The role of EphB6 and ephrinbs in blood pressure regulation

L’hypertension artérielle est le facteur de risque le plus important dans les maladies cardiovasculaires (MCV) et les accidents vasculaires cérébraux (AVC). L’hypertension artérielle essentielle est une maladie complexe, multifactorielle et polygénique. Même si on a identifié de nombreux facteurs de risque de l’hypertension artérielle, on ne comprend pas encore clairement les mécanismes qui la régissent. Les kinases hépatocytes produisant l’érythropoïétine (Eph) constituent la plus grande famille des récepteurs tyrosine kinase qui se lient à des ligands de surface cellulaire appelés éphrines sur les cellules avoisinantes. On sait que les interactions de Eph et des éphrines sont essentielles aussi bien dans les processus de développement que dans le fonctionnement des organes et des tissus adultes. Cependant on n’a pas encore étudié la relation entre Eph/éphrines et l’hypertension artérielle. Nous avons créé des modèles de souris knockout (K.O.) Ephb6-/-, Efnb1-/- et Efnb3-/- pour cette étude. Dans le modèle EphB6-/-, nous avons observé que les souris K.O. Ephb6 castrées, mais pas les femelles, ainsi que les souris mâles non castrées présentaient une tension artérielle élevée (TA) par rapport à leurs homologues de type sauvage (TS). Ceci suggère que Ephb6 doit agir de concert avec l’hormone sexuelle mâle pour réguler la TA. Les petites artères des mâles castrés Ephb6-/- présentaient une augmentation de la contractilité, une activation de RhoA et une phosphorylation constitutive de la chaîne légère de la myosine (CLM) lorsque comparées à celles de leurs homologues TS. Ces deux derniers résultats indiquent que la phosphorylation de CLM et de RhoA passe par la voie de signalisation de Ephb6 dans les cellules du muscle lisse de la paroi vasculaire (CMLV). Nous avons démontré que la réticulation de Efnbs mais non celle de Ephb6 aboutit à une réduction de la contractilité des CMLV. Ceci montre que l’effet de Ephb6 passe par la signalisation inversée à travers Efnb. Dans le modèle Efnb1-/- conditionnel spécifique au muscle lisse, nous n’avons observé aucune différence entre Efnb1-/- et les souris de TS concernant la mesure de la TA dans des conditions normales. Cependant, la TA des souris K.O. Efnb1 lors d’un stress d’immobilisation est supérieure à celle des souris de TS. Dans les petites artères des souris K.O. Efnb1, le rétrécissement et la phosphorylation de CLM étaient élevés. In vitro, la contractilité et l’activation RhoA de la CMLV des souris TS étaient augmentées quand leur Efnb1 était réticulé. Ces résultats corroborent ceux des souris KO Ephb6 et prouvent que l’effet de Ephb6 dans le contrôle de la TA se produit au moins par l’intermédiaire d’un de ses ligands Efnb1 dans les CMLV. Dans le modèle Efnb3-/-, on a observé une augmentation de la TA et du rétrécissement des vaisseaux chez les femelles Efnb3-/-, mais non chez les mâles; l’échographie a aussi révélé une résistance accrue au débit sanguin des souris K.O. femelles. Cependant la mutation de Efnb3 ne modifie pas la phosphorylation de la CLM ou l’activation de RhoA in vivo. Dans l’expérience in vitro, les CMLV des souris femelles Efnb3-/- ont présenté une augmentation de la contractilité mais pas celle des souris mâles Efnb3-/-. La réticulation des CMLV chez les mâles ou les femelles de TS avec solide anti-Efnb3 Ab peut réduire leur contractilité. Notre étude est la première à évaluer le rôle de Eph/éphrines dans la régulation de la TA. Elle montre que les