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1.
  • Alsterfjord, Magnus, et al. (author)
  • Plasma membrane H+-ATPase and 14-3-3 Isoforms of Arabidopsis leaves: Evidence for isoform specificity in the 14-3-3/H+-ATPase interaction
  • 2004
  • In: Plant and Cell Physiology. - : Oxford University Press (OUP). - 1471-9053 .- 0032-0781. ; 45:9, s. 1202-1210
  • Journal article (peer-reviewed)abstract
    • The plasma membrane H+-ATPase is activated by binding of 14-3-3 protein to the phosphorylated C terminus. Considering the large number of 14-3-3 and H+-ATPase isoforms in Arabidopsis (13 and 11 expressed genes, respectively), specificity in binding may exist between 14-3-3 and H+-ATPase isoforms. We now show that the H'-ATPase is the main target for 14-3-3 binding at the plasma membrane, and that all twelve 14-3-3 istiforms tested bind to the H+-ATPase in vitro. Using specific antibodies for nine of the 14-3-3 isoforms, we show that GF14epsilon, mu, lambda, omega, chi, phi, nu, and upsilon are present in leaves, but that isolated plasma membranes lack GF14chi, phi and upsilon. Northern blots using isoform-specific probes for all 14-3-3 and H+-ATPase isoforms showed that transcripts were present for most of the isoforms. Based on mRNA levels, GF14epsilon, mu, lambda and chi are highly expressed 14-3-3 isoforms, and AHA1, 3, and 11 highly expressed H+-ATPase isoforms in leaves. However, mass peptide fingerprinting identified AHA1 and 2 with the highest score, and their presence could be confirmed by MS/MS. It may be calculated that under 'unstressed' conditions less than one percent of total 14-3-3 is attached to the H+-ATPase. However, during a condition requiring full activation of H+ pumping, as induced here by the presence of the fungal toxin fusicoccin, several percent of total 14-3-3 may be engaged in activation of the H+-ATPase.
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  • Larsson, Kjell (author)
  • Tätare uppdateringar behövs av riktlinjer vid astma och KOL
  • 2020
  • In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 117
  • Journal article (pop. science, debate, etc.)abstract
    • Rekommendationer för omhändertagande vid astma och kroniskt obstruktiv lungsjukdom (KOL) uppdateras av Läkemedelsverket cirka vart sjunde år och ligger till grund för diagnostik och behandling framför allt i primärvården. Internationella riktlinjer för omhändertagande av astma (Global initiative for asthma, GINA) och KOL (Global initiative for chronic obstructive lung disease, GOLD) uppdateras årligen för att ny kunskap om behandling snabbt ska nå patienterna.De långa intervallen mellan uppdateringarna innebär att rekommendationerna hinner bli inaktuella innan nästa version publiceras, och Sverige hamnar i otakt med internationella riktlinjer. Farmakologisk behandling uppdateras av regionala läkemedelskommittéer, men rekommendationerna skiljer sig i olika delar av landet och stäms ofta inte av mot internationella riktlinjer, vilket leder till ojämlik behandling över landet. Läkemedelsverkets kunskapsstöd Läkemedelsboken innehöll ett kapitel om astma och KOL där man vid behov kunde uppdatera riktlinjer för primärvården, men detta stöd har lagts ned.Vid astma rekommenderar riktlinjerna kortverkande beta-2-agonister vid behov som enda behandling vid lindrig astma (steg 1) samt som tillägg till underhållsbehandling vid svårare sjukdom vid symtomgenombrott [1]. Som alternativ vid svårare astma (steg 3–5) rekommenderas inhalationssteroider i fast kombination med formoterol (steroid + formoterol) vid behov i stället för kortverkande b2-agonister [1]. Vid lindrig astma ger steroid + formoterol vid behov som enda behandling bättre resultat än endast kortverkande beta-2-agonister vid behov [2-5]. Vidare har steroid + formoterol (inhalerat vid behov) lika god exacerbationsförebyggande effekt som regelbunden behandling med inhalationssteroider och kortverkande beta-2-agonister vid behov trots en betydligt lägre kortisonbelastning [3, 5].I juni 2019 uppdaterades GINA:s astmarekommendationer genomgripande [6]. Här rekommenderas steroid + formoterol vid behov vid alla svårighetsgrader av astma. Kortverkande beta-2-agonister (salbutamol, terbutalin) vid behov är struket som förstahandsalternativ. Data indikerar att endast kortverkande beta-2-agonister vid behov faktiskt ökar risken för svåra exacerbationer och astmarelaterad mortalitet. Genom tillägg av inhalationssteroid till en snabb- och långverkande beta-2-agonist reduceras risken signifikant [6]. Vidare rekommenderas steroid + formoterol vid behov som alternativ till regelbunden behandling med inhalationssteroider på steg 2. Riktlinjerna har redan godkänts i flera länder.Vid KOL-behandling är två viktiga mål att lindra symtom och förebygga exacerbationer. Basbehandlingen för att uppnå detta är långverkande antikolinergika. Tillägg av långverkande beta-2-agonist till långverkande antikolinergika ger ytterligare god effekt på symtom, men en mer blygsam tilläggseffekt på exacerbationer [8]. Vid KOL ges inhalationssteroid i syfte att förebygga exacerbation. Hög nivå av eosinofiler i blod förekommer ofta vid KOL. Nyare forskning visar att blodeosinofili varierar hos patienter med KOL. Inhalationssteroider förebygger exacerbationer mer effektivt hos KOL-patienter med eosinofili, och blodeosinofili kan vägleda den förebyggande behandlingen [9-12]. Kontroll av eosinofiler i blod förespråkas i det senaste GOLD-dokumentet inför val av terapi och nydiagnostiserad KOL. Vid KOL och samtidig eosinofili anges inhalationssteroid + långverkande beta-2-agonist som tänkbart förstahandsalternativ i förebyggande syfte [13].Vi anser att behandling av patienter med astma och/eller KOL i Sverige ska baseras på rekommendationer från Läkemedelverket och att de senaste landvinningarna inom området måste återfinnas i riktlinjerna. Läkemedelsverket bör uppdatera riktlinjerna kontinuerligt, helst årligen. Detta kan göras av en mindre grupp experter genom en begränsad arbetsinsats till låg kostnad. Potentiella bindningar eller jävsförhållanden: Samtliga författare har deltagit i expertgrupp och/eller föreläst/haft utbildningsuppdrag hos företag som verkar inom området.
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  • Larsson, Magnus, et al. (author)
  • Leadership in interaction
  • 2023. - 2
  • In: SAGE Handbook of leadership. - 9781529769067 ; , s. 28-39
  • Book chapter (peer-reviewed)
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  • Nordanskog, Pia, et al. (author)
  • Increase in Hippocampal Volume After Electroconvulsive Therapy in Patients With Depression : A Volumetric Magnetic Resonance Imaging Study
  • 2010
  • In: JOURNAL OF ECT. - 1095-0680 .- 1533-4112. ; 26:1, s. 62-67
  • Journal article (peer-reviewed)abstract
    • Background: Major depression has traditionally been regarded as a neurochemical disease, but findings of a decreased hippocampal volume in patients with depression have turned the pathophysiological focus toward impairments in structural plasticity. The mechanisms of action of the most effective antidepressive treatment, electroconvulsive therapy (ECT), still remains elusive, but recent animal research has provided evidence for a cell proliferative effect in the hippocampus. The aim of this prospective study was to determine if hippocampal volume changes after ECT in patients with depression.Methods: Twelve patients with depression and ongoing antidepressive pharmacological treatment were investigated with clinical ratings and 3 T magnetic resonance imaging within 1 week before and after the ECT series. Each hippocampus was manually outlined on coronal slices, and the volume was calculated.Results: The left as well as the right hippocampal volume increased significantly after ECT.Conclusions: The hippocampal volume increases after ECT, supporting the hypothesis that hippocampus may play a central role in the treatment of depression.
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7.
  • Alijagic, Andi, 1992-, et al. (author)
  • Particle Safety Assessment in Additive Manufacturing : From Exposure Risks to Advanced Toxicology Testing.
