| 1. |
- Ekelund Ugge, Gustaf Magnus Oskar, 1990-
(författare)
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Transcriptional biomarkers of toxicity – powerful tools or random noise? : An applied perspective from studies on bivalves
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Aquatic organisms are constantly at risk of being exposed to potentially harmful chemical compounds of natural or anthropogenic origin. Biological life can for instance respond to chemical stressors by changes in gene expression, and thus, certain gene transcripts can potentially function as biomarkers, i.e. early warnings, of toxicity and chemical stress. A major challenge for biomarker application is the extrapolation of transcriptional data to potential effects at the organism level or above. Importantly, successful biomarker use also requires basal understanding of how to distinguish actual responses from background noise. The aim of this thesis is, based on response magnitude and variation, to evaluate the biomarker potential in a set of putative transcriptional biomarkers of general toxicity and chemical stress.Specifically, I addressed a selection of six transcripts involved in cytoprotection and oxidative stress: catalase (cat), glutathione-S-transferase (gst), heat shock proteins 70 and 90 (hsp70, hsp90), metallothionein (mt) and superoxide dismutase (sod). Moreover, I used metal exposures to serve as a proxy for general chemical stress, and due to their ecological relevance and nature as sedentary filter-feeders, I used bivalves as study organisms.In a series of experiments, I tested transcriptional responses in the freshwater duck mussel, Anodonta anatina, exposed to copper or an industrial wastewater effluent, to address response robustness and sensitivity, and potential controlled (e.g. exposure concentration) and random (e.g. gravidness) sources of variation. In addition, I performed a systematic review and meta-analysis on transcriptional responses in metal exposed bivalves to (1) evaluate what responses to expect from arbitrary metal exposures, (2) assess the influence from metal concentration (expressed as toxic unit), exposure time and analyzed tissue, and (3) address potential impacts from publication bias in the scientific literature.Response magnitudes were generally small in relationship to the observed variation, both for A. anatina and bivalves in general. The expected response to an arbitrary metal exposure would generally be close to zero, based on both experimental observations and on the estimated impact from publication bias. Although many of the transcripts demonstrated concentration-response relationships, large background noise might in practice obscure the small responses even at relatively high exposures. As demonstrated in A. anatina under copper exposure, this can be the case already for single species under high resolution exposures to single pollutants. As demonstrated by the meta-regression, this problem can only be expected to increase further upon extrapolation between different species and exposure scenarios, due to increasing heterogeneity and random variation. Similar patterns can also be expected for time-dependent response variation, although the meta-regression revealed a general trend of slightly increasing response magnitude with increasing exposure times.In A. anatina, gravidness was identified as a source of random variability that can potentially affect the baseline of most assessed biomarkers, particularly when quantified in gills. Response magnitudes and variability in this species were generally similar for selected transcripts as for two biochemical biomarkers included for comparison (AChE, GST), suggesting that the transcripts might not capture early warnings more efficiently than other molecular endpoints that are more toxicologically relevant. Overall, high concentrations and long exposure durations presumably increase the likelihood of a detectable transcriptional response, but not to an extent that justifies universal application as biomarkers of general toxicity and chemical stress. Consequently, without a strictly defined and validated application, this approach on its own appears unlikely to be successful for future environmental risk assessment and monitoring. Ultimately, efficient use of transcriptional biomarkers might require additional implementation of complementary approaches offered by current molecular techniques.
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| 2. |
- Ekelund Ugge, Gustaf Magnus Oskar, et al.
(författare)
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Evaluation of transcriptional biomarkers using a high-resolution regression approach : Concentration-dependence of selected transcripts in copper-exposed freshwater mussels (Anodonta anatina)
- 2022
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Ingår i: Environmental Toxicology and Pharmacology. - : Elsevier. - 1382-6689 .- 1872-7077. ; 90
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Tidskriftsartikel (refereegranskat)abstract
- We tested concentration-dependence of selected gene transcripts (cat, gst, hsp70, hsp90, mt and sod) for evaluation as biomarkers of chemical stress. Contrary to the common approach of factorial designs and few exposure concentrations, we used regression across a high-resolution concentration series. Specifically, freshwater mussels (Anodonta anatina) were acutely (96 h) exposed to Cu (13 nominal concentrations, measuring 0.13–1 600 µg/L), and transcripts were measured by RT-qPCR. In digestive glands, cat, hsp90 and mt decreased with water Cu (p < 0.05), but response magnitudes saturated at < 2-fold decreases. In gills, gst, hsp70, hsp90 and mt increased with water Cu (p < 0.05). While hsp70, hsp90 and mt exceeded 2-fold increases within the exposure range, high Cu concentrations were required (38–160 µg/L). Although gill responses were generally more robust compared to digestive glands, overall small response magnitudes and moderate sensitivity may set limit for potential application as general biomarkers of chemical stress.
