| 1. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Cerebrospinal Fluid Microglial Markers in Alzheimer's Disease: Elevated Chitotriosidase Activity but Lack of Diagnostic Utility
- 2011
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 13:2, s. 151-159
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Tidskriftsartikel (refereegranskat)abstract
- Activated microglial cells, which are the resident macrophages of the central nervous system, surround amyloid beta-plaques in Alzheimer's disease (AD) brains. Inflammation including microglial activation may contribute in AD pathogenesis, and biomarkers for this process may thus be of value to study AD pathogenesis and might facilitate development of therapies targeting these cells. We therefore examined cerebrospinal fluid (CSF) biomarkers in patients with AD, other dementias, mild cognitive impairment and in healthy controls. Samples were analyzed for markers with known association to macrophage activity, including chitotriosidase, YKL-40 (CHI3L1, HC gp-39) and chemokine CC motif ligand 2 (CCL2, MCP1). Patients with AD had higher chitotriosidase activity than controls and patients with stable mild cognitive impairment, consistent with the presence of activated microglial cells in AD brains, but with large overlaps between groups. CCL2 and YKL-40 concentrations did not differ among groups. Microglial markers are unlikely to be useful for AD diagnosis, but might be useful for identification of distinct subgroups of patients, and for the development and implementation of drugs targeting microglial pathology.
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| 2. |
- Prade, Thomas, et al.
(författare)
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Vall som biogassubstrat : utvärdering av skördesystemets och odlingsintensitetens påverkan på biogasutbytet
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I ett fältförsök på marginalmark odlades och skördades olika vallblandningar som biogassubstrat. Syftet med studien var att (a) undersöka biomassa- och metanavkastningen för de olika vallblandningarna och (b) analysera spridningen av metanpotentialbestämningarnas resultat för att undersöka möjligheter till minskning av analyskostnaderna genom annan provtagnings- och provberedningsstrategi. En gödslad kommersiell vall gav med 8,1 ton ts/ha den högsta biomassaavkastningen vid två skördar per år. Vid bara en skörd per år var det den gödslade kommersiella vallen och den befintliga vegetationen som gav högst biomassaavkastning. Metanpotentialsskillnaderna mellan vallblandningarna var ganska små vid samma skördetidpunkt. Däremot ökar den specifika metanpotentialen (liter metan per kg VS) med två skördar per år. Beräkningarna visade att antalet analyser för metanpotentialbestämningen kan reduceras betydligt när samlingsprover används i analyserna. På detta sätt minskar man variationen inom leden, vilket bidrar till att skillnader mellan olika behandlingar enklare kan upptäckas.
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| 3. |
- Brinkmalm, Gunnar, et al.
(författare)
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An online nano-LC-ESI-FTICR-MS method for comprehensive characterization of endogenous fragments from amyloid β and amyloid precursor protein in human and cat cerebrospinal fluid.
- 2012
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Ingår i: Journal of mass spectrometry : JMS. - : Wiley. - 1096-9888 .- 1076-5174. ; 47:5, s. 591-603
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid precursor protein (APP) is the precursor protein to amyloid β (Aβ), the main constituent of senile plaques in Alzheimer's disease (AD). Endogenous Aβ peptides reflect the APP processing, and greater knowledge of different APP degradation pathways is important to understand the mechanism underlying AD pathology. When one analyzes longer Aβ peptides by low-energy collision-induced dissociation tandem mass spectrometry (MS/MS), mainly long b-fragments are observed, limiting the possibility to determine variations such as amino acid variants or post-translational modifications (PTMs) within the N-terminal half of the peptide. However, by using electron capture dissociation (ECD), we obtained a more comprehensive sequence coverage for several APP/Aβ peptide species, thus enabling a deeper characterization of possible variants and PTMs. Abnormal APP/Aβ processing has also been described in the lysosomal storage disease Niemann-Pick type C and the major large animal used for studying this disease is cat. By ECD MS/MS, a substitution of Asp7 → Glu in cat Aβ was identified. Further, sialylated core 1 like O-glycans at Tyr10, recently discovered in human Aβ (a previously unknown glycosylation type), were identified also in cat cerebrospinal fluid (CSF). It is therefore likely that this unusual type of glycosylation is common for (at least) species belonging to the magnorder Boreoeutheria. We here describe a detailed characterization of endogenous APP/Aβ peptide species in CSF by using an online top-down MS-based method.
