Les séries fluvio-éoliennes du "Cutler Group" :: Permien (Utah, USA). Modèle architectural et expression des unités génétiques

National audienceL'essor qu'a connu la stratigraphie séquentielle dans les environnements continentaux a permis de définir des modèles architecturaux pour des séries fluvio-lacustres. Plus récemment, les modèles proposés ont intégré les dépôts éoliens dans les systèmes continentaux côtiers ou lacustres (préservation de l'éolien vs variations de la table d'eau, e.g. Carr-Crabaugh & Kocurek, 1998) ou dans les systèmes continentaux endoréiques (préservation de l'éolien vs climat (e.g. Clemmensen et al., 1998) ou préservation de l'éolien vs accommodation et flux de sédiments, e.g. Bourquin et al., 2009). Cependant, peu de modèles discutent les variations de préservation des dépôts éoliens par rapport aux environnements continentaux associés (fluvial, lac, playa) afin de prédire un modèle architectural des dépôts éoliens (du réservoir au bassin) en fonction du contexte géodynamique. L'objectif de cet exposé est de contraindre l'expression des unités génétiques et de proposer un modèle architectural montrant les variations de préservation des dépôts éoliens en fonction du contexte tectonique, climatique et eustatique. L'étude des séries du Permien inférieur, " Cutler Group ", du " Paradox Basin " (SE Utah), caractérisées par des dépôts fluvio-éoliens (e.g. Condon, 1997), a été réalisée à partir de 5 sections sédimentologiques. Elles sont localisées sur un profil proximal représenté par des dépôts dominés fluvial jusqu'à des dépôts dominés éolien dans le domaine distal (e.g. Mountney & Jagger, 2004). Une étude sédimentologique et stratigraphique détaillée permet de proposer une évolution spatiale et temporelle des environnements de dépôt. Nous avons ainsi mis en évidence (1) les variations d'expression des unités génétiques d'un environnement proximal à un environnement distal en climat semi-aride, (2) plusieurs modèles architecturaux montrant l'évolution verticale depuis un contexte de bassin côtier, à dunes éoliennes faiblement préservées, vers des environnements plus continentaux dominés éolien puis vers des systèmes fluvio-lacustres à faible préservation des dépôts éoliens

The three lipocalins of egg-white: only Ex-FABP inhibits siderophore-dependent iron sequestration by Salmonella Enteritidis

Salmonella Enteritidis is the most prevalent food-borne pathogen associated with egg-related outbreaks in the European Union. During egg colonization, S. Enteritidis must resist the powerful anti-bacterial activities of egg white (EW) and overcome ovotransferrin-imposed iron-restriction (the most important anti-bacterial mechanism of EW). Many pathogens respond to iron restriction by secreting iron-chelating chemicals called siderophores but EW contains a siderophore-sequestering “lipocalin” protein (Ex-FABP) that is predicted to limit the usefulness of siderophores in EW. S. Enteritidis produces two siderophores: enterobactin, which is strongly bound by Ex-FABP; and the di-glucosylated enterobactin-derivative, salmochelin (a so-called “stealth” siderophore), which is not recognized by Ex-FABP. Thus, production of salmochelin may allow S. Enteritidis to escape Ex-FABP-mediated growth inhibition under iron restriction although it is unclear whether its EW concentration is sufficient to inhibit pathogens. Further, two other lipocalins (Cal-γ and α-1-ovoglycoprotein) are found in EW but their siderophore sequestration potential remains unexplored. In addition, the effect of EW lipocalins on the major EW pathogen, S. Enteritidis, has yet to be reported. We overexpressed and purified the three lipocalins of EW and investigated their ability to interact with the siderophores of S. Enteritidis, as well as their EW concentrations. The results show that Ex-FABP is present in EW at concentrations (5.1 μM) sufficient to inhibit growth of a salmochelin-deficient S. Enteritidis mutant under iron restriction but has little impact on the salmochelin-producing wildtype. Neither Cal-γ nor α-1-ovoglycoprotein bind salmochelin or enterobactin, nor do they inhibit iron-restricted growth of S. Enteritidis. However, both are present in EW at significant concentrations (5.6 and 233 μM, respectively) indicating that α-1-ovoglycoprotein is the 4th most abundant protein in EW, with Cal-γ and Ex-FABP at 11th and 12th most abundant. Further, we confirm the preference (16-fold) of Ex-FABP for the ferrated form (Kd of 5.3 nM) of enterobactin over the iron-free form (Kd of 86.2 nM), and its lack of affinity for salmochelin. In conclusion, our findings show that salmochelin production by S. Enteritidis enables this key egg-associated pathogen to overcome the enterobactin-sequestration activity of Ex-FABP when this lipocalin is provided at levels found in EW

