NERAZLIKOVNOST RAZLIKA

Analiziraju se leksikološko-leksikografska polazišta i metodološki postupci u izradi Razlikovnog rječnika srpskog i hrvatskog jezika Vladimira Brodnjaka

The factor H-binding fragment of PspC as a vaccine antigen for the induction of protective humoral immunity against experimental pneumococcal sepsis

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Protective role of the capsule and impact of serotype 4 switching on Streptococcus mitis

The polysaccharide capsule surrounding Streptococcus pneumoniae is essential for virulence. Recently, Streptococcus mitis, a human commensal and a close relative of S. pneumoniae, was also shown to have a capsule. In this study, the S. mitis type strain switched capsule by acquisition of the serotype 4 capsule locus of S. pneumoniae TIGR4, following induction of competence for natural transformation. Comparison of the wild type with the capsule-switching mutant and with a capsule deletion mutant showed that the capsule protected S. mitis against phagocytosis by RAW 264.7 macrophages. This effect was enhanced in the S. mitis strain expressing the S. pneumoniae capsule, which showed, in addition, increased resistance against early clearance in a mouse model of lung infection. Expression of both capsules also favored survival in human blood, and the effect was again more pronounced for the capsule-switching mutant. S. mitis survival in horse blood or in a mouse model of bacteremia was not significantly different between the wild type and the mutant strains. In all models, S. pneumoniae TIGR4 showed higher rates of survival than the S. mitis type strain or the capsule-switching mutant, except in the lung model, in which significant differences between S. pneumoniae TIGR4 and the capsule-switching mutant were not observed. Thus, we identified conditions that showed a protective function for the capsule in S. mitis. Under such conditions, S. mitis resistance to clearance could be enhanced by capsule switching to serotype 4, but it was enhanced to levels lower than those for the virulent strain S. pneumoniae TIGR4

Human Transcriptomic Response to the VSV-Vectored Ebola Vaccine

Ebolavirus Disease (EVD) is a severe haemorrhagic fever that occurs in epidemic outbreaks, with a high fatality rate and no specific therapies available. rVSVΔG-ZEBOV-GP (Ervebo®), a live-attenuated recombinant vesicular stomatitis virus vector expressing the glycoprotein G of Zaire Ebolavirus, is the first vaccine approved for prevention of EVD. Both innate and adaptive responses are deemed to be involved in vaccine-induced protection, yet the mechanisms are not fully elucidated. A global transcriptomic approach was used to profile the blood host-response in 51 healthy volunteers enrolled in a phase 1/2 clinical trial. Signatures of the host responses were investigated assessing the enrichment in differentially expressed genes (DEGs) of specific "blood transcription modules" (BTM). Comparison of gene-expression levels showed that vaccination produces a peak of 5469 DEGs at day one, representing 38.6% of the expressed genes. Out of 346 BTMs, 144 were significantly affected by vaccination. Innate immunity pathways were induced from day 1 to day 14. At days 2 and 3, neutrophil modules were downregulated and complement-related modules upregulated. T-cell and cell-cycle associated modules were upregulated at days 7 and 14, while at day 28, no modules remained activated. At day 14, a direct correlation was observed between ZEBOV glycoprotein-specific antibody titres and activation of seven BTMs, including two related to B-cell activation and B cell receptor signalling. Transcriptomic analysis identified an rVSVΔG-ZEBOV-GP-induced signature and demonstrated a direct correlation of blood transcriptomic changes with ZEBOV glycoprotein-specific antibody titres

Bacterial counts in blood and spleen of BALB/c mice depleted of neutrophils or macrophages.

<p>Twelve groups of BALB/c mice (n = 3–9) were infected by the i.v. route with four different strains of <i>S. pneumoniae</i> (TIGR4, D39, DP1004 and G54) at the challenge dose of 2.5×10⁵ CFU/each strain. Bacterial counts over time of each pneumococcal strain in the blood (black lines) and in the spleen (grey lines) were reported for untreated mice (A1, A2, A3 and A4), clodronate liposomes treated mice (B1, B2, B3 and B4) and anti-GR1 mAb treated mice (C1, C2, C3 and C4). Samples were collected over 13 h, with the exception of mice treated with clodronate (8 h). The cut off is 20 CFU/ml. Data are reported as the mean ± SD of bacterial counts.</p

Statistical analysis: number of blood cultures with one, two or three pneumococcal variants observed at 24 h in the experimental infection compared to those predicted from the statistical analysis.

<p>Statistical analysis: number of blood cultures with one, two or three pneumococcal variants observed at 24 h in the experimental infection compared to those predicted from the statistical analysis.</p

Co-infection of CD1 mice with three isogenic variants of <i>S. pneumoniae</i> TIGR4.

<p>A mixture of three isogenic <i>S. pneumoniae</i> TIGR4 variants (3×10⁵ CFU/each strain) was given to CD1 mice (n = 68) by the i.v. route. Bacterial counts were performed collecting blood at various time points. (A) Blood counts in the first 10 h after challenge. (B) Blood counts up to 72 h post-challenge, (including data reported in A). Each symbol indicates a single mouse. Blood cultures yielding all three variants are shown in downward white triangles, those yielding two variants as upward grey triangles, and samples yielding a monoclonal blood culture are shown as black squares. Samples from mice with negative blood cultures are shown as open circles. The ratio of infected over un-infected mice was 0.31 at 24 h, 0.37 at 48 h and 0.67 at 72 h. The cut off for detection is 100 CFU/ml. Data of two independent experiments are reported.</p

Pneumococcal strains.

<p>*see <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1004026#ppat-1004026-t003" target="_blank">Table 3</a> for detailed description.</p

Phenotypes of single-colony blood culture isolates.

<p>Growth profiles of wild type strains (coloured lines) and ATPase mutants (black lines) in standard laboratory media THY (A) and TSB (B). D39 is indicated in red while TIGR4, FP318 and FP321 in different shade of green. (C, D) Maximum OD₅₉₀ reached by wild type and ATPase mutants during growth with 80 mM K₂HPO₄ and pH 8.0 (D) and growth at pH 6.6 (E). Kinetics of opsono-phagocytosis assays in rotating blood with anti-type 4 serum (open symbols) and without antibodies (filled symbols) of parental strains (green) compared to a SP1507 <i>atpC</i> mutant (black). (F) Phagocytosis with primary cultures of spleen macrophages of TIGR4 and FP487 <i>atpC</i> mutant. (G) Bacterial counts in blood (squares) and spleen (triangles) at 72 h after i.v. infection of BALB/c mice (n = 6) with TIGR4 (green) and FP487 carrying a frame shifted SP1507 <i>atpC</i> gene (black). Data points below the cut off are negative. All data were analyzed by Student's <i>t</i>-test (<i>P</i><0.05).</p