Several pathogenic variants have been reported in the IMPG1 gene associated with the inherited retinal disorders vitelliform macular dystrophy (VMD) and retinitis pigmentosa (RP). IMPG1 and its ...paralog IMPG2 encode for two proteoglycans, SPACR and SPACRCAN, respectively, which are the main components of the interphotoreceptor matrix (IPM), the extracellular matrix surrounding the photoreceptor cells. To determine the role of SPACR in the pathological mechanisms leading to RP and VMD, we generated a knockout mouse model lacking Impg1, the mouse ortholog. Impg1-deficient mice show abnormal accumulation of autofluorescent deposits visible by fundus imaging and spectral-domain optical coherence tomography (SD-OCT) and attenuated electroretinogram responses from 9 months of age. Furthermore, SD-OCT of Impg1−/− mice shows a degeneration of the photoreceptor layer, and transmission electron microscopy shows a disruption of the IPM and the retinal pigment epithelial cells. The decrease in the concentration of the chromophore 11-cis-retinal supports this loss of photoreceptors. In conclusion, our results demonstrate the essential role of SPACR in maintaining photoreceptors. Impg1−/− mice provide a novel model for mechanistic investigations and the development of therapies for VMD and RP caused by IMPG1 pathogenic variants.
•Deteriorating raw water quality is considered as an “ordinary risk”.•The health standard perceived as arbitrary and contested by several local managers.•The answer is technical to secure the supply ...of water by network interconnections.•The technical and economical approach mask environmental origins of the crisis.•Perception of local water quality by inhabitants is more clearly divergent than at national level.
The closure of a drinking water catchment and deterioration of water quality raise questions about concepts such as water quality and territory. This prompts us to consider the interactions between resource and environmental policy, insofar as sensitivity to the standard of water used for human consumption is high and where its operation involves a large number of actors: state departments, public managers and private firms, land and water users and their representatives. Investigations by semi-directive interviews and surveys were conducted with users and water managers at three sites in Brittany (Finistère and in Ille-et-Vilaine) affected directly or indirectly by the Grenelle 1 bill. The results of the survey suggest that the crisis, if it exists, is attributed by the actors to the quantitative evolution of the resource and to regulations perceived as arbitrary in a context of poorly-controlled environmental dynamics. The socio-economic obstacles to quality improvement are frequently advanced in discussions, but management policies capable of removing these obstacles are very rarely mentioned. Instead, the stakeholders place their trust in technological solutions and work towards the political construction of functional solidarities.
Resistance mechanisms of
to ceftolozane/tazobactam (C/T) were assessed on a collection of 420 nonredundant strains nonsusceptible to ceftazidime (MIC > 8 μg/ml) and/or imipenem (>4 μg/ml), collected ...by 36 French hospital laboratories over a one-month period (the GERPA study). Rates of C/T resistance (MIC > 4/4 μg/ml) were equal to 10% in this population (42/420 strains), and 23.2% (26/112) among the isolates resistant to both ceftazidime and imipenem. A first group of 21 strains (50%) was found to harbor various extended-spectrum β-lactamases (1 OXA-14; 2 OXA-19; 1 OXA-35; 1 GES-9; and 3 PER-1), carbapenemases (2 GES-5; 1 IMP-8; and 8 VIM-2), or both (1 VIM-2/OXA-35 and 1 VIM-4/SHV-2a). All the strains of this group belonged to widely distributed epidemic clones (ST111, ST175, CC235, ST244, ST348, and ST654), and were highly resistant to almost all the antibiotics tested except colistin. A second group was composed of 16 (38%) isolates moderately resistant to C/T (MICs from 8/4 to 16/4 μg/ml), of which 7 were related to international clones (ST111, ST253, CC274, ST352, and ST386). As demonstrated by targeted mass spectrometry, cloxacillin-based inhibition tests, and gene
deletion experiments, this resistance phenotype was correlated with an extremely high production of cephalosporinase PDC. In part accounting for this strong PDC upregulation, genomic analyses revealed the presence of mutations in the regulator AmpR (D135N/G in 6 strains) and enzymes of the peptidoglycan recycling pathway, such as AmpD, PBP4, and Mpl (9 strains). Finally, all of the 5 (12%) remaining C/T-resistant strains (group 3) appeared to encode PDC variants with mutations known to improve the hydrolytic activity of the β-lactamase toward ceftazidime and C/T (F147L, ΔL223-Y226, E247K, and N373I). Collectively, our results highlight the importance of both intrinsic and transferable mechanisms in C/T-resistant
Which mutational events lead some clinical strains to massively produce the natural cephalosporinase PDC remains incompletely understood.
