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| 2. |
- Brogårdh, Christina, et al.
(författare)
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Shortened constraint-induced movement therapy in subacute stroke - no effect of using a restraint : a randomized controlled study with independent observers
- 2009
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Ingår i: Journal of Rehabilitation Medicine. - : Stiftelsen Rehabiliteringsinformation. - 1650-1977 .- 1651-2081. ; 41:4, s. 231-236
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To examine the effect of using a mitt during shortened constraint-induced movement therapy for patients in the subacute phase after stroke.Subjects: Twenty-four patients with stroke (mean age 57.6 (standard deviation 8.5) years; average 7 weeks post-stroke) with mild to moderate impaired hand function.Methods: The patients were randomized to mitt use or no mitt use on the less affected hand for 90% of waking hours for 12 days. All patients received 3 h of arm and hand training per day for 2 weeks. Assessments were made by blinded observers using the modified Motor Assessment Scale, the Sollerman hand function test, the 2-Point Discrimination test and Motor Activity Log test.Results: Patients in both groups showed significant improvements in arm and hand motor performance and on self-reported motor ability after 2 weeks of therapy and at 3 months follow-up. However, no statistically significant differences between the groups were found in any measures at any point in time.Conclusion: In this study, no effect of using a restraint in patients with subacute stroke was found. Thus, this component in the constraint-induced therapy concept seems to be of minor importance for the outcome.
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| 3. |
- Broman, Karolina, Universitetslektor, 1969-, et al.
(författare)
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Gymnasiearbete (GARB) – an upper secondary school recepit before entering university studiies
- 2021
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Konferensbidrag (refereegranskat)abstract
- At Swedish upper secondary school, all students have to pass a mandatory course with thename “Gymnasiearbete”. This course is different from all other courses due to severalreasons, for example, being a project work related only to the programme orientation andwithout an explicit course curriculum. In this project, we have followed students from theNatural Science Programme taking this course, and studied their interest, engagement andepistemic beliefs. Through observations, interviews, and questionnaires, we have foundtriggers important to emphasise to make students more engaged and interested to enhancetheir knowledge. We will, from both a teacher and researcher perspective, discuss this courserelated to both affective and cognitive variables.
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| 5. |
- Brännström, Kristoffer, et al.
(författare)
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A Generic Method for Design of Oligomer-Specific Antibodies
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:3, s. e90857-
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Tidskriftsartikel (refereegranskat)abstract
- Antibodies that preferentially and specifically target pathological oligomeric protein and peptide assemblies, as opposed to their monomeric and amyloid counterparts, provide therapeutic and diagnostic opportunities for protein misfolding diseases. Unfortunately, the molecular properties associated with oligomer-specific antibodies are not well understood, and this limits targeted design and development. We present here a generic method that enables the design and optimisation of oligomer-specific antibodies. The method takes a two-step approach where discrimination between oligomers and fibrils is first accomplished through identification of cryptic epitopes exclusively buried within the structure of the fibrillar form. The second step discriminates between monomers and oligomers based on differences in avidity. We show here that a simple divalent mode of interaction, as within e. g. the IgG isotype, can increase the binding strength of the antibody up to 1500 times compared to its monovalent counterpart. We expose how the ability to bind oligomers is affected by the monovalent affinity and the turnover rate of the binding and, importantly, also how oligomer specificity is only valid within a specific concentration range. We provide an example of the method by creating and characterising a spectrum of different monoclonal antibodies against both the A beta peptide and alpha-synuclein that are associated with Alzheimer's and Parkinson's diseases, respectively. The approach is however generic, does not require identification of oligomer-specific architectures, and is, in essence, applicable to all polypeptides that form oligomeric and fibrillar assemblies.
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| 6. |
- Johansson, Ann-Sofi, et al.
(författare)
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Cytotoxicity of superoxide dismutase 1 in cultured cells is linked to Zn2+ chelation
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:4, s. e36104-
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Tidskriftsartikel (refereegranskat)abstract
- Neurodegeneration in protein-misfolding disease is generally assigned to toxic function of small, soluble protein aggregates. Largely, these assignments are based on observations of cultured neural cells where the suspect protein material is titrated directly into the growth medium. In the present study, we use this approach to shed light on the cytotoxic action of the metalloenzyme Cu/Zn superoxide dismutase 1 (SOD1), associated with misfolding and aggregation in amyotrophic lateral sclerosis (ALS). The results show, somewhat unexpectedly, that the toxic species of SOD1 in this type of experimental setting is not an aggregate, as typically observed for proteins implicated in other neuro-degenerative diseases, but the folded and fully soluble apo protein. Moreover, we demonstrate that the toxic action of apoSOD1 relies on the protein's ability to chelate Zn(2+) ions from the growth medium. The decreased cell viability that accompanies this extraction is presumably based on disturbed Zn(2+) homeostasis. Consistently, mutations that cause global unfolding of the apoSOD1 molecule or otherwise reduce its Zn(2+) affinity abolish completely the cytotoxic response. So does the addition of surplus Zn(2+). Taken together, these observations point at a case where the toxic response of cultured cells might not be related to human pathology but stems from the intrinsic limitations of a simplified cell model. There are several ways proteins can kill cultured neural cells but all of these need not to be relevant for neurodegenerative disease.
