| 1. |
- Barrio, Isabel C., et al.
(författare)
-
Background invertebrate herbivory on dwarf birch (Betula glandulosa-nana complex) increases with temperature and precipitation across the tundra biome
- 2017
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Ingår i: Polar Biology. - : Springer. - 0722-4060 .- 1432-2056. ; 40:11, s. 2265-2278
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Tidskriftsartikel (refereegranskat)abstract
- Chronic, low intensity herbivory by invertebrates, termed background herbivory, has been understudied in tundra, yet its impacts are likely to increase in a warmer Arctic. The magnitude of these changes is however hard to predict as we know little about the drivers of current levels of invertebrate herbivory in tundra. We assessed the intensity of invertebrate herbivory on a common tundra plant, the dwarf birch (Betula glandulosa-nana complex), and investigated its relationship to latitude and climate across the tundra biome. Leaf damage by defoliating, mining and gall-forming invertebrates was measured in samples collected from 192 sites at 56 locations. Our results indicate that invertebrate herbivory is nearly ubiquitous across the tundra biome but occurs at low intensity. On average, invertebrates damaged 11.2% of the leaves and removed 1.4% of total leaf area. The damage was mainly caused by external leaf feeders, and most damaged leaves were only slightly affected (12% leaf area lost). Foliar damage was consistently positively correlated with mid-summer (July) temperature and, to a lesser extent, precipitation in the year of data collection, irrespective of latitude. Our models predict that, on average, foliar losses to invertebrates on dwarf birch are likely to increase by 6-7% over the current levels with a 1 degrees C increase in summer temperatures. Our results show that invertebrate herbivory on dwarf birch is small in magnitude but given its prevalence and dependence on climatic variables, background invertebrate herbivory should be included in predictions of climate change impacts on tundra ecosystems.
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| 2. |
- Barrio, Isabel C., et al.
(författare)
-
Publisher Correction to : Background invertebrate herbivory on dwarf birch (Betula glandulosa-nana complex) increases with temperature and precipitation across the tundra biome (vol 40, pg 2265, 2017)
- 2018
-
Ingår i: Polar Biology. - : Springer. - 0722-4060 .- 1432-2056. ; 41:8, s. 1653-1654
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Tidskriftsartikel (refereegranskat)abstract
- The above mentioned article was originally scheduled for publication in the special issue on Ecology of Tundra Arthropods with guest editors Toke T. Hoye . Lauren E. Culler. Erroneously, the article was published in Polar Biology, Volume 40, Issue 11, November, 2017. The publisher sincerely apologizes to the guest editors and the authors for the inconvenience caused.
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| 3. |
- Björkman, Anne, 1981, et al.
(författare)
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Tundra Trait Team: A database of plant traits spanning the tundra biome
- 2018
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 27:12, s. 1402-1411
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Tidskriftsartikel (refereegranskat)abstract
- © 2018 The Authors Global Ecology and Biogeography Published by John Wiley & Sons Ltd Motivation: The Tundra Trait Team (TTT) database includes field-based measurements of key traits related to plant form and function at multiple sites across the tundra biome. This dataset can be used to address theoretical questions about plant strategy and trade-offs, trait–environment relationships and environmental filtering, and trait variation across spatial scales, to validate satellite data, and to inform Earth system model parameters. Main types of variable contained: The database contains 91,970 measurements of 18 plant traits. The most frequently measured traits (>1,000 observations each) include plant height, leaf area, specific leaf area, leaf fresh and dry mass, leaf dry matter content, leaf nitrogen, carbon and phosphorus content, leaf C:N and N:P, seed mass, and stem specific density. Spatial location and grain: Measurements were collected in tundra habitats in both the Northern and Southern Hemispheres, including Arctic sites in Alaska, Canada, Greenland, Fennoscandia and Siberia, alpine sites in the European Alps, Colorado Rockies, Caucasus, Ural Mountains, Pyrenees, Australian Alps, and Central Otago Mountains (New Zealand), and sub-Antarctic Marion Island. More than 99% of observations are georeferenced. Time period and grain: All data were collected between 1964 and 2018. A small number of sites have repeated trait measurements at two or more time periods. Major taxa and level of measurement: Trait measurements were made on 978 terrestrial vascular plant species growing in tundra habitats. Most observations are on individuals (86%), while the remainder represent plot or site means or maximums per species. Software format: csv file and GitHub repository with data cleaning scripts in R; contribution to TRY plant trait database (www.try-db.org) to be included in the next version release.
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| 4. |
- Jones, Benedict C, et al.
(författare)
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To which world regions does the valence-dominance model of social perception apply?
- 2021
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Ingår i: Nature Human Behaviour. - : Springer Science and Business Media LLC. - 2397-3374. ; 5:1, s. 159-169
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Tidskriftsartikel (refereegranskat)abstract
- Over the past 10 years, Oosterhof and Todorov's valence-dominance model has emerged as the most prominent account of how people evaluate faces on social dimensions. In this model, two dimensions (valence and dominance) underpin social judgements of faces. Because this model has primarily been developed and tested in Western regions, it is unclear whether these findings apply to other regions. We addressed this question by replicating Oosterhof and Todorov's methodology across 11 world regions, 41 countries and 11,570 participants. When we used Oosterhof and Todorov's original analysis strategy, the valence-dominance model generalized across regions. When we used an alternative methodology to allow for correlated dimensions, we observed much less generalization. Collectively, these results suggest that, while the valence-dominance model generalizes very well across regions when dimensions are forced to be orthogonal, regional differences are revealed when we use different extraction methods and correlate and rotate the dimension reduction solution. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 5 November 2018. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.7611443.v1 .
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| 5. |
- Bergman, Martin, et al.
