| 1. |
- Kotta, Jonne, et al.
(författare)
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Assessing the potential for sea-based macroalgae cultivation and its application for nutrient removal in the Baltic Sea
- 2022
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 839
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Tidskriftsartikel (refereegranskat)abstract
- Marine eutrophication is a pervasive and growing threat to global sustainability. Macroalgal cultivation is a promising circular economy solution to achieve nutrient reduction and food security. However, the location of production hotspots is not well known. In this paper the production potential of macroalgae of high commercial value was predicted across the Baltic Sea region. In addition, the nutrient limitation within and adjacent to macroalgal farms was investigated to suggest optimal site-specific configuration of farms. The production potential of Saccharina latissima was largely driven by salinity and the highest production yields are expected in the westernmost Baltic Sea areas where salinity is >23. The direct and interactive effects of light availability, temperature, salinity and nutrient concentrations regulated the predicted changes in the production of Ulva intestinalis and Fucus vesiculosus. The western and southern Baltic Sea exhibited the highest farming potential for these species, with promising areas also in the eastern Baltic Sea. Macroalgal farming did not induce significant nutrient limitation. The expected spatial propagation of nutrient limitation caused by macroalgal farming was less than 100–250 m. Higher propagation distances were found in areas of low nutrient and low water exchange (e.g. offshore areas in the Baltic Proper) and smaller distances in areas of high nutrient and high water exchange (e.g. western Baltic Sea and Gulf of Riga). The generated maps provide the most sought-after input to support blue growth initiatives that foster the sustainable development of macroalgal cultivation and reduction of in situ nutrient loads in the Baltic Sea.
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| 2. |
- Aas, W., et al.
(författare)
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Lessons learnt from the first EMEP intensive measurement periods
- 2012
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:17, s. 8073-8094
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Tidskriftsartikel (refereegranskat)abstract
- The first EMEP intensive measurement periods were held in June 2006 and January 2007. The measurements aimed to characterize the aerosol chemical compositions, including the gas/aerosol partitioning of inorganic compounds. The measurement program during these periods included daily or hourly measurements of the secondary inorganic components, with additional measurements of elemental- and organic carbon (EC and OC) and mineral dust in PM1, PM2.5 and PM10. These measurements have provided extended knowledge regarding the composition of particulate matter and the temporal and spatial variability of PM, as well as an extended database for the assessment of chemical transport models. This paper summarise the first experiences of making use of measurements from the first EMEP intensive measurement periods along with EMEP model results from the updated model version to characterise aerosol composition. We investigated how the PM chemical composition varies between the summer and the winter month and geographically. The observation and model data are in general agreement regarding the main features of PM10 and PM2.5 composition and the relative contribution of different components, though the EMEP model tends to give slightly lower estimates of PM10 and PM2.5 compared to measurements. The intensive measurement data has identified areas where improvements are needed. Hourly concurrent measurements of gaseous and particulate components for the first time facilitated testing of modelled diurnal variability of the gas/aerosol partitioning of nitrogen species. In general, the modelled diurnal cycles of nitrate and ammonium aerosols are in fair agreement with the measurements, but the diurnal variability of ammonia is not well captured. The largest differences between model and observations of aerosol mass are seen in Italy during winter, which to a large extent may be explained by an underestimation of residential wood burning sources. It should be noted that both primary and secondary OC has been included in the calculations for the first time, showing promising results. Mineral dust is important, especially in southern Europe, and the model seems to capture the dust episodes well. The lack of measurements of mineral dust hampers the possibility for model evaluation for this highly uncertain PM component. There are also lessons learnt regarding improved measurements for future intensive periods. There is a need for increased comparability between the measurements at different sites. For the nitrogen compounds it is clear that more measurements using artefact free methods based on continuous measurement methods and/or denuders are needed. For EC/OC, a reference methodology (both in field and laboratory) was lacking during these periods giving problems with comparability, though measurement protocols have recently been established and these should be followed by the Parties to the EMEP Protocol. For measurements with no defined protocols, it might be a good solution to use centralised laboratories to ensure comparability across the network. To cope with the introduction of these new measurements, new reporting guidelines have been developed to ensure that all proper information about the methodologies and data quality is given.
