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The outcome of transplant recipients is variable depending on the study population, vaccination status and COVID-19 variants. Our aim was to study the impact of Omicron subvariants on the mortality of transplant recipients. We reviewed the results of SARS-CoV-2 whole genome sequence of random isolates collected from 29 December 2021 until 17 May 2022 in King Faisal Specialist Hospital and Research center, Jeddah (KFSHRC-J), Saudi Arabia performed as hospital genomic surveillance program for COVID-19 variants. We included 25 transplant patients infected with confirmed Omicron variants.17 (68%) and 8 (32%) patients had Omicron BA.1 and BA.2, respectively. 12 (68%) patients had renal transplants. Only 36% of patients received three doses of COVID-19 vaccines. 23 (92%) patients required hospitalization. 20 (80%) patients survived and 6 (25%) required intensive care unit (ICU) admission. Among ICU patients, 66.7% were more than 50 years, 50% had two to three comorbidities and 5 out of 6 (83%) died. The mortality of transplant patients infected with Omicron variants in our cohort was higher than other centers as a limited number of patients received booster vaccines. Optimizing booster vaccination is the most efficient method to improve the mortality of COVID-19 in transplant recipients recognizing the inefficacy of monoclonal antibodies in the presence of SARS-CoV-2 emerging variants. We did not show a difference in mortality in transplant patients infected with Omicron BA.1 and BA.2 knowing the limitation of our sample size.

Background Hospitalization is rare in anorexia nervosa (AN) and local application of indications is heterogeneous. However, no study has evaluated the effect of these different treatment modalities on the mean length of stay. Our objective was to describe the context and modalities of a wide range of hospital care programs offered to patients with anorexia nervosa in eleven specialized French psychiatric centers for patients from childhood to adulthood. This work was carried out within the framework of the EVHAN (Evaluation of Hospitalization for AN, Eudract number: 2007-A01110-53, registered in Clinical trials) research program. The EVHAN program comprises five main lines: weight objectives at discharge, the practice or not of a separation period, the use of clear nutritional dietary objectives (cognitive/behavioral), the intensity of family involvement in treatment, and the existence or absence of a stabilization phase before ending inpatient treatment. These main lines will make it possible to study the impact of treatment modalities on the future of patients in the short and medium term (at discharge and at 1-year follow-up). Methods The eleven centers are located in France (Bordeaux, Nantes, Paris and Ile-de-France, Rouen and Saint-Etienne). Various staff members (psychiatrists, somatic doctors, nurses, dieticians, psychologists) from each center were interviewed using a semi-structured questionnaire. Data on operating modalities and context of care were collected and analyzed. Results Four of the eleven centers were exclusively child/adolescent centers, and seven of 11 were adolescent (from 11, 13 or 16 years) and young adult centers. All centers offered a graduated approach from outpatient to full hospitalization. The majority had a number of beds allocated for patients with eating disorders. The criteria for hospitalization were homogeneous with respect to somatic and/or psychic severity prefiguring the consensus criteria defined by the French Health Authority (HAS) in 2010. Child/adolescent units used the weight curve to set weight objectives at discharge (between the 10th and 50th percentiles). Most adult units used weight objectives at discharge corresponding to a body mass index between 17 and 20kg/m2. Nine centers used a written or oral care contract. One unit did not separate the patient from her/his usual environment, the others had a practice gradient of partial separation and total separation times. These were either short, lasting a maximum of 3 weeks, or long, lasting more than 3 weeks. Conversely, patients were not isolated within the unit, and benefited from a rich social life, depending on her/his physical condition. The patient's family was in contact with the team and fully supported. The longest periods of separation involved adolescents and adults. Nutritional support varied from a group approach (meals in the dining room, standardized meals of the care center) to very individualized approaches within a specific framework. All the units reported meeting with families at least once during the hospitalization; with the patient's parents for child/adolescent patients and/or unmarried patients and with the husband/wife for married patients. The majority of the centers requested a phase of weight stabilization, whatever the age before hospital discharge. Conclusion There is international and national consensus regarding the indications for hospitalization, and the main lines of multidisciplinary care to be developed within this framework. However, local application of these indications was heterogeneous resulting in diverse modalities of hospital care for anorexia nervosa in France. Specialized teams have developed management strategies arising from their "team culture". The complexity of the anorexic pathology, due to the psyche-soma intrication and the diversity of age groups, highlights the complexity of care available. The impact of this diversity of hospital care on patient outcomes will be studied as a result of this work.