(författare)
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Contest outcome in a territorial butterfly : the role of motivation
- 2010
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 277:1696, s. 3027-3033
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Tidskriftsartikel (refereegranskat)abstract
- In many butterfly species, males compete over areas advantageous for encountering females. Rules for contest settlement are, however, largely unknown and neither morphological nor physiological traits can reliably predict the contest outcome. Here, we test the hypothesis that contests are settled in accordance with a motivation asymmetry. We staged contests between males of Pararge aegeria and after removing the resident, the non-resident was allowed (i) either to interact with a non-receptive female for 30 min (n = 30) or (ii) to spend 30 min alone in the cage (n = 30), after which the initial resident was reintroduced. The results show that males that had interacted with a female had a higher probability of becoming dominant and reversing contest outcome. Moreover, males that were faster to take over a vacant territory when the resident was removed were more likely to become dominant. Here, we show for the first time, to our knowledge, that frequent encounters with a mated female can increase male motivation to persist in a territorial contest in a butterfly. Further, we suggest that variation in intrinsic motivation reflects male eagerness to take over vacant territory. This study indicates that variation in resource value and motivational asymmetries are important for settling contests in butterflies.
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| 6. |
- Bergman, Martin, et al.
(författare)
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Mating success of resident versus non-resident males in a territorial butterfly
- 2007
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Ingår i: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 274:1618, s. 1659-1665
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Tidskriftsartikel (refereegranskat)abstract
- Male–male competition over territorial ownership suggests that winning is associated with considerable benefits. In the speckled wood butterfly, Pararge aegeria, males fight over sunspot territories on the forest floor; winners gain sole residency of a sunspot, whereas losers patrol the forest in search of females. It is currently not known whether residents experience greater mating success than nonresidents, or whether mating success is contingent on environmental conditions. Here we performed an experiment in which virgin females of P. aegeria were allowed to choose between a resident and a nonresident male in a large enclosure containing one territorial sunspot. Resident males achieved approximately twice as many matings as non-residents, primarily because matings were most often preceded by a female being discovered when flying through a sunspot. There was no evidence that territorial residents were more attractive per se, with females seen to reject them as often as nonresidents. Furthermore, in the cases where females were discovered outside of the sunspot, they were just as likely to mate with non-residents as residents. We hypothesize that the proximate advantage of territory ownership is that light conditions in a large sunspot greatly increase the male’s ability to detect and intercept passing receptive females.
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| 7. |
- Björkman, Anne, 1981, et al.
(författare)
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Plant functional trait change across a warming tundra biome
- 2018
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 562:7725, s. 57-62
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Tidskriftsartikel (refereegranskat)abstract
- The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature–trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.
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| 8. |
- Frisk, U., et al.
(författare)
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The Odin satellite - I. Radiometer design and test
- 2003
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Ingår i: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 402:3, s. L27-L34
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Tidskriftsartikel (refereegranskat)abstract
- The Sub-millimetre and Millimetre Radiometer (SMR) is the main instrument on the Swedish, Canadian, Finnish and French spacecraft Odin. It consists of a 1.1 metre diameter telescope with four tuneable heterodyne receivers covering the ranges 486-504 GHz and 541-581 GHz, and one fixed at 118.75 GHz together with backends that provide spectral resolution from 150 kHz to 1 MHz. This Letter describes the Odin radiometer, its operation and performance with the data processing and calibration described in Paper II.
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| 9. |
- Gad, Helge, et al.
(författare)
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MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool
- 2014
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7495, s. 215-221
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Tidskriftsartikel (refereegranskat)abstract
- Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. Although MTH1 is non-essential in normal cells, we show that cancer cells require MTH1 activity to avoid incorporation of oxidized dNTPs, resulting in DNA damage and cell death. We validate MTH1 as an anticancer target in vivo and describe small molecules TH287 and TH588 as first-in-class nudix hydrolase family inhibitors that potently and selectively engage and inhibit the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitors bindin the active site of MTH1. The inhibitors cause incorporation of oxidized dNTPs in cancer cells, leading to DNA damage, cytotoxicity and therapeutic responses in patient-derived mouse xenografts. This study exemplifies the non-oncogene addiction concept for anticancer treatment and validates MTH1 as being cancer phenotypic lethal.
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| 10. |
- Håkansson, Katarina, et al.
(författare)
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Process and system integration aspects of biomass torrefaction
- 2010
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Ingår i: 18th European Biomass Conference and Exhibition: Proceedings.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The pre-treatment method torrefaction has been shown to significantly improve biomass fuel characteristics such as energy density, moisture content, milling energy, feeding and hydrophobic properties. These improvements establish torrefaction as a key process in facilitating an expanding market for biomass raw materials. Most of the previous work has focused on evaluating and optimizing the torrefaction process alone. However, to fully explore the maximum energy/exergy and cost efficiency of biomass torrefaction, the entire fuel supply chain and site specific systems must be considered; including logistics, scale and integration with other processes. The present work in progress aims to develop a model that incorporates optimization of the biomass supply chain and process integration systems together with the torrefaction process in order to avoid sub-optimization.
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| 11. |
- Kühn, Ingolf, et al.
(författare)
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MACIS: Minimisation of and Adaptation to Climate Change Impacts on BiodiverSity
- 2008
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Ingår i: GAIA. - 0940-5550. ; 17:4, s. 393-395
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Tidskriftsartikel (refereegranskat)abstract
- The recently finished EU funded project MACIS reviewed observed and projected climate change impacts on biodiversity. It assessed mitigation and adaptation options. It also reviewed and developed methods to assess future impacts of climate change on biodiversity including the identification of policy options to prevent and minimise these impacts.
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| 12. |
- Lindén, Elin, et al.