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| 3. |
- Andersson, Camilla, 1979-, et al.
(författare)
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Interannual variation and trends in air pollution over Europe due to climate variability during 1958–2001 simulated with a regional CTM coupled to the ERA40 reanalysis
- 2007
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Ingår i: Tellus. Series B, Chemical and physical meteorology. - Stockholm : Tellus. - 0280-6509 .- 1600-0889. ; 59, s. 77-98
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Tidskriftsartikel (refereegranskat)abstract
- A three-dimensional Chemistry Transport Model was used to study the meteorologically induced interannual variability and trends in deposition of sulphur and nitrogen as well as concentrations of surface ozone (O3), nitrogen dioxide (NO2) and particulate matter (PM) and its constituents over Europe during 1958–2001. The model was coupled to the meteorological reanalysis ERA40, produced at the European Centre for Medium-range Weather Forecasts. Emissions and boundary conditions of chemical compounds and PM were kept constant at present levels. The average European interannual variation, due to meteorological variability, ranges from 3% for O3, 5%for NO2, 9% for PM, 6–9% for dry deposition, to about 20% for wet deposition of sulphur and nitrogen. For the period 1979–2001 the trend in ozone, due to climate variability is increasing in central and southwestern Europe and decreasing in northeastern Europe, the trend in NO2 is approximately opposite. The trend in PM is positive in eastern Europe. There are negative trends in wet deposition in southwestern and central Europe and positive trends in dry deposition overall. A bias in ERA40 precipitation could be partly responsible for the trends. The variation and trends need to be considered when interpreting measurements and designing measurement campaigns.
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| 4. |
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| 5. |
- Andersson, C., et al.
(författare)
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MATCH-SALSA - Multi-scale Atmospheric Transport and CHemistry model coupled to the SALSA aerosol microphysics model - Part 1: Model description and evaluation
- 2015
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 8:2, s. 171-189
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Tidskriftsartikel (refereegranskat)abstract
- © Author(s) 2015. We have implemented the sectional aerosol dynamics model SALSA (Sectional Aerosol module for Large Scale Applications) in the European-scale chemistry-transport model MATCH (Multi-scale Atmospheric Transport and Chemistry). The new model is called MATCH-SALSA. It includes aerosol microphysics, with several formulations for nucleation, wet scavenging and condensation. The model reproduces observed higher particle number concentration (PNC) in central Europe and lower concentrations in remote regions. The modeled PNC size distribution peak occurs at the same or smaller particle size as the observed peak at four measurement sites spread across Europe. Total PNC is underestimated at northern and central European sites and accumulation-mode PNC is underestimated at all investigated sites. The low nucleation rate coefficient used in this study is an important reason for the underestimation. On the other hand, the model performs well for particle mass (including secondary inorganic aerosol components), while elemental and organic carbon concentrations are underestimated at many of the sites. Further development is needed, primarily for treatment of secondary organic aerosol, in terms of biogenic emissions and chemical transformation. Updating the biogenic secondary organic aerosol (SOA) scheme will likely have a large impact on modeled PM2.5 and also affect the model performance for PNC through impacts on nucleation and condensation.
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| 6. |
- Andersson, Camilla, 1979-, et al.