OBJECTIVE The role of endovascular treatment in the management of patients with brain arteriovenous malformations (AVMs) remains uncertain. AVM embolization can be offered as stand-alone curative therapy or prior to surgery or stereotactic radiosurgery (SRS) (pre-embolization). The Treatment of Brain AVMs Study (TOBAS) is an all-inclusive pragmatic study that comprises two randomized trials and multiple registries. METHODS Results from the TOBAS curative and pre-embolization registries are reported. The primary outcome for this report is death or dependency (modified Rankin Scale [mRS] score > 2) at last follow-up. Secondary outcomes include angiographic results, perioperative serious adverse events (SAEs), and permanent treatment-related complications leading to an mRS score > 2. RESULTS From June 2014 to May 2021, 1010 patients were recruited in TOBAS. Embolization was chosen as the primary curative treatment for 116 patients and pre-embolization prior to surgery or SRS for 92 patients. Clinical and angiographic outcomes were available in 106 (91%) of 116 and 77 (84%) of 92 patients, respectively. In the curative embolization registry, 70% of AVMs were ruptured, and 62% were low-grade AVMs (Spetzler-Martin grade I or II), while the pre-embolization registry had 70% ruptured AVMs and 58% low-grade AVMs. The primary outcome of death or disability (mRS score > 2) occurred in 15 (14%, 95% CI 8%–22%) of the 106 patients in the curative embolization registry (4 [12%, 95% CI 5%–28%] of 32 unruptured AVMs and 11 [15%, 95% CI 8%–25%] of 74 ruptured AVMs) and 9 (12%, 95% CI 6%–21%) of the 77 patients in the pre-embolization registry (4 [17%, 95% CI 7%–37%] of 23 unruptured AVMs and 5 [9%, 95% CI 4%–20%] of 54 ruptured AVMs) at 2 years. Embolization alone was confirmed to occlude the AVM in 32 (30%, 95% CI 21%–40%) of the 106 curative attempts and in 9 (12%, 95% CI 6%–21%) of 77 patients in the pre-embolization registry. SAEs occurred in 28 of the 106 attempted curative patients (26%, 95% CI 18%–35%, including 21 new symptomatic hemorrhages [20%, 95% CI 13%–29%]). Five of the new hemorrhages were in previously unruptured AVMs (n = 32; 16%, 95% CI 5%–33%). Of the 77 pre-embolization patients, 18 had SAEs (23%, 95% CI 15%–34%), including 12 new symptomatic hemorrhages [16%, 95% CI 9%–26%]). Three of the hemorrhages were in previously unruptured AVMs (3/23; 13%, 95% CI 3%–34%). CONCLUSIONS Embolization as a curative treatment for brain AVMs was often incomplete. Hemorrhagic complications were frequent, even when the specified intent was pre-embolization before surgery or SRS. Because the role of endovascular treatment remains uncertain, it should preferably, when possible, be offered in the context of a randomized trial.

International audience; The melanocortin 4 receptor (MC4R) plays a role in energy homeostasis and represents a target for treating energy balance disorders. For decades, synthetic ligands have been derived from MC4R endogenous agonists and antagonists, such as setmelanotide used to treat rare forms of genetic obesity. Recently, animal venoms have demonstrated their capacity to provide melanocortin ligands with toxins from a scorpion and a spider. Here, we described a cone snail toxin, N-CTX-Ltg1a, with a nanomolar affinity for hMC4R but unrelated to any known toxins or melanocortin ligands. We then derived from the conotoxin the linear peptide HT1-0, a competitive antagonist of G s , G 15 , and β-arrestin2 pathways with a low nanomolar affinity for hMC4R. Similar to endogenous ligands, HT1-0 needs hydrophobic and basic residues to bind hMC4R. Altogether, it represents the first venom-derived peptide of high affinity on MC4R and paves the way for the development of new MC4R antagonists.

OBJECTIVE The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is a pragmatic study that includes 2 randomized trials and registries of treated or conservatively managed patients. The authors report the results of the surgical registry. METHODS TOBAS patients are managed according to an algorithm that combines clinical judgment and randomized allocation. For patients considered for curative treatment, clinicians selected from surgery, endovascular therapy, or radiation therapy as the primary curative method, and whether observation was a reasonable alternative. When surgery was selected and observation was deemed unreasonable, the patient was not included in the randomized controlled trial but placed in the surgical registry. The primary outcome of the trial was mRS score > 2 at 10 years (at last follow-up for the current report). Secondary outcomes include angiographic results, perioperative serious adverse events, and permanent treatment-related complications leading to mRS score > 2. RESULTS From June 2014 to May 2021, 1010 patients were recruited at 30 TOBAS centers. Surgery was selected for 229/512 patients (44%) considered for curative treatment; 77 (34%) were included in the surgery versus observation randomized trial and 152 (66%) were placed in the surgical registry. Surgical registry patients had 124/152 (82%) ruptured and 28/152 (18%) unruptured arteriovenous malformations (AVMs), with the majority categorized as low-grade Spetzler-Martin grade I–II AVM (118/152 [78%]). Thirteen patients were excluded, leaving 139 patients for analysis. Embolization was performed prior to surgery in 78/139 (56%) patients. Surgical angiographic cure was obtained in 123/139 all-grade (89%, 95% CI 82%–93%) and 105/110 low-grade (95%, 95% CI 90%–98%) AVM patients. At the mean follow-up of 18.1 months, 16 patients (12%, 95% CI 7%–18%) had reached the primary safety outcome of mRS score > 2, including 11/16 who had a baseline mRS score ≥ 3 due to previous AVM rupture. Serious adverse events occurred in 29 patients (21%, 95% CI 15%–28%). Permanent treatment-related complications leading to mRS score > 2 occurred in 6/139 patients (4%, 95% CI 2%–9%), 5 (83%) of whom had complications due to preoperative embolization. CONCLUSIONS The surgical treatment of brain AVMs in the TOBAS registry was curative in 88% of patients. The participation of more patients, surgeons, and centers in randomized trials is needed to definitively establish the role of surgery in the treatment of unruptured brain AVMs. Clinical trial registration no.: NCT02098252 (ClinicalTrials.gov)

The success of mRNA-based vaccines during the Covid-19 pandemic has highlighted the value of this new platform for vaccine development against infectious disease. However, the CD8+T cell response remains modest with mRNA vaccines, and these do not induce mucosal immunity, which would be needed to prevent viral spread in the healthy population. To address this drawback, we developed a dendritic cell targeting mucosal vaccination vector, the homopentameric STxB. Here, we describe the highly efficient chemical synthesis of the protein, and itsin vitrofolding. This straightforward preparation led to a synthetic delivery tool whose biophysical and intracellular trafficking characteristics were largely indistinguishable from recombinant STxB. The chemical approach allowed for the generation of new variants with bioorthogonal handles. Selected variants were chemically coupled to several types of antigens derived from the mucosal viruses SARS-CoV-2 and type 16 human papillomavirus. Upon intranasal administration in mice, mucosal immunity, including resident memory CD8+T cells and IgA antibodies was induced against these antigens. Our study thereby identifies a novel synthetic antigen delivery tool for mucosal vaccination with an unmatched potential to respond to an urgent medical need.

