195 research outputs found
Approaching the Gamow Window with Stored Ions : Direct Measurement of Xe 124 (p,γ) in the ESR Storage Ring
© 2019 American Physical Society. All rights reserved.We report the first measurement of low-energy proton-capture cross sections of Xe124 in a heavy-ion storage ring. Xe12454+ ions of five different beam energies between 5.5 and 8 AMeV were stored to collide with a windowless hydrogen target. The Cs125 reaction products were directly detected. The interaction energies are located on the high energy tail of the Gamow window for hot, explosive scenarios such as supernovae and x-ray binaries. The results serve as an important test of predicted astrophysical reaction rates in this mass range. Good agreement in the prediction of the astrophysically important proton width at low energy is found, with only a 30% difference between measurement and theory. Larger deviations are found above the neutron emission threshold, where also neutron and γ widths significantly impact the cross sections. The newly established experimental method is a very powerful tool to investigate nuclear reactions on rare ion beams at low center-of-mass energies.Peer reviewedFinal Published versio
Remodeling the Proteostasis Network to Rescue Glucocerebrosidase Variants by Inhibiting ER-Associated Degradation and Enhancing ER Folding
Gaucher’s disease (GD) is characterized by loss of lysosomal glucocerebrosidase (GC) activity. Mutations in the gene encoding GC destabilize the protein’s native folding leading to ER-associated degradation (ERAD) of the misfolded enzyme. Enhancing the cellular folding capacity by remodeling the proteostasis network promotes native folding and lysosomal activity of mutated GC variants. However, proteostasis modulators reported so far, including ERAD inhibitors, trigger cellular stress and lead to induction of apoptosis. We show herein that lacidipine, an L-type Ca2+ channel blocker that also inhibits ryanodine receptors on the ER membrane, enhances folding, trafficking and lysosomal activity of the most severely destabilized GC variant achieved via ERAD inhibition in fibroblasts derived from patients with GD. Interestingly, reprogramming the proteostasis network by combining modulation of Ca2+ homeostasis and ERAD inhibition remodels the unfolded protein response and dramatically lowers apoptosis induction typically associated with ERAD inhibition
The impact of dietary interventions on cardiometabolic health
Obesity and cardiometabolic diseases are leading causes of morbidity and mortality among adults worldwide. These conditions significantly contribute to and exacerbate other major causes of illness and death, including cancer, neurodegenerative diseases, and chronic kidney disease. The growing burden of these diseases has increased the interest of modern medicine in understanding metabolic processes and health, with diet emerging as a pivotal modifiable factor, alongside physical inactivity and smoking. In this review, we discuss the pathophysiological and evolutionary foundations of metabolic processes that may link “unhealthy” nutrition to obesity and cardiometabolic diseases and review the current literature to assess the effects of various diet interventions and patterns on cardiometabolic parameters. Special emphasis is placed on summarizing the latest, albeit partially contradictory, evidence to offer balanced dietary recommendations with the ultimate aim to improve cardiometabolic health. © The Author(s) 2025
Enzymatic Blockade of the Ubiquitin-Proteasome Pathway
Ubiquitin-dependent processes control much of cellular physiology. We show that expression of a highly active, Epstein-Barr virus-derived deubiquitylating enzyme (EBV-DUB) blocks proteasomal degradation of cytosolic and ER-derived proteins by preemptive removal of ubiquitin from proteasome substrates, a treatment less toxic than the use of proteasome inhibitors. Recognition of misfolded proteins in the ER lumen, their dislocation to the cytosol, and degradation are usually tightly coupled but can be uncoupled by the EBV-DUB: a misfolded glycoprotein that originates in the ER accumulates in association with cytosolic chaperones as a deglycosylated intermediate. Our data underscore the necessity of a DUB activity for completion of the dislocation reaction and provide a new means of inhibition of proteasomal proteolysis with reduced cytotoxicity.National Institutes of Health (U.S.)EMBO (long term Fellowship 2008-379)Boehringer Ingelheim Fond
Thermal (n, γ) cross section and resonance integral of 171Tm
Background: About 50% of the heavy elements are produced in stars during the slow neutron capture process.