(författare)
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Population exposure and mortality due to regional background PM in Europe – longterm simulations of source-region and shipping contributions
- 2009
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Ingår i: Atmospheric Environment. - : Elsevier BV. - 1352-2310 .- 1873-2844. ; 43:22-23, s. 3614-3620
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the contribution to population exposure (PE) of regional background fine primary (PPM2.5) and secondary inorganic (SIA) particulate matter and its impact on mortality in Europe during 1997–2003 calculated with a chemistry transport model. Contributions to concentrations and PE due to emissions from shipping, Western (WEU), Eastern (EEU), and Northern Europe are compared. WEU contributes about 40% to both PPM2.5 and SIA concentrations, whereas the EEU contribution to PPM2.5 is much higher (43% of total PPM2.5) than to SIA (29% of total SIA). The population weighted average concentration (PWC) of PPM2.5 is a factor of 2.3 higher than average (non-weighted) concentrations, whereas for SIA the PWC is only a factor 1.6 higher. This is due to PPM2.5 concentrations having larger gradients and being relatively high over densely populated areas, whereas SIA is formed outside populated areas. WEU emissions contribute relatively more than EEU to PWC and mortality due to both PPM2.5 and SIA in Europe. The number of premature deaths in Europe is estimated to 301 000 per year due to PPM2.5 exposure and 245 000 due to SIA, despite 3.3 times higher average SIA concentrations. This is due to population weighting and assumed (and uncertain) higher relative risk of mortality for PPM2.5 components (2.8 times higher RR for PPM2.5). This study indicates that it might be more efficient, for the health of the European population, to decrease primary PM emissions (especially in WEU) than to decrease precursors of SIA, but more knowledge on the toxicity of different PM constituents is needed before firm conclusions can be drawn.
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| 7. |
- Axelsson, Magnus A. B., et al.
(författare)
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Retrospective identification of new psychoactive substances in patient samples submitted for clinical drug analysis
- 2022
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Ingår i: Basic & Clinical Pharmacology & Toxicology. - : Wiley. - 1742-7835 .- 1742-7843. ; 131:5, s. 420-434
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Tidskriftsartikel (refereegranskat)abstract
- New psychoactive substances (NPS) are life threatening through unpredictable toxicity and limited analytical options for clinicians. We present the retrospective identification of NPS in raw data from a liquid chromatography-high resolution mass spectrometry (LC-HRMS)-based multidrug panel analysis on 14 367 clinical oral fluid samples requested during 2019 mainly by psychiatric and addiction care clinics. Retrospectively analysed NPS included 48 notified originally in 2019 by the European Union Early Warning System (EU EWS) and 28 frequently reported in Sweden. Of 88 included NPS, 34 (mitragynine, flualprazolam, 3F/4F-α-P(i)HP, etizolam, 4F-MDMB-BINACA, cyproheptadine, 5F-MDMB-PICA, isotonitazene, isohexedrone, MDPEP, N-ethylpentedrone, tianeptine, flubromazolam, 4′-methylhexedrone, α-P(i)HP, eutylone, mephedrone, N-ethylhexedrone, 5F-MDMB-PINACA, ADB-BUTINACA, 3-methoxy PCP, 4F-furanylfentanyl, 4F-isobuturylfentanyl, acrylfentanyl, furanylfentanyl, clonazolam, norfludiazepam, 3F-phenmetrazine, 3-MMC, 4-methylpentedrone, BMDP, ethylphenidate, methylone and α-PVP) were identified as 219 findings in 84 patients. Eight NPS notified in 2019 were identified, five before EWS release. NPS occurred in 1.20% of all samples and 1.53% of samples containing traditional drugs, and in 1.87% of all patients and 2.88% of patients using traditional drugs. NPS use was more common in men and polydrug users. Legal (not scheduled) NPS were more used than comparable illegal ones. Retrospective identification could be useful when prioritizing NPS for clinical routine analysis and when studying NPS epidemiology. © 2022 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society). Published by John Wiley & Sons Ltd.
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| 8. |
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| 9. |
- Bergström, Axel, et al.
