| 1. |
- Gustavsson, Anders, et al.
(författare)
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Corrigendum to “Cost of disorders of the brain in Europe 2010” [Eur. Neuropsychopharmacol. 21 (2011) 718–779]
- 2012
-
Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 22:3, s. 237-238
-
Tidskriftsartikel (refereegranskat)abstract
- The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.
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| 2. |
- Gustavsson, Anders, et al.
(författare)
-
Cost of disorders of the brain in Europe 2010.
- 2011
-
Ingår i: European Neuropsychopharmacology. - Amsterdam : Elsevier BV. - 0924-977X .- 1873-7862. ; 21:10, s. 718-79
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate of €386 billion for the year 2004. This estimate was limited in scope and conservative due to the lack of sufficiently comprehensive epidemiological and/or economic data on several important diagnostic groups. We are now in a position to substantially improve and revise the 2004 estimates. In the present report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people.AIMS: To estimate the number of persons with defined disorders of the brain in Europe in 2010, the total cost per person related to each disease in terms of direct and indirect costs, and an estimate of the total cost per disorder and country.METHODS: The best available estimates of the prevalence and cost per person for 19 groups of disorders of the brain (covering well over 100 specific disorders) were identified via a systematic review of the published literature. Together with the twelve disorders included in 2004, the following range of mental and neurologic groups of disorders is covered: addictive disorders, affective disorders, anxiety disorders, brain tumor, childhood and adolescent disorders (developmental disorders), dementia, eating disorders, epilepsy, mental retardation, migraine, multiple sclerosis, neuromuscular disorders, Parkinson's disease, personality disorders, psychotic disorders, sleep disorders, somatoform disorders, stroke, and traumatic brain injury. Epidemiologic panels were charged to complete the literature review for each disorder in order to estimate the 12-month prevalence, and health economic panels were charged to estimate best cost-estimates. A cost model was developed to combine the epidemiologic and economic data and estimate the total cost of each disorder in each of 30 European countries (EU27+Iceland, Norway and Switzerland). The cost model was populated with national statistics from Eurostat to adjust all costs to 2010 values, converting all local currencies to Euro, imputing costs for countries where no data were available, and aggregating country estimates to purchasing power parity adjusted estimates for the total cost of disorders of the brain in Europe 2010.RESULTS: The total cost of disorders of the brain was estimated at €798 billion in 2010. Direct costs constitute the majority of costs (37% direct healthcare costs and 23% direct non-medical costs) whereas the remaining 40% were indirect costs associated with patients' production losses. On average, the estimated cost per person with a disorder of the brain in Europe ranged between €285 for headache and €30,000 for neuromuscular disorders. The European per capita cost of disorders of the brain was €1550 on average but varied by country. The cost (in billion €PPP 2010) of the disorders of the brain included in this study was as follows: addiction: €65.7; anxiety disorders: €74.4; brain tumor: €5.2; child/adolescent disorders: €21.3; dementia: €105.2; eating disorders: €0.8; epilepsy: €13.8; headache: €43.5; mental retardation: €43.3; mood disorders: €113.4; multiple sclerosis: €14.6; neuromuscular disorders: €7.7; Parkinson's disease: €13.9; personality disorders: €27.3; psychotic disorders: €93.9; sleep disorders: €35.4; somatoform disorder: €21.2; stroke: €64.1; traumatic brain injury: €33.0. It should be noted that the revised estimate of those disorders included in the previous 2004 report constituted €477 billion, by and large confirming our previous study results after considering the inflation and population increase since 2004. Further, our results were consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe. Our estimates were lower than comparable estimates from the US.DISCUSSION: This study was based on the best currently available data in Europe and our model enabled extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in our estimates and may imply over- or underestimations in some disorders and countries. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. We therefore consider our estimate of the total cost of the disorders of the brain in Europe to be conservative. In terms of the health economic burden outlined in this report, disorders of the brain likely constitute the number one economic challenge for European health care, now and in the future. Data presented in this report should be considered by all stakeholder groups, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and define a coordinated plan of action of various levels to address the associated challenges.RECOMMENDATIONS: Political action is required in light of the present high cost of disorders of the brain. Funding of brain research must be increased; care for patients with brain disorders as well as teaching at medical schools and other health related educations must be quantitatively and qualitatively improved, including psychological treatments. The current move of the pharmaceutical industry away from brain related indications must be halted and reversed. Continued research into the cost of the many disorders not included in the present study is warranted. It is essential that not only the EU but also the national governments forcefully support these initiatives.