signalisations Eph/éphrines sont impliquées dans le contrôle de la TA. La signalisation inverse est principalement responsable du phénotype élevé de la TA. Bien que les Efnb1, Efnb3 appartiennent à la même famille, leur fonction et leur efficacité dans la régulation de la TA pourraient être différentes. La découverte de Eph/Efnb nous permet d’explorer plus avant les mécanismes qui gouvernent la TA.Hypertension is the most important risk factor for the cardiovascular diseases (CVD) and strokes. The essential hypertension is a complex, multifactorial and polygenic disease. Although many hypertension risk factors have been identified, the comprehensive understanding of mechanisms remains elusive. Erythropoietin-producing hepatocyte kinases (Ephs) are the largest family of receptor tyrosine kinases, which bind to cell surface ligands called ephrins on neighboring cells. Eph and ephrin interactions are known to be essential in developmental processes, as well as in functions of adult organs and tissues. However the relationship between Ephs/ephrins and hypertension has not been studied. Ephb6-/-, Efnb1-/- and Efnb3-/-knockout mice models were established for this study. In the EphB6-/- model, we observed that the castrated Ephb6 KO mice but not female or uncastrated male mice presented heightened blood pressure (BP) compared to the wild type (WT) counterparts. This suggests that Ephb6 needs to act in concert with sex hormone to regulate blood pressure. Small arteries from castrated Ephb6-/- males showed increased contractility, RhoA activation and constitutive myosin light chain (MLC) phosphorylation compared to their WT counterparts. The latter two findings indicate that RhoA and MLC phosphorylation are in the signaling pathway of Ephb6 in vascular smooth muscle cell (VSMC). We demonstrated that, crosslinking of Efnbs but not Ephb6 resulted in reduced VSMC contractility. This indicates that the effect of Ephb6 is via reverse signaling through Efnbs. In smooth muscle-specific conditional Efnb1-/- model, no difference was observed between Efnb1-/- and WT mice in BP measurement under a normal condition. However, the BP of Efnb1 KO mice during immobilization stress were higher than that of WT mice. In the small arteries from Efnb1 KO mice, the constriction and MLC phosphorylation were elevated. In vitro, the contractility and RhoA activation of WT VSMC were augmented when their Efnb1 was crosslinked. These results corroborate the findings from Ephb6 KO mice, and prove that the effect of Ephb6 in BP control is at least via one of its ligand Efnb1 in VSMC. In the Efnb3-/- model the heightened BP and increased vessel constriction were observed in Efnb3-/-females but not males; the echography also revealed the increased blood flow resistance of female KO mice. However the mutation of Efnb3 doesn’t alter the MLC phosphorylation or RhoA activation in vivo. In in vitro experiment, VSMCs from Efnb3-/- female mice showed increased contractility but did not Efnb3-/- male mice. Crosslinking of VSMCs from WT males or females with solid anti-Efnb3 Ab can reduce their contractility. Our study is the first to assess the role of Eph/ephrins in BP regulation. Eph/ephrins signalings are involved in the regulation of BP. The reverse signaling is mainly responsible for the elevated BP phenotype. Although the Efnb1, Efnb3 belongs to the same family, their function and effectiveness in the regulation of BP might be different. The discovery of Eph/Efnbs allows us to further explore the mechanism in BP

