| 1. |
- Koopman, J J E, et al.
(författare)
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Senescence rates in patients with end-stage renal disease: a critical appraisal of the Gompertz model.
- 2011
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Ingår i: Aging Cell. - : Wiley. - 1474-9726 .- 1474-9718. ; Dec, s. 233-238
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Tidskriftsartikel (refereegranskat)abstract
- The most frequently used model to describe the exponential increase in mortality rate over age is the Gompertz equation. Logarithmically transformed, the equation conforms to a straight line, of which the slope has been interpreted as the rate of senescence. Earlier, we proposed the derivative function of the Gompertz equation as a superior descriptor of senescence rate. Here, we tested both measures of the rate of senescence in a population of patients with end-stage renal disease. It is clinical dogma that patients on dialysis experience accelerated senescence, whereas those with a functional kidney transplant have mortality rates comparable to the general population. Therefore, we calculated the age-specific mortality rates for European patients on dialysis (n=274,221; follow-up=594,767 person-years), for European patients with a functioning kidney transplant (n=61,286; follow-up=345,024 person-years), and for the general European population. We found higher mortality rates, but a smaller slope of logarithmical mortality curve for patients on dialysis compared to both patients with a functioning kidney transplant and the general population (p<0.001). A classical interpretation of the Gompertz model would imply that the rate of senescence in patients on dialysis is lower than in patients with a functioning transplant and lower than in the general population. In contrast, the derivative function of the Gompertz equation yielded highest senescence rates for patients on dialysis, whereas the rate was similar in patients with a functioning transplant and the general population. We conclude that the rate of senescence is better described by the derivative function of the Gompertz equation.
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| 2. |
- Madar Johansson, Miralda, et al.
(författare)
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The binding mechanism of the virulence factor Streptococcus suis adhesin P subtype to globotetraosylceramide is associated with systemic disease
- 2020
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:42, s. 14305-14324
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Tidskriftsartikel (refereegranskat)abstract
- Streptococcus suis is part of the pig commensal microbiome but strains can also be pathogenic, causing pneumonia and meningitis in pigs as well as zoonotic meningitis. According to genomic analysis, S. suis is divided into asymptomatic carriage, respiratory and systemic strains with distinct genomic signatures. Because the strategies to target pathogenic S. suis are limited, new therapeutic approaches are needed. The virulence factor S. suis adhesin P (SadP) recognizes the galabiose Gal alpha 1-4Gal-oligosaccharide. Based on its oligosaccharide fine specificity, SadP can be divided into subtypes P-N and P-O. We show here that subtype P-N is distributed in the systemic strains causing meningitis, whereas type P-O is found in asymptomatic carriage and respiratory strains. Both types of SadP are shown to predominantly bind to pig lung globotriaosylceramide (Gb3). However, SadP adhesin from systemic subtype P-N strains also binds to globotetraosylceramide (Gb4). Mutagenesis studies of the galabiose-binding domain of type P-N SadP adhesin showed that the amino acid asparagine 285, which is replaced by an aspartate residue in type P-O SadP, was required for binding to Gb4 and, strikingly, was also required for interaction with the glycomimetic inhibitor phenylurea-galabiose. Molecular dynamics simulations provided insight into the role of Asn-285 for Gb4 and phenylurea-galabiose binding, suggesting additional hydrogen bonding to terminal GalNAc of Gb4 and the urea group. Thus, the Asn-285-mediated molecular mechanism of type P-N SadP binding to Gb4 could be used to selectively target S. suis in systemic disease without interfering with commensal strains, opening up new avenues for interventional strategies against this pathogen.
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| 3. |
- Munir, Arooj, et al.
(författare)
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Efficacy of copolymer scaffolds delivering human demineralised dentine matrix for bone regeneration
- 2019
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Ingår i: Journal of Tissue Engineering. - : SAGE PUBLICATIONS INC. - 2041-7314. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Poly(L-lactide-co-epsilon-caprolactone) scaffolds were functionalised by 10 or 20 mu g/mL of human demineralised dentine matrix. Release kinetics up to 21 days and their osteogenic potential on human bone marrow stromal cells after 7 and 21 days were studied. A total of 390 proteins were identified by mass spectrometry. Bone regeneration proteins showed initial burst of release. Human bone marrow stromal cells were cultured on scaffolds physisorbed with 20 mu g/mL and cultured in basal medium (DDM group) or physisorbed and cultured in osteogenic medium or cultured on non-functionalised scaffolds in osteogenic medium. The human bone marrow stromal cells proliferated less in demineralised dentine matrix group and activated ERK/1/2 after both time points. Cells on DDM group showed highest expression of IL-6 and IL-8 at 7 days and expressed higher collagen type 1 alpha 2, SPP1 and bone morphogenetic protein-2 until 21 days. Extracellular protein revealed higher collagen type 1 and bone morphogenetic protein-2 at 21 days in demineralised dentine matrix group. Cells on DDM group showed signs of mineralisation. The functionalised scaffolds were able to stimulate osteogenic differentiation of human bone marrow stromal cells.