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| 3. |
- Lindahl, Mattias, 1971-, et al.
(författare)
-
Industrial cleaning with Qlean Water : a case study of printed circuit boards
- 2013
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Ingår i: Journal of Cleaner Production. - : Elsevier BV. - 0959-6526 .- 1879-1786. ; 47, s. 19-25
-
Tidskriftsartikel (refereegranskat)abstract
- Many manufacturing companies are looking for ways to substitute environmentally problematic cleaning methods for surface treatments with more environmentally friendly ones. In this paper, one potential solution is described. The Qlean method, based on cleaning with highly pure water (in this paper defined as Qlean Water), is a novel cleaning method. This method, now utilized at one plant at a leading major international electronic company, has substituted previous chemical-based methods for cleaning printed circuit boards prior to lacquering. This paper presents, based on that company's primary data, a comparative study using environmental analysis and economic life cycle cost review between cleaning with Qlean Water and conventional cleaning. The focus is on the environmental and economic performance of the two alternatives. The conclusion is that Qlean Water offers both a significant economic and environmental cost reduction and a better product. This is the case even though all identified economic benefits derived from using Qlean Water, e.g. that the quality and technical lifetime have been extended for the printed circuit boards with the Qlean Water cleaning method, are not considered in the economic analysis.
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| 4. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
-
Ingår i: Aftonbladet. - 1103-9000.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 5. |
- Svensson, Arne, et al.
(författare)
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Utvärdering av Kunskapsprogrammet Hållbar Sanering
- 2009
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Kunskapsprogrammet Hållbar Sanering är en del av Naturvårdsverkets arbete med att nå miljömålet Giftfri miljö. Genom Hållbar Sanering har myndigheter, forskare och företag fått bidrag för att bygga upp och sprida kunskap om efterbehandling av förorenade mark- och vattenområden. Via Naturvårdsverkets hemsida kan all tillgänglig information inhämtas om kunskapsprogrammet Hållbar Sanering, inklusive samtliga projektrapporter och resultatet av syntesarbetet. Totalt har i kunskapsprogrammet genom tre utlysningar 2004 - 2006 finansierat 54 projekt (56 rapporter) inom områdena Undersökningsmetoder, Riskbedömning, Riskvärdering, Riskkommunikation och Åtgärdslösningar. Närmare hälften av projekten avser riskbedömning. En utvärdering har på Naturvårdsverkets uppdrag genomförts av Professional Management AB under perioden januari – april 2009. Utvärderingen visar att Hållbar Sanering har gjort en betydande insats för kunskapsförsörjningen, särskilt när det gäller riskbedömning och riskvärdering. Den ena utvärderingsfrågan handlar om i vilken utsträckning kunskapsprogrammets syfte har uppnåtts. Enligt 70 % av respondenterna i de primära målgrupperna (Naturvårdsverket, SGI, SGU, länsstyrelser, konsulter, forskare och forskningsfinansiärer) har syftet med Hållbar Sanering uppnåtts helt, nästan helt eller i stor utsträckning. Genom kunskapsprogrammet Hållbar Sanering har branschen fått ny kunskap och resultat kan användas i arbetet med att efterbehandla förorenad mark. Det finns en bred samstämmighet bland respondenterna om att Hållbar Sanering har gett användbara resultat för målgrupperna. Nio av tio instämmer helt eller delvis i att Hållbar Sanering erbjuder kunskap och resultat till nytta för myndigheter, forskare och företag. Närmare tre fjärdedelar av respondenterna har redan i viss eller betydande utsträckning själva använt resultatet från Hållbar Sanering i sitt arbete. Tre fjärdedelar anger även att de har haft stor nytta eller viss nytta av dessa resultat. Det bör noteras att denna utvärdering har genomförts innan kunskapsprogrammet är helt avslutat. Det är därför för tidigt att förvänta sig full effekt av programmet. Trots detta kan således påvisas att