Degradation of human kininogens with the release of kinin peptides by extracellular proteinases of Candida spp.

The secretion of proteolytic enzymes by pathogenic microorganisms is one of the most successful strategies used by pathogens to colonize and infect the host organism. The extracellular microbial proteinases can seriously deregulate the homeostatic proteolytic cascades of the host, including the kinin-forming system, repeatedly reported to he activated during bacterial infection. The current study assigns a kinin-releasing activity to secreted proteinases of Candida spp. yeasts, the major fungal pathogens of humans. Of several Candida species studied, C. parapsilosis and C. albicans in their invasive filamentous forms are shown to produce proteinases which most effectively degrade proteinaceous kinin precursors, the kininogens. These enzymes, classified as aspartyl proteinases, have the highest kininogen-degrading activity at low pH (approx. 3.5), but the associated production of bradykinin-related peptides from a small fraction of kininogen molecules is optimal at neutral pH (6.5). The peptides effectively interact with cellular B2-type kinin receptors. Moreover, kinin-related peptides capable of interacting with inflammation-induced B1-type receptors are also formed, but with a reversed pH dependence. The presented variability of the potential extracellular kinin production by secreted aspartyl proteinases of Candida spp. is consistent with the known adaptability of these opportunistic pathogens to different niches in the host organism

Low-temperature concentration of tellurium and gold in continental red bed successions

Acknowledgements This research was supported by NERC grants (NE/L001764/1, NE/M010953/1). We are grateful to J. Still and A. Sandison for technical support and to the gypsum mines and C. Brolley for access and sampling. Critical comments from Cristiana Ciobanu, Eric Gloaguen and Georges Calas are gratefully acknowledged. The authors have no conflicts of interest to declare.Peer reviewedPublisher PD

Synthesis of Novel Peptide Inhibitors of Thrombin-induced Platelet Activation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65762/1/j.1747-0285.2006.00442.x.pd

A Boron, Nitrogen, and Oxygen Doped π-Extended Helical Pure Blue Multiresonant Thermally Activated Delayed Fluorescent Emitter for Organic Light Emitting Diodes That Shows Fast kRISC Without the Use of Heavy Atoms

Narrowband emissive multiresonant thermally activated delayed fluorescence (MR-TADF) emitters are a promising solution to achieve the current industry-targeted color standard, Rec. BT.2020-2, for blue color without using optical filters, aiming for high-efficiency organic light-emitting diodes (OLEDs). However, their long triplet lifetimes, largely affected by their slow reverse intersystem crossing rates, adversely affect device stability. In this study, a helical MR-TADF emitter (f-DOABNA) is designed and synthesized. Owing to its π-delocalized structure, f-DOABNA possesses a small singlet-triplet gap, ΔEST, and displays simultaneously an exceptionally faster reverse intersystem crossing rate constant, kRISC, of up to 2 × 10⁶ s⁻¹ and a very high photoluminescence quantum yield, ΦPL, of over 90% in both solution and doped films. The OLED with f-DOABNA as the emitter achieved a narrow deep-blue emission at 445 nm (full width at half-maximum of 24 nm) associated with Commission Internationale de l'Éclairage (CIE) coordinates of (0.150, 0.041), and showed a high maximum external quantum efficiency, EQEmax, of ≈20%

Two Faces of High-Molecular-Weight Kininogen (HK) in Angiogenesis: Bradykinin Turns it on and Cleaved HK (HKa) Turns it off

High-molecular-weight kininogen (HK) is a plasma protein that possesses multiple physiological functions. Originally identified as a precursor of bradykinin, a bioactive peptide that regulates many cardiovascular processes, it is now recognized that HK plays important roles in fibrinolysis, thrombosis, and inflammation. HK binds to endothelial cells where it can be cleaved by plasma kallikrein to release bradykinin (13K). The remaining portion of the molecule, cleaved HK, is designated cleaved high-molecular-weight kininogen or HKa. While BK has been intensively studied, the physiological implication of the generation of HKa is not clear. Recent studies have revealed that HKa inhibits angiogenesis while BK promotes angiogenesis. These findings represent novel functions of the kallikrein-kinin system that have not yet been fully appreciated. In this review, we will briefly discuss the recent progress in the studies of the molecular mechanisms that mediate the antiangiogenic effect of HKa and the proangiogenic activity of BK

The regulation of human factor XIIa by plasma proteinase inhibitors.

Studies of the inactivation of factor XIIa by plasma protease inhibitors in purified systems and in plasma were initiated to determine the relative importance of these inhibitors to the neutralization of factor XIIa. Factor XIIa was measured by the amidolysis of H-D-prolyl-L-phenylalanyl-L-arginine-p-nitroanilide dihydrochloride or by coagulant activity. C1 inhibitor (C1INH), alpha 2-antiplasmin (alpha 2AP), alpha 2-macroglobulin (alpha 2M), and antithrombin III (ATIII) inhibited factor XIIa with second-order rate constants of 2.2 X 10(5), 1.1 X 10(4), 5.0 X 10(3), and 1.3 X 10(3) M-1 min-1. Factor XIIa activity was not affected by alpha 1-proteinase inhibitor. Incubation of 125I-radiolabeled factor XIIa resulted in 1:1 stoichiometric complexes with C1INH (Mr 190,000), ATIII (Mr 125,000), and alpha 2AP (Mr 150,000 and 125,000) using sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Incubation of 125I-Factor XIIa with alpha 2M resulted in a component of Mr 85,000 on a reduced sodium dodecyl sulfate-polyacrylamide gel, indicating that a subunit of factor XIIa was covalently bound to a proteolyzed portion of alpha 2M. The relative effectiveness of each inhibitor at plasma concentrations was 61:2:3:1 for C1INH, alpha 2AP, alpha 2M, and ATIII, respectively. Kinetic studies of the inactivation of purified factor XIIa added to various plasmas containing different concentrations of C1INH verified the predictions from the purified systems. Gel filtration of radiolabeled factor XIIa incubated with plasma confirmed that factor XIIa-C1INH was the major complex. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that the complexes in plasma had the same molecular size as those with purified inhibitors. C1INH functions as the predominant inhibitor of factor XIIa in plasma