| 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. |
- Vogelezang, Suzanne, et al.
(författare)
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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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| 3. |
- Forslund, Sofia K., et al.
(författare)
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Combinatorial, additive and dose-dependent drug–microbiome associations
- 2021
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 600:7889, s. 500-505
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Tidskriftsartikel (refereegranskat)abstract
- During the transition from a healthy state to cardiometabolic disease, patients become heavily medicated, which leads to an increasingly aberrant gut microbiome and serum metabolome, and complicates biomarker discovery1–5. Here, through integrated multi-omics analyses of 2,173 European residents from the MetaCardis cohort, we show that the explanatory power of drugs for the variability in both host and gut microbiome features exceeds that of disease. We quantify inferred effects of single medications, their combinations as well as additive effects, and show that the latter shift the metabolome and microbiome towards a healthier state, exemplified in synergistic reduction in serum atherogenic lipoproteins by statins combined with aspirin, or enrichment of intestinal Roseburia by diuretic agents combined with beta-blockers. Several antibiotics exhibit a quantitative relationship between the number of courses prescribed and progression towards a microbiome state that is associated with the severity of cardiometabolic disease. We also report a relationship between cardiometabolic drug dosage, improvement in clinical markers and microbiome composition, supporting direct drug effects. Taken together, our computational framework and resulting resources enable the disentanglement of the effects of drugs and disease on host and microbiome features in multimedicated individuals. Furthermore, the robust signatures identified using our framework provide new hypotheses for drug–host–microbiome interactions in cardiometabolic disease.
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| 4. |
- Fadista, João, et al.
(författare)
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Genetic regulation of spermine oxidase activity and cancer risk : a Mendelian randomization study
- 2021
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Spermine oxidase (SMOX) catalyzes the oxidation of spermine to spermidine. Observational studies have reported SMOX as a source of reactive oxygen species associated with cancer, implying that inhibition of SMOX could be a target for chemoprevention. Here we test causality of SMOX levels with cancer risk using a Mendelian randomization analysis. We performed a GWAS of spermidine/spermine ratio to identify genetic variants associated with regulation of SMOX activity. Replication analysis was performed in two datasets of SMOX gene expression. We then did a Mendelian randomization analysis by testing the association between the SMOX genetic instrument and neuroblastoma, gastric, lung, breast, prostate, and colorectal cancers using GWAS summary statistics. GWAS of spermidine/spermine ratio identified SMOX locus (P = 1.34 × 10–49) explaining 32% of the variance. The lead SNP rs1741315 was also associated with SMOX gene expression in newborns (P = 8.48 × 10–28) and adults (P = 2.748 × 10–8) explaining 37% and 6% of the variance, respectively. Genetically determined SMOX activity was not associated with neuroblastoma, gastric, lung, breast, prostate nor colorectal cancer (P > 0.05). A PheWAS of rs1741315 did not reveal any relevant associations. Common genetic variation in the SMOX gene was strongly associated with SMOX activity in newborns, and less strongly in adults. Genetic down-regulation of SMOX was not significantly associated with lower odds of neuroblastoma, gastric, lung, breast, prostate and colorectal cancer. These results may inform studies of SMOX inhibition as a target for chemoprevention.
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| 5. |
- Gyldenkerne, Christine, et al.
(författare)
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Coronary Artery Lesion Lipid Content and Plaque Burden in Diabetic and Nondiabetic Patients : PROSPECT II
- 2023
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 147:6, s. 469-481
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with diabetes have increased rates of major adverse cardiac events (MACEs). We hypothesized that this is explained by diabetes-associated differences in coronary plaque morphology and lipid content.METHODS: In PROSPECT II (Providing Regional Observations to Study Predictors of Events in the Coronary Tree), 898 patients with acute myocardial infarction with or without ST-segment elevation underwent 3-vessel quantitative coronary angiography and coregistered near-infrared spectroscopy and intravascular ultrasound imaging after successful percutaneous coronary intervention. Subsequent MACEs were adjudicated to either treated culprit lesions or untreated nonculprit lesions. This substudy stratified patients by diabetes status and assessed baseline culprit and nonculprit prevalence of high-risk plaque characteristics defined as maximum plaque burden ≥70% and maximum lipid core burden index ≥324.7. Separate covariate-adjusted multivariable models were performed to identify whether diabetes was associated with nonculprit lesion-related MACEs and high-risk plaque characteristics.RESULTS: Diabetes was present in 109 of 898 patients (12.1%). During a median 3.7-year follow-up, MACEs occurred more frequently in patients with versus without diabetes (20.1% versus 13.5% [odds ratio (OR), 1.94 (95% CI, 1.14-3.30)]), primarily attributable to increased risk of myocardial infarction related to culprit lesion restenosis (4.3% versus 1.1% [OR, 3.78 (95% CI, 1.12-12.77)]) and nonculprit lesion-related spontaneous myocardial infarction (9.3% versus 3.8% [OR, 2.74 (95% CI, 1.25-6.04)]). However, baseline prevalence of high-risk plaque characteristics was similar for patients with versus without diabetes concerning culprit (maximum plaque burden ≥70%: 90% versus 93%, P=0.34; maximum lipid core burden index ≥324.7: 66% versus 70%, P=0.49) and nonculprit lesions (maximum plaque burden ≥70%: 23% versus 22%, P=0.37; maximum lipid core burden index ≥324.7: 26% versus 24%, P=0.47). In multivariable models, diabetes was associated with MACEs in nonculprit lesions (adjusted OR, 2.47 [95% CI, 1.21-5.04]) but not with prevalence of high-risk plaque characteristics (adjusted OR, 1.21 [95% CI, 0.86-1.69]).CONCLUSIONS: Among patients with recent myocardial infarction, both treated and untreated lesions contributed to the diabetes-associated ≈2-fold increased MACE rate during the 3.7-year follow-up. Diabetes-related plaque characteristics that might underlie this increased risk were not identified by multimodality imaging.
