Shape and surface variations of syphon openings during complete tidal cycles in Mya arenaria in the intertidal zone

Since the degree of syphonal opening can be an index of the pumping activity, the shape and the surface of syphon openings in Mya arenaria were filmed with an underwater camera at two stations in the middle of the intertidal zone. The individuals were perpendicularly oriented to the main current direction or parallel with the inhalant syphon upstream during flood tide, causing refiltration risks during ebb tide. The surface of the inhalant opening (SI) was strongly reduced with increasing current speeds. Its shape (XI) varied with the individual's orientation and had a tendency to become more circular with time. The surface of the exhalant opening (SE) decreased and its shape (XE) flattened with increasing current velocity and with time. However, variations of XI and XE were weak. Current direction had no significant effect on SI, SE, and XE, but did cause a strong decrease of the SE/SI ratio during ebb in individuals exposed to important refiltration risks during ebb tide. Significant negative correlations between stomach content in phaeopigments and SI and SE suggest that a syphonal constriction could contribute to more efficient feeding. For parallel oriented individuals, the decreases of SE, SE/SI, and XE during ebb can then be interpreted as an attempt to deviate or increase the excurrent velocity relative to the incurrent so as to limit refiltration. We suggest that decreases in opening surface and shape may serve, above all, to increase syphon current jet velocity in syphonate bivalves

Diffuse transport in clay media: µm to nm scale characterization of pore space and mineral spatial organization

In the framework of radioactive waste repository, clayrock formations are foreseen as barrier materials due to their diffusion properties. In clay materials, the dominant transport mode is diffusive and depends mainly on various parameters such as the mobility of the species in water, the accessible porosity, the pore space geometry and the retardation as a result of reactions such as sorption or ion exchange (Tournassat and Appelo, 2011). In this way, the European CATCLAY project (EURATOM FP7), in the context with research on transport in porous materials, was proposed to describe the cation migration processes in natural clayrocks. The project is structured along 3 RTD workpackages, combining modeling and experimental studies from a simpler, analogous system (monophasic compacted clay system) to clayrocks (Callovo-Oxfordian argillites, Opalinus Clay and Boom Clay). Part of this experimental studies focuses on small scale structure (µm - nm) property of rocks in order to determine how the spatial distribution of mineral and pores at small scales can influence diffusion driven transport of sorbing cations. The present study focuses on compacted illite properties (simpler analogous system) in hopes to extent this study to the natural clayrock formation. Illite was chosen by the way that is the main constituent of clayrock. Compacted illite material represents thus an analogy with the clay matrix constituting clay-rocks. Our approach is mainly based on imaging the small scale structural organization of compacted illite material and analyzing the obtained images in order to extract information on pore space and mineral spatial distribution. Techniques for imaging the texture of illite material like water saturated, in compacted state, were first developed. The first step was to improve classic resin impregnation method in order to preserve the texture without losing the clay confinement and modifying the pore space geometry. This has been done by taking into account the molecule size of the monomer, the low viscosity, the dipole moment (adapted for the clayrock with swelling clay content) and the controlled time polymerization. MMA monomer proved to be the most suitable resin in our study. The small scale structure of impregnated sample was then imaged in 2D using Transmission Electron Microscopy (TEM) and in 3D using Focused Ion Beam coupled to Scanning Electron Microscopy (FIB/SEM). For TEM observations, a set of ultra-thin serial sections (50 - 100 nm) were cut using a microtome. A set of 2D images were then acquired using a resolution ranged between 100 nm and 10 Å. TEM images clearly show us the multi-scale organization of clay materials (Figure 1 and 2); we observe the 10 Å spacing sheets constituting the illite particles, nanometer size illite clay particles more or less aggregated and the surrounding pores having a size ranging from few hundred nanometers to nanometer. FIB/SEM analysis is currently in progress. From FIB/SEM, a set of serial images can be acquired using the "slice and view" method (Keller et al., 2011). Then, 2D FIB/SEM images need to be aligned to reconstruct a 3D volume. Image resolution is limited to 10-20 nm. Both methodologies (FIB-tomography and TEM techniques) are thus complementary method for the up-scaling characterization of the structural organization of compacted clayey materials. TEM images analysis allow to scale down the resolution size since only a part of the pore space could thus be imaged with FIB/SEM method (Keller et al., 2011). Viewing and performing a qualitative description of images constitute a major result and can help us to better understand how the transfer pathways and retention sites are organized in the porous media. Thanks to image analysis method, pores and minerals can be thresholded from grey level TEM and FIB/SEM images. Quantitative parameters can be then computed based from segmented images. In this objective, we currently focus our analysis in order to determine the size and the morphology of pores, the main geometrical features of clay particles (number of layers, size, shape...), the spatial distribution of clay particles (individual/aggregates, type of contact between the clay particles, orientation...) and the pores connectivity. Quantitative parameters are expected to be used in various transfer modeling approaches. This will be done in the framework of SIMISOL project which is focused on the modeling cation diffusion from atomic to nanometer scales

