| 1. |
- Astermark, Jan, et al.
(författare)
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Infrastructural considerations of implementing gene therapy for hemophilia in the Nordic context
- 2023
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Ingår i: Therapeutic advances in hematology. - 2040-6207. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite improvements in hemophilia care, challenges remain, including treatment burden and impaired quality of life. Gene therapy may overcome these. However, its introduction presents a challenge. Objectives: To outline a function-based gene therapy working model describing critical milestones associated with gene therapy handling, administration, and follow-up to facilitate and implement an effective infrastructure for gene therapy introduction. Design: Literature review and consensus discussion among Hemophilia Comprehensive Care centers (HCCCs) in the Nordic region. Methods: Representatives from six HCCCs sought to pinpoint milestones and key stakeholders for site readiness at the pre-, peri-, and post-infusion stages, including authority and genetically modified organism (GMO) product requirements, awareness, medical eligibility, logistics and product handling for infusion, laboratory monitoring, and follow-up. Results: A gene therapy transit map was developed with key stakeholders identified. The approach to prepare the vector will differ between the Nordic centers, but the contracted pharmacy unit will be a key stakeholder. Therefore, a pharmacy checklist for the implementation of gene therapy was developed. For the future, Advanced Therapy Medicinal Product centers will also be implemented. Patients’ expectations, commitments, and concerns need to be addressed repeatedly and education of patients and the expanded health-care professionals team will be the key to successful and optimal clinical management. Eligibility testing according to the product’s summary of product characteristics and frequent follow-up and monitoring post-infusion according to the World Federation of Hemophilia chart will be crucial. Conclusion: The approach to deliver gene therapy in the Nordic region will differ partly between the hemophilia centers, but the defined road map with checklists for the implementation of this advanced therapy will be applicable to all. The map may also serve as a platform for the use of future GMO product options both within and outside the area of hemophilia.
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| 2. |
- Birkedal, Maria, et al.
(författare)
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Effects of granivorous rodents on direct seeding of oak and beech in relation to site preparation and sowing date
- 2010
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Ingår i: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 259, s. 2382-2389
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Tidskriftsartikel (refereegranskat)abstract
- Planting bare-rooted seedlings is a rather expensive method to regenerate oak (Quercus robur) and beech (Fagus sylvatica). Direct seeding could reduce artificial regeneration costs substantially, but the method currently suffers from a number of problems, one of which is seed consumption by rodents. In the present study clear-cut areas in southern Sweden were prepared using one of four different mechanical site preparation methods - disc trenching, patch scarification, topsoil removal or mounding - - then manually sown with acorns and beech nuts. Acorns were sown in May and July 2006, and both acorns and beech nuts were sown in May 2007. Three years following sowing, best seedling establishment from viable acorns, 60-70%, was achieved after sowing in mounds in May, and the subsequent survival reached 90-100%. After the first growing season for beech, both seedling establishment and subsequent survival was lower than for oak, which coincides with a higher number of lost beech nuts at the excavation to investigate the fate of seeds. Granivorous rodents (Apodemus flavicollis, A. sylvaticus, Mus musculus, and Myodes glareolus) were live-trapped more frequently in the vicinity of slash piles compared to other micro-site features, such as uprooted stumps, snags and stones. In 2006, no connection was found between number of rodents captured and proportion of lost seeds, while in 2007 the two were in good accordance. No clear relationship was found between number of captured rodents, vegetation cover class and mechanical site preparation method. More rodents were captured in 2007 than in 2006, and there was an increase in captures from spring until late summer/autumn for both years, which was mirrored in the seedling establishment result from the three different times of sowing. Based on experiences from the present study the recommendation for successful direct seeding of oak on clear-cuts is a combination of mounding site preparation, removal of slash and sowing in May rather than July. However, the results indicate that successful direct seeding of beech is more difficult to achieve. (C) 2010 Elsevier B.V. All rights reserved.
