A national register of historic and contemporary anthrax foci

Anthrax in Russia has for a long time posed a serious problem for public health and veterinary services. At the beginning of the century, 40-60 thousand cases of this infection were annually reported in the country in agricultural animals and about 10-20 thousand cases in people where each fourth (25%) was dying. In the Russian Federation the registration of anthrax foci is obligatory for veterinary as well as for sanitary-epidemiological services. So our initial project, funded by the International Technical and Scientific Center in Moscow, has envisaged the collection of all data of known anthrax foci, including the village name, agricultural council, region, oblast and year of occurrence. The objective is to assemble a reference handbook, "Register of stable anthrax sites in the Russian Federation", containing organized information on more than 10 000 anthrax foci occurring during the past 100 years. Such a study makes it possible to identify regions characterized by the highest concentrations of stationary anthrax sites in Russia, to identify trends in expressed activity of such sites through the periodic emergence of disease in humans and animals, and to determine the factors contributing to the formation of such trends. In doing this, it makes it possible to develop contingency plans for different risk locations (i.e. high risk of persistent infection, high risk of sporadic occurrence, low risk areas, etc.) in terms of anthrax in Russia, to identify high risk areas and develop a differentiated strategy of vaccination and other control strategies, and to develop preventive recommendations to reduce risk in high risk areas. It is now important to develop the second step of the project: to develop in depth studies of particular clusters to determine which factors are associated with Russian anthrax outbreaks. Maps will greatly enhance the value of this work in terms of spatial analysis. Furthermore, this supplementary project will allow the incorporation of powerful Geographic Information System (GIS) electronic mapping technology so that natural geographic features, such as soil type, climate, etc., can be compared with anthrax distributions in Russia using standard GIS and statistical analysis. At the present time, it is imperative to develop a detailed understanding of the world's distribution of anthrax and what geographic factors determine its prevalence.     

The metalloproteolytic activity of the anthrax lethal factor is substrate-inhibited

The anthrax lethal factor (LF) is a Zn2+ endopeptidase specific for mitogen-activated protein kinase kinases (MAPKKs), which are cleaved within their N termini. Here, the proteolytic activity of LF has been investigated using novel chromogenic MAPKK-derived peptide substrates, which allowed us to determine the kinetic parameters of the reaction. LF displayed maximal proteolytic activity at the pH and temperature values of the cell cytosol, which is its site of action. LF undergoes substrate inhibition, in keeping with the non-productive binding geometry of the MAPPK-2 N terminus to LF.     

Patterns in the change in the number of carriers and epizootic activity in a floodplain local natural focus of tularemia in Voronezh Province]

Prolonged study of the population of Arvicola terrestris L. in connection with tularemia epizootic among these animals showed this animal to serve as the principal carrier of tularemia infection in the Povorinsk natural focus. Epizootics proved to originate with a definite threshold count of Arvicola terrestris L.; this threshold constituted about 30% of the trapped animals. Dynamics of the epizootic activity was characterized by alterations of cycles of various duration, coursing by waves, with 2--3-year periods. Reduction of the epizootic intensity coursed during a decade in 2 waves with 3-year periods, and during a 7-year period--in one 3-year wave. During the epizootics with the character of a 2-year wave the population of the principal carrier diminished, and with a 3-year wave the count of Arvicola terrestris L. decreased during the first year, and began to increase during the second year, despite the persistence of the epizootic. Detection of regularities attending the changes in the population of the principal carrier of the infection and its connection with the epizootics permitted to make long-period prognoses of the epizootic activity and to plan antiepidemic measures in the focus.     

Seasonal dynamics of scarab beetles (Coleoptera,Lamellicornia) in Voronezh Province

Thirteen seasonal groups of lamellicorn beetles are distinguished in Voronezh Province. Most of the species were found to belong to the spring, late spring-early summer, spring-summer, and summer groups.     

Louse Flies (Diptera,Hippoboscidae) in Bird Nests in Voronezh Province

Entomological Review - Eight species of louse flies were recorded on 22 bird species as the result of research carried out in 2008–2018 in Voronezh Province of Russia. Five species are...     

