621 research outputs found
Molecular studies of Neisseria : host cell interactions
No full textThe Neisseria family includes many non-pathogenic species but also two strict human pathogens; Neisseria gonorrhoeae and Neisseria meningitidis. Both organisms colonise mucosal surfaces and may cause disseminated infections upon passage of the epithelial barrier. A correlation between neisserial pathogenesis and deficiencies in complement factors has been observed.To investigate novel interactions between regulators of the complement system and Neisseria we focused on C4b-binding protein (C4BP), a cofactor for serine proteinase factor 1, preventing the assembly of C3-convertase. We found that the pilusassociated protein PilC of N. gonorrhoeae interacted with C4BP which may contribute to serum resistance by allowing the bacteria to escape complement attack. The human specificity of the pathogenic Neisseria strains has resulted in difficulties developing an animal model mimicking the course of disease seen in humans. Both organisms adhere to host cells by an interaction between pili and the cell surface complement regulator, CD46. By using mice expressing human CD46 we developed a model that resembles both the development of disease and the immune response seen in humans upon meningococcal infection. As in humans, meningococcal invasion of the intranasal epithelium was dependent on pilus expression and the production of proand anti-inflammatory cytokines in serum of CD46 transgenic mice were comparable to levels seen in humans with severe meningococcal disease. We also found that meningococcal passage of the blood-brain barrier required expression of human CD46.To identify important virulence factors in human meningococcal disease we studied clinical isolates from patients with invasive meningococcal disease. Our data showed that meningococcal strains from the upper respiratory tract, blood and CSF possessed different binding capacities to epithelial cells and that PilC was an important factor for the initial binding. We also found that phase variation in the pilus-adhesin PilC and sequence variation in the pilus subunit PilE occurred among strains isolated from different locations within one individual.List of scientific papersI. Blom AM, Rytkonen A, Vasquez P, Lindahl G, Dahlback B, Jonsson AB (2001). A novel interaction between type IV pili of Neisseria gonorrhoeae and the human complement regulator C4B-binding protein. J Immunol. 166(11): 6764-70. https://pubmed.ncbi.nlm.nih.gov/11359834II. Johansson L, Rytkonen A, Bergman P, Albiger B, Kallstrom H, Hokfelt T, Agerberth B, Cattaneo R, Jonsson AB (2003). CD46 in meningococcal disease. Science. 301(5631): 373-5. https://pubmed.ncbi.nlm.nih.gov/12869763III. Johansson L, Rytkonen A, Bergman P, Hokfelt T, Jonsson AB (2004). Meningococcal infection of CD46 transgenic mice induces human-like early immune responses. [Manuscript]IV. Rytkonen A, Albiger B, Hansson-Palo P, Kallstrom H, Olcen P, Fredlund H, Jonsson AB (2004). Neisseria meningitidis undergoes PilC phase variation and PilE sequence variation during invasive disease. J Infect Dis. 189(3): 402-9. Epub 2004 Jan 20 https://pubmed.ncbi.nlm.nih.gov/14745697</p
The International Convention for the Control and Management of Ships' Ballast Water and Sediments 2004: A Critical Appraisal
No full textDevelopment of a Sandwich ELISA to Measure Exposure to Occupational Cow Hair Allergens
No full textBackground: Cow hair and dander are important inducers of occupational allergies in cattle-exposed farmers. To estimate allergen exposure in farming environments, a sensitive enzyme immunoassay was developed to measure cow hair allergens. Methods: A sandwich ELISA was developed using polyclonal rabbit antibodies against a mixture of hair extracts from different cattle breeds. To assess the specificity of the assay, extracts from other mammalian epithelia, mites, molds and grains were tested. To validate the new assay, cow hair allergens were measured in passive airborne dust samples from the stables and homes of farmers. Dust was collected with electrostatic dust fall collectors (EDCs). Results: The sandwich ELISA was found to be very sensitive (detection limit: 0.1 ng/ml) and highly reproducible, demonstrating intra-and interassay coefficients of variation of 4 and 10%, respectively. The assay showed no reactivity with mites, molds and grains, but some cross-reactivity with other mammalian epithelia, with the strongest reaction with goat. Using EDCs for dust sampling, high concentrations of bovine allergens were measured in cow stables (4,760-559,400 mu g/m(2)). In addition, bovine allergens were detected in all areas of cattle farmer dwellings. A large variation was found between individual samples (0.3-900 mu g/m(2)) and significantly higher values were discovered in changing rooms. Conclusion: The ELISA developed for the detection of cow hair proteins is a useful tool for allergen quantification in occupational and home environments. Based on its low detection limit, this test is sensitive enough to detect allergens in passive airborne dust. Copyright (C) 2011 S. Karger AG, Base