Closing down a drinking water intake point and deteriorating water quality raise questions about concepts such as water quality and territory. This prompts us to consider the interactions between ...resource and environmental policy, to the extend of sensitivity to the standard of water used for human consumption is high and its operation involves a large number of actors: state departments, public managers and private firms, land and water users and their representatives. Investigations by semi-directive interviews and surveys were conducted with users and were affected water managers at three sites in Brittany (Finistère and Ille-et-Vilaine) directly or indirectly by the Grenelle 1 bill. The results of this surveys suggested that the crisis, if it exists, is created by the actors to the quantitative evolution of the resource and to regulations perceived as arbitrary in a context of poorly-controlled environmental dynamics. Socio-economic obstacles to quality improvement are frequently put forward in discussions, but management policies capable of removing these obstacles are very rarely mentioned. Instead, the stakeholders place their trust in technological solutions and work towards the political construction of functional solidarities.
Apple (Malus X domestica) trees naturally produce an excess of fruitlets that negatively affect the commercial value of fruits brought to maturity and impact their capacity to develop flower buds the ...following season. Therefore, chemical thinning has become an important cultural practice, allowing the selective removal of unwanted fruitlets. As the public pressure to limit the use of chemical agents increases, the control of thinning becomes a major issue. Here, we characterized the self-thinning capacity of an apple hybrid genotype from the tree scale to the molecular level. Additional amphivasal vascular bundles were identified in the pith of pedicels supporting the fruitlets with the lowest abscission potential (central fruitlet), indicating that these bundles might have a role in the acquisition of dominance over lateral fruitlets. Sugar content analysis revealed that central fruitlets were better supplied in sorbitol than lateral fruitlets. Transcriptomic profiles allowed us to identify genes potentially involved in the overproduction of vascular tissues in central pedicels. In addition, histological and transcriptomic data permitted a detailed characterization of abscission zone development and the identification of key genes involved in this process. Our data 'confirm the major role of ethylene, auxin, and cell wall-remodeling enzymes in abscission zone formation. The shedding process in this hybrid appears to be triggered by a naturally exacerbated dominance of central fruitlets over lateral ones, brought about by an increased supply of sugars, possibly through additional amphivasal vascular bundles. The characterization of this genotype opens new perspectives for the selection of elite apple cultivars.
The ageing population is rapidly increasing worldwide, and the alcohol-related disease burden in most Western countries is on the rise. However, very few studies assess alcohol use in older people. ...Here, a self-reported questionnaire was administered to all individuals aged 70 years or more who visited a social centre for older people in western France.
The average age of the 98 subjects included in the survey was 79 years (range, 70–97 years; SD=6), and 57.1% (n=56) reported weekly alcohol consumption. An average consumption of over two standard units each day during weekends was reported by 53% subjects (n=52), and the same on each weekday was reported by 34% (n=33). Thus, a significant proportion of subjects aged 70 years or over consumed more alcohol than is recommended in current guidelines. The participants also reported that they rarely discussed alcohol consumption with their general practitioners. Alcohol use should be assessed regularly. District nurses and members of the primary care team should recommend strategies to help older people reduce their alcohol consumption.
