Claude Bernard University Lyon 1

During the last decades, fluvial sediment cores have been used to reconstruct and model pollution trends, especially for the post-1945 period. Ecological changes have been rarely studied in such recent sediment archives due to low organic levels and high hydro-sedimentary dynamics. Here, we address the challenge of reconstructing ecosystem changes along highly anthropized rivers by analysing plant macrofossils (e.g. seeds, wood fragments, mosses), animal and abiotic remains (mainly iron slags) accumulated in side channels. The main objective is to determine whether this approach – inspired from palaeoecology – is reliable. Interestingly, macrofossil records offer a coherent history of the species habitats and biodiversity on different sites on either side of a bypassed section of the Rhône River (France). Three main hydro-ecological phases are identified, linked to river developments. (1) A lotic phase, before damming, is marked by various local riparian forest taxa: black alder and willow macrofossils were regularly found in the cores, while black poplar is not recorded, despite its historical presence. (2) A synchronous terrestrialization phase (transition from an aquatic to a terrestrial ecosystem) is highlighted on both side channels in the late 1970s, due to the bypassing of the river and the subsequent lowering of the water level. During this phase, nitrophilous plants (nettles) expanded on both sites. (3) Finally, the effects of restoration also appeared in fluvial sediment cores, marked by new aquatic flora and fauna macrofossil taxa since 2000. Overall, this research demonstrated the potential of studying macrofossils in side channel deposits to understand the post-1945 history of riparian habitats and biodiversity, and their evolution after developments and/or restoration actions. This macrofossil approach could be considered as a tool to supplement monitoring data and to better interpret wetland changes with regard to hydromorphological adjustments along a river system over decades or centuries.

Background DPANN archaea, including Woesearchaeota, encompass a large fraction of the archaeal diversity, yet their genomic diversity, lifestyle, and role in natural microbiomes remain elusive. With an archaeal assemblage naturally enriched in Woesearchaeota and steep vertical geochemical gradients, Lake Dziani Dzaha (Mayotte) provides an ideal model to decipher their in-situ activity and ecology. Results Using genome-resolved metagenomics and phylogenomics, we identified highly diversified Woesearchaeota populations and defined novel halophilic clades. Depth distribution of these populations in the water column showed an unusual double peak of abundance, located at two distinct chemoclines that are hotspots of microbial diversity in the water column. Genome-centric metatranscriptomics confirmed this vertical distribution and revealed a fermentative activity, with acetate and lactate as end products, and active cell-to-cell processes, supporting strong interactions with other community members at chemoclines. Our results also revealed distinct Woesearchaeota ecotypes, with different transcriptional patterns, contrasted lifestyles, and ecological strategies, depending on environmental/host conditions. Conclusions This work provides novel insights into Woesearchaeota in situ activity and metabolism, revealing invariant, bimodal, and adaptative lifestyles among halophilic Woesearchaeota. This challenges our precepts of an invariable host-dependent metabolism for all the members of this taxa and revises our understanding of their contributions to ecosystem functioning and microbiome assemblage. Bo26ccZX9sY8C76pvHyDeyVideo Abstract

Late postnatal steroids are given to premature infants who cannot be weaned from ventilation because of the possible development of bronchopulmonary dysplasia (BPD). At that time, some infants still have a patent ductus arteriosus (PDA). In our experience, the use of betamethasone (BTM) seems to reduce the need for surgical/endovascular treatment of PDA. We evaluated herein the impact of oral BTM on PDA in extremely preterm infants with BPD. Extremely preterm infants (GA < 29 weeks) with PDA and treated with BTM to facilitate extubation/avoid reintubation were included in this retrospective, single-centre study. BTM was administered orally at 0.3 mg/kg/day for 3 days, 0.15 mg/kg/day the following 2 days, and 0.05 mg/kg/day on the last day. An echocardiography was performed before and after BTM treatment. The 51 infants included were born at a median [IQR] GA of 25.7 [25.0–26.7] weeks. At the time of BTM treatment (28 [26–30] days), 94.1% (48/51) were on invasive ventilation, and most (44/48, 91.7%) were extubated after BTM treatment. At that time, nearly all infants had a closed or non-haemodynamically significant PDA (50/51, 98.0%). None required surgical or endovascular treatment after BTM. Adverse effects included transient moderate hypertension (68.6%), transient hyperglycaemia (15.7%), and transient slowing of postnatal weight gain during BTM treatment. Conclusion: In extremely preterm infants with a severe respiratory condition at 3 weeks of life, oral BTM treatment can help wean invasive ventilation and is associated with PDA closure. It could reduce the need for surgical or endovascular treatment that are associated with serious adverse effects. Trial registration: Clinicaltrials.gov NCT05987202. What is Known: • Patent ductus arteriosus and bronchopulmonary dysplasia are two most frequent complications of extreme prematurity. • Betamethasone is one of the corticosteroids used to help wean invasive ventilation in infants at risk for bronchopulmonary dysplasia. What is New: • In extremely preterm infants still ventilated after 3 weeks of life and suffering from patent ductus arteriosus, treatment with oral betamethasone facilitated ventilatory weaning • Oral betamethasone treatment was associated with patent ductus arteriosus closure in almost all infants.

