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Sökning: WFRF:(Persson Anders) > Umeå universitet

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1.
  • Brännström, Kristoffer, et al. (författare)
  • Ca2+ enhances Aβ polymerization rate and fibrillar stability in a dynamic manner
  • 2013
  • Ingår i: Biochemical Journal. - Portland Press. - 0264-6021. ; 450, s. 189-197
  • Tidskriftsartikel (refereegranskat)abstract
    • Identifying factors that affect the self-assembly of the amyloid-β peptide (Aβ) is of utmost importance in the quest to understand the molecular mechanisms causing Alzheimer's disease (AD). Ca2+ has previously been shown to accelerate both Aβ fibril nucleation and maturation, and a dysregulated Ca2+ homeostasis frequently correlates with development of AD. The mechanisms regarding Ca2+ binding as well as its effect on fibril kinetics are not fully understood. Using a polymerization assay we show that Ca2+ in a dynamic and reversible manner enhances both the elongation rate and fibrillar stability, where specifically the "dock and lock" phase mechanism is enhanced. Through NMR analysis we found that Ca2+ affects the fibrillar architecture. In addition, and unexpectedly, we found that Ca2+ does not bind the free Aβ monomer. This implies that Ca2+ binding requires an architecture adopted by assembled peptides, and consequently is mediated through intermolecular interactions between adjacent peptides. This gives a mechanistic explanation to the enhancing effect on fibril maturation and indicates structural similarities between prefibrillar structures and mature amyloid. Taken together we expose how Ca2+ levels affect the delicate equilibrium between the monomeric and assembled Aβ and how fluctuations in vivo may contribute to development and progression of the disease.
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2.
  • Lundström, Jan O, et al. (författare)
  • The geographic distribution of mosquito species in Sweden
  • 2013
  • Ingår i: Journal of the European Mosquito Control Association. - 1460-6127. ; 31, s. 21-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Surveillance of the actual distribution of mosquito species in Northern Europe is fundamental for evaluating risk for emerging pathogens, and for research on potential vectors. The Swedish mosquito fauna composition and geographic distribution, originally described by Professor Christine Dahl in the 1970´s, included 43 species. We have compiled the information published from 1978 to 2012, and our own surveillance data from 2001 to 2013, and compared this with the species list and geographic distribution provided in “Taxonomy and geographic distribution of Swedish Culicidae” by Dahl (1977). New species detected during these 36 years were Culiseta (Culicella) ochroptera (Peus, 1935) published 1984, Aedes (Aedes) rossicus Dolbeskin, Goritzkaja & Mitrofanova, 1930 published 1986, Anopheles (Anopheles) beklemishevi published 1986, Aedes (Ochlerotatus) euedes (Howard, Dyar & Knab, 1912) published 2001, Aedes (Ochlerotatus) nigrinus (Eckstein, 1918) first recorded in 2012, and Anopheles (Anopheles) algeriensis Theobald, 1903, first recorded in 2013. We provide maps with the distribution by province for each species, including historic information up until 1977, and new records from 1978 to 2013, showing the similarities and differences between the old and the new records. Important findings in recent years include the wide distribution of the Sindbis virus enzootic vector Culex (Culex) torrentium Martinii, 1925, and the more limited distribution of the potential West Nile virus vector Culex (Culex) pipiens Linnaeus, 1758. The updated list of mosquito species in Sweden now includes 49 species.
3.
  • Olofsson, Anders, et al. (författare)
  • Amide solvent protection analysis demonstrates that amyloid-beta(1-40) and amyloid-beta(1-42) form different fibrillar structures under identical conditions.