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| 7. |
- Lindhagen-Persson, Malin, et al.
(författare)
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Amyloid-β oligomer specificity mediated by the IgM isotype : implications for a specific protective mechanism exerted by endogenous auto-antibodies
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 5:11, s. e13928-
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Tidskriftsartikel (refereegranskat)abstract
- Background Alzheimers disease (AD) has been strongly linked to an anomalous self-assembly of the amyloid-β peptide (Aβ). The correlation between clinical symptoms of AD and Aβ depositions is, however, weak. Instead small and soluble Aβ oligomers are suggested to exert the major pathological effects. In strong support of this notion, immunological targeting of Aβ oligomers in AD mice-models shows that memory impairments can be restored without affecting the total burden of Aβ deposits. Consequently a specific immunological targeting of Aβ oligomers is of high therapeutic interest. Methodology/Principal Findings Previously the generation of conformational-dependent oligomer specific anti-Aβ antibodies has been described. However, to avoid the difficult task of identifying a molecular architecture only present on oligomers, we have focused on a more general approach based on the hypothesis that all oligomers expose multiple identical epitopes and therefore would have an increased binding to a multivalent receptor. Using the polyvalent IgM immunoglobulin we have developed a monoclonal anti-Aβ antibody (OMAB). OMAB only demonstrates a weak interaction with Aβ monomers and dimers having fast on and off-rate kinetics. However, as an effect of avidity, its interaction with Aβ-oligomers results in a strong complex with an exceptionally slow off-rate. Through this mechanism a selectivity towards Aβ oligomers is acquired and OMAB fully inhibits the cytotoxic effect exerted by Aβ(1-42) at highly substoichiometric ratios. Anti-Aβ auto-antibodies of IgM isotype are frequently present in the sera of humans. Through a screen of endogenous anti-Aβ IgM auto-antibodies from a group of healthy individuals we show that all displays a preference for oligomeric Aβ. Conclusions/Significance Taken together we provide a simple and general mechanism for targeting of oligomers without the requirement of conformational-dependent epitopes. In addition, our results suggest that IgM anti-Aβ auto-antibodies may exert a more specific protective mechanism in vivo than previously anticipated.
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| 8. |
- Olofsson, Anders, et al.
(författare)
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Quenched hydrogen/deuterium exchange NMR characterization of amyloid-β peptide aggregates formed in the presence of Cu2+ or Zn2
- 2009
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Ingår i: The FEBS Journal. - : Wiley InterScience. - 1742-464X .- 1742-4658. ; 276:15, s. 4051-4060
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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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| 9. |
- Ouberai, Myriam, et al.
(författare)
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Clicked tacrine conjugates as acetylcholinesterase and β-amyloid directed compounds
- 2011
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Ingår i: Organic and biomolecular chemistry. - : The Royal Society of Chemistry. - 1477-0520 .- 1477-0539. ; 9:4, s. 1140-1147
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Tidskriftsartikel (refereegranskat)abstract
- The multifaceted nature of Alzheimer's disease (AD) has led to the development of multi-targeted compounds based on the classical AD drug, tacrine, first known to inhibit the acetylcholine-degrading enzyme acetylcholinesterase (AChE). In the present work, we explore the potentiality of multimers of tacrine in this field. The synthesis using the so-called "click chemistry" and the in vitro study of the conjugates are described. Two or four copies of the tacrine molecule are "clicked" on a constrained cyclopeptide template proven to be a convenient tool for multimeric presentation. The multimers significantly inhibit self-induced amyloid fibril formation from Aβ(40) at low inhibitor to Aβ molar ratios at which the tacrine monomer is fully inactive (Thioflavin T assays and AFM observation). Moreover, they have the capacity to bind to Aβ(40) fibrils (SPR assays) while retaining the AChE inhibitory activity of the parent tacrine.
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