programmet redan har skapat verifierbar nytta hos målgrupperna. Den andra utvärderingsfrågan gäller arbetssättet. Två av tre respondenter i de primära målgrupperna anser att arbetssättet i stor eller mycket stor utsträckning har varit ändamålsenligt för att öka kunskapen. Färre bedömer dock att arbetssättet hittills har varit ändamålsenligt för att ge underlag för att prioritera insatser. I detta avseende är det bara 28 % som anser att arbetssättet i stor eller mycket stor utsträckning har varit ändamålsenligt. Detta kan möjligen sammanhänga med att tyngdpunkten i kunskapsprogrammet har legat på projekt som gäller riskbedömning och riskvärdering medan få projekt har gällt åtgärdslösningar. För att kunna göra prioriteringar krävs att det går att ställa kostnadseffektiviteten i olika åtgärdslösningar mot varandra. Här uppfattas Hållbar Sanering inte ha bidragit med det underlag som är nödvändigt för beslutsfattarna. Syntesarbetet har dock lett fram till att Naturvårdsverket vet inom vilka områden (inom ramen för programmets kunskapsområden) det finns ytterligare kunskapsbehov. En eventuell fortsatt satsning bör inriktas mot åtgärdslösningar. Samtliga intressenter som har medverkat i arbetet gör bedömningen att kunskapsprogrammet Hållbar Sanering har fokuserats på rätt områden och att områden med viktiga kunskapsluckor har prioriterats i utlysningarna. Det finns en bra balans mellan tekniska, ekonomiska och samhälleliga aspekter. De projekt som har fått stöd synes ha täckt prioriterade kunskapsluckor inom större delen av dessa områden. Dock skulle det ha funnits behov av mer insatser vad gäller åtgärdstekniker, varför Naturvårdsverket bör överväga att använda en del av anslaget för efterbehandlingsarbetet för en ny projektomgång som tydligt är inriktad mot åtgärdsteknik och annan empiri som inte har täckts av Hållbar Sanering. Medan Hållbar Sanering har haft en bred inriktning bör således en ny utlysning vara betydligt smalare och fokusera på ett fåtal frågeställningar av tillämpningskaraktär. Både programkommittén, projektledaren och beredningsgruppen i övrigt har enligt samstämmiga uppgifter genomfört sitt uppdrag på ett mycket bra sätt. Programkommittén har haft en bred sammansättning, vilket har skapat goda förutsättningar för en gemensam kunskapsutveckling. Dock har representant för konsulterna saknats i programkommittén. Generellt sett har arbetssättet inom kunskapsprogrammet varit ändamålsenligt. Programmet har varit välorganiserat och arbetet har lagts upp på ett målmedvetet sätt. Resultatet är av stort värde för intressenterna. Publiceringen av rapporterna på Naturvårdsverkets hemsida anses ha fungerat bra. Den bristande tidshållningen i vissa av projekten och i syntesarbetet borde dock ha kunnat motverkas genom kraftfullare styrning och tydligare incitament. Vidare kunde programmet ha marknadsförts mera offensivt både i utlysningsfasen och i spridningen av resultaten. Materialet från Hållbar Sanering kommer inte att uppdateras eller på annat sätt ändras efter det att programmet är avslutat, men materialet kommer att finnas tillgängligt för alla intressenter för sökning i Naturvårdsverkets webbibliotek. Därutöver kan det finnas skäl att kontinuerligt sprida riktad information om att materialet som helhet finns och om enskilda rapporter till specifika målgrupper. Vissa rapporter kommer att vara aktuella under längre tid, medan det på andra områden relativt snabbt kan komma fram ny kunskap. Naturvårdsverket bör därför systematiskt analysera vad som kan användas som underlag för verkets framtida vägledningsarbete. Beslutsfattare och utförare har behov av tydliga rekommendationer utifrån dagens tillgängliga kunskap. En del av de kunskapsluckor som återstår kan täckas genom internationellt samarbete. Detta gäller inte minst grundläggande studier av föroreningars öde i mark och vatten och olika toxikologiska effekter. Den kunskap som tas fram internationellt kan anpassas till svenska förhållanden och föras vidare av t.ex. forskare (universitet eller forskningsinstitut), konsulter, entreprenörer eller handläggare på en myndighet eller annan organisation. I utvärderingen skisseras också avslutningsvis tre alternativ när det gäller en senare effektstudie.
