| 1. |
- Alalam, Hanna, et al.
(författare)
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A High-Throughput Method for Screening for Genes Controlling Bacterial Conjugation of Antibiotic Resistance.
- 2020
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Ingår i: mSystems. - 2379-5077. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- The rapid horizontal transmission of antibiotic resistance genes on conjugative plasmids between bacterial host cells is a major cause of the accelerating antibiotic resistance crisis. There are currently no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation, which prevents understanding and targeting conjugation. We introduce a novel experimental framework to screen for conjugation-based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. Plasmid-carrying donor strains are constructed in high-throughput. We then mix the resistance plasmid-carrying donors with recipients in a design where only transconjugants can reproduce, measure growth in dense intervals, and extract transmission times as the growth lag. As proof-of-principle, we exhaustively explore chromosomal genes controlling F-plasmid donation within Escherichia coli populations, by screening the Keio deletion collection in high replication. We recover all seven known chromosomal gene mutants affecting conjugation as donors and identify many novel mutants, all of which diminish antibiotic resistance transmission. We validate nine of the novel genes' effects in liquid mating assays and complement one of the novel genes' effect on conjugation (rseA). The new framework holds great potential for exhaustive disclosing of candidate targets for helper drugs that delay resistance development in patients and societies and improve the longevity of current and future antibiotics. Further, the platform can easily be adapted to explore interspecies conjugation, plasmid-borne factors, and experimental evolution and be used for rapid construction of strains.IMPORTANCE The rapid transmission of antibiotic resistance genes on conjugative plasmids between bacterial host cells is a major cause of the accelerating antibiotic resistance crisis. There are currently no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation, which prevents understanding and targeting conjugation. We introduce a novel experimental framework to screen for conjugation-based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. As proof-of-principle, we exhaustively explore chromosomal genes controlling F-plasmid donation within E. coli populations. We recover all previously known and many novel chromosomal gene mutants that affect conjugation efficiency. The new framework holds great potential for rapid screening of compounds that decrease transmission. Further, the platform can easily be adapted to explore interspecies conjugation, plasmid-borne factors, and experimental evolution and be used for rapid construction of strains.
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| 2. |
- Alalam, Hanna, et al.
(författare)
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Conjugation factors controlling F-plasmid antibiotic resistance transmission
- 2018
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Ingår i: BioRxiv. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The rapid horizontal transmission of many antibiotic resistance genes between bacterial host cells on conjugative plasmids is a major cause of the accelerating antibiotic resistance crisis. Preventing understanding and targeting conjugation, there currently are no experimental platforms for fast and cost-efficient screening of genetic effects on antibiotic resistance transmission by conjugation. We introduce a novel experimental framework to screen for conjugation based horizontal transmission of antibiotic resistance between >60,000 pairs of cell populations in parallel. Plasmid-carrying donor strains are constructed in high throughput. We then mix the resistance plasmid carrying donors with recipients in a design where only transconjugants can reproduce, measure growth in dense intervals and extract transmission times as the growth lag. As proof-of-principle, we exhaustively explored chromosomal genes controlling F plasmid donation within E. coli populations, by screening the Keio deletion collection at high replication. We recover all six known chromosomal gene mutants affecting conjugation and identify >50 novel factors, all of which diminish antibiotic resistance transmission. We verify 10 of the novel genes' effects in a liquid mating assay. The new framework holds great potential for exhaustive disclosing of candidate targets for helper drugs that delay resistance development in patients and societies and improves the longevity of current and future antibiotics.
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| 3. |
- Bäckberg, Matilda, et al.
