39 research outputs found

    Full-length human placental sFlt-1-e15a isoform induces distinct maternal phenotypes of preeclampsia in mice

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    <div><p>Objective</p><p>Most anti-angiogenic preeclampsia models in rodents utilized the overexpression of a truncated soluble fms-like tyrosine kinase-1 (sFlt-1) not expressed in any species. Other limitations of mouse preeclampsia models included stressful blood pressure measurements and the lack of postpartum monitoring. We aimed to 1) develop a mouse model of preeclampsia by administering the most abundant human placental sFlt-1 isoform (hsFlt-1-e15a) in preeclampsia; 2) determine blood pressures in non-stressed conditions; and 3) develop a survival surgery that enables the collection of fetuses and placentas and postpartum (PP) monitoring.</p><p>Methods</p><p>Pregnancy status of CD-1 mice was evaluated with high-frequency ultrasound on gestational days (GD) 6 and 7. Telemetry catheters were implanted in the carotid artery on GD7, and their positions were verified by ultrasound on GD13. Mice were injected through tail-vein with adenoviruses expressing hsFlt-1-e15a (n = 11) or green fluorescent protein (GFP; n = 9) on GD8/GD11. Placentas and pups were delivered by cesarean section on GD18 allowing PP monitoring. Urine samples were collected with cystocentesis on GD6/GD7, GD13, GD18, and PPD8, and albumin/creatinine ratios were determined. GFP and hsFlt-1-e15a expression profiles were determined by qRT-PCR. Aortic ring assays were performed to assess the effect of hsFlt-1-e15a on endothelia.</p><p>Results</p><p>Ultrasound predicted pregnancy on GD7 in 97% of cases. Cesarean section survival rate was 100%. Mean arterial blood pressure was higher in hsFlt-1-e15a-treated than in GFP-treated mice (∆MAP = 13.2 mmHg, p = 0.00107; GD18). Focal glomerular changes were found in hsFlt-1-e15a -treated mice, which had higher urine albumin/creatinine ratios than controls (109.3±51.7μg/mg vs. 19.3±5.6μg/mg, p = 4.4x10<sup>-2</sup>; GD18). Aortic ring assays showed a 46% lesser microvessel outgrowth in hsFlt-1-e15a-treated than in GFP-treated mice (p = 1.2x10<sup>-2</sup>). Placental and fetal weights did not differ between the groups. One mouse with liver disease developed early-onset preeclampsia-like symptoms with intrauterine growth restriction (IUGR).</p><p>Conclusions</p><p>A mouse model of late-onset preeclampsia was developed with the overexpression of hsFlt-1-e15a, verifying the <i>in vivo</i> pathologic effects of this primate-specific, predominant placental sFlt-1 isoform. HsFlt-1-e15a induced early-onset preeclampsia-like symptoms associated with IUGR in a mouse with a liver disease. Our findings support that hsFlt-1-e15a is central to the terminal pathway of preeclampsia, and it can induce the full spectrum of symptoms in this obstetrical syndrome.</p></div

    Mechanical Behavior and Microstructural Development of Low-Carbon Steel and Microcomposite Steel Reinforcement Bars Deformed under Quasi-Static and Dynamic Shear Loading

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    Reinforcement bars of microcomposite (MC) steel, composed of lath martensite and minor amounts of retained austenite, possess improved strength and corrosion characteristics over low-carbon (LC) steel rebar; however, their performance under shear loading has not previously been investigated at the microstructural level. In this study, LC and MC steel cylinders were compression tested, and specimens machined into a forced-shear geometry were subjected to quasi-static and dynamic shear loading to determine their shear behavior as a function of the strain and strain rate. The as-received and sheared microstructures were examined using optical microscopy (OM), scanning electron microscopy (SEM), and electron backscatter diffraction (EBSD). Higher-resolution microstructural examinations were performed using transmission electron microscopy (TEM). The influence of the starting microstructure on the shear behavior was found to depend strongly on the strain rate; the MC steel exhibited not only greater strain-rate sensitivity than the LC steel but also a greater resistance to shear localization with load. In both steels, despite differences in the starting microstructure, post-mortem observations were consistent with a continuous mechanism operating within adiabatic shear bands (ASBs), in which subgrains rotated into highly misoriented grains containing a high density of dislocations

    Physical and Magnetic Modification of Co/Pt Multilayers by Ion Irradiation

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    Anionic and cationic diffusion in ionic conducting oxides

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    This paper concerns an analysis of the transport processes at high temperature in anionic conducting oxides subjected to a chemical potential gradient or an applied electrical field. The general equations are given. The principle of the cationic kinetic demixing under a "generalized" thermodynamical potential gradient is reviewed. Experimental results obtained with yttria-doped zirconia are reported. An experimental procedure for the determination of the oxygen diffusion coefficient in ionic and semiconducting oxides is also described. The results obtained with yttriastabilized zirconia are compared to both self diffusion and conductivity data. This has allowed us to obtain information concerning the defect structure
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