The analysis of branching points allows us to set constraints on the temperature and the neutron density in the
interior of stars.
Purpose: The temperature dependence of the branch point 171Tm is weak. Hence, the 171Tm neutron capture
cross section can be used to constrain the neutron density during the main component of the s process in thermally
pulsing asymptotic giant branch (TP-AGB) stars.
Methods: A 171Tm sample produced at the ILL was activated with thermal and epithermal neutrons at the
TRIGA research reactor at the Johannes Gutenberg-Universität Mainz.
Results: The thermal neutron capture cross section and the resonance integral have been measured for the first
time to be σth = 9.9 ± 0.9 b and σRI = 193 ± 14 b.
Conclusions: Based on our results, new estimations of the direct capture components’ impact on the
Maxwellian-nAveraged cross sections (MACS) are possible.European Unions’s Seventh Framework Programme (FP/2007-2013
Simulations of the High-Energy Beam-Transport (HEBT) section at FRANZ
The neutron source FRANZ (Frankfurter Neutronenquelle am
Stern-Gerlach-Zentrum), which is currently under construction, will be the neutron source with the highest intensity in the nuclear-astrophysically relevant energy
region. The TraceWin code was used to design the High-Energy Beam-Transport section with regard to the experimental requirements at different target positions
Neutron activation of Ga and Ga at kBT≈25 keV
Background: About 50% of heavy elements are produced by the slow neutron capture process (s process) in stars. The element gallium is mostly produced during the weak s process in massive stars.
Purpose: Our activation at kT≈25 keV is the first experiment in a series of activation and time-of-flight measurements on Ga and Ga relevant for astrophysics.
Methods: We activated Ga and Ga with a neutron distribution that corresponds to a quasistellar distribution with kT=25 keV at the Joint Research Centre (JRC), Geel, Belgium. Protons were provided by an electrostatic Van de Graaff accelerator to produce neutrons via the reaction Li(p,n). The produced activity was measured via the γ emission by the decaying product nuclei by high-purity germanium detectors.
Results: We provide spectrum-averaged cross sections (SACS) and ratios of the cross sections σ/σ for the neutron spectrum of the activation. We obtain values of σ=(186±12) mb and σ = (112±7) mb, and cross section ratios of σ/σ=0.29±0.02 and σ/σ = 0.17±0.01.
Conclusions: Our data disagree with the available evaluated data provided by KADoNiS v0.3, our cross-section ratio is about 20% higher for Ga and about 20% lower for Ga
IgE Mediated Autoallergy against Thyroid Peroxidase – A Novel Pathomechanism of Chronic Spontaneous Urticaria?
Chronic spontaneous urticaria (csU), which is characterized by recurrent episodes
of mast cell-driven wheal and flare-type skin reactions, is often associated with
elevated total IgE levels and thyroid autoimmunity. We speculate that some csU
patients express IgE autoantibodies against thyroid antigens such as thyroid
peroxidase (TPO), which could bind to skin mast cells and induce their
activation.We developed and used a site-directed human IgE capture ELISA to quantify
IgE-anti-TPO. We used this assay and investigated csU patients
(n = 478) and healthy control subjects
(n = 127) for IgE-anti-TPO and then assessed
IgE-anti-TPO-positive and -negative csU patients for clinical and serological
differences. ( = 61%, IgE-anti-TPO:
median 6.67, interquartile range 5.39–8.24). IgE-anti-TPO-positive and
-negative csU patients had very similar distributions of age and gender as well as
disease activity and duration. IgE-anti-TPO-positive csU patients exhibited
significantly higher IgG-anti-TPO levels and lymphocyte counts as well as
decreased C4 complement levels.Our findings show that a sizeable subgroup of csU patients expresses IgE
antibodies against thyroid peroxidase. These autoantibodies could cause
“autoallergic” mast cell activation, a novel pathomechanism of chronic
spontaneous urticaria
The TRC8 E3 ligase ubiquitinates MHC class I molecules before dislocation from the ER
Human cytomegalovirus uses an E3 ubiquitin ligase to divert MHC I molecules into the ER-associated degradation pathway for destruction
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