The hydrological response of steep slopes catchments is strongly conditioned by the connectivity of subsurface preferential flows. The objective of this research is to investigate the role played by stemflow infiltration in subsurface water flow dynamics, focusing on a forested hillslope located in an Aleppo pine Mediterranean forest (Pinus halepensis, Mill.) located at Sierra Calderona, Valencia province, Spain. We combined stemflow artificial experiments with ground-penetrating radar (GPR) techniques as a non-invasive method to investigate stemflow-induced preferential flow paths activated by different trees and the related hydrological connectivity at the hillslope scale. Our observations allowed us to identify different dynamics associated with the initiation of stemflow and then lateral preferential flow, including the activation of connected preferential flow paths in soils that received stemflow water from different trees. These observations provided empirical evidence of the role of stemflow in the formation of lateral preferential flow networks. Our measurements allow estimations of flow velocities and new insight on the magnitude of stem-induced lateral preferential flow paths. The applied protocol offers a simple, repeatable and non-invasive way to conceptualize hillslope responses to rainstorms.

Increasing volumes of mismanaged plastic waste have resulted in millions of tons of plastics entering the environment. While recent research has made substantial progress in determining the fate and transport of microplastics (MP) in river systems and their subsequent discharge to the worlds oceans, much less is known about the subsurface fate of MP as they enter soils, (riverine) sediments and global groundwater resources. Initial studies have identified MP in selected groundwater samples and there is great interest to understand entry pathyways of MPs into soils, in particular through agricultural pathways. The mechanisms of MP release from agricultural sources such as seed and agrochemical encapsulations or sewage sludges as well as the total quantity, spatial distribution, residence time scales as well as the impact of MP on soils and subsequently groundwater ecosystems are completely unknown. There is hence a critical need to study the role of soils and groundwater systems as a long-term sink for plastic pollution, including the development of legacy risks.Here we identify the significance of various entry pathways for MP into subsurface ecosystems, integrating experimental and model based quantifications of MP transport through streambed sediments with quantifications of MP inputs into agricultural soils through irrigation with river water. We present first results of MP impacts on the functioning of subsurface ecosystem services, by the particular example of MP exposure impacts on the behaviour of bioturbating invertebrates and the subsequent consequences for sediment biogeochemical cycling in order to draw attention to the potential risks for vital soil and groundwater ecosystem services.We complement this site specific mechanistic process understanding with global estimates of mismanaged plastic waste accumulation in river basins to quantify MP catchment wide loads available for leakage into soils and present first results of our recently started participatory approach that aims to develop a baseline of MP pollution in aquifers across the world. Such baseline data is imperative to increase our understanding of MP fate and transport processes, MP uptake by groundwater organisms and the interaction of MP with nutrients and potential co-contaminants. Our specifically tailored protocol allows for standardized MP sampling in boreholes, springs or wells across a wide range of geological settings and land cover classes. We invite and encourage the community to contribute to this global effort in order to enable estimates of the magnitude and expected time scales of soil and groundwater MP contamination.

A perennial criticism of provisioning ecotourism is that it alters the natural behavior and ecology of the target species by providing an artificial food source. Here we evaluate its impact on the long-term site fidelity patterns of tiger sharks in French Polynesia. We hypothesized that a significant impact of provisioning would lead to (1) increases in individual site fidelity over time, and (2) an increase in the number of resident individuals over time. Of 53 individuals photo-identified and monitored during > 500 dives over five years, 10 individuals accounted for > 75% of all sightings, whereas 35 sharks were sighted very infrequently. Even the most frequently observed tiger sharks exhibited overall low fidelity at the site and showed no increase in site fidelity over time. Furthermore, the number of tiger sharks sighted during each dive did not increase. The observed patterns of tiger shark sightings were best explained by natural movements, including general roaming within home ranges along the coastline and seasonal migrations. Despite the apparent lack of impact of provisioning ecotourism on tiger shark ecology in Tahitian waters, it would be prudent to implement a strict code of conduct during any future provisioning activities to maximize the safety of participants and animals involved.

Acoustic telemetry has helped overcome many of the challenges faced when studying the movement ecology of aquatic species, allowing to obtain unprecedented amounts of data. This has made it into one of the most widely used methods nowadays. Many ways to analyse acoustic telemetry data have been made available and deciding on how to analyse the data requires considering the type of research objectives, relevant properties of the data (e.g., resolution, study design, equipment), habits of the study species, researcher experience, among others. To ease this decision process, here we showcase (1) some of the methods used to estimate pseudo-positions and positions from raw acoustic telemetry data, (2) methods to estimate residency and (3) methods to estimate two-dimensional home and occurrence range using geometric or hull-based methods and density-distribution methods, a network-based approach, and three-dimensional methods. We provide examples of some of these were tested using a sample of real data. With this we intend to provide the necessary background for the selection of the method(s) that better fit specific research objectives when using acoustic telemetry. LCF/BQ/DI20/11780001; POSEUR-03-2215-FC-000047; LA/P/0101/2020; info:eu-repo/semantics/publishedVersion

