SwePub - search: WFRF:(Åslund Andreas)

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1.	Arja, Katriann, et al. (author) Enhanced Fluorescent Assignment of Protein Aggregates by an Oligothiophene-Porphyrin-Based Amyloid Ligand 2013 In: Macromolecular rapid communications. - : Wiley-VCH Verlag. - 1022-1336 .- 1521-3927. ; 34:9, s. 723-730 Journal article (peer-reviewed)abstract Fluorescent probes identifying protein aggregates are of great interest, as deposition of aggregated proteins is associated with many devastating diseases. Here, we report that a fluorescent amyloid ligand composed of two distinct molecular moieties, an amyloidophilic pentameric oligothiophene and a porphyrin, can be utilized for spectral and lifetime imaging assessment of recombinant A 1-42 amyloid fibrils and A deposits in brain tissue sections from a transgenic mouse model with Alzheimers disease pathology. The enhanced spectral range and distinct lifetime diversity of this novel oligothiopheneporphyrin-based ligand allow a more precise assessment of heterogeneous amyloid morphology compared with the corresponding oligothiophene dye.
2.	Borota, Ljubisa, et al. (author) Spot fluoroscopy : a novel innovative approach to reduce radiation dose in neurointerventional procedures 2017 In: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 58:5, s. 600-608 Journal article (peer-reviewed)abstract BACKGROUND: Increased interest in radiation dose reduction in neurointerventional procedures has led to the development of a method called "spot fluoroscopy" (SF), which enables the operator to collimate a rectangular or square region of interest anywhere within the general field of view. This has potential advantages over conventional collimation, which is limited to symmetric collimation centered over the field of view.PURPOSE: To evaluate the effect of SF on the radiation dose.MATERIAL AND METHODS: Thirty-five patients with intracranial aneurysms were treated with endovascular coiling. SF was used in 16 patients and conventional fluoroscopy in 19. The following parameters were analyzed: the total fluoroscopic time, the total air kerma, the total fluoroscopic dose-area product, and the fluoroscopic dose-area product rate. Statistical differences were determined using the Welch's t-test.RESULTS: The use of SF led to a reduction of 50% of the total fluoroscopic dose-area product (CF = 106.21 Gycm(2), SD = 99.06 Gycm(2) versus SF = 51.80 Gycm(2), SD = 21.03 Gycm(2), p = 0.003884) and significant reduction of the total fluoroscopic dose-area product rate (CF = 1.42 Gycm(2)/min, SD = 0.57 Gycm(2)/s versus SF = 0.83 Gycm(2)/min, SD = 0.37 Gycm(2)/min, p = 0.00106). The use of SF did not lead to an increase in fluoroscopy time or an increase in total fluoroscopic cumulative air kerma, regardless of collimation.CONCLUSION: The SF function is a new and promising tool for reduction of the radiation dose during neurointerventional procedures.
3.	Condén, Emelie, 1979-, et al. (author) Is type D personality an independent risk factor for recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients? 2017 In: European Journal of Preventive Cardiology. - : Sage Publications. - 2047-4873 .- 2047-4881. ; 24:5, s. 522-533 Journal article (peer-reviewed)abstract Background: Type D personality refers to a combination of simultaneously high levels of negative affectivity and social inhibition. The present study aimed to examine whether type D personality was independently associated with recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients, using any of the previously proposed methods for measuring type D personality. Design: This was a prospective cohort study. Methods: Utilising data from the Vastmanland Myocardial Infarction Study, 946 post-acute myocardial infarction patients having data on the DS14 instrument used to measure type D personality were followed-up for recurrent myocardial infarction and all-cause mortality until 9 December 2015. Data were analysed using Cox regression, adjusted for established risk factors. Results: In total, 133 (14.1%) patients suffered from type D personality. During a mean follow-up time for recurrent myocardial infarction of 5.7 (3.2) years, 166 (17.5%) patients were affected by recurrent myocardial infarction, of which 26 (15.7%) had type D personality, while during a mean follow-up time for all-cause mortality of 6.3 (2.9) years, 321 (33.9%) patients died, of which 42 (13.1%) had type D personality. After adjusting for established risk factors, type D personality was not significantly associated with recurrent myocardial infarction or all-cause mortality using any of the previously proposed methods for measuring type D personality. A weak association was found between the social inhibition part of type D personality and a decreased risk of all-cause mortality, but this association was not significant after taking missing data into account in a multiple imputation analysis. Conclusions: No support was found for type D personality being independently associated with recurrent myocardial infarction or all-cause mortality in post-acute myocardial infarction patients, using any of the previously proposed methods for measuring type D personality.
