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| 2. |
- Sundsten, Tea, et al.
(author)
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The use of proteomics in identifying differentially expressed serum proteins in humans with type 2 diabetes
- 2006
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In: Proteome Science. - : Springer Science and Business Media LLC. - 1477-5956. ; 4, s. 22-
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Journal article (peer-reviewed)abstract
- Background: The aim of the study was to optimize protocols for finding and identifying serum proteins that are differentially expressed in persons with normal glucose tolerance (NGT) compared to individuals with type 2 diabetes mellitus (T2DM). Serum from persons with NGT and persons with T2DM was profiled using ProteinChip arrays and time-of-flight mass spectra were generated by surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS). Results: Mass spectra from NGT- and T2DM-groups were compared. Fifteen proteins ranging from 5 to 79 kDa were differentially expressed (p < 0.05). Five of these proteins showed decreased and ten showed increased serum levels in individuals with T2DM. To be able to identify the proteins, the complexity of the sample was reduced by fractionation approaches. Subsequently, the purified fractions containing biomarkers were separated by one-dimensional SDS-polyacrylamide gel electrophoresis (SDS-PAGE) in two identical lanes. Protein bands of the first lane were excised and subjected to passive elution to recapture the biomarkers on ProteinChip arrays. The corresponding bands of the second lane were subjected to peptide-mass fingerprinting (PMF). Using this approach four of the differentially expressed proteins were identified as apolipoprotein C3 (9.4 kDa), transthyretin (13.9 kDa), albumin (66 kDa) and transferrin (79 kDa). Whereas apolipoprotein C3 and transthyretin were up-regulated, albumin and transferrin were down-regulated in T2DM. Conclusion: Protocols for protein profiling by SELDI-TOF MS and protein identification by fractionation, SDS-PAGE and PMF were optimized for serum from humans with T2DM. With these protocols differentially expressed proteins were discovered and identified when serum from NGT- and T2DM-individuals was analyzed.
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| 3. |
- Axelsson, Robert, et al.
(author)
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The Challenge of Transdisciplinary Research : A Case Study of Learning by Evaluation for Sustainable Transport Infrastructures
- 2020
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In: Sustainability. - : MDPI. - 2071-1050. ; 12:17, s. 1-24
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Journal article (peer-reviewed)abstract
- While transdisciplinary (TD) research is desired in order to solve real world sustainability issues, this may be challenging for both academic and non-academic participants. Supporting learning through evaluation, we analyzed a project aiming at sustainable transport infrastructures. After developing a TD research framework as a benchmark, two external independent evaluators interviewed all project researchers, representatives for end-users, and donors. The evaluators compared results with the framework, and evaluators and participants critically reflected on the results together. There were three inconsistencies relative to the framework: (1) limited understanding of TD research among project management, end-users, and most of the researchers; (2) no structured learning process among end-users; instead, they expressed very diverse opinions about what they expected from the project; (3) project leaders had limited understanding of the special challenges of TD research, did not fully understand the status of the project's social system, and thus did not act as facilitators of the required collaborative learning process. Non-academic participants saw themselves as customers and not as partners in the knowledge production process. We conclude that TD problem-solving research requires much time and needs facilitation and training. A preparatory phase with a lower level of funding would be helpful in preparing for TD processes.
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| 4. |
- Göransson, Erik
(author)
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Bridge Mediated Electron Transfer in Conjugated and Cross-Conjugated Donor-Acceptor Compounds
- 2012
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Doctoral thesis (other academic/artistic)abstract
- Detailed understanding of electron transfer reactions is important in many aspects of chemistry, biology and solar energy conversion.The main aim of this thesis is to provide further insight into electron transfer through highly conjugated bridge structures. Towards this end, three series of donor-acceptor dyads have been studied, all using an oligo(1,4-phenylene-ethynylene) moiety as the bridge. A common theme in these series is that they explore the effects of having either an ethynylene or phenylene as the attachment group between the bridge and the donor or acceptor. Photophysical characterization of these dyads was carried out by means of time resolved laser spectroscopy. The results show that having an ethynylene as attachment group results in higher rates for bridge mediated electron and energy transfer compared to similar systems, where a phenylene was used.It was also found that most of the investigated systems show a fast back electron transfer. A notable exception is a zinc(II) phthalocyanine- gold(III) porphyrin dyad, where very fast photoinduced electron transfer (kPET = 1.0×1012 s-1) was followed by relatively slow back electron transfer (kBET = 1.0×109 s-1). A complementary DFT investigation indicated that the charge shifted state involves a reduction of the gold ion, rather than the porphyrin ring. This results in lower electronic coupling between the reduced gold porphyrin and the bridge and thus slower back electron transfer.A series of zinc porphyrin platinum acetylide dyads was used to explore the effects on electronic coupling of different attachments points on the porphyrin ring. For the investigated system it was found that linking at the meso-position results in an eight-fold increase in electron transfer rate compared to the β-position.In addition, a series of mixed valence compounds was used to investigate electronic coupling mediated by cross-hyperconjugated or cross-π-conjugated bridges. The results indicate coupling elements of 100-400 cm-1, with the cross-π-conjugated bridge having the largest coupling. A complementary TD-DFT study indicates that both through bond and through space coupling can be active in these systems. The relative contribution of these two mechanisms to the electronic coupling is highly conformer dependent.
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| 5. |
- Göransson, Elisabet, et al.
