CHANGES OF INNATE IMMUNITY INDEXES IN SEVERE ASTHMA IN CHILDREN

At the present time, the role of innate immunity in pathogenesis of bronchial asthma (BA) is actively studied, in particular, significance of TLRs and cytokines. The study included 42 patients with severe bronchial asthma (from 3 to 12 years old), and 67 healthy children at the same age. Expression of TLR2, TLR4, and TLR9 genes was evaluated by PCR-RT from the scrapings of nasal mucosa; cytokines (IL-33, TSLP, IL-4, TGF-β1 and IL-28B) were assayed in nasal swabs by ELISA technique. The main results were as follows: an increased gene expression of TLR2, TLR4, TLR9 genes was revealed in the nasal mucosa scraps from the patients with bronchial asthma as compared to healthy children. We have also measured the contents of important cytokines secreted by the respiratory epithelium in the course of TLRs activation. The study of IL-33, TSLP, IL-4 in nasal samples revealed significantly increased concentrations of these cytokines in the patients with severe BA against the control group. A study of TGF-βlevels in nasal cavity swabs revealed a significant decrease of this regulatory cytokine in the group of pediatric patients with asthma. Worth of note, evaluation of antiviral IL-28B cytokine in the group of patients with severe BA showed a significant downward trend, in comparison to the control indexes. Hence, one may conclude on some disturbances of local innate immunity system in the patients with severe BA which manifest as hyperexpression of TLRs genes, increased production of proinflammatory and epithelial cytokines, decreased production of antiviral IL-28B cytokine, and TGF-β1

Газеты в системе медиакоммуникации городов-миллионников. Контент-аналитическое исследование

In the article the media structure of Russian cities with over one million people is analyzed. Special attention is paid to the content analysis of city newspapers. The study was carried out in correlation between particularities and development conditions of megacities and media system. Statistics on the composition of population, economic, environmental, industrial, transport and other infrastructure indicators were taken in account. The research concept was based on modern approaches to urbanism and sociology of the city, taken as a complex of territorial, managerial, economic, socio-demographic and sociocultural perspectives. Informational and communicative components in the functioning of a modern city, especially a large one, were considered to be especially important. The study has analyzed the content and communicative peculiarities of city newspapers in 13 million-plus cities (excluding Moscow and St. Petersburg).The results of the study showed that the system and content structure of the press in million-plus cities corresponds to the role of megacities in the life of the country. It reflects the functional and infrastructural features of such cities, although some areas of life and problems (economic, environmental and social) are not sufficiently represented by newspapers. In general, newspapers are aimed to serve the leisure function, following the commercial paradigm of communication in general. Although there is reason to say that the structure of the content reflects not only the objective needs of the audience, but rather its interests. Newspapers tend to entertain rather than draw attention to solving important problems. At the same time, the possibilities of professional journalism, which has significant resources not only to keep readers' attention, but to maintain a high level of urban communication, solve urgent problems of the population and the primary tasks, megacities are facing as drivers in the implementation of national projects, are underestimated.В статье анализируется медиаструктура российских городов-миллионников. Отдельное внимание уделяется контент-анализу содержания городских газет. Изучение медиасистемы с углубленным исследованием печатных изданий и их контента проводилось в соотнесенности с реальными особенностями и условиями развития мегаполисов, а именно с учетом статистических данных о составе населения, экономических, экологических, производственных, транспортных и других инфраструктурных показателях. Концепция исследования базировалась на современных подходах, свойственных урбанистике и социологии города, в рамках которых он рассматривается в комплексе территориально-поселенческих, управленческих, экономических, социально-демографических и социокультурных ракурсов. При этом в статье подчеркивается как особо важная информационно-коммуникационная составляющая функционирования современного города, особенно крупного. В ходе исследования были проанализированы содержание и коммуникативные особенности городских газет 13 городов-миллионников (за исключением Москвы и Санкт-Петербурга). Результаты показали, что система и содержательная структура прессы миллионников в целом соответствует специфике и роли мегаполисов в жизни страны, отражает функциональные и инфраструктурные особенности этого типа городов, хотя некоторые сферы жизни и проблемы миллионников, особенно экономические, экологические и социальные, недостаточно представлены в содержании газет. Но при этом есть основания говорить, что структура содержания отражает сферу не столько объективных потребностей аудитории, сколько ее интересов. Газеты стремятся скорее развлекать, чем привлекать внимание к решению важных насущных проблем. При этом недооцениваются возможности профессиональной журналистики у которой есть значительные ресурсы не только удерживать внимание читателей, но также поддерживать высокий уровень городской коммуникации, решать актуальные проблемы населения и первостепенные задачи, стоящие сегодня перед мегаполисами как драйверами в реализации национальных проектов

