A Tailward Moving Current Sheet Normal Magnetic Field Front Followed by an Earthward Moving Dipolarization Front

A case study is presented using measurements from the Cluster spacecraft and ground-based magnetometers that show a substorm onset propagating from the inner to outer plasma sheet. On 3 October 2005, Cluster, traversing an ion-scale current sheet at the near-Earth plasma sheet, detected a sudden enhancement of Bz, which was immediately followed by a series of flux rope structures. Both the local Bz enhancement and flux ropes propagated tailward. Approximately 5 min later, another Bz enhancement, followed by a large density decrease, was observed to rapidly propagate earthward. Between the two Bz enhancements, a significant removal of magnetic flux occurred, possibly resulting from the tailward moving Bz enhancement and flux ropes. In our scenario, this flux removal caused the magnetotail to be globally stretched so that the thinnest sheet formed tailward of Cluster. The thinned current sheet facilitated magnetic reconnection that quickly evolved from plasma sheet to lobe and generated the later earthward moving dipolarization front (DF) followed by a reduction in density and entropy. Ground magnetograms located near the meridian of Cluster's magnetic foot points show two-step bay enhancements. The positive bay associated with the first Bz enhancement indicates that the substorm onset signatures propagated from the inner to the outer plasma sheet, consistent with the Cluster observation. The more intense bay features associated with the later DF are consistent with the earthward motion of the front. The event suggests that current disruption signatures that originated in the near-Earth current sheet propagated tailward, triggering or facilitating midtail reconnection, thereby preconditioning the magnetosphere for a later strong substorm enhancement

Thiouronium Salt Derivatives Based on Vicinal Diamines as Potential Neuroprotectors

Most of the medicinal products that are currently approved and used in clinical practice for neurodegenerative diseases, in particular Alzheimer’s disease, have a compensatory mechanism of action that enhances neurotransmitter signalling. It is an urgent need to develop new medicinal products combining cognitive-enhancing, neuroprotective, and disease-specific effects resulting from a multi-target mechanism of action including, in particular, prevention of glutamate-induced neuronal calcium uptake and stabilisation of microtubules.The aim of this study was to search for potentially neuroprotective and tauopathy-alleviating medicines amongst new thiouronium salt derivatives based on vicinal diamines.Materials and methods. The study investigated the ability of thiouronium salts to block glutamate-induced 45Ca2+ uptake by synaptosomes prepared from the brain of Wistar rats. The authors evaluated effects of these new compounds on polymerisation of a preparation of C57bl mouse brain tubulin and microtubule-associated proteins. The evaluation was carried out in the presence of guanosine triphosphate (GTP) and based on specific absorbance changes at 355 nm due to formation of microtubules. The authors analysed the structure of these microtubules, using negative staining followed by transmission electron microscopy. The IC50 determination and the statistical analysis were performed using standard software (Excel and PRISM 6.02).Results. The authors developed a screening algorithm for a number of new thiouronium salt derivatives based on vicinal diamines and studied biological activity of these derivatives by the effects on glutamate-induced calcium uptake by synaptosomes and on microtubule assembly processes. The authors identified compounds suppressing glutamate-induced calcium uptake by synaptosomes, i.e. compounds with neuroprotective potential. In addition, a number of new compounds were able to stimulate GTP-dependent microtubule assembly processes. The authors observed formation of microtubules with a normal structure in the presence of isopropyl-N’-[2-(benzoylamino)-1,2-diphenylethyl]-N-ethylimidothiocarbamate hydrobromide and considered the compound a promising scaffold for further optimisation.Conclusions. Chemical modification of thiouronium salts is a promising direction for developing effective neuroprotectors and microtubule stabilisers

Biological Properties and Molecular Genetic Characteristics of Bacillus Anthracis Strains Isolated During Anthrax Outbreaks in Kazakhstan in 2016

