| 11. |
- Assogna, M., et al.
(författare)
-
Association of Choroid Plexus Volume With Serum Biomarkers, Clinical Features, and Disease Severity in Patients With Frontotemporal Lobar Degeneration Spectrum
- 2023
-
Ingår i: NEUROLOGY. - 0028-3878. ; 101:12
-
Tidskriftsartikel (refereegranskat)abstract
- Background and ObjectivesChoroid plexus (ChP) is emerging as a key brain structure in the pathophysiology of neurodegenerative disorders. In this observational study, we investigated ChP volume in a large cohort of patients with frontotemporal lobar degeneration (FTLD) spectrum to explore a possible link between ChP volume and other disease-specific biomarkers.MethodsParticipants included patients meeting clinical criteria for a probable syndrome in the FTLD spectrum. Structural brain MRI imaging, serum neurofilament light (NfL), serum phosphorylated-Tau181 (p-Tau181), and cognitive and behavioral data were collected. MRI ChP volumes were obtained from an ad-hoc segmentation model based on a Gaussian Mixture Models algorithm.ResultsThree-hundred and sixteen patients within FTLD spectrum were included in this study, specifically 135 patients diagnosed with behavioral variant frontotemporal dementia (bvFTD), 75 primary progressive aphasia, 46 progressive supranuclear palsy, and 60 corticobasal syndrome. In addition, 82 age-matched healthy participants were recruited as controls (HCs). ChP volume was significantly larger in patients with FTLD compared with HC, across the clinical subtype. Moreover, we found a significant difference in ChP volume between HC and patients stratified for disease-severity based on CDR plus NACC FTLD, including patients at very early stage of the disease. Interestingly, ChP volume correlated with serum NfL, cognitive/behavioral deficits, and with patterns of cortical atrophy. Finally, ChP volume seemed to discriminate HC from patients with FTLD better than other previously identified brain structure volumes.DiscussionConsidering the clinical, pathologic, and genetic heterogeneity of the disease, ChP could represent a potential biomarker across the FTLD spectrum, especially at the early stage of disease. Further longitudinal studies are needed to establish its role in disease onset and progression.Classification of EvidenceThis study provides Class III evidence that choroid plexus volume, as measured on MRI scan, can assist in differentiating patients with FTLD from healthy controls and in characterizing disease severity.
|
|
| 12. |
- Auffret, Alistair G., et al.
(författare)
-
More warm-adapted species in soil seed banks than in herb layer plant communities across Europe
- 2023
-
Ingår i: Journal of Ecology. - : John Wiley & Sons. - 0022-0477 .- 1365-2745. ; 111:5, s. 1009-1020
-
Tidskriftsartikel (refereegranskat)abstract
- Responses to climate change have often been found to lag behind the rate of warming that has occurred. In addition to dispersal limitation potentially restricting spread at leading range margins, the persistence of species in new and unsuitable conditions is thought to be responsible for apparent time-lags. Soil seed banks can allow plant communities to temporarily buffer unsuitable environmental conditions, but their potential to slow responses to long-term climate change is largely unknown. As local forest cover can also buffer the effects of a warming climate, it is important to understand how seed banks might interact with land cover to mediate community responses to climate change. We first related species-level seed bank persistence and distribution-derived climatic niches for 840 plant species. We then used a database of plant community data from grasslands, forests and intermediate successional habitats from across Europe to investigate relationships between seed banks and their corresponding herb layers in 2763 plots in the context of climate and land cover. We found that species from warmer climates and with broader distributions are more likely to have a higher seed bank persistence, resulting in seed banks that are composed of species with warmer and broader climatic distributions than their corresponding herb layers. This was consistent across our climatic extent, with larger differences (seed banks from even warmer climates relative to vegetation) found in grasslands. Synthesis. Seed banks have been shown to buffer plant communities through periods of environmental variability, and in a period of climate change might be expected to contain species reflecting past, cooler conditions. Here, we show that persistent seed banks often contain species with relatively warm climatic niches and those with wide climatic ranges. Although these patterns may not be primarily driven by species’ climatic adaptations, the prominence of such species in seed banks might still facilitate climate-driven community shifts. Additionally, seed banks may be related to ongoing trends regarding the spread of widespread generalist species into natural habitats, while cool-associated species may be at risk from both short- and long-term climatic variability and change.
|
|
| 13. |
- Bader, J. M., et al.