Genetic diagnostic criteria for periodontitis

The article assesses the results of the determination of gene polymorphism DEF-44, DEF-20, IL-10, TNF, TLR2_753, TLR2_677 in patients with chronic generalized periodontitis. The correlation presence of ENT diseases and the emergence of periodontal disease with a high probability of gene polymorphism DEF-44 and TLR-2.В статье проводится оценка результатов определения полиморфизма генов DEF-44, DEF-20, IL-10, TNF, TLR2.753, TLR2_677 у пациентов, больных хроническим генерализованным пародонтитом. Определена взаимосвязь наличия ЛОР патологии и возникновения заболеваний пародонта при высокой вероятности полиморфизма генов DEF-44 и TLR-2

Somatic evolution and global expansion of an ancient transmissible cancer lineage

Made available in DSpace on 2019-10-06T15:53:36Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-08-02GPD Charitable TrustLeverhulme TrustThe canine transmissible venereal tumor (CTVT) is a cancer lineage that arose several millennia ago and survives by “metastasizing” between hosts through cell transfer. The somatic mutations in this cancer record its phylogeography and evolutionary history. We constructed a time-resolved phylogeny from 546 CTVT exomes and describe the lineage's worldwide expansion. Examining variation in mutational exposure, we identify a highly context-specific mutational process that operated early in the cancer's evolution but subsequently vanished, correlate ultraviolet-light mutagenesis with tumor latitude, and describe tumors with heritable hyperactivity of an endogenous mutational process. CTVT displays little evidence of ongoing positive selection, and negative selection is detectable only in essential genes. We illustrate how long-lived clonal organisms capture changing mutagenic environments, and reveal that neutral genetic drift is the dominant feature of long-term cancer evolution.Transmissible Cancer Group Department of Veterinary Medicine University of CambridgeAnimal Management in Rural and Remote Indigenous Communities (AMRRIC)World VetsAnimal Shelter Stichting Dierenbescherming SurinameSikkim Anti-Rabies and Animal Health Programme Department of Animal Husbandry Livestock Fisheries and Veterinary Services Government of SikkimRoyal (Dick) School of Veterinary Studies Roslin Institute University of Edinburgh Easter Bush CampusConserLab Animal Preventive Medicine Department Faculty of Animal and Veterinary Sciences University of ChileCorozal Veterinary Hospital University of PanamáSt. George's UniversityNakuru District Veterinary Scheme LtdAnimal Medical CentreInternational Animal Welfare Training Institute UC Davis School of Veterinary MedicineCentro Universitário de Rio Preto (UNIRP)Department of Clinical and Veterinary Surgery São Paulo State University (UNESP)Ladybrand Animal ClinicVeterinary Clinic Sr. Dog'sWorld Vets Latin America Veterinary Training CenterNational Veterinary Research InstituteAnimal ClinicIntermunicipal Stray Animals Care Centre (DIKEPAZ)Animal Protection Society of SamoaFaculty of Veterinary Science University of ZuliaVeterinary Clinic BIOCONTROLFaculty of Veterinary Medicine School of Health Sciences University of ThessalyVeterinary Clinic El Roble Animal Healthcare Network Faculty of Animal and Veterinary Sciences University of ChileOnevetGroup Hospital Veterinário BernaUniversidade Vila VelhaVeterinary Clinic ZoovetservisÉcole Inter-états des Sciences et Médecine Vétérinaires de DakarDepartment of Small Animal Medicine Faculty of Veterinary Medicine Utrecht UniversityVetexpert Veterinary GroupVeterinary Clinic Lopez QuintanaClinique Veterinaire de Grand Fond Saint Gilles les BainsDepartment of Veterinary Sciences University of MessinaFacultad de Medicina Veterinaria y Zootecnia Universidad Autónoma del Estado de MéxicoSchool of Veterinary Medicine Universidad de las AméricasCancer Development and Innate Immune Evasion Lab Champalimaud Center for the UnknownTouray and Meyer Vet ClinicHillside Animal HospitalKampala Veterinary SurgeryAsavet Veterinary CharitiesVets Beyond BordersFaculty of Veterinary Medicine Autonomous University of YucatanLaboratorio de Patología Veterinaria Universidad de CaldasInterdisciplinary Centre of Research in Animal Health (CIISA) Faculty of Veterinary Medicine University of LisbonFour Paws InternationalHelp in SufferingVeterinary Clinic Dr José RojasDepartment of Biotechnology Balochistan University of Information Technology Engineering and Management SciencesCorozal Veterinary ClinicVeterinary Clinic VetmasterState Hospital of Veterinary MedicineJomo Kenyatta University of Agriculture and TechnologyLaboratory of Biomedicine and Regenerative Medicine Department of Clinical Sciences Faculty of Animal and Veterinary Sciences University of ChileFaculty of Veterinary and Agricultural Sciences University of MelbourneAnimal Anti Cruelty LeagueClinical Sciences Department Faculty of Veterinary Medicine BucharestDepartment of Pathology Faculty of Veterinary Medicine Ankara UniversityFaculty of Veterinary Sciences National University of AsuncionLilongwe Society for Protection and Care of Animals (LSPCA)Wellcome Sanger InstituteDepartment of Cellular and Molecular Medicine University of California San DiegoDepartment of Clinical and Veterinary Surgery São Paulo State University (UNESP)Leverhulme Trust: 102942/Z/13/