Karstic geomorphology of carbonate Ouarsenis Piedmont (Boukadir region, Chelif) in Algeria: The role of the Messinian Salinity Crisis

peer reviewedAlgeria displays various karst landscapes due to its diversity in lithology, relief, age and climate. On 16th June 1988, in the northwest of Algeria, a 60 m wide sudden collapse occurred in the Chelif Basin about 1 km north of a marginal carbonate platform. Despite this large event and visible karst dissolutions in the platform, this region has not been classified among the karst areas of Algeria yet. Our study focuses on this Messinian carbonates that form the northern piedmont of the Ouarsenis Mountain range and are covered to the north by Plio-Quaternary deposits. The geological and geomorphological data that we collected reveal that the present-day karstification is limited at the outcropping surface. Present-day carbonate dissolution is impeded by the absence of a topsoil supplying CO2 and by the presence of a calcrete improving the drainage. Although dissolution at depth is generally diffuse due to the porous and friable nature of the carbonates, two factors can, on the contrary, concentrate water infiltration: the presence of a network of more or less subvertical fractures and, occasionally, at the surface, the absence of calcrete, independently of the fracturing nodes There are few ponors and sinkholes present. The endokarst is still present as evidenced by rare caves. In epikarst, solution pipes and shelter caves are prevalent. The later results from differential weathering in relation with the carbonate facies and the progressive calcrete cementation in valleys and slopes during river incision. Near valley bottom, shelters are arranged in steps like terraces. This morphology is related to base-level lowering in relation with the deformation and uplift of the Ouarsenis piedmont. Near the southern edge of the Chelif Basin, deep (>55m) karstic voids are present and associated with paleo-valley incision presently burried by Plio-Quaternary deposits. We interpreted the large 1988 collapse in relation with this paleokarst and propose that its triggering was partly induced by a lowering of the aquifers due to a deficit of precipitation. The deep paleokarst formation and the buried river incision are attributed to the low base-level during the Messinian Salinity Crisis (5.97–5.33 Ma). We evidenced an upper karstic dissolution level filled that is attributed to a per ascendum evolution of the karstic phreatic network in relation with the following Pliocene aggradation

Novel 8-nitroquinolin-2(1H)-ones as NTR-bioactivated antikinetoplastid molecules:Synthesis, electrochemical and SAR study

International audienceTo study the antiparasitic 8-nitroquinolin-2(1H)-one pharmacophore, a series of 31 derivatives was synthesized in 1-5 steps and evaluated in vitro against both Leishmania infantum and Trypanosoma brucei brucei. In parallel, the reduction potential of all molecules was measured by cyclic voltammetry. Structure-activity relationships first indicated that antileishmanial activity depends on an intramolecular hydrogen bond (described by X-ray diffraction) between the lactam function and the nitro group, which is responsible for an important shift of the redox potential (+0.3 V in comparison with 8-nitroquinoline). With the assistance of computational chemistry, a set of derivatives presenting a large range of redox potentials (from -1.1 to -0.45 V) was designed and provided a list of suitable molecules to be synthesized and tested. This approach highlighted that, in this series, only substrates with a redox potential above -0.6 V display activity toward L. infantum. Nevertheless, such relation between redox potentials and in vitro antiparasitic activities was not observed in T. b. brucei. Compound 22 is a new hit compound in the series, displaying both antileishmanial and antitrypanosomal activity along with a low cytotoxicity on the human HepG2 cell line. Compound 22 is selectively bioactivated by the type 1 nitroreductases (NTR1) of L. donovani and T. brucei brucei. Moreover, despite being mutagenic in the Ames test, as most of nitroaromatic derivatives, compound 22 was not genotoxic in the comet assay. Preliminary in vitro pharmacokinetic parameters were finally determined and pointed out a good in vitro microsomal stability (half-life > 40 min) and a 92% binding to human albumin

The first wave of COVID-19 in Intensive care

In December 2019, in Wuhan, a new human infectious pathology was born, COVID-19, consisting above all in pneumoniae, induced by the coronavirus named SARS-CoV-2 because of the respiratory distress it caused (SARS for severe acute respiratory syndrome, and CoV for Coronavirus). A real health and planetary crisis has appeared, much more substantial than that linked to SARS-CoV-1 in 2002-2004 and to MERS-CoV (Middle East Respiratory Syndrome Coronavirus) in 2012. In addition to respiratory damage that can be dramatic, this pathology is complicated by the frequency of cardiovascular, renal and coagulation diseases. Health care systems have had to adapt urgently, in the absence of hindsight from the patho- logy, and without effective therapeutic weapons. Through this review of the literature, we detail our local practices for the overall management of patients hospitalized in Intensive care