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| 4. |
- Crespo, Ana, et al.
(författare)
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Phylogenetic generic classification of parmelioid lichens (Parmeliaceae,Ascomycota) based on molecular, morphological and chemical evidence.
- 2010
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Ingår i: Taxon. - : John Wiley & Sons. - 0040-0262 .- 1996-8175. ; 59:6, s. 1735-1753
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Tidskriftsartikel (refereegranskat)abstract
- Parmelioid lichens are a diverse and ubiquitous group of foliose lichens. Generic delimitation in parmelioid lichens has been in a state of flux since the late 1960s with the segregation of the large, heterogeneous genus Parmelia into numerous smaller genera. Recent molecular phylogenetic studies have demonstrated that some of these new genera were monophyletic, some were not, and others, previously believed to be unrelated, fell within single monophyletic groups, indicating the need for a revision of the generic delimitations. This study aims to give an overview of current knowledge of the major clades of all parmelioid lichens. For this, we assembled a dataset of 762 specimens, including 31 of 33 currently accepted parmelioid genera (and 63 of 84 accepted genera of Parmeliaceae). We performed maximum likelihood and Bayesian analyses of combined datasets including two, three and four loci. Based on these phylogenies and the correlation of morphological and chemical characters that characterize monophyletic groups, we accept 27 genera within nine main clades. We re-circumscribe several genera and reduce Parmelaria to synonymy with Parmotrema. Emodomelanelia Divakar & A. Crespo is described as a new genus (type: E. masonii). Nipponoparmelia (Kurok.) K.H. Moon, Y. Ohmura & Kashiw. ex A. Crespo & al. is elevated to generic rank and 15 new combinations are proposed (in the genera Flavoparmelia, Parmotrema, Myelochroa, Melanelixia and Nipponoparmelia). A short discussion of the accepted genera is provided and remaining challenges and areas requiring additional taxon sampling are identified.
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| 5. |
- Lättman, Håkan, 1958-
(författare)
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Studies on spatial and temporal distributions of epiphytic lichens
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lichens are an important group of organisms in terms of environmental issues, conservation biology and biodiversity, principally due to their sensitivity to changes in their environment. Therefore it is important that we develop our understanding of the factors that affect lichen distribution. In this thesis, both spatial and temporal distributions of epiphytic lichens at different scales have been studied in southern Sweden.Generation time of the red-listed lichen Cliostomum corrugatum was examined using Bjärka-Säby as the study site. The results showed that the average age of an individual of C. corrugatum is 25–30 years at the onset of spore production.The rarity of C. corrugatum was also examined. DNA analysis of an intron from 85 samples, collected at five sites in Östergötland, yielded 11 haplotypes. Results from coalescent analysis, mantel test and AMOVA indicated that C. corrugatum have a high ability to disperse. The study concluded that its rarity is most likely connected with the low amount of available habitat, old Quercus robur.The changes in the distribution of epiphytic lichens in southern Sweden, between 1986 and 2003, were also compared. For each year a centroid was calculated on all combinations of tree and lichen species. The three significant cases showed that the centroid movement pointed toward a north-east or north-north-east direction.Finally differences in species richness and cover of lichens on large Q. robur were examined between urban and rural environment. The results demonstrated that species number and percent cover was significantly higher on oaks standing rural compared to oaks standing urban. Effects of urban sprawl showed a decline in species richness and cover with increasing age of the surrounding buildings.
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| 6. |
- Mattsson, Jan-Eric, 1949-, et al.