Recurrent horizontal transfer identifies mitochondrial positive selection in a transmissible cancer

Abstract: Autonomous replication and segregation of mitochondrial DNA (mtDNA) creates the potential for evolutionary conflict driven by emergence of haplotypes under positive selection for ‘selfish’ traits, such as replicative advantage. However, few cases of this phenomenon arising within natural populations have been described. Here, we survey the frequency of mtDNA horizontal transfer within the canine transmissible venereal tumour (CTVT), a contagious cancer clone that occasionally acquires mtDNA from its hosts. Remarkably, one canine mtDNA haplotype, A1d1a, has repeatedly and recently colonised CTVT cells, recurrently replacing incumbent CTVT haplotypes. An A1d1a control region polymorphism predicted to influence transcription is fixed in the products of an A1d1a recombination event and occurs somatically on other CTVT mtDNA backgrounds. We present a model whereby ‘selfish’ positive selection acting on a regulatory variant drives repeated fixation of A1d1a within CTVT cells

Mitochondrial genetic diversity, selection and recombination in a canine transmissible cancer.

Canine transmissible venereal tumour (CTVT) is a clonally transmissible cancer that originated approximately 11,000 years ago and affects dogs worldwide. Despite the clonal origin of the CTVT nuclear genome, CTVT mitochondrial genomes (mtDNAs) have been acquired by periodic capture from transient hosts. We sequenced 449 complete mtDNAs from a global population of CTVTs, and show that mtDNA horizontal transfer has occurred at least five times, delineating five tumour clades whose distributions track two millennia of dog global migration. Negative selection has operated to prevent accumulation of deleterious mutations in captured mtDNA, and recombination has caused occasional mtDNA re-assortment. These findings implicate functional mtDNA as a driver of CTVT global metastatic spread, further highlighting the important role of mtDNA in cancer evolution.Wellcome Trust Investigator Award, 102942/Z/13/A Elizabeth P Murchison Leverhulme Trust Philip Leverhulme Prize Elizabeth P Murchison Royal Society Research Grant, RG130615 Elizabeth P Murchiso

Newspapers in the media-communication system of million cities. Content analytical study

