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Publications (10 of 35) Show all publications
Arner, P., Bernard, S., Appelsved, L., Fu, K.-Y. -., Andersson, D. P., Salehpour, M., . . . Spalding, K. L. (2019). Adipose lipid turnover and long-term changes in body weight. Nature Medicine, 25(9), 1385-1389
Open this publication in new window or tab >>Adipose lipid turnover and long-term changes in body weight
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2019 (English)In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 25, no 9, p. 1385-1389Article in journal (Refereed) Published
Abstract [en]

The worldwide obesity epidemic(1) makes it important to understand how lipid turnover (the capacity to store and remove lipids) regulates adipose tissue mass. Cross-sectional studies have shown that excess body fat is associated with decreased adipose lipid removal rates(2,3). Whether lipid turnover is constant over the life span or changes during long-term weight increase or loss is unknown. We determined the turnover of fat cell lipids in adults followed for up to 16 years, by measuring the incorporation of nuclear bomb test-derived C-14 in adipose tissue triglycerides. Lipid removal rate decreases during aging, with a failure to reciprocally adjust the rate of lipid uptake resulting in weight gain. Substantial weight loss is not driven by changes in lipid removal but by the rate of lipid uptake in adipose tissue. Furthermore, individuals with a low baseline lipid removal rate are more likely to remain weight-stable after weight loss. Therefore, lipid turnover adaptation might be important for maintaining pronounced weight loss. Together these findings identify adipose lipid turnover as an important factor for the long-term development of overweight/obesity and weight loss maintenance in humans.

National Category
Biophysics Cell and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-394253 (URN)10.1038/s41591-019-0565-5 (DOI)000484832800020 ()31501613 (PubMedID)
Funder
Swedish Research Council, K2014-54x-14510-12-5Swedish Research Council, K2012-55x-01034-46-5Swedish Research Council, 542-2013-8358Novo Nordisk, NNF120 C1016064Novo Nordisk, NNF15SA0018346Novo Nordisk, NNF15CC0018486Novo Nordisk, 120C101637Swedish Diabetes Association, DIA2016-097
Available from: 2019-10-09 Created: 2019-10-09 Last updated: 2019-10-09Bibliographically approved
Yeung, M. S. Y., Djelloul, M., Steiner, E., Bernard, S., Salehpour, M., Possnert, G., . . . Frisen, J. (2019). Dynamics of oligodendrocyte generation in multiple sclerosis. Nature, 566(7745), 538-+
Open this publication in new window or tab >>Dynamics of oligodendrocyte generation in multiple sclerosis
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2019 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 566, no 7745, p. 538-+Article in journal (Refereed) Published
Abstract [en]

Oligodendrocytes wrap nerve fibres in the central nervous system with layers of specialized cell membrane to form myelin sheaths(1). Myelin is destroyed by the immune system in multiple sclerosis, but myelin is thought to regenerate and neurological function can be recovered. In animal models of demyelinating disease, myelin is regenerated by newly generated oligodendrocytes, and remaining mature oligodendrocytes do not seem to contribute to this process(2-4). Given the major differences in the dynamics of oligodendrocyte generation and adaptive myelination between rodents and humans(5-9), it is not clear how well experimental animal models reflect the situation in multiple sclerosis. Here, by measuring the integration of C-14 derived from nuclear testing in genomic DNA(10), we assess the dynamics of oligodendrocyte generation in patients with multiple sclerosis. The generation of new oligodendrocytes was increased several-fold in normal-appearing white matter in a subset of individuals with very aggressive multiple sclerosis, but not in most subjects with the disease, demonstrating an inherent potential to substantially increase oligodendrocyte generation that fails in most patients. Oligodendrocytes in shadow plaques-thinly myelinated lesions that are thought to represent remyelinated areas-were old in patients with multiple sclerosis. The absence of new oligodendrocytes in shadow plaques suggests that remyelination of lesions occurs transiently or not at all, or that myelin is regenerated by pre-existing, and not new, oligodendrocytes in multiple sclerosis. We report unexpected oligodendrocyte generation dynamics in multiple sclerosis, and this should guide the use of current, and the development of new, therapies.

