| 1. |
- Gustafsson, Erika, et al.
(författare)
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Directed evolution of chemotaxis inhibitory protein of Staphylococcus aureus generates biologically functional variants with reduced interaction with human antibodies
- 2010
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Ingår i: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134. ; 23:2, s. 91-101
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Tidskriftsartikel (refereegranskat)abstract
- Chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS) is a protein that binds and blocks the C5a receptor (C5aR) and formylated peptide receptor, thereby inhibiting the immune cell recruitment associated with inflammation. If CHIPS was less reactive with existing human antibodies, it would be a promising anti-inflammatory drug candidate. Therefore, we applied directed evolution and computational/rational design to the CHIPS gene in order to generate new CHIPS variants displaying lower interaction with human IgG, yet retaining biological function. The optimization was performed in four rounds: one round of random mutagenesis to add diversity into the CHIPS gene and three rounds of DNA recombination by Fragment INduced Diversity (FIND((R))). Every round was screened by phage selection and/or ELISA for decreased interaction with human IgG and retained C5aR binding. The mean binding of human anti-CHIPS IgG decreased with every round of evolution. For further optimization, new amino acid substitutions were introduced by rational design, based on the mutations identified during directed evolution. Finally, seven CHIPS variants with low interaction with human IgG and retained C5aR blocking capacity could be identified.
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| 2. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 3. |
- Bengtsson, Selma, 1984, et al.
(författare)
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Criteria for Future Marine Fuels
- 2012
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Ingår i: The IAME 2012 Conference September 2012.
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Konferensbidrag (refereegranskat)
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| 4. |
- Björklund, Verna, et al.
(författare)
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Early-onset group B streptococcal infections in five Nordic countries with different prevention policies, 1995 to 2019
- 2024
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Ingår i: Eurosurveillance. - : European Centre for Disease Control and Prevention (ECDC). - 1025-496X .- 1560-7917. ; 29:3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Neonatal early-onset disease caused by group B Streptococcus (GBS) is a leading cause of infant morbidity. Intrapartum antibiotic prophylaxis (IAP) is effective in preventing early-onset GBS disease, but there is no agreement on the optimal strategy for identifying the pregnant women requiring this treatment, and both risk-based prophylaxis (RBP) and GBS screening-based prophylaxis (SBP) are used.Aim: The aim of this study was to evaluate the effect of SBP as a public health intervention on the epidemiology of early-onset GBS infections.Methods: In 2012, Finland started the universal SBP, while Denmark, Iceland, Norway and Sweden continued with RBP. We conducted an interrupted time series analysis taking 2012 as the intervention point to evaluate the impact of this intervention. The incidences of early- and late-onset GBS infections during Period I (1995-2011) and Period II (2012-2019) were collected from each national register, covering 6,605,564 live births.Results: In Finland, a reduction of 58% in the incidence of early-onset GBS disease, corresponding to an incidence rate ratio (IRR) of 0.42 (95% CI: 0.34-0.52), was observed after 2012. At the same time, the pooled IRR of other Nordic countries was 0.89 (95% CI: 0.80-1.0), specifically 0.89 (95% CI: 0.70-1.5) in Denmark, 0.34 (95% CI: 0.15-0.81) in Iceland, 0.72 (95% CI: 0.59-0.88) in Norway and 0.97 (95% CI: 0.85-1.1) in Sweden.Conclusions: In this ecological study of five Nordic countries, early-onset GBS infections were approximately halved following introduction of the SBP approach as compared with RBP.
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| 5. |
- Dunér, Fredrik, et al.
(författare)
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Permeability, ultrastructural changes, and distribution of novel proteins in the glomerular barrier in early puromycin aminonucleoside nephrosis.
- 2010
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Ingår i: Nephron. Experimental nephrology. - : S. Karger AG. - 1660-2129. ; 116:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND/AIMS: It is still unclear what happens in the glomerulus when proteinuria starts. Using puromycin aminonucleoside nephrosis (PAN) rats, we studied early ultrastructural and permeability changes in relation to the expression of the podocyte-associated molecules nephrin, α-actinin, dendrin, and plekhh2, the last two of which were only recently discovered in podocytes. METHODS: Using immune stainings, semiquantitative measurement was performed under the electron microscope. Permeability was assessed using isolated kidney perfusion with tracers. Possible effects of ACE inhibition were tested. RESULTS: By day 2, some patchy foot process effacement, but no proteinuria, appeared. The amount of nephrin was reduced in both diseased and normal areas. The other proteins showed few changes, which were limited to diseased areas. By day 4, foot process effacement was complete and proteinuria appeared in parallel with signs of size barrier damage. Nephrin decreased further, while dendrin and plekhh2 also decreased but α-actinin remained unchanged. ACE inhibition had no significant protective effect. CONCLUSIONS: PAN glomeruli already showed significant pathology by day 4, despite relatively mild proteinuria. This was preceded by altered nephrin expression, supporting its pivotal role in podocyte morphology. The novel proteins dendrin and plekhh2 were both reduced, suggesting roles in PAN, whereas α-actinin was unchanged.
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| 6. |
- Gustafsson, Erika, et al.
