| 1. |
- Dupont, Chris L., et al.
(författare)
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Functional Tradeoffs Underpin Salinity-Driven Divergence in Microbial Community Composition
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:2, s. e89549-
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial community composition and functional potential change subtly across gradients in the surface ocean. In contrast, while there are significant phylogenetic divergences between communities from freshwater and marine habitats, the underlying mechanisms to this phylogenetic structuring yet remain unknown. We hypothesized that the functional potential of natural bacterial communities is linked to this striking divide between microbiomes. To test this hypothesis, metagenomic sequencing of microbial communities along a 1,800 km transect in the Baltic Sea area, encompassing a continuous natural salinity gradient from limnic to fully marine conditions, was explored. Multivariate statistical analyses showed that salinity is the main determinant of dramatic changes in microbial community composition, but also of large scale changes in core metabolic functions of bacteria. Strikingly, genetically and metabolically different pathways for key metabolic processes, such as respiration, biosynthesis of quinones and isoprenoids, glycolysis and osmolyte transport, were differentially abundant at high and low salinities. These shifts in functional capacities were observed at multiple taxonomic levels and within dominant bacterial phyla, while bacteria, such as SAR11, were able to adapt to the entire salinity gradient. We propose that the large differences in central metabolism required at high and low salinities dictate the striking divide between freshwater and marine microbiomes, and that the ability to inhabit different salinity regimes evolved early during bacterial phylogenetic differentiation. These findings significantly advance our understanding of microbial distributions and stress the need to incorporate salinity in future climate change models that predict increased levels of precipitation and a reduction in salinity.
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| 2. |
- Ekberg, Karin, et al.
(författare)
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C-Peptide replacement therapy and sensory nerve function in type 1 diabetic neuropathy
- 2007
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 30:1, s. 71-76
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - C-peptide replacement in animals results in amelioration of diabetes-induced functional and structural abnormalities in peripheral nerves. The present study was undertaken to examine whether C-peptide administration to patients with type 1 diabetes and peripheral neuropathy improves sensory nerve function. RESEARCH DESIGN AND METHODS - This was an exploratory, double-blinded, randomized, and placebo-controlled study with three study groups that was carried out at five centers in Sweden. C-peptide was given as a replacement dose (1.5 mg/day, divided into four subcutaneous doses) or a dose three times higher (4.5 mg/day) during 6 months. Neurological examination and neurophysiological measurements were performed before and after 6 months of treatment with C-peptide or placebo. RESULTS - The age of the 139 patients who completed the protocol was 44.2 ± 0.6 (mean ± SE) years and their duration of diabetes was 30.6 ± 0.8 years. Clinical neurological impairment (NIA) (score >7 points) of the lower extremities was present in 86% of the patients at baseline. Sensory nerve conduction velocity (SCV) was 2.6 ± 0.08 SD below body height-corrected normal values at baseline and improved similarly within the two C-peptide groups (P < 0.007). The number of patients responding with a SCV peak potential improvement >1.0 m/s was greater in C-peptide-treated patients than in those receiving placebo (P < 0.03). In the least severely affected patients (SCV < 2.5 SD below normal at baseline, n = 70) SCV improved by 1.0 m/s (P < 0.014 vs. placebo). NIA score and vibration perception both improved within the C-peptide-treated groups (P < 0.011 and P < 0.002). A1C levels (7.6 ± 0.1% at baseline) decreased slightly but similarly in C-peptide- and placebo-treated patients during the study. CONCLUSIONS - C-peptide treatment for 6 months improves sensory nerve function in early-stage type 1 diabetic neuropathy.
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| 3. |
- Fristrup, Peter, et al.