National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:uu:diva-379035 (URN)10.1038/s41586-018-0842-3 (DOI)000459769100050 ()30675058 (PubMedID)
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Knut and Alice Wallenberg FoundationEU, European Research Council
Available from: 2019-03-11 Created: 2019-03-11 Last updated: 2019-03-11Bibliographically approved
Huttner, H. B., Bergmann, O., Salehpour, M., El Cheikh, R., Nakamura, M., Tortora, A., . . . Frisen, J. (2018). Meningioma growth dynamics assessed by radiocarbon retrospective birth dating. EBioMedicine, 27, 176-181
Open this publication in new window or tab >>Meningioma growth dynamics assessed by radiocarbon retrospective birth dating
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2018 (English)In: EBioMedicine, ISSN 0360-0637, E-ISSN 2352-3964, Vol. 27, p. 176-181Article in journal (Refereed) Published
Abstract [en]

It is not known how long it takes from the initial neoplastic transformation of a cell to the detection of a tumor, which would be valuable for understanding tumor growth dynamics. Meningiomas show a broad histological, genetic and clinical spectrum, are usually benign and considered slowly growing. There is an intense debate regarding their age and growth pattern and when meningiomas should be resected. We have assessed the age and growth dynamics of 14 patients with meningiomas (WHO grade I: n = 6 with meningothelial and n = 6 with fibrous subtype, as well as n = 2 atypical WHO grade II meningiomas) by combining retrospective birth-dating of cells by analyzing incorporation of nuclear-bomb-test-derived 14C, analysis of cell proliferation, cell density, MRI imaging and mathematical modeling. We provide an integrated model of the growth dynamics of benign meningiomas. The mean age of WHO grade I meningiomas was 22.1 ± 6.5 years, whereas atypical WHO grade II meningiomas originated 1.5 ± 0.1 years prior to surgery (p < 0.01). We conclude that WHO grade I meningiomas are very slowly growing brain tumors, which are resected in average two decades after time of origination.

Keywords
Radiocarbon, C14, Meningioma, Tumor growth
National Category
Cancer and Oncology Biomedical Laboratory Science/Technology
Identifiers
urn:nbn:se:uu:diva-348780 (URN)10.1016/j.ebiom.2017.12.020 (DOI)000425875400023 ()29277322 (PubMedID)
Funder
Swedish Research CouncilSwedish Cancer SocietySwedish Foundation for Strategic Research Knut and Alice Wallenberg FoundationEU, European Research CouncilRagnar Söderbergs stiftelseÅke Wiberg FoundationGerman Research Foundation (DFG), HU1961/1-1; HU1961/2-1
Available from: 2018-04-17 Created: 2018-04-17 Last updated: 2018-04-17Bibliographically approved
Landsverk, O. J. B., Snir, O., Casado, R. B., Richter, L., Mold, J. E., Reu, P., . . . Jahnsen, F. L. (2017). Antibody-secreting plasma cells persist for decades in human intestine. Journal of Experimental Medicine, 214(2), 309-317
Open this publication in new window or tab >>Antibody-secreting plasma cells persist for decades in human intestine
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2017 (English)In: Journal of Experimental Medicine, ISSN 0022-1007, E-ISSN 1540-9538, Vol. 214, no 2, p. 309-317Article in journal (Refereed) Published
Abstract [en]

Plasma cells (PCs) produce antibodies that mediate immunity after infection or vaccination. In contrast to PCs in the bone marrow, PCs in the gut have been considered short lived. In this study, we studied PC dynamics in the human small intestine by cell-turnover analysis in organ transplants and by retrospective cell birth dating measuring carbon-14 in genomic DNA. We identified three distinct PC subsets: a CD19(+) PC subset was dynamically exchanged, whereas of two CD19(-) PC subsets, CD45(+) PCs exhibited little and CD45(-) PCs no replacement and had a median age of 11 and 22 yr, respectively. Accumulation of CD45(-) PCs during ageing and the presence of rotavirus-specific clones entirely within the CD19(-) PC subsets support selection and maintenance of protective PCs for life in human intestine.