Haemodynamic Adaptive Mechanisms at High Altitude: Comparison between European Lowlanders and Nepalese Highlanders

Background: Exposure to high altitudes determines several adaptive mechanisms affecting in a complex way the whole cardiovascular, respiratory, endocrine systems because of the hypobaric hypoxic condition. The aim of our study was to evaluate the circulatory adaptive mechanisms at high altitudes, during a scientific expedition in the Himalayas. Methods: Arterial distensibility was assessed measuring carotid-radial and carotid-femoral pulse wave velocity. Tests were carried out at several altitudes, from 1350 to 5050 m above sea level, on 8 lowlander European researchers and 11 highlander Nepalese porters. Results: In Europeans, systolic blood pressure and pulse pressure increased slightly but significantly with altitude (p < 0.05 and p < 0.001, respectively). Norepinephrine showed a significant increase after the lowlanders had spent some time at high altitude (p < 0.001). With increasing altitude, a progressive increase in carotid-radial and carotid-femoral pulse wave velocity values was observed in lowlanders, showing a particularly significant increase (p < 0.001) after staying at high altitude (carotid-radial pulse wave velocity, median value (interquartile range) from 9.2 (7.9-10.0) to 11.2 (10.9-11.8) m/s and carotid-femoral pulse wave velocity from 8.5 (7.9-9.0) to 11.3 (10.9-11.8) m/s). At high altitudes (3400 and 5050 m above sea level), no significant differences were observed between highlanders and lowlanders in hemodynamic parameters (blood pressure, carotid-radial and carotid-femoral pulse wave velocity). Conclusions: The progressive arterial stiffening with altitude observed in European lowlanders could explain the increase in systolic and pulse pressure values observed at high altitudes in this ethnic group. Further studies are needed to evaluate the role of aortic stiffening in the pathogenesis of acute mountain sickness

Microcirculatory and Rheological Adaptive Mechanisms at High Altitude in European Lowlander Hikers and Nepalese Highlanders

Background: Physical activity at high-altitudes is increasingly widespread, both for tourist trekking and for the growing tendency to carry out sports and training activities at high-altitudes. Acute exposure to this hypobaric-hypoxic condition induces several complex adaptive mechanisms involving the cardiovascular, respiratory and endocrine systems. A lack of these adaptive mechanisms in microcirculation may cause the onset of symptoms of acute mountain sickness, a frequent disturbance after acute exposure at high altitudes. The aim of our study was to evaluate the microcirculatory adaptive mechanisms at different altitudes, from 1350 to 5050 m a.s.l., during a scientific expedition in the Himalayas. Methods: The main haematological parameters, blood viscosity and erythrocyte deformability were assessed at different altitudes on eight European lowlanders and on a group of eleven Nepalese highlanders. The microcirculation network was evaluated in vivo by conjunctival and periungual biomicroscopy. Results: Europeans showed a progressive and significant reduction of blood filterability and an increase of whole blood viscosity which correlate with the increase of altitude (p < 0.02). In the Nepalese highlanders, haemorheological changes were already present at their residence altitude, 3400 m a.s.l. (p < 0.001 vs. Europeans). With the increase in altitude, a massive interstitial oedema appeared in all participants, associated with erythrocyte aggregation phenomena and slowing of the flow rate in the microcirculation. Conclusions: High altitude causes important and significant microcirculatory adaptations. These changes in microcirculation induced by hypobaric-hypoxic conditions should be considered when planning training and physical activity at altitude

Global gene-expression analysis of the response of Salmonella Enteritidis to egg-white exposure reveals multiple egg-white-imposed stress responses

