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| 2. |
- Jönsson, Malin, et al.
(författare)
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CaRA – A multi-purpose phage display library for selection of calcium-regulated affinity proteins
- 2022
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Ingår i: New Biotechnology. - : Elsevier B.V.. - 1871-6784 .- 1876-4347. ; 72, s. 159-167
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Tidskriftsartikel (refereegranskat)abstract
- Protein activity regulated by interactions with metal ions can be utilized for many different purposes, including biological therapies and bioprocessing, among others. Calcium ions are known to interact with the frequently occurring EF-hand motif, which can alter protein activity upon binding through an induced conformational change. The calcium-binding loop of the EF-hand motif has previously been introduced into a small protein domain derived from staphylococcal Protein A in a successful effort to render antibody binding dependent on calcium. Presented here, is a combinatorial library for calcium-regulated affinity, CaRA, based on this domain. CaRA is the first alternative scaffold library designed to achieve novel target specificities with metal-dependent binding. From this library, several calcium-dependent binders could be isolated through phage display campaigns towards a set of unrelated target proteins (IgE Cε3-Cε4, TNFα, IL23, scFv, tPA, PCSK9 and HER3) useful for distinct applications. Overall, these monomeric CaRA variants showed high stability and target affinities within the nanomolar range. They displayed considerably higher melting temperatures in the presence of 1 mM calcium compared to without calcium. Further, all discovered binders proved to be calcium-dependent, with the great majority showing complete lack of target binding in the absence of calcium. As demonstrated, the CaRA library is highly capable of providing protein-binding domains with calcium-dependent behavior, independent of the type of target protein. These binding domains could subsequently be of great use in gentle protein purification or as novel therapeutic modalities.
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| 4. |
- Lindqvist, Magnus, et al.
(författare)
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Natural course of pollen-induced allergic rhinitis from childhood to adulthood : A 20-year follow up.
- 2023
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - 0105-4538 .- 1398-9995.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Allergic rhinitis (AR) is one of the most common chronic diseases worldwide. There are limited prospective long-term data regarding persistency and remission of AR. The objective of this study was to investigate the natural course of pollen-induced AR (pollen-AR) over 20 years, from childhood into early adulthood.METHODS: Data from 1137 subjects in the Barn/Children Allergi/Allergy Milieu Stockholm Epidemiologic birth cohort (BAMSE) with a completed questionnaire regarding symptoms, asthma, treatment with allergen immunotherapy (AIT) and results of allergen-specific IgE for inhalant allergens at 4, 8, 16 and 24 years were analyzed. Pollen-AR was defined as sneezing, runny, itchy or blocked nose; and itchy or watery eyes when exposed to birch and/or grass pollen in combination with allergen-specific IgE ≥0.35kUA /L to birch and/or grass.RESULTS: Approximately 75% of children with pollen-AR at 4 or 8 years had persistent disease up to 24 years, and 30% developed asthma. The probability of persistency was high already at low levels of pollen-specific IgE. The highest rate of remission from pollen-AR was seen between 16 and 24 years (21.5%); however, the majority remained sensitized. This period was also when pollen-specific IgE-levels stopped increasing and the average estimated annual incidence of pollen-AR decreased from 1.5% to 0.8% per year.CONCLUSION: Children with pollen-AR are at high risk of persistent disease for at least 20 years. Childhood up to adolescence seems to be the most dynamic period of AR progression. Our findings underline the close cross-sectional and longitudinal relationship between sensitization, AR and asthma.
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| 6. |
- Möller, Per, et al.
