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- Underwood, J, et al.
(author)
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Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
- 2019
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In: Open forum infectious diseases. - : Oxford University Press (OUP). - 2328-8957. ; 6:6, s. ofz198-
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Journal article (peer-reviewed)abstract
- BackgroundThe optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient– reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts.MethodsDifferences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria.ResultsThe prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment (P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres (P < .05), as well as smaller brain volumes (P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker.ConclusionDifferent methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
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| 2. |
- Clément, E, et al.
(author)
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Spectroscopic Quadrupole Moments in ^{96,98}Sr: Evidence for Shape Coexistence in Neutron-Rich Strontium Isotopes at N=60.
- 2016
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In: Physical Review Letters. - 1079-7114. ; 116:2
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Journal article (peer-reviewed)abstract
- Neutron-rich ^{96,98}Sr isotopes have been investigated by safe Coulomb excitation of radioactive beams at the REX-ISOLDE facility. Reduced transition probabilities and spectroscopic quadrupole moments have been extracted from the differential Coulomb excitation cross sections. These results allow, for the first time, the drawing of definite conclusions about the shape coexistence of highly deformed prolate and spherical configurations. In particular, a very small mixing between the coexisting states is observed, contrary to other mass regions where strong mixing is present. Experimental results have been compared to beyond-mean-field calculations using the Gogny D1S interaction in a five-dimensional collective Hamiltonian formalism, which reproduce the shape change at N=60.
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| 3. |
- Louchart, C., et al.
(author)
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Collective nature of low-lying excitations in Zn-70,Zn-72,Zn-74 from lifetime measurements using the AGATA spectrometer demonstrator
- 2013
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In: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 87:5
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Journal article (peer-reviewed)abstract
- Background: Neutron-rich nuclei with protons in the fp shell show an onset of collectivity around N=40. Spectroscopic information is required to understand the underlying mechanism and to determine the relevant terms of the nucleon-nucleon interaction that are responsible for the evolution of the shell structure in this mass region. Methods: We report on the lifetime measurement of the first 2(+) and 4(+) states in Zn-70,Zn-72 ,Zn-74 and the first 6(+) state in Zn-72 using the recoil distance Doppler shift method. The experiment was carried out at the INFN Laboratory of Legnaro with the AGATA demonstrator, first phase of the Advanced Gamma Tracking Array of highly segmented, high-purity germanium detectors coupled to the PRISMA magnetic spectrometer. The excited states of the nuclei of interest were populated in the deep inelastic scattering of a Ge-76 beam impinging on a U-238 target. Results: The maximum of collectivity along the chain of Zn isotopes is observed for Zn-72 at N=42. An unexpectedly long lifetime of 20(-5.2)(+1.8) ps was measured for the 4(+) state in Zn-74. Conclusions: Our results lead to small values of the B(E2;4(1)(+) -> 21(+))/B(E2;2(1)(+->)0(1)(+)) ratio for Zn-72,Zn-74, suggesting a significant noncollective contribution to these excitations. These experimental results are not reproduced by state-of-the-art microscopic models and call for lifetime measurements beyond the first 2(+) state in heavy zinc and nickel isotopes.
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| 9. |
- El Kharraz, S., et al.
(author)
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The androgen receptor depends on ligand-binding domain dimerization for transcriptional activation
- 2021
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In: Embo Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 22:12
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Journal article (peer-reviewed)abstract
- Whereas dimerization of the DNA-binding domain of the androgen receptor (AR) plays an evident role in recognizing bipartite response elements, the contribution of the dimerization of the ligand-binding domain (LBD) to the correct functioning of the AR remains unclear. Here, we describe a mouse model with disrupted dimerization of the AR LBD (AR(Lmon/Y)). The disruptive effect of the mutation is demonstrated by the feminized phenotype, absence of male accessory sex glands, and strongly affected spermatogenesis, despite high circulating levels of testosterone. Testosterone replacement studies in orchidectomized mice demonstrate that androgen-regulated transcriptomes in AR(Lmon/Y) mice are completely lost. The mutated AR still translocates to the nucleus and binds chromatin, but does not bind to specific AR binding sites. In vitro studies reveal that the mutation in the LBD dimer interface also affects other AR functions such as DNA binding, ligand binding, and co-regulator binding. In conclusion, LBD dimerization is crucial for the development of AR-dependent tissues through its role in transcriptional regulation in vivo. Our findings identify AR LBD dimerization as a possible target for AR inhibition.
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| 10. |
- Kananen, L, et al.
(author)
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Circulating cell-free DNA in health and disease - the relationship to health behaviours, ageing phenotypes and metabolomics
- 2023
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In: GeroScience. - : Springer Science and Business Media LLC. - 2509-2723 .- 2509-2715. ; 45:1, s. 85-103
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Journal article (peer-reviewed)abstract
- Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.
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