(författare)
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Differences in production of disfluencies in children with typical language development and children with mixed receptive-expressive language disorder
- 2017
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Ingår i: Proceedings of DiSS 2017, the 8th Workshop on Disfluency in Spontaneous Speech. - Stockholm : KTH Royal Institute of Technology. ; , s. 9-12
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Konferensbidrag (refereegranskat)abstract
- There are several studies about non-fluency inpeople who stutter, but comparatively few regardingchildren with language impairment. The currentresearch body regarding disfluencies in childrenwith language impairment has been using differentstudy-designs and definitions, making some resultsrather contradictory.The purpose of the present study is to expand theknowledge about disfluencies in children withlanguage impairment and compare the occurrenceof disfluencies between children with languageimpairment and children with typical languagedevelopment in the same age group.A total of ten children with language impairmentand six children with typical language developmentparticipated in this study. The subjects wererecorded when talking freely about a thematicpicture or toys and then analysed by calculatingdisfluencies per 50 words including frequency ofdifferent kinds of disfluencies according to Johnsonand Associates’ (1959) classic taxonomy.Our results show that children with languageimpairment do produce statistically significant moredisfluency in general, notably sound and syllablerepetition, broken words and prolongations.
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| 10. |
- Bergström, Anders, et al.
(författare)
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Origins and genetic legacy of prehistoric dogs
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6516, s. 557-563
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Tidskriftsartikel (refereegranskat)abstract
- Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry.
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| 11. |
- Bergström, Christel A. S., et al.
(författare)
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Early pharmaceutical profiling to predict oral drug absorption : Current status and unmet needs
- 2014
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 57, s. 173-199
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Tidskriftsartikel (refereegranskat)abstract
- Preformulation measurements are used to estimate the fraction absorbed in vivo for orally administered compounds and thereby allow an early evaluation of the need for enabling formulations. As part of the Oral Biopharmaceutical Tools (OrBiTo) project, this review provides a summary of the pharmaceutical profiling methods available, with focus on in silica and in vitro models typically used to forecast active pharmaceutical ingredient's (APIs) in vivo performance after oral administration. An overview of the composition of human, animal and simulated gastrointestinal (GI) fluids is provided and state-of-the art methodologies to study API properties impacting on oral absorption are reviewed. Assays performed during early development, i.e. physicochemical characterization, dissolution profiles under physiological conditions, permeability assays and the impact of excipients on these properties are discussed in detail and future demands on pharmaceutical profiling are identified. It is expected that innovative computational and experimental methods that better describe molecular processes involved in vivo during dissolution and absorption of APIs will be developed in the OrBiTo. These methods will provide early insights into successful pathways (medicinal chemistry or formulation strategy) and are anticipated to increase the number of new APIs with good oral absorption being discovered. (C) 2013 Elsevier B.V. All rights reserved.
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| 12. |
- Bergström, Christel A S, et al.
(författare)
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Hepatitis C virus NS3 protease inhibitors : large, flexible molecules of peptide origin show satisfactory permeability across Caco-2 cells
- 2009
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 38:5, s. 556-563
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the intestinal absorption of tripeptide-based compounds intended for treatment of hepatitis C virus (HCV) infection. The intestinal permeability of 11 HCV NS3 protease inhibitors (Mw 687-841, ClogD(pH 7.4) 1.2-7.3 and 10-13 hydrogen bond donors/acceptors) was measured using Caco-2 cells. Each compound was investigated in the apical to basolateral (a-b) and basolateral to apical (b-a) direction at pH 7.4. For compounds displaying efflux the experiment was repeated in the presence of 1 microM GF120918 to investigate possible involvement of P-glycoprotein (Pgp; ABCB1). All compounds displayed intermediate to high permeability. Seven of them showed extensive efflux, with 31-114-fold higher permeability in the b-a direction than the a-b direction. Addition of the Pgp inhibitor GF120918 reduced the b-a transport rate for the effluxed compounds. However, for inhibitors with a C-terminal carboxylic acid and the acidic bioisosteres thereof the efflux was still significant. Hence, the negative charge resulted in efflux by other ABC-transporters than Pgp. From this study it can be concluded that small changes in the overall structure can lead to a large variation in permeability and efflux as shown by the inhibitors herein, properties that also may influence the resulting inhibition potency of the compounds when performing cell-based pharmacological assays.
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| 13. |
- Bergström, Gunnar, et al.
