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| 2. |
- Abdelhameed, A. H., et al.
(författare)
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Cryogenic characterization of a LiAlO2 crystal and new results on spin-dependent dark matter interactions with ordinary matter: CRESST Collaboration
- 2020
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Ingår i: European Physical Journal C. - : Springer Science and Business Media LLC. - 1434-6044 .- 1434-6052. ; 80:9
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Tidskriftsartikel (refereegranskat)abstract
- In this work, a first cryogenic characterization of a scintillating LiAlO2 single crystal is presented. The results achieved show that this material holds great potential as a target for direct dark matter search experiments. Three different detector modules obtained from one crystal grown at the Leibniz-Institut fur Kristallzuchtung (IKZ) have been tested to study different properties at cryogenic temperatures. Firstly, two 2.8 g twin crystals were used to build different detector modules which were operated in an above-ground laboratory at the Max Planck Institute for Physics (MPP) in Munich, Germany. The first detector module was used to study the scintillation properties of LiAlO2 at cryogenic temperatures. The second achieved an energy threshold of (213.02 +/- 1.48) eV which allows setting a competitive limit on the spin-dependent dark matter particle-proton scattering cross section for dark matter particle masses between 350 MeV/c2 and 1.50 GeV/c2. Secondly, a detector module with a 373 g LiAlO2 crystal as the main absorber was tested in an underground facility at the Laboratori Nazionali del Gran Sasso (LNGS): from this measurement it was possible to determine the radiopurity of the crystal and study the feasibility of using this material as a neutron flux monitor for low-background experiments.
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| 3. |
- Bertoldo, E., et al.
(författare)
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Lithium-Containing Crystals for Light Dark Matter Search Experiments
- 2020
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Ingår i: Journal of Low Temperature Physics. - : Springer Science and Business Media LLC. - 0022-2291 .- 1573-7357. ; 199:1-2, s. 510-518
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Tidskriftsartikel (refereegranskat)abstract
- In the current direct dark matter search landscape, the leading experiments in the sub-GeV mass region mostly rely on cryogenic techniques which employ crystalline targets. One attractive type of crystals for these experiments is those containing lithium, due to the fact that 7Li is an ideal candidate to study spin-dependent dark matter interactions in the low mass region. Furthermore, 6Li can absorb neutrons, a challenging background for dark matter experiments, through a distinctive signature which allows the monitoring of the neutron flux directly on site. In this work, we show the results obtained with three different detectors based on LiAlO 2, a target crystal never used before in cryogenic experiments.
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| 4. |
- Kluck, H., et al.
(författare)
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Latest results of CRESST-III's search for sub-GeV/c(2) dark matter
- 2020
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6596 .- 1742-6588. ; 1468:1
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Konferensbidrag (refereegranskat)abstract
- The CRESST-III experiment searches for direct interactions of dark matter with ordinary matter. The main event signature would be a nuclear recoil inside one of the scintillating CaWO4 crystals. Operating the crystals as cryogenic calorimeters provides a phonon signal as measure of the deposited energy. The simultaneous readout of both signals is used to actively discriminate backgrounds. CRESST-III focuses on the sub-GeV/c(2) mass region where the sensitivity is driven by the threshold. In the first data taking campaign of CRESST-III from 2016-2018 an unprecedented low threshold of 30.1 eV for nuclear recoils was obtained. In this contribution, we will report the status of the experiment and the latest results. [GRAPHICS]
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| 5. |
- Mancuso, M., et al.