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| 6. |
- Svensson, Katrin, et al.
(författare)
-
Exosome uptake depends on ERK1/2-heat shock protein 27 signalling and lipid raft-mediated endocytosis negatively regulated by caveolin-1.
- 2013
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 288:24, s. 17713-17724
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Tidskriftsartikel (refereegranskat)abstract
- The role of exosomes in cancer can be inferred from the observation that they transfer tumor cell derived genetic material and signalling proteins, resulting in e.g. increased tumor angiogenesis and metastasis. However, the membrane transport mechanisms and the signalling events involved in the uptake of these virus-like particles remain ill-defined. We now report that internalization of exosomes derived from glioblastoma (GBM) cells involves nonclassical, lipid raft-dependent endocytosis. Importantly, we show that the lipid raft associated protein caveolin-1 (CAV1), in analogy with its previously described role in virus uptake, negatively regulates the uptake of exosomes. We find that exosomes induce the phosphorylation of several downstream targets known to associate with lipid rafts as signalling and sorting platforms, such as extracellular signal-regulated kinase-1/2 (ERK1/2) and heat shock protein 27 (HSP27). Interestingly, exosome uptake appears dependent on unperturbed ERK1/2-HSP27 signalling, and ERK1/2 phosphorylation is under negative influence by CAV1 during internalization of exosomes. These findings significantly advance our general understanding of exosome-mediated uptake and offer potential strategies for how this pathway may be targeted through modulation of CAV1 expression and ERK1/2 signaling.
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| 7. |
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| 8. |
- Svensson, Marina, et al.
(författare)
-
Making Law Work in China
- 2011
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Ingår i: Making Law Work : Chinese Laws in Context. - 9781933947242
-
Bokkapitel (refereegranskat)
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| 9. |
- Aarnio, Harri, et al.
(författare)
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Recombination studies in a polyfluorene copolymer for photovoltaic applications
- 2005
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Ingår i: Synthetic Metals. - : Elsevier BV. - 0379-6779. ; 155:2, s. 299-302
-
Tidskriftsartikel (refereegranskat)abstract
- We present detailed continuous wave (cw) and transient photoinduced absorption (PA) measurements in thin films of a novel alternating polyfluorene copolymer, poly[2,7-(9,9-dioctyl-fluorene)-alt-5,5-(4',7'-di-2-thienyl-2',1',3-benzo-thiadiazole)] (DiO-PFDTBT), and its blends with the sol. fullerene deriv. [6,6]-phenyl-C61-butyric acid Me ester (PCBM) in wt. ratios of 1:0, 4:1 and 1:4. We measure the frequency, intensity and temp. dependence of the PA signal in the frequency domain, and compare with the results obtained from the transient PA decay measurements in the time domain. In all blends, the PA spectrum shows a broad high energy PA band ranging from .apprx.1 eV to 2 eV as well as a low energy band peaking at .apprx.0.35 eV. We attribute the low energy band to the P1 transition of polarons and part of the high energy band to the correlated P2 transition of polarons. Both frequency and time domain measurements show that the high energy band has two decay components, a faster component in the microsecond time regime and a slower component in the millisecond time regime. The slow component is strongly dispersive, whereas the fast component is practically non-dispersive. [on SciFinder (R)]
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| 10. |
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| 11. |
- Adlercreutz, Patrick, et al.