(författare)
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Circum-Arctic distribution of chemical anti-herbivore compounds suggests biome-wide trade-off in defence strategies in Arctic shrubs
- 2022
-
Ingår i: Ecography. - : John Wiley & Sons. - 0906-7590 .- 1600-0587. ; :11
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Tidskriftsartikel (refereegranskat)abstract
- Spatial variation in plant chemical defence towards herbivores can help us understand variation in herbivore top–down control of shrubs in the Arctic and possibly also shrub responses to global warming. Less defended, non-resinous shrubs could be more influenced by herbivores than more defended, resinous shrubs. However, sparse field measurements limit our current understanding of how much of the circum-Arctic variation in defence compounds is explained by taxa or defence functional groups (resinous/non-resinous). We measured circum-Arctic chemical defence and leaf digestibility in resinous (Betula glandulosa, B. nana ssp. exilis) and non-resinous (B. nana ssp. nana, B. pumila) shrub birches to see how they vary among and within taxa and functional groups. Using liquid chromatography–mass spectrometry (LC–MS) metabolomic analyses and in vitro leaf digestibility via incubation in cattle rumen fluid, we analysed defence composition and leaf digestibility in 128 samples from 44 tundra locations.We found biogeographical patterns in anti-herbivore defence where mean leaf triterpene concentrations and twig resin gland density were greater in resinous taxa and mean concentrations of condensing tannins were greater in non-resinous taxa. This indicates a biome-wide trade-off between triterpene- or tannin-dominated defences. However, we also found variations in chemical defence composition and resin gland density both within and among functional groups (resinous/non-resinous) and taxa, suggesting these categorisations only partly predict chemical herbivore defence. Complex tannins were the only defence compounds negatively related to in vitro digestibility, identifying this previously neglected tannin group as having a potential key role in birch anti-herbivore defence.We conclude that circum-Arctic variation in birch anti-herbivore defence can be partly derived from biogeographical distributions of birch taxa, although our detailed mapping of plant defence provides more information on this variation and can be used for better predictions of herbivore effects on Arctic vegetation.
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| 13. |
- Liu, Meng, 1976, et al.
(författare)
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Targeting the protein prenyltransferases efficiently reduces tumor development in mice with K-RAS-induced lung cancer
- 2010
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 107:14, s. 6471-6476
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Tidskriftsartikel (refereegranskat)abstract
- RAS and RHO proteins, which contribute to tumorigenesis and metastasis, undergo posttranslational modification with an isoprenyl lipid by protein farnesyltransferase (FTase) or protein geranylgeranyltransferase-I (GGTase-I). Inhibitors of FTase and GGTase-I were developed to block RAS-induced malignancies, but their utility has been difficult to evaluate because of off-target effects, drug resistance, and toxicity. Moreover, the impact of FTase deficiency and combined FTase/GGTase-I deficiency has not been evaluated with genetic approaches. We found that inactivation of FTase eliminated farnesylation of HDJ2 and H-RAS, prevented H-RAS targeting to the plasma membrane, and blocked proliferation of primary and K-RAS(G12D)-expressing fibroblasts. FTase inactivation in mice with K-RAS-induced lung cancer reduced tumor growth and improved survival, similar to results obtained previously with inactivation of GGTase-I. Simultaneous inactivation of FTase and GGTase-I markedly reduced lung tumors and improved survival without apparent pulmonary toxicity. These data shed light on the biochemical and therapeutic importance of FTase and suggest that simultaneous inhibition of FTase and GGTase-I could be useful in cancer therapeutics.
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| 14. |
- Adiels, Martin, 1976, et al.
(författare)
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A brief review of lipoprotein metabolism
- 2009
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Ingår i: Evidence-Based Management of Lipid Disorders. - : Tfm Publishing. - 1903378710
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 15. |
- Adiels, Martin, 1976, et al.
(författare)
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A new combined multicompartmental model for apolipoprotein B-100 and triglyceride metabolism in VLDL subfractions
- 2005
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Ingår i: J Lipid Res. - 0022-2275 .- 1539-7262. ; 46:1, s. 58-67
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Tidskriftsartikel (refereegranskat)abstract
- The use of stable isotopes in conjunction with compartmental modeling analysis has greatly facilitated studies of the metabolism of the apolipoprotein B (apoB)-containing lipoproteins in humans. The aim of this study was to develop a multicompartment model that allows us to simultaneously determine the kinetics of apoB and triglyceride (TG) in VLDL(1) and VLDL(2) after a bolus injection of [(2)H(3)]leucine and [(2)H(5)]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Here, we describe the model and present the results of its application in a fasting steady-state situation in 17 subjects with lipid values representative of a Western population. Analysis of the correlations showed that plasma TG was determined by the VLDL(1) and VLDL(2) apoB and TG fractional catabolic rate. Furthermore, the model showed a linear correlation between VLDL(1) TG and apoB production. A novel observation was that VLDL TG entered the circulation within 21 min after its synthesis, whereas VLDL apoB entered the circulation after 33 min. These observations are consistent with a sequential assembly model of VLDL and suggest that the TG is added to a primordial apoB-containing particle in the liver.
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| 16. |
- Adiels, Martin, 1976, et al.
(författare)
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Acute suppression of VLDL(1) secretion rate by insulin is associated with hepatic fat content and insulin resistance
- 2007
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 50:11, s. 2356-2365
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: Overproduction of VLDL(1) seems to be the central pathophysiological feature of the dyslipidaemia associated with type 2 diabetes. We explored the relationship between liver fat and suppression of VLDL(1) production by insulin in participants with a broad range of liver fat content. METHODS: A multicompartmental model was used to determine the kinetic parameters of apolipoprotein B and TG in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol during a hyperinsulinaemic-euglycaemic clamp in 20 male participants: eight with type 2 diabetes and 12 control volunteers. The participants were divided into two groups with low or high liver fat. All participants with diabetes were in the high liver-fat group. RESULTS: The results showed a rapid drop in VLDL(1)-apolipoprotein B and -triacylglycerol secretion in participants with low liver fat during the insulin infusion. In contrast, participants with high liver fat showed no significant change in VLDL(1) secretion. The VLDL(1) suppression following insulin infusion correlated with the suppression of NEFA, and the ability of insulin to suppress the plasma NEFA was impaired in participants with high liver fat. A novel finding was an inverse response between VLDL(1) and VLDL(2) secretion in participants with low liver fat: VLDL(1) secretion decreased acutely after insulin infusion whereas VLDL(2) secretion increased. CONCLUSIONS/INTERPRETATION: Insulin downregulates VLDL(1) secretion and increases VLDL(2) secretion in participants with low liver fat but fails to suppress VLDL(1) secretion in participants with high liver fat, resulting in overproduction of VLDL(1). Thus, liver fat is associated with lack of VLDL(1) suppression in response to insulin.
