| 1. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)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. |
- Hendus-Altenburger, Ruth, et al.
(author)
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The intracellular lipid-binding domain of human Na+/H+ exchanger 1 forms a lipid-protein co-structure essential for activity
- 2020
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In: Communications Biology. - : Nature Publishing Group. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Dynamic interactions of proteins with lipid membranes are essential regulatory events in biology, but remain rudimentarily understood and particularly overlooked in membrane proteins. The ubiquitously expressed membrane protein Na+/H+-exchanger 1 (NHE1) regulates intracellular pH (pHi) with dysregulation linked to e.g. cancer and cardiovascular diseases. NHE1 has a long, regulatory cytosolic domain carrying a membrane-proximal region described as a lipid-interacting domain (LID), yet, the LID structure and underlying molecular mechanisms are unknown. Here we decompose these, combining structural and biophysical methods, molecular dynamics simulations, cellular biotinylation- and immunofluorescence analysis and exchanger activity assays. We find that the NHE1-LID is intrinsically disordered and, in presence of membrane mimetics, forms a helical αα-hairpin co-structure with the membrane, anchoring the regulatory domain vis-a-vis the transport domain. This co-structure is fundamental for NHE1 activity, as its disintegration reduced steady-state pHi and the rate of pHi recovery after acid loading. We propose that regulatory lipid-protein co-structures may play equally important roles in other membrane proteins.
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| 3. |
- Watson, Hunna J., et al.
(author)
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Common Genetic Variation and Age of Onset of Anorexia Nervosa
- 2022
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In: BIOLOGICAL PSYCHIATRY: GLOBAL OPEN SCIENCE. - : Elsevier BV. - 2667-1743. ; 2:4, s. 368-378
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Journal article (peer-reviewed)abstract
- BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.
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| 4. |
- Alme, Tomas Nordheim, et al.
(author)
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Chronic fatigue syndromes: real illnesses that people can recover from
- 2023
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In: Scandinavian Journal of Primary Health Care. - : TAYLOR & FRANCIS LTD. - 0281-3432 .- 1502-7724. ; 41:4, s. 372-376
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Journal article (peer-reviewed)abstract
- The Oslo Chronic Fatigue Consortium consists of researchers and clinicians who question the current narrative that chronic fatigue syndromes, including post-covid conditions, are incurable diseases. Instead, we propose an alternative view, based on research, which offers more hope to patients. Whilst we regard the symptoms of these conditions as real, we propose that they are more likely to reflect the brains response to a range of biological, psychological, and social factors, rather than a specific disease process. Possible causes include persistent activation of the neurobiological stress response, accompanied by associated changes in immunological, hormonal, cognitive and behavioural domains. We further propose that the symptoms are more likely to persist if they are perceived as threatening, and all activities that are perceived to worsen them are avoided. We also question the idea that the best way to cope with the illness is by prolonged rest, social isolation, and sensory deprivation.Instead, we propose that recovery is often possible if patients are helped to adopt a less threatening understanding of their symptoms and are supported in a gradual return to normal activities. Finally, we call for a much more open and constructive dialogue about these conditions. This dialogue should include a wider range of views, including those of patients who have recovered from them.
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| 5. |
- Andreasen, Charlotte, et al.
(author)
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Incidence of Ischemic Stroke in Individuals with and without Aortic Valve Stenosis : A Danish Retrospective Cohort Study
- 2020
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In: Stroke. - 0039-2499. ; 51:1, s. 1364-1371
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Journal article (peer-reviewed)abstract
- Background and Purpose - Aortic valve stenosis may lead to atrial and ventricular remodeling, predisposes to atrial fibrillation, and may also be an independent risk factor of ischemic stroke. However, information on stroke rates among persons with aortic valve stenosis are sparse. We aimed to determine the incidence rates and relative risks of ischemic stroke in individuals with diagnosed aortic valve stenosis compared with age- and sex-matched controls. Methods - All patients with incident aortic valve stenosis aged >18 years (n=79 310) and age- and sex-matched controls were identified using the Danish nationwide registries (1997-2017). Incidence rates per 1000 person-years (PY) and multivariable adjusted hazard ratios with 95% CIs were reported. Results - In total, 873 373 individuals (median age 77 years, 51.5% men, 9.1% with aortic valve stenosis) were included. Ischemic stroke occurred in 70 205 (8.0%) individuals during 4 880 862 PY of follow-up. Incidence rates of ischemic stroke were 13.3/1000 PY among the controls compared with 30.4/1000 PY in patients with aortic valve stenosis, corresponding to a hazard ratio of 1.31 (95% CI, 1.28-1.34). In all age-groups, the incidence rates and relative risks were significantly increased in patients with aortic valve stenosis compared with controls, but the relative risk was greater for younger individuals (eg, age group, 18-45 years: hazard ratio, 5.94 [95% CI, 4.10-8.36]). In patients with aortic valve stenosis above 65 years of age, the risk of ischemic stroke was markedly lower after aortic valve replacement (30.3 versus 19.6/1000 PY before and after valve replacement). Among people with atrial fibrillation the incidence rate of ischemic stroke was 1.5 times higher when aortic valve stenosis was present (33.0/1000 PY versus 49.9/1000 PY). Conclusions - People with aortic valve stenosis have a significantly increased risk of ischemic stroke compared with age- and sex-matched controls. Future studies are warranted to explore whether antithrombotic therapy may be beneficial in some individuals.
