56 research outputs found
Poly(ADP-ribose)glycohydrolase is an upstream regulator of Ca2+ fluxes in oxidative cell death
Oxidative DNA damage to cells activates poly(ADP-ribose)polymerase-1 (PARP-1) and the poly(ADP-ribose) formed is rapidly degraded to ADP-ribose by poly(ADP-ribose)glycohydrolase (PARG). Here we show that PARP-1 and PARG control extracellular Ca2+ fluxes through melastatin-like transient receptor potential 2 channels (TRPM2) in a cell death signaling pathway. TRPM2 activation accounts for essentially the entire Ca2+ influx into the cytosol, activating caspases and causing the translocation of apoptosis inducing factor (AIF) from the inner mitochondrial membrane to the nucleus followed by cell death. Abrogation of PARP-1 or PARG function disrupts these signals and reduces cell death. ADP-ribose-loading of cells induces Ca2+ fluxes in the absence of oxidative damage, suggesting that ADP-ribose is the key metabolite of the PARP-1/PARG system regulating TRPM2. We conclude that PARP-1/PARG control a cell death signal pathway that operates between five different cell compartments and communicates via three types of chemical messengers: a nucleotide, a cation, and protein
Comparability of radiocarbon measurements in dissolved inorganic carbon of seawater produced at ETH-Zurich
Radiocarbon observations (Δ14C) in dissolved inorganic carbon (DIC) of seawater provide useful information about ocean carbon cycling and ocean circulation. To deliver high-quality observations, the Laboratory of Ion Beam Physics (LIP) at ETH-Zurich developed a new simplified method allowing the rapid analysis of radiocarbon in DIC of small seawater samples, which is continually assessed by following internal quality controls. However, a comparison with externally produced 14C measurements to better establish an equivalency between methods was still missing. Here, we make the first intercomparison with the National Ocean Sciences Accelerator Mass Spectrometry (NOSAMS) facility based on 14 duplicate seawater samples collected in 2020. We also compare with prior deep-water observations from the 1970s to 1990s. The results show a very good agreement in both comparisons. The mean Δ14C of 12 duplicate samples measured by LIP and NOSAMS were statistically identical within one sigma uncertainty while two other duplicate samples agreed within two sigma. Based on this small number of duplicate samples, LIP values appear to be slightly lower than the NOSAMS values, but more measurements will be needed for confirmation. We also comment on storage and preservation techniques used in this study, including the freezing of samples collected in foil bags
In situ uniaxial pressure cell for x-ray and neutron scattering experiments
We present an in situ uniaxial pressure device optimized for small angle x-ray and neutron scattering experiments at low-temperatures and high magnetic fields. A stepper motor generates force, which is transmitted to the sample via a rod with an integrated transducer that continuously monitors the force. The device has been designed to generate forces up to 200 N in both compressive and tensile configurations, and a feedback control allows operating the system in a continuous-pressure mode as the temperature is changed. The uniaxial pressure device can be used for various instruments and multiple cryostats through simple and exchangeable adapters. It is compatible with multiple sample holders, which can be easily changed depending on the sample properties and the desired experiment and allow rapid sample changes
In situ uniaxial pressure cell for x-ray and neutron scattering experiments
We present an in situ uniaxial pressure device optimized for small angle x-ray and neutron scattering experiments at low-temperatures and high magnetic fields. A stepper motor generates force, which is transmitted to the sample via a rod with an integrated transducer that continuously monitors the force. The device has been designed to generate forces up to 200 N in both compressive and tensile configurations, and a feedback control allows operating the system in a continuous-pressure mode as the temperature is changed. The uniaxial pressure device can be used for various instruments and multiple cryostats through simple and exchangeable adapters. It is compatible with multiple sample holders, which can be easily changed depending on the sample properties and the desired experiment and allow rapid sample changes
Design and performance of the multiplexing spectrometer CAMEA
The cold neutron multiplexing secondary spectrometer CAMEA (Continuous Angle
Multiple Energy Analysis) was commissioned at the Swiss spallation neutron
source SINQ at the Paul Scherrer Institut at the end of 2018. The spectrometer
is optimised for an efficient data collection in the horizontal scattering
plane, allowing for detailed and rapid mapping of excitations under extreme
conditions. The novel design consists of consecutive, upward scattering
analyzer arcs underneath an array of position sensitive detectors mounted
inside a low permeability stainless-steel vacuum vessel. The construction of
the world's first continuous angle multiple energy analysis instrument required
novel solutions to many technical challenges, including analyzer mounting,
vacuum connectors, and instrument movement. These were solved by extensive
prototype experiments and in-house developments. Here we present a technical
overview of the spectrometer describing in detail the engineering solutions and
present our first experimental data taken during the commissioning. Our results
demonstrate the tremendous gains in data collection rate for this novel type of
spectrometer design
Poly(ADP-ribose)glycohydrolase is an upstream regulator of Ca2+ fluxes in oxidative cell death
Oxidative DNA damage to cells activates poly(ADP-ribose)polymerase-1 (PARP-1) and the poly(ADP-ribose) formed is rapidly degraded to ADP-ribose by poly(ADP-ribose)glycohydrolase (PARG). Here we show that PARP-1 and PARG control extracellular Ca2+ fluxes through melastatin-like transient receptor potential 2 channels (TRPM2) in a cell death signaling pathway. TRPM2 activation accounts for essentially the entire Ca2+ influx into the cytosol, activating caspases and causing the translocation of apoptosis inducing factor (AIF) from the inner mitochondrial membrane to the nucleus followed by cell death. Abrogation of PARP-1 or PARG function disrupts these signals and reduces cell death. ADP-ribose-loading of cells induces Ca2+ fluxes in the absence of oxidative damage, suggesting that ADP-ribose is the key metabolite of the PARP-1/PARG system regulating TRPM2. We conclude that PARP-1/PARG control a cell death signal pathway that operates between five different cell compartments and communicates via three types of chemical messengers: a nucleotide, a cation, and proteins
Findings from an in-depth annual tree-ring radiocarbon intercomparison
The radiocarbon (¹⁴C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties
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