and near-infrared remote sensing datasets. The objectives of this map are (i) to identify where the most astrobiologically relevant rocks are likely to be found, (ii) to show where hypotheses about their geological context (within Oxia Planum and in the wider geological history of Mars) can be tested, (iii) to inform both the long-term (hundreds of metres to ∼1 km) and the short-term (tens of metres) activity planning for rover exploration, and (iv) to allow the samples analysed by the rover to be interpreted within their regional geological context.

ABSTRACTGreening initiatives are urban planning strategies that rely on the development of public green spaces supporting multiple urban system functions. In a global water scarcity context, however, green space irrigation is a key aspect. Dynamic optimisation of irrigation plans is one viable answer for water consumption mitigation, which is not widely implemented at municipal levels in the EU. Yet, hydroinformatics-based mature and market-ready methods and technologies can support its implementation and should allow its embedment within the smart-city concept. Here, a simple interoperable approach for optimisation of dynamic irrigation planning has been implemented in public green space parcels of a French Mediterranean coastal city. The approach relies on smart sensors, a water balance model, an optimisation algorithm, and weather forecast data integration, all encapsulated in the standardised and open-source FIWARE ecosystem. The results of the dynamic irrigation plan led to a 35% water saving during the dry season and to more than 60% water saving during the dry–wet season transition period. The used standard technologies and approach could fit a broad range of smart-city digital platforms without any technical challenge.

Exposure to polycyclic aromatic hydrocarbons (PAHs), ubiquitously environmental contaminant, leads to the development of major toxic effects on human health, such as carcinogenic and immunosuppressive alterations reported for the most studied PAH, i.e., benzo(a)pyrene (B(a)P). In order to assess the risk associated with this exposure, it is necessary to have predictive biomarkers. Thus, extracellular vesicles (EVs) and their microRNA (miRNA) contents, have recently been proposed as potentially interesting biomarkers in Toxicology. Our study here explores the use of vesicles secreted and found in blood fluids, and their miRNAs, as biomarkers of exposure to B(a)P alone and within a realistic occupational mixture. We isolated EVs from primary human cultured blood mononuclear cells (PBMCs) and rat plasma after PAH exposure and reported an increased EV production by B(a)P, used either alone or in the mixture, in vitro and in vivo. We then investigated the association of this EV release with the blood concentration of the 7,8,9,10-hydroxy (tetrol)-B(a)P reactive metabolite, in rats. By performing RNA-sequencing (RNA-seq) of miRNAs in PBMC-derived EVs, we analyzed miRNA profiles and demonstrated the regulation of the expression of miR-342–3p upon B(a)P exposure. We then validated B(a)P-induced changes of miR-342–3p expression in vivo in rat plasma-derived EVs. Overall, our study highlights the feasibility of using EVs and their miRNA contents, as biomarkers of PAH exposure and discusses their potential in environmental Toxicology.

Background: Recent advances have significantly expanded our understanding of the gut microbiome's influence on host physiology and metabolism. However, the specific role of certain microorganisms in gestational health and fetal development remains underexplored. Objective: This study investigates the impact of Bifidobacterium breve UCC2003 on fetal brain metabolism when colonized in the maternal gut during pregnancy. Methods: Germ-free pregnant mice were colonized with or without B. breve UCC2003 during pregnancy. The metabolic profiles of fetal brains were analyzed, focusing on the presence of key metabolites and the expression of critical metabolic and cellular pathways. Results: Maternal colonization with B. breve resulted in significant metabolic changes in the fetal brain. Specifically, ten metabolites, including citrate, 3-hydroxyisobutyrate, and carnitine, were reduced in the fetal brain. These alterations were accompanied by increased abundance of transporters involved in glucose and branched-chain amino acid uptake. Furthermore, supplementation with this bacterium was associated with elevated expression of critical metabolic pathways such as PI3K-AKT, AMPK, STAT5, and Wnt-β-catenin signaling, including its receptor Frizzled-7. Additionally, there was stabilization of HIF-2 protein and modifications in genes and proteins related to cellular growth, axogenesis, and mitochondrial function. Conclusions: The presence of maternal B. breve during pregnancy plays a crucial role in modulating fetal brain metabolism and growth. These findings suggest that Bifidobacterium could modify fetal brain development, potentially offering new avenues for enhancing gestational health and fetal development through microbiota-targeted interventions.