(författare)
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Stem cell derived in vivo-like human cardiac bodies in a microfluidic device for toxicity testing by beating frequency imaging
- 2015
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Ingår i: Lab on a Chip. - : Royal Society of Chemistry. - 1473-0197 .- 1473-0189. ; 15:15, s. 3242-3249
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Tidskriftsartikel (refereegranskat)abstract
- Beating in vivo-like human cardiac bodies (CBs) were used in a microfluidic device for testing cardiotoxicity. The CBs, cardiomyocyte cell clusters derived from induced pluripotent stem cells, exhibited typical structural and functional properties of the native human myocardium. The CBs were captured in niches along a perfusion channel in the device. Video imaging was utilized for automatic monitoring of the beating frequency of each individual CB. The device allowed assessment of cardiotoxic effects on the 3D clustered cardiomyocytes from the drug substances doxorubicin, verapamil and quinidine. Beating frequency data recorded over a period of 6 hours are presented and compared to literature data. The results indicate that this microfluidic setup with imaging of CB characteristics provides a new opportunity for label-free, non-invasive investigation of toxic effects in a 3D microenvironment.
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| 14. |
- Bergström, Jan Robert
(författare)
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Carbonaceous Aerosol in Europe - out of the woods and into the blue?
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Particulate matter (PM) in the atmosphere influences weather and climate and may have important health impacts. Regional scale chemical transport modelling aims to describe the composition of particulate matter, to track different sources, estimate their relative importance, and to give realistic predictions of responses to changes in emissions and atmospheric conditions. The focus of this thesis is the modelling of an important constituent of PM — carbon containing PM. The EMEP MSC-W chemical transport model is used for European policy making regarding air pollution, to provide scientific support to the convention on long-range transboundary air pollution (CLRTAP). The organic aerosol (OA) treatment in the EMEP model has been extended to include more realistic primary OA emissions, and new schemes for the formation of secondary OA, based on the volatility basis set method. Long-term model simulations of OA and elemental carbon (EC) over Europe have been performed for the period 2002–2010. The model results were compared to observations, including source-apportionment data. Total organic carbon concentrations matched measured concentrations for summer periods, but problems were found during winter, with poor agreement between modelled and measured organic carbon, and tracers of wood-burning. To tackle these problems a new inventory for emissions of OA and EC from residential wood combustion (RWC) was developed. Total European OA emissions from RWC are almost 3 times larger in the new inventory than in the old one. According to the new inventory, about 60% of the primary OA emissions in Europe are due to RWC. EC emissions are to a larger extent due to fossil fuel combustion; RWC emissions contribute about 1/5 of the total anthropogenic fine particle EC-emissions in Europe. The model results indicate that many sources contribute to OA in Europe. During summer, fossil fuel combustion, biomass burning and biogenic secondary OA all contribute considerably. RWC is the dominant OA source during winter, contributing more than 50% to the model OA. According to the model results, non-fossil sources contribute more to regional scale OA than fossil fuel, except in the Po Valley during summer. EC comes mainly from fossil fuel during the warm seasons, but EC from RWC is important during winter. Modelling is useful to investigate potential impacts of newly discovered sources of organic aerosol. Biotic stress-induced emissions (SIE) were investigated in this thesis. The fractions of stressed trees in European forests were estimated, based on observed tree damage. Emission estimates for sesquiterpenes, methyl salicylate and unsaturated C17-compounds, and the SOA yield from the oxidation of these SIE, were based on plant chamber experiments. The model results suggest that SIE may contribute substantially to SOA in Europe. During some periods, SIE may contribute more to OA than the non-stressed biogenic emissions of volatile organic compounds. Thus, further research on SIE is warranted.
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| 15. |
- Bergström, Robert, et al.
(författare)
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Biotic stress: a significant contributor to organic aerosol in Europe?