This study focuses on the modulatory effects of gold nanoclusters with 25 gold atoms and 18 acetyl cysteines (Au 25 AcCys 18) in human microglia, human iPSC-derived neurons and SH-SY5Y differentiated human neuronal cells. The combination of chemical, biological, and computational methods shows the well-retained viability of these human cells treated with Au 25 AcCys 18 , interactions between Au 25 AcCys 18 and transcription factor TFEB (computational approach), interactions between TFEB and HMGB1 (proxi-mity ligation assay and molecular modeling using AlphaFold), modulation of the abundance and location of acHMGB1 by Au 25 AcCys 18 (immunocytochemistry), and the reduction of ROS in cells treated with Au 25 AcCys 18 (CellROX live imaging). These novel findings in human neural cells, particularly neurons, encourage further studies in experimental animal models of neurological disorders and/or human orga-noids to exploit the unique structural and photophysical properties of gold nanoclusters and to better understand their ability to modulate molecular mechanisms in human cells.

Very high-average optical enhancement cavities (OECs) are being used both in fundamental and applied research. The most demanding applications require stable megawatt level average power of infrared picosecond pulses with repetition rates of several tens of MHz. Toward reaching this goal, we report on the achievement of 710 kW of stable average power in a two-mirror hemispherical optical enhancement cavity. This result further improves the state of the art. So far, in compact high-power systems, cavity geometry optimization has been driven by the need to limit the deformation of radii of curvatures due to thermal effects. Here we explicitly demonstrate that thermal lensing must be accounted for, too, and that it can be used to assess the absorption of coatings. Experimental observations are matched with a simple model of thermal effects in the mirror’s coatings. These results set a further stage for designing an optimized optical system for several applications where very high-average power enhancement cavities are expected to be operated.

The triple combination elexacaftor-tezacaftor-ivacaftor (ETI) has provided unprecedented clinical benefits for people with cystic fibrosis (pwCF) and drastically transformed the outcome of this disease. We aimed to describe the evolution of lung bacterial colonization in 198 French adult pwCF taking into account the use of concomitantly respiratory treatment. We collected sputum cultures produced during the entire follow-up period starting 3 years before and ending 1 year after ETI initiation. All sputum cultures were centralized and analyzed at our bacteriological laboratory. Clinical data included pulmonary function, respiratory treatments, physiotherapy, number of IV antibiotics treatment, as well as inpatient stays. We observed a significant decrease in colonization prevalence by any CF pathogen after one year of treatment with ETI (p < 0.001). This decrease was confirmed for Pseudomonas aeruginosa, MRSA and MSSA, Stenotrophomonas maltophilia, Achromobacter spp. and nontuberculous mycobacteria (NTM). The maximal density of bacteria documented in sputum cultures decreased from 2.10⁷ CFU/ml to 1.10⁶ CFU/ml after one year of ETI. We also found a decrease in prevalence of Pseudomonas aeruginosa chronic colonization and in the density of Pseudomonas aeruginosa after one year of ETI. These results confirm the decrease in prevalence and bacterial density of lung colonisation for most of the CF pathogens, including Achromobacter spp, Stenotrophomonas maltophilia concomitantly to the clinical improvement. Further studies are needed to better understand the underlying mechanisms of these microbiological changes.