In the article the media structure of Russian cities with over one million people is analyzed. Special attention is paid to the content analysis of city newspapers. The study was carried out in correlation between particularities and development conditions of megacities and media system. Statistics on the composition of population, economic, environmental, industrial, transport and other infrastructure indicators were taken in account. The research concept was based on modern approaches to urbanism and sociology of the city, taken as a complex of territorial, managerial, economic, socio-demographic and sociocultural perspectives. Informational and communicative components in the functioning of a modern city, especially a large one, were considered to be especially important. The study has analyzed the content and communicative peculiarities of city newspapers in 13 million-plus cities (excluding Moscow and St. Petersburg).The results of the study showed that the system and content structure of the press in million-plus cities corresponds to the role of megacities in the life of the country. It reflects the functional and infrastructural features of such cities, although some areas of life and problems (economic, environmental and social) are not sufficiently represented by newspapers. In general, newspapers are aimed to serve the leisure function, following the commercial paradigm of communication in general. Although there is reason to say that the structure of the content reflects not only the objective needs of the audience, but rather its interests. Newspapers tend to entertain rather than draw attention to solving important problems. At the same time, the possibilities of professional journalism, which has significant resources not only to keep readers' attention, but to maintain a high level of urban communication, solve urgent problems of the population and the primary tasks, megacities are facing as drivers in the implementation of national projects, are underestimated

The role of epithelial cells in atopy pathogenesis

Aim. The study of the mechanisms of atopic disease formation and a model of immunopathogenesis of the atopic diseases.Methods. Determination of surface lymphocytes receptors in peripheral blood of atopic bronchial asthma and atopic dermatitis patients with the help of monoclonal antibodies using the indirect immunofluorescence method. Expression of genes encoding TLR2, TLR4 and TLR9 receptors of airborne epithelial cells by real-time polymerase chain reaction, as well as determination of cytokine TSLP, IL-33, IL-4 and TGFβ (eBioscience) in airway flushes in atopic asthma patients and healthy people.Results. During the exacerbation of atopic diseases in peripheral blood lymphocytes, an intensive activation process develops with impaired lymphocytes activating apoptosis aimed at the formation of plasma cells capable of developing intensive IgE synthesis. To search for signals that could explain the mechanism of rearrangement of the B-cell part of the immune system during atopy, the epithelium cells of the airways were examined in a group of patients with atopic asthma and found an increase in gene expression coding for TLR2, TLR4, TLR9 in 6, 3 and 2.5 times respectively. Along with increased expression of TLRs genes in patients with bronchial asthma, an increased content of TSLP and IL-33 cytokines secreted by epithelial cells of the airways was detected. These cytokines have an immunoregulatory action - their nearby antigen presenting functions format the Th2 type of immune response, promote the production of cytokines (IL-4, IL-9, IL-13) and cause the development of an allergic type of inflammation.Conclusion. We suppose that the main link in pathogenesis is a disruption of the interaction of TLRs with the corresponding ligands caused by spontaneous dimerization of TLRs under the malonic dialdehyde influence. The intake of slowly metabolized dimers of TLRs into epithelial cells is a signal for genome activation, which leads to the synthesis of allergic cytokines IL-33 and TSLP. Thus, the main immunopathogenesis pathway of atopic diseases is the pathological functional interaction between epithelial cells and peripheral blood B-lymphocytes

EXPRESSION FEATURES OF TOLL-LIKE RECEPTOR 2 AND TOLL-LIKE RECEPTOR 4 IN CHILDREN WITH ASTHMA

Currently actively  discussed  the  role  of innate immunity receptors, in particular TLRs  in the immunopathogenesis of bronchial asthma (BA).The aim of our work was to study the expression of ТLR2 and TLR4 on the nasal mucosal cells and peripheral blood leukocytes  of patients with BA of different  severity.The study included 40 children with asthma (3-12 years) and 10 healthy  children. Methods: real-time PCR, flow cytometry and multiplex immunofluorescence analysis evaluated the levels of pro and anti-inflammatory cytokines (IL-1β, IL-1ra, IL-6, IL-8, IL-10, TNFα) in nasal swabs.The result of the study hyperactivation of the factors of innate immunity at the level of the mucosal  of the nasal cavity in patients with asthma, manifested by increased gene expression  of TLR2, TLR4, and production of proinflammatory as well as anti-inflammatory cytokines. Correlation between cytokine levels and the severity of asthma. In the  peripheral blood  identified a significant  increase  in the  expression  of TLR2  and  TLR4  on circulating CD14+  monocytes in children with BA.Thus,  the  increase  of gene expression  of TLRs  mucosa of the  nasal cavity, increase  surface  expression  of TLR2  and TLR4  on circulating monocytes of patients with bronchial asthma compared to healthy  children. The revealed changes indicate the involvement of the system of TLRs in the immunopathogenesis of bronchial asthma. In the future, TLRs can be used as markers  to predict the course of ad and possible therapeutic targets