1,959 research outputs found
COMMD1 Promotes pVHL and O2-Independent Proteolysis of HIF-1α via HSP90/70
BACKGROUND:The Copper Metabolism MURR1 Domain containing 1 protein COMMD1 has been associated with copper homeostasis, NF-kappaB signaling, and sodium transport. Recently, we identified COMMD1 as a novel protein in HIF-1 signaling. Mouse embryos deficient for Commd1 have increased expression of hypoxia/HIF-regulated genes i.e. VEGF, PGK and Bnip3. Hypoxia-inducible factors (HIFs) are master regulators of oxygen homeostasis, which control angiogenesis, erythropoiesis, glycolysis and cell survival/proliferation under normal and pathologic conditions. Although HIF activity is mainly controlled by ubiquitination and protein degradation by the von Hippel Lindau (pVHL) tumor suppressor gene other mechanisms have recently been identified that regulate HIF signaling independently of pVHL. PRINCIPAL FINDINGS:Here we characterized the mechanism by which COMMD1 regulates HIF-1alpha protein degradation. We show that COMMD1 competes with the chaperone heat shock protein HSP90beta for binding to the NH(2)-terminal DNA-binding and heterodimerization domain of HIF-1alpha to regulate HIF-1alpha stability together with HSP70. Inhibition of HSP90 activity with 17-Allylamino-17-demethoxygeldanamycin (17-AAG) increased COMMD1-mediated HIF-1alpha degradation independent of ubiquitin and pVHL. CONCLUSION/SIGNIFICANCE:These data reveal a novel role for COMMD1 in conjunction with HSP90beta/HSP70 in the ubiquitin and O(2)-independent regulation of HIF-1alpha
IVUS detects more coronary calcifications than MSCT; matter of both resolution and cross-sectional assessment?
Vascular Biology and Interventio
Time Course of Diastolic and Systolic Function Improvement After Pulmonary Valve Replacement in Adult Patients With Tetralogy of Fallot
ObjectivesThe aim of this research was to assess right ventricular diastolic and systolic function before and after pulmonary valve replacement (PVR) in adult patients after repair of tetralogy of Fallot.BackgroundPulmonary valve replacement (PVR) in adult patients late after repair of tetralogy of Fallot leads to rapid improvement of right ventricular (RV) systolic function.MethodsA total of 16 patients and 8 healthy subjects were included. Median age at initial repair was 4.9 (0.9 to 13.1) years, and mean age at PVR was 28.7 (19.5 to 45.6) years. Cardiac magnetic resonance imaging was performed before and 8 and 22 months after PVR. Right ventricular volumes and function as well as RV in- and outflow patterns were assessed.ResultsThe volume of the early filling of the RV (Evol) increased from 49.8 ± 14.7 ml to 53.8 ± 19.3 ml (not significant) and 62.0 ± 18.9 ml, respectively (p < 0.05), whereas the volume of the atrial contraction (Avol) remained unchanged. Consequently, the Evol/Avol ratio increased from 1.4 ± 0.7 before PVR to 1.6 ± 0.7 at 8 months (not significant) and 2.3 ± 1.2 at 22 months (p < 0.01). The Evol/Avol ratio was not significantly different from the healthy subjects at 22 months, indicating late recovery of diastolic function. Systolic function improved rapidly after PVR; the indexed RV end-systolic volume decreased from 93.7 ± 33.0 ml/m2to 60.9 ± 18.4 ml/m2(p < 0.01) and 54.8 ± 21.0 ml/m2(p < 0.01).ConclusionsIn adult patients late after total repair of Fallot, PVR leads to late improvement of diastolic function. We speculate that the rapid volume unloading after PVR increases systolic performance, whereas improvement in diastolic function requires long-term remodeling
Kleinverpakte gesneden witlof : haalbaarheidsstudie naar het minstens acht dagen bewaren van kleinverpakte gesneden witlof, met behoud van kwaliteit
320-row CT: does beat-to-beat motion of the coronary arteries affect image quality?
Vascular Biology and Interventio
p120-catenin prevents multinucleation through control of MKLP1-dependent RhoA activity during cytokinesis.
Spatiotemporal activation of RhoA and actomyosin contraction underpins cellular adhesion and division. Loss of cell-cell adhesion and chromosomal instability are cardinal events that drive tumour progression. Here, we show that p120-catenin (p120) not only controls cell-cell adhesion, but also acts as a critical regulator of cytokinesis. We find that p120 regulates actomyosin contractility through concomitant binding to RhoA and the centralspindlin component MKLP1, independent of cadherin association. In anaphase, p120 is enriched at the cleavage furrow where it binds MKLP1 to spatially control RhoA GTPase cycling. Binding of p120 to MKLP1 during cytokinesis depends on the N-terminal coiled-coil domain of p120 isoform 1A. Importantly, clinical data show that loss of p120 expression is a common event in breast cancer that strongly correlates with multinucleation and adverse patient survival. In summary, our study identifies p120 loss as a driver event of chromosomal instability in cancer
Semiclassical time--dependent propagation in three dimensions: How accurate is it for a Coulomb potential?
A unified semiclassical time propagator is used to calculate the
semiclassical time-correlation function in three cartesian dimensions for a
particle moving in an attractive Coulomb potential. It is demonstrated that
under these conditions the singularity of the potential does not cause any
difficulties and the Coulomb interaction can be treated as any other
non-singular potential. Moreover, by virtue of our three-dimensional
calculation, we can explain the discrepancies between previous semiclassical
and quantum results obtained for the one-dimensional radial Coulomb problem.Comment: 8 pages, 4 figures (EPS
320-row CT scanning: reduction in tube current parallels reduction in radiation exposure?
Cardiac Dysfunction and Arrhythmia
- …