| 1. |
- Johansson, Maria U, et al.
(author)
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Structure, specificity, and mode of interaction for bacterial albumin-binding modules.
- 2002
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In: Journal of Biological Chemistry. - 1083-351X .- 0021-9258. ; 277:10, s. 8114-8120
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Journal article (peer-reviewed)abstract
- We have determined the solution structure of an albumin binding domain of protein G, a surface protein of group C and G streptococci. We find that it folds into a left handed three-helix bundle similar to the albumin binding domain of protein PAB from Peptostreptococcus magnus. The two domains share 59% sequence identity, are thermally very stable, and bind to the same site on human serum albumin. The albumin binding site, the first determined for this structural motif known as the GA module, comprises residues spanning the first loop to the beginning of the third helix and includes the most conserved region of GA modules. The two GA modules have different affinities for albumin from different species, and their albumin binding patterns correspond directly to the host specificity of C/G streptococci and P. magnus, respectively. These studies of the evolution, structure, and binding properties of the GA module emphasize the power of bacterial adaptation and underline ecological and medical problems connected with the use of antibiotics.
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| 2. |
- Berglund, Per, et al.
(author)
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Linking Education and Research : A Roadmap for Higher Education Institutions at the Dawn of the Knowledge Society
- 2019
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In: Linking education and research. - Basel, Switzerland : MDPI. ; , s. 11-33
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Book chapter (other academic/artistic)abstract
- In an era characterized by a move towards a “knowledge society”, universities are central in fostering “knowledgeability”, that is the reflexive understanding of knowledge in knowledge societies. The objective of “knowledgeability” can be met through creating a stronger link between education and research. Furthermore, overall student performance, for example in critical thinking and problem solving, can be improved if research-related activities are incorporated into the curriculum.The aim of this paper is to use international examples to discuss the research- education nexus from four different perspectives, namely context, policy, implementation and quality, with case studies from higher education institutions in Singapore and Sweden.We suggest that different integrative technologies can be used to enhance the links, but it will be essential to consider the inputs of training, service and support in using new technology. Interestingly, the act of evaluating the link between education and research will increase awareness of this linkage by stakeholders involved in both education and research. In turn the link can be strengthened, contributing to increased quality in both education and research.
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| 3. |
- Elksnis, Andris, et al.
(author)
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Pharmacological Inhibition of NOX4 Improves Mitochondrial Function and Survival in Human Beta-Cells
- 2021
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In: Biomedicines. - : MDPI. - 2227-9059. ; 9:12
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Journal article (peer-reviewed)abstract
- Previous studies have reported beneficial effects of NADPH oxidase 4 (NOX4) inhibition on beta-cell survival in vitro and in vivo. The mechanisms by which NOX4 inhibition protects insulin producing cells are, however, not known. The aim of the present study was to investigate the effects of a pharmacological NOX4 inhibitor (GLX7013114) on human islet and EndoC-beta H1 cell mitochondrial function, and to correlate such effects with survival in islets of different size, activity, and glucose-stimulated insulin release responsiveness. We found that maximal oxygen consumption rates, but not the rates of acidification and proton leak, were increased in islets after acute NOX4 inhibition. In EndoC-beta H1 cells, NOX4 inhibition increased the mitochondrial membrane potential, as estimated by JC-1 fluorescence; mitochondrial reactive oxygen species (ROS) production, as estimated by MitoSOX fluorescence; and the ATP/ADP ratio, as assessed by a bioluminescent assay. Moreover, the insulin release from EndoC-beta H1 cells at a high glucose concentration increased with NOX4 inhibition. These findings were paralleled by NOX4 inhibition-induced protection against human islet cell death when challenged with high glucose and sodium palmitate. The NOX4 inhibitor protected equally well islets of different size, activity, and glucose responsiveness. We conclude that pharmacological alleviation of NOX4-induced inhibition of beta-cell mitochondria leads to increased, and not decreased, mitochondrial ROS, and this was associated with protection against cell death occurring in different types of heterogeneous islets. Thus, NOX4 inhibition or modulation may be a therapeutic strategy in type 2 diabetes that targets all types of islets.
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| 4. |
- Elksnis, Andris, et al.
