| 1. |
- Adman, Per, et al.
(författare)
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171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
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Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
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| 2. |
- Andersson, Karl, 1972-
(författare)
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Bringing time into molecular and cellular biology
- 2013
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Ingår i: Journal of Analytical Oncology. - : Neoplasia Research. - 1927-7229. ; 2:2, s. 65-68
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Tidskriftsartikel (refereegranskat)abstract
- In conjunction with the defense of a doctoral thesis on the deciphering of complex protein interactions on living cells, six scientists shared their view on time in molecular and cellular biology. This brief review takes the form of a conference report and summarizes the contributions of the speakers and the defense. Opportunities and challenges for time resolved assays in molecular and cellular biology were vividly discussed during two days with a pan-European audience. Awareness of biological timeframes and understanding the temporal aspects were claimed critical for analytical applications in biology.
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| 3. |
- Andersson, Karl, 1972-
(författare)
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Characterization of Biomolecular Interactions Using a Multivariate Approach
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis presents a novel bioinformatic methodology denoted the bio-chemometric approach. The methodology is designed for generation of detailed descriptions and predictions of biomolecular interactions. It is based on multivariate analysis of the sensitivity of a biomolecular interaction to multiple minor changes in the experimental conditions. In this work, either the chemical environment where the interaction takes place, or the molecular structure of one of the interacting molecules, was varied. The sensitivity of the interaction to the performed variations was presented as a vector called the sensitivity fingerprint. The bio-chemometric approach was tested on several biomolecular interactions. Useful descriptions of the interactions were obtained by measuring binding kinetics for each interaction in 12-20 different buffers and correlating buffer composition to binding kinetics. The obtained chemical sensitivity fingerprints were reproducible, significantly different and showed a weak correlation to binding site properties for the tested interactions. The results indicate that the fingerprints contained useful information about the binding site. The predictive ability of the bio-chemometric approach was tested on two different biomolecular interactions where one of the binding partners was slightly modified into multiple analogues by amino acid exchanges. In one example, interactions of 18 peptide analogues with an antibody gave data that could be used for accurate prediction of the dissociation rates of novel analogues. Reliable predictions of binding kinetics and affinity were also obtained for single domain camel antibody analogues binding to a protein antigen. By using the three-dimensional structure of camel antibodies and data obtained using the bio-chemometric approach, even the importance of non-exchanged amino acids for the binding could be estimated. The bio-chemometric approach can potentially improve the development of peptides and proteins for therapeutic and diagnostic use. It is suggested to be valid for general use in biochemistry.
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| 4. |
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| 5. |
- Andersson, Stefanie, 1989, et al.
(författare)
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Genome-wide imaging screen uncovers molecular determinants of arsenite-induced protein aggregation and toxicity
- 2021
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 134:11
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Tidskriftsartikel (refereegranskat)abstract
- The toxic metalloid arsenic causes widespread misfolding and aggregation of cellular proteins. How these protein aggregates are formed in vivo, the mechanisms by which they affect cells and how cells prevent their accumulation is not fully understood. To find components involved in these processes, we performed a genome-wide imaging screen and identified Saccharomyces cerevisiae deletion mutants with either enhanced or reduced protein aggregation levels during arsenite exposure. We show that many of the identified factors are crucial to safeguard protein homeostasis (proteostasis) and to protect cells against arsenite toxicity. The hits were enriched for various functions including protein biosynthesis and transcription, and dedicated follow-up experiments highlight the importance of accurate transcriptional and translational control for mitigating protein aggregation and toxicity during arsenite stress. Some of the hits are associated with pathological conditions, suggesting that arsenite-induced protein aggregation may affect disease processes. The broad network of cellular systems that impinge on proteostasis during arsenic stress identified in this current study provides a valuable resource and a framework for further elucidation of the mechanistic details of metalloid toxicity and pathogenesis. This article has an associated First Person interview with the first authors of the paper.
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| 6. |
- Andersson, Tommy, et al.
(författare)
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Multiobjective Optimization of a Heat-Sink Design Using the Sandwiching Algorithm and an Immersed Boundary Conjugate Heat Transfer Solver
- 2018
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Ingår i: Journal of Heat Transfer. - : ASME International. - 1528-8943 .- 0022-1481. ; 140:10, s. 102002 -
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Tidskriftsartikel (refereegranskat)abstract
- The thermal management is an ever increasing challenge in advanced electronic devices. In this paper, simulation-based optimization is applied to improve the design of a plate-fin heat-sink in terms of operational cost and thermal performance. The proposed framework combines a conjugate heat transfer solver, a CAD engine and an adapted Sandwiching algorithm. A key feature is the use of novel immersed boundary (IB) techniques that allows for automated meshing which is perfectly suited for parametric design optimization.
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| 7. |
- Bondza, Sina, et al.
