Year of publication
- Staphylococcus aureus Proteins Sbi and Efb Recruit Human Plasmin to Degrade Complement C3 and C3b (2012)
- Upon host infection, the human pathogenic microbe Staphylococcus aureus (S. aureus) immediately faces innate immune reactions such as the activated complement system. Here, a novel innate immune evasion strategy of S. aureus is described. The staphylococcal proteins surface immunoglobulin-binding protein (Sbi) and extracellular fibrinogen-binding protein (Efb) bind C3/C3b simultaneously with plasminogen. Bound plasminogen is converted by bacterial activator staphylokinase or by host-specific urokinase-type plasminogen activator to plasmin, which in turn leads to degradation of complement C3 and C3b. Efb and to a lesser extend Sbi enhance plasmin cleavage of C3/C3b, an effect which is explained by a conformational change in C3/C3b induced by Sbi and Efb. Furthermore, bound plasmin also degrades C3a, which exerts anaphylatoxic and antimicrobial activities. Thus, S. aureus Sbi and Efb comprise platforms to recruit plasmin(ogen) together with C3 and its activation product C3b for efficient degradation of these complement components in the local microbial environment and to protect S. aureus from host innate immune reactions.
- Influence of genetic variations in TLR4 and TIRAP/Mal on the course of sepsis and pneumonia and cytokine release: an observational study in three cohorts (2010)
- Introduction: It has been proposed that individual genetic variation contributes to the course of severe infections and sepsis. Recent studies of single nucleotide polymorphisms (SNPs) within the endotoxin receptor and its signaling system showed an association with the risk of disease development. This study aims to examine the response associated with genetic variations of TLR4, the receptor for bacterial LPS, and a central intracellular signal transducer (TIRAP/Mal) on cytokine release and for susceptibility and course of severe hospital acquired infections in distinct patient populations. Methods: Three intensive care units in tertiary care university hospitals in Greece and Germany participated. 375 and 415 postoperative patients and 159 patients with ventilator associated pneumonia (VAP) were included. TLR4 and TIRAP/Mal polymorphisms in 375 general surgical patients were associated with risk of infection, clinical course and outcome. In two prospective studies, 415 patients following cardiac surgery and 159 patients with newly diagnosed VAP predominantly caused by Gram-negative bacteria were studied for cytokine levels in-vivo and after ex-vivo monocyte stimulation and clinical course. Results: Patients simultaneously carrying polymorphisms in TIRAP/Mal and TLR4 and patients homozygous for the TIRAP/Mal SNP had a significantly higher risk of severe infections after surgery (odds ratio (OR) 5.5; confidence interval (CI): 1.34 - 22.64; P = 0.02 and OR: 7.3; CI: 1.89 - 28.50; P < 0.01 respectively). Additionally we found significantly lower circulating cytokine levels in double-mutant individuals with ventilator associated pneumonia and reduced cytokine production in an ex-vivo monocyte stimulation assay, but this difference was not apparent in TIRAP/Mal-homozygous patients. In cardiac surgery patients without infection, the cytokine release profiles were not changed when comparing different genotypes. Conclusions: Carriers of mutations in sequential components of the TLR signaling system may have an increased risk for severe infections. Patients with this genotype showed a decrease in cytokine release when infected which was not apparent in patients with sterile inflammation following cardiac surgery.
- Superimposed high-frequency jet ventilation combined with continuous positive airway pressure/assisted spontaneous breathing improves oxygenation in patients with H1N1-associated ARDS (2012)
- Background: Numerous cases of swine-origin 2009 H1N1 influenza A virus (H1N1)-associated acute respiratory distress syndrome (ARDS) bridged by extracorporeal membrane oxygenation (ECMO) therapy have been reported; however, complication rates are high. We present our experience with H1N1-associated ARDS and successful bridging of lung function using superimposed high-frequency jet ventilation (SHFJV) in combination with continuous positive airway pressure/assisted spontaneous breathing (CPAP/ASB). Methods: We admitted five patients with H1N1 infection and ARDS to our intensive care unit. Although all patients required pure oxygen and controlled ventilation, oxygenation was insufficient. We applied SHFJV/CPAP/ASB to improve oxygenation. Results: Initial PaO2/FiO2 ratio prior SHFJV was 58-79 mmHg. In all patients, successful oxygenation was achieved by SHFJV (PaO2/FiO2 ratio 105-306 mmHg within 24 h). Spontaneous breathing was set during first hours after admission. SHFJV could be stopped after 39, 40, 72, 100, or 240 h. Concomitant pulmonary herpes simplex virus (HSV) infection was observed in all patients. Two patients were successfully discharged. The other three patients relapsed and died within 7 weeks mainly due to combined HSV infection and in two cases reoccurring H1N1 infection. Conclusions: SHFJV represents an alternative to bridge lung function successfully and improve oxygenation in the critically ill.