- 2014
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Ingår i: Atmospheric Chemistry And Physics. - : Copernicus Publications. - 1680-7316 .- 1680-7324. ; 14:24, s. 13643-13660
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Tidskriftsartikel (refereegranskat)abstract
- We have investigated the potential impact on organic aerosol formation from biotic stress-induced emissions (SIE) of organic molecules from forests in Europe (north of lat. 45° N). Emission estimates for sesquiterpenes (SQT), methyl salicylate (MeSA) and unsaturated C17 compounds, due to different stressors, are based on experiments in the Jülich Plant Atmosphere Chamber (JPAC), combined with estimates of the fraction of stressed trees in Europe based on reported observed tree damage. SIE were introduced in the EMEP MSC-W chemical transport model and secondary organic aerosol (SOA) yields from the SIE were taken from the JPAC experiments. Based on estimates of current levels of infestation and the JPAC aerosol yields, the model results suggest that the contribution to SOA in large parts of Europe may be substantial. It is possible that SIE contributes as much, or more, to organic aerosol than the constitutive biogenic VOC emissions, at least during some periods. Based on the assumptions in this study, SIE-SOA are estimated to constitute between 50 and 70 % of the total biogenic SOA (BSOA) in a current-situation scenario where the biotic stress in northern and central European forests causes large SIE of MeSA and SQT. An alternative current-situation scenario with lower SIE, consisting solely of SQT, leads to lower SIE-SOA, between 20 and 40 % of the total BSOA. Hypothetical future scenarios with increased SIE, due to higher degrees of biotic stress, show that SOA formation due to SIE can become even larger. Unsaturated C17 BVOC (biogenic volatile organic compounds) emitted by spruce infested by the forest-honey generating bark louse, Cinara pilicornis, have a high SOA-forming potential. A model scenario investigating the effect of a regional, episodic infestation of Cinara pilicornis in Baden-Württemberg, corresponding to a year with high production of forest honey, shows that these types of events could lead to very large organic aerosol formation in the infested region. We have used the best available laboratory data on biotic SIE applicable to northern and central European forests. Using these data and associated assumptions, we have shown that SIE are potentially important for SOA formation but the magnitude of the impact is uncertain and needs to be constrained by further laboratory, field and modelling studies. As an example, the MeSA, which is released as a consequence of various types of biotic stress, is found to have a potentially large impact on SIE-SOA in Europe, but different assumptions regarding the nighttime chemistry of MeSA can change its SOA potential substantially. Thus, further investigations of the atmospheric chemistry of MeSA and observational field studies are needed to clarify the role of this compound in the atmosphere.
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| 16. |
- Bergström, Robert, et al.
(författare)
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Modelling of organic aerosols over Europe (2002-2007) using a volatility basis set (VBS) framework: application of different assumptions regarding the formation of secondary organic aerosol
- 2012
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Ingår i: Atmospheric Chemistry and Physics. - : Copernicus GmbH. - 1680-7316 .- 1680-7324. ; 12:18, s. 8499-8527
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Tidskriftsartikel (refereegranskat)abstract
- A new organic aerosol module has been implemented into the EMEP chemical transport model. Four different volatility basis set (VBS) schemes have been tested in long-term simulations for Europe, covering the six years 2002-2007. Different assumptions regarding partitioning of primary organic aerosol and aging of primary semi-volatile and intermediate volatility organic carbon (S/IVOC) species and secondary organic aerosol (SOA) have been explored. Model results are compared to filter measurements, aerosol mass spectrometry (AMS) data and source apportionment studies, as well as to other model studies. The present study indicates that many different sources contribute significantly to organic aerosol in Europe. Biogenic and anthropogenic SOA, residential wood combustion and vegetation fire emissions may all contribute more than 10% each over substantial parts of Europe. This study shows smaller contributions from biogenic SOA to organic aerosol in Europe than earlier work, but relatively greater anthropogenic SOA. Simple VBS based organic aerosol models can give reasonably good results for summer conditions but more observational studies are needed to constrain the VBS parameterisations and to help improve emission inventories. The volatility distribution of primary emissions is one important issue for further work. Emissions of volatile organic compounds from biogenic sources are also highly uncertain and need further validation. We can not reproduce winter levels of organic aerosol in Europe, and there are many indications that the present emission inventories substantially underestimate emissions from residential wood combustion in large parts of Europe.
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| 17. |
- Bergström, Sofia, et al.
