Spatiotemporal Patterns of African Swine Fever in Wild Boar in the Russian Federation (2007-2022): Using Clustering Tools for Revealing High-Risk Areas.

African swine fever (ASF) is an infectious disease that affects both domestic pigs (DPs) and wild boar (WB). The WB population plays an important role in the spread of ASF as the WB acts as a natural reservoir of the virus and transmits it to other susceptible wild and domestic pigs. Our study was aimed at revealing the areas with a high concentration of the WB population, and their potential relationships with the grouping of ASF cases in WB during the course of the ASF spread in the Russian Federation (2007-2022). We collected the annual data on WB numbers by municipalities within the regions of the most intensive ASF spread. We then conducted spatiotemporal analysis to identify clustering areas of ASF cases and compare them with the territories with a high density of WB population. We found that some of the territories with elevated ASF incidence in WB demonstrated spatial and temporal coincidence with the areas with a high WB population density. We also visualized the zones ("emerging hot spots") with a statistically significant rise in the WB population density in recent years, which may be treated as areas of paramount importance for the application of surveillance measures and WB population control.

Blackleg in Cattle in the Irkutsk Region.

Blackleg is an acute, toxic, infectious, non-contagious disease of domestic and wild ruminants that occurs while the animals are pastured. This article describes an outbreak of blackleg on a farm in Siberia (Russia) in 2019. We provide a detailed description of the cases based on the results of comprehensive diagnostic and epidemiological investigations. For description of case and evaluation, we used the following methods: owner observations, descriptive epidemiology, clinical diagnostics, pathological examination and bacteriology. The distinctive features (in addition to the characteristic features) were as follows: the outbreak of the disease occurred in early spring when there was abundant snow cover and under unfavorable living conditions of animals and traumas; the disease appeared in both vaccinated and unvaccinated cattle; the characteristic clinical signs were low-grade fever, the absence of crepitus, and the presence of haematomas containing erythrocytes with basophilic granularity; thrombs in vessel and vacuolization in tissue of the adrenal gland. This paper aimed to present classical and new clinical and pathology changes in cattle with blackleg in winter conditions of Russian Siberia.

Reindeer Anthrax in the Russian Arctic, 2016: Climatic Determinants of the Outbreak and Vaccination Effectiveness.

The Yamal Peninsula in the Russian Federation experienced a massive outbreak of anthrax in reindeer (Rangifer tarandus) in July-August 2016, with 2,650 (6.46% of the total susceptible population) animals infected, of which 2,350 died (case fatality rate of 88.67%). In our study, we analyzed climatic and epidemiological factors that could have triggered the outbreak. The cancelation of reindeer vaccination against anthrax in 2007 resulted in an increase in population susceptibility. In response to the outbreak, total vaccination of all susceptible animals was resumed. To assess the vaccination effectiveness, we tested 913 samples of blood serum taken from vaccinated reindeer using an antigenic erythrocyte diagnostic kit to detect specific anti-anthrax antibodies via an indirect hemagglutination assay (IHA) 9 months after vaccination. We found that 814 samples had sufficiently high levels of anti-anthrax antibodies to indicate a protection level of 89% (95% confidence interval: 87-91%) of the whole reindeer population. Abnormally high ambient temperature in the summer of 2016 contributed to the thawing of permafrost and viable Bacillus anthracis spores could have become exposed to the surface; the monthly average air temperatures in June, July, and August 2016 were 20-100% higher than those of the previous 30-year period, while the maximum air temperatures were 16-75% higher. Using the projected climate data for 2081-2100 according to the "worst case" RCP8.5 scenario, we demonstrated that the yearly air temperature may average above 0°C across the entire Yamal Peninsula, while the yearly number of days with a mean temperature above 0°C may rise by 49 ± 6 days, which would provide conditions for reactivation of soil anthrax reservoirs. Our results showed that the outbreak of anthrax occurred under conditions of a significant increase in air temperature in the study area, underlined the importance of vaccination for controlling the epidemic process, and demonstrated the effectiveness of monitoring studies using the IHA diagnostic kit for detecting erythrocyte anthrax antigens.