(författare)
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Data set on sedimentology, palaeoecology and chronology of Middle to Late Pleistocene deposits on the Taimyr Peninsula, Arctic Russia
- 2019
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Ingår i: Data in Brief. - : Elsevier. - 2352-3409. ; 25, s. 1-35
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Tidskriftsartikel (refereegranskat)abstract
- This Data in Brief paper contains data (including images) from Quaternary sedimentary successions investigated along the Bol'shaya Balakhnya River and the Luktakh-Upper Taimyra-Logata river system on southern Taimyr Peninsula, NW Siberia (Russia). Marine foraminifera and mollusc fauna composition, extracted from sediment samples, is presented. The chronology (time of deposition) of the sediment successions is reconstructed from three dating methods; (i) radiocarbon dating of organic detritus (from lacustrine/fluvial sediment) and molluscs (marine sediment) as finite ages (usually <42 000 years) or as non-finite ages (>42 000-48 000 years) on samples/sediments beyond the radiocarbon dating limit; (ii) Electron Spin Resonance (ESR) dating on marine molluscs (up to ages >400 000 years); (iii) Optically Stimulated Luminescence (OSL) dating, usually effective up to 100-150 0000 years. Terrestrial Cosmogenic Nuclide (TCN) exposure dating has been applied to boulders resting on top of moraine ridges (Ice Marginal Zones). See (Moller et al., 2019) (doi.org/10.1016/j.earscirev.2019.04.004) for interpretation and discussion of all data. (c) 2019 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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| 7. |
- Möller, Per, et al.
(författare)
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Glacial history and palaeo-environmental change of southern Taimyr Peninsula, Arctic Russia, during the Middle and Late Pleistocene
- 2019
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Ingår i: Earth-Science Reviews. - : Elsevier. - 0012-8252 .- 1872-6828. ; 196
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Forskningsöversikt (refereegranskat)abstract
- We here reconstruct a glacial and climate history of arctic NW Siberia for the last similar to 600,000 years, based on the stratigraphy and chronology of 35 studied river sections on the southern Taimyr Peninsula. From this strati graphic mosaic we have identified four glacial events, marked by tills/glaciotectonics, which are intercalated with mainly marine sediments deposited in proglacial settings during transitions from glacial conditions into subsequent interglacials/interstadials. The traces of early shelf-based Kara Sea Ice Sheet (KSIS) glaciations in marine isotope stages (MIS) 12-14 and 8 are sparsely preserved, but these ice advances are suggested to have terminated far south into the central Siberian uplands, as also was the case with the younger Taz glaciation (MIS 6). The inception phase of the latter glaciation was complex, with ice advancing into a proglacial marine basin both from the south (Putorana - Anabar uplands) and the north. The deglaciation leading into the Karginsky interglacial (MIS 5e) was marked by the development of the southerrunost ice-marginal zones (IMZs) on the Taimyr lowlands - the Urdakh and Sampesa IMZs. The most recent (late Pleistocene) glacial cycle is recorded by three successively smaller KSIS advances from the Kara Sea shelf onto Taimyr, of which only the first, during Early Zyryanka (MIS 5d), reached south of the Byrranga Mountains, with its maximum extent marked by the Jangoda - Syntabul - Severokokorsky IMZ. Retreat of the ice margin during MIS 5c-b was accompanied by deposition of glaciomarine sediment in the proglacial basin and deposition of large successions of delta sediments in the foothills of the Byrranga Motmtains, reaching a >= 100 m above present sea level. The region north of the Byrranga Mountains was subjected to two subsequent KSIS glaciations, during MIS 4 and MIS 2, while the area south of the Byrranga Mountains transitioned to a terrestrial environment from the Middle into the Lower Zyryanka, as evidenced by deposition of fluvial, aeolian and ice-complex (Yedoma) sediments.
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| 8. |
- von Witting, Emma, et al.
