| 1. |
- Aad, G, et al.
(författare)
-
- 2015
-
swepub:Mat__t
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Chatterjee, P., et al.
(författare)
-
Serum Hepcidin Levels in Cognitively Normal Older Adults with High Neocortical Amyloid-beta Load
- 2020
-
Ingår i: Journal of Alzheimers Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 76:1, s. 291-301
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Objective: Hepcidin, an iron-regulating hormone, suppresses the release of iron by binding to the iron exporter protein, ferroportin, resulting in intracellular iron accumulation. Given that iron dyshomeostasis has been observed in Alzheimer's disease (AD) together with elevated serum hepcidin levels, the current study examined whether elevated serum hepcidin levels are an early event in AD pathogenesis by measuring the hormone in cognitively normal older adults at risk of AD, based on high neocortical amyloid-beta load (NAL). Methods: Serum hepcidin levels in cognitively normal participants (n = 100) aged between 65-90 years were measured using ELISA. To evaluate NAL, all participants underwent 18F-florbetaben positron emission tomography. A standard uptake value ratio (SUVR)<1.35 was classified as low NAL (n = 65) and >= 1.35 (n = 35) was classified as high NAL. Results: Serum hepcidin was significantly higher in participants with high NAL compared to those with low NAL before and after adjusting for covariates: age, gender, and APOE epsilon 4 carriage (p < 0.05). A receiver operating characteristic curve based on a logistic regression of the same covariates, the base model, distinguished high from low NAL (area under the curve, AUC = 0.766), but was outperformed when serum hepcidin was added to the base model (AUC = 0.794) and further improved with plasma A beta(42/40) ratio (AUC = 0.829). Conclusion: The present findings indicate that serum hepcidin is increased in individuals at risk for AD and contribute to the body of evidence supporting iron dyshomeostasis as an early event of AD. Further, hepcidin may add value to a panel of markers that contribute toward identifying individuals at risk of AD; however, further validation studies are required.
|
|
| 5. |
- Sheikh, U., et al.
(författare)
-
Benign termination of runaway electron beams on ASDEX Upgrade and TCV
- 2024
-
Ingår i: Plasma Physics and Controlled Fusion. - : IOP Publishing. - 0741-3335 .- 1361-6587. ; 66:3
-
Tidskriftsartikel (refereegranskat)abstract
- This paper discusses the development of a benign termination scenario for runaway electron (RE) beams on ASDEX Upgrade and TCV. A systematic study revealed that a low electron density (n e) companion plasma was required to achieve a large MHD instability, which expelled the confined REs over a large wetted area and allowed for the conversion of magnetic energy to radiation. Control of the companion plasma ne was achieved via neutral pressure regulation and was agnostic to material injection method. The neutral pressure required for recombination was found to be dependent on impurity species, quantity and RE current. On TCV, n e increased at neutral pressures above 1 Pa, indicating that higher collisionality between the REs and neutrals may lead to an upper pressure limit. The conversion of magnetic energy to radiated energy was measured on both machines and a decrease in efficiency was observed at high neutral pressure on TCV. The benign termination technique was able to prevent any significant increase in maximum heat flux on AUG from 200 to 600 kA of RE current, highlighting the ability of this approach to handle fully formed RE beams.
|
|
| 6. |
- Chatterjee, P., et al.