Malignant Catarrhal Fever in Cattle in the Irkutsk Region.

INTRODUCTION: Malignant catarrhal fever (MCF) is a rare, under-explored lethal viral infection of cattle with gammaherpesvirus aetiological agents. Most often, the disease occurs on farms where cattle and sheep are kept together. However, other trigger mechanisms and environmental factors contribute. This study investigates the causation of MCF. MATERIAL AND METHODS: An outbreak of MCF occurred in June - August 2017 in Kharchev village in Irkutsk Oblast, Russia. In this paper, we provide epidemiological (sanitary status of pastures, watering places, and premises) and weather data during the outbreak, and descriptions of the clinical signs and post-mortem changes in cattle. The virus was detected and isolated from pathological material samples and identified by molecular methods. RESULTS: Extreme weather conditions, mixed-herd cattle and sheep farming, and unsatisfactory feed quality contributed to the outbreak. A virus related to herpesvirus OvHV2 was isolated and typed (MCF/Irkutsk/2017). Phylogenetic analysis showed its close genetic relationship to isolates from cattle and sheep in Germany, USA, and the Netherlands. CONCLUSION: Sporadic outbreaks of MCF caused by biotic and abiotic factors together are typical for the Russian Federation, and the Irkutsk outbreak epitomised this. Temperature anomalies caused pasture depletion, resulting in feed and water deficiency for grazing animals and dehydration and acidosis. Heat stress in animals ultimately led to the occurrence of MCF in the herd.

Environmental Risk of Leptospirosis in Animals: The Case of The Republic of Sakha (Yakutia), Russian Federation.

Leptospirosis is a zoonotic natural focal disease caused by the pathogenic bacteria Leptospira. Its spread is related to certain ecological factors. The aim of the current research was to assess potential exposure to the infection as a function of environmental determinants in the Republic of Sakha (Yakutia), Russian Federation. We applied environmental niche modeling using leptospirosis cases in livestock and wild animals in 1995-2019 with regard to a set of landscape, climatic, and socioeconomic variables, both for the current climate and for the projected climate for 2041-2060. The MaxEnt model performed well (AUC = 0.930), with the mean temperature of the warmest quarter, mean diurnal range, land cover type, and altitude being the most contributing variables. Consequent zoning based on the proportion of high-risk cells within each administrative unit suggested that five out of the 36 districts of the Republic are at high risk in the current climate conditions, with three more districts expected to demonstrate a high risk by 2060. This study presents the first-ever attempt at leptospirosis ecological modeling in Russia. Its results correspond well to the findings of other authors and underline the importance of considering ecological factors when conducting a leptospirosis risk assessment.

Two forms of substrate for the bioluminescent reaction in three species of basidiomycetes.

The luminescent response of the enzymatic system of Armillaria borealis on the cold and hot extracts from cell-free culture liquids of Inonotus obliquus, Pholiota sp. and A. borealis was examined. The greatest influence on the light emission produced by the luminescent system of A. borealis was provided by the temperature at which the probes were prepared for assay. Boiling a culture liquid on water bath for a few minutes promoted a multifold increase in the luminescence. The results of luminescence assay suggest that the substance involved in the bioluminescent reaction in higher fungi is presented in culture liquids and mycelia in two forms. In one form, it is ready to interact with the enzymatic system and in the second form, it becomes accessible for the reaction after heat treatment. The pool of thermoactivated substance was found to be much large than the amount of the ready accessible one. We suggest that predecessors of hispidin, which is fungal luciferin precursor, are responsible for this phenomenon. They are not involved in bioluminescence at their original state and are converted into the substrate under the influence of high temperature.

Immunological monitoring for prediction of clinical response to antitumor vaccine therapy.