(författare)
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ADAPT as a single-domain bispecific scaffold capable of albumin-associated haf-life extension for therapeutic applications
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Albumin-binding fusion partners are frequently used as a means for the in vivo half-life extension of small therapeutic molecules that would normally be cleared very rapidly from circulation. However, in applications where small size is key, fusion to an additional molecule can be disadvantageous. ABD-Derived Affinity ProTeins (ADAPTs) are a type of scaffold proteins based on one of the albumin binding domains of streptococcal Protein G, with newly introduced binding specificities against numerous targets. Here we engineered this scaffold further and showed that this domain, as small as 6 kDa, can harbor two distinct binding surfaces and utilize them to interact with two targets simultaneously. These novel ADAPTs were developed to bind to both serum albumin as well as another clinically relevant target, thus circumventing the need for an albumin binding fusion partner. To accomplish this, we designed a novel phage display library and used it to successfully select for single-domain bispecific binders towards a panel of targets: TNFa, PSA (Prostate Specific Antigen), CRP (C-reactive protein), renin, angiogenin and insulin. Apart from successfully identifying bispecific binders for all targets, we also demonstrated the formation of the ternary complex of the ADAPT together with albumin and each of the four targets TNFa, PSA, angiogenin and insulin. This simultaneous binding of albumin and other targets presents an opportunity to combine the advantages of small molecules with those of larger ones allowing for lower cost of goods and non-invasive administration routes while still maintaining a sufficient in vivo half-life.
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| 9. |
- von Witting, Emma, et al.
(författare)
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Small Bispecific Affinity Proteins for Simultaneous Target Binding and Albumin-Associated Half-Life Extension
- 2021
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Ingår i: Molecular Pharmaceutics. - : American Chemical Society (ACS). - 1543-8384 .- 1543-8392. ; 18:1, s. 328-337
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Tidskriftsartikel (refereegranskat)abstract
- Albumin-binding fusion partners are frequently used as a means for the in vivo half-life extension of small therapeutic molecules that would normally be cleared very rapidly from circulation. However, in applications where small size is key, fusion to an additional molecule can be disadvantageous. Albumin-derived affinity proteins (ADAPTs) are a new type of scaffold proteins based on one of the albumin-binding domains of streptococcal protein G, with engineered binding specificities against numerous targets. Here, we engineered this scaffold further and showed that this domain, as small as 6 kDa, can harbor two distinct binding surfaces and utilize them to interact with two targets simultaneously. These novel ADAPTs were developed to possess affinity toward both serum albumin as well as another clinically relevant target, thus circumventing the need for an albumin-binding fusion partner. To accomplish this, we designed a phage display library and used it to successfully select for single-domain bispecific binders toward a panel of targets: TNFα, prostate-specific antigen (PSA), C-reactive protein (CRP), renin, angiogenin, myeloid-derived growth factor (MYDGF), and insulin. Apart from successfully identifying bispecific binders for all targets, we also demonstrated the formation of the ternary complex consisting of the ADAPT together with albumin and each of the five targets, TNFα, PSA, angiogenin, MYDGF, and insulin. This simultaneous binding of albumin and other targets presents an opportunity to combine the advantages of small molecules with those of larger ones allowing for lower cost of goods and noninvasive administration routes while still maintaining a sufficient in vivo half-life.
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| 10. |
- Wikström, Fredrik, 1964-, et al.
(författare)
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Packaging Strategies That Save Food : A Research Agenda for 2030
- 2019
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Ingår i: Journal of Industrial Ecology. - : Wiley-Blackwell. - 1088-1980 .- 1530-9290. ; 23:3, s. 532-540
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Tidskriftsartikel (refereegranskat)abstract
- Summary Thoroughly considering and optimizing packaging systems can avoid food loss and waste. We suggest a number of issues that must be explored and review the associated challenges. Five main issues were recognized through the extensive experience of the authors and engagement of multiple stakeholders. The issues promoted are classified as follows: (1) identify and obtain specific data of packaging functions that influence food waste; (2) understand the total environmental burden of product/package by considering the trade‐off between product protection and preservation and environmental footprint; (3) develop understanding of how these functions should be treated in environmental footprint evaluations; (4) improve packaging design processes to also consider reducing food waste; and (5) analyze stakeholder incentives to reduce food loss and waste. Packaging measures that save food will be important to fulfill the United Nations Sustainable Development goal to halve per capita global food waste at the retail and consumer levels and to reduce food losses along production and supply chains.
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