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| 17. |
- Adiels, Martin, 1976, et al.
(författare)
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Diabetic dyslipidaemia
- 2006
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Ingår i: Curr Opin Lipidol. - 0957-9672 .- 1473-6535. ; 17:3, s. 238-46
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE OF REVIEW: Diabetic dyslipidaemia is a cluster of plasma lipid and lipoprotein abnormalities that are metabolically interrelated. The increase of large type 1 very low density lipoprotein particles in type 2 diabetes initiates a sequence of events that generates atherogenic remnants, small dense low-density lipoprotein and small dense high-density lipoprotein particles. Thus, it is of great importance to elucidate the mechanisms behind the overproduction of large very low density lipoprotein particles in diabetic dyslipidaemia. This review discusses the pathophysiology of very low density lipoprotein metabolism in type 2 diabetes and recent concepts of lipid management of diabetic dyslipidaemia. RECENT FINDINGS: Results indicate that triglyceride and apolipoprotein B production in types 1 and 2 very low density lipoprotein are significantly correlated, suggesting a coupling of the two processes governing the metabolism of these lipoprotein subpopulations. Insulin resistance, hyperglycaemia, and liver fat were associated with excess hepatic production of type 1 but not type 2 very low density lipoprotein particles. These data provide support for the independent regulation of types 1 and 2 very low density lipoprotein apolipoprotein B production. SUMMARY: Recent data suggest that the assembly of very low density lipoprotein is fundamentally altered in type 2 diabetes, explaining the overproduction of large type 1 very low density lipoprotein as well as the inability of insulin to suppress production of type 1 very low density lipoprotein in type 2 diabetes. Future discoveries hopefully will delineate the regulatory steps to allow more targeted treatment of diabetic dyslipidaemia.
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| 18. |
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| 19. |
- Adiels, Martin, 1976, et al.
(författare)
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Overproduction of large VLDL particles is driven by increased liver fat content in man
- 2006
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 49:4, s. 755-65
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Tidskriftsartikel (refereegranskat)abstract
- AIMS/HYPOTHESIS: We determined whether hepatic fat content and plasma adiponectin concentration regulate VLDL(1) production. METHODS: A multicompartment model was used to simultaneously determine the kinetic parameters of triglycerides (TGs) and apolipoprotein B (ApoB) in VLDL(1) and VLDL(2) after a bolus of [(2)H(3)]leucine and [(2)H(5)]glycerol in ten men with type 2 diabetes and in 18 non-diabetic men. Liver fat content was determined by proton spectroscopy and intra-abdominal fat content by MRI. RESULTS: Univariate regression analysis showed that liver fat content, intra-abdominal fat volume, plasma glucose, insulin and HOMA-IR (homeostasis model assessment of insulin resistance) correlated with VLDL(1) TG and ApoB production. However, only liver fat and plasma glucose were significant in multiple regression models, emphasising the critical role of substrate fluxes and lipid availability in the liver as the driving force for overproduction of VLDL(1) in subjects with type 2 diabetes. Despite negative correlations with fasting TG levels, liver fat content, and VLDL(1) TG and ApoB pool sizes, adiponectin was not linked to VLDL(1) TG or ApoB production and thus was not a predictor of VLDL(1) production. However, adiponectin correlated negatively with the removal rates of VLDL(1) TG and ApoB. CONCLUSIONS/INTERPRETATION: We propose that the metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, increases fatty acid flux from adipose tissue to the liver and induces the accumulation of fat in the liver. Elevated plasma glucose can further increase hepatic fat content through multiple pathways, resulting in overproduction of VLDL(1) particles and leading to the characteristic dyslipidaemia associated with type 2 diabetes.
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| 20. |
- Adiels, Martin, 1976, et al.
(författare)
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Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome.
- 2008
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636 .- 1079-5642. ; 28:7, s. 1225-36
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Forskningsöversikt (refereegranskat)abstract
- Insulin resistance is a key feature of the metabolic syndrome and often progresses to type 2 diabetes. Both insulin resistance and type 2 diabetes are characterized by dyslipidemia, which is an important and common risk factor for cardiovascular disease. Diabetic dyslipidemia is a cluster of potentially atherogenic lipid and lipoprotein abnormalities that are metabolically interrelated. Recent evidence suggests that a fundamental defect is an overproduction of large very low-density lipoprotein (VLDL) particles, which initiates a sequence of lipoprotein changes, resulting in higher levels of remnant particles, smaller LDL, and lower levels of high-density liporotein (HDL) cholesterol. These atherogenic lipid abnormalities precede the diagnosis of type 2 diabetes by several years, and it is thus important to elucidate the mechanisms involved in the overproduction of large VLDL particles. Here, we review the pathophysiology of VLDL biosynthesis and metabolism in the metabolic syndrome. We also review recent research investigating the relation between hepatic accumulation of lipids and insulin resistance, and sources of fatty acids for liver fat and VLDL biosynthesis. Finally, we briefly discuss current treatments for lipid management of dyslipidemia and potential future therapeutic targets.
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| 21. |
- Adiels, Martin, 1976, et al.
(författare)
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Overproduction of VLDL1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia
- 2005
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Ingår i: Arterioscler Thromb Vasc Biol. - 1524-4636 .- 1079-5642. ; 25:8, s. 1697-703
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We sought to compare the synthesis and metabolism of VLDL1 and VLDL2 in patients with type 2 diabetes mellitus (DM2) and nondiabetic subjects. METHODS AND RESULTS: We used a novel multicompartmental model to simultaneously determine the kinetics of apolipoprotein (apo) B and triglyceride (TG) in VLDL1 and VLDL2 after a bolus injection of [2H3]leucine and [2H5]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Our results show that the overproduction of VLDL particles in DM2 is explained by enhanced secretion of VLDL1 apoB and TG. Direct production of VLDL2 apoB and TG was not influenced by diabetes per se. The production rates of VLDL1 apoB and TG were closely related, as were the corresponding pool sizes. VLDL1 and VLDL2 compositions did not differ in subjects with DM2 and controls, and the TG to apoB ratio of newly synthesized particles was very similar in the 2 groups. Plasma glucose, insulin, and free fatty acids together explained 55% of the variation in VLDL1 TG production rate. CONCLUSIONS: Insulin resistance and DM2 are associated with excess hepatic production of VLDL1 particles similar in size and composition to those in nondiabetic subjects. We propose that hyperglycemia is the driving force that aggravates overproduction of VLDL1 in DM2.