(författare)
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Enzymatic conversions of polar lipids. Principles, problems and solutions
- 2001
-
Ingår i: Journal of Molecular Catalysis - B Enzymatic. - 1381-1177. ; 11:4-6, s. 173-178
-
Forskningsöversikt (refereegranskat)abstract
- This text provides a brief overview of the principles of enzymatic lipid conversion and some recent advances in the enzymatic conversion of glycerophospholipids and galactolipids. Lipases and phospholipases are used to exchange fatty acids or the polar group in the lipids. The reactions can be carried out either as hydrolysis-esterification sequences or as one-step transferase reactions. The scope and limitations of the different methods are discussed.
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| 12. |
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| 13. |
- Admassie, Shimelis, et al.
(författare)
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A polymer photodiode using vapour-phase polymerized PEDOT as an anode
- 2006
-
Ingår i: Solar Energy Materials & Solar Cells. ; 90:2, s. 133-141
-
Tidskriftsartikel (refereegranskat)abstract
- We report the photovoltaic properties of devices made using a highly conducting polymer electrode, from vapor-phase polymd. poly (3,4-ethylenedioxy) thiophene (VPP PEDOT) on glass substrate as an anode and a polyfluorene copolymer poly[2,7-(9,9-dioctyl-fluorene)-alt-5,5-(4',7'-di-2thienyl-2',1'3'-benzothiadiazole)] (APFO-3) mixed with [6,6]-phenyl-C61-butyric acid methylester (PCBM) in the ratio of 1:4 as the active layer. The device performance was compared with that of devices made with PEDOT-PSS on glass substrates. The surfaces of VPP PEDOT were imaged using at. force microscopy (AFM). [on SciFinder (R)]
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| 14. |
- Ahlberg, Erik, et al.
(författare)
-
"Vi klimatforskare stödjer Greta och skolungdomarna"
- 2019
-
Ingår i: Dagens nyheter (DN debatt). - 1101-2447.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 15/3. Sedan industrialiseringens början har vi använt omkring fyra femtedelar av den mängd fossilt kol som får förbrännas för att vi ska klara Parisavtalet. Vi har bara en femtedel kvar och det är bråttom att kraftigt reducera utsläppen. Det har Greta Thunberg och de strejkande ungdomarna förstått. Därför stödjer vi deras krav, skriver 270 klimatforskare.
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| 15. |
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| 16. |
- Ainsworth, Richard I, et al.
(författare)
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Systems-biology analysis of rheumatoid arthritis fibroblast-like synoviocytes implicates cell line-specific transcription factor function.
- 2022
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is an immune-mediated disease affecting diarthrodial joints that remains an unmet medical need despite improved therapy. This limitation likely reflects the diversity of pathogenic pathways in RA, with individual patients demonstrating variable responses to targeted therapies. Better understanding of RA pathogenesis would be aided by a more complete characterization of the disease. To tackle this challenge, we develop and apply a systems biology approach to identify important transcription factors (TFs) in individual RA fibroblast-like synoviocyte (FLS) cell lines by integrating transcriptomic and epigenomic information. Based on the relative importance of the identified TFs, we stratify the RA FLS cell lines into two subtypes with distinct phenotypes and predicted activepathways. We biologically validate these predictions for the top subtype-specific TF RARα and demonstrate differential regulation of TGFβ signaling in the two subtypes. This study characterizes clusters of RA cell lines with distinctive TF biology by integrating transcriptomic and epigenomic data, which could pave the way towards a greater understanding of disease heterogeneity.
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| 17. |
- Ali, Abukar, 1988, et al.
