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Tet3 is the main α-ketoglutarate (αKG)-dependent dioxygenase in neurons that converts 5-methyl-dC into 5-hydroxymethyl-dC and further on to 5-formyl- and 5-carboxy-dC. Neurons possess high levels of 5-hydroxymethyl-dC that further increase during neural activity to establish transcriptional plasticity required for learning and memory functions. How αKG, which is mainly generated in mitochondria as an intermediate of the tricarboxylic acid cycle, is made available in the nucleus has remained an unresolved question in the connection between metabolism and epigenetics. We show that in neurons the mitochondrial enzyme glutamate dehydrogenase, which converts glutamate into αKG in an NAD + -dependent manner, is redirected to the nucleus by the αKG-consumer protein Tet3, suggesting on-site production of αKG. Further, glutamate dehydrogenase has a stimulatory effect on Tet3 demethylation activity in neurons, and neuronal activation increases the levels of αKG. Overall, the glutamate dehydrogenase-Tet3 interaction might have a role in epigenetic changes during neural plasticity. α-ketoglutarate (αKG) is an intermediate in the tricarboxylic acid cycle that is required in the nucleus for genomic DNA demethylation by Tet3. Here, the authors show that the enzyme glutamate dehydrogenase, which converts glutamate to αKG, is redirected from the mitochondria to the nucleus.

The objective of the Karlsruhe Tritium Neutrino (KATRIN) experiment is to determine the effective electron neutrino mass \\[m(\\upnu _\\text {e})\\] with an unprecedented sensitivity of \\[0.2 \\hbox {eV}/\\hbox {c}^2\\] (\\[90 \\%\\,\\hbox {C.L.}\\]) by precision electron spectroscopy close to the endpoint of the \\[\\upbeta \\]-decay of tritium. We present a consistent theoretical description of the \\[\\upbeta \\]-electron energy spectrum in the endpoint region, an accurate model of the apparatus response function, and the statistical approaches suited to interpret and analyze tritium \\[\\upbeta \\]-decay data observed with KATRIN with the envisaged precision. In addition to providing detailed analytical expressions for all formulae used in the presented model framework with the necessary detail of derivation, we discuss and quantify the impact of theoretical and experimental corrections on the measured \\[m(\\upnu _\\text {e})\\]. Finally, we outline the statistical methods for parameter inference and the construction of confidence intervals that are appropriate for a neutrino mass measurement with KATRIN. In this context, we briefly discuss the choice of the \\[\\upbeta \\]-energy analysis interval and the distribution of measuring time within that range.

Mutations in the CNGA3 gene, which encodes the A subunit of the cyclic guanosine monophosphate (cGMP)-gated cation channel in cone photoreceptor outer segments, cause total colour blindness, also referred to as achromatopsia. Cones lacking this channel protein are non-functional, accumulate high levels of the second messenger cGMP and degenerate over time after induction of ER stress. The cell death mechanisms that lead to loss of affected cones are only partially understood. Here, we explored the disease mechanisms in the Cnga3 knockout (KO) mouse model of achromatopsia. We found that another important effector of cGMP, the cGMP-dependent protein kinase 2 (Prkg2) is crucially involved in cGMP cytotoxicity of cones in Cnga3 KO mice. Virus-mediated knockdown or genetic ablation of Prkg2 in Cnga3 KO mice counteracted degeneration and preserved the number of cones. Analysis of markers of endoplasmic reticulum stress and unfolded protein response confirmed that induction of these processes in Cnga3 KO cones also depends on Prkg2. In conclusion, we identified Prkg2 as a novel key mediator of cone photoreceptor degeneration in achromatopsia. Our data suggest that this cGMP mediator could be a novel pharmacological target for future neuroprotective therapies.

The Nab experiment will measure the correlation a between the momenta of the beta particle and antineutrino in neutron decay as well as the Fierz term b which distorts the beta spectrum.