4.	Condén, Emelie, 1979-, et al. (author) Prevalence of Type D Personality and Factorial and Temporal Stability of the DS14 after Myocardial Infarction in a Swedish Population 2014 In: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 55:6, s. 601-610 Journal article (peer-reviewed)abstract This study examined the prevalence of Type D personality and the temporal stability, internal consistency, and construct validity of the DS14 at three time points after myocardial infarction. The prevalence of Type D personality was 14.0% during hospitalization, 25.1% at 1 month, and 19.2% at 12 months. A total of 6.1% of patients were classified as Type D personality at all three assessments, whereas 68.4% were stable non-Type D and 25.6% changed between personality classifications. The DS14 had stable structural validity, but low temporal stability over time, especially from hospitalization to the 1-month and 12-month follow-ups (k = 0.365 and 0.397, respectively).
5.	Gyllenhammar, Andreas, et al. (author) Flodpärlmussla, Resultat från inventeringarna 1996-2005 2005 Reports (other academic/artistic)abstract I denna rapport redovisas de insatser som gjorts för att kartlägga Jämtlands läns bestånd av flodpärlmussla (Margaritifera margaritifera). En kartläggning av historiska bestånd har gjorts, mestadels baserad på litteraturstudier. I rapporten redovisas resultaten från det inventeringsarbete som utförts av Länsstyrelsen i Jämtlands län åren 1996-2005. Resultaten presenteras i form av kartor, figurer och tabeller där beståndens geografiska lokalisering, storlek och reproduktionsstatus redovisas. Länet har idag 53 lokaler med bestånd av flodpärlmussla. I 30 stycken av dessa bestånd förekommer reproduktion men i över hälften (18st) är reproduktionen svag. 12 av bestånden har ett uppskattat individantal på över 10000 individer. Jämtland har i dagsläget Sveriges största bestånd av flodpärlmussla. I Storån, norr om Hammerdal, har antalet individer beräknats till 4,5 miljoner. En mer omfattande analys av läget för flodpärlmusslan i länet kommer att göras då inventeringsmaterialet datalagts i större omfattning och då ytterligare miljödata finns sammanställda. Slutsatserna pekar på vikten av att ytterligare miljödata tillgängliggörs för att möjliggöra en fördjupad analys av musselbeståndens och omgivningsparametrarnas status. Slutligen presenteras hur Länsstyrelsens arbete med flodpärlmussla kommer att fortskrida under 2006, med bl a utformning av ett miljöövervakningsprogram och planering av skyddsåtgärder.
6.	Hammarström, Per, et al. (author) A Fluorescent Pentameric Thiophene Derivative Detects in Vitro-Formed Prefibrillar Protein Aggregates 2010 In: BIOCHEMISTRY. - : ACS American Chemical Society. - 0006-2960 .- 1520-4995. ; 49:32, s. 6838-6845 Journal article (peer-reviewed)abstract Protein aggregation is associated with a wide range of diseases, and molecular probes that are able to detect a diversity of misfolded protein assemblies are of great importance. The identification of prefibrillar states preceding the formation of well-defined amyloid fibrils is of particular interest both because of their likely role in the mechanism of fibril formation and because of the growing awareness that these species are likely to play a critical role in the pathogenesis of protein deposition diseases. Herein, we explore the use of an anionic oligothiophene derivative, p-FTAA, for detection of prefibrillar protein aggregates during in vitro fibrillation of three different amyloidogenic proteins (insulin, lysozyme, and prion protein). p-FTAA generally detected prefibrillar protein aggregates that could not be detected by thioflavine T fluorescence and in addition showed high fluorescence when bound to mature fibrils. Second, the kinetics of protein aggregation or the formation of amyloid fibrils of insulin was not extensively influenced by the presence of various concentrations of p-FTAA. These results establish the use of p-FTAA as an additional tool for studying the process of protein aggregation.
7.	Heilbronner, Goetz, et al. (author) Seeded strain-like transmission of beta-amyloid morphotypes in APP transgenic mice 2013 In: EMBO Reports. - : NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND. - 1469-221X .- 1469-3178. ; 14:11, s. 1017-1022 Journal article (peer-reviewed)abstract The polymorphic beta-amyloid lesions present in individuals with Alzheimers disease are collectively known as cerebral beta-amyloidosis. Amyloid precursor protein (APP) transgenic mouse models similarly develop beta-amyloid depositions that differ in morphology, binding of amyloid conformation-sensitive dyes, and A beta 40/A beta 42 peptide ratio. To determine the nature of such beta-amyloid morphotypes, beta-amyloid-containing brain extracts from either aged APP23 brains or aged APPPS1 brains were intracerebrally injected into the hippocampus of young APP23 or APPPS1 transgenic mice. APPPS1 brain extract injected into young APP23 mice induced beta-amyloid deposition with the morphological, conformational, and A beta 40/A beta 42 ratio characteristics of beta-amyloid deposits in aged APPPS1 mice, whereas APP23 brain extract injected into young APP23 mice induced b-amyloid deposits with the characteristics of beta-amyloid deposits in aged APP23 mice. Injecting the two extracts into the APPPS1 host revealed a similar difference between the induced beta-amyloid deposits, although less prominent, and the induced deposits were similar to the beta-amyloid deposits found in aged APPPS1 hosts. These results indicate that the molecular composition and conformation of aggregated A beta in APP transgenic mice can be maintained by seeded conversion.