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| 6. |
- Lojewski, Tobias, et al.
(författare)
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The interplay of local electron correlations and ultrafast spin dynamics in fcc Ni
- 2023
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Ingår i: Materials Research Letters. - : Taylor & Francis. - 2166-3831. ; 11:8, s. 655-661
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Tidskriftsartikel (refereegranskat)abstract
- The complex electronic structure of metallic ferromagnets is determined by a balance between exchange interaction, electron hopping leading to band formation, and local Coulomb repulsion. By combining high energy and temporal resolution in femtosecond time-resolved X-ray absorption spectroscopy with ab initio time-dependent density functional theory we analyze the electronic structure in fcc Ni on the time scale of these interactions in a pump-probe experiment. We distinguish transient broadening and energy shifts in the absorption spectra, which we demonstrate to be captured by electron repopulation respectively correlation-induced modifications of the electronic structure, requiring to take the local Coulomb interaction into account.
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| 7. |
- Quarsten, H., et al.
(författare)
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Tick-borne Pathogens Detected in the Blood of Immunosuppressed Norwegian Patients Living in a Tick-endemic Area
- 2021
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 73:7
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Tidskriftsartikel (refereegranskat)abstract
- Background. The knowledge regarding the occurrence and the clinical implications of tick-borne infections in immunosuppressed patients living in tick-endemic areas is limited. Methods. Adult patients with autoimmune conditions requiring immunosuppressive treatment such as infliximab and rituximab were invited to participate in the study when they attended the hospital for treatment and/or control of the disease. Whole-blood samples were analyzed by real-time polymerase chain reaction for Borrelia burgdorferi sensu lato, Borrelia miyamotoi, Anaplasma phagocytophilum, Rickettsia spp., Candidatus Neoehrlichia mikurensis, and Babesia spp. Results. The occurrence of tick-borne pathogens in the blood of patients (n = 163) with autoimmune conditions requiring immunosuppressive treatment was evaluated. Pathogen DNA was detected in 8.6% (14/163) of the patients. The predominant pathogen was Ca. Neoehrlichia mikurensis (12/14), which was carried in the blood of infected patients for 10-59 days until treatment with doxycycline. B. burgdorferi s.l. and Rickettsia spp. were detected in 1 patient each. The B. burgdorferi-infected patient presented with fever, whereas the remaining patients were judged to have subclinical infections. B. miyamotoi, A. phagocytophilum, and Babesia spp. were not detected in any patient. Conclusions. Patients treated with biologicals and living in a tick-endemic area seem to have a high risk of contracting Ca. Neoehrlichia mikurensis infection, which, if left untreated, could result in thromboembolic complications.
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| 8. |
- Rasmussen, Sune Olander, et al.
(författare)
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Ice-core data used for the construction of the Greenland Ice-Core Chronology 2005 and 2021 (GICC05 and GICC21)
- 2023
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Ingår i: Earth System Science Data. - 1866-3508 .- 1866-3516. ; 15:8, s. 3351-3364
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Tidskriftsartikel (refereegranskat)abstract
- We here describe, document, and make available a wide range of data sets used for annual-layer identification in ice cores from DYE-3, GRIP, NGRIP, NEEM, and EGRIP. The data stem from detailed measurements performed both on the main deep cores and shallow cores over more than 40 years using many different setups developed by research groups in several countries and comprise both discrete measurements from cut ice samples and continuous-flow analysis data.The data series were used for counting annual layers 60 000 years back in time during the construction of the Greenland Ice-Core Chronology 2005 (GICC05) and/or the revised GICC21, which currently only reaches 3800 years back. Now that the underlying data are made available (listed in Table 1) we also release the individual annual-layer positions of the GICC05 timescale which are based on these data sets.We hope that the release of the data sets will stimulate further studies of the past climate taking advantage of these highly resolved data series covering a large part of the interior of the Greenland ice sheet.
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