Expression of ergotope-associated markers of T lymphocytes in atopic dermatitis after in vitro polyclonal activation

The antiergotypic response leads to the formation of effector T cells able to eliminate activated lymphocytes independently of their antigenic specificity, since the targets of these cells are molecules produced during cell activation (ergotopes). In this paper, we describe the level of expression of the ergotope-associated markers CD25, HSP60, and HLA-DR by the T lymphocytes isolated from the blood of atopic dermatitis patients immediately after isolation and after cultivation. After 10-day cultivation in the presence of anti-CD3 antibodies and IL-2, the expression levels of early and late activation markers in T cells have changed: the shares of CD25-positive CD4⁺ and CD8⁺ lymphocytes increase to 68 and 47%, respectively, and the share of HLA-DR-positive cells increases to 26 and 33%. The density of HLA-DR molecules on the surface of activated T cells increases more than fivefold. Almost all T cells before and after cultivation express 60 kDa heatshock protein (HSP60); however, the CD4⁺ cells activated in vitro contain more HSP60 molecules than do the in vitro-activated CD8⁺ cells and the CD4⁺ cells of peripheral blood. Thus, the T cells of atopic-dermatitis patients have the status of activated cells because they express sufficient amounts of early and late activation markers; presumably, they can enhance the induction of antiergotypic response when administered to patients. Taking into account that antiergotypic regulation acts on activated T cells independently of their antigenic specificity, immunotherapy utilizing autologous activated T lymphocytes can be of interest as a method for targeted action on pathogenetic components of atopic dermatitis.     

Behavioral and morphological asymmetries in roach <Emphasis Type="Italic">Rutilus rutilus</Emphasis> (Cyprinidae: Cypriniformes) underyearlings

The underyearlings of roach, Rutilus rutilus, displayed a bilateral asymmetry of C-bend—the initial stage of escape behavior. Most individuals exhibited a significant bias to turn leftward or rightward after being stimulated by electrical current. This individual asymmetry was consistent when the same fish were retested ten days later. A significant correlation was revealed between the behavioral asymmetry and the bilateral asymmetry of surface area of frontal (positive correlation) and parietal (negative correlation) cranial bones. No significant correlation was found with the bilateral asymmetry of other morphological characteristics: numbers of pores of the seismosensory canals (praeopercular-mandibular, supraorbital, and supratemporal) in flat cranial bones (dental, praeopercular, frontal, and parietal numbers of lateral line pores, and numbers of rays in pectoral and ventral fins.     

Comparison of the Interferon γ-Binding Proteins of the Variola and Monkeypox Viruses

PCR was used to amplify DNA fragments containing the genes for interferon γ (IFNγ)-binding proteins (IFNγBPs) of the variola virus (VARV) and monkeypox virus (MPXV). The genes were expressed from baculovirus DNAs in Sf21 insect cells. The recombinant proteins were isolated from the culture medium by affinity chromatography. PAGE and Western blot analysis of the culture media and affinity-purified recombinant proteins showed that, in contrast to their cell analogs, the viral IFNγBPs form dimers in the absence of the ligand, human IFNγ. The biological activity of recombinant IFNγBPs was inferred from suppression of the protective effect of human IFNγ on L68 cells infected with the mouse encephalomyocarditis virus. The viral proteins showed a dose-dependent IFNγ-neutralizing effect. The prospects of using IFNγBPs as IFNγ antagonists are discussed.     

Laterality of the initial stage of escape response in roach (<Emphasis Type="Italic">Rutilus rutilus</Emphasis>) upon impact of alternating electric current

The initial stage of the escape response (C-bend of the body) upon sudden impact of electric current on free-swimming fish was studied in young roach (Rutilus rutilus). More than half of the fish showed distinct behavioral laterality, i.e., a stabile tendency to bend either to the left or to the right, and retained it until the next test conducted 10 days later. The majority of fish bent to the left, but the difference between the proportions of individuals that showed opposite lateralities lacked statistical significance. This response and the type of laterality are stable and simple to record, which makes the C-bend a convenient experimental model for studying behavioral asymmetry in fishes.     

Laterality of behavioral responses in bony fishes: Inheritance,adaptive importance,and morphofunctional correlates

Current data on the relation of locomotory responses laterality to taxonomy and mode of life in fish, as well as to asymmetry of CNS, sensory, and somatic organs, are examined. Although the correlations of behavioral laterality with some of the abovementioned features are already found, the causes inducing lateralities of many fish responses remain unclear. It is concluded that, to understand the causes of laterality, it is necessary to study simultaneously its relation to different morphofunctional features in the same specimens.     

Recombinant TNF-binding protein from variola virus as a novel potential TNF antagonist

Gel-filtration chromatographic separation of the lysate of Sf21 insect cells infected with recombinant baculovirus BVi67 containing the gene for TNF-binding protein (CrmB) of variola virus (VARV) revealed that hTNF-cytotoxicity neutralization activity is associated with a fraction corresponding mainly to high molecular weight proteins (above 500 kDa) and less with fractions corresponding to proteins of 270 or 90 kDa. The recombinant VARV-CrmB protein has been purified by affinity chromatography. Difference in the experimentally determined and estimated (according to amino acid composition) VARV-CrmB molecular weight is due to glycosylation of the recombinant protein expressed in the insect cells. VARV-CrmB neutralizes in vitro the cytotoxic effect of hTNF and hLTα, and its TNF-neutralizing activity is two to three orders of magnitude higher compared to the analogous effects of type I and II soluble TNF receptors, comparable with the activity of mAb MAK195, and somewhat lower than the effect of the commercial drug Remicade.     