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| 22. |
- Adiels, Martin, 1976, et al.
(författare)
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Postprandial accumulation of chylomicrons and chylomicron remnants is determined by the clearance capacity.
- 2012
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Ingår i: Atherosclerosis. - : Elsevier BV. - 1879-1484 .- 0021-9150. ; 222:1, s. 222-8
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Tidskriftsartikel (refereegranskat)abstract
- Objective To better understand the postprandial clearance of triglyceride-rich lipoproteins (TRLs) and its relation to the fasting kinetics of TRLs. Methods Two studies were performed on 30 male subjects: a fasting kinetic study to determine the fasting secretion and clearance rates of apolipoprotein B (apoB) 100 and triglycerides in the very low-density lipoprotein 1 and 2 (VLDL1 and VLDL2) fractions; and a postprandial study to determine the postprandial accumulation of apoB48, apoB100 and triglycerides in the chylomicron, VLDL1 and VLDL2 fractions. Results from these two studies were combined to characterize the postprandial clearance of TRLs in a physiologically relevant setting. Results Our results show that postprandial accumulation of the apoB48-carrying chylomicrons can be predicted from the clearance capacity of the lipolytic pathway, determined in the fasting state. Furthermore, we show that chylomicrons and VLDL1 particles are not cleared equally by the lipoprotein lipase pathway, and that chylomicrons seem to be the preferred substrate. Subjects with a rapid fasting lipid metabolism accumulate lower levels of postprandial triglycerides with less accumulation of apoB100 in the VLDL1 fraction and a faster transfer of apoB100 into the VLDL2 fraction. In contrast, fasting VLDL1 secretion does not predict postprandial triglyceride accumulation. Conclusions Non-fasting triglyceride levels have recently been identified as a major predictor of future cardiovascular events. Here we show that the capacity of the lipolytic pathway is a common determinant of both the fasting and non-fasting triglyceride levels and may thus play an important role in the development of dyslipemia and atherosclerosis.
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| 23. |
- Alkner, Sara, et al.
(författare)
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Quality assessment of radiotherapy in the prospective randomized SENOMAC trial
- 2024
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Ingår i: Radiotherapy and Oncology. - 0167-8140 .- 1879-0887. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial.Materials and Methods: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1–2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015–2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail.Results: CRF-data and RT plans agreed in 99.3 % (breast/chest wall) and in 96.6 % of patients (regional RT). Congruence for whether level I was an intended RT target was lower (78 %). In accordance with Danish national guidelines, level I was more often an intended target in the SLN biopsy only arm (N = 334/611, 55 %,) than in the cALND arm (N = 174/565, 31 %,). When an intended target, level I received prescribed dose to 100 % (IQR 98–100 %) of the volume. However, even when not an intended target, full dose was delivered to > 80 % of level I (IQR 75–90 %). The intentional inclusion of level I in the target volume more than doubled the dose received by ≥ 50 % of the humeral head.Conclusion: Congruence between CRF data and RT plans was excellent. Level I received a high dose coverage even when not intentionally included in the target. Including level I in target significantly increased dose to the humeral head.
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| 24. |
- Alkner, Sara, et al.
(författare)
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Quality assessment of radiotherapy in the prospective randomized SENOMAC trial
- 2024
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Ingår i: Radiotherapy and Oncology. - : Elsevier. - 0167-8140 .- 1879-0887. ; 197
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Recommendations for regional radiotherapy (RT) of sentinel lymph node (SLN)-positive breast cancer are debated. We here report a RT quality assessment of the SENOMAC trial. Materials and Methods: The SENOMAC trial randomized clinically node-negative breast cancer patients with 1-2 SLN macrometastases to completion axillary lymph node dissection (cALND) or SLN biopsy only between 2015-2021. Adjuvant RT followed national guidelines. RT plans for patients included in Sweden and Denmark until June 2019 were collected (N = 1176) and compared to case report forms (CRF). Dose to level I (N = 270) and the humeral head (N = 321) was analyzed in detail.
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| 25. |
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| 26. |
- Andersson, Martin
(författare)
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An experimental investigation of spur gear efficiency and temperature : A comparison between ground and superfinished surfaces
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis focuses on reliability when testing gear efficiency and on how gear mesh efficiency can be increased without detrimental effects on the gears. Test equipment commonly used in gear research was analysed to identify important parameters for gear efficiency testing. The effect of the bearing model's load-dependent losses on gear mesh efficiency was also investigated. Two different surface finishes of gears, ground and superfinished, were investigated to determine how two different load levels during running-in affect gear mesh efficiency and changes in surface roughness. Efficiency and gear temperature were also measured for ground and superfinished gears with dip lubrication, as well as two different forms of spray lubrication (before and after gear mesh contact).Tests on a gear test rig, showed that different assemblies of the same test setup can yield different measurements of torque loss. The applied bearing model had a significant effect on the estimated gear mesh efficiency. The mesh efficiency of ground gears is affected by the running-in procedure, with a higher running-in load resulting in a higher mesh efficiency than a lower load. This effect was not seen for superfinished gears, which show the same gear mesh efficiency for both running-in loads. Gearbox efficiency increased with spray lubrication rather than dip lubrication. The gear mesh efficiency increased, and thus gear temperatures were reduced, when superfinished gears were used rather than ground gears. A lower gear temperature was measured when gears were spray lubricated at the mesh inlet rather than the mesh outlet.