20 pages, 3 tables, 5 figures.-- Samantha Andrzejaczek ... et al.-- Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC), Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements, Data analysis was funded by the Bertarelli Foundation through the Marine Science program through grants to D.J.C., B.A.B., and S.A. D.J.C. is also funded through Research England, UK. S.A. and B.A.B. thank the Moore Foundation and the Packard Foundation. F.G.-M. thanks the Instituto Politecnico Nacional for fellowships (COFAA, EDI). S.B.W. thanks funding from the Darwin Initiative (DPLUS046). A.D.M.D. acknowledges funding from the Research and Conservation Budget at Georgia Aquarium, including philanthropic gifts from several anonymous donors. K.F. acknowledges funding from the Rolex Awards for Enterprise and the Whitley Fund for Nature

Amblyomin-X is a Kunitz-type FXa inhibitor identified through the transcriptome analysis of the salivary gland from Amblyomma sculptum tick. This protein consists of two domains of equivalent size, triggers apoptosis in different tumor cell lines, and promotes regression of tumor growth, and reduction of metastasis. To study the structural properties and functional roles of the N-terminal (N-ter) and C-terminal (C-ter) domains of Amblyomin-X, we synthesized them by solid-phase peptide synthesis, solved the X-Ray crystallographic structure of the N-ter domain, confirming its Kunitz-type signature, and studied their biological properties. We show here that the C-ter domain is responsible for the uptake of Amblyomin-X by tumor cells and highlight the ability of this domain to deliver intracellular cargo by the strong enhancement of the intracellular detection of molecules with low cellular-uptake efficiency (p15) after their coupling with the C-ter domain. In contrast, the N-ter Kunitz domain of Amblyomin-X is not capable of crossing through the cell membrane but is associated with tumor cell cytotoxicity when it is microinjected into the cells or fused to TAT cell-penetrating peptide. Additionally, we identify the minimum length C-terminal domain named F2C able to enter in the SK-MEL-28 cells and induces dynein chains gene expression modulation, a molecular motor that plays a role in the uptake and intracellular trafficking of Amblyomin-X.

Mitochondria, apart from being the powerhouses of our cells, are key players in cellular metabolism and homeostasis. As a consequence, the core bioenergetics and metabolism of mitochondria are well studied considering the role that dysregulated mitochondrial metabolism plays in disease. Flux Balance Analysis, used in conjunction with metabolic model reconstructions is a powerful computational tool that predicts metabolism. The resulting quantitative descriptions of metabolic dysregulation not only allows current hypotheses to be testedin silico, but can also lead to novel model driven hypotheses that can be experimentally verified. Several metabolic reconstructions for human and mouse metabolism exist, but no model specific to mouse mitochondrial metabolism exists. Here, we have created a mouse-specific mitochondrial metabolic model, mitoMouse, which is based on the high-quality human MitoCore mode. MitoMouse contains 390 genes and 445 metabolites involved in 560 unique reactions, is able to model central carbon metabolism and has been extended to contain reduction of the CoQ complex of Oxidative Phosphorylation by the enzyme DHODH. MitoMOuse was validated to accurately model the important metabolic switch involving CoQ reduction resulting from increased malate import, as recently shown in mouse cardiac tissue. We expect this model to be of immense interest and relevance to researchers working on murine mitochondrial metabolism.

International audience; Designing appropriate management plans requires knowledge of both the dispersal ability and what has shaped the current distribution of the species under consideration. Here, we investigated the evolutionary history of the endangered gray reef shark (Carcharhinus amblyrhynchos) across its range by sequencing thousands of RADseq loci in 173 individuals in the Indo-Pacific (IP). We first bring evidence of the occurrence of a range expansion (RE) originating close to the Indo-Australian Archipelago (IAA) where two stepping-stone waves (east and westward) colonized almost the entire IP. Coalescent modeling additionally highlighted a homogenous connectivity (Nm ~ 10 per generation) throughout the range, and isolation by distance model suggested the absence of barriers to dispersal despite the affinity of C. amblyrhynchos to coral reefs. This coincides with long-distance swims previously recorded, suggesting that the strong genetic structure at the IP scale (FST ~ 0.56 between its ends) is the consequence of its broad current distribution and organization in a large number of demes. Our results strongly suggest that management plans for the gray reef shark should be designed on a range-wide rather than a local scale due to its continuous genetic structure. We further contrasted these results with those obtained previously for the sympatric but strictly lagoon-associated Carcharhinus melanopterus, known for its restricted dispersal ability. Carcharhinus melanopterus exhibits a similar RE dynamic but is characterized by a stronger genetic structure and a nonhomogeneous connectivity largely dependent on local coral reefs availability. This sheds new light on shark evolution, emphasizing the roles of IAA as source of biodiversity and of life-history traits in shaping the extent of genetic structure and diversity.

MicroRNAs (miRNAs) are small noncoding RNAs that can play critical roles in regulating various cellular processes, including during many parasitic infections. Here, we report a regulatory role for miR-34c-3p in cAMP-independent regulation of host cell protein kinase A (PKA) activity in Theileria annulata-infected bovine leukocytes. We identified prkar2b (cAMP-dependent protein kinase A type II-beta regulatory subunit) as a novel miR-34c-3p target gene and demonstrate how infection-induced upregulation of miR-34c-3p repressed PRKAR2B expression to increase PKA activity. As a result, the disseminating tumorlike phenotype of T. annulata-transformed macrophages is enhanced. Finally, we extend our observations to Plasmodium falciparum-parasitized red blood cells, where infection-induced augmentation in miR-34c-3p levels led to a drop in the amount of prkar2b mRNA and increased PKA activity. Collectively, our findings represent a novel cAMP-independent way of regulating host cell PKA activity in infections by Theileria and Plasmodium parasites. IMPORTANCE Small microRNA levels are altered in many diseases, including those caused by parasites. Here, we describe how infection by two important animal and human parasites, Theileria annulata and Plasmodium falciparum, induce changes in infected host cell miR-34c-3p levels to regulate host cell PKA kinase activity by targeting mammalian prkar2b. Infection-induced changes in miR-34c-3p levels provide a novel epigenetic mechanism for regulating host cell PKA activity independent of fluxes in cAMP to both aggravate tumor dissemination and improve parasite fitness.