8.	Herrmann, Uli S., et al. (author) Structure-based drug design identifies polythiophenes as antiprion compounds 2015 In: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 7:299, s. 299ra123- Journal article (peer-reviewed)abstract Prions cause transmissible spongiform encephalopathies for which no treatment exists. Prions consist of PrPSc, a misfolded and aggregated form of the cellular prion protein (PrPC). We explore the antiprion properties of luminescent conjugated polythiophenes (LCPs) that bind and stabilize ordered protein aggregates. By administering a library of structurally diverse LCPs to the brains of prion-infected mice via osmotic minipumps, we found that antiprion activity required a minimum of five thiophene rings bearing regularly spaced carboxyl side groups. Solid-state nuclear magnetic resonance analyses and molecular dynamics simulations revealed that anionic side chains interacted with complementary, regularly spaced cationic amyloid residues of model prions. These findings allowed us to extract structural rules governing the interaction between LCPs and protein aggregates, which we then used to design a new set of LCPs with optimized binding. The new set of LCPs showed robust prophylactic and therapeutic potency in prion-infected mice, with the lead compound extending survival by greater than80% and showing activity against both mouse and hamster prions as well as efficacy upon intraperitoneal administration into mice. These results demonstrate the feasibility of targeted chemical design of compounds that may be useful for treating diseases of aberrant protein aggregation such as prion disease.
9.	Ilkhanizadeh, Shirin, et al. (author) Live Detection of Neural Progenitors and Glioblastoma Cells by an Oligothiophene Derivative 2023 In: ACS Applied Bio Materials. - : American Chemical Society (ACS). - 2576-6422. ; 6:9, s. 3790-3797 Journal article (peer-reviewed)abstract There is an urgent need for simple and non-invasive identification of live neural stem/progenitor cells (NSPCs) in the developing and adult brain as well as in disease, such as in brain tumors, due to the potential clinical importance in prognosis, diagnosis, and treatment of diseases of the nervous system. Here, we report a luminescent conjugated oligothiophene (LCO), named p-HTMI, for non-invasive and non-amplified real-time detection of live human patient-derived glioblastoma (GBM) stem cell-like cells and NSPCs. While p-HTMI stained only a small fraction of other cell types investigated, the mere addition of p-HTMI to the cell culture resulted in efficient detection of NSPCs or GBM cells from rodents and humans within minutes. p-HTMI is functionalized with a methylated imidazole moiety resembling the side chain of histidine/histamine, and non-methylated analogues were not functional. Cell sorting experiments of human GBM cells demonstrated that p-HTMI labeled the same cell population as CD271, a proposed marker for stem cell-like cells and rapidly migrating cells in glioblastoma. Our results suggest that the LCO p-HTMI is a versatile tool for immediate and selective detection of neural and glioma stem and progenitor cells.
10.	Johansson, Leif B. G., et al. (author) An azide functionalized oligothiophene ligand - A versatile tool for multimodal detection of disease associated protein aggregates 2015 In: Biosensors & bioelectronics. - : Elsevier. - 0956-5663 .- 1873-4235. ; 63, s. 204-211 Journal article (peer-reviewed)abstract Ligands for identifying protein aggregates are of great interest as such deposits are the pathological hallmark of a wide range of severe diseases including Alzheimers and Parkinsons disease. Here we report the synthesis of an azide functionalized fluorescent pentameric oligothiophene that can be utilized as a ligand for multimodal detection of disease-associated protein aggregates. The azide functionalization allows for attachment of the ligand to a surface by conventional click chemistry without disturbing selective interaction with protein aggregates and the oligothiophene-aggregate interaction can be detected by fluorescence or surface plasmon resonance. In addition, a methodology where the oligothiophene ligand is employed as a capturing molecule selective for aggregated proteins in combination with an antibody detecting a distinct peptide/protein is also presented. We foresee that this methodology will offer the possibility to create a variety of multiplex sensing systems for sensitive and selective detection of protein aggregates, the pathological hallmarks of several neurodegenerative diseases.