This paper presents the latest development of HyGenSys, a new sustainable process and technology for the conversion of natural gas to hydrogen and power. The concept combines a specific steam reforming reactor-exchanger with a gas turbine. The heat necessary for the steam reforming reaction comes from hot pressurized flue gases produced in a gas turbine instead of a conventional furnace. Thanks to this high level of heat integration, the overall efficiency is improved and the natural gas consumption is reduced which represents an advantage with regard to economics and CO2 emission reduction. In addition to the efficient HyGenSys process scheme itself, the technology of the reactorexchanger also offers a high level of heat integration for even more energy saving. Two main alternatives are examined in order to meet two different requirements. The first one, named HyGenSys-0, focuses on the hydrogen production for the refining and petrochemical application. The second one named HyGenSys-1, concerns the centralized power production with pre-combustion CO2capture. In that case, the produced hydrogen is fully used to fuel a power gas turbine. HyGenSys-1 has been developed and optimised in CACHET, a European Community funded project. The CACHET electrical power objective was 400 MW at the minimum. HyGenSys-0 and HyGenSys-1 are described in detail with challenges and advantages compared to existing technologies. For both alternatives, the heart of the technology is the reactor-exchanger. The reactor-exchanger design relies on an innovative arrangement of bayonet tubes that allows, at large scale, multiple heat exchanges between hot pressurized flue gas, natural gas feed and hydrogen rich stream produced. Cet article présente les développements récents d’HyGenSys, nouvel éco-procédé de conversion du gaz naturel en hydrogène et électricité. Le concept combine un réacteur-échangeur spécifique de reformage à la vapeur avec une turbine à gaz. En fait, la chaleur nécessaire pour la réaction de reformage à la vapeur provient des fumées pressurisées produites dans une turbine à gaz au lieu d’un four conventionnel. Grâce à cette intégration thermique poussée, l’efficacité globale est améliorée et la consommation de gaz naturel réduite, ce qui représente un avantage d’un point de vue économique et environnemental notamment vis-à-vis de la réduction des émissions de CO2. Deux déclinaisons du procédé sont détaillées, elles répondent chacune à des besoins différents. La première, appelée HyGenSys-0, correspond à la production d’hydrogène pour le raffinage et la pétrochimique. La deuxième, appelée HyGenSys-1, permet la production d’énergie centralisée avec la capture de CO2 en précombustion. Dans ce cas, l’hydrogène produit est entièrement utilisé pour alimenter une turbine de production d’électricité. HyGenSys-1 a été développé et optimisé au cours du projet CACHET, financé par la Communauté européenne, avec comme objectif de fournir une puissance de 400 MW minimum. Les versions HyGenSys-0 et HyGenSys-1 du procédé sont décrites en détail avec les défis et avantages comparés aux technologies existantes. Dans les deux cas, le coeur de la technologie est le réacteuréchangeur dont le développement est également présenté en détail. La conception de réacteur-échangeur est basée sur un arrangement innovant de tubes à baïonnette autorisant une conception à grande échelle, de l’échange thermique multiple entre la fumée pressurisée chaude, l’alimentation de gaz naturel et l’effluent riche en hydrogène.

Abstract Microbial α-l-fucosidases catalyse the hydrolysis of terminal α-l-fucosidic linkages and can perform transglycosylation reactions. Based on sequence identity, α-l-fucosidases are classified in glycoside hydrolases (GHs) families of the carbohydrate-active enzyme database. Here we explored the sequence-function space of GH29 fucosidases. Based on sequence similarity network (SSN) analyses, 15 GH29 α-l-fucosidases were selected for functional characterisation. HPAEC-PAD and LC-FD-MS/MS analyses revealed substrate and linkage specificities for α1,2, α1,3, α1,4 and α1,6 linked fucosylated oligosaccharides and glycoconjugates, consistent with their SSN clustering. The structural basis for the substrate specificity of GH29 fucosidase from Bifidobacterium asteroides towards α1,6 linkages and FA2G2 N-glycan was determined by X-ray crystallography and STD NMR. The capacity of GH29 fucosidases to carry out transfucosylation reactions with GlcNAc and 3FN as acceptors was evaluated by TLC combined with ESI–MS and NMR. These experimental data supported the use of SSN to further explore the GH29 sequence-function space through machine-learning models. Our lightweight protein language models could accurately allocate test sequences in their respective SSN clusters and assign 34,258 non-redundant GH29 sequences into SSN clusters. It is expected that the combination of these computational approaches will be used in the future for the identification of novel GHs with desired specificities.