Place, publisher, year, edition, pages
NewYork, USA: , 2017
National Category
Biophysics Immunology in the medical area
Research subject
Physics with specialization in Ion Physics
Identifiers
urn:nbn:se:uu:diva-317759 (URN)10.1084/jem.20161590 (DOI)000394251400004 ()28104812 (PubMedID)
Projects
The Human Regenerative Map
Funder
Swedish Research CouncilSwedish Cancer SocietyThe Karolinska Institutet's Research FoundationKnut and Alice Wallenberg FoundationTorsten Söderbergs stiftelse
Available from: 2017-03-17 Created: 2017-03-17 Last updated: 2018-01-13Bibliographically approved
Spalding, K. L., Bernard, S., Näslund, E., Salehpour, M., Possnert, G., Appelsved, L., . . . Arner, P. (2017). Impact of fat mass and distribution on lipid turnover in human adipose tissue. Nature Communications, 8, Article ID 15253.
Open this publication in new window or tab >>Impact of fat mass and distribution on lipid turnover in human adipose tissue
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2017 (English)In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 8, article id 15253Article in journal (Refereed) Published
Abstract [en]

Differences in white adipose tissue (WAT) lipid turnover between the visceral (vWAT) and subcutaneous (sWAT) depots may cause metabolic complications in obesity. Here we compare triglyceride age and, thereby, triglyceride turnover in vWAT and sWAT biopsies from 346 individuals and find that subcutaneous triglyceride age and storage capacity are increased in overweight or obese individuals. Visceral triglyceride age is only increased in excessively obese individuals and associated with a lower lipid removal capacity. Thus, although triglyceride storage capacity in sWAT is higher than in vWAT, the former plateaus at substantially lower levels of excess WAT mass than vWAT. In individuals with central or visceral obesity, lipid turnover is selectively increased in vWAT. Obese individuals classified as 'metabolically unhealthy' (according to ATPIII criteria) who have small subcutaneous adipocytes exhibit reduced triglyceride turnover. We conclude that excess WAT results in depot-specific differences in lipid turnover and increased turnover in vWAT and/or decreased turnover in sWAT may result in metabolic complications of overweight or obesity.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-325697 (URN)10.1038/ncomms15253 (DOI)000401831600001 ()28534500 (PubMedID)
Funder
EU, European Research CouncilSwedish Research CouncilNovo Nordisk, NNF15CC0018486
Available from: 2017-06-27 Created: 2017-06-27 Last updated: 2017-11-29Bibliographically approved
Reu, P., Khosravi, A., Bernard, S., Mold, J. E., Salehpour, M., Alkass, K., . . . Frisen, J. (2017). The Lifespan and Turnover of Microglia in the Human Brain. Cell reports, 20(4), 779-784
Open this publication in new window or tab >>The Lifespan and Turnover of Microglia in the Human Brain
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2017 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 20, no 4, p. 779-784Article in journal (Refereed) Published
Abstract [en]

The hematopoietic system seeds the CNS with microglial progenitor cells during the fetal period, but the subsequent cell generation dynamics and maintenance of this population have been poorly understood. We report that microglia, unlike most other hematopoietic lineages, renew slowly at a median rate of 28% per year, and some microglia last for more than two decades. Furthermore, we find no evidence for the existence of a substantial population of quiescent long-lived cells, meaning that the microglia population in the human brain is sustained by continuous slow turnover throughout adult life.