(författare)
-
Proteome profiling in cerebrospinal fluid reveals novel biomarkers of Alzheimer's disease
- 2020
-
Ingår i: Molecular Systems Biology. - : EMBO. - 1744-4292. ; 16:6
-
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.
|
|
| 14. |
|
|
| 15. |
- Bashkanov, M., et al.
(författare)
-
Double-Pionic Fusion of Nuclear Systems and the "ABC" Effect : Approaching a Puzzle by Exclusive and Kinematically Complete Measurements
- 2009
-
Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 102:5, s. 052301-
-
Tidskriftsartikel (refereegranskat)abstract
- The ABC effect-a puzzling low-mass enhancement in the pi pi invariant mass spectrum, first observed by Abashian, Booth, and Crowe-is well known from inclusive measurements of two-pion production in nuclear fusion reactions. Here we report on the first exclusive and kinematically complete measurements of the most basic double-pionic fusion reaction pn -> d pi(0)pi(0) at beam energies of 1.03 and 1.35 GeV. The measurements, which have been carried out at CELSIUS-WASA, reveal the ABC effect to be a (pi pi)(I=L=0) channel phenomenon associated with both a resonancelike energy dependence in the integral cross section and the formation of a Delta Delta system in the intermediate state. A corresponding simple s-channel resonance ansatz provides a surprisingly good description of the data.
|
|
| 16. |
- Bashkanov, M., et al.
(författare)
-
Measurement of the slope parameter for the η → 3π0 decay in the pp → ppη reaction
- 2007
-
Ingår i: Physical Review C. Nuclear Physics. - 0556-2813 .- 1089-490X. ; 76:4, s. 048201-
-
Tidskriftsartikel (refereegranskat)abstract
- The CELSIUS-WASA setup is used to measure the 3π0 decay of η mesons produced in pp interactions with beam kinetic energies of 1.36 and 1.45 GeV. The efficiency-corrected Dalitz plot and density distributions for this decay are shown, together with a fit of the quadratic slope parameter α yielding α = −0.026 ± 0.010(stat) ± 0.010(syst). This value is compared to recent experimental results and theoretical predictions.
|
|
| 17. |
- Baumeister, Ulf, et al.
(författare)
-
Association of Csk to VE-cadherin and inhibition of cell proliferation
- 2005
-
Ingår i: EMBO Journal. - : Wiley-Blackwell Publishing Inc.. - 0261-4189 .- 1460-2075. ; 24:9, s. 1686-1695
-
Tidskriftsartikel (refereegranskat)abstract
- Vascular endothelial cadherin (VE-cadherin) mediates contact inhibition of cell growth in quiescent endothelial cell layers. Searching for proteins that could be involved in VE-cadherin signaling, we found the cytosolic C-terminal Src kinase (Csk), a negative regulator of Src family kinases. We show that Csk binds via its SH2 domain to the phosphorylated tyrosine 685 of VE-cadherin. VE-cadherin recruits Csk to cell contacts and both proteins can be co-precipitated from cell lysates of transfected cells and endothelial cells. Association of VE-cadherin and Csk in endothelial cells increased with increasing cell density. CHO cells expressing the tyrosine replacement mutant VE-cadherin-Y685F grow to higher cell densities than cells expressing wild-type VE-cadherin. Overexpression of Csk in these cells under an inducible promoter inhibits cell proliferation in the presence and absence of VE-cadherin, but not in the presence of VE-cadherin-Y685F. Reduction of Csk expression by RNA interference enhances endothelial cell proliferation. Our results suggest that the phosphorylated tyrosine residue 685 of VE-cadherin and probably the binding of Csk to this site are involved in inhibition of cell growth triggered by cell density.
|
|
| 18. |
- Berlowski, M., et al.