Immunotherapy has shown promising results in a variety of cancers, including melanoma. However, the responses to therapy are usually heterogeneous, and understanding the factors affecting clinical outcome is still not achieved. Here, we show that immunological monitoring of the vaccine therapy for melanoma patients may help to predict the clinical course of the disease. We studied cytokine profile of cellular Th1 (IL-2, IL-12, IFN-γ) and humoral Th2 (IL-4, IL-10) immune response, vascular endothelial growth factor (VEGFA), transforming growth factor-ß 2 (TGF-ß 2), S100 protein (S100A1B and S100BB), adhesion molecule CD44 and serum cytokines ß2-microglobulin to analyze different peripheral blood mononuclear cell subpopuations of patients treated with dendritic vaccines and/or cyclophosphamide in melanoma patients in the course of adjuvant treatment. The obtained data indicate predominance of cellular immunity in the first adjuvant group of patients with durable time to progression and shift to humoral with low cellular immunity in patients with short-term period to progression (increased levels of IL-4 and IL- 10). Beta-2 microglobulin was differentially expressed in adjuvant subgroups: its higher levels correlated with shorter progression-free survival and the total follow-up time. Immunoregulatory index was overall higher in patients with disease progression compared to the group of patients with no signs of disease progression.

Inhibitor of vasculogenic mimicry restores sensitivity of resistant melanoma cells to DNA-damaging agents.

The increasing incidence of melanoma makes this cancer an important public health problem. Therapeutic resistance is still a major obstacle to the therapy of patients with metastatic melanomas. The aim of this study was to develop the melanoma cell line resistant to DNA-alkylating agents and to elucidate the mechanisms involved in acquired drug resistance. We established a unique melanoma subline Mel MeR resistant to DNA-alkylating drug aranoza by continuous stepwise selection of the Mel Me/WT cell line with increasing concentrations of this drug. Mel MeR cells were also cross-resistant to streptozotocin or cisplatin. Here, we show that aranoza-resistant melanoma cells modulate the ABC transporter activity, upregulate the expression of PRAME, adopt a vascular-related phenotype and engage in vasculogenic mimicry. LCS1269, a vasculogenic mimicry low-molecular-weight inhibitor, reverses the sensitivity of resistant melanoma cells to DNA-damaging agents. In this study, we provide experimental evidence that LCS1269 might be considered as a new potential anticancer agent capable of overcoming multidrug resistance for DNA-damaging agents in melanoma.

Nutrient and metal pollution of the eastern Gulf of Finland coastline: Sediments, macroalgae, microbiota.

The anthropogenic pollution along the coastline of the eastern Gulf of Finland was studied through a range of methods, including analyses of metal contamination in water, surface sediments, accumulated algal biomass and its correlation with resistant microbiota. According to concentrations, the main pollutants in water were copper and manganese. Influence of Nuclear Power Plant was remarkable in adjacent areas and was expressed in high concentrations of molybdenum, nickel, copper and other elements in the water. Relatively high concentrations of copper, lead and zinc were found in sediments. Microbial tolerance appeared to be correlated with the concentration of the metals in sediments. Higher tolerance levels were found in sediment samples from more polluted stations. Macroalgae, which were massively developed in the coastal zone, had shown high level of metal bioaccumulation. Analyses of carbon, nitrogen and phosphorus content of algal tissues allowed the estimation of additional nutrient loading from accumulated decaying algal biomass on the coastal zone of the eastern Gulf of Finland. Mass development of algae in coastal area may contribute to accumulation of organic matter and associated metals. In our study the highest metal concentrations in sediments were found at the sites with dense and continuous layer of fresh and decaying macroalgal biomass, accompanied by hypoxic conditions. Also our study has shown that accumulated biomass may be a significant source of nutrients in the coastal ecosystem.

Neuroendocrine tumor in the liver of a patient with isolated polycystic liver disease: A case report and review of the literature.

Neuroendocrine tumors (NETs) frequently metastasize to the liver, but it is rare to find them there as primary tumors. Isolated polycystic liver disease (PCLD) is a rare autosomal dominant disease. There is no known association between polycystic liver disease and neuroendocrine or other tumors. We report a case of a 64-year-old female with a past medical history of isolated PCLD who presented with increasing abdominal pain over a two-week period. Our patient underwent open surgical biopsy one month after presentation. The histological examination and immunohistochemical findings suggested an intermediate grade neuroendocrine tumor. A 24-h delayed whole-body scintigraphy technique was utilized for the identification and localization of neuroendocrine tumors via the administration of In-111-labeled OctreoScan; however, no extrahepatic accumulation was observed. No previous studies in the literature describe a patient with PCLD and a primary or metastatic neuroendocrine tumor of the liver.