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| 27. |
- Andersson, Martin
(författare)
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Churning losses and efficiency in gearboxes
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Efficient transmissions systems are key to producing competitive motor vehicles that have a smaller environmental impact. Gears are the main components in vehicle transmissions and although they are already highly efficient, there is still room for improvement. In this study, the focus falls on the lubricant used to create separating films between gears and todissipate heat. When driving, the gears churn this lubricant, giving rise to power losses that are related to the amount and properties of the lubricant. However, any attempt to reduce these losses must not compromise the required lubrication and heat dissipation. Paper A reports on the use of an FZG gear test rig to investigate power losses and heat generation for different gear immersion depths, surface roughness and coatings. The results show that lower gear roughness reduces gear mesh losses and heat generation. A polishing affect was obtained when a non-coated gear ran against a coated gear.The aim of the research reported in paper B was to increase the accuracy of efficiency testing. It investigated how and whether repeated disassembly and re-assembly of the same test equipment, as well as test performance and rig conditions, affect the measured torque loss in an FZG gear test rig. It was shown that the measured torque loss changes between one assembly and another. Repeatability between tests is crucial for accurate conclusions.The aim of the research reported in paper C was to study whether gear efficiency could be increased by a running-in procedure, which would reduce the need for a coolant. A back-to-back gear test rig was used to test two running-in loads. Higher gear mesh efficiency was seen when a higher running-in load was used.
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| 28. |
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| 29. |
- Andersson, Martin, et al.
(författare)
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Effect of Assembly Errors in Back-to-Back Gear Efficiency Testing
- 2014
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Ingår i: International Gear Conference 2014. - : Woodhead Publishing Limited. - 9781782421955 - 9781782421948 ; , s. 784-793
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Konferensbidrag (refereegranskat)abstract
- As gear efficiency is improved in small steps, it is important to be able to distinguish actual improvements from scatter that can occur while testing. An FZG back-to-back gear test rig was used to investigate how the assembly and re-assembly of the same test setup affects the measurements. A spread in loss torque between one assembly and another of the same test setup were observed. Rig conditions also affected the spread in input torque. With knowledge of how the spread in loss torque varies due to assembly, test results could be distinguished between changes due to assembly and actual differences between tests.
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| 30. |
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| 31. |
- Andersson, Martin, et al.
(författare)
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Efficiency and temperature of spray lubricated superfinished spur gears
- 2022
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Ingår i: Proceedings of the Institution of mechanical engineers. Part J, journal of engineering tribology. - : SAGE Publications. - 1350-6501 .- 2041-305X. ; 236:11, s. 2283-2291
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Tidskriftsartikel (refereegranskat)abstract
- Gearboxes are one of the most power dense systems used today, and in certain instances their limiting factor is the ability to evacuate heat from the gear contact. This work analyses the efficiency (i.e. heat generation) and tooth temperature in the three lubricating conditions dip, into mesh spray and out of mesh spray for superfinished gears which are then compared to ground gears. A back-to-back gear test rig is employed to test maximum contact pressures at the pitch of 0.59 to 0.96 GPa and pitch velocities from 0.5 to 20 m/s at a controlled lubricant temperature of 90 °C. The results show superfinished gears have higher mesh efficiency and lower gear tooth and bulk temperatures, hence lower heat flux compared to ground gears in all lubricating conditions.
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| 32. |
- Andersson, Martin, et al.
(författare)
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Efficiency and temperature of spur gears using spray lubrication compared to dip lubrication
- 2017
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Ingår i: Proceedings of the Institution of mechanical engineers. Part J, journal of engineering tribology. - : SAGE PUBLICATIONS LTD. - 1350-6501 .- 2041-305X. ; 231:11, s. 1390-1396
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Tidskriftsartikel (refereegranskat)abstract
- Increased machine efficiency is a requirement in today's world and geared transmissions are no exception. A back-to-back gear test rig was used to compare dip lubrication with spray lubrication regarding gearbox efficiency, mesh efficiency, gear temperature and surface roughness. Gears lubricated at the inlet of the mesh show a lower measured temperature when compared to spray lubrication at the outlet of the mesh. Spray lubrication, when compared to dip lubrication, yields the same efficiency for both rotating directions at the tested speeds of 0.5 to 20 m/s. Spray lubrication shows a significantly higher total gearbox efficiency at higher speeds, higher measured tooth temperature and no measurable change in surface roughness.
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| 33. |
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| 34. |
- Andersson, Martin, et al.
(författare)
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The effect of running-in on the efficiency of superfinished gears
- 2016
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Ingår i: Tribology International. - : Elsevier. - 0301-679X .- 1879-2464. ; 93, s. 71-77
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Tidskriftsartikel (refereegranskat)abstract
- Reduced gear contact losses are necessary to keep operating temperatures, as well as fuel consumption low. In this work, an FZG gear test rig was used to investigate the effect of running-in on superfinished gears with respect to efficiency. This was compared to ground gears where a higher contact pressure yielded higher efficiency. No difference was found between the two running-in procedures when analysing superfinished gears. The effect of running-in on gears decreased when the initial surface roughness was reduced, which initially had an Ra, Rz and Rpk value of 0.08, 0.75 and 0.08 μm respectively. Superfinished gears showed an overall higher efficiency; however, a distinctly lower efficiency was present below 2 m/s when compared to ground gears.
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| 35. |
- Andersson-Sköld, Yvonne, 1957-, et al.
(författare)
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Development of the SUNRA Tool to Improve Regional and Local Sustainability of the Transportation Sector
- 2022
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Ingår i: Sustainability. - : MDPI AG. - 2071-1050. ; 14:18, s. 11275-
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Tidskriftsartikel (refereegranskat)abstract
- To fulfil the global sustainable development goals (SDGs), achieving sustainable development is becoming urgent, not least in the transportation sector. In response to this, the sustainability framework Sustainability National Road Administrations (SUNRA) was developed to contribute to improving the sustainability performance of national road administrations across Europe. In the present study, the framework has been tested, applied and further developed to be applicable for target setting and follow-up at the project level at both the Swedish Transport Administration (STA) and at municipal levels. The aim was a framework relevant for investment, re-investments, maintenance and operation projects and also to make it more user applicable. The study also investigated how the framework can contribute to sustainability, identified drivers and barriers for applying the framework and examined whether the framework can be applied and adapted to projects of different complexities. The adaptations and developments were done in collaboration between researchers and practitioners. The results show that the framework could easily be used and adapted for investment, re-investment, maintenance and operation projects in the planning stage, as well as for small municipal establishments, construction or reconstruction of residential areas and frequent maintenance. The framework contributes to increased awareness on sustainability, and it provides a common structure and transparency on how infrastructure project goals/targets are set and fulfilled. The framework can also be applied to follow the fulfilment of the goals/targets and thereby adapt the project to better fulfil the goals. Identified barriers include the lack of obligations and lack of experience in using sustainability frameworks.