(författare)
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Novel Real-Time Proximity Assay for Characterizing Multiple Receptor Interactions on Living Cells
- 2017
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 89:24, s. 13212-13218
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Tidskriftsartikel (refereegranskat)abstract
- Cellular receptor activity is often controlled through complex mechanisms involving interactions with multiple molecules, which can be soluble ligands and/or other cell surface molecules. In this study, we combine a fluorescence-based technology for real-time interaction analysis with fluorescence quenching to create a novel time-resolved proximity assay to study protein-receptor interactions on living cells. This assay extracts the binding kinetics and affinity for two proteins if they bind in proximity on the cell surface. One application of real-time proximity interaction analysis is to study relative levels of receptor dimerization. The method was primarily evaluated using the HER2 binding antibodies Trastuzumab and Pertuzumab and two EGFR binding antibodies including Cetuximab. Using Cetuximab and Trastuzumab, proximity of EGFR and HER2 was investigated before and after treatment of cells with the tyrosine-kinase inhibitor Gefitinib. Treated cells displayed 50% increased proximity signal, whereas the binding characteristics of the two antibodies were not significantly affected, implying an increase in the EGFR-HER2 dimer level. These results demonstrate that real-time proximity interaction analysis enables determination of the interaction rate constants and affinity of two ligands while simultaneously quantifying their relative colocalization on living cells.
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| 8. |
- Bondza, Sina, et al.
(författare)
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Real-time Characterization of Antibody Binding to Receptors on Living Immune Cells
- 2017
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Understanding molecular interactions on immune cells is crucial for drug development to treat cancer and autoimmune diseases. When characterizing molecular interactions, the use of a relevant living model system is important, as processes such as receptor oligomerization and clustering can influence binding patterns. We developed a protocol to enable time-resolved analysis of ligand binding to receptors on living suspension cells. Different suspension cell lines and weakly adhering cells were tethered to Petri dishes with the help of a biomolecular anchor molecule, and antibody binding was analyzed using LigandTracer. The protocol and assay described in this report were used to characterize interactions involving eight cell lines. Experiments were successfully conducted in three different laboratories, demonstrating the robustness of the protocol. For various antibodies, affinities and kinetic rate constants were obtained for binding to CD20 on both Daudi and Ramos B-cells, the T-cell co-receptor CD3 on Jurkat cells, and the Fc gamma receptor CD32 on transfected HEK293 cells, respectively. Analyzing the binding of Rituximab to B-cells resulted in an affinity of 0.7-0.9 nM, which is similar to values reported previously for living B-cells. However, we observed a heterogeneous behavior for Rituximab interacting with B-cells, which to our knowledge has not been described previously. The understanding of complex interactions will be facilitated with the possibility to characterize binding processes in real-time on living immune cells. This provides the chance to broaden the understanding of how binding kinetics relate to biological function.
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| 9. |
- Encarnacao, Joao Crispim, Master, 1990-, et al.
(författare)
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A real-time cell-binding assay reveals dynamic features of STxB-Gb3 cointernalization and STxB-mediated cargo delivery into cancer cells
- 2020
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Ingår i: FEBS Letters. - : WILEY. - 0014-5793 .- 1873-3468. ; 594:15, s. 2406-2420
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between the Shiga toxin B-subunit (STxB) and its globotriaosylceramide receptor (Gb3) has a high potential for being exploited for targeted cancer therapy. The primary goal of this study was to evaluate the capacity of STxB to carry small molecules and proteins as cargo into cells. For this purpose, an assay was designed to provide real-time information about the StxB-Gb3 interaction as well as the dynamics and mechanism of the internalization process. The assay revealed the ability to distinguish the process of binding to the cell surface from internalization and presented the importance of receptor and STxB clustering for internalization. The overall setup demonstrated that the binding mechanism is complex, and the concept of affinity is difficult to apply. Hence, time-resolved methods, providing detailed information about the interaction of STxB with cells, are critical for the optimization of intracellular delivery.
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| 10. |
- Encarnacao, Joao Crispim, et al.
(författare)
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Detecting ligand interactions in real time on living bacterial cells
- 2018
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Ingår i: Applied Microbiology and Biotechnology. - : SPRINGER. - 0175-7598 .- 1432-0614. ; 102:9, s. 4193-4201
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Tidskriftsartikel (refereegranskat)abstract
- Time-resolved analysis assays of receptor-ligand interactions are fundamental in basic research and drug discovery. Adequate methods are well developed for the analysis of recombinant proteins such as antibody-antigen interactions. However, assays for time-resolved ligand-binding processes on living cells are still rare, in particular within microbiology. In this report, the real-time cell-binding assay (RT-CBA) technology LigandTracerA (R), originally designed for mammalian cell culture, was extended to cover Gram-positive and Gram-negative bacteria. This required the development of new immobilization methods for bacteria, since LigandTracer depends on cells being firmly attached to a Petri dish. The evaluated Escherichia coli CJ236 and BL21 as well as Staphylococcus carnosus TM300 strains were immobilized to plastic Petri dishes using antibody capture, allowing us to depict kinetic binding traces of fluorescently labeled antibodies directed against surface-displayed bacterial proteins for as long as 10-15 h. Interaction parameters, such as the affinity and kinetic constants, could be estimated with high precision (coefficient of variation 9-44%) and the bacteria stayed viable for at least 16 h. The other tested attachment protocols were inferior to the antibody capture approach. Our attachment protocol is generic and could potentially also be applied to other assays and purposes.
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