(författare)
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The Mechanism for the Rhodium-Catalyzed Decarbonylation of Aldehydes: A Combined Experimental and Theoretical Study
- 2008
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Ingår i: J.Am.Chem.Soc.. - : American Chemical Society (ACS). ; 130, s. 5206-5215
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Tidskriftsartikel (refereegranskat)abstract
- The mechanism for the rhodium-catalyzed decarbonylation of aldehydes was investigated by experimental techniques (Hammett studies and kinetic isotope effects) and extended by a computational study (DFT calculations). For both benzaldehyde and phenyl acetaldehyde derivatives, linear Hammett plots were obtained with positive slopes of +0.79 and +0.43, respectively, which indicate a buildup of negative charge in the selectivity-determining step. The kinetic isotope effects were similar for these substrates (1.73 and 1.77 for benzaldehyde and phenyl acetaldehyde, respectively), indicating that similar mechanisms are operating. A DFT (B3LYP) study of the catalytic cycle indicated a rapid oxidative addition into the C(O)−H bond followed by a rate-limiting extrusion of CO and reductive elimination. The theoretical kinetic isotope effects based on this mechanism were in excellent agreement with the experimental values for both substrates, but only when migratory extrusion of CO was selected as the rate-determining step.
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| 4. |
- Gøgsig, Thomas M, et al.
(författare)
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Mild and efficient nickel-catalyzed Heck reactions with electron-rich olefins.
- 2012
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 134:1, s. 443-52
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Tidskriftsartikel (refereegranskat)abstract
- A new efficient protocol for the nickel-catalyzed Heck reaction of aryl triflates with vinyl ethers is presented. Mild reaction conditions that equal those of the corresponding palladium-catalyzed Heck reaction are applied, representing a practical and more sustainable alternative to the conventional regioselective arylation of vinyl ethers. A catalytic system comprised of Ni(COD)(2) and 1,1'-bis(diphenylphosphino)ferrocene (DPPF) in combination with the tertiary amine Cy(2)NMe proved effective in the olefination of a wide range of aryl triflates. Both electron-deficient and electron-rich arenes proved compatible, and the corresponding aryl methyl ketone could be secured after hydrolysis in yields approaching quantitative. Good functional group tolerance was observed matching the characteristics of the analogous Pd-catalyzed Heck reaction. The high levels of catalytic activity were explained by the intermediacy of a cationic nickel(II) complex potentially responsible for the successive β-hydride elimination and base promoted catalyst regeneration. Although these elementary reactions are normally considered challenging, DFT calculations suggested this pathway to be favorable under the applied reaction conditions.
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| 5. |
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| 6. |
- Helge, Bormann, et al.
(författare)
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Guiding regional climate adaptation in coastal areas
- 2015
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Ingår i: Handbook of Climate Change Adaptation. - Berlin, Heidelberg : Springer Berlin Heidelberg. ; , s. 337-357
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Bokkapitel (refereegranskat)abstract
- Global climate change will have significant impacts on natural systems and human societies throughout the world. Therefore, climate adaptation strategies need to be developed at multiple scales. The Interreg IVB project “Climate Proof Areas” (CPA) has focused on climate adaptation at a regional scale in twelve pilot areas across four North Sea countries. It showed that the regional scale provides challenging opportunities of cross-sectoral climate adaptation. This paper gives an overview of experiences from the CPA pilot studies and embeds these in a generic approach for regional climate adaptation. Attention is paid to typical issues of coastal regions: water management, coastal protection, freshwater supply, land use, and spatial planning. Based on typical challenges of climate adaptation such as low sense of urgency, high degree of uncertainty regarding future development, and decision-making on a long term, a number of illustrative components are discussed which can contribute to the guidance of regional climate adaptation. These components cover different themes including communication issues, physical solutions, knowledge, and process-oriented approaches and result in a so-called adaptation toolkit. Finally we draw conclusions and derive recommendations about how certain approaches and policies at different levels can contribute to successful regional climate adaptation in coastal areas.
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| 7. |
- Hertzen, Erika, et al.