Chicken egg white protects the embryo from bacterial invaders by presenting an assortment of antagonistic activities that combine together to both kill and inhibit growth. The key features of the egg-white anti-bacterial system are iron restriction, high pH, antibacterial peptides and proteins, and viscosity. Salmonella enterica serovar Enteritidis is the major pathogen responsible for egg-borne infection in humans, which is partly explained by its exceptional capacity for survival under the harsh conditions encountered within egg white. However, at temperatures up to 42 ˚C, egg white exerts a much stronger bactericidal effect on S. Enteritidis than at lower tempertaures, although the mechanism of egg-white-induced killing is only partly understood. Here, for the first time, the impact of exposure of S. Enteritidis to egg white under bactericidal conditions (45 ˚C) is explored by global-expression analysis. A large-scale (18.7% of genome) shift in transcription is revealed suggesting major changes in specific aspects of S. Enteritidis physiology: induction of egg-white related stress-responses (envelope damage, exposure to heat and alkalinity, and translation shutdown); shift in energy metabolism from respiration to fermentation; and enhanced micronutrient provision (due to iron and biotin restriction). Little evidence of DNA damage or redox stress was obtained. Instead, data are consistent with envelope damage resulting in cell death by lysis. A surprise was the high degree of induction of hexonate/hexuronate utilisation genes, despite no evidence indicating the presence of these substrates in egg white

Altered Ca2+ Homeostasis in Red Blood Cells of Polycythemia Vera Patients Following Disturbed Organelle Sorting during Terminal Erythropoiesis

The authors thank Thierry Peyrard, Dominique Gien, Sirandou Tounkara, and Eliane Véra at Centre National de Référence pour les Groupes Sanguins for the management of blood samples. The authors thank Sandrine Genetet and Isabelle Mouro-Chanteloup at the Inserm UMR_S1134 unit for their assistance in experiments. The authors also thank Michaël Dussiot at the Institute Imagine for his assistance in imaging flow cytometry. We thank Johanna Bruce and Virginie Salnot at 3P5 Proteomics Platform for sample preparation and analysis, and François Guillonneau and Patrick Mayeux for their management and strategies. Funding: The work was supported by Institut National de la Santé et de la Recherche Médicale (Inserm); Institut National de la Transfusion Sanguine (INTS); the University of Paris; and grants from Laboratory of Excellence (Labex) GR-Ex, reference No. ANR-11-LABX-0051. The Labex GR- Ex is funded by the IdEx program “Investissements d’avenir” of the French National Research Agency, reference No. ANR-11-IDEX-0005-02 and ANR-18-IDEX-0001. R.B., M.G.R., and D.M.A. were funded by the European Union’s Horizon 2020 Research and Innovation Program under grant agreement No. 675115-RELEVANCE-H2020-MSCA-ITN-2015. R.B. also received financial support from Société Française d’Hématologie (SFH) and Club du Globule Rouge et du Fer (CGRF). R.B. is currently funded by the Innovate UK Research and Innovation Knowledge Transfer Partnership (KTP) between University of Aberdeen and Vertebrate Antibodies Ltd. (Partnership No. KTP12327). T.D. was supported by PhD grants from Université Paris Saclay MESR (Ministère Enseignement Supérieur et de la Recherche) and then FRM (Fondation recherche médicale). The Orbitrap Fusion mass spectrometer was acquired with funds from Fonds Europeen de Developpement Regional (FEDER) through the Operational Program for Competitiveness Factors and Employment 2007-2013 and from the Canceropole Ile de France.Peer reviewedPublisher PD

Myocardial oxygen supply and demand imbalance predicts mortality in older nursing home residents: The PARTAGE study