Today, anthrax is recorded in many countries around the world, in Kazakhstan – in the form of sporadic cases or small outbreaks. Despite the endemicity of anthrax in Kazakhstan, the genetic diversity strains is not well described. At the moment, MLVA-25, which is sufficient for molecular and epidemiological monitoring, is recognized as one of the most discriminatory methods of genotyping.Objective: to determine the cultural and morphological properties, the genomic characteristics of the strains of the anthrax pathogen, their geographical distribution in the territory of Kazakhstan during the outbreaks in 2016, a comparative analysis with collection strains isolated since 1962.Methods: microbiological, genetic research methods were used in the work.Results. We investigated 11 strains of B. anthracis, which were isolated in 2016 in Kazakhstan. For comparison of genotypes, 26 strains were used from the collection of pathogenic microorganisms of the A.M. Aykimbaev’s Kazakh Scientific Center for Quarantine and Zoonotic Diseases. Phylogenetic analysis clustered 37 strains of B. anthracis into three clusters and 23 genotypes.The results of studying the phenotypic properties of anthrax strains by the main identification tests showed that all the strains studied in the experiment and isolated from 1961 to 2016 had biological properties characteristic of typical of B. anthracis strains.The anthrax strains isolated in 2016 are characterized as significant variability, as well as the circulation of the same genotypes and clusters in different areas of Kazakhstan. MLVA-profiles of analyzed Kazakhstan strains are unique and do not fully coincide with any studied strain from MLVAbank. On the MST-tree, Kazakhstan’s strains are located in three clusters, as on the phylogenetic tree.Conclusion: Molecular genetic analysis of B. anthracis strains enhances the ability of epidemiologists to track the sources and pathways of infection.It is necessary to improve the tracking system for strains of especially dangerous infections in  Kazakhstan using modern molecular genetic methods

Эпидемиология ротавирусной инфекции и тактика вакцинопрофилактики

Rotavirus infection is a widespread cause of severe gastroenteritis in children in low-income countries. Specific prophylaxis in young children has become the most important means of combating severe rotavirus gastroenteritis. The review presents current data on the molecular biology and genetic diversity of rotaviruses, interaction of viral proteins with host cell receptors, molecular aspects of infectivity and pathogenesis of rotavirus infection, and the development of immunity. It addresses a new approach to the epidemiology of rotavirus infection which regards it as a manageable infection, it illustrates the specificity of the epidemic process based on data gained from extensive experience in vaccination, and summarises relevant information on the introduction of rotavirus vaccines into the international healthcare practice. The paper summarises risks associated with the use of vaccines based on the analysis of WHO statistics, scientific publications on the epidemiology of rotavirus infection, and the results of vaccination. It analyses approaches of the competent authorities of some countries to the tactics of vaccination against rotavirus infection and the WHO stance on the use of existing vaccines for the prevention of rotavirus infection. A conclusion was made that it is necessary to further improve the tactics of vaccine prevention of rotavirus infection in Russia, to study the incidence of idiopathic intussusception, and to conduct further studies aimed at characterisation of existing and newly emerging genotypes of rotavirus.Ротавирусная инфекция повсеместно является причиной тяжелого гастроэнтерита, приводящего к смерти детей в странах с низким бюджетом. Специфическая профилактика среди детей младшего возраста стала важнейшим средством борьбы с тяжелой формой ротавирусного гастроэнтерита. В обзоре приведены актуальные данные о молекулярной биологии и генетическом разнообразии ротавирусов, взаимодействии вирусных белков с рецепторами клеток организма-хозяина, изучении молекулярных аспектов инфекционности и патогенеза ротавирусной инфекции и развитии иммунитета. Отражен новый подход к пониманию эпидемиологии ротавирусной инфекции как контролируемой инфекции, показаны особенности эпидемического процесса с учетом многолетнего опыта вакцинопрофилактики, обобщена актуальная информация о внедрении в практику здравоохранения вакцин против ротавирусной инфекции в мире. Уделено внимание рискам применения вакцин на основе анализа статистических материалов ВОЗ и научных публикаций об эпидемиологии ротавирусной инфекции и результатов применения вакцин. Рассмотрены подходы уполномоченных органов в области здравоохранения отдельных государств к тактике вакцинопрофилактики ротавирусной инфекции и позиция ВОЗ в отношении применения существующих вакцин для профилактики ротавирусной инфекции. Сделан вывод о необходимости дальнейшего совершенствования тактики вакцинопрофилактики ротавирусной инфекции в России, изучения уровня идиопатической инвагинации, проведения дальнейших исследований по характеристике существующих и вновь появляющихся генотипов ротавирусов

Drosophila histone locus bodies form by hierarchical recruitment of components

An assembly process involving sequential recruitment of components and hierarchical dependency drives formation of the nuclear structures known as histone locus bodies