(författare)
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Purification of truncated and mutated chemotaxis inhibitory protein of Staphylococcus aureus—an anti-inflammatory protein
- 2009
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Ingår i: Protein Expression and Purification. - : Elsevier BV. - 1046-5928. ; 63:2, s. 95-101
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Tidskriftsartikel (refereegranskat)abstract
- The Chemotaxis Inhibitory Protein of Staphylococcus aureus (CHIPS) binds and blocks the C5a receptor (C5aR) and formyl-peptide receptor (FPR). This way, CHIPS is a potent inhibitor of the immune cell recruitment associated with inflammation. Truncation of the protein and the introduction of mutations, shifts the expression towards the insoluble fraction of Escherichia coli, whereas the wild-type protein can be solubly expressed. A protocol for expression and tag independent purification of biologically active CHIPS variants has been established to enable further characterization of an improved CHIPS variant, called ADC-1004. The CHIPS variants were purified by washing of E. coli inclusion bodies followed by refolding and gel filtration. New techniques were utilized to optimize the purification process. Expression in inclusion bodies was increased by the use of Ultra Yield™ flasks and optimal refolding conditions were determined by the use of the iFOLD Refolding System 2™. The folding and biological activity of the purified proteins were analyzed by circular dichroism (CD) spectroscopy and flow cytometry, respectively, and compared to solubly produced CHIPS31–113 and wild-type CHIPS1–121. We show that the CHIPS variants produced in inclusion bodies can be refolded and purified to achieve equal biological activity as solubly produced CHIPS31–113 and wild-type CHIPS1–121. The truncation causes minor structural changes while purification from inclusion bodies or the soluble fraction does not further affect the structure.
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| 7. |
- Hanse, Eric, 1962, et al.
(författare)
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[The medical education in Gothenburg is being reformed. Professional development, research and internationalization]
- 2011
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Ingår i: Läkartidningen. - 0023-7205. ; 108:12, s. 669-73
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Tidskriftsartikel (refereegranskat)abstract
- The medical education at the Sahlgrenska Academy, University of Gothenburg, is being reformed by an emphasis on professional development, international contacts and research. Students’ professional development consists of five core areas: Communication and self-reflection, Leadership and teamwork, Ethical attitude, Human rights and gender issues, and a Scientific and critical attitude. A learning progression of students’ professional competence is organised by five process leaders, coordinating core learning objectives and examinations within the existing curriculum. By promoting international exchange, more than half of the students in undergraduate medical education have had international contacts. The Sahlgrenska Academy aims to promote medical students’ interest for research and to increase the percentage among medical doctors that have a PhD degree. A program for combining medical education with research and teaching is being launched along with a MD/PhD program for medical basic science and a special PhD/MD program.
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| 8. |
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| 9. |
- Haraldsson, Patrik, et al.
(författare)
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Framgångsrikt arbetsmiljöarbete på Medicin- och geriatrikkliniken Värnamo sjukhus
- 2021
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Kartläggning 2015 visade stora problem i arbetsmiljön på kliniken. Förbättringsarbete med Arbetsmiljöenheten som stöd i det systematiska arbetsmiljöarbete påbörjades omgående och har genomsyrat klinikens arbete under åren fram till idag. Strukturerad Multidisciplinär Arbetsmiljökartläggning (SMAK) metoden användes i det praktiska arbetet. Arbetsinsatserna visar stora effekter på sjuktal och möjligheten att rekrytera ny personal.
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| 10. |
- Ingelsten, Madeleine, 1978, et al.
(författare)
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Is Indoleamine 2,3-Dioxygenase Important for Graft Acceptance in Highly Sensitized Patients After Combined Auxiliary Liver-Kidney Transplantation?
- 2009
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Ingår i: Transplantation. - 0041-1337. ; 88:7, s. 911-919
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Tidskriftsartikel (refereegranskat)abstract
- Background. In the clinical setting, transplanted liver seems to protect other grafts from the same donor from rejection. Our previous findings suggest that an auxiliary liver transplantation a few hours before a renal transplantation not only inhibits hyperacute antibody-mediated rejection but also improves long-term kidney graft survival in sensitized recipients. Here, we investigated indoleamine 2,3-dioxygenase (IDO) activity, as one potential mechanism for liver-induced long-term acceptance of kidney grafts. Methods. Tryptophan degradation was measured to estimate IDO activity in patient sera and cell culture supernatants with high performance liquid chromatography. Gene expression in the grafted organs and cell lysates was studied using real time polymerase chain reaction analysis. Results. Tryptophan degradation increased in peripheral blood from patients undergoing combined auxiliary liver-kidney transplantation, whereas it decreased in patients after regular renal transplantation. A 100-fold increase in IDO mRNA, preceded by upregulation of the IDO-inducing cytokines tumor necrosis factor-[alpha], interleukin-1[beta], and interferon-[gamma], was observed in the transplanted organs after graft reperfusion in patients undergoing combined graft transplantation. Subsequent studies in vitro revealed that immature dendritic cells, but not hepatocytes, strongly activated IDO on maturation with tumor necrosis factor-[alpha], interleukin-1[beta], and interferon-[gamma]. Finally, serum from liver-transplanted patients elicited an even stronger IDO-activity in such cytokine-stimulated dendritic cells. Conclusions. Taken together these findings suggest that the liver-induced long-term acceptance seen in human combined auxiliary liver and kidney transplantation is at least partly mediated by IDO activity. (C) 2009 Lippincott Williams & Wilkins, Inc.
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