Herpes simplex virus 1 (HSV-1) latently infected neurons display diverse patterns in the distribution of the viral genomes within the nucleus. A key pattern involves quiescent HSV-1 genomes sequestered in promyelocytic leukemia nuclear bodies (PML NBs) forming viral DNA-containing PML-NBs (vDCP NBs). Using a cellular model that replicates vDCP NB formation, we previously demonstrated that these viral genomes are chromatinized with the H3.3 histone variant modified on its lysine 9 by trimethylation (H3.3K9me3), a mark associated with transcriptional repression. Here, we identify the HUSH complex and its effectors, SETDB1 and MORC2, as crucial for the acquisition of H3K9me3 on PML NB-associated HSV-1 and the maintenance of HSV-1 transcriptional repression. ChIP-seq analyses show H3K9me3 association with the entire viral genome. Inactivating the HUSH–SETDB1–MORC2 complex before infection significantly reduces H3K9me3 on the viral genome, with minimal impact on the cellular genome, aside from expected changes in LINE-1 retroelements. Depletion of HUSH, SETDB1, or MORC2 alleviates HSV-1 repression in infected primary human fibroblasts and human induced pluripotent stem cell–derived sensory neurons (hiPSDN). We found that the viral protein ICP0 induces MORC2 degradation via the proteasome machinery. This process is concurrent with ICP0 and MORC2 depletion capability to reactivate silenced HSV-1 in hiPSDN. Overall, our findings underscore the robust antiviral function of the HUSH–SETDB1–MORC2 repressor complex against a herpesvirus by modulating chromatin marks linked to repression, thus presenting promising avenues for anti-herpesvirus therapeutic strategies.

Background Personalized alignment in total knee arthroplasty (TKA) has demonstrated good functional outcomes for knees with varus alignment. However, limited research has explicitly addressed optimal alignment strategies for valgus knees. The aims of the current study were to assess the impact of the postoperative knee alignment and of the degree of correction of knee alignment on functional outcomes and satisfaction in a population with preoperative valgus and to evaluate the complication and revision rates based on postoperative alignment. Methods This retrospective study included primary posterior-stabilized TKA with a preoperative hip-knee-ankle (HKA) angle of ≥180°, with a minimum follow-up of 32 months. There were 460 knees included, divided into 3 groups: (1) preoperative neutral alignment (180° to 183°) (n = 162), (2) preoperative mild valgus (184° to 190°) (n = 204), and (3) preoperative severe valgus (>190°) (n = 94). A standardized surgical technique was employed with a goal of achieving neutral postoperative alignment. Data on radiographs, Knee Society Scores (KSS), range of motion, satisfaction, complications, and revisions were collected at the last follow-up. Results The mean follow-up was 74.3 ± 12.4 months. In the preoperative mild valgus group, 10.8% of patients had postoperative varus, 81.4% had postoperative neutral alignment, and 7.8% had postoperative valgus. In the preoperative severe valgus group, 4.3% had postoperative varus, 83.0% had postoperative neutral alignment, and 12.8% had postoperative valgus. In the preoperative mild valgus group, patients with postoperative neutral alignment had significantly higher satisfaction (p = 0.0004) and KSS function score (p = 0.031) than patients with postoperative valgus alignment. In the preoperative severe valgus group, patients with postoperative valgus alignment had significantly higher satisfaction (p = 0.035) and greater improvement of the KSS knee score (p = 0.014) than patients with postoperative neutral alignment. Functional outcomes were not impacted by the degree of HKA angle correction. There were significantly fewer complications (p = 0.022) and revisions (p = 0.007) in the preoperative mild valgus group when patients had a postoperative neutral alignment compared with a postoperative valgus alignment. Conclusions For preoperative mild valgus, correction to neutral alignment achieved better outcomes and fewer complications than leaving residual valgus. For preoperative severe valgus, retaining residual valgus postoperatively ensured satisfactory functional outcomes without increased complications. Level of Evidence Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