In this study, we reassess the phylogenetic relationships of the genus Sesamia Guenée, 1852 and examine in more detail the members of the nonagrioides species group, for which three distinct species complexes are identified. The calamistis subgroup comprises eight species, of which four new species are described: Sesamia kabirara Le Ru sp. nov., Sesamia kalale Le Ru sp. nov., Sesamia mapalense Le Ru sp. nov. and Sesamia teke Le Ru sp. nov. The incerta subgroup consists of 11 species, of which four new species are described: Sesamia kamba Le Ru sp. nov., Sesamia lalaci Le Ru sp. nov., Sesamia lusese Le Ru sp. nov. and Sesamia msowero Le Ru sp. nov. The nonagrioides subgroup comprises ten species of which two new species are described: Sesamia libode Le Ru sp. nov. and Sesamia satauensis Le Ru sp. nov. Phylogenetic and molecular species delimitation analyses of a multi-marker molecular dataset allow us to investigate and clarify the status of Sesamia species and species complexes. Our results yield a well-supported phylogenetic hypothesis for the genus, which supports the monophyletic nature of all but one species subgroup. The results of 16 distinct molecular species delimitation analyses show some levels of incongruence and, overall, a tendency towards over-splitting. We also present an updated list of species for the genus Sesamia and provide morphological keys based on male and female genitalia to determine the species group of any Sesamia species and to identify all species belonging to the nonagrioides species group.

Abstract Due to their exceptional solubility and stability, nanobodies have emerged as powerful building blocks for research tools and therapeutics. However, their generation in llamas is cumbersome and costly. Here, by inserting an engineered llama immunoglobulin heavy chain (IgH) locus into IgH-deficient mice, we generate a transgenic mouse line, which we refer to as ‘LamaMouse’. We demonstrate that LamaMice solely express llama IgH molecules without association to Igκ or λ light chains. Immunization of LamaMice with AAV8, the receptor-binding domain of the SARS-CoV-2 spike protein, IgE, IgG2c, and CLEC9A enabled us to readily select respective target-specific nanobodies using classical hybridoma and phage display technologies, single B cell screening, and direct cloning of the nanobody-repertoire into a mammalian expression vector. Our work shows that the LamaMouse represents a flexible and broadly applicable platform for a facilitated selection of target-specific nanobodies.

Locusts and other migratory grasshoppers are transboundary pests. Monitoring and control, therefore, involve a complex system made up of social, ecological, and technological factors. Researchers and those involved in active management are calling for more integration between these siloed but often interrelated sectors. In this paper, we bring together 38 coauthors from six continents and 34 unique organizations, representing much of the social-ecological-technological system (SETS) related to grasshopper and locust management and research around the globe, to introduce current topics of interest and review recent advancements. Together, the paper explores the relationships, strengths, and weaknesses of the organizations responsible for the management of major locust-affected regions. The authors cover topics spanning humanities, social science, and the history of locust biological research and offer insights and approaches for the future of collaborative sustainable locust management. These perspectives will help support sustainable locust management, which still faces immense challenges such as fluctuations in funding, focus, isolated agendas, trust, communication, transparency, pesticide use, and environmental and human health standards. Arizona State University launched the Global Locust Initiative (GLI) in 2018 as a response to some of these challenges. The GLI welcomes individuals with interests in locusts and grasshoppers, transboundary pests, integrated pest management, landscape-level processes, food security, and/or cross-sectoral initiatives.

Abstract Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we find that SF3B1-mutated MDS show reduced R-loop formation predominating in gene bodies associated with intron retention reduction, not found in U2AF1- or SRSF2-mutated MDS. Compared to erythroblasts from SRSF2- or U2AF1-mutated patients, SF3B1-mutated erythroblasts exhibit augmented DNA synthesis, accelerated replication forks, and single-stranded DNA exposure upon differentiation. Importantly, histone deacetylase inhibition using vorinostat restores R-loop formation, slows down DNA replication forks and improves SF3B1-mutated erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress represents a hallmark of SF3B1-mutated MDS ineffective erythropoiesis, which could be used as a therapeutic target.