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| 3. |
- Ekelund Ugge, Gustaf Magnus Oskar, et al.
(författare)
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Molecular biomarker responses in the freshwater mussel Anodonta anatina exposed to an industrial wastewater effluent
- 2022
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Ingår i: Environmental Science and Pollution Research. - : Springer. - 0944-1344 .- 1614-7499. ; 29:2, s. 2158-2170
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Tidskriftsartikel (refereegranskat)abstract
- Using a selection of molecular biomarkers, we evaluated responses in freshwater mussels (Anodonta anatina) exposed to effluent from an industrial wastewater treatment facility. The aims of this work were to (1) assess biomarkers of general toxicity under sublethal exposure to an anthropogenic mixture of chemicals, represented by an arbitrary effluent, and (2) evaluate the potential of A. anatina as a bioindicator of pollution. Adult mussels (n = in total 32; 24 males and 8 females) were exposed (96 h) in the laboratory to a fixed dilution of effluent or to a control treatment of standardized freshwater. Metal concentrations were in general higher in the effluent, by an order of magnitude or more, compared to the control. Toxic unit estimates were used as proxies of chemical stress, and Cu, Ni, and Zn were identified as potential major contributors (Cu> Ni > Zn). Six transcriptional (cat, gst, hsp70, hsp90, mt, sod) and two biochemical (AChE, GST) biomarkers were analyzed in two tissues, gills, and digestive glands. Out of the 16 responses (eight biomarkers x two tissues), 14 effect sizes were small (within +/- 28 % of control) and differences non-significant (p > 0.05). Results did however show that (1) AChE activity increased by 40% in gills of exposed mussels compared to control, (2) hsp90 expression was 100% higher in exposed female gills compared to control, and (3) three marker signals (AChE in both tissues, and hsp70 in gills) differed between sexes, independent of treatment. Results highlight a need for further investigation of molecular biomarker variability and robustness in A. anatina.
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| 4. |
- Ekelund Ugge, Gustaf Magnus Oskar, et al.
(författare)
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Transcriptional Responses as Biomarkers of General Toxicity : A Systematic Review and Meta-Analysis on Metal-Exposed Bivalves
- 2023
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Ingår i: Environmental Toxicology and Chemistry. - : John Wiley & Sons. - 0730-7268 .- 1552-8618. ; 42:3, s. 628-641
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Forskningsöversikt (refereegranskat)abstract
- Through a systematic review and a series of meta-analyses, we evaluated the general responsiveness of putative transcriptional biomarkers of general toxicity and chemical stress. We targeted metal exposures performed on bivalves under controlled laboratory conditions, and selected six transcripts associated with general toxicity for evaluation: catalase (cat), glutathione-S-transferase (gst), heat shock proteins 70 and 90 (hsp70, hsp90), metallothionein (mt) and superoxide dismutase (sod). Transcriptional responses (n = 396) were extracted from published scientific articles (k = 22) and converted to log response ratios (lnRRs). By estimating toxic units (TUs), we normalized different metal exposures to a common scale, as a proxy of concentration. Using Bayesian hierarchical random effect models, we then tested the effects of metal exposure on lnRR, both for metal exposure in general and in meta-regressions using TU and exposure time as independent variables. Corresponding analyses were also repeated with transcript and tissue as additional moderators. Observed patterns were similar for general as for transcript- and tissue-specific responses. The expected overall response to arbitrary metal exposure was a lnRR of 0.50, corresponding to a 65 % increase relative a non-exposed control. However, when accounting for publication bias, the estimated ‘true’ response showed no such effect. Furthermore, expected response magnitude increased slightly with exposure time, but there was little support for general monotonic concentration-dependence with regards to TU. Altogether, this work reveals potential limitations that need consideration prior to applying the selected transcripts as biomarkers in environmental risk assessment. This article is protected by copyright. All rights reserved. Environ Toxicol Chem 2022;00:0–0.
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| 5. |
- Eriksson, Jens, et al.