(författare)
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M1 Protein-Dependent Intracellular Trafficking Promotes Persistence and Replication of Streptococcus pyogenes in Macrophages
- 2010
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Ingår i: Journal of Innate Immunity. - : S. Karger AG. - 1662-811X .- 1662-8128. ; 2:6, s. 534-545
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes is an important human pathogen that causes a variety of diseases including life-threatening invasive diseases, such as toxic shock and deep tissue infections. Although S. pyogenes are classically considered extracellular pathogens, a clinical significance of an intracellular source has been emphasized. In patients with deep tissue infections, an intracellular reservoir of S. pyogenes within macrophages was shown to contribute to prolonged bacterial persistence. Here we demonstrate that intracellular survival of S. pyogenes in macrophages is associated with an M1 protein-dependent intracellular trafficking in the phagosomal-lysosomal pathway, which results in impaired fusion with lysosomes. The phagocytic vacuoles harbouring M1 protein-expressing bacteria not only served as a safe haven for the bacteria, but also as a replicating niche. An M1 protein-dependent modulation of macrophages was further supported by differences in NF-kappa B signalling between cells infected with either the wild-type or M1 protein-deficient strains, thereby indicating a suppressed inflammatory response when M1 protein was involved. Evidence of egress of bacteria out of their host cell and subsequent re-infection of new cells emphasize the importance of intracellular bacteria as a reservoir for dissemination of infection and continued tissue injury. Copyright (C) 2010 S. Karger AG, Basel
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| 8. |
- Kahn, Fredrik, et al.
(författare)
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Antibodies against a surface protein of Streptococcus pyogenes promote a pathological inflammatory response.
- 2008
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 4:9
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcal toxic shock syndrome (STSS) caused by Streptococcus pyogenes is a clinical condition with a high mortality rate despite modern intensive care. A key feature of STSS is excessive plasma leakage leading to hypovolemic hypotension, disturbed microcirculation and multiorgan failure. Previous work has identified a virulence mechanism in STSS where M1 protein of S. pyogenes forms complexes with fibrinogen that activate neutrophils to release heparin-binding protein (HBP), an inducer of vascular leakage. Here, we report a marked inter-individual difference in the response to M1 protein-induced HBP release, a difference found to be related to IgG antibodies directed against the central region of the M1 protein. To elicit massive HBP release, such antibodies need to be part of the M1 protein-fibrinogen complexes. The data add a novel aspect to bacterial pathogenesis where antibodies contribute to the severity of disease by promoting a pathologic inflammatory response.
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| 9. |
- Lidskog, Anna, et al.
(författare)
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Experimental and Computational Models for Side Chain Discrimination in Peptide–Protein Interactions
- 2021
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 27:42, s. 10883-10897
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Tidskriftsartikel (refereegranskat)abstract
- A bis(18-crown-6) Tröger's base receptor and 4-substituted hepta-1,7-diyl bisammonium salt ligands have been used as a model system to study the interactions between non-polar side chains of peptides and an aromatic cavity of a protein. NMR titrations and NOESY/ROESY NMR spectroscopy were used to analyze the discrimination of the ligands by the receptor based on the substituent of the ligand, both quantitatively (free binding energies) and qualitatively (conformations). The analysis showed that an all-anti conformation of the heptane chain was preferred for most of the ligands, both free and when bound to the receptor, and that for all of the receptor-ligand complexes, the substituent was located inside or partly inside of the aromatic cavity of the receptor. We estimated the free binding energy of a methyl- and a phenyl group to an aromatic cavity, via CH-π, and combined aromatic CH-π and π-π interactions to be −1.7 and −3.3 kJ mol−1, respectively. The experimental results were used to assess the accuracy of different computational methods, including molecular mechanics (MM) and density functional theory (DFT) methods, showing that MM was superior.
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| 10. |
- Loof, Torsten, et al.
