| 1. |
- Beal, Jacob, et al.
(författare)
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Robust estimation of bacterial cell count from optical density
- 2020
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Ingår i: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Tidskriftsartikel (refereegranskat)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Gorski, Mathias, et al.
(författare)
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Genetic loci and prioritization of genes for kidney function decline derived from a meta-analysis of 62 longitudinal genome-wide association studies
- 2022
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Ingår i: Kidney International. - : Elsevier. - 0085-2538 .- 1523-1755. ; 102:3, s. 624-639
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Tidskriftsartikel (refereegranskat)abstract
- Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genomewide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR- baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant- by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with agedependency of genetic cross- section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in- silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03- 1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
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| 3. |
- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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| 4. |
- Wuttke, Matthias, et al.
(författare)
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A catalog of genetic loci associated with kidney function from analyses of a million individuals
- 2019
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Ingår i: Nature Genetics. - : NATURE PUBLISHING GROUP. - 1061-4036 .- 1546-1718. ; 51:6, s. 957-972
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Tidskriftsartikel (refereegranskat)abstract
- Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
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| 5. |
- Young, William J., et al.
(författare)
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Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways
- 2022
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- The QT interval is a heritable electrocardiographic measure associated with arrhythmia risk when prolonged. Here, the authors used a series of genetic analyses to identify genetic loci, pathways, therapeutic targets, and relationships with cardiovascular disease. The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.
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| 6. |
- Ahmed, Haseeb, et al.
(författare)
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Planned Behavior, Social Networks, and Perceived Risks: Understanding Farmers' Behavior toward Precision Dairy Technologies
- 2024
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Ingår i: Journal of Dairy Science. - 0022-0302 .- 1525-3198. ; 107, s. 2968-2982
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Tidskriftsartikel (refereegranskat)abstract
- Precision dairy tools (PDT) can provide timely information on individual cow's physiological and behavioral parameters, which can lead to more efficient management of the dairy farm. Although the economic rationale behind the adoption of PDT has been extensively discussed in the literature, the socio-psychological aspects related to the adoption of these technologies have received far less attention. Therefore, this paper proposes a socio-psychological model that builds upon the theory of planned behavior and develops hypotheses regarding cognitive constructs, their interaction with the farmers' perceived risks and social networks, and their overall influence on adoption. These hypotheses are tested using a generalized structural equation model for (a) the adoption of automatic milking systems (AMS) on the farms and (b) the PDT that are usually adopted with the AMS. Results show that adoption of these technologies is affected directly by intention, and the effects of subjective norms, perceived control, and attitudes on adoption are mediated through intention. A unit increase in perceived control score is associated with an increase in marginal probability of adoption of AMS and PDT by 0.05 and 0.19, respectively. Subjective norms are associated with an increase in marginal probability of adoption of AMS and PDT by 0.009 and 0.05, respectively. These results suggest that perceived control exerts a stronger influence on adoption of AMS and PDT, particularly compared with their subjective norms. Technology-related social networks are associated with an increase in marginal probability of adoption of AMS and PDT by 0.026 and 0.10, respectively. Perceived risks related to AMS and PDT negatively affect probability of adoption by 0.042 and 0.16, respectively, by having negative effects on attitudes, perceived self-confidence, and intentions. These results imply that integrating farmers within knowledge-sharing networks, minimizing perceived risks associated with these technologies, and enhancing farmers' confidence in their ability to use these technologies can significantly enhance uptake.
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| 7. |
- Andersson, Linus, et al.
(författare)
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Chemosensory perception, symptoms and autonomic responses during chemical exposure in multiple chemical sensitivity
- 2016
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Ingår i: International Archives of Occupational and Environmental Health. - : Springer. - 0340-0131 .- 1432-1246. ; 89:1, s. 79-88
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Multiple chemical sensitivity (MCS) is a prevalent medically unexplained symptom characterized by symptom reactions to everyday chemical exposure below hygienic thresholds. The aim of this study was to investigate the expressions of hyper-reactivity in MCS during whole-body exposure to low concentrations of the odorant n-butanol.Methods: We exposed 18 participants with MCS and 18 non-ill controls to a low concentration of the odorantn-butanol using an exposure chamber. The first 10 min constituted blank exposure, after which then-butanol concentration increased and reached a plateau at 11.5 mg/m3.Results: MCS participants, compared with controls, reported greater perceived odor intensities, more unpleasantness to the exposure and increasing symptoms over time. MCS participants also expressed higher pulse rate and lower pulse rate variability than controls did. No group differences were found for breathing rate or tonic electrodermal activity responses.Conclusions: We conclude that MCS sufferers differ from healthy controls in terms of autonomic responses, symptoms and chemosensory perception during chemical exposure.
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| 8. |
- Claeson, Anna-Sara, 1974-, et al.
(författare)
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Human exposure to acrolein : Time-dependence and individual variation in eye irritation
- 2016
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Ingår i: Environmental Toxicology and Pharmacology. - : Elsevier. - 1382-6689 .- 1872-7077. ; 45, s. 20-27
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to examine the time dependence on sensory irritation detection following exposure to threshold levels of acrolein, in humans. The exposures occurred in an exposure chamber and the subjects were breathing fresh air through a mask that covered the nose and mouth. All participants participated in four exposure conditions, of which three consisted of a mixture of acrolein and heptane and one of only heptane. Exposure to acrolein at a concentration half of the TLV-C lead to sensory irritation. The perceived sensory irritation resulted in both increased detectability and sensory irritation after about6.8 min of exposure in 58% of the participants. The study confirm the previously suggested LOAEL of about 0.34 mg/m3 for eye irritation due to acrolein exposure. The sensory irritation was still significant 10 min after exposure. These results have implications for risk assessment and limit setting in occupational hygiene.
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| 9. |
- Claeson, Anna-Sara, 1974-, et al.
(författare)
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Symptom-trigger factors other than allergens in asthma and allergy
- 2016
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Ingår i: International Journal of Environmental Health Research. - : Taylor & Francis Group. - 0960-3123 .- 1369-1619. ; 26:4, s. 448-457
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Tidskriftsartikel (refereegranskat)abstract
- Several environmental exposures of particular relevance for indoor air quality, such as exposure to odorants, may be associated with asthma and allergy. The aim of this study was to investigate attribution of symptoms and behavioral disruptions to various chemical and physical environmental sources in persons with self-reported asthma and allergy. Data from a population-based study, the Västerbotten Environmental Health Study, were used to compare persons with asthma, allergic rhinitis, allergic dermatitis, multiple diagnoses of asthma/allergy and no asthma or allergy. Persons with asthma and multiple diagnoses reported odorous/pungent and buildingrelated environmental factors to trigger symptoms to a larger extent than did the reference group, mainly due to perfume and odors from flowers. They also reported behavioral disruptions and affective reactions to odorous/ pungent environments. These findings increase the understanding of the role of odorants in symptom development and thereby the prevention of health problems in asthma and allergy in indoor air.
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| 10. |
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