11.	Karlsson, Roger H., et al. (author) Iron Catalyzed Polymerization of Alkoxysulfonate-Functionalized EDOT gives 2007 In: Chemistry of Materials. - 0897-4756 .- 1520-5002. Journal article (peer-reviewed)
12.	Karlsson, Roger, et al. (author) Iron-Catalyzed Polymerization of Alkoxysulfonate-Functionalized 3,4-Ethylenedioxythiophene Gives Water-Soluble Poly(3,4-ethylenedioxythiophene) of High Conductivity 2009 In: Chemistry of Materials. - : American Chemical Society (ACS). - 0897-4756 .- 1520-5002. ; 21:9, s. 1815-1821 Journal article (peer-reviewed)abstract Chemical polymerization of a 3,4-ethylenedioxythiophene derivative bearing a sulfonate group (EDOTS) is reported. The polymer, PEDOT-S, is fully water-soluble and has been produced by polymerizing EDOT-S in water, using Na2S2O8 and a catalytic amount of FeCl 3. Elemental analysis and XPS measurements indicate that PEDOT-S is a material with a substantial degree of self-doping, but also contains free sulfate ions as charge-balancing counterions of the oxidized polymer. Apart from selfdoping PEDOT-S, the side chains enable full water solubility of the material; DLS studies show an average cluster size of only 2 nm. Importantly, the solvation properties of the PEDOT-S are reflected in spin-coated films, which show a surface roughness of 1.2 nm and good conductivity (12 S/cm) in ambient conditions. The electro-optical properties of this material are shown with cyclic voltammetry and spectroelectrochemical experiment reveals an electrochromic contrast (̃48% at λmax ) 606 nm).
13.	Klingstedt, Therése, et al. (author) Synthesis of a library of oligothiophenes and their utilization as fluorescent ligands for spectral assignment of protein aggregates 2011 In: Organic and biomolecular chemistry. - : Royal Society of Chemistry. - 1477-0520 .- 1477-0539. ; 9:24, s. 8356-8370 Journal article (peer-reviewed)abstract Molecular probes for selective identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying protein aggregation diseases. Here we report the chemical design of a library of anionic luminescent conjugated oligothiophenes (LCOs), which can be utilized as ligands for detection of protein aggregates. Certain molecular requirements were shown to be necessary for detecting (i) early non-thioflavinophilic protein assemblies of A beta 1-42 and insulin preceding the formation of amyloid fibrils and (ii) for obtaining distinct spectral signatures of the two main pathological hallmarks observed in human Alzheimers diease brain tissue (A beta plaques and neurofibrillary tangles). Our findings suggest that a superior anionic LCO-based ligand should have a backbone consisting of five to seven thiophene units and carboxyl groups extending the conjugated thiophene backbone. Such LCOs will be highly useful for studying the underlying molecular events of protein aggregation diseases and could also be utilized for the development of novel diagnostic tools for these diseases.
14.	Klingstedt, Therése, et al. (author) The structural basis for optimal performance of oligothiophene based fluorescent amyloid ligands : Conformational flexibility is essential for spectral assignment of a diversity of protein aggregates Other publication (other academic/artistic)abstract Protein misfolding diseases are characterized by deposition of protein aggregates and optical ligands for molecular characterization of these disease-associated structures are important for understanding their potential role in the pathogenesis of the disease. Luminescent conjugated oligothiophenes (LCOs) have proven useful for optical identification of a broader subset of disease-associated protein aggregates than conventional ligands, such as Thioflavin T (ThT) and Congo red. Herein, the molecular requirements for achieving LCOs able to detect non-thioflavinophilic Aβ aggregates or non-congophilic prion aggregates, as well as spectrally discriminate Aβ and tau aggregates, were investigated. An anionic pentameric LCO was subjected to chemical engineering by i) replacing thiophene units with selenophene or phenylene moieties or ii) alternating the anionic substituents along the thiophene backbone. In addition, two asymmetric tetrameric ligands were generated. Overall, the results from this study identified conformational freedom and extended conjugation of the conjugated backbone as crucial determinants for obtaining superior thiophene-based optical ligands for sensitive detection and spectral assignment of diseaseassociated protein aggregates.
15.	Klingstedt, Therése, et al. (author) The Structural Basis for Optimal Performance of Oligothiophene-Based Fluorescent Amyloid Ligands : Conformational Flexibility is Essential for Spectral Assignment of a Diversity of Protein Aggregates 2013 In: Chemistry - A European Journal. - : Wiley-VCH Verlag. - 0947-6539 .- 1521-3765. ; 19:31, s. 10179-10192 Journal article (peer-reviewed)abstract Protein misfolding diseases are characterized by deposition of protein aggregates, and optical ligands for molecular characterization of these disease-associated structures are important for understanding their potential role in the pathogenesis of the disease. Luminescent conjugated oligothiophenes (LCOs) have proven useful for optical identification of a broader subset of disease-associated protein aggregates than conventional ligands, such as thioflavin T and Congo red. Herein, the molecular requirements for achieving LCOs able to detect nonthioflavinophilic Aβ aggregates or non-congophilic prion aggregates, as well as spectrally discriminate Aβ and tau aggregates, were investigated. An anionic pentameric LCO was subjected to chemical engineering by: 1) replacing thiophene units with selenophene or phenylene moieties, or 2) alternating the anionic substituents along the thiophene backbone. In addition, two asymmetric tetrameric ligands were generated. Overall, the results from this study identified conformational freedom and extended conjugation of the conjugated backbone as crucial determinants for obtaining superior thiophene-based optical ligands for sensitive detection and spectral assignment of disease-associated protein aggregates.
