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Synchronization is one of the interesting collective behaviors of oscillators. It refers to a phenomenon in which some dynamically connected systems behave the same. In dynamic systems, as the bifurcation points of the system approach, the system slows down and returns to its steady-state later with a slight disturbance. The system's slowness before bifurcation points is called critical slowing down, which can be measured using early warning (EW) indicators. This paper considers two dynamic systems: the Kuramoto model and the Rössler system. Two networks are considered to show continuous and explosive synchronization in each system. Then the synchronization bifurcation point (SBP) of each case is indicated using the EW signals calculated using the time series of synchronization measures. EW signals measure the slowness in the synchronous benchmark time series. Two EW signals, skewness and kurtosis, are applied. The results show that the SBPs in various cases and systems can be predicted using the EW signals. • Synchronization is one of the interesting collective behaviors of oscillators. • Two dynamic systems are studied: the Kuramoto model and the Rössler system. • Two networks are considered to show continuous and explosive synchronization in each system. • The synchronization bifurcation points (SBPs) are predicted. [ABSTRACT FROM AUTHOR]

Lyme neuroborreliosis, caused by the spirochete Borrelia burgdorferi, often manifests by causing neurocognitive deficits. As a possible mechanism for Lyme neuroborreliosis, we hypothesized that B. burgdorferiinduces the production of inflammatory mediators in the central nervous system with concomitant neuronal and/or glial apoptosis. To test our hypothesis, we constructed an ex vivomodel that consisted of freshly collected slices from brain cortex of a rhesus macaque and allowed live B. burgdorferito penetrate the tissue. Numerous transcripts of genes that regulate inflammation as well as oligodendrocyte and neuronal apoptosis were significantly altered as assessed by DNA microarray analysis. Transcription level increases of 7.43-fold (P= 0.005) for the cytokine tumor necrosis factor-α and 2.31-fold (P= 0.016) for the chemokine interleukin (IL)-8 were also detected by real-time-polymerase chain reaction array analysis. The immune mediators IL-6, IL-8, IL-1β, COX-2, and CXCL13 were visualized in glial cells in situby immunofluorescence staining and confocal microscopy. Concomitantly, significant proportions of both oligodendrocytes and neurons undergoing apoptosis were present in spirochete-stimulated tissues. IL-6 production by astrocytes in addition to oligodendrocyte apoptosis were also detected, albeit at lower levels, in rhesus macaques that had received in vivointraparenchymal stereotaxic inoculations of live B. burgdorferi. These results provide proof of concept for our hypothesis that B. burgdorferiproduces inflammatory mediators in the central nervous system, accompanied by glial and neuronal apoptosis.

ABSTRACTPreviously, we had demonstrated the upregulation in the expression of several proteins, including the lipoproteins OspC and P35, ofBorrelia burgdorferiin the stationary growth phase. Since the expression of OspC is also known to be affected by culture temperature and pH, we examined the effects of both variables on the expression of the remaining stationary-phase-upregulated proteins. Our study revealed that the expression of each of the remaining stationary-phase-upregulated proteins, P35 included, was also influenced by culture temperature; these proteins were selectively expressed at 34°C but not at 24°C. Significantly, the expression of a majority of these proteins was also affected by culture pH, since they were abundantly expressed at pH 7.0 (resembling the tick midgut pH of 6.8 during feeding) but only sparsely at pH 8.0 (a condition closer to that of the unfed tick midgut pH of 7.4). We propose that this group of B. burgdorferiproteins, which in culture is selectively expressed under conditions of 34°C and pH 7.0, may be induced in the tick midgut during the feeding event. Furthermore, the differential and coordinate expression of these proteins under different environmental conditions suggests that the encoding genes may be coregulated.