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| 36. |
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| 37. |
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| 38. |
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| 39. |
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| 40. |
- Bengtsson, Kenneth, et al.
(författare)
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Så kan Sverige bli ledande nation i resurseffektivitet
- 2016
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Ingår i: Dagens Nyheter. - 1101-2447. ; :2016-04-30
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Ny rapport. Det svenska näringslivet kan bli mer hållbart, resurssmart och därmed internationellt konkurrenskraftigt. Men för det behövs en tydlig politisk avsiktsförklaring och riktlinjer. Vi har listat sex områden där policyutveckling brådskar, skriver företrädare för näringsliv, forskning och myndigheter i en gemensam uppmaning.
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| 41. |
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| 42. |
- Berger, David, et al.
(författare)
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Ecological Constraints on Female Fitness in a Phytophagous Insect
- 2012
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Ingår i: American Naturalist. - : University of Chicago Press. - 0003-0147 .- 1537-5323. ; 180:4, s. 464-480
-
Tidskriftsartikel (refereegranskat)abstract
- Although understanding female reproduction is crucial for population demography, determining how and to what relative extent it is constrained by different ecological factors is complicated by difficulties in studying the links between individual behavior, life history, and fitness in nature. We present data on females in a natural population of the butterfly Leptidea sinapis. These data were combined with climate records and laboratory estimates of life-history parameters to predict the relative impact of different ecological constraints on female fitness in the wild. Using simulation models, we partitioned effects of male courtship, host plant availability, and temperature on female fitness. Results of these models indicate that temperature is the most constraining factor on female fitness, followed by host plant availability; the short-term negative effects of male courtship that were detected in the field study were less important in models predicting female reproductive success over the entire life span. In the simulations, females with more reproductive reserves were more limited by the ecological variables. Reproductive physiology and egg-laying behavior were therefore predicted to be co-optimized but reach different optima for females of different body sizes; this prediction is supported by the empirical data. This study thus highlights the need for studying behavioral and life-history variation in orchestration to achieve a more complete picture of both demographic and evolutionary processes in naturally variable and unpredictable environments.
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| 43. |
- Berger, David, et al.
(författare)
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Intraspecific variation in body size and the rate of reproduction in female insects- adaptive allometry or biophysical constraint?
- 2012
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Ingår i: Journal of Animal Ecology. - : Wiley. - 0021-8790 .- 1365-2656. ; 81:6, s. 1244-1258
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Tidskriftsartikel (refereegranskat)abstract
- 1. A high rate of reproduction may be costly if ecological factors limit immediate reproductive output as a fast metabolism compromises own future survival. Individuals with more reserves need more time and opportunity to realize their reproductive potential. Theory therefore predicts that the reproductive rate, defined as the investment in early reproduction in proportion to total potential, should decrease with body size within species. 2. However, metabolic constraints on body size- and temperature-dependent biological rates may impede biophysical adaptation. Furthermore, the sequential manner resources that are allocated to somatic vs. reproductive tissue during ontogeny may, when juveniles develop in unpredictable environments, further contribute to non-adaptive variation in adult reproductive rates. 3. With a model on female egg laying in insects, we demonstrate how variation in body reserves is predicted to affect reproductive rate under different ecological scenarios. Small females always have higher reproductive rates but shorter lifespans. However, incorporation of female host selectivity leads to more similar reproductive rates among female size classes, and oviposition behaviour is predicted to co-evolve with reproductive rate, resulting in small females being more selective in their choice and gaining relatively more from it. 4. We fed simulations with data on the butterfly Pararge aegeria to compare model predictions with reproductive rates of wild butterflies. However, simulated reproductive allometry was a poor predictor of that observed. Instead, reproductive rates were better explained as a product of metabolic constraints on rates of egg maturation, and an empirically derived positive allometry between reproductive potential and size. However, fitness is insensitive to moderate deviations in reproductive rate when oviposition behaviour is allowed to co-evolve in the simulations, suggesting that behavioural compensation may mitigate putative metabolic and developmental constraints. 5. More work is needed to understand how physiology and development together with compensatory behaviours interact in shaping reproductive allometry. Empirical studies should evaluate adaptive hypotheses against proper null hypotheses, including prediction from metabolic theory, preferentially by studying reproductive physiology in combination with behaviour. Conversely, inferences of constraint explanations on reproductive rates must take into consideration that adaptive scenarios may predict similar allometric exponents.
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| 44. |
- Bergfrid, Martin, et al.
(författare)
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Having plans for the future in very old people
- 2024
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Ingår i: The International Journal of Aging & Human Development. - : Sage Publications. - 0091-4150 .- 1541-3535.
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to investigate the prevalence of having plans for the future among very old people and the factors associated with having such plans. A longitudinal population-based study with home visits for 85-, 90-, and ≥95-year-old participants in Sweden and Finland was used. Multivariate logistic regression and Cox proportional-hazards regression models with a maximum 5-year follow-up period were used. The prevalence of having plans for the future was 18.6% (174/936). More men than women and more people living in Sweden than in Finland had plans for the future. In multivariate models, having plans for the future was associated with speaking Swedish, being dentate, and living in the community in the total sample; speaking Swedish and being dentate among women; and speaking Swedish, having a lower Geriatric Depression Scale score, and urban residence among men. Having plans for the future was associated univariately, but not multivariately, with increased survival.