16.	Lerouge, Frederic, et al. (author) In vivo targeting and multimodal imaging of cerebral amyloid-beta aggregates using hybrid GdF3 nanoparticles 2022 In: Nanomedicine. - : FUTURE MEDICINE LTD. - 1743-5889 .- 1748-6963. ; 17:29, s. 2173-2187 Journal article (peer-reviewed)abstract Aim: To propose a new multimodal imaging agent targeting amyloid-beta (A beta) plaques in Alzheimers disease. Materials & methods: A new generation of hybrid contrast agents, based on gadolinium fluoride nanoparticles grafted with a pentameric luminescent-conjugated polythiophene, was designed, extensively characterized and evaluated in animal models of Alzheimers disease through MRI, two-photon microscopy and synchrotron x-ray phase-contrast imaging. Results & conclusion: Two different grafting densities of luminescent-conjugated polythiophene were achieved while preserving colloidal stability and fluorescent properties, and without affecting biodistribution. In vivo brain uptake was dependent on the blood-brain barrier status. Nevertheless, multimodal imaging showed successful A beta targeting in both transgenic mice and A beta fibril-injected rats.
17.	Li, Feng, et al. (author) Formation of nanotapes by co-assembly of triblock peptide copolymers and polythiophenes in aqueous solution 2009 In: SOFT MATTER. - : Royal Society of Chemistry (RSC). - 1744-683X .- 1744-6848. ; 5:8, s. 1668-1673 Journal article (peer-reviewed)abstract Nanotapes are formed by the co-assembly of triblock peptide copolymers with an amino acid-substituted polythiophene derivative (PTT). The driving force for the assembly is ionic interaction (complex coacervation). These nanotapes were visualized by atomic force microscopy and confocal laser scanning microscopy. The interactions between the triblock peptide copolymers and the PTT are also expressed in the steady state and time resolved fluorescence spectra. The steady-state spectra indicate that upon interaction with the peptide copolymer, the backbone of the PTT adopts a rather twisted, and definitely less, aggregated conformation. The time-resolved fluorescence decay studies further confirm this interpretation. The structure of these nanotapes at the mesoscopic scale depends, among other physical chemical parameters, on the concentrations of its constituents.
18.	Li, Feng, et al. (author) Nanowires Formed by the Co-Assembly of a Negatively Charged Low-Molecular Weight Gelator and a Zwitterionic Polythiophene 2010 In: ChemPhysChem. - : John Wiley and Sons, Ltd. - 1439-4235 .- 1439-7641. ; 11:9, s. 1956-1960 Journal article (peer-reviewed)abstract Conjugated organic nanowires have been prepared by co-assembling a carboxylate containing low-molecular weight gelator (LMWG) and an amino acid substituted polythiophene derivative (PTT). Upon introducing the zwitterionic polyelectrolyte PTT to a basic molecular solution of the organogelator, the negative charges on the LMWG are compensated by the positive charges of the PTT. As a result, nanowires form through co-assembly. These nanowires are visualized by both transmission electron microscopy (TEM) and atomic force microscopy (AFM). Depending on the concentration and ratio of the components these nanowires can be micrometers long. These measurements further suggest that the aggregates adopt a helical conformation. The morphology of these nanowires are studied with fluorescent confocal laser scanning microscopy (CLSM). The interactions between LMWG and PTT are characterized by steady-state and time-resolved fluorescence spectroscopy studies. The steady-state spectra indicate that the backbone of the PTT adopts a more planar and more aggregated conformation when interacting with LMWG. The time-resolved fluorescence decay studies confirm this interpretation.