•Three littoral systems, eight embayments and one estuary were studied•POC composition was related to ‘Continent-Ocean’ and trophic-status gradients•Forcings were sedimentary processes, ...hydrodynamics, water column depth, nutrient availability•At local scale POC composition appears to be station-specific but still related to the above-mentioned forcings•A typology of systems was drawn based on POM composition
In costal systems, particulate organic matter (POM) results from a multiplicity of sources having their respective dynamics in terms of production, decomposition, transport and burial. The POM pool experiences thus considerable spatial and temporal variability. In order to better understand this variability, the present study employs statistical multivariate analyses to investigate links between POM composition and environmental forcings for a panel of twelve coastal systems distributed along the three maritime regions of France and monitored weekly to monthly for 1 to 8 years.
At multi-system scale, two main gradients of POC composition have been identified: a ‘Continent-Ocean’ gradient associated with hydrodynamics, sedimentary dynamics and depth of the water column, and a gradient of trophic status related to nutrient availability. At local scale, seasonality of POC composition appears to be station-specific but still related to part of the above-mentioned forcings. A typology of systems was established by coupling spatial and temporal variability of POC composition. Four groups were highlighted: (1) the estuarine stations where POC composition is dominated by terrestrial POM and driven by hydrodynamics and sedimentary processes, (2) the oligotrophic systems, characterized by the contribution of diazotrophs due to low nutrient availability, and the marine meso/eutroph systems whose POC composition is (3) either deeply dominated by phytoplankton or (4) dominated by phytoplankton but where the contribution of continental and benthic POC is not negligible and is driven by hydrodynamics, sedimentary processes and the height of the water column.
Finally, the present study provides several insights into the different forcings to POM composition and dynamics in temperate coastal systems at local and multi-system scales. This work also presents a methodological approach that establishes statistical links between forcings and POM composition, helping to gain more objectively insight of forcings.
Neuromuscular blocking agents (NMBAs) are among the leading cause of perioperative anaphylaxis, and most of these reactions are IgE mediated. Allergic sensitisation induced by environmental exposure ...to other quaternary ammonium-containing compounds, such as pholcodine, has been suggested. The aim of this study was to assess the relationship between pholcodine exposure and NMBA-related anaphylaxis.
ALPHO was a multicentre case-control study, comparing pholcodine exposure within a year before anaesthesia between patients with NMBA-related perioperative anaphylaxis (cases) and control patients with uneventful anaesthesia in France. Each case was matched to two controls by age, sex, type of NMBA, geographic area, and season. Pholcodine exposure was assessed by a self-administered questionnaire and pharmaceutical history retrieved from pharmacy records. The diagnostic values of anti-pholcodine and anti-quaternary ammonium specific IgE (sIgE) were also evaluated.
Overall, 167 cases were matched with 334 controls. NMBA-related anaphylaxis was significantly associated with pholcodine consumption (odds ratio 4.2; 95% confidence interval 2.3–7.0) and occupational exposure to quaternary ammonium compounds (odds ratio 6.1; 95% confidence interval 2.7–13.6), suggesting that apart from pholcodine, other environmental factors can also lead to sensitisation to NMBAs. Pholcodine and quaternary ammonium sIgEs had a high negative predictive value (99.9%) but a very low positive predictive value (<3%) for identifying NMBA-related reactions.
Patients exposed to pholcodine 12 months before NMBA exposure have a significantly higher risk of an NMBA-related anaphylaxis. The low positive predictive values of pholcodine and quaternary ammonium sIgEs precludes their use to identify a population with a high risk of NMBA-related anaphylaxis.
NCT02250729.
When spreading onto a protein microlattice living cells spontaneously acquire simple shapes determined by the lattice geometry. This suggests that, on a lattice, living cells' shapes are in ...thermodynamic metastable states. Using a model at thermodynamic equilibrium we are able to reproduce the observed shapes. We build a phase diagram based on two adimensional parameters characterizing essential cellular properties involved in spreading: the cell's compressibility and fluctuations.
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