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| 3. |
- Birkedal, Maria
(författare)
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Reforestation by direct seeding of beech and oak : influence of granivorous rodents and site preparation
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In southern Scandinavia there is a general desire to increase the amount of broadleaved forest using, for example, beech and oak, in order to preserve biodiversity and spread risk in the face of climate change. In order to realise this goal cheaper regeneration methods are needed. Although there are a number of uncertainties at present, direct seeding has the potential to fulfill this role. Two of the greatest obstacles to successful regeneration of beech and oak using direct seeding are seed removal by granivorous rodents and competition from ground vegetation. These issues need to be addressed before direct seeding can become a reliable regeneration method. The work described in papers I, II and IV in this thesis investigated the influence of site, sowing dates, rodent population densities, site preparation and repellents on rodent damage to sown beech nuts and acorns. Paper III describes a study which examined the effect of different mechanical site preparation methods, and different sowing dates, on the growth of young oak seedlings. Seedling establishment was more successful at large sites surrounded by mixed forests, compared to smaller areas surrounded by broadleaved forest (I, II). Oak seedling establishment was more successful than that of beech. Fewer acorns were lost and seedling establishment was better following spring sowing compared with summer sowing. In all years, more rodents were captured in the summer/autumn period than the spring. However, no clear correlation between rodent numbers and the success of direct seeding could be established. More rodents were captured in traps close to features providing cover, for example slash piles and the remains of stone walls. There were no clear relationships between the various mechanical site preparation treatments and rodent distribution and seed removal. In a laboratory study, mink excrement was found to have potential as a bank vole repellent, since it reduced consumption of beech nuts to half that of water soaked seeds, and reduced consumption of acorns was also indicated. No decrease in the germination of acorns treated with mink excrement was found, and there was only a minor negative effect on beech nuts (IV). The growth of young oak seedlings was better following sowing in spring than in summer, and mounding was the mechanical site preparation treatment most beneficial for oak seedling growth (III). The results indicate that successful direct seeding of oak on clear-cuts is most likely when acorns are sown at large sites situated in areas surrounded by coniferous forest, in spring rather than summer. In addition, more successful regeneration could be achieved through preparing sites by mounding, removing slash and sowing seeds treated with mink excrement. The data collected in this study indicate it is more difficult to achieve successful direct seeding of beech, than of oak.
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| 4. |
- Birkedal, Maria, et al.
(författare)
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Rodent impact on establishment of direct-seeded Fagus sylvatica, Quercus robur and Quercus petraea on forest land
- 2009
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Ingår i: Scandinavian Journal of Forest Research. - : Informa UK Limited. - 0282-7581 .- 1651-1891. ; 24, s. 298-307
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Tidskriftsartikel (refereegranskat)abstract
- Seed predation by granivorous rodents constitutes a major problem during reforestation using direct seeding. Acorns or beech nuts were sown at 14 different sites in Denmark and southern Sweden, and seedling establishment was inventoried during the first three growing seasons. Around the time of sowing, rodents were either snap-trapped or live-trapped. At some sites, perches for raptors were installed, and at other sites, signs of predation were investigated or predation was monitored by camera surveillance. Granivorous rodents had a profound negative influence on sowings, and the removal of beech nuts occurred rapidly following sowing. Establishment of oak was better when surroundings consisted of mixed forests rather than broadleaved forests. Fewer rodents were caught, and establishment was better, in large reforestation areas. Rodent captures indicated that forest edges, slash piles and stone wall remains were suitable rodent microhabitats. Snap-trapping or raptor perches did not result in increased oak establishment. Neither sowing in summer nor increased seeding depth decreased predation by rodents on beech nuts. In conclusion, seeds need protection from rodents immediately at the time of sowing. Choosing large regeneration areas combined with removal of suitable rodent habitats seems to be a practical alternative for the development of successful strategies for direct seeding.
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| 5. |
- Fields, James K., et al.
(författare)
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Antibodies targeting the shared cytokine receptor IL-1 receptor accessory protein invoke distinct mechanisms to block all cytokine signaling
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Ingår i: Cell Reports. - 2211-1247.
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Tidskriftsartikel (refereegranskat)abstract
- Interleukin-1 (IL-1)-family cytokines are potent modulators of inflammation, coordinating a vast array of immunological responses across innate and adaptive immune systems. Dysregulated IL-1-family cytokine signaling, however, is involved in a multitude of adverse health effects, such as chronic inflammatory conditions, autoimmune diseases, and cancer. Within the IL-1 family of cytokines, six—IL-1α, IL-1β, IL-33, IL-36α, IL-36β, and IL-36γ—require the IL-1 receptor accessory protein (IL-1RAcP) as their shared co-receptor. Common features of cytokine signaling include redundancy of signaling pathways, sharing of cytokines and receptors, pleiotropy of the cytokines themselves, and multifaceted immune responses. Accordingly, targeting multiple cytokines simultaneously is an emerging therapeutic strategy and can provide advantages over targeting a single cytokine pathway. Here, we show that two monoclonal antibodies, CAN10 and 3G5, which target IL-1RAcP for broad blockade of all associated cytokines, do so through distinct mechanisms and provide therapeutic opportunities for the treatment of inflammatory diseases.
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| 6. |
- Löf, Magnus, et al.