A dataset describing chip parameters for rock breaking by chisel pick under deep-sea hydrostatic pressure

Chip is a visual representation of rock breaking by cutter, and their related parameters are crucial for revealing the rock breaking mechanism in deep-sea mining. Based on sieving and three-dimensional size measurement methods widely used in mining engineering, this paper reports a dataset of chip parameters for rock breaking by chisel pick under deep-sea hydrostatic pressure. Specifically, we first designed an experimental setup that can accurately simulate deep-sea hydrostatic pressure, conducted rock breaking experiments and carefully collected chips. Subsequently, those chips were sieved, high-resolution images were collected, and the coarseness index (CI), chip size uniformity (n), absolute chip size (de), and fractal dimension (D) were measured. Finally, three-dimensional size (long, intermediate and short) was measured for 3064 chips with particle sizes greater than 4.75 mm. This dataset will be used by researchers to validate numerical simulations or optimize equipment structures related to deep-sea mining, including deep-sea rock mechanics, mining cutter and conveyor pipes

Reactions of Chinese adults to warning labels on cigarette packages: A survey in Jiangsu Province

<p>Abstract</p> <p>Background</p> <p>To compare reactions to warning labels presented on cigarette packages with a specific focus on whether the new Chinese warning labels are better than the old labels and international labels.</p> <p>Methods</p> <p>Participants aged 18 and over were recruited in two cities of Jiangsu Province in 2008, and 876 face-to-face interviews were completed. Participants were shown six types of warning labels found on cigarette packages. They comprised one old Chinese label, one new label used within the Chinese market, and one Chinese overseas label and three foreign brand labels. Participants were asked about the impact of the warning labels on: their knowledge of harm from smoking, giving cigarettes as a gift, and quitting smoking.</p> <p>Results</p> <p>Compared with the old Chinese label, a higher proportion of participants said the new label provided clear information on harm caused by smoking (31.2% vs 18.3%). Participants were less likely to give cigarettes with the new label on the package compared with the old label (25.2% vs 20.8%). These proportions were higher when compared to the international labels. Overall, 26.8% of participants would quit smoking based on information from the old label and 31.5% from the new label. When comparing the Chinese overseas label and other foreign labels to the new Chinese label with regard to providing knowledge of harm warning, impact of quitting smoking and giving cigarettes as a gift, the overseas labels were more effective.</p> <p>Conclusion</p> <p>Both the old and the new Chinese warning label are not effective in this target population.</p

Impact of hypertension and smoking on the rupture of intracranial aneurysms and their joint effect

Background In general population, the prevalence of intracranial aneurysm reaches as high as three percent. The goal of the study was to analyze retrospectively the independent risk factors for the rupture of intracranial aneurysms and their joint effect. Methods The records and angiographies of continuous 519 intracranial aneurysm patients treated at our center between February 2013 and July 2014 were retrospectively analyzed. Ruptured group and unruptured group were included in the study according to their clinical and imaging information. Univariate analysis and multivariate logistic regression analysis was used to identified independent risk factors for the rupture of intracranial aneurysms. We assessed the joint effect of independent risk factors for the rupture of intracranial aneurysms with an additional logistic regression analysis. Results The results of multivariate analysis show that hypertension (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.05–2.18) and smoking (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.06–2.33) were independent risk factors for rupture of intracranial aneurysms. The joint risk of hypertension and smoking was higher (OR, 2.28; 95% CI, 1.29–4.02) than the risks of hypertension (OR, 1.74; 95% CI, 1.11–2.72) and smoking (OR, 1.86; 95% CI, 1.05–3.29) independently. Conclusions Hypertension and smoking increase of the rupture risk of intracranial aneurysms. And the joint risk of hypertension and smoking was higher than the risks of hypertension and smoking independently

Stent-assisted coiling of very small wide-necked intracranial aneurysms: Complications, anatomical results and clinical outcomes

Background and objective Treatment of very small (≤3mm) wide-necked intracranial aneurysms remains controversial, we investigated the efficacy and safety of stent-assisted coiling of such aneurysms. Methods From September 2008 to December 2012, 112 very small wide-necked intracranial aneurysms in 108 patients were embolized with stent-assisted coiling. We assessed the initial neurological conditions, complications and anatomic results. The follow-up results were evaluated with DSA and mRS. Results Stent deployment was successful in 104 of 108 procedures (96.3%). 11 complications (10.2%) occurred during procedures, including 5 events of aneurysm rupture, 3 events of thromboembolism. The rate of complication, rupture and thromboembolism was not statistically different between the ruptured and unruptured patients (P=0.452, P=0.369, P=1.000, respectively). The initial aneurysmal occlusion was Raymond scale (RS) 1 in 34 patients (31.5%), RS2 in 53 patients (49.1%), and RS3 in 21 patients (19.4%). 79 aneurysms were available for anatomic follow-up of 12–47 months, stable occlusion in 45 aneurysms (57.0%), progressive complete occlusion in 34 aneurysms (43.0%). 95 patients(88.0%) were available for a clinical follow-up of 12–52 months, 92 patients (96.8%) had favorable clinical outcomes (mRS ≤2), 3 patients (3.2%) had morbidity (mRS: 3–5). The morbidity was not statistically different between the ruptured and unruptured patients (P=1.000). Conclusions Stent-assisted coiling of very small wide-necked intracranial aneurysms may be effective and safe. Because of low risk of rupture in such aneurysms, the coiling of unruptured such aneurysms must be selective. The long-term efficacy and safety of coiling such aneurysms remains to be determined in larger prospective series