Signal behavior in cranes (the Siberian Crane Sarcogeranus leucogeranus, the White-naped Crane Grus vipio, and the Red-crowned Crane Grus japonensis) in the context of the ritualization hypothesis

Signal behavior of three crane species was chosen to test the logic of the ritualization hypothesis. Its claims to explain the origin and functioning of the “highly ritualized” communication signals in birds are discussed. It is shown that such signals are observed in a wide range of situations, including those in the absence of a social partner for communication (perceiver). In its presence a signal may be performed in a way that it cannot be perceived by the partner. The same actions (“ritualized preening”) vary in length and intensity, and such variability is present in nearly all situations. In each situation, it is difficult to discriminate between the ritualized preening and actual comfort behavior. It may take place even when a social partner is present. Short preening that may be readily considered as ritualized signals are more common in the all situations, including those with an absent partner. The endogenous cyclicity in unison calling by mates indicates that communication cannot be regarded as a simple exchange of signals in accordance to the ‘stimulus-reaction’ principle. Similar actions by the more ancestral Siberian Crane may appear to be more ritualized than in the evolutionary advanced Red-crowned Crane. All these findings contradict the concept of emancipation and ritualization of behavioral actions during evolution and selection for increasing communication efficiency. According to that hypothesis, during this process such actions, due to selection for more efficient communication, evolve into discrete meaningful communication signals (displays). They stand out against the background of the monotonous, unexpressive (non-signal) everyday behavior and thus appear as the main carriers of information serving principal communication functions. A more realistic approach seems to be the understanding of communication as a process of a continuous mutual fine-tuning of the social partners’ behavioral attitudes towards each other. In either participant, its behavior is an integral structure, inseparable into categories of more or less important signals (flow of behavior). Even minor changes in performance by one individual reflect alteration in its motivational state which, in its turn, changes that of the other participant and the subsequent lines of its behavior.     

Gene therapy of arthritis

Gene therapy can offer a new approach to arthritis treatment which acts at an inflammation site. Numerous studies show high efficacy of gene therapy in different models of arthritis in humans. Even a single injection of a recombinant vector results in a stable prolonged expression of a therapeutic gene and a longterm therapeutic effect. In contrast to biologic therapy involving numerous systemic injections of recombinant anti-inflammatory proteins, gene therapy does not produce systemic side effects. Vectors based on retroviruses, adenoviruses, adeno-associated viruses, and recombinant plasmids could provide delivery of target genes. Of significant importance is the development of noninvasive methods of gene therapy: intranasal and peroral. The current state of research in arthritis gene therapy is discussed in this review.     

Asymmetry of the behavioral response in roach Rutilus rutilus (L.) (Teleostei: Cyprinidae) to a new object

The young roach Rutilus rutilus (L.) (Cyprinidae) displays lateralized behavior when facing a barrier through which a simulated bigger fish was visible. The asymmetry consists in a significant tendency to detour a barrier rightwards in the presence of a dummy fish. However, asymmetry is insignificant without the model. A comparison with the available literature shows that the roach has the same direction of this lateral bias as some other shoaling cyprinid fishes, which also preferentially turn to the right in the presence of a dummy fish. This seems to be a characteristic of cyprinids, as opposed to species of some other families displaying a leftward bias or a lack of asymmetry. The results of the study testify to the hypothesis that behavioral lateralization is associated with the taxonomic status of fishes. Currently, it is unclear whether the asymmetry found in roach in a detour test is due to the preferential use of the lateral fields of the right and left eyes as in some other fishes, or if it is a result of motor lateralization, which becomes evident in the presence of an unfamiliar and potentially dangerous object.     

Properties of the recombinant TNF-binding proteins from variola, monkeypox, and cowpox viruses are different

Tumor necrosis factor (TNF), a potent proinflammatory and antiviral cytokine, is a critical extracellular immune regulator targeted by poxviruses through the activity of virus-encoded family of TNF-binding proteins (CrmB, CrmC, CrmD, and CrmE). The only TNF-binding protein from variola virus (VARV), the causative agent of smallpox, infecting exclusively humans, is CrmB. Here we have aligned the amino acid sequences of CrmB proteins from 10 VARV, 14 cowpox virus (CPXV), and 22 monkeypox virus (MPXV) strains. Sequence analyses demonstrated a high homology of these proteins. The regions homologous to cd00185 domain of the TNF receptor family, determining the specificity of ligand-receptor binding, were found in the sequences of CrmB proteins. In addition, a comparative analysis of the C-terminal SECRET domain sequences of CrmB proteins was performed. The differences in the amino acid sequences of these domains characteristic of each particular orthopoxvirus species were detected. It was assumed that the species-specific distinctions between the CrmB proteins might underlie the differences in these physicochemical and biological properties. The individual recombinant proteins VARV-CrmB, MPXV-CrmB, and CPXV-CrmB were synthesized in a baculovirus expression system in insect cells and isolated. Purified VARV-CrmB was detectable as a dimer with a molecular weight of 90 kDa, while MPXV- and CPXV-CrmBs, as monomers when fractioned by non-reducing SDS-PAGE. The CrmB proteins of VARV, MPXV, and CPXV differed in the efficiencies of inhibition of the cytotoxic effects of human, mouse, or rabbit TNFs in L929 mouse fibroblast cell line. Testing of CrmBs in the experimental model of LPS-induced shock using SPF BALB/c mice detected a pronounced protective effect of VARV-CrmB. Thus, our data demonstrated the difference in anti-TNF activities of VARV-, MPXV-, and CPXV-CrmBs and efficiency of VARV-CrmB rather than CPXV- or MPXV-CrmBs against LPS-induced mortality in mice.