Approaches to Reduce Adverse Effect of Vaccinia Virus in Orally Immunized Mice

Objective of the investigation was to model the adverse action of vaccinia virus (VV), caused by oral immunization of mice and to evaluate efficacy of its reduction, using therapeutic and prophylactic drugs. Materials and methods. Virological and immunological research methods were used. Results and conclusions. Reproduced was pathological action of VV in the orally infected mice. The ability to reduce the side effect and protect mice from lethal infection was demonstrated by such preparations as Metisazon, Likopid, and NIOCH-14 orally administered in the investigated schemes. Moreover preliminary single oral immunization with TEOVak smallpox vaccine before oral infection with Neurovaccine-92 strain of VV also lowered pathogenic effect and protected mice against death. All the investigated schemes of drug administration did not affect the immune response if used alongside with TEOVak smallpox vaccine and can be deployed to develop safe schemes of primary oral vaccination against smallpox. In addition, such drugs as Ribomunil, Immudon, Ingavirin can be used as means to enhance the immune response to smallpox vaccines

Внесение изменений в документы регистрационных досье на вакцины: анализ нормативно-методических подходов в Российской Федерации и за рубежом

The management of post-approval changes to registration dossiers for medicinal products is one of the most important factors for ensuring sustainable quality, safety and efficacy of medicines. Competent authorities that use the module format of the registration dossier, i.e. the regulatory authorities of the European Union, USA and other members of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), and the Eurasian Economic Union (EEU), issue guidelines on changes to registration dossiers for pharmaceuticals and biologicals (immunological products). Vaccines (finished dosage forms) and vaccine antigens (active ingredients) are a specific group of immunobiological products which have great prophylactic importance for healthcare, and which are associated with challenging development and specific methods of manufacturing and quality control. The procedure of introducing post-approval variations to dossiers for immunobiological medicinal products is poorly reflected in the current Russian and EEU regulations. The World Health Organization (WHO) established a procedure described in the «Guidelines on procedures and data requirements for changes to approved vaccines». The purpose of the present study was to compare current Russian and international legislation in terms of regulatory requirements for post-approval сhanges to dossiers for immunobiological products. The Federal State Budgetary Institution «Scientific Centre for Expert Evaluation of Medicinal Products» of the Ministry of Health of the Russian Federation is drafting Guideline on introducing post-approval changes into dossiers for immunobiological medicines. The draft includes a detailed review of various categories of changes based on their importance, and a list of conditions and required documents for specific groups of medicines. This article summarises scientific and methodological approaches to evaluation of changes introduced in registration dossiers for vaccines in order to further improve the regulatory framework of the Russian Federation and the EEU.Регулирование процесса внесения изменений в документы регистрационного  досье является одним из важных факторов обеспечения стабильности качества, безопасности и эффективности лекарственных препаратов. Уполномоченные органы государств, поддерживающих модульный формат регистрационного досье: Европейского Союза, США, других стран-участниц Международного совета по гармонизации технических требований к лекарственным средствам для медицинского применения и Евразийского экономического союза (ЕАЭС), издают руководящие документы о внесении изменений в документы регистрационных досье на химико-фармацевтические и биологические (иммунологические) лекарственные средства. Вакцины (готовые формы) и вакцинные антигены (действующие вещества) представляют собой особую группу иммунобиологических лекарственных средств, характеризующихся высокой профилактической значимостью для здравоохранения, сложностью разработки, особыми методами производства и контроля. Порядок внесения изменений в документы регистрационного досье на иммунобиологическое лекарственное средство недостаточно отражен в действующих нормативно-правовых документах Российской Федерации и ЕАЭС. Всемирная организация здравоохранения рекомендует процедуру, описанную в документе «Руководство по процедурам и требованиям к данным, связанным с внесением изменений в зарегистрированные вакцины». Цель работы – проведение сравнительного анализа действующих отечественных и международных нормативно-методических документов в части регуляторных требований к процедуре внесения изменений в регистрационные досье зарегистрированных иммунобиологических лекарственных препаратов. В ФГБУ «НЦЭСМП» Минздрава России разрабатывается Проект методических рекомендаций по внесению изменений в регистрационные досье на зарегистрированные иммунобиологические препараты, который включает в себя детальное рассмотрение категорий значимости вносимых изменений, содержит условия и перечень необходимых документов для данной группы препаратов. В статье обобщены научно-методические подходы к экспертизе изменений, вносимых в регистрационное досье вакцины с целью дальнейшего совершенствования нормативно-правовой базы Российской Федерации и ЕАЭС