Nongenotoxic 3-Nitroimidazo[1,2-a]pyridines Are NTR1 Substrates That Display Potent in Vitro Antileishmanial Activity

Twenty nine original 3-nitroimidazo[1,2-a]pyridine derivatives, bearing a phenylthio (or benzylthio) moiety at position 8 of the scaffold, were synthesized. In vitro evaluation highlighted compound 5 as an antiparasitic hit molecule displaying low cytotoxicity for the human HepG2 cell line (CC50 > 100 mu M) alongside good antileishmanial activities (IC50 = 1-2.1 mu M) against L. donovani, L. infantum, and L. major; and good antitrypanosomal activities (IC50 = 1.3-2.2 mu M) against T. brucei brucei and T. cruzi, in comparison to several reference drugs such as miltefosine, fexinidazole, eflornithine, and benznidazole (IC50 = 0.6 to 13.3 mu M). Molecule 5, presenting a low reduction potential (E degrees = -0.63 V), was shown to be selectively bioactivated by the L. donovani type 1 nitroreductase (NTR1). Importantly, molecule 5 was neither mutagenic (negative Ames test), nor genotoxic (negative comet assay), in contrast to many other nitroaromatics. Molecule 5 showed poor microsomal stability; however, its main metabolite (sulfoxide) remained both active and nonmutagenic, making 5 a good candidate for further in vivo studies

Corticosteroid therapy is associated with a decrease in mortality in a multicenter cohort of mechanically ventilated COVID-19 patients

peer reviewedRetrospectively analyzing the data of a multicenter cohort, we observed that mortality of patients with SARS-CoV-2 pneumoniatreated with mechanical ventilation was as high as 45% and median survival time was 82 days. In this series, the risk factors for mortality included age, renal and circulatory dysfunction, lymphopenia and the absence of corticosteroid use during the first week of mechanical ventilation. Corticosteroid therapy during the first week of mechanical ventilation was associated with a lower mortality (34% vs 48%) (p = 0,01)

Haploinsufficiency of ARFGEF1 is associated with developmental delay, intellectual disability, and epilepsy with variable expressivity

ADP ribosylation factor guanine nucleotide exchange factors (ARFGEFs) are a family of proteins implicated in cellular trafficking between the Golgi apparatus and the plasma membrane through vesicle formation. Among them is ARFGEF1/BIG1, a protein involved in axon elongation, neurite development, and polarization processes. ARFGEF1 has been previously suggested as a candidate gene for different types of epilepsies, although its implication in human disease has not been well characterized. International data sharing, in silico predictions, and in vitro assays with minigene study, western blot analyses, and RNA sequencing. We identified 13 individuals with heterozygous likely pathogenic variants in ARFGEF1. These individuals displayed congruent clinical features of developmental delay, behavioral problems, abnormal findings on brain magnetic resonance image (MRI), and epilepsy for almost half of them. While nearly half of the cohort carried de novo variants, at least 40% of variants were inherited from mildly affected parents who were clinically re-evaluated by reverse phenotyping. Our in silico predictions and in vitro assays support the contention that ARFGEF1-related conditions are caused by haploinsufficiency, and are transmitted in an autosomal dominant fashion with variable expressivity. We provide evidence that loss-of-function variants in ARFGEF1 are implicated in sporadic and familial cases of developmental delay with or without epilepsy

Elastin Peptides Signaling Relies on Neuraminidase-1-Dependent Lactosylceramide Generation

The sialidase activity of neuraminidase-1 (Neu-1) is responsible for ERK 1/2 pathway activation following binding of elastin peptide on the elastin receptor complex. In this work, we demonstrate that the receptor and lipid rafts colocalize at the plasma membrane. We also show that the disruption of these microdomains as well as their depletion in glycolipids blocks the receptor signaling. Following elastin peptide treatment, the cellular GM3 level decreases while lactosylceramide (LacCer) content increases consistently with a GM3/LacCer conversion. The use of lactose or Neu-1 siRNA blocks this process suggesting that the elastin receptor complex is responsible for this lipid conversion. Flow cytometry analysis confirms this elastin peptide-driven LacCer generation. Further, the use of a monoclonal anti-GM3 blocking antibody shows that GM3 is required for signaling. In conclusion, our data strongly suggest that Neu-1-dependent GM3/LacCer conversion is the key event leading to signaling by the elastin receptor complex. As a consequence, we propose that LacCer is an early messenger for this receptor