The Organelle Paralogy Hypothesis (OPH) posits a mechanism to explain the evolution of non-endosymbiotically derived organelles, predicting that lineage-specific pathways organelles should result when identity-encoding membrane trafficking components duplicate and co-evolve. Here we investigate the presence of such lineage-specific membrane-trafficking machinery paralogs in the globally important lineage of parasites, the Apicomplexa. Using a new phylogenetic workflow, we are able to identify 18 novel paralogs of known membrane-trafficking machinery, the emergence of several of which correlate with the presence of new endomembrane organelles in apicomplexans or their larger lineage. Gene coregulation analysis of a large set of membrane-trafficking proteins in Toxoplasma both corroborate known molecular cell biological interactions between characterized machinery and suggest involvement of many of these new components into established pathways for biogenesis of or trafficking to the microneme and rhoptry invasion organelles. Moreover, focused molecular parasitological analysis of the apicomplexan Arf-like small GTPases, and the ArlX3 protein specifically, revealed a novel post-Golgi trafficking pathways involved in delivery of proteins to micronemes and rhoptries, with knock down demonstrating reduced invasion capacity. The totality of our data has identified an unforeseen post-Golgi trafficking pathway in apicomplexans and is consistent with the OPH mechanism acting to produce novel endomembrane pathways or organelles at various evolutionary stages across the Alveolate lineage.Significance statementThe mechanism of non-endosymbiotic organelle evolution has been relatively poorly explored and yet is relevant to many eukaryotic compartments, including the endomembrane system. The Organelle Paralogy Hypothesis predicts novel lineage-specific paralogs evolutionarily concurrent with emergence of new endomembrane organelles or pathways. By investigating this phenomenon in the apicomplexan parasites and their relatives, we identify and profile over a dozen new trafficking factors, several correlating with emergence of lineage-specific organelles. Cell biological study of one such factor demonstrates the existence of a novel post-Golgi trafficking pathway for components to the invasion organelles in the parasiteToxoplasma gondii. This work reveals how non-endosymbiotic organelle evolution has shaped cellular novelty in this lineage, relevant both to global health and fundamental evolutionary biology.

Resume Introduction La chirurgie rachidienne est l’une des specialites a haut risque medicolegal avec un recours en justice tous les 17 mois par praticien. L’une des complications redoutees est l’hematome epidural complique d’un deficit postoperatoire. La gestion de cette complication reste debattue. Aussi, nous avons mene une etude retrospective de la base de donnees d’un assureur medical, afin d’evaluer les facteurs perioperatoires influencant la mise en cause du chirurgien ou de l’equipe paramedicale, lors d’une expertise, en cas d’hematome epidural postoperatoire symptomatique. Hypothese Identifier les facteurs influencant la mise en cause de l’equipe medicale en cas de survenue d’un hematome epidural postoperatoire symptomatique. Materiel et methode Nous avons analyse retrospectivement le plus grand registre francais d’expertises medicolegales entre 2011 et 2018. En saisissant, dans cette base de donnees, les mots-cles suivants : « chirurgie rachidienne », « complications » et « hematome epidural », nous avons identifie 68 dossiers. Apres lecture de chaque dossier, 14 correspondaient veritablement au sujet etudie. Pour chaque patient, nous avons recueilli les donnees perioperatoires, les complications survenues, dont les deficits neurologiques, ainsi que leur evolution. Resultats Un seul chirurgien a ete mis en cause et reconnu fautif pour absence de reprise chirurgicale dans un delai raisonnable (delai de reprise de 11 jours). Dans deux cas, la responsabilite d’une infirmiere du service de chirurgie a ete mise en cause suite a un retard d’appel du chirurgien par rapport a l’apparition des symptomes. Dans les autres cas (11 patients, 79 %), la survenue d’un hematome epidural symptomatique a ete consideree comme un accident medical non fautif sans implication du chirurgien. La presence d’un drain n’a pas eu de consequence medicolegale parmi les dossiers examines. Conclusion L’element cle dans la decision medicolegale est le delai de reactivite des equipes soignantes, particulierement le delai entre la survenue des symptomes et la reprise chirurgicale. D’apres ces donnees d’expertise, la mise en place d’un drain n’est pas rentree en compte dans la discussion medicolegale en cas d’hematome epidural postoperatoire symptomatique. Niveau de preuve II ; etude retrospective pronostique, investigation des caracteristiques des patients et leur impact sur le devenir fonctionnel.

The tourism activities linked to artificial provisioning of blacktip reef sharks (Carcharhinus melanopterus) and pink whiprays (Pateobatis fai) on a specific site in French Polynesia were suddenly and completely stopped due to a COVID-19 lockdown that lasted 6 weeks from March 20 until April 30, 2020. Using both drone footage and underwater counting, we were able to track the abundance of those two species before, during, and after reopening and thus investigate the impact of provisioning on wild shark populations. The absence of any stimulus during this long period resulted in almost total desertion of the site by the elasmobranchs. However, 1 day prior to reopening, some individuals of both species positively reacted to the single acoustic stimulus of an engine boat, showing the resilience of conditioning, and some elasmobranchs reacted to acoustic and olfactive stimuli linked to the provisioning practice from the first day after reopening. During the first 2 weeks after reopening, the abundance of both species remained at reduced levels comparable to those observed between 2008 and 2010 for sharks;i.e., around 9 animals in the presence of local tourists. Pre-lockdown abundance levels, reaching approximatively 15 individuals for sharks and 10 for rays, were considered restored 1 and 2 months after reopening for blacktip reef sharks and pink whiprays, respectively. These findings improve our capacity to better understand the potential effects of artificial provisioning tourism on the abundance of elasmobranchs by showing that conditioning is resilient for several weeks, suggesting that intermittent interruption of elasmobranchs feeding would not really help to decrease its impact on animal welfare.