The anthrax lethal factor and its MAPK kinase-specific metalloprotease activity

The anthrax lethal factor is a multi-domain protein toxin released by Bacillus anthracis which enters cells in a process mediated by the protective antigen and specific cell receptors. In the cytosol, the lethal factor cleaves the N-terminal tail of many MAPK kinases, thus deranging a major cell signaling pathway. The structural features at the basis of these activities of LF are reviewed here with particular attention to the proteolytic activity and to the identification of specific inhibitors. A significant similarity between the metalloprotease domain of the lethal factor and of that of the clostridial neurotoxins has been noted and is discussed.     

The roles of anthrax toxin in pathogenesis

Anthrax lethal toxin is a multi-functional virulence factor that has evolved to target multiple host functions to allow for optimal establishment of Bacillus anthracis infection. The toxin appears to play a role in all stages of infection, from germination to the induction of vascular collapse leading to host death. Early in infection, at sublethal doses, it acts to suppress immune cell and cytokine responses, thereby promoting bacterial outgrowth. Later in the disease, lethal levels of toxin induce the cytokine-independent shock-like death associated with anthrax. The understanding of the molecular events induced by anthrax toxin in different target cells at each stage of infection will aid in deciphering the pathogenesis of this bacterium and developing therapies.     

Hereditary resistance to anthrax and sensitivity to the anthrax toxin in mice

The degree of the hereditary susceptibility of mice to anthrax caused by noncapsular and capsule-forming Bacillus anthracis strains has been found to be directly related to the sensitivity of the animals to the edematogenic and immunosuppressing action of anthrax toxin. The genetic analysis indicates that resistance to anthrax is probably controlled by a dominant gene, not linked with histocompatibility complex H-2 and, probably, unrelated to the presence of hemolytic activity in mouse sera, determined by component C5 of the complement.     

The effects of anthrax lethal factor on the macrophage proteome: potential activity on nitric oxide synthases

Anthrax lethal factor (LeTx) is a critical virulence factor in toxin-challenged cells, as lethal factor (LF) cleaves mitogen-activated protein kinase kinases (MKKs), inhibiting their activity. The physiological importance of this cleavage for macrophage cytolysis remains unclear, because similar proteolysis has been also observed in LeTx-resistant macrophages. Here, we analyzed in vitro proteomic profiles of Raw264.7 lysates treated with LF. In our experiments, neuronal NO synthase (nNOS) was found to be a fragment, suggesting that LF may act on nNOS cleavage. A similar cleavage of nNOS was shown in LeTx-challenged HEK293 cells expressing nNOS by a transient transfection. However, the cleavage site on nNOS is a unique leader sequence among the NOS family and this LF-mediated cleavage was not observed in iNOS, a major NOS isoform for anti-bactericidal NO production, even though NO level in LeTx-challenged cells was dramatically reduced. Our findings suggest that LF is directly capable of cleaving cellular protein(s) other than MKKs, and that these actions potentiate to promote the cytotoxic mechanisms of anthrax.     

Effect of acupuncture on the activity of experimental epileptogenic foci in the hippocampus of rabbits

Experiments were performed on rabbits with electrochemotrodes implanted into the left and right dorsal hippocamp. The evidence was obtained for the first time as to the marked inhibitory effect of acupuncture on epileptogenic foci created by penicillin microinjections into the hippocamp. The most effective was stimulation of the Min-Men point. The antiepileptic effect was potentiated on combined stimulation of the Min-Men and Yao-Yan-Guan points. The efficacy of the procedure was significantly decreased on stimulation of the points of another acupunctural canal. The epileptiform activity was potentiated by affecting the knowingly inactive points. The antiepileptic effect of acupuncture was significantly reduced with an increase in the number of acupunctures. This might be connected with the development of tolerance to enkephalins by which the effect of acupuncture is most likely mediated.     

The detection of specific antigens in experimental anthrax

The dynamics of various specific antigens was studied in guinea pigs infected with strain 72/12 of Tsenkovski?'s second vaccine. The study showed that at the acute stage of the disease toxin antigens prevailed over the levels of somatic antigens and nonprotective protein with a molecular weight of 79 KD. The enzyme immunoassay system for the detection of the lethal toxin factor permitted the detection of the antigen in the blood sera of 100% of infected animals at the prodromal period and the acute stage of the disease. In pathological material obtained from skin lesions the presence of toxin antigens and nonprotective protein was registered in 90-100% of the animals. The diagnostic significance of these assays for the early rapid diagnosis of anthrax during lifetime, as well as for the postmortem rapid diagnosis of the disease.