Intrinsically disordered protein regions (IDRs) are well established as contributors to intermolecular interactions and the formation of biomolecular condensates. In particular, RNA-binding proteins (RBPs) often harbor IDRs in addition to folded RNA-binding domains that contribute to RBP function. To understand the dynamic interactions of an IDR–RNA complex, we characterized the RNA-binding features of a small (68 residues), positively charged IDR-containing protein, Small ERDK-Rich Factor (SERF). At high concentrations, SERF and RNA undergo charge-driven associative phase separation to form a protein- and RNA-rich dense phase. A key advantage of this model system is that this threshold for demixing is sufficiently high that we could use solution-state biophysical methods to interrogate the stoichiometric complexes of SERF with RNA in the one-phase regime. Herein, we describe our comprehensive characterization of SERF alone and in complex with a small fragment of the HIV-1 Trans-Activation Response (TAR) RNA with complementary biophysical methods and molecular simulations. We find that this binding event is not accompanied by the acquisition of structure by either molecule; however, we see evidence for a modest global compaction of the SERF ensemble when bound to RNA. This behavior likely reflects attenuated charge repulsion within SERF via binding to the polyanionic RNA and provides a rationale for the higher-order assembly of SERF in the context of RNA. We envision that the SERF–RNA system will lower the barrier to accessing the details that support IDR–RNA interactions and likewise deepen our understanding of the role of IDR–RNA contacts in complex formation and liquid–liquid phase separation.

Despite the numerous published syntheses and applications of sulfoximines, very few studies describe their physico‐chemical properties and in particular their acidic, basic and lipophilic or hydrophilic characters. We report for the first time the acidity values (pKa) of fluorinated sulfoximines in water and in acetonitrile, as well as the basicity (pKaH) measurements of fluorinated and non‐fluorinated sulfoximines in acetonitrile. The same sulfoximine library was also studied in terms of lipophilicity with measurement of the Hansch parameters of the sulfoximine moieties. Finally, these new data allowed us to optimize the N‐alkylation reaction of fluorinated sulfoximines.

To improve patient safety, surgeons can continually monitor the surgical outcomes of their patients. To this end, they can use statistical process control tools, which primarily originated in the manufacturing industry and are now widely used in healthcare. These tools belong to a broad family, making it challenging to identify the most suitable methodology to monitor surgical outcomes. The selected tools must balance statistical rigour with surgeon usability, enabling both statistical interpretation of trends over time and comprehensibility for the surgeons, their primary users. On one hand, the observed minus expected (O-E) chart is a simple and intuitive tool that allows surgeons without statistical expertise to view and interpret their activity; however, it may not possess the sophisticated algorithms required to accurately identify important changes in surgical performance. On the other hand, a statistically robust tool like the cumulative sum (CUSUM) method can be helpful but may be too complex for surgeons to interpret and apply in practice without proper statistical training. To address this issue, we developed a new risk-adjusted (RA) O-E CUSUM chart that aims to provide a balanced solution, integrating the visualisation strengths of a user-friendly O-E chart with the statistical interpretation capabilities of a CUSUM chart. With the RA O-E CUSUM chart, surgeons can effectively monitor patients’ outcomes and identify sequences of statistically abnormal changes, indicating either deterioration or improvement in surgical outcomes. They can also quantify potentially preventable or avoidable adverse events during these sequences. Subsequently, surgical teams can try implementing changes to potentially improve their performance and enhance patient safety over time. This paper outlines the methodology for building the tool and provides a concrete example using real surgical data to demonstrate its application.

Mobile elements (ME) can transpose by copy‐and‐paste mechanisms. A heterozygous insertion in APOB exon 3 coding sequence was suspected in a patient with hypobetalipoproteinemia (HBL), by gel electrophoresis of the PCR products. An insertion of a 85 bp fragment flanked by a polyA stretch and a target replication site duplication was identified as a ME insertion (MEI) from the AluYa5 subfamily, NM_000384.3(APOB):c.135_136ins(160). Then, the DNA was reanalyzed using our NGS custom panel. Routine analysis did not reveal any causative variant, but manual inspection of the alignments and MELT enabled us to detect this MEI from NGS data. A functional study revealed that this MEI introduces a stop codon p.(Phe46Alafs*2) and additionally leads to p.(Lys41Serfs*2) due to an exon skipping. This is the first report of a MEI into APOB, as a cause of HBL. Furthermore, our study highlights the value of including MEI‐callers in routine pipelines to improve primary dyslipidemia diagnosis.