(författare)
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Coagulation, an ancestral serine protease cascade, exerts a novel function in early immune defense
- 2011
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 118:9, s. 2589-2598
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Tidskriftsartikel (refereegranskat)abstract
- Phylogenetically conserved serine protease cascades play an important role in invertebrate and vertebrate immunity. The mammalian coagulation system can be traced back some 400 million years and shares homology with ancestral serine proteinase cascades that are involved in, for example, Toll receptor signaling in insects and release of antimicrobial peptides during hemolymph clotting. In the present study, we show that the induction of coagulation by bacteria leads to immobilization and killing of Streptococcus pyogenes bacteria inside the clot. The entrapment is mediated via cross-linking of bacteria to fibrin fibers by the action of coagulation factor XIII (fXIII), an evolutionarily conserved transglutaminase. In a streptococcal skin infection model, fXIII(-/-) mice developed severe signs of patho-logic inflammation at the local site of infection, and fXIII treatment of wild-type animals dampened bacterial dissemination during early infection. Bacterial killing and cross-linking to fibrin networks was also detected in tissue biopsies from patients with streptococcal necrotizing fasciitis, supporting the concept that coagulation is part of the early innate immune system.
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| 11. |
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| 12. |
- Madej, Malgorzata, et al.
(författare)
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The Effect of Boar Seminal Plasma on the Release of Prostaglandins and Interleukin-6 by Porcine Endometrial and Cervical Cells and Bovine Endometrial Cells
- 2012
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Ingår i: Reproduction in Domestic Animals. - : Wiley. - 0936-6768 .- 1439-0531. ; 47, s. 113-124
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Tidskriftsartikel (refereegranskat)abstract
- Artificial insemination (AI) of sows results in a significant elevation of prostaglandin F2a metabolite (PGFM) levels in peripheral plasma, whereas in mated sows such elevation is not seen. The aim of this study was to investigate whether boar seminal plasma (SP) has any effect on the release of PGFM, prostaglandin F2a (PGF2a), prostaglandin E2 (PGE2) or interleukin-6 (IL-6) by in vitro cultured porcine endometrial (epithelial pUE and stromal pUS), cervical (pCE and pCS) and bovine endometrial epithelial cells (bUE). This study shows that boar SP inhibits the release of PGFM, PGF2a and PGE2 by porcine endometrial and cervical cells and bovine endometrial cells after 3 and 24 h incubation. Boar SP stimulated IL-6 release by pUE, pUS and even bUE after 3 h incubation. Tumour necrosis factor a (TNFa) stimulated the release of IL-6 by pUS only after 24 h incubation, but in the presence of boar SP, this stimulation was attenuated. The overall results from these in vitro studies give us possibility to understand the difference in prostaglandin response between mated and inseminated sows. Furthermore, we demonstrated that frozen-stored epithelial and stromal cells from pig endometrium, as well as from the cervix are suitable for studying the effect of SP on the release of prostaglandins. The only prerequisite is to incubate these thawed cells with arachidonic acid as a source for the synthesis of prostaglandins. A similar effect of boar SP on porcine and bUE cells may suggest inter-species reactivity.
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| 13. |
- Norrby, Ulla, 1937, et al.
(författare)
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Health-related quality of life in children diagnosed with asthma, diabetes, juvenile chronic arthritis or short stature
- 2006
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Ingår i: Acta Paediatr. - : Wiley. - 0803-5253 .- 1651-2227. ; 95:4, s. 450-6
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Tidskriftsartikel (refereegranskat)abstract
- AIM: 1) To assess the reliability and validity of the Swedish version of the Child Health Questionnaire (CHQ), 2) to determine the correlation between children's and parents' responses to the CHQ, and 3) to describe and compare responses to the CHQ of four diagnostic groups. METHODS: A total of 199 Swedish children aged 9-16 with diagnoses of asthma (n = 53), diabetes (n = 48), short stature (n = 51) and juvenile chronic arthritis (JCA, n = 47) and their parents answered the CHQ and relevant validation instruments at a clinic check-up. Coefficient alphas were determined for all dimensions of the instrument, and all but four had acceptable to very good reliability (0.75-0.94). RESULTS: Concerning construct validity, the CHQ correlated significantly with appropriate dimensions of the validation instruments. In general, there were significant correlations between the children's and parents' responses. Comparisons between the diagnostic groups showed several significant differences. The short stature group had the highest quality of life and the JCA group the lowest. There were no sex differences, but children who had not reached puberty scored better on the dimensions of mental health and self-esteem. CONCLUSION: The Swedish version of the CHQ is a reliable and valid instrument. Furthermore, it is recommended to ask children themselves about their health-related quality of life.