(author)
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The selective NOX4 inhibitor GLX7013159 decreases blood glucose concentrations and human beta-cell apoptotic rates in diabetic NMRI nu/nu mice transplanted with human islets
- 2023
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In: Free radical research. - : Taylor & Francis. - 1071-5762 .- 1029-2470. ; 57:6-12, s. 460-469
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Journal article (peer-reviewed)abstract
- NADPH oxidase 4 (NOX4) inhibition has been reported to mitigate diabetes-induced beta-cell dysfunction and improve survival in vitro, as well as counteract high-fat diet-induced glucose intolerance in mice. We investigated the antidiabetic effects of the selective NOX4 inhibitor GLX7013159 in vivo in athymic diabetic mice transplanted with human islets over a period of 4 weeks. The GLX7013159-treated mice achieved lower blood glucose and water consumption throughout the treatment period. Furthermore, GLX7013159 treatment resulted in improved insulin and c-peptide levels, better insulin secretion capacity, as well as in greatly reduced apoptotic rates of the insulin-positive human cells, measured as colocalization of insulin and cleaved caspase-3. We conclude that the antidiabetic effects of NOX4 inhibition by GLX7013159 are observed also during a prolonged study period in vivo and are likely to be due to an improved survival and function of the human beta-cells.
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| 5. |
- Källberg, Eva, et al.
(author)
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S100A9 Interaction with TLR4 Promotes Tumor Growth
- 2012
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In: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 7:3, s. e34207-
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Journal article (peer-reviewed)abstract
- By breeding TRAMP mice with S100A9 knock-out (S100A9(-/-)) animals and scoring the appearance of palpable tumors we observed a delayed tumor growth in animals devoid of S100A9 expression. CD11b(+) S100A9 expressing cells were not observed in normal prostate tissue from control C57BL/6 mice but were readily detected in TRAMP prostate tumors. Also, S100A9 expression was observed in association with CD68(+) macrophages in biopsies from human prostate tumors. Delayed growth of TRAMP tumors was also observed in mice lacking the S100A9 ligand TLR4. In the EL-4 lymphoma model tumor growth inhibition was observed in S100A9(-/-) and TLR4(-/-), but not in RAGE(-/-) animals lacking an alternative S100A9 receptor. When expression of immune-regulating genes was analyzed using RT-PCR the only common change observed in mice lacking S100A9 and TLR4 was a down-regulation of TGF beta expression in splenic CD11b(+) cells. Lastly, treatment of mice with a small molecule (ABR-215050) that inhibits S100A9 binding to TLR4 inhibited EL4 tumor growth. Thus, S100A9 and TLR4 appear to be involved in promoting tumor growth in two different tumor models and pharmacological inhibition of S100A9-TLR4 interactions is a novel and promising target for anti-tumor therapies.
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| 6. |
- Leden, Lars, et al.
(author)
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Safety and accessibility effects of code modifications and traffic calming of an arterial road
- 2006
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In: Accident Analysis and Prevention. - : Elsevier BV. - 0001-4575 .- 1879-2057. ; 38:3, s. 455-461
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Journal article (peer-reviewed)abstract
- The European Road E12 through the community center of Storuman, Sweden was reconstructed in 1999 and 2000. Pedestrian walkways, traffic islands, chicanes of a type referred to as "Danish buns", a roundabout and a two-directional cycle track along the E12 were installed. The purpose of the reconstruction was to improve safety for pedestrians and bicyclists, primarily for children, the elderly and the disabled, and to reduce the barrier effect of the E12 thoroughfare. In May 2000, the code governing the conduct of drivers at marked crosswalks in Sweden became stricter to improve safety and mobility for pedestrians. The combined effect of reconstructions and change of code was analyzed. Traffic behavior was studied at the intersection where the roundabout was constructed. Yield behavior towards pedestrians changed significantly. The difference was even greater with respect to yielding to child bicyclists - from 6% before to 84% after - even though the code change only related to pedestrians. Crash data analysis suggests a minor increase in fall injuries after reconstructions and change of code. Measures of speed, behavioral studies, questionnaires, face-to-face interviews and crash data analysis suggest that safety has increased not only along the E12 but also along adjacent roads. The final conclusion is that a bypass is not needed in a case like Storuman. Traffic calming of the main arterial through the town seems sufficient.
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| 7. |
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| 8. |
- Wang, Xuan, 1984-, et al.
