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- 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. |
- 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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4. |
- 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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5. |
- Lin, Audrey T., et al.
(author)
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The history of Coast Salish "woolly dogs" revealed by ancient genomics and Indigenous Knowledge
- 2023
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In: Science. - 0036-8075 .- 1095-9203. ; 382:6676, s. 1303-1308
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Journal article (peer-reviewed)abstract
- Ancestral Coast Salish societies in the Pacific Northwest kept long-haired woolly dogs that were bred and cared for over millennia. However, the dog wool-weaving tradition declined during the 19th century, and the population was lost. In this study, we analyzed genomic and isotopic data from a preserved woolly dog pelt from "Mutton", collected in 1859. Mutton is the only known example of an Indigenous North American dog with dominant precolonial ancestry postdating the onset of settler colonialism. We identified candidate genetic variants potentially linked with their distinct woolly phenotype. We integrated these data with interviews from Coast Salish Elders, Knowledge Keepers, and weavers about shared traditional knowledge and memories surrounding woolly dogs, their importance within Coast Salish societies, and how colonial policies led directly to their disappearance.
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6. |
- 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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7. |
- 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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