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Contractile deficits in engineered cardiac microtissues as a result of MYBPC3 deficiency and mechanical overload.
The integration of in vitro cardiac tissue models, human induced pluripotent stem cells (hiPSCs) and genome-editing tools allows for the enhanced interrogation of physiological phenotypes and recapitulation of disease pathologies. Here, using a cardiac tissue model consisting of filamentous three-dimensional matrices populated with cardiomyocytes derived from healthy wild-type (WT) hiPSCs (WT hiPSC-CMs) or isogenic hiPSCs deficient in the sarcomere protein cardiac myosin-binding protein C (MYBPC3-/- hiPSC-CMs), we show that the WT microtissues adapted to the mechanical environment with increased contraction force commensurate to matrix stiffness, whereas the MYBPC3-/- microtissues exhibited impaired force development kinetics regardless of matrix stiffness and deficient contraction force only when grown on matrices with high fibre stiffness. Under mechanical overload, the MYBPC3-/- microtissues had a higher degree of calcium transient abnormalities, and exhibited an accelerated decay of calcium dynamics as well as calcium desensitization, which accelerated when contracting against stiffer fibres. Our findings suggest that MYBPC3 deficiency and the presence of environmental stresses synergistically lead to contractile deficits in cardiac tissues
Maternal Periodontal Disease is Associated with Oxidative Stress during Pregnancy
We sought to determine if maternal periodontal disease is associated with oxidative stress as measured by serum 8-isoprostane. A secondary analysis was conducted using prospective data from the Oral Conditions and Pregnancy Study. Healthy women enrolled at <26 weeks’ gestational age underwent oral examination and serum sampling. Maternal periodontal disease status was categorized as healthy, mild, or moderate to severe by clinical criteria. Maternal serum was analyzed for 8-isoprostane using ultrasensitive enzyme-linked immunosorbent assay. Elevated 8-isoprostane level was defined as ≥75th percentile. Maternal factors associated with elevated 8-isoprostane were determined using chi-square or t test. Multivariable logistic regression was used to assess association between elevated 8-isoprostane and maternal factors. Seven hundred ninety-one women had complete data. Median (interquartile) 8-isoprostane serum level was 1806 (16 to 81,870) pg/dL. Using bivariate analysis, maternal age, race, marital status, utilization of public assistance, and mild or moderate to severe periodontal disease were associated with elevated serum 8-isoprostane. Using logistic regression, moderate to severe periodontal disease (adjusted odds ratio 2.9, 95% confidence interval: 1.7 to 5.0) remained significantly associated with an elevated serum 8-isoprostane level. Maternal periodontal disease is associated with oxidative stress during pregnancy. Further study is needed to determine the role of maternal oxidative stress in periodontal disease-associated adverse pregnancy outcomes
Intrinsic Absorption Lines in Seyfert 1 Galaxies. I. Ultraviolet Spectra from the Hubble Space Telescope
We present a study of the intrinsic absorption lines in the ultraviolet
spectra of Seyfert 1 galaxies. We find that the fraction of Seyfert 1 galaxies
that show absorption associated with their active nuclei is more than one-half
(10/17), which is much higher than previous estimates (3 - 10%) . There is a
one-to-one correspondence between Seyferts that show intrinsic UV absorption
and X-ray ``warm absorbers''. The intrinsic UV absorption is generally
characterized by high ionization: C IV and N V are seen in all 10 Seyferts with
detected absorption (in addition to Ly-alpha), whereas Si IV is present in only
four of these Seyferts, and Mg II absorption is only detected in NGC 4151. The
absorption lines are blueshifted (or in a few cases at rest) with respect to
the narrow emission lines, indicating that the absorbing gas is undergoing net
radial outflow. At high resolution, the absorption often splits into distinct
kinematic components that show a wide range in widths (20 - 400 km/s FWHM),
indicating macroscopic motions (e.g., radial velocity subcomponents or
turbulence) within a component. The strong absorption components have cores
that are much deeper than the continuum flux levels, indicating that the
regions responsible for these components lie completely outside of the broad
emission-line regions. The covering factor of the absorbing gas in the line of
sight, relative to the total underlying emission, is C > 0.86, on average. The
global covering factor, which is the fraction of emission intercepted by the
absorber averaged over all lines of sight, is C > 0.5.Comment: 56 pages, Latex, includes 4 figures (encapsulated postscript), Fig. 1
has 2 parts and Fig. 2 has 3 parts, to appear in the Astrophysical Journa
Periodontal Disease, Oxidative Stress, and Risk for Preeclampsia
Maternal periodontal infection is associated with an increased risk for preeclampsia. Periodontal infection is also associatedwith increased oxidative stress. Our objective was to determine the relationship among maternal periodontal disease, maternal oxidative stress, and the development of preeclampsia
Racial differences in C-reactive protein levels during normal pregnancy
Characterization of serum C-Reactive Protein (CRP) levels in a diverse population of healthy pregnant women using a high sensitivity assay
Periodontal Disease Early in Pregnancy Is Associated With Maternal Systemic Inflammation Among African American Women
Maternal periodontal disease is a chronic oral infection with local and systemic inflammatory responses and may be associated with adverse pregnancy outcomes. This study determined whether maternal periodontal disease in early pregnancy is associated with elevated serum C-reactive protein (CRP) levels and whether maternal race influences the relationship between maternal periodontal disease and systemic inflammatory responses
International Ultraviolet Explorer (IUE) ultraviolet spectral atlas of selected astronomical objects
The IUE Ultraviolet Spectral Atlas of Selected Astronomical Objects (or 'the Atlas'), is based on the data that were available in the IUE archive in 1986, and is intended to be a quick reference for the ultraviolet spectra of many categories of astronomical objects. It shows reflected sunlight from the Moon, planets, and asteroids, and also shows emission from comets. Comprehensive compilations of UV spectra for main sequence, subgiant, giant, bright giant, and supergiant stars are published elsewhere. This Atlas contains the spectra for objects occupying other areas of the Hertzsprung-Russell diagram: pre-main sequence stars, chemically peculiar stars, pulsating variables, subluminous stars, and Wolf-Rayet stars. This Atlas also presents phenomena such as the chromospheric and transition region emissions from late-type stars; composite spectra of stars, gas streams, accretion disks and gas envelopes of binary systems; the behavior of gas ejecta shortly after the outburst of novac and supernovac; and the H II regions, planetary nebulae, and supernova remnants. Population 2 stars, globular clusters, and luminous stars in the Magellanic Clouds, M31, and M33, are also included in this publication. Finally, the Atlas gives the ultraviolet spectra of galaxies of different Hubble types and of active galaxies
First-Trimester Maternal Serum C-reactive Protein as a Predictor of Third-Trimester Impaired Glucose Tolerance
We evaluated whether first-trimester high-sensitivity C-reactive protein (hsCRP), a suggested marker of pregnancy-associated hyperglycemia, predicts third-trimester impaired glucose tolerance (IGT) in a secondary analysis of a prospective cohort of nondiabetic singletons enrolled at <26 weeks gestation