We report the measurement of the two-neutrino double-beta ($2\nu\beta\beta$) decay of $^{100}$Mo to the ground state of $^{100}$Ru using lithium molybdate (\crystal) scintillating bolometers. The ...detectors were developed for the CUPID-Mo program and operated at the EDELWEISS-III low background facility in the Modane underground laboratory. From a total exposure of $42.235$ kg$\times$d, the half-life of $^{100}$Mo is determined to be $T_{1/2}^{2\nu}=7.12^{+0.18}_{-0.14}\,\mathrm{(stat.)}\pm0.10\,\mathrm{(syst.)}\times10^{18}$ years. This is the most accurate determination of the $2\nu\beta\beta$ half-life of $^{100}$Mo to date. We also confirm, with the statistical significance of $>3\sigma$, that the single-state dominance model of the $2\nu\beta\beta$ decay of $^{100}$Mo is favored over the high-state dominance model.
Ricochet Progress and Status Augier, C.; Beaulieu, G.; Belov, V. ...
Journal of low temperature physics,
08/2023, Letnik:
212, Številka:
3-4
Journal Article
Recenzirano
Odprti dostop
We present an overview of recent progress toward the
Ricochet
coherent elastic neutrino nucleus scattering (CE
ν
NS) experiment. The ILL research reactor in Grenoble, France has been selected as the ...experiment site, after in situ studies of vibration and particle backgrounds. We present background rate estimates specific to that site, along with descriptions of the planned CryoCube and Q-Array detector payloads.
We report the measurement of the two-neutrino double-beta (
2
ν
β
β
) decay of
100
Mo to the ground state of
100
Ru using lithium molybdate (
Li
2
100
MoO
4
) scintillating bolometers. The detectors ...were developed for the CUPID-Mo program and operated at the EDELWEISS-III low background facility in the Modane underground laboratory (France). From a total exposure of 42.235 kg
×
day, the half-life of
100
Mo is determined to be
T
1
/
2
2
ν
=
7
.
12
-
0.14
+
0.18
(
stat
.
)
±
0.10
(
syst
.
)
×
10
18
years. This is the most accurate determination of the
2
ν
β
β
half-life of
100
Mo to date.
Abstract
We report the measurement of the two-neutrino double-beta (
$$2\nu \beta \beta $$
2
ν
β
β
) decay of
$$^{100}$$
100
Mo to the ground state of
$$^{100}$$
100
Ru using lithium molybdate (
...$$\hbox {Li}_2^{\;\;100}\hbox {MoO}_4$$
Li
2
100
MoO
4
) scintillating bolometers. The detectors were developed for the CUPID-Mo program and operated at the EDELWEISS-III low background facility in the Modane underground laboratory (France). From a total exposure of 42.235 kg
$$\times $$
×
day, the half-life of
$$^{100}$$
100
Mo is determined to be
$$T_{1/2}^{2\nu }=7.12^{+0.18}_{-0.14}\,\mathrm {(stat.)}\pm 0.10\,\mathrm {(syst.)}\times 10^{18}$$
T
1
/
2
2
ν
=
7
.
12
-
0.14
+
0.18
(
stat
.
)
±
0.10
(
syst
.
)
×
10
18
years. This is the most accurate determination of the
$$2\nu \beta \beta $$
2
ν
β
β
half-life of
$$^{100}$$
100
Mo to date.
Abstract We report the measurement of the two-neutrino double-beta ($$2\nu \beta \beta $$ 2νββ ) decay of $$^{100}$$ 100 Mo to the ground state of $$^{100}$$ 100 Ru using lithium molybdate ($$\hbox ...{Li}_2^{\;\;100}\hbox {MoO}_4$$ Li2100MoO4 ) scintillating bolometers. The detectors were developed for the CUPID-Mo program and operated at the EDELWEISS-III low background facility in the Modane underground laboratory (France). From a total exposure of 42.235 kg$$\times $$ × day, the half-life of $$^{100}$$ 100 Mo is determined to be $$T_{1/2}^{2\nu }=7.12^{+0.18}_{-0.14}\,\mathrm {(stat.)}\pm 0.10\,\mathrm {(syst.)}\times 10^{18}$$ T1/22ν=7.12-0.14+0.18(stat.)±0.10(syst.)×1018 years. This is the most accurate determination of the $$2\nu \beta \beta $$ 2νββ half-life of $$^{100}$$ 100 Mo to date.