(författare)
-
Plasma metabolites associated with biomarker evidence of neurodegeneration in cognitively normal older adults
- 2021
-
Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042 .- 1471-4159. ; 159:2, s. 389-402
-
Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) is a progressive neurodegenerative disorder that currently has no cure. Identifying biochemical changes associated with neurodegeneration prior to symptom onset, will provide insight into the biological mechanisms associated with neurodegenerative processes, that may also aid in identifying potential drug targets. The current study therefore investigated associations between plasma neurofilament light chain (NF-L), a marker of neurodegeneration, with plasma metabolites that are products of various cellular processes. Plasma NF-L, measured by ultrasensitive Single molecule array (Simoa) technology (Quanterix) and plasma metabolites, measured by mass-spectrometry (AbsoluteIDQ (R) p400HR kit, BIOCRATES), were assessed in the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort comprising 100 cognitively normal older adults. Metabolites belonging to biogenic amine (creatinine, symmetric dimethylarginine, asymmetric dimethylarginine; ADMA, kynurenine, trans-4-hydroxyproline), amino acid (citrulline, proline, arginine, asparagine, phenylalanine, threonine) and acylcarnitine classes were observed to have positive correlations with plasma NF-L, suggesting a link between neurodegeneration and biological pathways associated with neurotransmitter regulation, nitric oxide homoeostasis, inflammation and mitochondrial function. Additionally, after stratifying participants based on low/high brain amyloid-beta load (A beta +/-) assessed by positron emission tomography, while creatinine, SDMA and citrulline correlated with NF-L in both A beta- and A beta+ groups, ADMA, proline, arginine, asparagine, phenylalanine and acylcarnitine species correlated with NF-L only in the A beta+ group after adjusting for confounding variables, suggesting that the association of these metabolites with neurodegeneration may be relevant to AD-related neuropathology. Metabolites identified to be associated with plasma NF-L may have the potential to serve as prognostic markers for neurodegenerative diseases, however, further studies are required to validate the current findings in an independent cohort, both cross-sectionally and longitudinally.
|
|
| 7. |
- Chatterjee, Pratishtha, et al.
(författare)
-
Plasma neurofilament light chain and amyloid-β are associated with the kynurenine pathway metabolites in preclinical Alzheimer's disease.
- 2019
-
Ingår i: Journal of neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 16:1
-
Tidskriftsartikel (refereegranskat)abstract
- Blood markers indicative of neurodegeneration (neurofilament light chain; NFL), Alzheimer's disease amyloid pathology (amyloid-β; Aβ), and neuroinflammation (kynurenine pathway; KP metabolites) have been investigated independently in neurodegenerative diseases. However, the association of these markers of neurodegeneration and AD pathology with neuroinflammation has not been investigated previously. Therefore, the current study examined whether NFL and Aβ correlate with KP metabolites in elderly individuals to provide insight on the association between blood indicators of neurodegeneration and neuroinflammation.Correlations between KP metabolites, measured using liquid chromatography and gas chromatography coupled with mass spectrometry, and plasma NFL and Aβ concentrations, measured using single molecule array (Simoa) assays, were investigated in elderly individuals aged 65-90years, with normal global cognition (Mini-Mental State Examination Score≥26) from the Kerr Anglican Retirement Village Initiative in Ageing Health cohort.A positive correlation between NFL and the kynurenine to tryptophan ratio (K/T) reflecting indoleamine 2,3-dioxygenase activity was observed (r=.451, p<.0001). Positive correlations were also observed between NFL and kynurenine (r=.364, p<.0005), kynurenic acid (r=.384, p<.0001), 3-hydroxykynurenine (r=.246, p=.014), anthranilic acid (r=.311, p=.002), and quinolinic acid (r=.296, p=.003). Further, significant associations were observed between plasma Aβ40 and the K/T (r=.375, p<.0005), kynurenine (r=.374, p<.0005), kynurenic acid (r=.352, p<.0005), anthranilic acid (r=.381, p<.0005), and quinolinic acid (r=.352, p<.0005). Significant associations were also observed between plasma Aβ42 and the K/T ratio (r=.215, p=.034), kynurenic acid (r=.214, p=.035), anthranilic acid (r=.278, p=.006), and quinolinic acid (r=.224, p=.027) in the cohort. On stratifying participants based on their neocortical Aβ load (NAL) status, NFL correlated with KP metabolites irrespective of NAL status; however, associations between plasma Aβ and KP metabolites were only pronounced in individuals with high NAL while associations in individuals with low NAL were nearly absent.The current study shows that KP metabolite changes are associated with biomarker evidence of neurodegeneration. Additionally, the association between KP metabolites and plasma Aβ seems to be NAL status dependent. Finally, the current study suggests that an association between neurodegeneration and neuroinflammation manifests in the periphery, suggesting that preventing cytoskeleton cytotoxicity by KP metabolites may have therapeutic potential.
|
|
| 8. |
- Chatterjee, P., et al.
