| 1. |
- Omattage, Natalie S., et al.
(författare)
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Structural basis for usher activation and intramolecular subunit transfer in P pilus biogenesis in Escherichia coli
- 2018
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Ingår i: Nature Microbiology. - : NATURE PUBLISHING GROUP. - 2058-5276. ; 3:12, s. 1362-1368
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Tidskriftsartikel (refereegranskat)abstract
- Chaperone-usher pathway pili are extracellular proteinaceous fibres ubiquitously found on Gram-negative bacteria, and mediate host-pathogen interactions and biofilm formation critical in pathogenesis in numerous human diseases(1). During pilus assembly, an outer membrane macromolecular machine called the usher catalyses pilus biogenesis from the individual subunits that are delivered as chaperone-subunit complexes in the periplasm. The usher orchestrates pilus assembly using all five functional domains: a 24-stranded transmembrane beta-barrel translocation domain, a beta-sandwich plug domain, an amino-terminal periplasmic domain and two carboxy-terminal periplasmic domains (CTD1 and CTD2)(2-6). Despite extensive structural and functional characterization, the mechanism by which the usher is activated to initiate pilus biogenesis is unknown. Here, we present the crystal structure of the full-length PapC usher from Escherichia coli in complex with its cognate PapDG chaperone-subunit complex in a pre-activation state, elucidating molecular details of how the usher is specifically engaged by allosteric interactions with its substrate preceding activation and how the usher facilitates the transfer of subunits from the amino-terminal periplasmic domain to the CTDs during pilus assembly. This work elucidates the intricate workings of a molecular machine that catalyses chaperone-usher pathway pilus assembly and opens the door for the development of potent inhibitors to block pilus biogenesis.
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| 2. |
- Ambite, Ines, et al.
(författare)
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Fimbriae reprogram host gene expression - Divergent effects of P and type 1 fimbriae
- 2019
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7366 .- 1553-7374. ; 15:6, s. 1007671-1007671
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Tidskriftsartikel (refereegranskat)abstract
- Pathogens rely on a complex virulence gene repertoire to successfully attack their hosts. We were therefore surprised to find that a single fimbrial gene reconstitution can return the virulence-attenuated commensal strain Escherichia coli 83972 to virulence, defined by a disease phenotype in human hosts. E. coli 83972pap stably reprogrammed host gene expression, by activating an acute pyelonephritis-associated, IRF7-dependent gene network. The PapG protein was internalized by human kidney cells and served as a transcriptional agonist of IRF-7, IFN-β and MYC, suggesting direct involvement of the fimbrial adhesin in this process. IRF-7 was further identified as a potent upstream regulator (-log (p-value) = 61), consistent with the effects in inoculated patients. In contrast, E. coli 83972fim transiently attenuated overall gene expression in human hosts, enhancing the effects of E. coli 83972. The inhibition of RNA processing and ribosomal assembly indicated a homeostatic rather than a pathogenic end-point. In parallel, the expression of specific ion channels and neuropeptide gene networks was transiently enhanced, in a FimH-dependent manner. The studies were performed to establish protective asymptomatic bacteriuria in human hosts and the reconstituted E. coli 83972 variants were developed to improve bacterial fitness for the human urinary tract. Unexpectedly, P fimbriae were able to drive a disease response, suggesting that like oncogene addiction in cancer, pathogens may be addicted to single super-virulence factors.
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| 3. |
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| 6. |
- Linne, A, et al.
(författare)
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Abdominal aortic aneurysm screening attendance: Effect of removing the examination fee
- 2018
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Ingår i: Journal of medical screening. - : SAGE Publications. - 1475-5793 .- 0969-1413. ; 25:4, s. 223-224
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Tidskriftsartikel (refereegranskat)abstract
- The organized population-based screening programme for abdominal aortic aneurysm in Stockholm, Sweden, started in 2010. An examination fee was initially charged, but later removed because of a policy change. We examined the effect on screening attendance of removing the fee. Methods The periods before and after removing the examination fee were compared with regard to screening attendance, overall, by municipality and by district. Results Screening attendance was 79.2% in the period with an examination fee and 79.9% in the period without an examination fee (p = 0.1787), with no significant change in screening attendance between the periods. Conclusions Although removing examination fees has been shown to have a positive impact on attendance in other screening programmes, we did not find this association in our study.
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| 7. |
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| 8. |
- Matic, L. P., et al.
(författare)
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Novel Multiomics Profiling of Human Carotid Atherosclerotic Plaques and Plasma Reveals Biliverdin Reductase B as a Marker of Intraplaque Hemorrhage
- 2018
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Ingår i: JACC: Basic to Translational Science. - : Elsevier BV. - 2452-302X. ; 3:4, s. 464-480
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Tidskriftsartikel (refereegranskat)abstract
- Clinical tools to identify individuals with unstable atherosclerotic lesions are required to improve prevention of myocardial infarction and ischemic stroke. Here, a systems-based analysis of atherosclerotic plaques and plasma from patients undergoing carotid endarterectomy for stroke prevention was used to identify molecular signatures with a causal relationship to disease. Local plasma collected in the lesion proximity following clamping prior to arteriotomy was profiled together with matched peripheral plasma. This translational workflow identified biliverdin reductase B as a novel marker of intraplaque hemorrhage and unstable carotid atherosclerosis, which should be investigated as a potential predictive biomarker for cardiovascular events in larger cohorts.
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| 9. |
- Norman, M., et al.
(författare)
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Urinary fluoride excretion in preschool children after intake of fluoridated milk and use of fluoride-containing toothpaste
- 2017
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Ingår i: Community Dental Health. - Suffolk : FDI World Dental Press Ltd.. - 0265-539X. ; 34:1, s. 27-31
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the urinary fluoride excretion in preschool children after drinking fluoridated milk with 0.185 mg F and 0.375 mg F and to study the impact of use of fluoride toothpaste.Basic research design: Double-blind cross-over study.Participants: Nine healthy children, 2.5-4.5 years of age.Intervention: In a randomized order, participants drank 1.5 dl milk once daily for 7 days with no fluoride added (control), 0.185 mg fluoride added and 0.375 mg fluoride added. The experiment was performed twice with (Part I) and without (Part II) parental tooth brushing with 1,000 ppm fluoride toothpaste. The fluoride content in the piped drinking water was 0.5 mg F/L.Main outcome measure: Urinary fluoride excretion.Results: The 24-hour urinary fl uoride excretion/kg body weight varied from 0.014 mg F for the placebo intervention and non-fluoride toothpaste to 0.027 mg F for the 0.375 mg intervention with use of 1,000 ppm fluoride toothpaste. The difference compared with the placebo intervention was not statistically significant for any of the interventions when fluoride toothpaste was used (p⟩0.05) while it was statistically significantly different when non-fluoride toothpaste was used (p⟨0.05).Conclusions: All sources of fluoride must be considered when designing community programs. With 0.5 mg F/L in the drinking water and daily use of fluoride toothpaste, most children had a fluoride intake optimal for dental health. In this setting, additional intake of fluoride milk was within safe limits up to 0.185 mg/day while conclusions about the safety of 0.375 mg/day were uncertain.
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| 10. |
- Nowak-Sliwinska, Patrycja, et al.
(författare)
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Consensus guidelines for the use and interpretation of angiogenesis assays
- 2018
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Ingår i: Angiogenesis. - : Springer. - 0969-6970 .- 1573-7209. ; 21:3, s. 425-532
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Forskningsöversikt (refereegranskat)abstract
- The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference.
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