ABSTRACTIn an earlier paper we described the transcriptionally regulated differential levels of expression of two lipoproteins of Borrelia burgdorferi, P35 and P7.5, during growth of the spirochetes in culture from logarithmic phase to stationary phase (K. J. Indest, R. Ramamoorthy, M. Solé, R. D. Gilmore, B. J. B. Johnson, and M. T. Philipp, Infect. Immun. 65:1165–1171, 1997). Here we further assess this phenomenon by investigating whether the expression of other antigens of B. burgdorferi, including some well-characterized ones, are also regulated in a growth-phase-dependent manner in vitro. These studies revealed 13 additional antigens, including OspC, BmpD, and GroEL, that were upregulated 2- to 66-fold and a 28-kDa protein that was downregulated 2- to 10-fold, during the interval between the logarithmic- and stationary-growth phases. Unlike with these in vitro-regulated proteins, the levels of expression of OspA, OspB, P72, flagellin, and BmpA remained unchanged throughout growth of the spirochetes in culture. Furthermore, ospAB, bmpAB,groEL, and flaall exhibited similar mRNA profiles, which is consistent with the constitutive expression of these genes. By contrast, the mRNA and protein profiles of ospCand bmpDindicated regulated expression of these genes. While bmpDexhibited a spike in mRNA expression in early stationary phase, ospCmaintained a relatively higher level of mRNA throughout culture. These findings demonstrate that there are additional genes besides P7.5and P35whose regulated expression can be investigated in vitro and which may thus serve as models to facilitate the study of regulatory mechanisms in an organism that cycles between an arthropod and a vertebrate host.

The major surface protease, gp63, of Leishmania chagasiis encoded by 18 or more tandem mspgenes that can be grouped into three classes on the basis of their unique 3’-untranslated sequences (3’-UTRs) and their differential expression. RNAs from the mspLs occur predominantly during the logarithmic phase of promastigote growth in vitro, RNAs from the mspSs are present mainly in stationary phase, and RNAs from mspCs occur throughout growth in culture. All three classes of gp63 genes are constitutively transcribed during all growth phases, indicating that their expression is post-transcriptionally regulated. Chimeric plasmids containing the three different 3’-UTRs and downstream intergenic regions (IRs) fused downstream of the β-galactosidase (β-gal) coding region were transfected into L. chagasi, and their effects on β-gal RNA processing and enzymatic activity were examined. The presence of the 3’-UTRs by themselves had no substantive effect on β-gal expression. However, the 3’-UTR from a mspS plus its IR resulted in about 20-fold more β-gal activity and RNA in stationary phase relative to logarithmic phase cells. In contrast, the 3’-UTRs plus IRs of mspL and mspC had either no or little effect, respectively, on β-gal expression. Thus, differential expression of the mspLs and mspSs is post-transcriptionally controlled by different mechanisms.

ABSTRACTAs an initial attempt to investigate the possible role of outer surface protein A (OspA) escape mutants of Borrelia burgdorferiin decreasing the efficacy of the OspA vaccine, mutants of the HB19 strain of B. burgdorferisensu stricto were selected in vitro from an uncloned, low-passage-number isolate. The antiserum used for selection was obtained from rhesus monkeys that had been given a vaccine of the same formulation and dose, and by the same route of administration, as that given to humans in several trials. All of the mutants selected in liquid medium and subsequently cloned twice in solid medium expressed a single abundant protein of 28 to 34 kDa instead of both OspA and OspB. Depending on the mutant, this protein reacted strongly, weakly, or not detectably with the anti-OspA antibody used for selection. Analysis of the ospABlocus of each of four representatives from these three groups of mutants by PCR with oligonucleotide primers that hybridize to flanking regions of theospABoperon, and of the corresponding phenotype with monoclonal antibodies that bind to the amino or carboxyl terminus of the OspA or OspB polypeptide, indicated that in all cases a deletion within the operon had occurred. Spirochetes from the four mutant strains chosen for further analysis could be killed in antibody-dependent, complement-mediated killing assays with the selecting anti-OspA antibody, despite their resistance to killing with this antibody in the absence of complement. Complement-mediated killing occurred at an antibody concentration higher than that required to kill wild-type spirochetes. If anti-OspA antibody acts only within the tick, where complement is probably ineffective due to tick-derived decomplementing factors, then OspA escape mutants, if infectious, could seriously diminish the efficacy of OspA vaccines. On the other hand, if the killing of B. burgdorferiwith anti-OspA antibody also takes place within the human host, then our results indicate that chimeric/deletion escape mutants will be killed as well.

Strong pauses at nucleotides +118 and +121 relative to the transcriptional start occur during in vitro transcription of the E. coli rnpBgene encoding the catalytic M1 RNA subunit of Ribonuclease P. These pauses are immediately downstream of 2 phylogenetically conserved stem-loop structures in the RNA. In the present work, single-base changes which disrupted Watson-Crick base-pairing in the hairpins were introduced into rnpB. Transcription studies in vitro with these modified templates revealed that none of the nucleotide changes predicted to increase or decrease the stability of the first hairpin significantly affected the pause half-lives. A mutation which disrupted the second hairpin increased the pause half-life 2-fold. The data suggest that the upstream stem and loop structures in the transcript are not involved in the pausing event.