Background Rennes, a midsize city in France, features many opportunities for active travel. City officials seek to increase walking and cycling by 2030 to improve public health. Physical inactivity, a leading risk factor for premature mortality around the globe, has been shown to be associated with many chronic diseases including heart disease, type 2 diabetes, and cancer. Methods Using the 2018 household travel survey of Rennes residents, we apply the Health-Oriented Transportation statistical model to assess health impacts associated with population-level rates of walking and cycling. We consider two proposed mobility and climate objectives which outline sustainable transportation goals by 2030. These include a shift in transportation mode share to increase walking and cycling trips, as well as a broad reduction in vehicle miles traveled (VMT) across the metropolitan area. Results Our regression analysis demonstrated that factors of household car access and inner-city residency were predictors of prevalence (observed one-day proportion engaging in walking or cycling), participation (weekly proportion), and intensity (mean individual physical activity achieved through walking/cycling) of active travel. Age and education were additionally associated with prevalence. The 2030 mobility objective (mode share: 9% cycle, 35% walk) was associated with a reduction of 1,051 DALYs (disability-adjusted life-years), translating to $73 million USD ($23-$177) in averted costs. The climate objective (10% reduction in VMT) was associated with a reduction of 369 DALYs when replaced entirely by walking and 714 DALYs with cycling, translating to $26 million ($8-$62) and $50 million ($15-$121) saved, respectively. Conclusions Rennes residents experience high participation in active travel, particularly those in the inner city. If residents achieve the city’s active travel goals for 2030, there is potential for a large reduction in health burden and subsequent costs. Reaching these goals may require significant investment in transportation programming and infrastructure to improve active travel opportunities.

Three heterocyclic diazenyl compounds were synthesized by diazotization of 3-aminopyridine and aniline, followed by coupling with 8-aminoquinoleine, morpholine, 1,2,3,4-tetrahydroquinoleine, respectively. The obtained azo compounds are brown to yellow in color and were characterized by various methods such as NMR and X-rays. The synthesized compounds were evaluated for their antimicrobial activity against Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, and Candida albicans. The MIC of the tested compounds, determined by the microdilution method, showed potential antimicrobial activity against all tested microorganisms. 1-(3-pyridyl)-2-(morpholin-4-yl)diazene (8) and 1-(3-pyridyl)-2-(tetrahydroquinolin-1-yl)diazene (10) showed strong activities against C. albicans with MIC values of 150 µM and 120 µM respectively. 1-(4-trifluoromethylphenyl)-2-(8-aminoquinolin-5-yl)diazene (4) showed the broadest spectrum of activity with good MICs of 1380–2760 µM on the four strains. These diazenyl compounds were also screened for their anticancer activity against breast (MCF-7), lung (Calu-3), pancreas (PANC-1) and prostate (PC-3) cancer cells and on normal fibroblasts. The results showed good anticancer activities on tumor lines with IC50 values ranging from 9.4 to 98 µM. The best anticancer activity was obtained with compound 4 on Calu-3 cancer cells with an IC50 of 9.4 µM. The results suggest that compound 4 is an interesting scaffold for pharmacomodulation as suggested by ADME study.

Mesophotic Coral Ecosystems (MCEs) represent unique ecological habitats that range from 30 to 150 m deep, harbouring phylogenetically distinct species and offering refuge for many taxa during times of environmental stress. Yet owing to inaccessibility of ecosystems at these depths, most MCEs remain unexplored, with quantifications of ecological communities in these habitats lacking across many regions. Here, using open- and closed-circuit technical diving, we quantified benthic and fish community composition at four mesophotic reef sites (45 m depth) in Grand Cayman. We show significant differences in benthic community composition over a small spatial scale driven by disparate coverage of sponges, crustose coralline algae, and sand/rubble, yet consistent patterns of macroalgal dominance representing >50% coverage at each site and low hard coral cover at an average of 2.4%. Reef fish species richness, biomass, and density was consistent across sites, however the relative contribution of individual species to community composition differed significantly. Macrocarnivores were found to be the dominant contributors to biomass, with invertivores the most speciose, and omnivores and planktivores at the highest densities, consistent with previous descriptions of mesophotic fish assemblages in other regions. Similarly, the low hard coral cover and high macroalgae and sponge cover of the benthic communities also appear ecologically similar to several described mesophotic reefs yet is not uniform across the Caribbean. The ecological organisation of Grand Cayman’s MCEs may result from a variety of factors such as isolation from other major land masses, geology, local geography, and anthropogenic activity at both the local and global scale and highlight the importance of continued exploration and documentation of MCE communities.