(författare)
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CTLA4-Ig but not anti-TNF therapy promotes staphylococcal septic arthritis in mice.
- 2015
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 212:8, s. 1308-1316
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Tidskriftsartikel (refereegranskat)abstract
- The development of biologics has greatly increased the quality of life as well as the life expectancy of many RA patients. However, a large number of these patients are at an increased risk of developing serious infections. The aim of this study was to examine differential effects of anti-TNF versus CTLA4-Ig treatment on both immunological response and host defense in a murine model of septic arthritis.
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| 18. |
- Ali, Abukar, 1988, et al.
(författare)
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IL-1 Receptor Antagonist Treatment Aggravates Staphylococcal Septic Arthritis and Sepsis in Mice.
- 2015
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-1 receptor antagonist (IL-1Ra) is the primary therapy against autoinflammatory syndromes with robust efficacy in reducing systemic inflammation and associated organ injury. However, patients receiving IL-1Ra might be at increased risk of acquiring serious infections.
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| 19. |
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| 20. |
- Anava, Sarit, et al.
(författare)
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Illuminating Genetic Mysteries of the Dead Sea Scrolls
- 2020
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Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 181:6, s. 1218-
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of the 2,000-year-old Dead Sea Scrolls had an incomparable impact on the historical understanding of Judaism and Christianity. "Piecing together'' scroll fragments is like solving jigsaw puzzles with an unknown number of missing parts. We used the fact that most scrolls are made from animal skins to "fingerprint'' pieces based on DNA sequences. Genetic sorting of the scrolls illuminates their textual relationship and historical significance. Disambiguating the contested relationship between Jeremiah fragments supplies evidence that some scrolls were brought to the Qumran caves from elsewhere; significantly, they demonstrate that divergent versions of Jeremiah circulated in parallel throughout Israel (ancient Judea). Similarly, patterns discovered in non-biblical scrolls, particularly the Songs of the Sabbath Sacrifice, suggest that the Qumran scrolls represent the broader cultural milieu of the period. Finally, genetic analysis divorces debated fragments from the Qumran scrolls. Our study demonstrates that interdisciplinary approaches enrich the scholar's toolkit.
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| 21. |
- Andersson, Karin, 1972, et al.
(författare)
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Down-regulation of survivin alleviates experimental arthritis.
- 2015
-
Ingår i: Journal of leukocyte biology. - 1938-3673. ; 97:1, s. 135-45
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Tidskriftsartikel (refereegranskat)abstract
- Survivin is a proto-oncogene that regulates cell division and apoptosis. It is a molecular marker of cancer. Recently, survivin has emerged as a feature of RA, associated with severe joint damage and poor treatment response. The present study examined if inhibition of survivin affects experimental arthritis, which was induced in mBSA-immunized mice by an injection of mBSA in the knee joint or developed spontaneously in collagen type II-immunized mice. The inhibition of survivin transcription by a lentivirus shRNA construct alleviated joint inflammation and reduced bone damage. The inhibition of survivin reduced the levels of metalloproteinases, β-catenin, and vimentin, limiting the invasive capacity of synovia, while no inhibition of osteoclastogenesis could be found. The inhibition of survivin led to a p53-independent reduction of T cell proliferation and favored the transcription and activity of Blimp-1, which limited IL-2 production and facilitated formation of regulatory Foxp3(+)CD4(+) and effector CD8(+) T cells. The study shows that the inhibition of survivin is sufficient to reduce joint inflammation and bone damage in preclinical models of arthritis. Antiarthritic effects of survivin inhibition are related to p53-independent control of lymphocyte proliferation.
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| 22. |
- Andersson, Karin, 1972, et al.