  • 2007
  • Ingår i: Biochem J. - 1470-8728. ; 404:1, s. 63-70
  • Tidskriftsartikel (refereegranskat)abstract
    • AD (Alzheimer's disease) is a neurodegenerative disorder characterized by self-assembly and amyloid formation of the 39–43 residue long Ab (amyloid-b)-peptide. The most abundant species, Ab(1–40) and Ab(1–42), are both present within senile plaques, but Ab(1–42) peptides are considerably more prone to self-aggregation and are also essential for the development of AD. To understand the molecular and pathological mechanisms behind AD, a detailed knowledge of the amyloid structures of Ab-peptides is vital. In the present study we have used quenched hydrogen/deuterium-exchange NMR experiments to probe the structure of Ab(1–40) fibrils. The fibrils were prepared and analysed identically as in our previous study on Ab(1–42) fibrils, allowing a direct comparison of the two fibrillar structures. The solvent protection pattern of Ab(1–40) fibrils revealed two well-protected regions, consistent with a structural arrangement of two b-strands connected with a bend. This protection pattern partly resembles the pattern found in Ab(1–42) fibrils, but the Ab(1–40) fibrils display a significantly increased protection for the N-terminal residues Phe4–His14, suggesting that additional secondary structure is formed in this region. In contrast, the C-terminal residues Gly37–Val40 show a reduced protection that suggests a loss of secondary structure in this region and an altered filament assembly. The differences between the present study and other similar investigations suggest that subtle variations in fibril-preparation conditions may significantly affect the fibrillar architecture.
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4.
  • Olofsson, Anders, et al. (författare)
  • Quenched hydrogen/deuterium exchange NMR characterization of amyloid-β peptide aggregates formed in the presence of Cu2+ or Zn2
  • 2009
  • Ingår i: The FEBS Journal. - Wiley InterScience. - 1742-464X. ; 276:15, s. 4051-4060
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease, a neurodegenerative disorder causing synaptic impairment and neuronal cell death, is strongly correlated with aggregation of the amyloid-β peptide (Aβ). Divalent metal ions such as Cu2+ and Zn2+ are known to significantly affect the rate of aggregation and morphology of Aβ assemblies in vitro and are also found at elevated levels within cerebral plaques in vivo. The present investigation characterized the architecture of the aggregated forms of Aβ(1–40) and Aβ(1–42) in the presence or absence of either Cu2+ or Zn2+ using quenched hydrogen/deuterium exchange combined with solution NMR spectroscopy. The NMR analyses provide a quantitative and residue-specific structural characterization of metal-induced Aβ aggregates, showing that both the peptide sequence and the type of metal ion exert an impact on the final architecture. Common features among the metal-complexed peptide aggregates are two solvent-protected regions with an intervening minimum centered at Asn27, and a solvent-accessible N-terminal region, Asp1–Lys16. Our results suggest that Aβ in complex with either Cu2+ or Zn2+ can attain an aggregation-prone β-strand–turn–β-strand motif, similar to the motif found in fibrils, but where the metal binding to the N-terminal region guides the peptide into an assembly distinctly different from the fibril form.
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5.
  • Tieva, Åse, et al. (författare)
  • Effect on energy and macronutrient intake with partial replacement of external food supply by in-house cooking at a nursing home for older people in Sweden
  • 2015
  • Ingår i: International Journal of Consumer Studies. - 1470-6423. ; 39:4, s. 369-379
  • Tidskriftsartikel (refereegranskat)abstract
    • An increased awareness of the importance of nutrition for older people's health and quality of life has underpinned projects and quality improvements for the meal situation in care establishments. The present study took place in a nursing home in a village outside an average-sized town situated in mid-Sweden. Care staff had initiated a change from external catered meals to purchase the food and cook the main meals themselves. The intention was to increase flexibility in accommodating the requests and needs of the elderly and, in doing so, to achieve increased professional pride and satisfaction. To ensure that no negative effects resulted for the residents in the nursing home, outcomes were evaluated through the present intervention study. The objective was to investigate whether and, if so, how their energy and nutrient intake and weight were affected. At the start, only one main hot meal was exchanged for home cooking to avoid work load problems as no increased costs were allowed and no extra staff were to be recruited. The study population consisted of 21 residents, aged 69-97 years. Weight, energy and nutrient intake were recorded before and during the intervention by 3-day food records validated by Goldberg's cutoff method. The same 3 days of the weekSunday to Tuesdayand the same menus were used for both measurement periods. At group level, the energy intake corresponded to the estimated energy requirements, both at baseline and at follow-up, although the intervention resulted in a significantly higher energy intake from the meals cooked in the ward kitchens. Two-thirds of the residents (n=13) slightly increased in weight from baseline to follow-up, while two participants (with body mass index 27.5 kg/m(2) and 33.5 kg/m(2), respectively) lost 5.0 kg and 6.9 kg, respectively. The total protein intake was insufficient both at baseline and follow-up and only met the participants' needs to 8122% and 83 +/- 26%, respectively. In conclusion, the intervention resulted in no adverse consequences for participants in terms of energy and nutrient intake. Most participants were weight stable or had small increases in weight, and the greatest weight gain was observed in the lighter clients. The low protein intake at both time points causes concern and suggests the need for further nutritional interventions to optimize older people's protein intake.