(författare)
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Using in vitro receptor activity studies of synthetic cannabinoids to support the risk assessment of new psychoactive substances – A Swedish strategy to protect public health from harm
- 2023
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Ingår i: Forensic Science International. - : Elsevier Ireland Ltd. - 0379-0738 .- 1872-6283. ; 348
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Tidskriftsartikel (refereegranskat)abstract
- In the past 15 years, close to 1000 of new psychoactive substances (NPS) have been reported in Europe and globally. At the time of identification, data on safety, toxicity and carcinogenic potential of many NPS are not available or very limited. To work more efficiently, a strategy and collaboration between the Public Health Agency of Sweden (PHAS) and the National Board of Forensic Medicine was established involving in vitro receptor activity assays to demonstrate neurological activity of NPS. This report summarizes the first results on the synthetic cannabinoid receptor agonists (SCRAs), and subsequent actions taken by PHAS. A total of 18 potential SCRAs were selected by PHAS for in vitro pharmacological characterization. 17 compounds could be acquired and investigated for their activity on the human cannabinoid-1 (CB1) receptors expressed together with the AequoScreen system in CHO-K1 cells. Dose-response curves were established using eight different concentrations in triplicates at three occasions with JWH-018 as reference. For the MDMB-4en-PINACA, MMB-022, ACHMINACA, ADB-BUTINACA, 5F-CUMYL-PeGACLONE, 5C-AKB48, NM-2201, 5F-CUMYL-PINACA, JWH-022, 5Cl-AB-PINACA, MPhP-2201, 5F-AKB57 the half maximal effective concentration values ranged from 2.2 nM (5F-CUMYL-PINACA) to 171 nM (MMB-022). EG-018 and 3,5-AB-CHMFUPPYCA were none-active. The results contributed to 14 of these compounds being scheduled as narcotics in Sweden. In conclusion, many of the emerging SCRAs are potent activators of the CB1 receptor in vitro, although some lack activity or are partial agonists. The new strategy proved useful when data on psychoactive effects of the SCRAs under investigation were not available or limited. © 2023 The Authors
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| 4. |
- Cloetens, Lieselotte, et al.
(författare)
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Role of dietary beta-glucans in the prevention of the metabolic syndrome.
- 2012
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Ingår i: Nutrition Reviews. - : Oxford University Press (OUP). - 1753-4887 .- 0029-6643. ; 70:8, s. 444-458
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Tidskriftsartikel (refereegranskat)abstract
- The present review examines the evidence regarding the effect of β-glucan on variables linked to the metabolic syndrome (MetS), including appetite control, glucose control, hypertension, and gut microbiota composition. Appetite control can indirectly influence MetS by inducing a decreased energy intake, and promising results for a β-glucan intake to decrease appetite have been found using gut hormone responses and subjective appetite indicators. Beta-glucan also improves the glycemic index of meals and beneficially influences glucose metabolism in patients with type 2 diabetes or MetS, as well as in healthy subjects. Furthermore, a blood-pressure-lowering effect of β-glucan in hypertensive subjects seems fairly well substantiated. The gut microbiota composition might be an interesting target to prevent MetS, and preliminary results indicate the prebiotic potential of β-glucan. The evidence that β-glucan influences appetite control and gut microbiota in a positive way is still insufficient or difficult to interpret, and additional studies are needed in this field. Still, much evidence indicates that increased β-glucan intake could prevent MetS. Such evidence should encourage increased efforts toward the development of β-glucan-containing functional foods and promote the intake of β-glucan-rich foods, with the aim of reducing healthcare costs and disease prevalence.
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| 5. |
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| 6. |
- Folkenant, Matilda, et al.
(författare)
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Structure and properties of Cr–C/Ag films deposited by magnetron sputtering
- 2015
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Ingår i: Surface & Coatings Technology. - : Elsevier. - 0257-8972 .- 1879-3347. ; 281, s. 184-192
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Tidskriftsartikel (refereegranskat)abstract
- Cr–C/Ag thin films with 0–14 at.% Ag have been deposited by magnetron sputtering from elemental targets. The samples were analyzed by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy (XPS) and scanning electron microscopy (SEM) to study their structure and chemical bonding. A complex nanocomposite structure consisting of three phases; nanocrystalline Ag, amorphous CrCx and amorphous carbon is reported. The carbon content in the amorphous carbide phase was determined to be 32–33 at.% C, independent of Ag content. Furthermore, SEM and XPS results showed higher amounts of Ag on the surface compared to the bulk. The hardness and Young's modulus were reduced from 12 to 8 GPa and from 270 to 170 GPa, respectively, with increasing Ag content. The contact resistance was found to decrease with Ag addition, with the most Ag rich sample approaching the values of an Ag reference sample. Initial tribological tests gave friction coefficients in the range of 0.3 to 0.5, with no clear trends. Annealing tests show that the material is stable after annealing at 500 °C for 1 h, but not after annealing at 800 °C for 1 h. In combination, these results suggest that sputtered Cr–C/Ag films could be potentially applicable for electric contact applications.