The DARWIN observatory is a proposed next-generation experiment to search for particle dark matter and for the neutrinoless double beta decay of$$^{136}$$136 Xe. Out of its 50 t total natural xenon inventory, 40 t will be the active target of a time projection chamber which thus contains about 3.6 t of$$^{136}$$136 Xe. Here, we show that its projected half-life sensitivity is$$2.4\\times {10}^{27}\\,{\\hbox {year}}$$2.4 × 10 27 year , using a fiducial volume of 5 t of natural xenon and 10 year of operation with a background rate of less than 0.2 events/(t $$\\cdot $$·  year) in the energy region of interest. This sensitivity is based on a detailed Monte Carlo simulation study of the background and event topologies in the large, homogeneous target. DARWIN will be comparable in its science reach to dedicated double beta decay experiments using xenon enriched in$$^{136}$$136 Xe.

Precision spectroscopy of the electron spectrum of the tritium β-decay near the kinematic endpoint is a direct method to determine the effective electron antineutrino mass. The KArlsruhe TRItium Neutrino (KATRIN) experiment aims to determine this quantity with a sensitivity of better than 0.3 eV (90% C.L.). An inhomogeneous electric potential in the tritium source of KATRIN can lead to distortions of the β-spectrum, which directly impact the neutrino-mass observable. This effect can be quantified through precision spectroscopy of the conversion-electrons of co-circulated metastable 83mKr. Therefore, dedicated, several-weeks long measurement campaigns have been performed within the KATRIN data taking schedule. In this work, we infer the tritium source potential observables from these measurements, and present their implications for the neutrino-mass determination.

Precision spectroscopy of the electron spectrum of the tritium β-decay near the kinematic endpoint is a direct method to determine the effective electron antineutrino mass. The KArlsruhe TRItium Neutrino (KATRIN) experiment aims to determine this quantity with a sensitivity of better than 0.3 eV (90% C.L.). An inhomogeneous electric potential in the tritium source of KATRIN can lead to distortions of the β-spectrum, which directly impact the neutrino-mass observable. This effect can be quantified through precision spectroscopy of the conversion-electrons of co-circulated metastable 83mKr. Therefore, dedicated, several-weeks long measurement campaigns have been performed within the KATRIN data taking schedule. In this work, we infer the tritium source potential observables from these measurements, and present their implications for the neutrino-mass determination.

Precision spectroscopy of the electron spectrum of the tritium$$\\upbeta $$β -decay near the kinematic endpoint is a direct method to determine the effective electron antineutrino mass. The KArlsruhe TRItium Neutrino (KATRIN) experiment aims to determine this quantity with a sensitivity of better than$${0.3}{\\hbox { eV}}$$0.3 eV ($$90\\%$$90 %  C.L.). An inhomogeneous electric potential in the tritium source of KATRIN can lead to distortions of the$$\\upbeta $$β -spectrum, which directly impact the neutrino-mass observable. This effect can be quantified through precision spectroscopy of the conversion-electrons of co-circulated metastable$$^{83\\text {m}}\\text {Kr}$$83 m Kr . Therefore, dedicated, several-weeks long measurement campaigns have been performed within the KATRIN data taking schedule. In this work, we infer the tritium source potential observables from these measurements, and present their implications for the neutrino-mass determination.

We correct an overestimation of the production rate of 137 Xe in the DARWIN detector operated at LNGS. This formerly dominant intrinsic background source is now at a level similar to the irreducible background from solar 8 B neutrinos, thus unproblematic at the LNGS depth. The projected half-life sensitivity for the neutrinoless double beta decay ( 0 ν β β ) of 136 Xe improves by 22 % compared to the previously reported number and is now T 1 / 2 0 ν = 3.0 × 10 27 yr (90% C.L.) after 10 years of DARWIN operation.

We correct an overestimation of the production rate of$$^{137}$$137 Xe in the DARWIN detector operated at LNGS. This formerly dominant intrinsic background source is now at a level similar to the irreducible background from solar$$^8$$8 B neutrinos, thus unproblematic at the LNGS depth. The projected half-life sensitivity for the neutrinoless double beta decay ($$0\\nu \\beta \\beta $$0 ν β β ) of$$^{136}$$136 Xe improves by$$22\\%$$22 % compared to the previously reported number and is now$$T^{0\\nu }_{1/2}= {3.0\\times 10^{27}} \\hbox { yr}$$T 1 / 2 0 ν = 3.0 × 10 27 yr (90% C.L.) after 10 years of DARWIN operation.