(författare)
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Aim: To practise scientific methods. Result: Personal development
- 2014
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Ingår i: Ebook proceedings of the ESERA 2013 Conference. - Nicosia, Cypern : European Science Education Research Association. - 9789963700776 ; , s. 2410-2417
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Konferensbidrag (refereegranskat)abstract
- Field work in a teacher training program was focussed on the collection and presentation of data showing changes in the environment depending on variable factors. The observations should be possible to use as models for studies performed by children at school. The instructions were sparse and many of the observations from the first visit to the sites were impossible to repeat. The first four observations were made during autumn every month while the last was made in late spring sixteen months later. After this the students wrote short reflections on their impressions and experiences during the last visit compared to the earlier ones. These were analysed in order to reveal the impact on the students. Most of the students were very uncertain about what to do the first time. Almost none of them complained about this afterwards. Many were astonished over their own incapability of understanding or declared their lack of understanding general ideas. Many students wrote about strong emotions when returning to a familiar site that appeared to have changed and described how this created a strong attachment to the site. What was more surprising was that some students experienced their own development, in some cases towards becoming a teacher but also on a more private or personal level. They not only recognized themselves as the inexperienced student from the first visit and what was achieved later. They also realized how the relation between themselves and the site had a chronological development in accordance with their own development. The simple activity of field observations in combination with personal reflection created complicated processes beneficial for the student.Thus, we achieved and observed unexpected results together with what was expected.
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| 7. |
- Mattsson, Jan-Eric, 1949-, et al.
(författare)
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Betygsättning av naturvetenskap enligt 2011 års läroplaner : Workshop
- 2012
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Bedömningstillfällen i naturvetenskap vid lärarutbildning som kan användas i skolanInom lärarutbildningen vid Södertörns högskola har vi inom de naturvetenskapliga ämnena sedan flera år arbetat med olika typer av bedömningstillfällen vid examinationen av studenter. Oftast är dessa bedömningstillfällen konstruerade för att vara examinerande av olika lärandemål som representerar önskade didaktiska förmågor hos den blivande läraren. De kan därför samtidigt fungera som modeller för hur man som lärare kan arbeta inom grund- och gymnasieskolan för bedömning av elevers förmågor. Förutom muntliga och skriftliga redovisningar kan dessa t.ex. bestå av redovisande exkursioner i natur- eller kulturmiljöer, laborationer, självreflektioner, traditionella eller estetiska loggböcker, självdiagnoser med kamratbedömning, museivisningar och webbaserade laborationer. För att studenterna skall få motsvarande träning har undervisningen på högskolan i allt högre utsträckning utvecklats från föreläsningar och demonstrativa laborationer och exkursioner mot många olika typer av interaktiva aktiviteter. Motsvarande utveckling återspeglas internationellt där sedan tio år den traditionella läroboken med beskrivande texter som skall läsas och läras ersatts av läromedel, fortfarande ofta i bokform, som ger anvisningar om hur studenter tillsammans kan arbeta med sin kunskapsutveckling, genom exempel, arbetsuppgifter, diskussionsfrågor, problematiseringar, lärande diagnoser etc.Bedömning av naturvetenskap enligt Lgr 11 och Lgy 11I de nya läroplanerna Lgr 11 och Lgy 11 skall elevers förmåga, att använda sina kunskaper, användas som grund för betygsättningen. Detta innebär stora förändringar jämfört med tidigare betygsystem där fokus oftast låg på bedömning utifrån elevers redovisning av kunskaper inhämtade från olika typer av läromedel. Enkelt uttryckt kan man säga att tidigare bedömningar försökte värdera elevens förmögenhet i form av samlad (minnes)kunskap medan dagens läroplaner fokuserar på bedömning av elevers förmåga att använda sina kunskaper inom olika områden. Det har följaktligen skett en stor förändring i synsättet på det som skall bedömas och hur detta kan genomföras vilket även får konsekvenser för undervisningen.Av reportage, diskussioner och andra inslag i massmedia framkommer att många, även