| 1. |
- Ballan, M., et al.
(author)
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Nuclear physics midterm plan at Legnaro National Laboratories (LNL)
- 2023
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In: European Physical Journal Plus. - 2190-5444. ; 138:8, s. 3-26
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Journal article (peer-reviewed)abstract
- The next years will see the completion of the radioactive ion beam facility SPES (Selective Production of Exotic Species) and the upgrade of the accelerators complex at Istituto Nazionale di Fisica Nucleare – Legnaro National Laboratories (LNL) opening up new possibilities in the fields of nuclear structure, nuclear dynamics, nuclear astrophysics, and applications. The nuclear physics community has organised a workshop to discuss the new physics opportunities that will be possible in the near future by employing state-of-the-art detection systems. A detailed discussion of the outcome from the workshop is presented in this report.
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| 2. |
- Shrine, N, et al.
(author)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Journal article (peer-reviewed)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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| 3. |
- Liu, X., et al.
(author)
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Evidence for enhanced neutron-proton correlations from the levelstructure of the N= Z+ 1 nucleus 8743Tc44
- 2021
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In: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 104:2
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Journal article (peer-reviewed)abstract
- The low-lying excited states in the neutron-deficient N = Z + 1 nucleus (87)(43)Tcc(44) have been studied via the fusion-evaporation reaction Fe-54(Ar-36, 2n1p)Tc-87 at the Grand Accelerateur National d'Ions Lourds (GANIL), France. The AGATA spectrometer was used in conjunction with the auxiliary NEDA, Neutron Wall, and DIAMANT detector arrays to measure coincident prompt gamma rays, neutrons, and charged particles emitted in the reaction. A level scheme of Tc-87 from the (9/2(g.s.)(+)) state to the (33/2(1)(+)) state was established based on six mutually coincident gamma-ray transitions. The constructed level structure exhibits a rotational behavior with a sharp backbending at (h) over bar omega approximate to 0.50 MeV. A decrease in alignment frequency and increase in alignment sharpness in the odd-mass isotonic chains around N = 44 is proposed as an effect of the enhanced isoscalar neutron-proton interactions in odd-mass nuclei when approaching the N = Z line.
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| 4. |
- Liu, Xiaoyu, et al.
(author)
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Evidence for spherical-oblate shape coexistence in Tc-87
- 2022
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In: Physical Review C. - : American Physical Society. - 2469-9985 .- 2469-9993. ; 106:3
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Journal article (peer-reviewed)abstract
- Excited states in the neutron-deficient nucleus Tc-87 have been studied via the fusion-evaporation reaction 54Fe(36Ar, 2n1p) Tc-87 at 115 MeV beam energy. The AGATA gamma-ray spectrometer coupled to the DIAMANT, NEDA, and Neutron Wall detector arrays for light-particle detection was used to measure the prompt coincidence of gamma rays and light particles. Six transitions from the deexcitation of excited states belonging to a new band in Tc-87 were identified by comparing gamma-ray intensities in the spectra gated under different reaction channel selection conditions. The constructed level structure was compared with the shell model and total Routhian surface calculations. The results indicate that the new band structure in 87Tc is built on a spherical configuration, which is different from that assigned to the previously identified oblate yrast rotational band.
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| 5. |
- Iram, T., et al.
(author)
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Young CSF restores oligodendrogenesis and memory in aged mice via Fgf17
- 2022
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 605, s. 509-515
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Journal article (peer-reviewed)abstract
- Recent understanding of how the systemic environment shapes the brain throughout life has led to numerous intervention strategies to slow brain ageing(1-3). Cerebrospinal fluid (CSF) makes up the immediate environment of brain cells, providing them with nourishing compounds(4,5). We discovered that infusing young CSF directly into aged brains improves memory function. Unbiased transcriptome analysis of the hippocampus identified oligodendrocytes to be most responsive to this rejuvenated CSF environment. We further showed that young CSF boosts oligodendrocyte progenitor cell (OPC) proliferation and differentiation in the aged hippocampus and in primary OPC cultures. Using SLAMseq to metabolically label nascent mRNA, we identified serum response factor (SRF), a transcription factor that drives actin cytoskeleton rearrangement, as a mediator of OPC proliferation following exposure to young CSF. With age, SRF expression decreases in hippocampal OPCs, and the pathway is induced by acute injection with young CSF. We screened for potential SRF activators in CSF and found that fibroblast growth factor 17 (Fgf17) infusion is sufficient to induce OPC proliferation and long-term memory consolidation in aged mice while Fgf17 blockade impairs cognition in young mice. These findings demonstrate the rejuvenating power of young CSF and identify Fgf17 as a key target to restore oligodendrocyte function in the ageing brain.
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| 8. |
- Duran-Castells, C., et al.
(author)
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Sirtuin-2, NAD-Dependent Deacetylase, Is a New Potential Therapeutic Target for HIV-1 Infection and HIV-Related Neurological Dysfunction
- 2023
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In: Journal of Virology. - : American Society for Microbiology. - 0022-538X .- 1098-5514. ; 97:2
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Journal article (peer-reviewed)abstract
- Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (n = 9) or delayed initiation (n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure.IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD(+) deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction.
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| 9. |
- Ertoprak, Aysegul, et al.
(author)
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Evidence for octupole collectivity in 172Pt
- 2020
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In: European Physical Journal A. - : Springer. - 1434-6001 .- 1434-601X. ; 56:2
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Journal article (peer-reviewed)abstract
- Excited states in the extremely neutron-deficient nucleus 172Pt were populated via 96Ru(78Kr,2p) and 92Mo(83Kr,3n) reactions. The level scheme has been extended up to an excitation energy of ~ 5 MeV and tentative spin-parity assignments up to Iπ = 18+. Linear polarization and angular distribution measurements were used to determine the electromagnetic E1 character of the dipole transitions connecting the positive-parity ground-state band with an excited side-band, firmly establishing it as a negative-parity band. The lowest member of this negative-parity structure was firmly assigned spin-parity 3-. In addition, we observed an E3 transition from this 3- state to the ground state, providing direct evidence for octupole collectivity in 172Pt. Large-scale shell model (LSSM) and total Routhian surface (TRS) calculations have been performed, supporting the interpretation of the 3- state as a collective octupole-vibrational state.
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