(författare)
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A panel of CSF proteins separates genetic frontotemporal dementia from presymptomatic mutation carriers : a GENFI study
- 2021
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Ingår i: Molecular Neurodegeneration. - : Springer Nature. - 1750-1326. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background A detailed understanding of the pathological processes involved in genetic frontotemporal dementia is critical in order to provide the patients with an optimal future treatment. Protein levels in CSF have the potential to reflect different pathophysiological processes in the brain. We aimed to identify and evaluate panels of CSF proteins with potential to separate symptomatic individuals from individuals without clinical symptoms (unaffected), as well as presymptomatic individuals from mutation non-carriers. Methods A multiplexed antibody-based suspension bead array was used to analyse levels of 111 proteins in CSF samples from 221 individuals from families with genetic frontotemporal dementia. The data was explored using LASSO and Random forest. Results When comparing affected individuals with unaffected individuals, 14 proteins were identified as potentially important for the separation. Among these, four were identified as most important, namely neurofilament medium polypeptide (NEFM), neuronal pentraxin 2 (NPTX2), neurosecretory protein VGF (VGF) and aquaporin 4 (AQP4). The combined profile of these four proteins successfully separated the two groups, with higher levels of NEFM and AQP4 and lower levels of NPTX2 in affected compared to unaffected individuals. VGF contributed to the models, but the levels were not significantly lower in affected individuals. Next, when comparing presymptomatic GRN and C9orf72 mutation carriers in proximity to symptom onset with mutation non-carriers, six proteins were identified with a potential to contribute to a separation, including progranulin (GRN). Conclusion In conclusion, we have identified several proteins with the combined potential to separate affected individuals from unaffected individuals, as well as proteins with potential to contribute to the separation between presymptomatic individuals and mutation non-carriers. Further studies are needed to continue the investigation of these proteins and their potential association to the pathophysiological mechanisms in genetic FTD.
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| 18. |
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| 19. |
- Bergström, Stig M., et al.
(författare)
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The age of the Middle Ordovician Winneshiek Shale : reply to a critical review by Lindskog & Young (2019) of a paper by Bergström et al. (2018a)
- 2020
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Ingår i: Lethaia. - : Scandinavian University Press / Universitetsforlaget AS. - 0024-1164 .- 1502-3931. ; 53:1, s. 1-4
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Tidskriftsartikel (refereegranskat)abstract
- A recent review by Lindskog & Young (2019) of a paper published in Lethaia by Bergström et al. (2018a) contains many errors, misleading statements and unsupported opinions. Their review claims that we did not consider biostratigraphy in our efforts to chemostratigraphically date the Winneshiek Shale. That this is incorrect is shown by the fact that Liu et al. (2017), which contains a two-page review of all fossil evidence that has a bearing on the age of the Winneshiek Shale and was written by Bergström, was cited in Bergström et al. (2018a) and used extensively in our chemostratigraphical age assessment of the unit. Interestingly, recent research provides support for our conclusion regarding the age of the Winneshiek Shale, indicating that at least its upper part is coeval with the Nicholsonograptus fasciculatus Graptolite Zone and the Eoplacognathus pseudoplanus Conodont Zone. In constructing their arguments, Lindskog & Young (2019) provide no alternative interpretations or corrections of scientific value.
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| 20. |
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| 21. |
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| 22. |
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| 23. |
- Blomgran, Robert, et al.