Modeling of the Rating of Perceived Exertion Based on Heart Rate Using Machine Learning Methods

Abstract Rating of perceived exertion (RPE) can serve as a more convenient and economical alternative to heart rate (HR) for exercise intensity control. This study aims to explore the influence of factors, such as indicators of demographic, anthropometric, body composition, cardiovascular function and basic exercise ability on the relationship between HR and RPE, and to develop the model predicting RPE from HR. 48 healthy participants were recruited to perform an incrementally 6-stage pedaling test. HR and RPE were collected during each stage. The influencing factors were identified with the forward selection method to train Gaussian Process regression (GPR), support vector machine (SVM) and linear regression models. Metrics of R2, adjusted R2 and RMSE were calculated to evaluate the performance of the models. The GPR model outperformed the SVM and linear regression models, and achieved an R2 of 0.95, adjusted R2 of 0.89 and RMSE of 0.52. Indicators of age, resting heart rate (RHR), Central arterial pressure (CAP), body fat rate (BFR) and body mass index (BMI) were identified as factors that best predicted the relationship between RPE and HR. It is possible to use GPR model to estimate RPE from HR accurately, after adjusting for age, RHR, CAP, BFR and BMI

Effect of diesel detergent synergists on VOCs emissions from engine

In this study, the volatile organic compounds (VOCs) emissions from engine fueled diesel with and without detergent synergist were measured by gas chromatography mass spectrometry(GC-MS). The test results show that compared with reference diesel fuel (without diesel detergent synergist), the use of different diesel detergent synergists has different effects on the VOCs emissions while without after-treatment device. Whether with or without after-treatment device, alkanes always account for the highest proportion of VOCs emissions while engine fuels with different diesel detergent synergists. After-treatment device diesel oxidation catalyst coupled with diesel particulate filter (DOC+DPF) has high catalytic efficiency for VOCs emissions from engine fueled with different fuels, and most of the catalytic efficiency could reach more than 95%. With the catalytic treatment of after-treatment device,the concentrations of carcinogens (detected in this study) in VOCs emissions from engine fueled with and without detergent synergist are far lower than that specified in reference standard GBZ 2.1-2007 “Occupational Exposure Limits for Hazardous Factors in the Workplace and Chemical Hazardous Factors”, respectively. The test results indicate that the use of diesel detergent synergist will not have an adverse impact on human health and it can be safely used

Metal-insulator transition in vanadium dioxide nanobeams: probing sub-domain properties of strongly correlated materials

Many strongly correlated electronic materials, including high-temperature superconductors, colossal magnetoresistance and metal-insulator-transition (MIT) materials, are inhomogeneous on a microscopic scale as a result of domain structure or compositional variations. An important potential advantage of nanoscale samples is that they exhibit the homogeneous properties, which can differ greatly from those of the bulk. We demonstrate this principle using vanadium dioxide, which has domain structure associated with its dramatic MIT at 68 degrees C. Our studies of single-domain vanadium dioxide nanobeams reveal new aspects of this famous MIT, including supercooling of the metallic phase by 50 degrees C; an activation energy in the insulating phase consistent with the optical gap; and a connection between the transition and the equilibrium carrier density in the insulating phase. Our devices also provide a nanomechanical method of determining the transition temperature, enable measurements on individual metal-insulator interphase walls, and allow general investigations of a phase transition in quasi-one-dimensional geometry.Comment: 9 pages, 3 figures, original submitted in June 200