Although microplastics (MP) archiving processes are suggested in river sediments, few studies have analysed temporal records of MP in sediment cores. However, sediment cores give access to past anthropogenic contamination on basin and multi-decade scales. This work focus on the MP contamination (25 – 5 000 µm) in sedimentary archives of the Rhône River, recovered in 2021 upstream and downstream of Lyon. Sediment cores were described and sampled by 4 cm slides. Based on radionuclides analysis age-models were proposed. MP were extracted from about 10 g ww of sediment sieved at 5 000 µm, using density separation and oxidative degradation of organic matter, and then filtered on aluminum oxide membrane filters for µFTIR imaging analysis. 25 µm pixel resolution maps were performed and MP were characterised using siMPle. Results revealed a significant impact of the Lyon metropolis on MP content from 1986 to present with range between 800 and 3'750 particles/kg/year in the upstream station and between 3'180 and 73'000 particles/kg/year in the downstream station. Furthermore, results show a significant difference in the polymers composition between stations. In the upstream one, polypropylene (PP) and polyethylene (PE) are the most abundant polymers with respectively 70% and 20% of the MP, whereas in the downstream one, most represented polymers are PP (53%) and polyvinyl chloride (PVC) (33%). Over the recorded period, the MP content is maximum around 2010 in both stations. In the downstream station, PVC content shows a decreasing trend since the mid-1980s. Using well-dated and well-described sediment cores we reconstituted temporal evolution of MP pollution along a river section crossed by a highly industrialized and urbanized area. We highlighted contrasted trends and MP abundances and the diversity of polymers in relation with the influence of the urban area. Also see: https://micro2022.sciencesconf.org/426792/document, In MICRO 2022, Online Atlas Edition: Plastic Pollution from MACRO to nano

Microplastic (MP) pollution has become a key concern in rivers and streambed sediments in recent years. Due to the heterogeneity and complexity of particle transfer in river corridors, the identification of MP distributions (concentrations and types) at the sediment-water interface and the impact of such contamination on the related ecosystem is a major challenge. Within the framework of the Aquaplast Project, we investigate transport and accumulation mechanisms of MP along gravel-bed rivers. We focus on a challenging case: the Ain River (France) because (i) its catchment area includes major plastic industries, (ii) it is influenced by a diversity of urban, rural and water recreation activities, (iii) and it is equipped with several dams potentially trapping MPs. The land-use and the distribution of plastic factories were analysed using GIS in order to identify potential MP sources in the catchment area. In the field, fourteen key sites were sampled at -20cm under the water-sediment interface (upstream and downstream of dams and plastic factories). Sediment grain size, stream temperature, conductivity, piezometric heads and MPs concentrations were measured at each site in order to describe the hydro-sedimentological conditions influencing MP transport and deposition. This work highlighted the accumulation efficiency of coarse alluvial bars for MPs. MPs hotspots were mainly found along the most urbanized and industrialized sections. A significant breakpoint was also identified in the area of the main dams, indicating their major role in the trapping of MPs. The variability in MPs concentrations and types suggested a local origin for most particles. Finally, a particular feature was the dominance of hard plastics, especially polypropylene (PP), which appears as an industrial heritage. Also see: https://micro2022.sciencesconf.org/422186/document, In MICRO 2022, Online Atlas Edition: Plastic Pollution from MACRO to nano

Designing appropriate management plans requires knowledge of both the dispersal ability and what has shaped the current distribution of the species under consideration. Here we investigated the evolutionary history of the endangered grey reef shark (Carcharhinus amblyrhynchos) across its range by sequencing thousands of RAD-seq loci in 173 individuals in the Indo-Pacific (IP) . We first bring evidence of the occurrence of a range expansion (RE) originating close to the Indo-Australian Archipelago (IAA) where two stepping-stone waves (east and westward) colonized almost the entire IP. Coalescent modeling additionally highlighted a homogenous connectivity (Nm~10 per generation) throughout the range, and an isolation by distance model suggested the absence of barriers to dispersal despite the affinity of C. amblyrhynchos to coral reefs. This coincides with long-distance swims previously recorded, suggesting that the strong genetic structure at the IP scale (FST ~ 0.56 between its ends) is the consequence of its broad current distribution and organization in a large number of demes. Our results strongly suggest that management plans for the grey reef shark should be designed on a range-wide rather than a local scale due to its continuous genetic structure. We further contrasted these results with those obtained previously for the sympatric but strictly lagoon-associated Carcharhinus melanopterus, known for its restricted dispersal ability. C. melanopterus exhibits similar RE dynamic, but is characterized by stronger genetic structure and a non-homogeneous connectivity largely dependent on local coral reefs availability. This sheds new light on shark evolution, emphasizing the roles of IAA as source of biodiversity and of life history traits in shaping the extent of genetic structure and diversity.