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6.
  • Arnqvist, Anders, et al. (författare)
  • En kunskapsbas : Sätt att organisera för att individanpassa skolgången
  • 2010
  • Ingår i: I rättan tid : Om ålder och skolstart. - Stockholm : Fritzes. - 978-91-38-23447-1 ; s. 67-87
  • Bokkapitel (övrigt vetenskapligt)abstract
    • De överväganden och förslag som redovisas i detta betänkande har tagits fram med utgångspunkt i en kunskapsbas. Kunskapsbasen består av dels översikter över aktuella forskningsresultat inom ett antal områden som har bäring på frågan om flexibel skolstart i grundskolan, dels några internationella utblickar. Vetenskapligt förankrade kunskapsöversikter har för utredningens räkning sammanställts av fyra forskare, nämligen professor Anders Arnqvist, Karlstads universitet, professor Sven Persson, Malmö högskola, fil dr Monika Vinterek, Umeå universitet och fil lic Helena Ackesjö, Linnéuniversitetet. Var och en har haft i uppdrag att inom respektive område redogöra för resultat inom svensk och internationell forskning från mitten av 1990-talet och senare. I uppdraget har ingått att uppmärksamma eventuella skillnader mellan olika elevgrupper samt effekter på både elevers kunskapsutveckling och sociala utveckling. I detta kapitel redovisas forskarnas egna sammanfattningar av forskningsöversikterna. Dessa återges i sin helhet i bilagorna 2–5. Av dem framgår också de frågeställningar och områden med bäring på flexibel skolstart som forskarna finner behov av att följa upp, utvärdera och beforska. Kunskapsbasen innehåller även en internationell utblick. I den återges hur barn på Nya Zeeland börjar skolan successivt på sin födelsedag och hur barn i England kan börja skolan vid fler tillfällen under läsåret. Lite mer utförligt redovisas dessutom diskussionen inför och införandet av rullande skolstart i Danmark och flexibel skolstart i Norge.
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7.
  • Björk, Glenn, et al. (författare)
  • A conserved modified wobble nucleoside (mcm5s2U) in lysyl-tRNA is required for viability in yeast.
  • 2007
  • Ingår i: RNA. - 1355-8382. ; 13:8, s. 1245-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Transfer RNAs specific for Gln, Lys, and Glu from all organisms (except Mycoplasma) and organelles have a 2-thiouridine derivative (xm(5)s(2)U) as wobble nucleoside. These tRNAs read the A- and G-ending codons in the split codon boxes His/Gln, Asn/Lys, and Asp/Glu. In eukaryotic cytoplasmic tRNAs the conserved constituent (xm(5)-) in position 5 of uridine is 5-methoxycarbonylmethyl (mcm(5)). A protein (Tuc1p) from yeast resembling the bacterial protein TtcA, which is required for the synthesis of 2-thiocytidine in position 32 of the tRNA, was shown instead to be required for the synthesis of 2-thiouridine in the wobble position (position 34). Apparently, an ancient member of the TtcA family has evolved to thiolate U34 in tRNAs of organisms from the domains Eukarya and Archaea. Deletion of the TUC1 gene together with a deletion of the ELP3 gene, which results in the lack of the mcm(5) side chain, removes all modifications from the wobble uridine derivatives of the cytoplasmic tRNAs specific for Gln, Lys, and Glu, and is lethal to the cell. Since excess of the unmodified form of these three tRNAs rescued the double mutant elp3 tuc1, the primary function of mcm(5)s(2)U34 seems to be to improve the efficiency to read the cognate codons rather than to prevent mis-sense errors. Surprisingly, overexpression of the mcm(5)s(2)U-lacking tRNA(Lys) alone was sufficient to restore viability of the double mutant.
