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Background: Interleukin (IL)-17 is the main Th-1 cytokine, produced by activated T-lymphocytes. The potential IL-17 value in rheumatoid arthritis (RA) pathogenesis consists of its independent inflammatory response induction and mediated stimulation of proinflammatory factors synthesis resulting in joint destruction. The aim of study was to determine the role of IL-17 in immuno-inflammatory/autoimmune reactions development and to reveal IL-17 serum level associations with clinical and immunological characteristics of RA. Methods: 50 patients with early RA (disease duration >, Russia), anti-CCP antibodies (Axies-Shield Diagnostic, UK) were revealed using ELISA immunoassay. Results: On the base of IL-17 serum level patients were divided in two groups: group1 (n = 28) were patients with normal IL-17 serum level and group2 (n = 22) were those with high IL-17 serum level. In the group2, the rate of patients' pain assessment by visual analogue scale (67.3 ± 7.2 vs 32.8 ± 4.6; P

This paper considers the occurrence of explosive resonant triads in fluid mechanics. These are weakly nonlinear waves whose amplitudes become unbounded in finite time. Previous work is expanded to include interfacial flow systems with continuously varying basic velocities and densities. The first paper in this series [10] discussed the surprisingly strong singular nature of explosive triads. Many of the problems to be studied here will be found to have additional singularities, and the techniques for analyzing these difficulties will be developed. This will involve the concept of a critical layer in a fluid, a level at which a wave phase speed equals the unperturbed fluid velocity in the direction of propagation. Examples of such waves in this context are presented.

In this paper, a collection of results pertaining to resonant triads in fluid flow systems is presented. The main topic is the extension of the analysis by Mahoney for wind-driven shear flows to general, layered flows, that is to say, flows which have piecewise continuous velocity and density profiles. It is seen how the results for calculating the triad interaction coefficients for two-layer flows generalize and carry over for multilayer flows.

In the linear inviscid theory of shear flow stability, the eigenvalue problem for a neutral or weakly amplified mode revolves around possible discontinuities in the eigenfunction as the singular critical point is crossed. Extensions of the linear normal mode approach to include nonlinearity and/or wave packets lead to amplitude evolution equations where, again, critical point singularities are an issue because the coefficients of the amplitude equations generally involve singular integrals. In the past, viscosity, nonlinearity, or time dependence has been introduced in a critical layer centered upon the singular point to resolve these integrals. The form of the amplitude evolution equation is greatly influenced by which choice is made. In this paper, a new approach is proposed in which wave packet effects are dominant in the critical layer and it is argued that in many applications this is the appropriate choice. The theory is applied to two-dimensional wave propagation in homogeneous shear flows and also to stratified shear flows. Other generalizations are indicated.

The product of the Saccharomyces cerevisiae SIR4 gene, in conjunction with at least three other gene products, prevents expression of mating-type genes resident at loci at either end of chromosome III, but not of the same genes resident at the MAT locus in the middle of the chromosome. To address the mechanism of this novel position effect regulation, we have conducted a structural and genetic analysis of the SIR4 gene. We have determined the nucleotide sequence of the gene and found that it encodes a lysine-rich, serine-rich protein of 152 kilodaltons. Expression of the carboxy half of the protein complements a chromosomal nonsense mutation of sir4 but not a complete deletion of the gene. These results suggest that SIR4 protein activity resides in two portions of the molecule, but that these domains need not be covalently linked to execute their biological function. We also found that high-level expression of the carboxy domain of the protein yields dominant derepression of the silent loci. This anti-Sir activity can be reversed by increased expression of the SIR3 gene, whose product is normally also required for maintaining repression of the silent loci. These results are consistent with the hypothesis that SIR3 and SIR4 proteins physically associate to form a multicomponent complex required for repression of the silent mating-type loci.

Mating-type genes resident in the silent cassette HML at the left arm of chromosome III are repressed by the action of four SIR gene products, most likely mediated through two cis-acting sites located on opposite sides of the locus. We showed that deletion of either of these two cis-acting sites from the chromosome did not yield any detectable derepression of HML, while deletion of both sites yielded full expression of the locus. In addition, each of these sites was capable of exerting repression of heterologous genes inserted in their vicinity. Thus, HML expression is regulated by two independent silencers, each fully competent for maintaining repression. This situation was distinct from the organization of the other silent locus, HMR, at which a single silencer served as the predominant repressor of expression. Examination of identifiable domains and binding sites within the HML silencers suggested that silencing activity can be achieved by a variety of combinations of various functional domains.

Mating-type genes resident in the silent cassette HML at the left arm of chromosome III are repressed by the action of four SIR gene products, mediated independently through two cis-acting sites, termed the E and I silencers. We have found that in the absence of the I silencer, deletion of any one of three distinct elements within E yields partial derepression of the mating-type genes resident at HML, whereas deletion of any two yields full derepression. These elements correspond to a binding site for the abundant DNA-binding protein RAP1, an autonomous replicating sequence (ARS), and an as yet undistinguished region. From detailed deletion analysis of the E site we conclude that the ARS element contributes to silencer function in a capacity distinct from its role as an initiator of DNA replication. In addition, we find that strains deleted for any one of these elements comprise two genetically identical but phenotypically distinct types of cells: Those with HML apparently fully derepressed, and those with HML apparently completely repressed. These results reinforce the notion that epigenetic inheritance is an intrinsic characteristic of silencer action.