We report the measurement of the two-neutrino double-beta ($2\nu \beta \beta $) decay of $^{100}$Mo to the ground state of $^{100}$Ru using lithium molybdate ($\hbox {Li}_2^{\;\;100}\hbox {MoO}_4$) ...scintillating bolometers. The detectors were developed for the CUPID-Mo program and operated at the EDELWEISS-III low background facility in the Modane underground laboratory (France). From a total exposure of 42.235 kg$\times $day, the half-life of $^{100}$Mo is determined to be $T_{1/2}^{2\nu }=7.12^{+0.18}_{-0.14}\,\mathrm {(stat.)}\pm 0.10\,\mathrm {(syst.)}\times 10^{18}$ years. This is the most accurate determination of the $2\nu \beta \beta $ half-life of $^{100}$Mo to date.
Background:
Small nucleolar RNAs (snoRNAs) are a group of non‐coding RNAs. The most prominent role for snoRNA is to guide small nucleolar ribonucleoproteins (snoRNPs) to complementary regions of ...ribosomal (rRNA), where the snoRNP complexes catalyze ribosomal modifications. snoRNAs are divided into the two major classes: box C/D and box H/ACA snoRNAs. C/D box snoRNAs are involved in 2‐O‐methylation, whereas H/ACA snoRNAs guide pseudouridylation. Beyond the role in rRNA modification, functions in splicing and chromatin have been proposed. Recently, we demonstrated that snoRNAs play a critical role for AML1‐ETO induced leukemia (Zhou et al., Nat Cell Biol 2017).
Aims:
We aimed to elucidate snoRNA expression patterns and functions in acute myeloid leukemia and establish the first global map of 2’‐methylation of rRNA in AML patients.
Methods:
We analyzed snoRNA expression patterns in a cohort of 161 AML patients using small‐RNA sequencing. All patient samples were obtained at the time of diagnosis. Expression levels were calculated for known C/D‐box and H/ACA‐box snoRNA. Only regions with at least one reads per million (RPM) in at least one patient sample were included for further investigation. We applied ribomethseq to elucidate the entire ribosomal 2’‐0 methylation pattern in AML patients. We calculated the methylation scoreC from 5’‐read ends for all known sites from snOPY and an updated list from Krogh et al. 2016, Further, methylation patterns and snoRNA patterns were analysed with regard to AML mutations as analysed by panel sequencing.
Results:
Next generation sequencing data revealed expression o 354 known C/D box snoRNAs and 160 H/ACA box snoRNAs in primary AML patient samples. Expression patterns of snoRNAs varied according to specific genetic risk groups. High levels of snoRNA expression were observed in intermediate molecular risk group patients (215 C/D box and 68 H/ACA box snoRNAs, p≤0.05). Also, high levels of snoRNA were found in patients with a poor response to the first cycle of induction therapy (144 C/D box and 61 H/ACA box snoRNAs, p≤0.05). Of note, NPM1 mutations were associated with wide ranging changes in expression (almost all downregulation) in 232 C/D box and 61 H/ACA box snoRNA. In contrast, AMLs with ASXL1 or RUNX1 mutations predominantly expressed higher levels of snoRNA expression. We established the first map of ribosomal 2’‐0 methylation patterns in AML patients on published modification sites. This resulted in RiboMethylome data constituting 107 high quality ribosomal sites which were methylated in AML patients. In most instances, C/D box snoRNA expression was positively correlated with the respective levels of 2́‐O‐methylation in rRNA. Importantly, NPM1 mutation status strongly influenced the RiboMethylome in affected AML blasts.
Summary/Conclusion:
AML with different mutation patterns exhibit striking differences in snoRNA expression levels. Our data reveal widespread plasticity of epitranscriptomic modifications in the ribosomes of AML patients. These findings suggest that driver mutations in AML could induce specialized ribosomes which may contribute to leukemic transformation.