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| 4. |
- Ohlsson, Jörgen, et al.
(författare)
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Structure–activity relationships of galabioside derivatives as inhibitors of E. coli and S. suis adhesins: nanomolar inhibitors of S. suis adhesins
- 2005
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Ingår i: Organic and Biomolecular Chemistry. - : Royal Society of Chemistry (RSC). - 1477-0539 .- 1477-0520. ; 3:5, s. 886-900
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Tidskriftsartikel (refereegranskat)abstract
- Four collections of Gal1-4Gal derivatives were synthesised and evaluated as inhibitors of the PapG class II adhesin of uropathogenic Escherichia coli and of the PN and PO adhesins of Streptococcus suis strains. Galabiosides carrying aromatic structures at C1, methoxyphenyl O-galabiosides in particular, were identified as potent inhibitors of the PapG adhesin. Phenylurea derivatisation at C3 and methoxymethylation at O2 of galabiose provided inhibitors of the S. suis strains type PN adhesin with remarkably high affinities (30 and 50 nM, respectively). In addition, quantitative structure–activity relationship models for E. coli PapG adhesin and S. suis adhesin type PO were developed using multivariate data analysis. The inhibitory lead structures constitute an advancement towards high-affinity inhibitors as potential anti-adhesion therapeutic agents targeting bacterial infections.
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| 5. |
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| 6. |
- Spillmann, Dorothe, et al.
(författare)
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Characterization of a novel pyruvylated carbohydrate unit implicated in the cell aggregation of the marine sponge Microciona prolifera
- 1993
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 268:18, s. 13378-13387
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Tidskriftsartikel (refereegranskat)abstract
- The species-specific Ca(2+)-dependent reaggregation of dissociated cells of the marine sponge Microciona prolifera is mediated by a large extracellular adhesion proteoglycan. The glycans of this molecule are involved in the interactions of the proteoglycan with itself and with the sponge cells. Monoclonal antibodies against the glycans block the aggregation of sponge cells (Misevic, G. N., Finne, J., and Burger, M. M. (1987) J. Biol. Chem. 262, 5870-5877). Proteoglycan oligosaccharides were prepared by partial acid hydrolysis of the isolated glycans, and their reactivity with the monoclonal antibodies was monitored after linkage to phospholipid and immunostaining of thin layer chromatograms. One major antibody-reactive oligosaccharide was detected and purified by ion-exchange chromatography and high performance liquid chromatography. 1H NMR spectroscopy, fast atom bombardment-mass spectrometry, methylation analysis, and sequential chemical and enzymatic degradation studies indicated the structure [formula: see text] for the oligosaccharide. The depyruvylated derivative of the oligosaccharide did not react with the aggregation-blocking antibody, which indicates that the pyruvate acetal is an essential part of the epitope.
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| 7. |
- Spillmann, Dorothe, et al.
(författare)
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Characterization of a Novel Sulfated Carbohydrate Unit Implicated in the CarbohydrateCarbohydrate-mediated Cell Aggregation of the Marine Sponge Microciona prolifera
- 1995
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 270, s. 5089-5097
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Tidskriftsartikel (refereegranskat)abstract
- Species-specific cell reaggregation in the marine sponge Microciona prolifera is mediated by an adhesion proteoglycan. Two interactions are involved in the process: a Ca(2+)-dependent homophilic binding between proteoglycan molecules and a Ca(2+)-independent binding between the molecule and cells. Both interactions are mediated by the glycan moieties of the proteoglycan. The interaction of the proteoglycan with itself has been characterized as a carbohydrate-carbohydrate interaction of multiple low affinity sites. The monoclonal antibodies Block 1 and Block 2 raised against the purified aggregation proteoglycan and selected for inhibition of aggregation bind to these glycans. In a previous report the structure, [formula: see text] was assigned to the oligosaccharide reacting with Block 1 antibody (Spillmann, D., Hård, K., Thomas-Oates, J., Vliegenthart, J. F. G., Misevic, G., Burger, M. M., and Finne, J. (1993) J. Biol. Chem. 268, 13378-13387). By the technique of attaching the water-soluble acid-degraded fragments to a lipid carrier for immunochemical detection and by chemical, enzymatic and spectroscopic methods the structure, [formula: see text] was assigned to the oligosaccharide reacting with the aggregation-blocking monoclonal antibody Block 2. The structure, [formula: see text] was assigned to a major nonreactive oligosaccharide, which outlined the molecular requirements of antibody binding of the two aggregation-associated epitopes. These data demonstrate that two different functional sites with distinct structural characteristics and antibody reactivities are involved in the reaggregation of sponge cells, a model of carbohydrate-carbohydrate-mediated cell interactions.
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