| 11. |
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| 12. |
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| 13. |
- Basini, M., et al.
(författare)
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Low-temperature anomalies in muon spin relaxation of solid and hollow gamma-Fe2O3 nanoparticles : A pathway to detect unusual local spin dynamics
- 2020
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Ingår i: Physical Review B. - : American Physical Society (APS). - 2469-9950 .- 2469-9969. ; 102:19
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Tidskriftsartikel (refereegranskat)abstract
- By means of muon spin relaxation measurements we unraveled the temperature spin dynamics in monodisperse maghemite spherical nanoparticles with different surface to volume ratio, in two samples with a full core (diameter D similar to 4 and D similar to 5 nm) and one with a hollow core (external diameter D similar to 7.4 nm). The behavior of the muon longitudinal relaxation rates as a function of temperature allowed us to identify two distinct spin dynamics. The first is well witnessed by the presence of a characteristic peak for all the samples around the so-called muon blocking temperature T-B(mu+). A Bloembergen-Purcell-Pound (BPP)-like model reproduces the experimental data around the peak and at higher temperatures (20 < T < 100 K) by assuming the Neel reversal time of the magnetization as the dominating correlation time. An additional dynamic emerges in the samples with higher surface to volume ratio, namely, full 4 nm and hollow samples. This is witnessed by a shoulder of the main peak for T < 20 K at low longitudinal field (mu H-0 approximate to 15 mT), followed by an abrupt increase of the relaxation rate at T < 10 K, which is more evident for the hollow sample. These unusual anomalies of the longitudinal relaxation rate for T < T-B(mu+) are suggested to be due to the surface spins' dynamical behavior. Furthermore, for weak applied longitudinal magnetic field (mu H-0 approximate to 15 mT) and T < T-B(mu+) we observed damped coherent oscillations of the muon asymmetry, which are a signature of a quasistatic local field at the muon site as probed by muons implanted in the inner magnetic core of the nanoparticles. The muon spin relaxation technique turns out to be very successful to study the magnetic behavior of maghemite nanoparticles and to detect their unusual local spin dynamics in low magnetic field conditions.
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| 14. |
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| 15. |
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| 16. |
- Arosio, B, et al.
(författare)
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Peripheral blood mononuclear cells as a laboratory to study dementia in the elderly
- 2014
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Ingår i: BioMed research international. - : Hindawi Limited. - 2314-6141 .- 2314-6133. ; 2014, s. 169203-
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Tidskriftsartikel (refereegranskat)abstract
- The steady and dramatic increase in the incidence of Alzheimer’s disease (AD) and the lack of effective treatments have stimulated the search for strategies to prevent or delay its onset and/or progression. Since the diagnosis of dementia requires a number of established features that are present when the disease is fully developed, but not always in the early stages, the need for a biological marker has proven to be urgent, in terms of both diagnosis and monitoring of AD. AD has been shown to affect peripheral blood mononuclear cells (PBMCs) that are a critical component of the immune system which provide defence against infection. Although studies are continuously supplying additional data that emphasize the central role of inflammation in AD, PBMCs have not been sufficiently investigated in this context. Delineating biochemical alterations in AD blood constituents may prove valuable in identifying accessible footprints that reflect degenerative processes within the Central Nervous System (CNS). In this review, we address the role of biomarkers in AD with a focus on the notion that PBMCs may serve as a peripheral laboratory to find molecular signatures that could aid in differential diagnosis with other forms of dementia and in monitoring of disease progression.
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| 17. |
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| 18. |
- Kakkar, Vaishali, et al.
(författare)
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The S/T-Rich Motif in the DNAJB6 Chaperone Delays Polyglutamine Aggregation and the Onset of Disease in a Mouse Model
- 2016
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Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765. ; 62:2, s. 272-283
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Tidskriftsartikel (refereegranskat)abstract
- Expanded CAG repeats lead to debilitating neurodegenerative disorders characterized by aggregation of proteins with expanded polyglutamine (polyQ) tracts. The mechanism of aggregation involves primary and secondary nucleation steps. We show how a noncanonical member of the DNAJ-chaperone family, DNAJB6, inhibits the conversion of soluble polyQ peptides into amyloid fibrils, in particular by suppressing primary nucleation. This inhibition is mediated by a serine/threonine-rich region that provides an array of surface-exposed hydroxyl groups that bind to polyQ peptides and may disrupt the formation of the H bonds essential for the stability of amyloid fibrils. Early prevention of polyQ aggregation by DNAJB6 occurs also in cells and leads to delayed neurite retraction even before aggregates are visible. In a mouse model, brain-specific coexpression of DNAJB6 delays polyQ aggregation, relieves symptoms, and prolongs lifespan, pointing to DNAJB6 as a potential target for disease therapy and tool for unraveling early events in the onset of polyQ diseases. Kakkar et al. show that DNAJB6 is a chaperone that inhibits early steps in the formation of polyQ amyloid fibrils. An S/T-rich region in DNAJB6 is crucial for this function. In a polyQ mouse model, the inhibitory effects of DNAJB6 delay disease onset and increase lifespan.