Production of (anti-)He-3 and (anti-)H-3 in p-Pb collisions at root s(NN)=5.02 TeV
No full textThe transverse momentum (p(T)) differential yields of (anti-)He-3 and (anti-)H-3 measured in p-Pb collisions at root s(NN) = 5.02 TeV with ALICE at the Large Hadron Collider (LHC) are presented. The ratios of the p(T)-integrated yields of (anti-)He-3 and (anti-)H-3 to the proton yields are reported, as well as the pT dependence of the coalescence parameters B-3 for (anti-)He-3 and (anti-)H-3. For (anti-)He-3, the results obtained in four classes of the mean charged-particle multiplicity density are also discussed. These results are compared to predictions from a canonical statistical hadronization model and coalescence approaches. An upper limit on the total yield of (4)(He) over bar is determined.Peer reviewe
Intraperitoneal seeding from hepatocellular carcinoma following percutaneous ethanol ablation therapy
No full textMeasurement of the Lifetime and Λ Separation Energy of _{Λ}^{3}H
No full textThe most precise measurements to date of the _{Λ}^{3}H lifetime τ and Λ separation energy B_{Λ} are obtained using the data sample of Pb-Pb collisions at sqrt[s_{NN}]=5.02 TeV collected by ALICE at the LHC. The _{Λ}^{3}H is reconstructed via its charged two-body mesonic decay channel (_{Λ}^{3}H→^{3}He+π^{-} and the charge-conjugate process). The measured values τ=[253±11(stat)±6(syst)] ps and B_{Λ}=[102±63(stat)±67(syst)] keV are compatible with predictions from effective field theories and confirm that the _{Λ}^{3}H structure is consistent with a weakly bound system
Production of (anti-)He-3 and (anti-)H-3 in p-Pb collisions at root s(NN)=5.02 TeV
No full textThe transverse momentum (p(T)) differential yields of (anti-)He-3 and (anti-)H-3 measured in p-Pb collisions at root s(NN) = 5.02 TeV with ALICE at the Large Hadron Collider (LHC) are presented. The ratios of the p(T)-integrated yields of (anti-)He-3 and (anti-)H-3 to the proton yields are reported, as well as the pT dependence of the coalescence parameters B-3 for (anti-)He-3 and (anti-)H-3. For (anti-)He-3, the results obtained in four classes of the mean charged-particle multiplicity density are also discussed. These results are compared to predictions from a canonical statistical hadronization model and coalescence approaches. An upper limit on the total yield of (4)(He) over bar is determined
Host responses and bacterial virulence factors in Neisseria infections
No full textNeisseria meningitidis and Neisseria gonorrhoeae are human specific pathogens. N. meningitidis is a major cause of meningitis and sepsis, whilst N. gonorrhoeae causes many millions of cases of gonorrhea in the world every year. A key factor in neisserial pathogenesis is the ability of the bacteria to attach to human host cell receptors. The initial binding is mediated by pili, long hairlike structures that extend from the bacterial cell surface. Pili bind to the cellular pilus receptor, CD46.Lipopolysaccharide (LPS) of N. meningitidis is an extremely potent endotoxin that is largely responsible for tissue damage and shock in infected individuals. To examine the basis for bacterium-host cell contact, an LPS-deficient N. meningitidis mutant was constructed. LPS deficiency was without exception accompanied by altered colony opacity and morphology. It was also observed that LPS was essential for pilus-associated adherence but dispensable for fiber formation and twitching motility. The absence of attachment to host cells could not be attributed to altered levels of piliation or defects in the pilus adhesion phenotype. Furthermore, the LPS mutants did not invade epithelial cells and lost the natural competence for genetic transformation.In order to develop an improved experimental infection model that mimics the human host, transgenic mice expressing the human pilus receptor CD46 were used. These mice were found to be highly susceptible to meningococcal disease after intraperitoneal infection. Crossing of the bloodbrain barrier by bacteria occurred in CD46 transgenic mice but not in nontransgenic mice. CD46 transgenic mice challenged with wild-type bacteria had high levels of pro- and antiinflammatory cytokines in sera whilst LPS-deficient bacteria only induced low cytokine levels at early time points post-challenge. Intranasal infection of CD46 mice required piliation of the bacteria for development of disease, supporting that CD46 facilitates pilus-dependent interactions at the epithelial mucosa. Taken together, these data demonstrate a crucial role of CD46 in meningococcal disease and reveal a novel experimental system for rapid