(författare)
-
Ultrasensitive Detection of Plasma Amyloid-beta as a Biomarker for Cognitively Normal Elderly Individuals at Risk of Alzheimer's Disease
- 2019
-
Ingår i: Journal of Alzheimers Disease. - 1387-2877. ; 71:3, s. 775-783
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Aberrant amyloid-beta (A beta) deposition in the brain occurs two decades prior to the manifestation of Alzheimer's disease (AD) clinical symptoms and therefore brain A beta load measured using PET serves as a gold standard biomarker for the early diagnosis of AD. However, the uneconomical nature of PET makes blood markers, that reflect brain A beta deposition, attractive candidates for investigation as surrogate markers. Objective: Investigation of plasma A beta as a surrogate marker for brain A beta deposition in cognitively normal elderly individuals. Methods: Plasma A beta(40) and A beta(42) concentrations were measured using the ultrasensitive Single Molecule Array (Simoa) assay in 95 cognitively normal elderly individuals, who have all undergone PET to assess brain A beta deposition. Based on the standard uptake value ratios (SUVR) obtained from PET imaging, using the tracer F-18-Florbetaben, plasma A beta was compared between 32 participants assessed to have low brain A beta load (A beta-, SUVR <1.35) and 63 assessed to have high brain A beta load (A beta+, SUVR >= 1.35). Results: Plasma A beta(42)/A beta(40) ratios were lower in the A beta+ group compared to the A beta- group. Plasma A beta(40) and A beta(42) levels were not significantly different between A beta- and A beta+ groups, although a trend of higher plasma A beta(40) was observed in the A beta+ group. Additionally, plasma A beta(42)/A beta(40) ratios along with the known AD risk factors, age and APOE epsilon 4 status, resulted in A beta+ participants being distinguished from A beta- participants based on an area under the receiver operating characteristic curve shown to be 78%. Conclusion: Plasma A beta ratios in this study are a potential biomarker for brain A beta deposition and therefore, for preclinical AD. However, this method to measure plasma A beta needs further development to increase the accuracy of this promising AD blood biomarker.
|
|
| 9. |
- Frank, Matthias, et al.
(författare)
-
Femtosecond X-ray diffraction from two-dimensional protein crystals
- 2014
-
Ingår i: IUCrJ. - 2052-2525. ; 1:2, s. 95-100
-
Tidskriftsartikel (refereegranskat)abstract
- X-ray diffraction patterns from two-dimensional (2-D) protein crystals obtained using femtosecond X-ray pulses from an X-ray free-electron laser (XFEL) are presented. To date, it has not been possible to acquire transmission X-ray diffraction patterns from individual 2-D protein crystals due to radiation damage. However, the intense and ultrafast pulses generated by an XFEL permit a new method of collecting diffraction data before the sample is destroyed. Utilizing a diffract-before-destroy approach at the Linac Coherent Light Source, Bragg diffraction was acquired to better than 8.5 Å resolution for two different 2-D protein crystal samples each less than 10 nm thick and maintained at room temperature. These proof-of-principle results show promise for structural analysis of both soluble and membrane proteins arranged as 2-D crystals without requiring cryogenic conditions or the formation of three-dimensional crystals.
|
|
| 10. |
- Rodriguez-Fernandez, A., et al.