19.	Lindgren, M., et al. (author) Luminescence and two-photon absorption cross section of novel oligomeric luminescent conjugated polythiophenes for diagnostics of amyloid fibrils 2010 In: Nonlinear Optics Quantum Optics. - : Old City Publishing Inc. - 1543-0537. ; 40:1-4, s. 241-251 Journal article (peer-reviewed)abstract Here we present the TPA cross section and quantum efficiencies of a series of novel oligomeric luminescent conjugated polythiophenes used for detection and spectral diagnostics of amyloid protein aggregates of the amyloid-beta peptide associated with Alzheimers disease. Specifically, these probes consist of pentameric or heptameric thiophenes derivatives with carboxylic substituents attached onto various thiophene rings. The probes absorbs over a broad range approx. 400-500 nm with quantum efficiency of approx. 20% in at neutral pH conditions, and also showed TPA cross sections of 5-50 GM in the range 700-840 nm, in the same order of magnitude as commonly used fluorescein derivatives. Importantly, the multiphoton excitation capabilities of LCPs provided excellent performance when compared to imaging using conventional "single photon" excitation. It is also demonstrated their utilization in both one-and two-photon excitation laser scanning microscope spectral imaging for diagnostics of Alzheimer disease pathology in ex vivo histological sections.
20.	Margalith, Ilan, et al. (author) Polythiophenes Inhibit Prion Propagation by Stabilizing Prion Protein (PrP) Aggregates 2012 In: Journal of Biological Chemistry. - : American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 287:23, s. 18872-18887 Journal article (peer-reviewed)abstract Luminescent conjugated polymers (LCPs) interact with ordered protein aggregates and sensitively detect amyloids of many different proteins, suggesting that they may possess antiprion properties. Here, we show that a variety of anionic, cationic, and zwitterionic LCPs reduced the infectivity of prion-containing brain homogenates and of prion-infected cerebellar organotypic cultured slices and decreased the amount of scrapie isoform of PrPC (PrPSc) oligomers that could be captured in an avidity assay. Paradoxically, treatment enhanced the resistance of PrPSc to proteolysis, triggered the compaction, and enhanced the resistance to proteolysis of recombinant mouse PrP(23-231) fibers. These results suggest that LCPs act as antiprion agents by transitioning PrP aggregates into structures with reduced frangibility. Moreover, ELISA on cerebellar organotypic cultured slices and in vitro conversion assays with mouse PrP(23-231) indicated that poly(thiophene-3-acetic acid) may additionally interfere with the generation of PrPSc by stabilizing the conformation of PrPC or of a transition intermediate. Therefore, LCPs represent a novel class of antiprion agents whose mode of action appears to rely on hyperstabilization, rather than destabilization, of PrPSc deposits.
21.	Nilsson, K. Peter R., et al. (author) Imaging distinct conformational states of amyloid-beta fibrils in Alzheimer's disease using novel luminescent probes 2007 In: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 2:8, s. 553-560 Journal article (peer-reviewed)abstract Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1–42 peptide (Aβ1–42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1–42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APP swe) of Alzheimer’s disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.
22.	Nilsson, Peter, et al. (author) Imaging distinct conformational states of amyloid-β fibrils in Alzheimer's disease using novel luminescent probes 2007 In: ACS Chemical Biology. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 2:8, s. 553-560 Journal article (peer-reviewed)abstract Using luminescent conjugated polyelectrolyte probes (LCPs), we demonstrate the possibility to distinguish amyloid-β 1-42 peptide (Aβ1-42) fibril conformations, by analyzing in vitro generated amyloid fibrils of Aβ1-42 formed under quiescent and agitated conditions. LCPs were then shown to resolve such conformational heterogeneity of amyloid deposits in vivo. A diversity of amyloid deposits depending upon morphology and anatomic location was illustrated with LCPs in frozen ex vivo brain sections from a transgenic mouse model (tg-APPswe) of Alzheimer's disease. Comparative LCP fluorescence showed that compact-core plaques of amyloid β precursor protein transgenic mice were composed of rigid dense amyloid. A more abundant form of amyloid plaque displayed morphology of a compact center with a protruding diffuse exterior. Surprisingly, the compact center of these plaques showed disordered conformations of the fibrils, and the exterior was composed of rigid amyloid protruding from the disordered center. This type of plaque appears to grow from more loosely assembled regions toward solidified amyloid tentacles. This work demonstrates how application of LCPs can prove helpful to monitor aggregate structure of in vivo formed amyloid deposits such as architecture, maturity, and origin.
23.	Nilsson, Peter, et al. (author) Structural typing of systemic amyloidoses by luminescent-conjugated polymer spectroscopy. 2010 In: The American journal of pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 176:2, s. 563-574 Journal article (peer-reviewed)abstract Most systemic amyloidoses are progressive and lethal, and their therapy depends on the identification of the offending proteins. Here we report that luminescent-conjugated thiophene polymers (LCP) sensitively detect amyloid deposits. The heterodisperse polythiophene acetic acid derivatives, polythiophene acetic acid (PTAA) and trimeric PTAA, emitted yellow-red fluorescence on binding to amyloid deposits, whereas chemically homogeneous pentameric formic thiophene acetic acid emitted green-yellow fluorescence. The geometry of LCPs modulates the spectral composition of the emitted light, thereby reporting ligand-induced steric changes. Accordingly, a screen of PTAA-stained amyloid deposits in histological tissue arrays revealed striking spectral differences between specimens. Blinded cluster assignments of spectral profiles of tissue samples from 108 tissue samples derived from 96 patients identified three nonoverlapping classes, which were found to match AA, AL, and ATTR immunotyping. We conclude that LCP spectroscopy is a sensitive and powerful tool for identifying and characterizing amyloid deposits.