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| 45. |
- Bergseth, Ellen, 1979-, et al.
(författare)
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A note on the pitting life of IQ steel versus 16MnCr5 steel in a back to back gear test rig
- 2018
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Konferensbidrag (refereegranskat)abstract
- IQ-steel is isotropic (i.e. equally strong in all directions), cleaner, and with less inclusions than 16MnCr5 regular gear steel (RS). IQ-steel is used in diesel inlets and for bearings but to date has not been used for gears. Previous studies, has shown good potential to increase the bending fatigue life of gears. The method in this study is a mechanical test procedure to determine the pitting load capacity of gear transmission lubricants, but with the focus on comparing the pitting load capacity of the two steel types IQ-steel with RS. Times to failures, photographs of the fatigue damage are presented in the study. Gear teeth from each steel type were analysed using SEM. The results, which are based on six tests in total (three IQ-steel and three RS-steel gear pairs), indicate that the IQ-steel may have at least similar surface capacity as the regular steel.Keywords: Pitting life, Gear, IQ-steel
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| 46. |
- Bergseth, Ellen, 1979-, et al.
(författare)
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A Wear Detection Parameter for the Wheel–Rail Contact Based on Emitted Noise
- 2019
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Ingår i: Tribology Transactions. - : Informa UK Limited. - 1040-2004 .- 1547-397X. ; 62:3, s. 496-503
-
Tidskriftsartikel (refereegranskat)abstract
- This article describes how a wheel–rail wear detection parameter based on noise was developed by running a rapid transit train instrumented with microphones in a depot with a small curve radius. This full-scale test made use of previous knowledge gained from lab-scale tests. The lab- and full-scale tests showed that noise could be used as an indicator of wear transition, when normal wear turns into severe or catastrophic wear. This transition was accompanied by a significant increase in sound pressure and a broader sound pressure amplitude spectrum; that is, a narrow initial amplitude distribution in the normal wear regime and a broader distribution in the severe wear regime. The measured noise from the inner/low and outer/high rails was analyzed in conjunction with the wear from the outer wheel and comparisons were made between cleaned (exposed to severe wear) and lubricated (no wear) rail. Based on those analyses, a wear detection parameter criterion was developed for this specific train. This wear parameter has been implemented in a real-time condition monitoring system so that warnings of the risk for severe wear could be sent to the maintenance department. Validation of the wear parameter and challenges linked to open system conditions are discussed in this article.
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| 47. |
- Bergseth, Ellen, 1979-, et al.
(författare)
-
EXPERIENCES OF STUDYING GEAR TRIBOLOGY IN A FZG TEST SET-UP
- 2018
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Konferensbidrag (refereegranskat)abstract
- The main objective of this study is to review the last decade of experimental work in the field of gear pitting life andefficiency of an FZG gear test rig. Located at KTH Machine Design, the FZG rig has led to critical findings with an impacton gear transmissions, such as high efficiency and long fatigue life. The different FZG test set-ups, the sampling methodsand the results (and their limitations) are discussed, and measures are proposed to reduce the limitations. The findingsof this study are used as input to an impact case on how research at a university can provide the major transportindustry in Sweden with the knowledge and the methods to evaluate gear performance.
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| 48. |
- Bergseth, Ellen, 1979-, et al.
(författare)
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Investigation of pitting resistance in ultra clean IQ-Steel vs commonly used conventional steel; 158Q vs 16MnCr5 : Back-to-back pitting tests
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- KTH Machine Design has conducted pitting tests on gears made out of two different types of steel in a standard back-to-back pitting test rig (FZG). The tested gears were produced from Ovako’s IQ-Steel in grade 158Q and compared to the behaviour of a reference steel, commonly used conventional steel in grade 16MnCr5 (reference steel, RS). The test method is a mechanical test procedure generally used to determine the pitting load capacity of gear transmission lubricants, but in this study the purpose was to compare the pitting load capacity of the two steel types. The report is based on the test procedure described in FVA – Information sheet Research Project No. 371 (Practice Relevant Pitting Test) with minor changes. Time to failure and photographs of the fatigue damages are presented in this report. One gear tooth from each steel type was analysed using SEM. The results, which are based on six tests in total (three gear pairs IQ-Steel and three RS-steel), indicate that the IQ-Steel has better surface durability than the reference steel. To better understand the mechanisms involved, further tests are suggested.
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| 49. |
- Bergström, Sofia, et al.
(författare)
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Multi-cohort profiling reveals elevated CSF levels of brain-enriched proteins in Alzheimer's disease
- 2021
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 8:7, s. 1456-1470
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Decreased amyloid beta (A beta) 42 together with increased tau and phospho-tau in cerebrospinal fluid (CSF) is indicative of Alzheimer's disease (AD). However, the molecular pathophysiology underlying the slowly progressive cognitive decline observed in AD is not fully understood and it is not known what other CSF biomarkers may be altered in early disease stages. Methods: We utilized an antibody-based suspension bead array to analyze levels of 216 proteins in CSF from AD patients, patients with mild cognitive impairment (MCI), and controls from two independent cohorts collected within the AETIONOMY consortium. Two additional cohorts from Sweden were used for biological verification. Results: Six proteins, amphiphysin (AMPH), aquaporin 4 (AQP4), cAMP-regulated phosphoprotein 21 (ARPP21), growth-associated protein 43 (GAP43), neurofilament medium polypeptide (NEFM), and synuclein beta (SNCB) were found at increased levels in CSF from AD patients compared with controls. Next, we used CSF levels of A beta 42 and tau for the stratification of the MCI patients and observed increased levels of AMPH, AQP4, ARPP21, GAP43, and SNCB in the MCI subgroups with abnormal tau levels compared with controls. Further characterization revealed strong to moderate correlations between these five proteins and tau concentrations. Interpretation: In conclusion, we report six extensively replicated candidate biomarkers with the potential to reflect disease development. Continued evaluation of these proteins will determine to what extent they can aid in the discrimination of MCI patients with and without an underlying AD etiology, and if they have the potential to contribute to a better understanding of the AD continuum.
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| 50. |
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