(författare)
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Characterization of motility and piliation in pathogenic Neisseria
- 2015
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Ingår i: BMC Microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 15
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Tidskriftsartikel (refereegranskat)abstract
- Background: The type IV pili (Tfp) of pathogenic Neisseria (i. e., N. gonorrhoeae and N. meningitidis) are essential for twitching motility. Tfp retraction, which is dependent on the ATPase PilT, generates the forces that move bacteria over surfaces. Neisseria motility has mainly been studied in N. gonorrhoeae whereas the motility of N. meningitidis has not yet been characterized. Results: In this work, we analyzed bacterial motility and monitored Tfp retraction using live- cell imaging of freely moving bacteria. We observed that N. meningitidis moved over surfaces at an approximate speed of 1.6 mu m/s, whereas N. gonorrhoeae moved with a lower speed (1.0 mu/s). An alignment of the meningococcal and gonococcal pilT promoters revealed a conserved single base pair variation in the -10 promoter element that influence PilT expression. By tracking mutants with altered pilT expression or pilE sequence, we concluded that the difference in motility speed was independent of both. Live-cell imaging using total internal reflection fluorescence microscopy demonstrated that N. gonorrhoeae more often moved with fewer visible retracting filaments when compared to N. meningitidis. Correspondingly, meningococci also displayed a higher level of piliation in transmission electron microscopy. Nevertheless, motile gonococci that had the same number of filaments as N. meningitidis still moved with a lower speed. Conclusions: These data reveal differences in both speed and piliation between the pathogenic Neisseria species during twitching motility, suggesting a difference in Tfp-dynamics.
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| 6. |
- Wiklund Lindström, Susanne, et al.
(författare)
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The importance of balanced data sets for partial least squares discriminant analysis : classification problems using hyperspectral imaging data
- 2011
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Ingår i: Journal of Near Infrared Spectroscopy. - : IM Publications. - 0967-0335 .- 1751-6552. ; 19:4, s. 233-241
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Tidskriftsartikel (refereegranskat)abstract
- This study investigates the effect of imbalanced spectral data in the training set, when developing partial least squares discriminant analysis (PLS-DA) classification models for use in future predictions. The experimental study was performed using a real hyperspectral short-wavelength infrared image data set collected from bakery products (buns) containing contaminants (flies) but similar applications for other insects, paper and plastic were also tested. The contaminants represent a very small proportion of the images relative to the bun. The PLS-DA model aims at accurately detecting and classifying the contaminants and this requires a modification of the calibration data set. The paper deals with problems caused by unbalanced calibration data sets and how to remedy them. In the example it was demonstrated that, by balancing the calibration data from 58,476 bun pixels + 279 fly pixels to 279 bun + 279 fly pixels, the number of true predictions could be improved with a smaller number of PLS components used in the model. The improvement for flies increased from 65% true predictions with ten PLS components to >99% true prediction with five to six PLS components. The true prediction for bun went from 100% to 99.5% with six PLS components which is an acceptable reduction. Theoretical explanations are included.
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| 7. |
- Beskow, Jonas, et al.
(författare)
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Speech technology in the European project MonAMI
- 2008
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Ingår i: Proceedings of FONETIK 2008. - Gothenburg, Sweden : University of Gothenburg. - 9789197719605 ; , s. 33-36
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This paper describes the role of speech and speech technology in the European project MonAMI, which aims at “mainstreaming ac-cessibility in consumer goods and services, us-ing advanced technologies to ensure equal ac-cess, independent living and participation for all”. It presents the Reminder, a prototype em-bodied conversational agent (ECA) which helps users to plan activities and to remember what to do. The prototype merges speech technology with other, existing technologies: Google Cal-endar and a digital pen and paper. The solution allows users to continue using a paper calendar in the manner they are used to, whilst the ECA provides notifications on what has been written in the calendar. Users may also ask questions such as “When was I supposed to meet Sara?” or “What’s on my schedule today?”
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| 8. |
- Borgmästars, Emmy, et al.