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8.
  • Björk, Glenn R, et al. (författare)
  • A primordial tRNA modification required for the evolution of life?
  • 2001
  • Ingår i: EMBO Journal. - 0261-4189. ; 20:1-2, s. 231-239
  • Tidskriftsartikel (refereegranskat)abstract
    • The evolution of reading frame maintenance must have been an early event, and presumably preceded the emergence of the three domains Archaea, Bacteria and Eukarya. Features evolved early in reading frame maintenance may still exist in present-day organisms. We show that one such feature may be the modified nucleoside 1-methylguanosine (m(1)G37), which prevents frameshifting and is present adjacent to and 3' of the anticodon (position 37) in the same subset of tRNAs from all organisms, including that with the smallest sequenced genome (Mycoplasma genitalium), and organelles. We have identified the genes encoding the enzyme tRNA(m(1)G37)methyltransferase from all three domains. We also show that they are orthologues, and suggest that they originated from a primordial gene. Lack of m(1)G37 severely impairs the growth of a bacterium and a eukaryote to a similar degree. Yeast tRNA(m(1)G37)methyltransferase also synthesizes 1-methylinosine and participates in the formation of the Y-base (yW). Our results suggest that m(1)G37 existed in tRNA before the divergence of the three domains, and that a tRNA(m(1)G37)methyltrans ferase is part of the minimal set of gene products required for life.
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9.
  • Björklund, Emmelie, et al. (författare)
  • Involvement of Fatty Acid Amide Hydrolase and Fatty Acid Binding Protein 5 in the Uptake of Anandamide by Cell Lines with Different Levels of Fatty Acid Amide Hydrolase Expression: A Pharmacological Study
  • 2014
  • Ingår i: PLoS ONE. - PLoS ONE. - 1932-6203. ; 9:7, s. e103479
  • Tidskriftsartikel (refereegranskat)abstract
    • Background:The endocannabinoid ligand anandamide (AEA) is removed from the extracellular space by a process ofcellular uptake followed by metabolism. In many cells, such as the RBL-2H3 cell line, inhibition of FAAH activity reduces theobserved uptake, indicating that the enzyme regulates uptake by controlling the intra- : extracellular AEA concentrationgradient. However, in other FAAH-expressing cells, no such effect is seen. It is not clear, however, whether these differencesare methodological in nature or due to properties of the cells themselves. In consequence, we have reinvestigated the roleof FAAH in gating the uptake of AEA.Methodology/Principal Findings: The effects of FAAH inhibition upon AEA uptake were investigated in four cell lines: AT1rat prostate cancer, RBL-2H3 rat basophilic leukaemia, rat C6 glioma and mouse P19 embryonic carcinoma cells. SemiquantitativePCR for the cells and for a rat brain lysate confirmed the expression of FAAH. No obvious expression of atranscript with the expected molecular weight of FLAT was seen. FAAH expression differed between cells, but all four couldaccumulate AEA in a manner inhibitable by the selective FAAH inhibitor URB597. However, there was a difference in thesensitivities seen in the reduction of uptake for a given degree of FAAH inhibition produced by a reversible FAAH inhibitor,with C6 cells being more sensitive than RBL-2H3 cells, despite rather similar expression levels and activities of FAAH. Thefour cell lines all expressed FABP5, and AEA uptake was reduced in the presence of the FABP5 inhibitor SB-FI-26, suggestingthat the different sensitivities to FAAH inhibition for C6 and RBL2H3 cells is not due to differences at the level of FABP-5.Conclusions/Significance: When assayed using the same methodology, different FAAH-expressing cells display differentsensitivities of uptake to FAAH inhibition.
10.
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