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- 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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- Allard, Christina, 1971-, et al.
(författare)
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Girjas Reindeer Herding Community v. Sweden : Analysing the Merits of the Girjas Case
- 2021
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Ingår i: Arctic Review on Law and Politics. - Oslo : Cappelen Damm AS. - 1891-6252 .- 2387-4562. ; 12, s. 56-79
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Tidskriftsartikel (refereegranskat)abstract
- For the first time in the Swedish Supreme Court, a small Sami reindeer herding community has won an important victory affirming the community’s small game hunting and fishing rights. Because of protracted use and the concept of immemorial prescription, the Court recognised the community’s exclusive hunting and fishing rights, including the right to lease these rights to others. Such leases have long been prohibited by legislation and the State has retained its powers to administer such leases. This case signifies a considerable development in the area of Sami law. In its decision, the Supreme Court made some adjustments to the age-old doctrine of immemorial prescription, and provided insights into how historic evidence should be evaluated when the claimant is an Indigenous people. A common motivator for these adjustments is an enhanced awareness of international standards protecting Indigenous peoples and minorities. Even ILO Convention No. 169 – the only legally binding convention concerning Indigenous rights, but which Sweden has not yet ratified – is relevant when it comes to evaluating Sami customary uses. The Court addressed the problem of gaps in the historical material and used evidence from other parts of Swedish Lapland and adjacent time-periods, making reasonable assumptions to fill in these gaps. The Court imposes on the State the burden of proof regarding the extinguishment of already established Sami rights, as well as proof that extinguishment by legislation or expropriation, is “clear and definitive”. These conditions were not met in this case.
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- Allard, Christina, 1971-, et al.
(författare)
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Girjas sameby mot staten: En analys av Girjasdomen
- 2020
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Ingår i: Svensk Juristtidning. - : Föreningen för utgivande av Svensk Juristtidning. - 0039-6591. ; :5, s. 429-452
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Tidskriftsartikel (refereegranskat)abstract
- I januari 2020 avgjorde Högsta domstolen det s.k. Girjasmålet, där rätten att upplåta småviltsjakt och fiske i fjällområdena prövats. Stridigheter om huruvida det är staten eller samebyn som har rätt att göra sådana upplåtelser har pågått i decennier och har inte gått att lösa politiskt. I artikeln analyseras domen och vilka konsekvenser den får; domens längd och komplexitet motiverar en längre rättsfallsanalys. Det konstateras att domen klargör viktiga förhållanden såsom att samiska markrättigheter upparbetats genom urminnes hävd och att ILO:s konvention nr 169 om urfolks rättigheter i delar är bindande även om den inte har ratificerats. Domen innebär att en betydande rättsutveckling skett inom det samerättsliga området.
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- Asp-Onsjö, Lisa, 1951, et al.
(författare)
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Om examensarbetet på grundlärarprogrammet
- 2019
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Ingår i: Vetenskaplighet i högre utbildning. - Lund : Studentlitteratur AB. - 9789144130637
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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- Avango, Dag, 1965-, et al.
(författare)
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Heritage for the future : narrating abandoned mining sites
- 2022
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Ingår i: Resource extraction and arctic communities. - Cambridge : Cambridge University Press. - 9781009110044 ; , s. 206-228, s. 206-228
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Bokkapitel (refereegranskat)abstract
- This chapter compares the post-extraction dynamics of two mining regions in the Fennoscandinavian Arctic: the Pite valley, Sweden, and Kolari, Finland. In 1946 the Swedish mining company Boliden closed a mine in Laver, which became a ghost town. Decades later, state authorities tried to turn Laver into a cultural heritage site. Boliden joined the effort to support its plan to re-start mining at Laver, a project that has, however, become highly controversial. The Finnish case deals with a similar controversy. Hannukainen mining company wants to re-open an iron ore mine that was in operation 1975-1990. As part of their strategy to gain acceptance for re-opening, the company and supporters of the project have mobilized the history of the mining sites and argues mining is a core element of the heritage of the Kolar municipality. Both cases have generated tension regarding the type of history and heritage of these regions: those of reindeer herding by Sámi and other local communities, or that of extractive industries? The cases show that heritage making can be useful, but it can also be a source of conflict, further underscoring the importance of the long-term view of extraction.
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- Brännström, Fredrik, et al.
(författare)
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Multidisciplinary team conferences promote treatment according to guidelines in rectal cancer
- 2015
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 54:4, s. 447-453
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Tidskriftsartikel (refereegranskat)abstract
- Background. Multidisciplinary team (MDT) conferences have been introduced into standard cancer care, though evidence that it benefits the patient is weak. We used the national Swedish Rectal Cancer Register to evaluate predictors for case discussion at a MDT conference and its impact on treatment.Material and methods. Of the 6760 patients diagnosed with rectal cancer in Sweden between 2007 and 2010, 78% were evaluated at a MDT. Factors that influenced whether a patient was discussed at a preoperative MDT conference were evaluated in 4883 patients, and the impact of MDT evaluation on the implementation of preoperative radiotherapy was evaluated in 1043 patients with pT3c-pT4 M0 tumours, and in 1991 patients with pN+ M0 tumours.Results. Hospital volume, i.e. the number of rectal cancer surgical procedures performed per year, was the major predictor for MDT evaluation. Patients treated at hospitals with < 29 procedures per year had an odds ratio (OR) for MDT evaluation of 0.15. Age and tumour stage also influenced the chance of MDT evaluation. MDT evaluation significantly predicted the likelihood of being treated with preoperative radiotherapy in patients with pT3c-pT4 M0 tumours (OR 5.06, 95% CI 3.08–8.34), and pN+ M0 (OR 3.55, 95% CI 2.60–4.85), even when corrected for co-morbidity and age.Conclusion. Patients with rectal cancer treated at high-volume hospitals are more likely to be discussed at a MDT conference, and that is an independent predictor of the use of adjuvant radiotherapy. These results indirectly support the introduction into clinical practice of discussing all rectal cancer patients at MDT conferences, not least those being treated at low-volume hospitals.
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- Brännström, Kristoffer, et al.
(författare)
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Ca2+ enhances Aβ polymerization rate and fibrillar stability in a dynamic manner
- 2013
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Ingår i: Biochemical Journal. - : Portland Press. - 0264-6021 .- 1470-8728. ; 450, s. 189-197
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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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