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| 7. |
- Hallberg, Pär, et al.
(författare)
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Genetic variants associated with angiotensin-converting enzyme inhibitor-induced cough : a genome-wide association study in a Swedish population
- 2017
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Ingår i: Pharmacogenomics (London). - : FUTURE MEDICINE LTD. - 1462-2416 .- 1744-8042. ; 18:3, s. 201-213
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Tidskriftsartikel (refereegranskat)abstract
- Aim: We conducted a genome-wide association study on angiotensin-converting enzyme inhibitor-induced cough and used our dataset to replicate candidate genes iden-tified in previous studies. Patients & methods: A total of 124 patients and 1345 treated controls were genotyped using Illumina arrays. The genome-wide significance level was set to p < 5 x 10(-8). Results: We identified nearly genome-wide significant associations in CLASP1, PDE11A, KCNMB2, TGFA, SLC38A6 and MMP16. The strongest association was with rs62151109 in CLASP1 (odds ratio: 3.97; p = 9.44 x 10(-8)). All top hits except two were located in intronic or noncoding DNA regions. None of the candidate genes were significantly associated in our study. Conclusion: Angiotensin-converting enzyme inhibitor-induced cough is potentially associated with genes that are independent of bradykinin pathways.
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| 8. |
- Johansson Persson, Anna, et al.
(författare)
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A high intake of dietary fiber influences C-reactive protein and fibrinogen, but not glucose and lipid metabolism, in mildly hypercholesterolemic subjects.
- 2014
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6215 .- 1436-6207. ; 53:1, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of the study was to investigate how a diet high in dietary fiber, with several fiber sources included, modulates glucose and lipid metabolism and the inflammatory response in humans. METHODS: Subjects (n = 25) aged 58.6 (1.1) years (mean and SD) with a BMI of 26.6 (0.5) kg/m(2) and a total cholesterol (TC) of 5.8 (0.1) mmol/L (mean and SEM) were given a high fiber (HF) and low fiber (LF) diet, in a randomized controlled 5-week crossover intervention, separated by a 3-week washout. The HF diet consisted of oat bran, rye bran, and sugar beet fiber incorporated into test food products; one bread roll, one ready meal, and two beverages consumed daily. Equivalent food products, without added fibers, were provided in the LF diet. RESULTS: Total dietary fiber intake was 48.0 g and 30.2 g per day for the HF and LF diet, respectively. Significant reduction in C-reactive protein (CRP) was observed between the diets (P = 0.017) and a significant reduction in fibrinogen within the HF diet (P = 0.044). There were no significant effects in other measured circulating cytokines or in glucose, insulin, and lipid levels. CONCLUSIONS: Our study suggests that a 5-week high dietary fiber intake of oat bran, rye bran, and sugar beet fiber might reduce the low-grade inflammatory response measured as CRP which could, together with reduced fibrinogen, help to prevent the risk of cardiovascular disease.
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| 9. |
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| 10. |
- Johansson Persson, Anna, et al.
(författare)
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LC-QTOF/MS metabolomic profiles in human plasma after a 5-week high dietary fiber intake.
- 2013
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 405:14, s. 4799-4809
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Tidskriftsartikel (refereegranskat)abstract
- The objective was to investigate the alterations of plasma metabolome profiles to identify exposure and effect markers of dietary fiber intake. Subjects (n = 25) aged 58.6 (1.1) years (mean and SD) with a body mass index of 26.6 (0.5) kg/m(2) were given a high fiber (HF) and a low fiber (LF) diet, in a 5-week randomized controlled crossover intervention. The HF diet consisted of oat bran, rye bran, and sugar beet fiber incorporated into test food products, whereas the LF diet was made of equivalent food products to the HF diet, but without adding fibers. Blood plasma samples were collected at the start and end of each intervention period and analyzed by LC-QTOF/MS. In total, 6 features in positive mode and 14 features in negative mode were significantly different between the HF and the LF diet (p < 0.01, q < 0.05). Two markers, 2,6-dihydroxybenzoic acid and 2-aminophenol sulfate, were increased after HF diet, along with a tentatively identified saponin derived from oat avenacosides. The untargeted metabolomics approach enabled the identification of two new markers of dietary fiber intake in human plasma. Further studies will be needed to verify if these markers could serve as compliance markers of fiber intake.
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