Place, publisher, year, edition, pages
Cambridge, MA 02139, USA: , 2017
Keywords
Cell turnover, regeneration, microglia, human brain
National Category
Biophysics Cell Biology
Research subject
Ion Physics; Biology with specialization in Molecular Cell Biology
Identifiers
urn:nbn:se:uu:diva-328314 (URN)10.1016/j.celrep.2017.07.004 (DOI)000406198900002 ()28746864 (PubMedID)
Projects
The Human Regeneration Map
Available from: 2017-08-21 Created: 2017-08-21 Last updated: 2017-11-29Bibliographically approved
Persson, A. & Salehpour, M. (2016). Comment on “Intracavity OptoGalvanic Spectroscopy Not Suitable for Ambient Level Radiocarbon Detection". Analytical Chemistry, 88(8), 4578-4579
Open this publication in new window or tab >>Comment on “Intracavity OptoGalvanic Spectroscopy Not Suitable for Ambient Level Radiocarbon Detection"
2016 (English)In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 88, no 8, p. 4578-4579Article in journal (Refereed) Published
Abstract [en]

Every new discovery must undergo thorough scientific scrutiny before being recognized. One important step in the process is confirmation by independent experiments. The case at hand is intracavity optogalvanic spectroscopy (ICOGS), which was first published by Murnick et al. in 2008, and claimed to have the potential to revolutionize rare-isotope measurements in general and those of radiocarbon in particular. Since then, no data has been reported in any shape or form to support it. On the contrary, in spite of extensive efforts at five different sites around the world – apart from Murnick’s group at Rutgers University, Professor Meijer’s group at the Energy and Sustainability Research Institute Groningen at University of Groningen, Professor Lackner’s group at the Department of Earth and Environmental Engineering at Columbia University, our group at the Department of Physics and Astronomy at Uppsala University, and the company Planetary Emission Management Inc. – the original data still remains unconfirmed, and a number of publications have seriously questioned the scientific validity of the original report.

Keywords
Intracavity optogalvanic spectroscopy
National Category
Other Electrical Engineering, Electronic Engineering, Information Engineering Atom and Molecular Physics and Optics Analytical Chemistry
Research subject
Engineering Science with specialization in Microsystems Technology
Identifiers
urn:nbn:se:uu:diva-283695 (URN)10.1021/acs.analchem.6b00613 (DOI)000374706000057 ()27015441 (PubMedID)
Funder
Swedish Research Council
Available from: 2016-04-14 Created: 2016-04-14 Last updated: 2017-10-30Bibliographically approved
Salehpour, M., Håkansson, K., Possnert, G., Wacker, L. & Synal, H.-A. (2016). Performance report for the low energy compact radiocarbon accelerator mass spectrometer at Uppsala University. In: : . Paper presented at 22nd International Conference on Ion Beam Analysis (IBA), JUN 14-19, 2015, Opatija, CROATIA (pp. 360-364). , 371
Open this publication in new window or tab >>Performance report for the low energy compact radiocarbon accelerator mass spectrometer at Uppsala University
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2016 (English)Conference paper, Published paper (Refereed)
Abstract [en]

A range of ion beam analysis activities are ongoing at Uppsala University, including Accelerator Mass Spectrometry (AMS). Various isotopes are used for AMS but the isotope with the widest variety of applications is radiocarbon. Up until recently, only the 5 MV Pelletron tandem accelerator had been used at our site for radiocarbon AMS, ordinarily using 12 MeV C-14,13,12(3+) ions. Recently a new radiocarbon AMS system, the Green-MICADAS, developed at the ion physics group at ETH Zurich, was installed. The system has a number of outstanding features which will be described. The system operates at a terminal voltage of 175 kV and uses helium stripper gas, extracting singly charged carbon ions. The low- and high energy mass spectrometers in the system are stigmatic dipole permanent magnets (0.42 and 0.97 T) requiring no electrical power nor cooling water. The system measures both the C-14/C-12 and the C-13/C-12 ratios on-line. Performance of the system is presented for both standard mg samples as well as mu g-sized samples.

