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- Thrane, Kim, et al.
(author)
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Single-Cell and Spatial Transcriptomic Analysis of Human Skin Delineates Intercellular Communication and Pathogenic Cells
- 2023
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In: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 143:11, s. 13-2177
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Journal article (peer-reviewed)abstract
- Epidermal homeostasis is governed by a balance between keratinocyte proliferation and differentiation with contributions from cell–cell interactions, but conserved or divergent mechanisms governing this equilibrium across species and how an imbalance contributes to skin disease are largely undefined. To address these questions, human skin single-cell RNA sequencing and spatial transcriptomics data were integrated and compared with mouse skin data. Human skin cell–type annotation was improved using matched spatial transcriptomics data, highlighting the importance of spatial context in cell-type identity, and spatial transcriptomics refined cellular communication inference. In cross-species analyses, we identified a human spinous keratinocyte subpopulation that exhibited proliferative capacity and a heavy metal processing signature, which was absent in mouse and may account for species differences in epidermal thickness. This human subpopulation was expanded in psoriasis and zinc-deficiency dermatitis, attesting to disease relevance and suggesting a paradigm of subpopulation dysfunction as a hallmark of the disease. To assess additional potential subpopulation drivers of skin diseases, we performed cell-of-origin enrichment analysis within genodermatoses, nominating pathogenic cell subpopulations and their communication pathways, which highlighted multiple potential therapeutic targets. This integrated dataset is encompassed in a publicly available web resource to aid mechanistic and translational studies of normal and diseased skin.
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- Bech, Sara, et al.
(author)
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Amyloid-related biomarkers and axonal damage proteins in parkinsonian syndromes.
- 2012
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In: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 18:1, s. 69-72
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Journal article (peer-reviewed)abstract
- Clinical differentiation between parkinsonian syndromes (PS) remains a challenge despite well-established clinical diagnostic criteria. Specific diagnostic biomarkers have yet to be identified, though in recent years, studies have been published on the aid of certain brain related proteins (BRP) in the diagnosing of PS. We investigated the levels of the light subunit of neurofilament triplet protein (NF-L), total tau and phosphorylated tau, amyloid-β(1-42), and the soluble α- and β-cleaved fragments of amyloid precursor proteins in a cohort of patients with various PS.
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| 4. |
- Elmståhl, S., et al.
(author)
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Increased sweat sodium concentration in patients with Alzheimer's disease
- 1993
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In: Dementia (Switzerland). - 1013-7424. ; 4:1, s. 50-53
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Journal article (peer-reviewed)abstract
- Sweat sodium concentration was estimated with pilocarpine iontophoresis in I 15 women with Alzheimer's disease (AD) and 29 healthy control women. The age ranged from 76 to 96 years with a mean age of 85 years in both groups. The mean sodium concentration of 91 ± 41 mmol/l (n = 11) in the Alzheimer patients was significantly higher than in the control group (62 ± 29 mmol/l, n=27, p=0.0011). 27% of AD patients and 7% of the control women did not respond to stimulation. The impaired sweating in AD patients make them more vulnerable to heat stress. Further studies are needed to reveal whether the neurophysiological mechanism involved is located in the hypothalamus, in cortical projections to the hypothalamus or in postganglionic sympathetic fibers.
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- Salvesen, L, et al.
(author)
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The influence of preanalytical conditions on the DJ-1 concentration in human cerebrospinal fluid
- 2014
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In: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 8:3, s. 387-394
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Journal article (peer-reviewed)abstract
- Aim: The purpose of this study was to establish the influence of centrifugation and protease activity on the cerebrospinal fluid (CSF) concentrations of DJ-1 and hemoglobin. Materials & methods: The concentrations of DJ-1 and hemoglobin were determined in 12 (DJ-1) and six (hemoglobin) pairs of CSF samples, with one sample being stored without centrifugation and the other being centrifuged at 2000 × g before storage. The DJ-1 concentration was also determined in centrifuged and uncentrifuged CSF containing protease inhibitors and compared with values determined in centrifuged and uncentrifuged CSF samples without protease inhibitors. Furthermore, specific protein concentrations were determined in CSF from two groups, each comprising 23 patients with Parkinson’s disease. In one group the CSF was centrifuged at 1300−1800 × g, 4°C, 10 min, and in the other at 2000 × g, 4°C, 10 min. Results: Centrifugation at 2000 × g resulted in significantly lower CSF DJ-1 concentrations compared with no centrifugation and centrifugation at a lower g-force. There was a significant difference in the hemoglobin concentration between centrifuged and uncentrifuged CSF. In all centrifuged samples the hemoglobin concentration was <200 ng/ml including blood contaminated samples centrifuged at 2000 × g. When a protease inhibitor cocktail was added to the CSF prior to centrifugation, the DJ-1 concentration was significantly higher. Conclusion: Preanalytical factors such as centrifugation and protease inhibition must be carefully controlled when handling CSF for analysis of DJ-1 and other biomarkers, as DJ-1 was influenced by blood contamination, centrifugation and protease activity.
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