Knowledge about spatial and temporal variability in the distribution and abundance of predators is necessary to adapt measures to mitigate human–wildlife interactions. Acoustic telemetry and network analyses were used to investigate the spatial ecology of bull sharks, the species responsible for most shark bites in Reunion Island, one of the world's shark bite hotspots. The west coast of the island was not used uniformly by every individual, with size predicting the movements of sharks along the coast. Node-based metrics – closeness, node strength, and cumulated continuous residency times – derived from up to 181 monthly movement networks from 20 individuals, revealed that smaller sharks (

Recent acoustic telemetry positioning systems are able to reconstruct the positions and trajectories of organisms at a scale of a few centimeters to a few meters. However, they present several logistical constraints including receiver maintenance, calibration procedures and limited access to real-time data. We present here a novel, easy-to-deploy, energy self-sufficient underwater positioning system based on the time difference of arrival (TDOA) algorithm and the Global System for Mobile (GSM) communication technology, capable of locating tagged marine organisms in real time. We provide an illustration of the application of this system with empirical examples using continuous and coded tags in fish and benthic invertebrates. In situ experimental tests of the operational system demonstrated similar performances to currently available acoustic positioning systems, with a global positioning error of 7.13 ± 5.80 m (mean ± SD) and one-third of the pings can be localized within 278 m of the farthest buoy. Despite some required improvements, this prototype is designed to be autonomous and can be deployed from the surface in various environments (rivers, lakes, and oceans). It was proven to be useful to monitor a wide variety of species (benthic and pelagic) in real time. Its real-time property can be used to rapidly detect system failure, optimize deployment design, or for ecological or conservation applications.

Dam reservoirs can strongly influence the spatial distribution of sediment pollution by microplastics (MP). The Villerest reservoir (Loire River, 36 km long) is a good candidate to study the relationship between MP pollution and hydrosedimentary processes. Sediments were collected from the dam-controlled river section and from 3 km downstream. Geomorphological and sedimentological analyses were performed and microplastics were analysed using µFTIR imaging (polymer identification for particle sizes ≥ 25 µm). This paper highlights strong MP levels (on an order of 10

Many molecular targets for cancer therapy are located in the cytosol. Therapeutic macromolecules are generally not able to spontaneously translocate across membranes to reach these cytosolic targets. Therefore a strong need exists for tools that enhance cytosolic delivery. Shiga toxin B-subunit (STxB) is used to deliver therapeutic principles to disease-relevant cells that express its receptor, the glycolipid Gb3. Based on its naturally existing membrane translocation capacity, STxB delivers antigens to the cytosol of Gb3-positive dendritic cells, leading to the induction of CD8+ T cells. Here, we have explored the possibility of further increasing the membrane translocation of STxB to enable other therapeutic applications. For this, our capacity to synthesize STxB chemically was exploited to introduce unnatural amino acids at different positions of the protein. These were then functionalized with hydrophobic entities to locally destabilize endosomal membranes. Intracellular trafficking of these functionalized STxB was measured by confocal microscopy and their cytosolic arrival with a recently developed highly robust, sensitive, and quantitative translocation assay. From different types of hydrophobic moieties that were linked to STxB, the most efficient configuration was determined. STxB translocation was increased by a factor of 2.5, paving the path for new biomedical opportunities.

Observers of the Polynesian Shark Observatory (ORP), a citizen science network organized mainly through the Polynesian dive centers, collected an unprecedented amount of data from more than 13,916 dives spanning 43% of the islands of French Polynesia between July 8, 2011, and April 11, 2018. The objective for this type of data collection, which is not accessible within the standard research context, was to provide a unique dataset, and the opportunity to explore the specific diversity, distribution, seasonality and abundance of many elasmobranch species spread out throughout the territory of French Polynesia. Since the data are based on random citizen observations, the spatial distribution was biased toward the most frequented sites and islands where scuba diving is most developed. Overall, the increase in observed abundance of rays and sharks observed in French Polynesia, and the three most sampled islands as well as the high specific diversity recorded for the region, provide first evidence on the effectiveness of the French Polynesia’s Shark Sanctuary, established in 2006. These data, collected randomly by the volunteers, also provide insights into potential movement patterns and site fidelity of some of the more commonly observed species. While no final conclusions can be drawn, it is clear that the network of volunteers that regularly contributes information to the Polynesian Shark Observatory plays a very important role in the delivery of much needed data for conservation and management action, as well as providing perspectives for new directions in research on sharks and rays in French Polynesia.

Recent applications require vertical chip stacking to increase the performance of many devices without the need of advanced node components. Image sensors and vision systems will embed more and more smart functions, for instance, image processing, object recognition, and movement detection. In this perspective, the combination of Cu-to-Cu direct hybrid bonding technology with Through-Silicon-Via (TSV) will allow 3D interconnection between pixels and the associated computing and memory structures, each function fabricated on a separate wafer. Wafer-to-wafer hybrid bonding was achieved with multi-pitch design—1–4 µm—of single levels of Cu damascene patterned on 300 mm silicon substrates. Defect-free bonding, as far as the extreme edge of the wafer, was demonstrated on a stack with three wafers. Middle wafers thinning was done with grinding only and with a thickness uniformity (TTV)

International audience; Electrochemical impedance spectroscopy (EIS) is widely accepted as an effective and non-destructive method to assess cell health during cell-culture. However, there is a lack of compact devices compatible with microfluidic integration and microscopy that could provide the real-time and non-invasive monitoring of cell-cultures using EIS. In this paper, we reported the design and characterization of a modular EIS testing system based on a patented technology. This device was fabricated using easily processable methodologies including screen-printing of the impedance electrodes and molding or micromachining of the cell culture chamber with an easy assembly procedure. Accordingly, to obtain processable, biocompatible and sterilizable electrode materials that lower the impact of interfacial impedance on TEER (Transepithelial electrical resistance) measurements, and to enable concomitant microscopy observations, we optimized the formulation of the electrode inks and the design of the EIS electrodes, respectively. First, electrode materials were based on carbon biocompatible inks enriched with IrOx particles to obtain low interfacial impedance electrodes approaching the performances of classical non-biocompatible Ag/AgCl second-species electrodes. Secondly, we proposed three original electrode designs, which were compared to classical disk electrodes that were optically compatible with microscopy. We assessed the impact of the electrode design on the response of the impedance sensor using COMSOL Multiphysics. Finally, the performance of the impedance spectroscopy devices was assessed in vitro using human airway epithelial cell cultures.