(författare)
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Common Genetic Variations in the NALP3 Inflammasome Are Associated with Delayed Apoptosis of Human Neutrophils
- 2012
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Ingår i: PLOS ONE. - San Francisco, USA : Public Library of Science. - 1932-6203. ; 7:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neutrophils are key-players in the innate host defense and their programmed cell death and removal are essential for efficient resolution of inflammation. These cells recognize a variety of pathogens, and the NOD-like receptors (NLRs) have been suggested as intracellular sensors of microbial components and cell injury/stress. Some NLR will upon activation form multi-protein complexes termed inflammasomes that result in IL-1 beta production. NLR mutations are associated with auto-inflammatory syndromes, and our previous data propose NLRP3 (Q705K)/CARD-8 (C10X) polymorphisms to contribute to increased risk and severity of inflammatory disease by acting as genetic susceptibility factors. These gene products are components of the NALP3 inflammasome, and approximately 6.5% of the Swedish population are heterozygote carriers of these combined gene variants. Since patients carrying the Q705K/C10X polymorphisms display leukocytosis, the aim of the present study was to find out whether the inflammatory phenotype was related to dysfunctional apoptosis and impaired clearance of neutrophils by macrophages. less thanbrgreater than less thanbrgreater thanMethods and Findings: Patients carrying the Q705K/C10X polymorphisms displayed significantly delayed spontaneous as well as microbe-induced apoptosis compared to matched controls. Western blotting revealed increased levels and phosphorylation of Akt and Mcl-1 in the patients neutrophils. In contrast to macrophages from healthy controls, macrophages from the patients produced lower amounts of TNF; suggesting impaired macrophage clearance response. less thanbrgreater than less thanbrgreater thanConclusions: The Q705K/C10X polymorphisms are associated with delayed apoptosis of neutrophils. These findings are explained by altered involvement of different regulators of apoptosis, resulting in an anti-apoptotic profile. Moreover, the macrophage response to ingestion of microbe-induced apoptotic neutrophils is altered in the patients. Taken together, the patients display impaired turnover and clearance of apoptotic neutrophils, pointing towards a dysregulated innate immune response that influences the resolution of inflammation. The future challenge is to understand how microbes affect the activation of inflammasomes, and why this interaction will develop into severe inflammatory disease in certain individuals.
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| 24. |
- Bolin, Sara, 1988-, et al.
(författare)
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Dormant SOX9-positive cells behind MYC-driven medulloblastoma recurrence
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Tidskriftsartikel (refereegranskat)abstract
- Tumor recurrence is a slow biological process involving therapy resistance, immune escape, and metastasis and is the leading cause of death in medulloblastoma, the most frequent malignant pediatric brain tumor. By studying paired primary-recurrent patient samples and patient-derived xenografts we identified a significant accumulation of SOX9-positive cells in relapses and metastases. They exist as rare, quiescent cells in Group 3 and Group 4 patients that constitute two-thirds of medulloblastoma. To follow relapse at the single-cell level we developed an inducible dual Tet model of MYC-driven MB, where MYC can be directed from treatment-sensitive bulk cells to resistant, dormant SOX9-positive cells by doxycycline. SOX9 promoted immune es-cape, DNA repair suppression and was essential for recurrence. Tumor cell dormancy was non-hierarchical, migratory, and depended on MYC suppression by SOX9 to promote relapse. By using computational modeling and treatment we further showed how doxorubicin and MGMT inhibitors are specifically targeting relapsing cells.
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| 25. |
- Bonow, Johan M., et al.
(författare)
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A multi-disciplinary study of Phanerozoic landscape development in West Greenland
- 2007
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Ingår i: Geological Survey of Denmark and Greenland Bulletin: Review of Survey activities 2006. - 1604-8156. ; :13, s. 33-36
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Tidskriftsartikel (refereegranskat)abstract
- The western margin of the Greenland craton has been muchless stable in the Phanerozoic than previously thought. Thisnew insight has come from close integration of independentdata sets: geomorphological analysis of large-scale landscapes,apatite fission track analysis (AFTA), onshore and offshorestratigraphy and analysis of onshore fault and fracture sys -tems. Each data set records specific and unique parts of theevent chronology and is equally important to establish a con-sistent model. A key area for understanding the Mesozoic-Cenozoic landscape evolution and into the present is theuplifted part of the Nuussuaq Basin, where remnants of pla-nation surfaces cut across the Cretaceous to Eocene sedimen-tary and volcanic rocks. Our integrated analysis concludedthat the West Greenland mountains were formed by lateNeogene tectonic uplift (Fig. 1) and also provided newinsight into early Phanerozoic development. To understandour model, we present the different methods and the resultsthat can be deduced from them.
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