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- Hannan, Katherine M., et al.
(författare)
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Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway
- 2022
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 41:5
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Tidskriftsartikel (refereegranskat)abstract
- The nucleolar surveillance pathway monitors nucleolar integrity and responds to nucleolar stress by mediating binding of ribosomal proteins to MDM2, resulting in p53 accumulation. Inappropriate pathway activation is implicated in the pathogenesis of ribosomopathies, while drugs selectively activating the pathway are in trials for cancer. Despite this, the molecular mechanism(s) regulating this process are poorly understood. Using genome-wide loss-of-function screens, we demonstrate the ribosome biogenesis axis as the most potent class of genes whose disruption stabilizes p53. Mechanistically, we identify genes critical for regulation of this pathway, including HEATR3. By selectively disabling the nucleolar surveillance pathway, we demonstrate that it is essential for the ability of all nuclear-acting stresses, including DNA damage, to induce p53 accumulation. Our data support a paradigm whereby the nucleolar surveillance pathway is the central integrator of stresses that regulate nuclear p53 abundance, ensuring that ribosome biogenesis is hardwired to cellular proliferative capacity.
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- Jonsson, Caroline, 1977, et al.
(författare)
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Adsorption of glyphosate on goethite (alpha-FeOOH): Surface complexation modeling combining spectroscopic and adsorption data
- 2008
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Ingår i: Environmental Science & Technology. - 0013-936X. ; 42:7, s. 2464-2469
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Tidskriftsartikel (refereegranskat)abstract
- N-(phosphonomethyl)glycine (glyphosate, PMG) is the most widely used herbicide, and its adsorption onto soil minerals plays a significant role in its mobility and rate of degradation. In this work, we present the results of the first serious effort to find a realistic surface complexation model that fits both adsorption and total proton concentration data for PMG on the common soil mineral, goethite. Special attention was focused on making sure that the final model was in good semiquantitative agreement with previously reported X-ray photoelectron spectroscopy and Fourier-transform infrared spectroscopic measurements. Electrostatic effects were accounted for using the Basic Stern model, and the charges of the PMG-containing surface complexes were assumed to be distributed across the O- and beta-planes. The reactions for the protonation of the goethite surface were described using the 1 pK model, We optimized on the intrinsic formation constants and the charge distributions of the complexes, as well as the initial total proton concentration (l = 0.1 M Na(NO3), 25.0 degrees C), and the following model was obtained. FeOH0.5- + H3L reversible arrow FeHL1.5- +H++H2O Log10 beta = 4.70 +/- 0.08, Q(0) = -0.18 +/- 0.02 FeOH0.5- + H3L reversible arrow FeL2.5- + 2H(+) + H2O Log(10) beta = -3.9 +/- 0. 1, Q(0) = -0.7 +/- 0.1 Here, beta is the intrinsic formation constant, Q(0) is the charge at the 0-plane, and the errors are reported as one standard deviation. The charge distributions of the complexes are rationalized by considering intramolecular hydrogen bonding between the protons of the amine group and both the phosphonate and carboxylate groups.
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- Loring, Zak, et al.
(författare)
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Acute echocardiographic and hemodynamic response to his-bundle pacing in patients with first-degree atrioventricular block
- 2022
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Ingår i: Annals of Noninvasive Electrocardiology. - : Wiley. - 1082-720X .- 1542-474X. ; 27:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Atrial pacing and right ventricular (RV) pacing are both associated with adverse outcomes among patients with first-degree atrioventricular block (1°AVB). His-bundle pacing (HBP) provides physiological activation of the ventricle and may be able to improve both atrioventricular (AV) and inter-ventricular synchrony in 1°AVB patients. This study evaluates the acute echocardiographic and hemodynamic effects of atrial, atrial-His-bundle sequential (AH), and atrial-ventricular (AV) sequential pacing in 1°AVB patients. Methods: Patients with 1°AVB undergoing atrial fibrillation ablation were included. Following left atrial (LA) catheterization, patients underwent atrial, AH- and AV-sequential pacing. LA/left ventricular (LV) pressure and echocardiographic measurements during the pacing protocols were compared. Results: Thirteen patients with 1°AVB (mean PR 221 ± 26 ms) were included. The PR interval was prolonged with atrial pacing compared to baseline (275 ± 73 ms, p =.005). LV ejection fraction (LVEF) was highest during atrial pacing (62 ± 11%), intermediate with AH-sequential pacing (59 ± 7%), and lowest with AV-sequential pacing (57 ± 12%) though these differences were not statistically significant. No significant differences were found in LA or LV mean pressures or LV dP/dT. LA and LV volumes, isovolumetric times, electromechanical delays, and global longitudinal strains were similar across pacing protocols. Conclusion: Despite pronounced PR prolongation, the acute effects of atrial pacing were not significantly different than AH- or AV-sequential pacing. Normalizing atrioventricular and/or inter-ventricular dyssynchrony did not result in acute improvements in cardiac output or loading conditions.
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