24.	Simon, Rozalyn, et al. (author) Pentameric Thiophene-Based Ligands that Spectrally Discriminate Amyloid-b and Tau Aggregates Display Distinct Solvatochromism and Viscosity-Induced Spectral Shifts 2014 In: Chemistry - A European Journal. - : Wiley-VCH Verlagsgesellschaft. - 0947-6539 .- 1521-3765. ; 20:39, s. 12537-12543 Journal article (peer-reviewed)abstract A wide range of neurodegenerative diseases are characterized by the deposition of multiple protein aggregates. Ligands for molecular characterization and discrimination of these pathological hallmarks are thus important for understanding their potential role in pathogenesis as well as for clinical diagnosis of the disease. In this regard, luminescent conjugated oligothiophenes (LCOs) have proven useful for spectral discrimination of amyloid-beta (Aβ) and tau neurofibrillary tangles (NFTs), two of the pathological hallmarks associated with Alzheimer’s disease. Herein, the solvatochromism of a library of anionic pentameric thiophene-based ligands, as well as their ability to spectrally discriminate Aβ and tau aggregates, were investigated. Overall, the results from this study identified distinct solvatochromic and viscosity-dependent behavior of thiophene-based ligands that can be applied as indices to direct the chemical design of improved LCOs for spectral separation of Aβ and tau aggregates in brain tissue sections. The results also suggest that the observed spectral transitions of the ligands are due to their ability to conform by induced fit to specific microenvironments within the binding interface of each particular protein aggregate. We foresee that these findings might aid in the chemical design of thiophene-based ligands that are increasingly selective for distinct disease-associated protein aggregates.
25.	Snipstad, Sofie, et al. (author) Labeling nanoparticles : Dye leakage and altered cellular uptake 2017 In: Cytometry Part A. - : John Wiley & Sons. - 1552-4922 .- 1552-4930. ; 91:8, s. 760-766 Journal article (peer-reviewed)abstract In vitro and in vivo behavior of nanoparticles (NPs) is often studied by tracing the NPs with fluorescent dyes. This requires stable incorporation of dyes within the NPs, as dye leakage may give a wrong interpretation of NP biodistribution, cellular uptake, and intracellular distribution. Furthermore, NP labeling with trace amounts of dye should not alter NP properties such as interactions with cells or tissues. To allow for versatile NP studies with a variety of fluorescence-based assays, labeling of NPs with different dyes is desirable. Hence, when new dyes are introduced, simple and fast screening methods to assess labeling stability and NP-cell interactions are needed. For this purpose, we have used a previously described generic flow cytometry assay; incubation of cells with NPs at 4 and 37C. Cell-NP interaction is confirmed by cellular fluorescence after 37C incubation, and NP-dye retention is confirmed when no cellular fluorescence is detected at 4C. Three different NP-platforms labeled with six different dyes were screened, and a great variability in dye retention was observed. Surprisingly, incorporation of trace amounts of certain dyes was found to reduce or even inhibit NP uptake. This work highlights the importance of thoroughly evaluating every dye-NP combination before pursuing NP-based applications. © 2016 International Society for Advancement of Cytometry.
26.	Åslund, Andreas, 1978- (author) Designing thiophene-based fluorescent probes for the study of neurodegenerative protein aggregation diseases : From test tube to in vivo experiments 2009 Doctoral thesis (other academic/artistic)abstract Protein aggregation is an event related to numerous neurodegenerative diseases, such as Alzhemier’s disease and prion diseases. However little is known as to how and why the aggregates form and furthermore, the toxic specie may not be the mature fibril but an on route or off route specie towards mature aggregates. During this project molecular probes were synthesized that may shed some light to these questions. The probes are thiophene based and the technique used for detection was mainly fluorescence. It was shown that the previously established thiophene based in vitro staining technique is valid ex vivo and in vivo. This would not have been possible without the synthesis of a variety of functionalized polymeric thiophene based probes; their in vitro and ex vivo staining properties were taken into consideration when the design of the small oligomeric probes were decided upon. These probes were shown to spectrally distinguish different types of amyloid, pass the bloodbrain barrier within minutes and specifically and selectively stain protein aggregates in the brains of mice.