(författare)
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Multi-omics profiling to identify early plasma biomarkers in pre-diagnostic pancreatic ductal adenocarcinoma : a nested case-control study
- 2024
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Ingår i: Translational Oncology. - : Elsevier. - 1944-7124 .- 1936-5233. ; 48
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with poor survival. Novel biomarkers are urgently needed to improve the outcome through early detection. Here, we aimed to discover novel biomarkers for early PDAC detection using multi-omics profiling in pre-diagnostic plasma samples biobanked after routine health examinations.A nested case-control study within the Northern Sweden Health and Disease Study was designed. Pre-diagnostic plasma samples from 37 future PDAC patients collected within 2.3 years before diagnosis and 37 matched healthy controls were included. We analyzed metabolites using liquid chromatography mass spectrometry and gas chromatography mass spectrometry, microRNAs by HTG edgeseq, proteins by multiplex proximity extension assays, as well as three clinical biomarkers using milliplex technology. Supervised and unsupervised multi-omics integration were performed as well as univariate analyses for the different omics types and clinical biomarkers. Multiple hypothesis testing was corrected using Benjamini-Hochberg's method and a false discovery rate (FDR) below 0.1 was considered statistically significant.Carbohydrate antigen (CA) 19-9 was associated with PDAC risk (OR [95 % CI] = 3.09 [1.31–7.29], FDR = 0.03) and increased closer to PDAC diagnosis. Supervised multi-omics models resulted in poor discrimination between future PDAC cases and healthy controls with obtained accuracies between 0.429–0.500. No single metabolite, microRNA, or protein was differentially altered (FDR < 0.1) between future PDAC cases and healthy controls.CA 19-9 levels increase up to two years prior to PDAC diagnosis but extensive multi-omics analysis including metabolomics, microRNAomics and proteomics in this cohort did not identify novel early biomarkers for PDAC.
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| 9. |
- Ekelund Ugge, Gustaf Magnus Oskar, et al.
(författare)
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Transcriptional and biochemical biomarker responses in a freshwater mussel (Anodonta anatina) under environmentally relevant Cu exposure
- 2020
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Ingår i: Environmental Science and Pollution Research. - : Springer Berlin/Heidelberg. - 0944-1344 .- 1614-7499. ; 27:9, s. 9999-10010
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Tidskriftsartikel (refereegranskat)abstract
- Molecular biomarkers, like gene transcripts or enzyme activities, are potentially powerful tools for early warning assessment of pollution. However, a thorough understanding of response and baseline variation is required to distinguish actual effects from pollution. Here, we assess the freshwater mussel Anodonta anatina as a biomarker model species for freshwater ecosystems, by testing responses of six transcriptional (cat, gst, hsp70, hsp90, mt, and sod) and two biochemical (AChE and GST) biomarkers to environmentally relevant Cu water concentrations. Mussels (n = 20), collected from a stream free from point source pollution, were exposed in the laboratory, for 96 h, to Cu treatments (< 0.2 mu g/L, 0.77 +/- 0.87 mu g/L, and 6.3 +/- 5.4 mu g/L). Gills and digestive glands were extracted and analyzed for transcriptional and biochemical responses. Biological and statistical effect sizes from Cu treatments were in general small (mean log(2) fold-change <= 0.80 and Cohen's f <= 0.69, respectively), and no significant treatment effects were observed. In contrast, four out of eight biomarkers (cat, gst, hsp70, and GST) showed a significant sex:tissue interaction, and additionally one (sod) showed significant overall effects from sex. Specifically, three markers in gills (cat, mt, GST) and one in digestive gland (AChE) displayed significant sex differences, independent of treatment. Results suggest that sex or tissue effects might obscure low-magnitude biomarker responses and potential early warnings. Thus, variation in biomarker baselines and response patterns needs to be further addressed for the future use of A. anatina as a biomarker model species.
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| 10. |
- Nilsson, Måns, et al.
(författare)
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Analytical framework and tool kit for SEA follow-up
- 2009
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Ingår i: Environmental impact assessment review. - : Elsevier BV. - 0195-9255 .- 1873-6432. ; 29:3, s. 186-199
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Tidskriftsartikel (refereegranskat)abstract
- Most Strategic Environmental Assessment (SEA) research and applications have so far neglected the ex post stages of the process, also called SEA follow-up. Tool kits and methodological frameworks for engaging effectively with SEA follow-up have been conspicuously missing. In particular. little has so far been learned from the much more mature evaluation literature although many aspects are similar. This paper provides an analytical framework and tool kit for SEA follow-up. It is based on insights and tools developed within programme evaluation and environmental systems analysis. It is also grounded in empirical studies into real planning and programming practices at the regional level, but should have relevance for SEA processes at all levels. The purpose of the framework is to promote a learning-oriented and integrated use of SEA follow-up in strategic decision making. It helps to identify appropriate tools and their use in the process, and to systematise the use of available data and knowledge across the planning organization and process. It distinguishes three stages in follow-up: scoping, analysis and learning, identifies the key functions and demonstrates the informational linkages to the strategic decision-making process. The associated tool kit includes specific analytical and deliberative tools. Many of these are applicable also ex ante. but are then used in a predictive mode rather than on the basis of real data. The analytical element of the framework is organized on the basis of programme theory and "DPSIR" tools. The paper discusses three issues in the application of the framework: understanding the integration of organizations and knowledge; understanding planners' questions and analytical requirements; and understanding interests, incentives and reluctance to evaluate.
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