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| 6. |
- Bane, Octavia, et al.
(author)
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Consensus-based technical recommendations for clinical translation of renal BOLD MRI
- 2020
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In: Magnetic Resonance Materials in Physics, Biology and Medicine. - : Springer. - 0968-5243 .- 1352-8661. ; 33:1, s. 199-215
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Research review (peer-reviewed)abstract
- Harmonization of acquisition and analysis protocols is an important step in the validation of BOLD MRI as a renal biomarker. This harmonization initiative provides technical recommendations based on a consensus report with the aim to move towards standardized protocols that facilitate clinical translation and comparison of data across sites. We used a recently published systematic review paper, which included a detailed summary of renal BOLD MRI technical parameters and areas of investigation in its supplementary material, as the starting point in developing the survey questionnaires for seeking consensus. Survey data were collected via the Delphi consensus process from 24 researchers on renal BOLD MRI exam preparation, data acquisition, data analysis, and interpretation. Consensus was defined as >= 75% unanimity in response. Among 31 survey questions, 14 achieved consensus resolution, 12 showed clear respondent preference (65-74% agreement), and 5 showed equal (50/50%) split in opinion among respondents. Recommendations for subject preparation, data acquisition, processing and reporting are given based on the survey results and review of the literature. These technical recommendations are aimed towards increased inter-site harmonization, a first step towards standardization of renal BOLD MRI protocols across sites. We expect this to be an iterative process updated dynamically based on progress in the field.
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| 7. |
- Casey, Jackie, et al.
(author)
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Incidence and sequence of scoliosis and windswept hip deformity : which comes first in 4148 children with cerebral palsy? A longitudinal cohort study
- 2024
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In: BMC Musculoskeletal Disorders. - : BioMed Central (BMC). - 1471-2474. ; 25:1
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Journal article (peer-reviewed)abstract
- BackgroundThe aim was to analyse whether scoliosis or windswept hip deformity (WSH) occurs first for children with cerebral palsy (CP).MethodsThis longitudinal cohort study using data from 1994 − 2020 (26 years) involved 41,600 measurements of 4148 children (2419 [58.3%] boys) with CP born 1990 − 2018 and registered into the Swedish CP follow-up program. Children were followed from a mean age of 2.8 [SD 1.4] years, until they developed either scoliosis or WSH or were removed at surgery.ResultsWSH developed first in 16.6% of the children (mean age 8.1 [SD 5.0] years), and scoliosis in 8.1% (mean age 8.1 [SD 4.9] years). The incidence of WSH was higher than scoliosis across all levels I–V of the Gross Motor Function Classification System (GMFCS), both sexes, and for those with dyskinetic (20.0%) or spastic (17.0%) CP. The incidence of scoliosis was highest (19.8%) and developed earliest in children with GMFCS level V (mean age 5.5 [SD 3.5] years), and in children with dyskinetic (17.9%) CP (mean age 7.0 [SD 4.7] years).ConclusionsWSH presents earlier than scoliosis in most children with CP. Children with higher GMFCS level or dyskinetic CP are more likely to develop these deformities at a younger age.
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| 10. |
- Jordet, Geir, et al.
(author)
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Scanning, Contextual Factors, and Association With Performance in English Premier League Footballers : An Investigation Across a Season
- 2020
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In: Frontiers in Psychology. - Lausanne : Frontiers Media S.A.. - 1664-1078. ; 11
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Journal article (peer-reviewed)abstract
- Scanning in football (soccer) denotes an active head movement where a player’s face is temporarily directed away from the ball to gather information in preparation for subsequently engaging with the ball. The aim of this study was to learn more about the ways that 27 elite professional football players in an English Premier League club use scanning in competitive matches, the conditions under which this behavior is exhibited, and the relationships between these behaviors and performance. Players were filmed across 21 matches, producing a total number of 9,574 individual ball possessions for analysis. Close-up video analyses of scanning show positional differences (with central midfielders and central defenders scanning most frequently, forwards least) and contextual differences (with relatively lower scanning frequency in situations with tight opponent pressure, in positions wide in the field and closer to the opponent’s goal, and under certain game state conditions). Players scan more frequently prior to giving passes than when they dribble, shoot, or only receive it, as well as prior to more long/forward passes compared to short/backward ones, although these differences are small. A Bayesian hierarchical model, which accounts for individual player differences and pass difficulty, suggests that the more a player scans, the higher the probability of completing a pass. In conclusion, match demands are likely to constrain the extent to which highly elite players scan, and scanning seems to have a small, but positive role in elite football players’ performance. © 2020 Jordet, Aksum, Pedersen, Walvekar, Trivedi, McCall, Ivarsson and Priestley.
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