(författare)
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Direct seeding of Quercus robur L. for reforestation: The influence of mechanical site preparation and sowing date on early growth of seedlings
- 2009
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Ingår i: Forest Ecology and Management. - : Elsevier BV. - 0378-1127 .- 1872-7042. ; 258, s. 704-711
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Tidskriftsartikel (refereegranskat)abstract
- Compared with conventional planting, direct seeding of Quercus spp. is a method that can reduce the costs of reforestation considerably. However, interference from natural vegetation and predation on acorns contribute to regeneration failures. Mechanical site preparation has the potential to reduce both these problems. To study the influence of sowing date and of different mechanical site preparation treatments on early seedling growth, an experiment was carried out in storm-felled areas, formerly Norway spruce forests, in southern Sweden from May 2006 to September 2008. Five treatments were applied and acorns were planted in May and July 2006. The treatments were: disc trenching, patch scarification, topsoil removal, mounding and an undisturbed control. A delay of less than two months in seeding resulted in the equivalent of one year's growth reduction with respect to oak seedling's height and biomass. This could be explained by delayed emergence of seedlings, and by the dry conditions during summer seeding. The seedlings only exhibited a weak positive biomass growth response following disc trenching, patch scarification and top soil removal. In the latter case this might be explained by increased soil compaction and extensive removal of the humus layer. Site preparation by mounding resulted in good vegetation control, an increased biomass growth response and deeper seedling roots. In this treatment, we found high relative light levels near seedlings, reduced soil moisture and dry bulk density of the soil and higher soil temperatures. One or more of these environmental factors could have influenced the growth response. Whether this increased early growth rate persists throughout young stand development is, however, uncertain. (C) 2009 Elsevier B.V. All rights reserved.
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| 7. |
- Löf, Magnus, et al.
(författare)
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Restoring broadleaved forests in southern Sweden as climate changes
- 2012
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Ingår i: A Goal-Oriented Approach to Forest Landscape Restoration. - Dordrecht : Springer. - 9789400753372 ; , s. 373-391
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Bokkapitel (refereegranskat)abstract
- Temperate broadleaved forests in southern Sweden are important for biodiversity and policies have, so far, been concentrated on protecting the few valuable forests that still remain. This approach is now being challenged by rapid climate change. Using a vegetation model, we present transient and potential long-term predictions for changes in the natural distribution of different tree species and forest composition. Our model analyses show that temperate broadleaved tree species will be able to be established further north than their present distribution. In addition, this region will probably be an area of high species turnover, with the loss of boreal species and gains of temperate species. New broadleaved forests need to be restored in order to enhance reintegration. Current forest policies may not be relevant under a climate change scenario. Research is needed in climate change impacts on species and habitats, habitat restoration, migration of species, alternative silvicultural systems and efficient regeneration systems. It would probably be too expensive for the society to rely only on governmental resources for sustainable landscape level restorations programs. Instead a pragmatic approach, which considers the economic aspects of private forest owners, as well as other goals, should be adopted. In addition, policies must be based on a holistic understanding of the interactions between management, climate change and biodiversity.
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| 8. |
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| 9. |
- Svensson Birkedal, Gabriel, et al.
(författare)
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Crystal structure of N-glycosylated human glypican-1 core protein: Structure of two loops evolutionarily conserved in vertebrate glypican-1.
- 2012
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 287:17, s. 14040-14051
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Tidskriftsartikel (refereegranskat)abstract
- Glypicans are a family of cell-surface proteoglycans that regulate Wnt, hedgehog, bone morphogenetic protein and fibroblast growth factor signaling. Loss-of-function mutations in glypican core proteins and in glycosaminoglycan synthezing enzymes have revealed that glypican core proteins and their glycosaminoglycan chains are important in shaping animal development. Glypican core proteins consist of a stable alpha-helical domain containing 14 conserved Cys residues followed by a glycosaminoglycan attachment domain that becomes exclusively substituted with heparan sulfate (HS) and presumably adopts a random coil conformation. Removal of the alpha-helical domain results in almost exclusive addition of the glycosaminoglycan chondroitin sulfate, suggesting that factors in the alpha-helical domain promote assembly of HS. Glypican-1 is involved in brain development and is one of six members of the vertebrate family of glypicans. We expressed and crystallized N-glycosylated human glypican-1 lacking HS and N-glycosylated glypican-1 lacking the HS attachment domain. The crystal structure of glypican-1 was solved using crystals of selenomethionine labelled glypican-1 core protein lacking the HS domain. No additional electron density was observed for crystals of glypican-1 containing the HS attachment domain, and CD spectra of the two protein species were highly similar. The crystal structure of N- glycosylated human glypican-1 core protein at 2.5 Å, the first crystal structure of a vertebrate glypican, reveals the complete disulfide bond arrangement of the conserved Cys residues, and also extends the structural knowledge of glypicans for one alpha helix and two long loops. Importantly, the loops are evolutionarily conserved in vertebrate glypican-1 and one of them is involved in glycosaminoglycan class determination.
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