(författare)
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Searches for Light Dark Matter with the CRESST-III Experiment
- 2020
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Ingår i: Journal of Low Temperature Physics. - : Springer Science and Business Media LLC. - 0022-2291 .- 1573-7357. ; 199:1-2, s. 547-555
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Tidskriftsartikel (refereegranskat)abstract
- Cryogenic Rare Event Search with Superconducting Thermometers (CRESST) is a long-standing direct dark matter detection experiment with cryogenic detectors located at the underground facility Laboratori Nazionali del Gran Sasso in Italy. CRESST-III, the third generation of CRESST, was specifically designed to have a world-leading sensitivity for low-mass dark matter (DM) (less than 2 GeV/c 2) to probe the spin-independent DM-nucleus cross section. At present, a large part of the parameter space for spin-independent scattering off nuclei remains untested for dark matter particles with masses below few GeV/c 2 although many motivated theoretical models having been proposed. The CRESST-III experiment employs scintillating CaWO 4 crystals of ∼ 25 g as target material for dark matter interactions operated as cryogenic scintillating calorimeters at ∼ 10 mK. CRESST-III first data taking was successfully completed in 2018, achieving an unprecedented energy threshold for nuclear recoils. This result extended the present sensitivity to DM particles as light as ∼ 160 MeV/c 2. In this paper, an overview of the CRESST-III detectors and results will be presented.
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| 6. |
- Whytock, K. L., et al.
(författare)
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A 7-day high-fat, high-calorie diet induces fibre-specific increases in intramuscular triglyceride and perilipin protein expression in human skeletal muscle
- 2020
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Ingår i: Journal of Physiology-London. - : Wiley. - 0022-3751 .- 1469-7793. ; 598:6, s. 1151-1167
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Tidskriftsartikel (refereegranskat)abstract
- Key points We have recently shown that a high-fat, high-calorie (HFHC) diet decreases whole body glucose clearance without impairing skeletal muscle insulin signalling, in healthy lean individuals. These diets are also known to increase skeletal muscle IMTG stores, but the effect on lipid metabolites leading to skeletal muscle insulin resistance has not been investigated. This study measured the effect of 7 days' HFHC diet on (1) skeletal muscle concentration of lipid metabolites, and (2) potential changes in the perilipin (PLIN) content of the lipid droplets storing intramuscular triglyceride (IMTG). The HFHC diet increased PLIN3 protein expression and redistributed PLIN2 to lipid droplet stores in type I fibres. The HFHC diet increased IMTG content in type I fibres, while lipid metabolite concentrations remained the same. The data suggest that the increases in IMTG stores assists in reducing the accumulation of lipid metabolites known to contribute to skeletal muscle insulin resistance. A high-fat, high-calorie (HFHC) diet reduces whole body glucose clearance without impairing skeletal muscle insulin signalling in healthy lean individuals. HFHC diets also increase skeletal muscle lipid stores. However, unlike certain lipid metabolites, intramuscular triglyceride (IMTG) stored within lipid droplets (LDs) does not directly contribute to skeletal muscle insulin resistance. Increased expression of perilipin (PLIN) proteins and colocalisation to LDs has been shown to assist in IMTG storage. We aimed to test the hypothesis that 7 days on a HFHC diet increases IMTG content while minimising accumulation of lipid metabolites known to disrupt skeletal muscle insulin signalling in sedentary and obese individuals. We also aimed to identify changes in expression and subcellular distribution of proteins involved in IMTG storage. Muscle biopsies were obtained from the m. vastus lateralis of 13 (11 males, 2 females) healthy lean individuals (age: 23 +/- 2.5 years; body mass index: 24.5 +/- 2.4 kg m(-2)), following an overnight fast, before and after consuming a high-fat (64% energy), high-calorie (+47% kcal) diet for 7 days. After the HFHC diet, IMTG content increased in type I fibres only (+101%; P < 0.001), whereas there was no change in the concentration of either total diacylglycerol (P = 0.123) or total ceramides (P = 0.150). Of the PLINs investigated, only PLIN3 content increased (+50%; P 0.01) solely in type I fibres. LDs labelled with PLIN2 increased (+80%; P < 0.01), also in type I fibres only. We propose that these adaptations of LDs support IMTG storage and minimise accumulation of lipid metabolites to protect skeletal muscle insulin signalling following 7 days' HFHC diet.
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| 7. |
- Galluzzi, L, et al.
(författare)
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Consensus guidelines for the definition, detection and interpretation of immunogenic cell death
- 2020
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Ingår i: Journal for immunotherapy of cancer. - : BMJ. - 2051-1426. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.