Keywords
Uppsala, Accelerator Mass Spectrometry, Green MICADAS, Ultra small samples, Biomedical
National Category
Accelerator Physics and Instrumentation
Identifiers
urn:nbn:se:uu:diva-295579 (URN)10.1016/j.nimb.2015.10.034 (DOI)000373412000072 ()
Conference
22nd International Conference on Ion Beam Analysis (IBA), JUN 14-19, 2015, Opatija, CROATIA
Available from: 2016-06-22 Created: 2016-06-08 Last updated: 2016-07-15Bibliographically approved
Bergmann, O., Zdunek, S., Felker, A., Salehpour, M., Alkass, K., Bernard, S., . . . Frisen, J. (2015). Dynamics of Cell Generation and Turnover in the Human Heart. Cell, 161(7), 1566-1575
Open this publication in new window or tab >>Dynamics of Cell Generation and Turnover in the Human Heart
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2015 (English)In: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 161, no 7, p. 1566-1575Article in journal (Refereed) Published
Abstract [en]

The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived C-14 revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart.

National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-258335 (URN)10.1016/j.cell.2015.05.026 (DOI)000356618200014 ()26073943 (PubMedID)
Funder
Swedish Research CouncilSwedish Heart Lung FoundationSwedish Cancer SocietyKnut and Alice Wallenberg Foundation
Available from: 2015-07-14 Created: 2015-07-13 Last updated: 2017-12-04Bibliographically approved
Persson, A. & Salehpour, M. (2015). Intracavity optogalvanic spectroscopy: Is there any evidence of a radiocarbon signal?. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 361, 8-12
Open this publication in new window or tab >>Intracavity optogalvanic spectroscopy: Is there any evidence of a radiocarbon signal?
2015 (English)In: Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, ISSN 0168-583X, E-ISSN 1872-9584, Vol. 361, p. 8-12Article in journal (Refereed) Published
Abstract [en]

In 2008, the first report of an ultrasensitive method for ro-vibrational spectrometry of radiocarbon dioxide was published. The method, called intracavity optogalvanic spectroscopy (ICOGS), claimed a sensitivity and limit-of-detection comparable to accelerator mass spectroscopy. ICOGS was claimed to utilize the isotope-dependent ro-vibrational absorption lines of carbon dioxide in the infrared spectrum. In order to facilitate unambiguous detection of radiocarbon, the sample was placed inside the cavity of a radiocarbon dioxide laser. This intracavity approach was claimed to increase the sensitivity by seven orders of magnitude compared with traditional optogalvanic methods. However, despite the methodical and thorough efforts of several research groups worldwide, these claims have not been possible to reproduce. Instead, we have previously reported serious deviations from the original results, where we found that ICOGS suffers from considerable problems with the stability and reproducibility of the optogalvanic signal, and that misinterpretations of these uncertainties likely are the explanation for the claimed sensitivity in the first reports. Having identified the stability and reproducibility of the detection as major concerns, we decided to improve the setup by with state-of-the-art plasma source technology. Deploying a custom-made stripline split-ring resonator optogalvanic detector, we have now investigated the applicability of ICOGS to radiocarbon detection even further. Measurements have been made with a wide range of parameters including different gas mixtures at various pressures and wavelengths. We have also conducted measurements with gas flowing through the sample cell to investigate the effect of plasma induced decomposition of the sample. Still, we have seen no indications of a significant radiocarbon signal in a concentration range between 0.29 Modern and 9.7 Modern, i.e., the range of interest to the radiocarbon community. Hence, our conclusions after four years of working in this field, is that ICOGS is not a viable method for radiocarbon detection. 

Keywords
Intracavity optogalvanic spectroscopy; Split-ring resonator; Radiocarbon; Cavity-enhanced; Infrared spectroscopy
National Category
Atom and Molecular Physics and Optics Electrical Engineering, Electronic Engineering, Information Engineering
Research subject
Engineering Science with specialization in Microsystems Technology; Physics with specialization in Applied Nuclear Physics
Identifiers
urn:nbn:se:uu:diva-244249 (URN)10.1016/j.nimb.2014.12.065 (DOI)000363345900002 ()
Funder
Swedish Research Council, A0442201
Available from: 2015-02-13 Created: 2015-02-13 Last updated: 2017-12-04Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/mehran.salehpour@physics.uu.se

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