  • 2022
  • In: Frontiers in Toxicology. - : Frontiers Media S.A.. - 2673-3080. ; 4
  • Research review (peer-reviewed)abstract
    • Additive manufacturing (AM) or industrial three-dimensional (3D) printing drives a new spectrum of design and production possibilities; pushing the boundaries both in the application by production of sophisticated products as well as the development of next-generation materials. AM technologies apply a diversity of feedstocks, including plastic, metallic, and ceramic particle powders with distinct size, shape, and surface chemistry. In addition, powders are often reused, which may change the particles' physicochemical properties and by that alter their toxic potential. The AM production technology commonly relies on a laser or electron beam to selectively melt or sinter particle powders. Large energy input on feedstock powders generates several byproducts, including varying amounts of virgin microparticles, nanoparticles, spatter, and volatile chemicals that are emitted in the working environment; throughout the production and processing phases. The micro and nanoscale size may enable particles to interact with and to cross biological barriers, which could, in turn, give rise to unexpected adverse outcomes, including inflammation, oxidative stress, activation of signaling pathways, genotoxicity, and carcinogenicity. Another important aspect of AM-associated risks is emission/leakage of mono- and oligomers due to polymer breakdown and high temperature transformation of chemicals from polymeric particles, both during production, use, and in vivo, including in target cells. These chemicals are potential inducers of direct toxicity, genotoxicity, and endocrine disruption. Nevertheless, understanding whether AM particle powders and their byproducts may exert adverse effects in humans is largely lacking and urges comprehensive safety assessment across the entire AM lifecycle-spanning from virgin and reused to airborne particles. Therefore, this review will detail: 1) brief overview of the AM feedstock powders, impact of reuse on particle physicochemical properties, main exposure pathways and protective measures in AM industry, 2) role of particle biological identity and key toxicological endpoints in the particle safety assessment, and 3) next-generation toxicology approaches in nanosafety for safety assessment in AM. Altogether, the proposed testing approach will enable a deeper understanding of existing and emerging particle and chemical safety challenges and provide a strategy for the development of cutting-edge methodologies for hazard identification and risk assessment in the AM industry.
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8.
  • Annersten Gershater, Magdalena, et al. (author)
  • Complexity of factors related to outcome of neuropathic and neuroischaemic/ischaemic diabetic foot ulcers: a cohort study
  • 2009
  • In: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 52:3, s. 398-407
  • Journal article (peer-reviewed)abstract
    • We sought to identify factors related to short-term outcome of foot ulcers in patients with diabetes treated in a multidisciplinary system until healing was achieved. Consecutively presenting patients with diabetes and worst foot ulcer (Wagner grade 1-5, below ankle) (n = 2,511) were prospectively followed and treated according to a standardised protocol until healing was achieved or until death. The number of patients lost to dropout was 31. The characteristics of the remaining 2,480 patients were: 1,465 men, age 68 +/- 15 years (range 18-96), type 1 diabetes 18%, type 2 diabetes 82% and insulin-treated 62%. The healing rate without major amputation in surviving patients was 90.6% (n = 1,867). Sixty-five per cent (n = 1,617) were healed primarily, 9% (n = 250) after minor amputation and 8% after major amputation; 17% (n = 420) died unhealed. Out of 2,060 surviving patients, 1,007 were neuroischaemic (48.8%). In a multiple regression analysis, primary healing was related to co-morbidity, duration of diabetes, extent of peripheral vascular disease and type of ulcer. In neuropathic ulcers, deep foot infection, site of ulcer and co-morbidity were related to amputation. Amputation in neuroischaemic ulcers was related to co-morbidity, peripheral vascular disease and type of ulcer. Age, sex, duration of diabetes, neuropathy, deformity and duration of ulcer or site of ulcer did not have an evident influence on probability of amputation. Patients with diabetic foot ulcer suffer from multi-organ disease. Factors related to outcome are correspondingly complex.
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  • Axelsson, Magnus, et al. (author)
  • GRB110721A : AN EXTREME PEAK ENERGY AND SIGNATURES OF THE PHOTOSPHERE
  • 2012
  • In: Astrophysical Journal Letters. - 2041-8205. ; 757:2
  • Journal article (peer-reviewed)abstract
    • GRB110721A was observed by the Fermi Gamma-ray Space Telescope using its two instruments, the Large Area Telescope (LAT) and the Gamma-ray Burst Monitor (GBM). The burst consisted of one major emission episode which lasted for similar to 24.5 s (in the GBM) and had a peak flux of (5.7 +/- 0.2) x 10(-5) erg s(-1) cm(-2). The time-resolved emission spectrum is best modeled with a combination of a Band function and a blackbody spectrum. The peak energy of the Band component was initially 15 +/- 2 MeV, which is the highest value ever detected in a GRB. This measurement was made possible by combining GBM/BGO data with LAT Low Energy events to achieve continuous 10-100 MeV coverage. The peak energy later decreased as a power law in time with an index of -1.89 +/- 0.10. The temperature of the blackbody component also decreased, starting from similar to 80 keV, and the decay showed a significant break after similar to 2 s. The spectrum provides strong constraints on the standard synchrotron model, indicating that alternative mechanisms may give rise to the emission at these energies.
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