Biomedical subjects

Kristin Persson

Publications and source records attributed to Kristin Persson.

4 recordsLinked to original sources

PubMed2003

Predicting crystal structures with data mining of quantum calculations.

Predicting and characterizing the crystal structure of materials is a key problem in materials research and development. It is typically addressed with highly accurate quantum mechanical computations on a small set of candidate structures, or with empirical rules that have been extracted from a large amount of experimental information, but have limited predictive power. In this Letter, we transfer the concept of heuristic rule extraction to a large library of ab initio calculated information, and we demonstrate that this can be developed into a tool for crystal structure prediction.

Journal Article↗

PubMed2003

The conversion of fibrinogen to fibrin at the surface of curliated Escherichia coli bacteria leads to the generation of proinflammatory fibrinopeptides.

The inflammatory response to bacterial infection is the result of a complex interplay between bacterial products and host effector systems, such as the immune and complement systems. Here we show that Escherichia coli bacteria expressing fibrous surface proteins, known as curli, assemble and activate factors of the human coagulation cascade at their surface. As a result of this interaction, fibrinogen is converted to fibrin and fibrinogen-derived peptides, termed fibrinopeptides, are generated. The molecular mechanisms behind the bacteria-induced formation of fibrinopeptides were investigated and shown to be triggered by the activation of the contact system, also known as the kallikrein/kinin system or the intrinsic pathway of coagulation. Samples containing fibrinopeptides generated by the interaction between bacteria and plasma were injected into animals and the inflammatory response was monitored. We found that this treatment provoked an infiltration of white blood cells, and the induction of the proinflammatory cytokine MCP-1 at the inflamed site. Our results therefore demonstrate that activation of the coagulation system at the bacterial surface contributes to the pathophysiology of bacterial infectious diseases.

Amino Acid Sequence↗

PubMed2002

Identification of two protein-binding and functional regions of curli, a surface organelle and virulence determinant of Escherichia coli.

Curli are surface organelles of Escherichia coli. These fibrous proteins, formed by polymerization of a 15-kDa subunit, are expressed by E. coli strains associated with severe infections in humans. A remarkable property of curli is their ability to interact with a wide range of human proteins, interactions that contribute to the enhanced virulence of curli-expressing E. coli. To define the protein-binding region(s) of curli, we investigated the binding properties of overlapping synthetic peptides covering the curli subunit. Two peptides, one covering a 24-amino acid residue sequence in the NH(2)-terminal half of the subunit (NNS24) and one corresponding to the 26 COOH-terminal residues (VDQ26), were found to bind a number of human proteins. Physiochemical analysis revealed that NNS24 adopts a thermally stable beta-structure, and in solution the peptide forms soluble multimers, predominantly octamers. Intact curli are known to activate the proinflammatory and procoagulant contact system, and when added to human plasma, the NNS24 and VDQ26 peptides induced the release of the potent vasoactive peptide bradykinin. The results map important curli functions to the regions corresponding to the NNS24 and VDQ26 sequences.

Amino Acid Sequence↗

PubMed2002

Islet function phenotype in gastrin-releasing peptide receptor gene-deficient mice.

Gastrin-releasing peptide (GRP) is an islet neuropeptide that stimulates insulin secretion. To explore whether islet GRP contributes to neurally mediated insulin secretion, we studied GRP receptor (GRPR)-deleted mice. By using RT-PCR we showed that GRPR mRNA is expressed in islets of wild-type mice, but is lost in GRPR-deleted mice. Functional studies revealed that GRP potentiates glucose-stimulated insulin secretion in wild-type animals, but not in GRPR-deleted mice. This shows that GRPR is the receptor subtype mediating GRP-induced insulin secretion and that GRPR-deleted mice are tools for studying the physiological role of islet GRP. We found that GRPR-deleted mice display 1) augmentation of the insulin response to glucose by a mechanism inhibited by ganglionic blockade; 2) increased insulin responsiveness also to the cholinergic agonist carbachol, but not to arginine; 3) impaired insulin and glucagon responses to autonomic nerve activation by 2-deoxyglucose; 4) normal islet adaptation to high fat-induced insulin resistance and fasting; and 5) normal islet cytoarchitecture, as revealed by immunocytochemistry of insulin and glucagon. In conclusion, 1) GRPR is the receptor subtype mediating the islet effects of GRP; 2) GRP contributes to insulin secretion induced by activation of the autonomic nerves; and 3) deletion of GRPR is compensated by increased cholinergic sensitivity.

Adaptation, Physiological↗