(author)
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Improved distance measures for “mixed-content miscellanies" : an adaptation for the collections of sayings of the desert fathers and mothers
- 2022
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In: Digital Scholarship in the Humanities. - : Oxford University Press. - 2055-7671 .- 2055-768X. ; 38:1, s. 127-150
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Journal article (peer-reviewed)abstract
- Collections of sayings of the desert fathers and mothers are extant in manuscripts in many languages and are organized differently. They are ‘fixed-content miscellanies’ (FCM): they include material that belongs to the same genre, but is variable both when it comes to appearance and order. Distance measurement methods are particularly suitable for large text traditions including variable content in the so-called mixed-content miscellanies, such as recipes, anthological compilations of shorter text passages, or catalogues, but can also be suitable for text genres like collections of sayings, that are equally variable in appearance and order of sayings, even though the genre is fixed; hence ‘fixed-content miscellanies’. In the article, collections of sayings in seven languages were compared using four distance measures methods. Each segment of the sayings was given a unique id to be comparable. The first method used, the Jaccard distance measure, disregards the linear order of items and instead considers each collection compared only as a ‘bag of stories’. In two other methods used (Birnbaum and Levenshtein methods), the order in which the narratives of each saying appear is compared. All three methods yielded interesting results, but the collections that were apparently closely related were clustered together so tightly that it was not possible to make more nuanced analyses. In order to remove false negatives, particulars concerning lacunes in the material were taken into account in the proposed modified Levenshtein method, the fixed-content miscellanies (FCM)-Levenshtein method. By applying the FCM-Levenshtein method, previously unknown relations between collections witnessed in different languages could be detected.
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| 6. |
- Göransson, Hanna, et al.
(author)
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Quantification of normal cell fraction and copy number neutral LOH in clinical lung cancer samples using SNP array data
- 2009
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In: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:6, s. e6057-
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Journal article (peer-reviewed)abstract
- BACKGROUND: Technologies based on DNA microarrays have the potential to provide detailed information on genomic aberrations in tumor cells. In practice a major obstacle for quantitative detection of aberrations is the heterogeneity of clinical tumor tissue. Since tumor tissue invariably contains genetically normal stromal cells, this may lead to a failure to detect aberrations in the tumor cells. PRINCIPAL FINDING: Using SNP array data from 44 non-small cell lung cancer samples we have developed a bioinformatic algorithm that accurately models the fractions of normal and tumor cells in clinical tumor samples. The proportion of normal cells in combination with SNP array data can be used to detect and quantify copy number neutral loss-of-heterozygosity (CNNLOH) in the tumor cells both in crude tumor tissue and in samples enriched for tumor cells by laser capture microdissection. CONCLUSION: Genome-wide quantitative analysis of CNNLOH using the CNNLOH Quantifier method can help to identify recurrent aberrations contributing to tumor development in clinical tumor samples. In addition, SNP-array based analysis of CNNLOH may become important for detection of aberrations that can be used for diagnostic and prognostic purposes.
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| 7. |
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| 8. |
- Kirkpatrick, Christine L., et al.
(author)
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The "PepSAVI-MS" Pipeline for Natural Product Bioactive Peptide Discovery
- 2017
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In: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 89:2, s. 1194-1201
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Journal article (peer-reviewed)abstract
- The recent increase in extensively drug-resistant bacterial pathogens and the associated increase of morbidity and mortality demonstrate the immediate need for new antibiotic backbones with novel mechanisms of action. Here, we report the development of the PepSAVI-MS pipeline for bioactive peptide discovery. This highly versatile platform employs mass spectrometry and statistics to identify bioactive peptide targets from complex biological samples. We validate the use of this platform through the successful identification of known bioactive peptides from a botanical species, Viola odorata. Using this pipeline, we have widened the known antimicrobial spectrum for V. odorata cyclotides, including antibacterial activity of cycloviolacin O2 against A. baumannii. We further demonstrate the broad applicability of the platform through the identification of novel anticancer activities for cycloviolacins by their cytotoxicity against ovarian, breast, and prostate cancer cell lines.
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| 9. |
- Koehbach, Johannes, et al.
(author)
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Oxytocic plant cyclotides as templates for peptide G protein-coupled receptor ligand design
- 2013
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 110:52, s. 21183-21188
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Journal article (peer-reviewed)abstract
- Cyclotides are plant peptides comprising a circular backbone and three conserved disulfide bonds that confer them with exceptional stability. They were originally discovered in Oldenlandia affinis based on their use in traditional African medicine to accelerate labor. Recently, cyclotides have been identified in numerous plant species of the coffee, violet, cucurbit, pea, potato, and grass families. Their unique structural topology, high stability, and tolerance to sequence variation make them promising templates for the development of peptide-based pharmaceuticals. However, the mechanisms underlying their biological activities remain largely unknown; specifically, a receptor for a native cyclotide has not been reported hitherto. Using bioactivity-guided fractionation of an herbal peptide extract known to indigenous healers as "kalata-kalata," the cyclotide kalata B7 was found to induce strong contractility on human uterine smooth muscle cells. Radioligand displacement and second messenger-based reporter assays confirmed the oxytocin and vasopressin V-1a receptors, members of the G protein-coupled receptor family, as molecular targets for this cyclotide. Furthermore, we show that cyclotides can serve as templates for the design of selective G protein-coupled receptor ligands by generating an oxytocin-like peptide with nanomolar affinity. This nonapeptide elicited dose-dependent contractions on human myometrium. These observations provide a proof of concept for the development of cyclotide-based peptide ligands.
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| 10. |
- Kottyan, Leah C., et al.
(author)
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The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.
- 2015
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596
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Journal article (peer-reviewed)abstract
- Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
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