(författare)
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Survivin co-ordinates formation of follicular T-cells acting in synergy with Bcl-6
- 2015
-
Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 6:24, s. 20043-20057
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Tidskriftsartikel (refereegranskat)abstract
- Follicular T helper (Tfh) cells are recognized by the expression of CXCR5 and the transcriptional regulator Bcl-6. Tfh cells control B cell maturation and antibody production, and if deregulated, may lead to autoimmunity. Here, we study the role of the proto-oncogene survivin in the formation of Tfh cells. We show that blood Tfh cells of patients with the autoimmune condition rheumatoid arthritis, have intracellular expression of survivin. Survivin was co-localized with Bcl-6 in the nuclei of CXCR5(+)CD4 lymphocytes and was immunoprecipitated with the Bcl-6 responsive element of the target genes. Inhibition of survivin in arthritic mice led to the reduction of CXCR5(+) Tfh cells and to low production of autoantibodies. Exposure to survivin activated STAT3 and induced enrichment of PD-1(+)Bcl-6(+) subset within Tfh cells. Collectively, our study demonstrates that survivin belongs to the Tfh cell phenotype and ensures their optimal function by regulating transcriptional activity of Bcl-6.
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| 23. |
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| 24. |
- Andersson, Martin N, et al.
(författare)
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Characterization of olfactory sensory neurons in the white clover seed weevil, Apion fulvipes (Coleoptera: Apionidae).
- 2012
-
Ingår i: Journal of Insect Physiology. - : Elsevier BV. - 1879-1611 .- 0022-1910. ; 58:10, s. 1325-1333
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Tidskriftsartikel (refereegranskat)abstract
- Seed-eating Apion weevils (Coleoptera: Apionidae) cause large economic losses in white and red clover seed production across Europe. Monitoring and control of clover weevils would be facilitated by semiochemical-based methods. Until now, however, nothing was known about physiological or behavioral responses to semiochemicals in this insect group. Here we analyzed the antenna of the white clover (Trifolium repens L.) specialist Apion fulvipes Geoffroy with scanning electron microscopy, and used single sensillum recordings with a set of 28 host compounds to characterize 18 classes of olfactory sensory neurons (OSNs). Nine of the OSN classes responded strongly to synthetic compounds with high abundance in clover leaves, flowers, or buds. Eight classes responded only weakly to the synthetic stimuli, whereas one collective class responded exclusively to volatiles released from a crushed clover leaf. The OSNs showed a remarkable degree of specificity, responding to only one or a few chemically related compounds. In addition, we recorded a marked difference in the temporal dynamics of responses between different neurons, compounds, and doses. The identified physiologically active compounds will be screened for behavioral activity, with the ultimate goal to develop an odor-based control strategy for this pest.
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| 25. |
- Andersson, Sofia E M, 1979, et al.
(författare)
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Activation of Fms-like tyrosine kinase 3 signaling enhances survivin expression in a mouse model of rheumatoid arthritis.
- 2012
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 7:10
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Tidskriftsartikel (refereegranskat)abstract
- Survivin is known as an inhibitor of apoptosis and a positive regulator of cell division. We have recently identified survivin as a predictor of joint destruction in patients with rheumatoid arthritis (RA). Flt3 ligand (Flt3L) is expressed in the inflamed joints and has adjuvant properties in arthritis. Studies on 90 RA patients (median age 60.5 years [range, 24-87], disease duration 10.5 years [range, 0-35]) show a strong positive association between the levels of survivin and Flt3L in blood. Here, we present experimental evidence connecting survivin and Flt3L signaling. Treatment of BALB/c mice with Flt3L led to an increase of survivin in the bone marrow and in splenic dendritic cells. Flt3L changed the profile of survivin splice variants, increasing transcription of the short survivin40 in the bone marrow. Treatment with an Flt3 inhibitor reduced total survivin expression in bone marrow and in the dendritic cell population in spleen. Inhibition of survivin transcription in mice, by shRNA lentiviral constructs, reduced the gene expression of Flt3L. We conclude that expression of survivin is a downstream event of Flt3 signaling, which serves as an essential mechanism supporting survival of leukocytes during their differentiation, and maturation of dendritic cells, in RA.
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