(författare)
-
Measurement of eta meson decays into lepton-antilepton pairs
- 2008
-
Ingår i: Physical Review D. Particles and fields. - : American Physical Society. - 0556-2821 .- 1089-4918. ; 77:3, s. 032004-
-
Tidskriftsartikel (refereegranskat)abstract
- A search for rare lepton decays of the eta meson was performed using the WASA detector at CELSIUS. Two candidates for double Dalitz decay eta -> e(+)e(-)e(+)e(-) events are reported with a background of 1.3 +/- 0.2 events. This allows to set an upper limit to the branching ratio of 9.7x10(-5) (90% CL). The branching ratio for the decay eta -> e(+)e(-)gamma is determined to (7.8 +/- 0.5(stat)+/- 0.8(syst))x10(-3) in agreement with world average value. An upper limit (90% CL) for the branching ratio for the eta -> e(+)e(-) decay is 2.7x10(-5) and a limit for the sum of the eta ->mu(+)mu(-)mu(+)mu(-) and eta ->pi(+)pi(-)mu(+)mu(-) decays is 3.6x10(-4).
|
|
| 19. |
- Cam, Morgane, et al.
(författare)
-
Induction of Amyloid-β42 Production by Fipronil and Other Pyrazole Insecticides.
- 2018
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 62:4, s. 1663-1681
-
Tidskriftsartikel (refereegranskat)abstract
- Generation of amyloid-β peptides (Aβs) by proteolytic cleavage of the amyloid-β protein precursor (AβPP), especially increased production of Aβ42/Aβ43 over Aβ40, and their aggregation as oligomers and plaques, represent a characteristic feature of Alzheimer's disease (AD). In familial AD (FAD), altered Aβ production originates from specific mutations ofAβPP or presenilins 1/2 (PS1/PS2), the catalytic subunits of γ-secretase. In sporadic AD, the origin of altered production of Aβs remains unknown. We hypothesize that the 'human chemical exposome' contains products able to favor the production of Aβ42/Aβ43 over Aβ40 and shorter Aβs. To detect such products, we screened a library of 3500+compounds in a cell-based assay for enhanced Aβ42/Aβ43 production. Nine pyrazole insecticides were found to induce a β- and γ-secretase-dependent, 3-10-fold increase in the production of extracellular Aβ42 in various cell lines and neurons differentiated from induced pluripotent stem cells derived from healthy and FAD patients. Immunoprecipitation/mass spectrometry analyses showed increased production of Aβs cleaved at positions 42/43, and reduced production of peptides cleaved at positions 38 and shorter. Strongly supporting a direct effect on γ-secretase activity, pyrazoles shifted the cleavage pattern of another γ-secretase substrate, alcadeinα, and shifted the cleavage of AβPP by highly purified γ-secretase toward Aβ42/Aβ43. Focusing on fipronil, we showed that some of its metabolites, in particular the persistent fipronil sulfone, also favor the production of Aβ42/Aβ43 in both cell-based and cell-free systems. Fipronil administered orally to mice and rats is known to be metabolized rapidly, mostly to fipronil sulfone, which stably accumulates in adipose tissue and brain. In conclusion, several widely used pyrazole insecticides enhance the production of toxic, aggregation prone Aβ42/Aβ43 peptides, suggesting the possible existence of environmental "Alzheimerogens" which may contribute to the initiation and propagation of the amyloidogenic process in sporadic AD.
|
|
| 20. |
- Castagnola, Matteo, et al.
(författare)
-
Collective Strong Coupling Modifies Aggregation and Solvation
- 2024
-
Ingår i: Journal of Physical Chemistry Letters. - 1948-7185. ; 15, s. 1428-1434
-
Tidskriftsartikel (refereegranskat)abstract
- Intermolecular (Coulombic) interactions are pivotal for aggregation, solvation, and crystallization. We demonstrate that the collective strong coupling of several molecules to a single optical mode results in notable changes in the molecular excitations around a single perturbed molecule, thus representing an impurity in an otherwise ordered system. A competition between short-range coulombic and long-range photonic correlations inverts the local transition density in a polaritonic state, suggesting notable changes in the polarizability of the solvation shell. Our results provide an alternative perspective on recent work in polaritonic chemistry and pave the way for the rigorous treatment of cooperative effects in aggregation, solvation, and crystallization.
|
|