rutinerade lärare, har svårt att förstå hur de skall arbeta med lärande bedömning och vill ha klarare anvisningar och exempel.Lärande bedömningJönsson (Lärande bedömning, 2012) beskriver hur undervisning bör planeras utifrån den bedömning av förmågor baserade på betygskriterier som läraren skall utföra. Till skillnad från tidigare där undervisningen först planerades och genomfördes och där resultatet slutligen bedömdes genom skrivningar eller förhör utgår Jönsson från bedömningen och utformar undervisningen utifrån denna. I korthet ser modellen ut så här:Läraren konstruerar utifrån betygskriterierna ett bedömningstillfälle (performance assessment) och skapar en bedömningsmatris inför observationen av nivån på de förmågor hos eleven som skall bedömas. Det är inte nödvändigt att betrakta en viss handling, bedömningen kan göras genom av produkter som eleven producerar. Därefter planeras undervisningen dvs. de tillfällen där eleverna skall få möjlighet att träna de förmågor som skall bedömas.Workshop med olika bedömningstillfällen i naturvetenskapVi kommer att i mindre grupper genomföra olika bedömningstillfällen anpassade till de nya betygskriterierna och med användande av olika metoder som samtidigt kan utgöra exempel på hur man t.ex. kan arbeta med estetiska lärprocesser (ELP), IKT, laborationer, kamratbedömning utifrån de nya läroplanernas betygskriterier för naturvetenskapliga ämnen inkl. naturgeografi. De modellerar bedömningstillfällen men blir samtidigt exempel på hur man kan arbeta med undervisning enligt de nya läroplanerna. Alla kan inte få pröva allt men genom att erbjuda ett antal olika moment kan deltagarna snabbt få en inblick i olika sätt att bedöma elevers utvecklingsnivå utifrån betygskriterierna. Den tid som krävs vid bedömning, enligt den nu i läroplanerna introducerade betygsskalan, där flera färdigheter förekommer i olika former i flera ämnen, medför ett behov av bedömning av kvaliteten hos flera färdigheter under samma bedömningstillfälle. Därför kommer exemplen i hög utsträckning vara ämnesintegrerade och med vissa modifieringar kunna användas i olika årskurser.
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| 8. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Amyloid-β metabolism in Niemann-Pick C disease models and patients.
- 2012
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Ingår i: Metabolic brain disease. - : Springer Science and Business Media LLC. - 1573-7365 .- 0885-7490. ; 27:4, s. 573-85
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Tidskriftsartikel (refereegranskat)abstract
- Niemann-Pick type C (NPC) is a progressive neurodegenerative lysosomal disease with altered cellular lipid trafficking. The metabolism of amyloid-β (Aβ) - previously mainly studied in Alzheimer's disease - has been suggested to be altered in NPC. Here we aimed to perform a detailed characterization of metabolic products from the amyloid precursor protein (APP) in NPC models and patients. We used multiple analytical technologies, including immunoassays and immunoprecipitation followed by mass spectrometry (IP-MS) to characterize Aβ peptides and soluble APP fragments (sAPP-α/β) in cell media from pharmacologically (U18666A) and genetically (NPC1 ( -/- ) ) induced NPC cell models, and cerebrospinal fluid (CSF) from NPC cats and human patients. The pattern of Aβ peptides and sAPP-α/β fragments in cell media was differently affected by NPC-phenotype induced by U18666A treatment and by NPC1 ( -/- ) genotype. U18666A treatment increased the secreted media levels of sAPP-α, AβX-40 and AβX-42 and reduced the levels of sAPP-β, Aβ1-40 and Aβ1-42, while IP-MS showed increased relative levels of Aβ5-38 and Aβ5-40 in response to treatment. NPC1 ( -/- ) cells had reduced media levels of sAPP-α and Aβ1-16, and increased levels of sAPP-β. NPC cats had altered CSF distribution of Aβ peptides compared with normal cats. Cats treated with the potential disease-modifying compound 2-hydroxypropyl-β-cyclodextrin had increased relative levels of short Aβ peptides including Aβ1-16 compared with untreated cats. NPC patients receiving β-cyclodextrin had reduced levels over time of CSF Aβ1-42, AβX-38, AβX-40, AβX-42 and sAPP-β, as well as reduced levels of the axonal damage markers tau and phosphorylated tau. We conclude that NPC models have altered Aβ metabolism, but with differences across experimental systems, suggesting that NPC1-loss of function, such as in NPC1 ( -/- ) cells, or NPC1-dysfunction, seen in NPC patients and cats as well as in U18666A-treated cells, may cause subtle but different effects on APP degradation pathways. The preliminary findings from NPC cats suggest that treatment with cyclodextrin may have an impact on APP processing pathways. CSF Aβ, sAPP and tau biomarkers were dynamically altered over time in human NPC patients.