- Separation of strangeness from antistrangeness in the phase transition from quark to hadron matter: Possible formation of strange quark matter in heavy-ion collisions (1987)
- We present a mechanism for the separation of strangeness from antistrangeness in the deconfinement transition. For a net strangeness of zero in the total system, the population of s quarks is greatly enriched in the quark-gluon plasma, while the s¯ quarks drift into the hadronic phase. This separation could result in ‘‘strangelet’’ formation, i.e., metastable blobs of strange-quark matter, which could serve as a unique signature for quark-gluon plasma formation in heavy-ion collisions. PACS: 25.70.Np, 12.38.Mh
- Creation of strange-quark-matter droplets as a unique signature for quark-gluon plasma formation in relativistic heavy-ion collisions (1988)
- We demonstrate that strangeness separates in the Gibbs-phase coexistence between a baryon-rich quark-gluon plasma and hadron matter, even at T=0. For finite temperatures this is due to the associated production of kaons (containing s¯ quarks) in the hadron phase while s quarks remain in the deconfined phase. The s-s¯ separation results in a strong enhancement of the s-quark abundance in the quark phase. This mechanism is further supported by cooling and net strangeness enrichment due to the prefreezeout evaporation of pions and K+, K0, which carry away entropy and anti- strangeness from the system. Metastable droplets (i.e., stable as far as weak interactions are not regarded) of strange-quark matter (‘‘strangelets’’) can thus be formed during the phase transition. Such cool, compact, long-lived clusters could be experimentally observed by their unusually small Z/A ratio (≤0.1–0.3). Even if the strange-quark-matter phase is not stable under strong interactions, it should be observable by the delayed correlated emission of several hyperons. This would serve as a unique signature for the transient formation of a quark-gluon plasma.
- Canonical suppression in microscopic transport models (2006)
- We demonstrate the occurrence of canonical suppression associated with the conservation of an U(1)-charge in current transport models. For this study a pion gas is simulated within two different transport approaches by incorporating inelastic and volume-limited collisions pi pi leftrightarrow K bar-K for the production of kaon pairs. Both descriptions can dynamically account for the suppression in the yields of rare strange particles in a limited box, being in full accordance with a canonical statistical description.
- Chemical equilibration due to heavy Hagedorn states (2004)
- A scenario of heavy resonances, called massive Hagedorn states, is proposed which exhibits a fast (t H 1 fm/c) chemical equilibration of (strange) baryons and anti-baryons at the QCD critical temperature Tc. For relativistic heavy ion collisions this scenario predicts that hadronization is followed by a brief expansion phase during which the equilibration rate is higher than the expansion rate, so that baryons and antibaryons reach chemical equilibrium before chemical freeze-out occurs. PACS-Nr.: 12.38.Mh
- Dynamic canonical suppression of strangeness in transport models (2005)
- It is investigated whether canonical suppression associated with the exact conservation of an U(1)-charge can be reproduced correctly by current transport models. Therefore a pion-gas having a volume-limited cross section for kaon production and annihilation is simulated within two different transport prescriptions for realizing the inelastic collisions. It is found that both models can indeed dynamically account for the canonical suppression in the yields of rare strange particles.
- Untersuchung eines nichtselektiven Kationenkanals in M-1-Zellen aus dem Sammelrohr der Maus und in anderen Geweben mit der Patch-Clamp-Technik (1999)
- APADB: a database for alternative polyadenylation and microRNA regulation events (2014)
- Alternative polyadenylation (APA) is a widespread mechanism that contributes to the sophisticated dynamics of gene regulation. Approximately 50% of all protein-coding human genes harbor multiple polyadenylation (PA) sites; their selective and combinatorial use gives rise to transcript variants with differing length of their 3' untranslated region (3'UTR). Shortened variants escape UTR-mediated regulation by microRNAs (miRNAs), especially in cancer, where global 3'UTR shortening accelerates disease progression, dedifferentiation and proliferation. Here we present APADB, a database of vertebrate PA sites determined by 3' end sequencing, using massive analysis of complementary DNA ends. APADB provides (A)PA sites for coding and non-coding transcripts of human, mouse and chicken genes. For human and mouse, several tissue types, including different cancer specimens, are available. APADB records the loss of predicted miRNA binding sites and visualizes next-generation sequencing reads that support each PA site in a genome browser. The database tables can either be browsed according to organism and tissue or alternatively searched for a gene of interest. APADB is the largest database of APA in human, chicken and mouse. The stored information provides experimental evidence for thousands of PA sites and APA events. APADB combines 3' end sequencing data with prediction algorithms of miRNA binding sites, allowing to further improve prediction algorithms. Current databases lack correct information about 3'UTR lengths, especially for chicken, and APADB provides necessary information to close this gap. Database URL: http://tools.genxpro.net/apadb/