consideration of vaccine candidates, as well as a model to study Neisseria pathogenesis. Antimicrobial peptides are part of the innate immunity and can be considered as endogenous antibiotics.The antimicrobial peptide LL-37 was shown to exhibit potent bactericidal activity against N. gonorrhoeae and real-time quantitative PCR and immunocytochemistry showed that gonococcal infection caused a consistent down-regulation of LL-37 in a human cervical cell line. These data suggest that down-regulation of the expression of LL-37 by live N. gonorrhoeae may be a part of an invasive strategy in the female genital tract.List of scientific papersI. Albiger B, Johansson L, Jonsson AB (2003). Lipooligosaccharide-deficient Neisseria meningitidis shows altered pilus-associated characteristics. Infect Immun. 71(1): 155-62. https://pubmed.ncbi.nlm.nih.gov/12496161II. Johansson L, Rytkonen A, Bergman P, Albiger B, Kallstrom H, Hokfelt T, Agerberth B, Cattaneo R, Jonsson AB (2003). CD46 in meningococcal disease. Science. 301(5631): 373-5. https://pubmed.ncbi.nlm.nih.gov/12869763III. Johansson L, Rytkonen A, Bergman P, Agerberth B, Hokfelt T, Jonsson AB (2004). Meningococcal infection of CD46 transgenic mice induces human-like early immune responses. [Manuscript]IV. Bergman P, Johansson L, Asp V, Gudmundsson G, Jonsson AB, Agerberth B (2004). Neisseria gonorrhoeae down-regulates expression of the human antimicrobial peptide LL-37. [Manuscript]</p
Subfunctionalization of cyprinid hypoxia-inducible factors in development and oxygen sensing
No full textAmong vertebrates, teleost fishes have evolved the most impressive adaptations to variable oxygen tensions in water (Shoubridge and Hochachka 1980; Nilsson and Randall 2010). Under conditions of oxygen deprivation (hypoxia), major changes in gene expression are mediated by hypoxia-inducible factors (HIF alpha). Here we show that hif alpha genes were duplicated in the teleost specific whole-genome duplication. Although one of each paralogous gene pair was lost in most teleosts, both copies were retained in cyprinids. Computational analyses suggest that these duplicates have become subfunctionalized with complementary changes in coding and regulatory sequences within each paralogous gene pair. We tested our predictions with comparisons of hif alpha transcription in zebrafish, a cyprinid, and sturgeon, an outgroup that diverged from teleosts before the duplication event. Our experiments revealed distinct transcriptional profiles in the cyprinid duplicates: while one of each paralogous pair maintained the ancestral developmental response, the other was more sensitive to changes in oxygen tension. These results demonstrate the subfunctionalization of cyprinid hif alpha paralogs for specialized roles in development and the hypoxic stress response
Production of (anti-)He and (anti-)H in p-Pb collisions at = 5.02 TeV
No full textThe transverse momentum () differential yields of (anti-)He and (anti-)H measured in p-Pb collisions at = 5.02 TeV with ALICE at the LHC are presented. The ratios of the -integrated yields of (anti-)He and (anti-)H to the proton yields are reported, as well as the dependence of the coalescence parameters for (anti-)He and (anti-)H. For (anti-)He, the results obtained in four classes of the mean charged-particle multiplicity density are also discussed. These results are compared to predictions from a canonical statistical hadronization model and coalescence approaches. An upper limit on the total yield of is determined.The transverse momentum (pT) differential yields of (anti-)He3 and (anti-)H3 measured in p-Pb collisions at sNN = 5.02 TeV with ALICE at the Large Hadron Collider (LHC) are presented. The ratios of the pT-integrated yields of (anti-)He3 and (anti-)H3 to the proton yields are reported, as well as the pT dependence of the coalescence parameters B3 for (anti-)He3 and (anti-)H3. For (anti-)He3, the results obtained in four classes of the mean charged-particle multiplicity density are also discussed. These results are compared to predictions from a canonical statistical hadronization model and coalescence approaches. An upper limit on the total yield of 4He¯ is determined.The transverse momentum () differential yields of (anti-)He and (anti-)H measured in p-Pb collisions at = 5.02 TeV with ALICE at the Large Hadron Collider (LHC) are presented. The ratios of the -integrated yields of (anti-)He and (anti-)H to the proton yields are reported, as well as the dependence of the coalescence parameters for (anti-)He and (anti-)H. For (anti-)He, the results obtained in four classes of the mean charged-particle multiplicity density are also discussed. These results are compared to predictions from a canonical statistical hadronization model and coalescence approaches. An upper limit on the total yield of is determined
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