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| 8. |
- Obara, EAA, et al.
(författare)
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SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4709-
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Tidskriftsartikel (refereegranskat)abstract
- Glioblastoma cancer-stem like cells (GSCs) display marked resistance to ionizing radiation (IR), a standard of care for glioblastoma patients. Mechanisms underpinning radio-resistance of GSCs remain largely unknown. Chromatin state and the accessibility of DNA lesions to DNA repair machineries are crucial for the maintenance of genomic stability. Understanding the functional impact of chromatin remodeling on DNA repair in GSCs may lay the foundation for advancing the efficacy of radio-sensitizing therapies. Here, we present the results of a high-content siRNA microscopy screen, revealing the transcriptional elongation factor SPT6 to be critical for the genomic stability and self-renewal of GSCs. Mechanistically, SPT6 transcriptionally up-regulates BRCA1 and thereby drives an error-free DNA repair in GSCs. SPT6 loss impairs the self-renewal, genomic stability and tumor initiating capacity of GSCs. Collectively, our results provide mechanistic insights into how SPT6 regulates DNA repair and identify SPT6 as a putative therapeutic target in glioblastoma.
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| 9. |
- Bader, J. M., et al.
(författare)
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Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease
- 2020
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Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:6
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegenerative diseases are a growing burden, and there is an urgent need for better biomarkers for diagnosis, prognosis, and treatment efficacy. Structural and functional brain alterations are reflected in the protein composition of cerebrospinal fluid (CSF). Alzheimer's disease (AD) patients have higherCSFlevels of tau, but we lack knowledge of systems-wide changes ofCSFprotein levels that accompanyAD. Here, we present a highly reproducible mass spectrometry (MS)-based proteomics workflow for the in-depth analysis ofCSFfrom minimal sample amounts. From three independent studies (197 individuals), we characterize differences in proteins byADstatus (> 1,000 proteins,CV < 20%). Proteins with previous links to neurodegeneration such as tau,SOD1, andPARK7 differed most strongly byADstatus, providing strong positive controls for our approach.CSFproteome changes in Alzheimer's disease prove to be widespread and often correlated with tau concentrations. Our unbiased screen also reveals a consistent glycolytic signature across our cohorts and a recent study. Machine learning suggests clinical utility of this proteomic signature.
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| 10. |
- Dominguez-Valentin, M, et al.
(författare)
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Risk-Reducing Gynecological Surgery in Lynch Syndrome: Results of an International Survey from the Prospective Lynch Syndrome Database
- 2020
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Ingår i: Journal of clinical medicine. - : MDPI AG. - 2077-0383. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To survey risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) practice and advice regarding hormone replacement therapy (HRT) in women with Lynch syndrome. Methods: We conducted a survey in 31 contributing centers from the Prospective Lynch Syndrome Database (PLSD), which incorporates 18 countries worldwide. The survey covered local policies for risk-reducing hysterectomy and BSO in Lynch syndrome, the timing when these measures are offered, the involvement of stakeholders and advice regarding HRT. Results: Risk-reducing hysterectomy and BSO are offered to path_MLH1 and path_MSH2 carriers in 20/21 (95%) contributing centers, to path_MSH6 carriers in 19/21 (91%) and to path_PMS2 carriers in 14/21 (67%). Regarding the involvement of stakeholders, there is global agreement (~90%) that risk-reducing surgery should be offered to women, and that this discussion may involve gynecologists, genetic counselors and/or medical geneticists. Prescription of estrogen-only HRT is offered by 15/21 (71%) centers to women of variable age range (35–55 years). Conclusions: Most centers offer risk-reducing gynecological surgery to carriers of path_MLH1, path_MSH2 and path_MSH6 variants but less so for path_PMS2 carriers. There is wide variation in how, when and to whom this is offered. The Manchester International Consensus Group developed recommendations to harmonize clinical practice across centers, but there is a clear need for more research.
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