In heparin, some 3-O-sulfated sequences do not meet the structural requirements of the ATIII binding pentasaccharide. These “non-conventional” sequences are the object of this study. In a previous paper (Mourier P. Heparinase digestion of 3-O-sulfated sequences: selective heparinase II digestion for separation and identification of binding sequences present in ATIII affinity fractions of bovine intestine heparins), we demonstrated that unsaturated 3-O-sulfated disaccharides detected in exhaustive heparin digests were specifically cleaved by heparinase I. Consequently, building blocks analyses of heparins using heparinases I+II+III digestion could be compared with experiments where only heparinase II is used. In these latter conditions of depolymerization, the 3-O-sulfated sequences digested into unsaturated 3-O-sulfated disaccharides with heparinases I+II+III, were heparinase II-resistant on their non-reducing side, resulting in longer new building blocks. These properties were used to study the structural neighborhood of these 3-O-sulfated moieties, which have still-undefined biological functions. In this part, heparinases I+II+III and heparinase II digestions of porcine mucosa, bovine mucosa and bovine lung heparins were compared in six fractions of increasing affinity for ATIII. Tagging of building blocks by reductive amination with sulfanilic acid was used. The distribution of 3-O-sulfated building blocks in the ATIII affinity fractions was used to examine the ATIII binding of these sequences.

Binding to antithrombin-III (ATIII) determines the anticoagulant activity of heparin. The complexes formed between heparin and ATIII result from a specific pentasaccharide sequence containing a 3-O-sulfated glucosamine in medium position. Building block analysis of heparins, following heparinase digestion, is a critical method in quality control that provides a simple structural characterization of a complex product. Hence, in these applications, study of the digestion of 3-O-sulfated moieties merits special attention. With heparinase II, specific inhibition of cleavage of the non-reducing bond of 3-O-sulfated units is observed. This specificity was erroneously generalized to other heparinases when it was observed that in exhaustive digests of heparins with the heparinase mixture, resistant 3-O-sulfated tetrasaccharides were also obtained from the specific ATIII-binding pentasaccharides. In fact, the detection of unsaturated 3-O-sulfated disaccharides in digests of heparin by heparinases I+II+III, resulting from the cleavage of the 3-O sulfated unit by heparinase I in non-conventional sequences, shows that this inhibition has exceptions. Thus, in experiments where heparinase II is selectively applied, these sequences can only be digested into tetra- or hexasaccharides where the 3-O-sulfated glucosamine is shifted on the reducing end. Heparinase I+II+III and heparinase II digests with additional tagging by reductive amination with sulfanilic acid were used to study the structural neighborhood of 3-O-sulfated disaccharides in bovine mucosal heparin fractions with increasing affinity for ATIII. The 3-O-sulfated disaccharides detected in heparinase I+II+III digests turn into numerous specific 3-O-sulfated tetrasaccharides in heparinase II digests. Additionally, ATIII-binding pentasaccharides with an extra 3-O-sulfate at the reducing glucosamine are detected in fractions of highest affinity as heparinase II-resistant hexasaccharides with two consecutive 3-O-sulfated units.

Microplastic pollution has been found to be ubiquitous in freshwater ecosystems around the world, with global models predicting river network contributions to the oceans to present major and still increasing sources of marine plastic waste. While previous research has to a large degree focussed on identifying potential sources of plastic pollution to freshwater ecosystems (such as wastewater treatment plants, storm sewers, urban areas), and attributing these to observed microplastic pollution patterns in river corridors, little is known under what conditions potential pollution sources become activated and connected to surface waters, and how the fluvial transport of different micro- and nanoplastic size fractions determines spatial patterns of plastics along river networks, including long-term deposition, storage and potential resuspension.This paper integrates field-based evidence of our global river microplastic survey and several comparative large river network studies (including the rivers Ganges, Boulder Creek, Rhone, and others) with river basin to global scale plastic fate and transport models to identify major drivers of hotspots and hot moments of riverine plastic pollution. Our results highlight under what conditions prior knowledge of the source distributions of plastic pollution carries significant predictive capacity for expected river corridor microplastic concentrations and when (and where) these patters can get transformed substantially by fluvial transport (and transformation) processes. Fusing this experimental evidence with our model predictions revealed significant differences in the downstream footprint, longevity and legacy of dominant sources and transport controls of plastics in the water column and in streambed sediments, driven by gravitational settling, hyporheic exchange flow and resuspension processes.

In the past, we developed a method inferring physicochemical properties from ion mobility mass spectrometry (IM-MS) data from polydisperse synthetic homopolymers. We extend here the method to biomolecules that are generally monodisperse. Similarities in the IM-MS behavior were illustrated on proteins and peptides. This allows one to identify ionic species for which intramolecular interactions lead to specific structures.

Additional file 3: Figure S17. DBP1 alignment. Complete alignment of DBP1 protein sequences. The presence of the DBL domain (Pfam: PF0311) and the trans-membrane domain is indicated.