27.	Åslund, Andreas K. O., et al. (author) Nanoparticle delivery to the brain - By focused ultrasound and self-assembled nanoparticle-stabilized microbubbles 2015 In: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 220, s. 287-294 Journal article (peer-reviewed)abstract The blood-brain barrier (BBB) constitutes a significant obstacle for the delivery of drugs into the central nervous system(CNS). Nanoparticles have been able to partly overcome this obstacle and can thus improve drug delivery across the BBB. Furthermore, focused ultrasound in combination with gas filled microbubbles has opened the BBB in a temporospatial manner in animal models, thus facilitating drug delivery across the BBB. In the current study we combine these two approaches in our quest to develop a novel, generic method for drug delivery across the BBB and into the CNS. Nanoparticles were synthesized using the polymer poly(butyl cyanoacrylate) (PBCA), and such nanoparticles have been reported to cross the BBB to some extent. Together with proteins, these nanoparticles self-assemble into microbubbles. Using these novel microbubbles in combination with focused ultrasound, we successfully and safely opened the BBB transiently in healthy rats. Furthermore, we also demonstrated that the nanoparticles could cross the BBB and deliver a model drug into the CNS.
28.	Åslund, Andreas, et al. (author) Novel Pentameric Thiophene Derivatives for in Vitro and in Vivo Optical Imaging of a Plethora of Protein Aggregates in Cerebral Amyloidoses 2009 In: ACS CHEMICAL BIOLOGY. - : American Chemical Society (ACS). - 1554-8929 .- 1554-8937. ; 4:8, s. 673-684 Journal article (peer-reviewed)abstract Molecular probes for selective Identification of protein aggregates are important to advance our understanding of the molecular pathogenesis underlying cerebral amyloidoses. Here we report the chemical design of pentameric thiophene derivatives, denoted luminescent conjugated oligothiophenes (LCOs), which could be used for real-time visualization of cerebral protein aggregates in transgenic mouse models of neurodegenerative diseases by multiphoton microscopy. One of the LCOs, p-FTAA, could be utilized for ex vivo spectral assignment of distinct prion deposits from two, mouse-adapted prion strains. p-FTAA also revealed a transient soluble pre-fibrillar non-thioflavinophilic A beta-assemblies during in vitro fibrillation of A beta peptides. In brain tissue samples, A beta deposits and neurofibrillary tangles (NFTs) were readily identified by a strong fluorescence from p-FTAA and the LCO staining showed complete co-localliation with conventional antibodies (6E10 and AT8). In addition, a patchy islet-like staining of individual A beta plaque was unveiled by the anti-oligomer A11 antibody during co-staining with p-FTAA. The major hallmarks of Alzheimers disease, namely, A beta aggregates versus NFTs, could also be distinguished because of distinct emission spectra from p-FTAA. Overall, we demonstrate that LCOs can be utilized as powerful practical research tools for studying protein aggregation diseases and facilitate the study of amyloid origin, evolution and maturation, A beta-tau interactions, and pathogenesis both ex vivo and in vivo.
29.	Åslund, Andreas, et al. (author) Studies of luminescent conjugated polythiophene derivatives-Enhanced spectral discrimination of protein conformational states 2007 In: Bioconjugate chemistry. - : American Chemical Society (ACS). - 1043-1802 .- 1520-4812. ; 18:6, s. 1860-1868 Journal article (peer-reviewed)abstract Improved probes for amyloid fibril formation are advantageous for the early detection and better understanding of this disease-associated process. Here, we report a comparative study of eight luminescent conjugated polythiophene derivates (LCPs) and their discrimination of a protein (insulin) in the native or amyloid-like fibrillar state. For two of the LCPs, the synthesis is reported. Compared to their monomer-based analogues, trimer-based LCPs showed significantly better optical signal specificity for amyloid-like fibrils, seen from increased quantum yield and spectral shift. The trimer-based LCPs alone were highly quenched and showed little interaction with native insulin, as seen from analytical ultracentrifugation and insignificant spectral differences from the trimer-based LCP in buffered and native protein solution. Hence, the trimer-based LCPs showed enhanced discrimination between the amyloid-like fibrillar state and the corresponding native protein.
30.	Åslund, Andreas, 1978-, et al. (author) Synthesis of a pentathiophene fluorescent probe, 4’,3’’’-Bis-carboxymethyl-[2,2’;5’,2’’;5’’,2’’’;5’’’,2’’’‘]quinquethiophene-5,5’ 2010 In: Nature Protocols. - : Nature Publishing Group. - 1754-2189. Journal article (other academic/artistic)abstract Poly and oligo-thiophenes have previously been used for in vitro, ex vivo and in vivo imaging of protein aggregates. The probe (p-FTAA) has been developed for the purpose of in vivo staining of protein aggregates such as amyloid deposits. It effectively passes the blood brain barrier and imaging can be performed live with two-photon imaging or ex vivo. The straightforward synthesis of p-FTAA, including two Suzuki couplings, makes it an attractive probe for studies of most diseases involving protein aggregates.

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