Three-dimensional in vivo imaging of tumors expressing red fluorescent proteins.

3D imaging of genetically-engineered fluorescent tumors enables quantitative monitoring of tumor growth/regression, metastatic processes, including during anticancer therapy in real-time.Fluorescent tumor models for 3D imaging require stable expression of genetically encoded fluorescent proteins and maintenance of the properties of tumor cell line including growth rate, morphology, and immunophenotype.In this chapter, the protocol for 3D imaging of tumors expressing red fluorescent protein are described in detail.

Cancer/testis genes expression in human melanoma cell lines.

We analyzed the expression of 15 cancer/testis and four melanoma differentiation antigens in 21 metastatic melanoma cell lines using reverse transcriptase-polymerase chain reaction (RT-PCR) assay. On the basis of morphological characteristics, tumor cell lines were divided into three groups with high, moderate, and low grade of differentiation. Evaluation of gene expression and melanoma cell morphology has revealed a correlation between increased expression of cancer/testis genes and differentiation grade of cancer cells. The gene expression pattern for lymph node metastases and primary tumors exhibits the distribution of expression level and frequency similar to that found for established cell lines. Nevertheless, only 60% lymph node metastases or primary tumor tissue of randomly selected patients show marked expression of the most prominent cancer/testis genes, and almost 90% lesion tissue expresses at least one of 15 cancer/testis genes.

Melanoma vasculogenic mimicry is strongly related to reactive oxygen species level.

The concept of 'vasculogenic mimicry' (VM) was introduced to describe the unique ability of highly invasive tumor cells to form capillary-like structures (CLS) and matrix-rich patterned network in three-dimensional culture that mimic embryonic vasculogenic network. Recently, we have shown that CLS formation requires apoptotic cell death through activation of caspase-3-dependent mechanism. In this study, to identify some molecular determinants driving aggressive melanoma cells to express a latent 'angiogenic program' that recapitulates the early events of CLS formation, we focused on the involvement of antioxidants (AOs) in the process of melanoma VM. We have studied the effects of resveratrol, (-)-epigallocathechin gallate, N-acetyl-cysteine (NAC) and Trolox on the ability of melanoma cells to form/destroy CLS. We observed that the formation of CLS was strongly related to reactive oxygen species level. In vivo animal experiments confirmed the involvement of reactive oxygen species level in melanoma VM. To understand the molecular mechanisms of this phenomenon, we specifically looked for induction of apoptosis and vascular endothelial growth factor (VEGF) release. Western blot analysis revealed that the level of VEGF, VEGF receptors (VEGF-Rs) and active caspase-3 dramatically decreased in cells treated with AOs. Here, we also report further experiments designed to determine whether the crosstalk between AOs and apoptosis exists in melanoma VM.

The involvement of apoptosis in melanoma vasculogenic mimicry.

During development, the formation and remodeling of the primary vascular network occurs by vasculogenesis and angiogenesis. In 1999, the concept of vasculogenic mimicry was introduced to describe the unique ability of highly aggressive tumor cells to form a capillary-like structure and a matrix-rich patterned network in three-dimensional culture that mimic the embryonic vasculogenic network. In this study, we examined the ability of melanoma cells derived from patients with disseminated melanoma to engage in vasculogenic mimicry in order to identify key parameters in the complexity of the formation of capillary-like structure. We showed that disseminated melanoma as well as uveal and cutaneous melanoma adopts a vascular-related phenotype and engages in vasculogenic mimicry: the main geometrical features of capillary-like structure are determined during the first step of the vascular network assembly. We provided experimental evidence that capillary-like structure formation requires apoptotic cell death through activation of a caspase-dependent mechanism: a broad range caspase inhibitor zVAD-fmk and a caspase-3 inhibitor DEVD blocked capillary-like structure formation. Apoptosis occurs before capillary-like structure formation but not after capillary-like structures have assembled. These observations may provide a better understanding of the mechanisms involved in melanoma vasculogenic mimicry.