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| 19. |
- Martel-Duguech, Luciana Maria, et al.
(författare)
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ESE audit on management of Adult Growth Hormone Deficiency in clinical practice.
- 2021
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Ingår i: European journal of endocrinology. - 1479-683X. ; 184:2, s. 323-334
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Tidskriftsartikel (refereegranskat)abstract
- Guidelines recommend adults with pituitary disease in whom GH therapy is contemplated, to be tested for GH deficiency (AGHD); however, clinical practice is not uniform.1) To record current practice of AGHD management throughout Europe and benchmark it against guidelines; 2) To evaluate educational status of healthcare professionals about AGHD.On-line survey in endocrine centres throughout Europe.Endocrinologists voluntarily completed an electronic questionnaire regarding AGHD patients diagnosed or treated in 2017-2018.Twenty-eight centres from 17 European countries participated, including 2139 AGHD patients, 28% of childhood-onset GHD. Aetiology was most frequently non-functioning pituitary adenoma (26%), craniopharyngioma (13%) and genetic/congenital mid-line malformations (13%). Diagnosis of GHD was confirmed by a stimulation test in 52% (GHRH+arginine, 45%; insulin-tolerance, 42%, glucagon, 6%; GHRH alone and clonidine tests, 7%); in the remaining, ≥3 pituitary deficiencies and low serum IGF-I were diagnostic. Initial GH dose was lower in older patients, but only women <26 years were prescribed a higher dose than men; dose titration was based on normal serum IGF-I, tolerance and side-effects. In one country, AGHD treatment was not approved. Full public reimbursement was not available in four countries and only in childhood-onset GHD in another. AGHD awareness was low among non-endocrine professionals and healthcare administrators. Postgraduate AGHD curriculum training deserves being improved.Despite guideline recommendations, GH replacement in AGHD is still not available or reimbursed in all European countries. Knowledge among professionals and health administrators needs improvement to optimize care of adults with GHD.
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| 20. |
- Månsson, Cecilia, et al.
(författare)
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Interaction of the molecular chaperone DNAJB6 with growing amyloid-beta 42 (Aβ42) aggregates leads to sub-stoichiometric inhibition of amyloid formation.
- 2014
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 289:45, s. 31066-31076
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Tidskriftsartikel (refereegranskat)abstract
- The human molecular chaperone protein DNAJB6 was recently found to inhibit the formation of amyloid fibrils from polyglutamine peptides associated with neurodegenerative disorders such as Huntington's disease. We show in the present study that DNAJB6 also inhibits amyloid formation by an even more aggregation-prone peptide (the amyloid-beta peptide, (Aβ42)(2), implicated in Alzheimer's disease)in a highly efficient manner. By monitoring fibril formation using Thioflavin T fluorescence and far-UV CD spectroscopy, we have found that the aggregation of Aβ42 is retarded by DNAJB6 in a concentration dependent manner, extending to very low sub-stoichiometric molar ratios of chaperone to peptide. Quantitative kinetic analysis and immunochemistry studies suggest that the high inhibitory efficiency is due to the interactions of the chaperone with aggregated forms of Aβ42 rather than the monomeric form of the peptide. This interaction prevents the growth of such species to longer fibrils and inhibits the formation of new amyloid fibrils through both primary and secondary nucleation. A low dissociation rate of DNAJB6 from Aβ42 aggregates leads to its incorporation into growing fibrils and hence to its gradual depletion from solution with time. When DNAJB6 is eventually depleted, fibril proliferation takes place, but the inhibitory activity can be prolonged by introducing DNAJB6 at regular intervals during the aggregation reaction. These results reveal the highly efficacious mode of action of this molecular chaperone against protein aggregation, and demonstrate that the role of molecular chaperones can involve interactions with multiple aggregated species leading to the inhibition of both principal nucleation pathways through which aggregates are able to form.
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