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| 9. |
- Mattsson, Niklas, 1979, et al.
(författare)
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{gamma}-Secretase-dependent amyloid-{beta} is increased in Niemann-Pick type C: A cross-sectional study.
- 2011
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Ingår i: Neurology. - 0028-3878. ; 76:4, s. 366-72
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Niemann-Pick disease type C (NPC) is an inherited disorder characterized by intracellular accumulation of lipids such as cholesterol and glycosphingolipids in endosomes and lysosomes. This accumulation induces progressive degeneration of the nervous system. NPC shows some intriguing similarities with Alzheimer disease (AD), including neurofibrillary tangles, but patients with NPC generally lack amyloid-β (Aβ) plaques. Lipids affect γ-secretase-dependent amyloid precursor protein (APP) metabolism that generates Aβ in vitro, but this has been difficult to prove in vivo. Our aim was to assess the effect of altered lipid constituents in neuronal membranes on amyloidogenic APP processing in humans. METHODS: We examined Aβ in CSF from patients with NPC (n = 38) and controls (n = 14). CSF was analyzed for Aβ(38), Aβ(40), Aβ(42), α-cleaved soluble APP, β-cleaved soluble APP, total-tau, and phospho-tau. RESULTS: Aβ release was markedly increased in NPC, with a shift toward the Aβ(42) isoform. Levels of α- and β-cleaved soluble APP were similar in patients and controls. Patients with NPC had increased total-tau. Patients on treatment with miglustat (n = 18), a glucosylceramide synthase blocker, had lower Aβ(42) and total-tau than untreated patients. CONCLUSION: Increased CSF levels of Aβ(38), Aβ(40), and Aβ(42) and unaltered levels of β-cleaved soluble APP are consistent with increased γ-secretase-dependent Aβ release in the brains of patients with NPC. These results provide the first in vivo evidence that neuronal lipid accumulation facilitates γ-secretase-dependent Aβ production in humans and may be of relevance to AD pathogenesis.
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| 10. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Miglustat treatment may reduce cerebrospinal fluid levels of the axonal degeneration marker tau in niemann-pick type C.
- 2012
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Ingår i: JIMD reports. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 2192-8304. ; 3, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Niemann-Pick disease type C (NPC) is a lysosomal storage disorder that leads to progressive neurodegeneration. The glucosylceramide synthase blocker miglustat is being used to treat NPC, but monitoring of disease progression and treatment response is difficult. NPC patients have elevated cerebrospinal fluid (CSF) levels of total-tau (T-tau) indicating axonal degeneration, and increased CSF amyloid β (Aβ) indicating abnormal brain amyloid metabolism, but it is unknown if start of miglustat treatment affects these biomarker levels. Methods: Biomarkers were measured in serial CSF samples from NPC patients who started miglustat between samplings (N=5), were untreated at both samplings (N=5) or received treatment during the whole study (N=6) (median time between samplings 309 days [range 175-644]). CSF was analyzed for Aβ(38), Aβ(40), Aβ(42), α-cleaved soluble APP, β-cleaved soluble APP, T-tau and phospho-tau. Results: T-tau levels decreased in patients who started miglustat treatment (median 955 [range 338-1,271]ng/L at baseline vs. 382 [187-736]ng/L at follow-up, p=0.043). Untreated patients and continuously treated patients had stable levels (p>0.05). No changes were seen in the other biomarkers. Conclusion: Reduced CSF T-tau suggests that miglustat treatment might affect axonal degeneration in NPC. However, the results must be interpreted with caution and verified in future studies, since this pilot study was small, treatment was not randomized, and patients starting treatment had higher baseline CSF T-tau than untreated patients.
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