(author)
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The novel NADPH oxidase 4 selective inhibitor GLX7013114 counteracts human islet cell death in vitro
- 2018
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In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 13:9
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Journal article (peer-reviewed)abstract
- It has been proposed that pancreatic beta-cell dysfunction in type 2 diabetes is promoted by oxidative stress caused by NADPH oxidase (Nox) over-activity. The aim of the present study was to evaluate the efficacy of novel Nox inhibitors as protective agents against cytokine- or high glucose + palmitate-induced human beta-cell death. The Nox2 protein was present mainly in the cytoplasm and was induced by cytokines. Nox4 protein immunoreactivity, with some nuclear accumulation, was observed in human islet cells, and was not affected by islet culture in the presence of cytokines or high glucose + palmitate. Nox inhibitors with partial or no isoform selectivity (DPI, dapsone, GLX351322, and GLX481372) all reduced ROS production of human islet cells exposed to high glucose + palmitate. This was paralleled by improved viability and reduced caspase 3 activation. The Nox1 selective inhibitor ML171 failed to reduce human islet cell death in response to both cytokines and high glucose + palmitate. The selective Nox2 inhibitor Phox-12 also failed to protect against cytokines, but protected partially against high glucose + palmitate-induced cellular death. The highly selective Nox4 inhibitor GLX7013114 protected islet cells against both cytokines and high glucose + palmitate. However, as no osmotic control for high glucose was used, we cannot exclude the possibility that the high glucose effect was due to osmosis. It is concluded that Nox4 may participate in stress-induced islet cell death in human islets in vitro. We propose that Nox4 mediates pro-apoptotic effects in intact islets under stressful conditions and that selective Nox4-inhibition may be a therapeutic strategy in type 2 diabetes.
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| 9. |
- Wikström, Christina, 1967-, et al.
(author)
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Prediction of study success : should selection instruments measure cognitive or non-cognitive factors?
- 2009
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In: Assessment for a creative world.
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Conference paper (peer-reviewed)abstract
- In a number of countries, both high school GPA and admission tests are used in the selection to higher education. The validity research on such instruments has mainly focused on their predictive validity, and the outcome generally shows that the GPA is a better predictor than the test. One explanation is that the grades also measure non-cognitive factors, which are considered important for school performance. Moreover, many admission tests have been criticised for being too alien to what is being taught in schools, hence lacking in relevance for future education. As a consequence, many admission tests are being revised, to be more similar to the school grades in terms of content. A relevant question is if this is the right way to proceed if the main purpose of the test is to predict future study success? This study compares the subtests of a traditional admissions test (the SweSAT) with high school grades in verbal and quantitative subjects in terms of content construct and predictive strength. Success in higher education is measured by the number of credits achieved by students in economics and business administration programmes at Swedish universities. The purpose is to find out if the difference in predictive strength can be related to cognitive or non-cognitive factors. The data is analysed by regression analysis and structural equation modelling (SEM). The findings show that there are differences in content as well as construct, but that variations in predictive strength have to do with both cognitive and non-cognitive factors, where quantitative grades and test scores are more similar in construct than verbal grades and test scores, but also better predictors of performance in higher education. The findings are discussed in relation to previous research, and some suggestions for future research are made.
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| 10. |
- Abbasi, R., et al.
(author)
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Calibration and characterization of the IceCube photomultiplier tube
- 2010
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In: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 618:1-3, s. 139-152
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Journal article (peer-reviewed)abstract
- Over 5000 PMTs are being deployed at the South Pole to compose the IceCube neutrino observatory. Many are placed deep in the ice to detect Cherenkov light emitted by the products of high-energy neutrino interactions, and others are frozen into tanks on the surface to detect particles from atmospheric cosmic ray showers. IceCube is using the 10-in. diameter R7081-02 made by Hamamatsu Photonics. This paper describes the laboratory characterization and calibration of these PMTs before deployment. PMTs were illuminated with pulses ranging from single photons to saturation level. Parameterizations are given for the single photoelectron charge spectrum and the saturation behavior. Time resolution, late pulses and afterpulses are characterized. Because the PMTs are relatively large, the cathode sensitivity uniformity was measured. The absolute photon detection efficiency was calibrated using Rayleigh-scattered photons from a nitrogen laser. Measured characteristics are discussed in the context of their relevance to IceCube event reconstruction and simulation efforts. (C) 2010 Elsevier B.V. All rights reserved.
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