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- Trkulja, C. L., et al.
(författare)
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Rational antibody design for undruggable targets using kinetically controlled biomolecular probes
- 2021
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:16
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Tidskriftsartikel (refereegranskat)abstract
- Several important drug targets, e.g., ion channels and G protein-coupled receptors, are extremely difficult to approach with current antibody technologies. To address these targets classes, we explored kinetically controlled proteases as structural dynamics-sensitive druggability probes in native-state and disease-relevant proteins. By using low-Reynolds number flows, such that a single or a few protease incisions are made, we could identify antibody binding sites (epitopes) that were translated into short-sequence antigens for antibody production. We obtained molecular-level information of the epitope-paratope region and could produce high-affinity antibodies with programmed pharmacological function against difficult-to-drug targets. We demonstrate the first stimulus-selective monoclonal antibodies targeting the transient receptor potential vanilloid 1 (TRPV1) channel, a clinically validated pain target widely considered undruggable with antibodies, and apoptosis-inducing antibodies selectively mediating cytotoxicity in KRAS-mutated cells. It is our hope that this platform will widen the scope of antibody therapeutics for the benefit of patients.
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- Ivarsson, A., et al.
(författare)
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Elite female footballers' stories of sociocultural factors, emotions, and behaviours prior to anterior cruciate ligament injury
- 2019
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Ingår i: International Journal of Sport and Exercise Psychology. - : Informa UK Limited. - 1612-197X .- 1557-251X. ; 17:6, s. 630-646
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to examine how players' perceptions of sociocultural factors and intra- and interpersonal aspects of sporting experiences may have influenced the emotions, cognitions, and behaviours of elite female soccer players prior to the occurrence of ACL injuries. The research questions guiding the study were: (a) how did female elite soccer players perceive that their psychosocial experiences were related to their cognitive, physiological, and emotional states prior to their ACL injuries, and (b) how did the players feel their perceived states influenced their behaviours prior to injury occurrence. The participants consisted of the total population of female players (N = 18) competing in the Swedish women's elite league, who incurred a total ACL tear during the 2012 season. Using a semi-structured interview guide, all players were interviewed post-season. We represented the data using a storytelling approach of aggregated creative nonfiction. The aggregated stories showed sociocultural rules and expectations of overtraining and placing pressure on athletes to play even if they were not physically or psychologically fit. Responding to pressures with potentially risk-increasing behaviours might raise the probability of becoming injured through a number of pathways. Team managers, coaches, and members of the medical team are recommended to develop environments that stimulate the players to engage in adaptive stress-recovery and risk-decreasing behaviours.
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- Sadeghi, B., et al.
(författare)
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The effect of administration order of BU and CY on engraftment and toxicity in HSCT mouse model
- 2008
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Ingår i: Bone Marrow Transplantation. - : Springer Science and Business Media LLC. - 0268-3369 .- 1476-5365. ; 41:10, s. 895-904
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Tidskriftsartikel (refereegranskat)abstract
- Conditioning regimens are an important issue determining the outcome of hematopoietic stem cell transplantation (HSCT). Less toxicity, early engraftment and no relapse are the aims of efficient conditioning. Our objective was to investigate the long-term effects of BU-CY and their administration order on the toxicity and chimerism in a mouse model of HSCT. Female BALB/c mice were treated with either BU (15 mg/kg/day x 4)-CY (100 mg/kg/day x 2) or CY-BU. Treated mice were transplanted with Sca-1+ cells from male BALB/c mice. Until 90 days after HSCT, the animals were monitored for body weight and analyzed for cellular phenotype of the thymus, spleen and BM, total chimerism, the spleen chimerism of DCs and T regulatory (Treg) cells, and hepatotoxicity. BU-CY and CY-BU treatments exerted comparable myeloablative and immunosuppressive effects. The long-term engraftment of donor cells in the BM and thymus regeneration showed the same features in both groups. However, the two regimens differed; in general, hepatotoxicity and chimerism of DC and Treg cells. In the long term, BU-CY, but not CY-BU caused a marked decrease in body weight and a significant increase in the activities of the liver enzymes, particularly aspartate amino transferase (AST). We conclude that the alteration of the administration order of BU-CY to CY-BU not only gives the same level of engraftment but also reduces the toxicity of the conditioning regimen that might be valuable specially in young patients who are undergoing HSCT.
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