Background: A mismatch between myocardial oxygen supply and demand is the most common cause of ischemic myocardial injury in older persons. The subendocardial viability ratio (SEVR) can usefully estimate the degree of myocardial perfusion relative to left-ventricular workload. The aim of the present study was to evaluate the ability of SEVR to predict long-term mortality in the older population. Additionally, we aimed to identify the SEVR cutoff value best predicting total mortality. Methods: This is a multicenter, longitudinal study involving a large population of individuals older than 80 years living in nursing homes. Patients with cancer, severe dementia, and very low level of autonomy were excluded from the study. Participants were monitored for 10 years. Adverse outcomes were recorded every 3 months from inclusion to the end of the study. SEVR reflects the balance between subendocardial oxygen supply and demand, and was estimated non-invasively by analyzing the carotid pressure waveform recorded by applanation arterial tonometry. Results: A total of 828 people were enrolled (mean age: 87.7 ± 4.7 years, 78% female). 735 patients died within 10 years and 24 were lost to follow-up. SEVR was inversely associated with mortality at univariate Cox-regression model (risk ratio, 0.683 per unit increase in SEVR; 95% confidence interval (CI) [0.502-0.930], p = 0.015) and in a model including age, sex, body mass index, Activity of Daily Living index and Mini-Mental State Examination score (risk ratio, 0.647; 95% CI [0.472-0.930]). The lowest tertile of SEVR was associated with higher 10-years total mortality than the middle (p < 0.001) and the highest (p < 0.004) tertile. A SEVR cutoff value of 83% was identified as the best predictor of total mortality. Conclusions: SEVR may be considered as a marker of "cardiovascular frailty." An accurate non-invasive estimation of SEVR could be a useful and independent parameter to assess survival probability in very old adults. Trial registration: NCT00901355, registered on ClinicalTrials.gov website

Molecular diagnosis of COVID-19 in Burkina Faso: successful challenge

COVID-19 has worsened the health situation in Burkina Faso. In fact, the country has known a peak of the second wave, which began in November, and ended around January 2021. Biological diagnosis has played a key role in the management of COVID-19. The aim of this review paper is to address the practical aspects that laboratories have faced in order to meet the challenge of SARS-CoV-2 diagnosis in Burkina Faso. According to international requirements, Burkina Faso has used real-time Reverse Transcription Polymerase Chain Reaction (rRT-PCR) as the “gold standard” for the diagnosis of COVID-19. From March 9, 2020 to July 31, 2021, in Burkina Faso, laboratories involved in COVID-19 diagnosis analyzed 226,189 samples by molecular tests and 2, 352 samples by rapid antigenic tests, whose peak was in January 2021 with 35,984 samples analyzed. The daily average rate of samples analysis was 456.02 tests. The majority of the individuals requesting COVID-19 tests were travelers (62.00%), followed by contact cases (18.42%), suspected cases (7.95%), voluntary screening (7.57%), and 4.06% of other applicants consisting of health care personnel and at-risk patients. In terms of prevention, vaccines are being administered to the general population. However, some efforts must be made to provide automated sample analysis equipment and complete sequencing of SARS-CoV-2 remains among the challenges

Egg-white proteins have a minor impact on the bactericidal action of egg white toward Salmonella Enteritidis at 45°C

Salmonella enterica serovar Enteritidis is noted for its ability to survive the harsh antibacterial activity of egg white which is presumed to explain its occurrence as the major food-borne pathogen associated with the consumption of eggs and egg products. Liquid egg white is a major ingredient for the food industry but, because of its thermal fragility, pasteurization is performed at the modest temperature of 57 °C (for 2 to 6 min). Unfortunately, such treatment does not lead to sufficient reduction in S. Enteritidis contamination, which is a clear health concern when the product is consumed without cooking. However, egg white is able to limit S. Enteritidis growth due to its alkaline pH, iron deficiency and multiple antimicrobial proteins. This anti-Salmonella activity of egg white is temperature dependent and becomes bactericidal once the incubation temperature exceeds 42°C. This property is exploited in highly-promising pasteurization treatment (42-45 °C for 1 to 5 days) which achieves complete killing of S. Enteritidis. However, the precise mechanism and the role of the egg-white proteins are not fully understood. Here, the impact of exposure of S. Enteritidis to egg white-based media, with or without egg-white proteins (>10 kDa), under bactericidal conditions (45 °C) was explored by measuring survival and global expression. Surprisingly, the bactericidal activity of egg white at 45 °C was only slightly affected by egg-white proteins indicating that they play a minor role in the bactericidal activity observed. Moreover, egg-white proteins had minimal impact on the global-gene-expression response to egg white such that very similar, major regulatory responses (20% genes affected) were observed both with and without egg-white proteins following 45 min at 45°C. Egg-white proteins caused a significant change in expression for just 64 genes, including the psp and lysozyme-inhibitor responses genes which is suggestive of an early membrane perturbation effect. Such damage was supported by disruption of the proton motive force by egg-white proteins. In summary, the results suggest that low-mass components of egg white are largely responsible for the bactericidal activity of egg white at 45 °C