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| 14. |
- Norrthon, Stefan, 1972-
(författare)
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Teaterrepetitionens interaktion : Professionella praktiker i ett repetitionsarbete från manus till föreställning
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis builds on three studies that explore a professional rehearsal process as situated interaction and as a longitudinal process. Primarily, the thesis contributes to the area of interactional linguistics, but it also seeks to contribute new knowledge to theatre studies. The empirical focus is on the participants’ interaction during the rehearsal process and how the performance develops procedurally over time. The main questions driving this research are: 1) What interactive, professional practices do the participants engage in during the rehearsal process, and in what way? 2) How is the script coordinated with other multimodal resources in the development from written text to performance?The theory and method used for this work is multimodal interaction analysis, that is, Ethnomethodological Conversation Analysis (EMCA) developed towards multimodal analysis of verbal and non-verbal resources in communication. The data collection was carried out at Riksteatern, Sweden’s largest touring theatre, where Effekten, by Lucy Prebble (2013), had its Swedish premiere in the fall of 2015. I followed rehearsals of a selection of five scenes from the first rehearsal day to opening night. The data consist of field notes, as well as video recordings of a total of 85 hours, filmed mainly with three cameras. In addition, the data include approximately four hours of audio recordings.The three studies focus on different practices involved in the theatrical rehearsal process. Study I follows the participants as they laminate (Goodwin 2018) eight lines in a scene where the characters are quarrelling. The aim is to document longitudinally how the actors develop, use and coordinate these and other multimodal resources in different phases of the rehearsal process. Study II focuses on one line in the script, with the aim of uncovering how the participants develop the performance by framing (Goffman 1974) various theatrical contexts in situated interactions and over time. Study III focuses on how the participants at the end of the rehearsal process create timing in transitions between rehearsed scenes by developing and using cues.The results show that, and how, rehearsing is a longitudinal process of collaborative creativity, in which the production team together, and moment by moment, develop the performance. Multimodal resources are used in different ways at different points in the process, and there is a shared authorship behind the theatrical performance. The results challenge previous research on theatre and theatre work, in which rehearsing has often been described as an asymmetric interaction between a director and an ensemble. Linguists’ interest in theatre has mainly focused on written scripts, also when the subject has been the relationship between scripts and performances. This thesis argues that the situated and collaborative process of rehearsing should be considered in order to understand the relationship between scripts and performances.
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| 15. |
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| 16. |
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| 17. |
- Påhlman, Lisa, et al.
(författare)
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Soluble M1 protein of Streptococcus pyogenes triggers potent T cell activation.
- 2008
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 10:2, s. 404-414
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus pyogenes of the M1 serotype is commonly associated with large outbreaks of invasive streptococcal infections and development of streptococcal toxic shock syndrome (STSS). The pathogenesis behind these infections is believed to involve bacterial superantigens that induce potent inflammatory responses, but the reason why strains of the M1 serotype are over-represented in STSS is still not understood. In the present investigation, we show that a highly purified soluble form of the M1 protein from S. pyogenes, which lacks the membrane-spanning region, is a potent inducer of T cell proliferation and release of Th1 type cytokines. M1 protein-evoked T cell proliferation was HLA class II-dependent but not MHC-restricted, did not require intracellular processing and was Vβ-restricted. Extensive mass spectrometry studies indicated that there were no other detectable proteins in the preparation. Taken together, our data demonstrate that soluble M1 protein is a novel streptococcal superantigen, which likely contributes to the excessive T cell activation and hyperinflammatory response seen in severe invasive streptococcal infections.
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| 19. |
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