Background:
Alternative splicing (AS) is essentially regulated by RNA‐binding proteins (RBPs) and is one of many deregulated cellular processes in Acute Myeloid Leukemia (AML). The alternative usage ...of exons substantially increases the coding potential of mRNAs and frequently leads to the expression of tumor‐promoting mRNA variants in cancer modulating apoptosis, proliferation, invasion and migration of cancer cells. This underlines the great plasticity of AS in cancer and justifies the need to elucidate the function of nuclear RBPs in specific cancer types. We found that the RNA helicase DDX17 is significantly more highly expressed in primary human AML specimens with high versus low Leukemia Stem Cell (LSC) frequency.
Aims:
In this study, we aimed to understand the functional role of DDX17 in normal hematopoietic stem and progenitor cells (HSPCs) and in AML cells. In particular, we sought to determine whether DDX17 exerts its function in the hematopoietic system primarily via AS or AS‐unrelated mechanisms.
Methods:
We performed knockdown (KD) experiments using small hairpin (sh) RNAs to determine whether DDX17 was essential for primary human cord blood CD34+ HSPCs and leukemia cells. Furthermore, mRFP tagged DDX17 was overexpressed through lentiviral transduction to track protein localization by immunofluorescence (IF) imaging. Lentivirally transduced HSPCs and leukemia cells were analyzed in vitro for proliferative output, viability, immunophenotype, and colony formation potential. RNA sequencing (RNA‐Seq) was used to determine how DDX17 KD affected gene expression and alternative exon usage. Pull down experiments combined with mass spectrometry revealed binding partners in presence and absence of chemotherapeutic agents. Finally, we performed homologous recombination (HR) and drug sensitivity assays to determine the role of DDX17 in DNA damage.
Results:
Knockdown of DDX17 induced DNA damage and severely impaired the function of healthy HSPCs and TP53 wild type AML cells. TP53 null cells maintained their proliferative capacity during short term in vitro expansion in absence of DDX17, but were significantly sensitized towards DNA damaging agents. In line, overexpression of DDX17 protected the cells against double strand break (DSB) inducing drugs. IF imaging revealed direct recruitment of DDX17 to DNA damage sites, while RNA‐Seq showed suppression of multiple DNA repair genes.
Summary/Conclusion:
RNA‐Seq, IF imaging, proteomics, and HR assays suggest an essential role of DDX17 in DNA repair via different mechanisms including direct recruitment to DNA damage sites, alternative splicing, and regulation of DNA repair genes on the transcriptional level.
Background Epigenetic marks are heritable, influenced by the environment, direct the maturation of T lymphocytes, and in mice enhance the development of allergic airway disease. Thus it is important ...to define epigenetic alterations in asthmatic populations. Objective We hypothesize that epigenetic alterations in circulating PBMCs are associated with allergic asthma. Methods We compared DNA methylation patterns and gene expression in inner-city children with persistent atopic asthma versus healthy control subjects by using DNA and RNA from PBMCs. Results were validated in an independent population of asthmatic patients. Results Comparing asthmatic patients (n = 97) with control subjects (n = 97), we identified 81 regions that were differentially methylated. Several immune genes were hypomethylated in asthma, including IL13 , RUNX3 , and specific genes relevant to T lymphocytes ( TIGIT ). Among asthmatic patients, 11 differentially methylated regions were associated with higher serum IgE concentrations, and 16 were associated with percent predicted FEV1 . Hypomethylated and hypermethylated regions were associated with increased and decreased gene expression, respectively ( P < 6 × 10−12 for asthma and P < .01 for IgE). We further explored the relationship between DNA methylation and gene expression using an integrative analysis and identified additional candidates relevant to asthma ( IL4 and ST2 ). Methylation marks involved in T-cell maturation (RUNX3) , TH 2 immunity (IL4) , and oxidative stress (catalase) were validated in an independent asthmatic cohort of children living in the inner city. Conclusions Our results demonstrate that DNA methylation marks in specific gene loci are associated with asthma and suggest that epigenetic changes might play a role in establishing the immune phenotype associated with asthma.
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