Combining a water‐tolerant oxide such as TiO2 with yttrium fluoride is expected to provide catalysts with enhanced acid–base properties for catalytic applications in water. We present here a new strategy of incorporating preformed YF3 nanoparticles (NPs) in a TiO2‐based metallogel, followed by its soft drying at room temperature to produce YF3‐TiO2 xerogel with high surface area. The as‐synthesized YF3‐TiO2 materials were calcinated at 300 and 400°C and characterized by X‐ray photoelectron spectroscopy (XPS), X‐ray diffraction (XRD), ¹⁹F NMR spectroscopy and N2 physisorption, calorimetry of NH3 adsorption, and FT‐IR of pyridine adsorption. These studies indicate that the fluorine is present under a stable form of YF3 for the catalysts calcined at 300°C. The acid–base properties of these YF3‐TiO2 catalysts were investigated in a model reaction, that is, dihydroxyacetone (DHA) conversion in water, and compared with the blank TiO2 and YF3 NPs alone. The incorporation of YF3 in the TiO2 matrix leads to enhanced initial rate of DHA dehydration into pyruvaldehyde, which is slowly converted to lactic acid as the reaction progresses. This suggests that the Brønsted acidity was boosted by the presence of YF3 species via water adsorption in a dissociative form.

Neurodegenerative dementias have a profound impact on higher-order cognitive and behavioural functions. Investigating macroscale functional networks through cortical gradients provides valuable insights into the neurodegenerative dementia process and overall brain function. This approach allows for the exploration of unimodal-multimodal differentiation and the intricate interplay between functional brain networks. We applied cortical gradients mapping to resting-state functional MRI data of patients with frontotemporal dementia (FTD) (behavioural-bvFTD, non-fluent and semantic) and healthy controls. In healthy controls, the principal gradient maximally distinguished sensorimotor from default-mode network (DMN) and the secondary gradient visual from salience network (SN). In all FTD variants, the principal gradient’s unimodal-multimodal differentiation was disrupted. The secondary gradient, however, showed widespread disruptions impacting the interactions among all networks specifically in bvFTD, while semantic and non-fluent variants exhibited more focal alterations in limbic and sensorimotor networks. Additionally, the visual network showed responsive and/or compensatory changes in all patients. Importantly, these disruptions extended beyond atrophy distribution and related to symptomatology in patients with bvFTD. In conclusion, optimal brain function requires networks to operate in a segregated yet collaborative manner. In FTD, our findings indicate a collapse and loss of differentiation between networks not solely explained by atrophy. These specific cortical gradients’ fingerprints could serve as a functional signature for identifying early changes in neurodegenerative diseases or potential compensatory processes.

Ventricular fibrillation (VF)-induced cardiac arrest frequently complicates ST-segment elevation myocardial infarction (STEMI). Although larger infarct sizes (IS) correlate with a higher risk of VF, the influence of VF itself on IS has remained poorly investigated. To address this knowledge gap, we analyzed the effect of VF on IS in patients and two experimental models. From a prospective cohort, 30 STEMI patients with VF were matched 1:2 with STEMI patients without VF on the common determinants of IS. The primary endpoint was IS, assessed using the 48-h area under the curve (AUC) for troponin. We also compared IS in pigs with/without spontaneous VF during STEMI (n = 15/group), and in an isolated rat heart model of myocardial infarction with/without electrically induced VF (n = 7/group). After matching, the patient characteristics, including the area at risk (AR), were similar. IS was 33% lower in the VF group compared to the control group (troponin AUC 1.6 [0.5–3.3] 10⁶ arbitrary units vs. 2.4 [0.9–4.1] 10⁶ arbitrary units; p < 0.05), but infarct scar size (assessed using MRI and ECG) did not differ between the groups at 1 and 6 months. In both experimental models, IS, expressed as a percentage of AR, was lower (p < 0.05) in the VF group than in the control group. When common determinants of IS are comparable, VF occurring prior to myocardial infarction reperfusion appears to be associated with smaller IS. Nevertheless, this finding, observed under specific experimental conditions and in a highly selected group of patients, was not associated with reduced infarct scar size. Registration (HIBISCUS-STEMI cohort): ClinicalTrials.gov NCT05794022.