(författare)
-
X-ray forward diffraction wave-front propagation in Si and C single crystals : Simulations and experiments
- 2020
-
Ingår i: Advances in Computational Methods for X-Ray Optics V. - : SPIE. - 1996-756X .- 0277-786X. - 9781510637924 ; 11493
-
Konferensbidrag (refereegranskat)abstract
- The emergence of new high brilliance and high coherence facilities such as X-ray Free Electron Lasers (XFELs) and 4th generation synchrotrons open a new era in X-ray optics. Dynamical diffraction effects before disregarded are starting to play a role in the beam control of large scale facilities. In the case of XFEL facilities the temporal characteristics of the dynamical diffraction by thin perfect crystals can be used as a tool to generate femtosecond monochromatic pulses, in the case of self-seeding in the hard X-ray regime, but could even be used as method to characterize materials in this temporal range. In this contribution we present the first steps in the understanding of the spatial-displacement dependence of forward beams diffracted by thin crystals. The data collected by this technique is compared with crystal models based in dynamical diffraction theory. This type of study could open a new field to understand low strain materials in the femtosecond regime.
|
|
| 11. |
|
|
| 12. |
- Villanueva-Perez, P., et al.
(författare)
-
Hard x-ray multi-projection imaging for single-shot approaches
- 2018
-
Ingår i: Optica. - 2334-2536. ; 5:12, s. 1521-1524
-
Tidskriftsartikel (refereegranskat)abstract
- High-brilliance x-ray sources (x-ray free-electron lasers or diffraction-limited storage rings) allow the visualization of ultrafast processes in a 2D manner using single exposures. Current 3D approaches scan the sample using multiple exposures, and hence they are not compatible with single-shot acquisitions. Here we propose and verify experimentally an x-ray multi-projection imaging approach, which uses a crystal to simultaneously acquire nine angularly resolved projections with a single x-ray exposure. When implemented at high-brilliance sources, this approach can provide volumetric information of natural processes and non-reproducible samples in the micrometer to nanometer resolution range, and resolve timescales from microseconds down to femto-seconds.
|
|
| 13. |
- Yuan, J., et al.
(författare)
-
Elevated plasma sclerostin is associated with high brain amyloid-β load in cognitively normal older adults
- 2023
-
Ingår i: Npj Aging. - 2731-6068. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Osteoporosis and Alzheimer's disease (AD) mainly affect older individuals, and the possibility of an underlying link contributing to their shared epidemiological features has rarely been investigated. In the current study, we investigated the association between levels of plasma sclerostin (SOST), a protein primarily produced by bone, and brain amyloid-beta (A ss) load, a pathological hallmark of AD. The study enrolled participants meeting a set of screening inclusion and exclusion criteria and were stratified into A ss(n = 65) and A ss+ (n = 35) according to their brain A ss load assessed using A ss-PET (positron emission tomography) imaging. Plasma SOST levels, apolipoprotein E gene (APOE) genotype and several putative AD blood-biomarkers including A ss 40, A ss 42, A ss 42/A ss 40, neurofilament light (NFL), glial fibrillary acidic protein (GFAP), total tau (t-tau) and phosphorylated tau (p-tau181 and p-tau231) were detected and compared. It was found that plasma SOST levels were significantly higher in the A ss+ group (71.49 +/- 25.00 pmol/L) compared with the A ss- group (56.51 +/- 22.14 pmol/L) (P < 0.01). Moreover, Spearman's correlation analysis showed that plasma SOST concentrations were positively correlated with brain A ss load (. = 0.321, P = 0.001). Importantly, plasma SOST combined with A ss 42/A ss 40 ratio significantly increased the area under the curve (AUC) when compared with using A ss 42/A ss 40 ratio alone (AUC = 0.768 vs 0.669, P = 0.027). In conclusion, plasma SOST levels are elevated in cognitively unimpaired older adults at high risk of AD and SOST could complement existing plasma biomarkers to assist in the detection of preclinical AD.
|
|
