The Echinococcus canadensis (G7) genome: A key knowledge of parasitic platyhelminth human diseases

Background: The parasite Echinococcus canadensis (G7) (phylum Platyhelminthes, class Cestoda) is one of the causative agents of echinococcosis. Echinococcosis is a worldwide chronic zoonosis affecting humans as well as domestic and wild mammals, which has been reported as a prioritized neglected disease by the World Health Organisation. No genomic data, comparative genomic analyses or efficient therapeutic and diagnostic tools are available for this severe disease. The information presented in this study will help to understand the peculiar biological characters and to design species-specific control tools. Results: We sequenced, assembled and annotated the 115-Mb genome of E. canadensis (G7). Comparative genomic analyses using whole genome data of three Echinococcus species not only confirmed the status of E. canadensis (G7) as a separate species but also demonstrated a high nucleotide sequences divergence in relation to E. granulosus (G1). The E. canadensis (G7) genome contains 11,449 genes with a core set of 881 orthologs shared among five cestode species. Comparative genomics revealed that there are more single nucleotide polymorphisms (SNPs) between E. canadensis (G7) and E. granulosus (G1) than between E. canadensis (G7) and E. multilocularis. This result was unexpected since E. canadensis (G7) and E. granulosus (G1) were considered to belong to the species complex E. granulosus sensu lato. We described SNPs in known drug targets and metabolism genes in the E. canadensis (G7) genome. Regarding gene regulation, we analysed three particular features: CpG island distribution along the three Echinococcus genomes, DNA methylation system and small RNA pathway. The results suggest the occurrence of yet unknown gene regulation mechanisms in Echinococcus. Conclusions: This is the first work that addresses Echinococcus comparative genomics. The resources presented here will promote the study of mechanisms of parasite development as well as new tools for drug discovery. The availability of a high-quality genome assembly is critical for fully exploring the biology of a pathogenic organism. The E. canadensis (G7) genome presented in this study provides a unique opportunity to address the genetic diversity among the genus Echinococcus and its particular developmental features. At present, there is no unequivocal taxonomic classification of Echinococcus species; however, the genome-wide SNPs analysis performed here revealed the phylogenetic distance among these three Echinococcus species. Additional cestode genomes need to be sequenced to be able to resolve their phylogeny.Fil: Maldonado, Lucas Luciano. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Assis, Juliana. Fundación Oswaldo Cruz; BrasilFil: Gomes Araújo, Flávio M.. Fundación Oswaldo Cruz; BrasilFil: Salim, Anna C. M.. Fundación Oswaldo Cruz; BrasilFil: Macchiaroli, Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Cucher, Marcela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Camicia, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Fox, Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Rosenzvit, Mara Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Oliveira, Guilherme. Instituto Tecnológico Vale; Brasil. Fundación Oswaldo Cruz; BrasilFil: Kamenetzky, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentin

CpG Islands Undermethylation in Human Genomic Regions under Selective Pressure

DNA methylation at CpG islands (CGIs) is one of the most intensively studied epigenetic mechanisms. It is fundamental for cellular differentiation and control of transcriptional potential. DNA methylation is involved also in several processes that are central to evolutionary biology, including phenotypic plasticity and evolvability. In this study, we explored the relationship between CpG islands methylation and signatures of selective pressure in Homo Sapiens, using a computational biology approach. By analyzing methylation data of 25 cell lines from the Encyclopedia of DNA Elements (ENCODE) Consortium, we compared the DNA methylation of CpG islands in genomic regions under selective pressure with the methylation of CpG islands in the remaining part of the genome. To define genomic regions under selective pressure, we used three different methods, each oriented to provide distinct information about selective events. Independently of the method and of the cell type used, we found evidences of undermethylation of CGIs in human genomic regions under selective pressure. Additionally, by analyzing SNP frequency in CpG islands, we demonstrated that CpG islands in regions under selective pressure show lower genetic variation. Our findings suggest that the CpG islands in regions under selective pressure seem to be somehow more “protected” from methylation when compared with other regions of the genome

Анализ основных параметров работы головного регионального сосудистого центра НИИ СП им. Н.В. Склифосовского

Introduction. The regional vascular centers (RVC) network was created throughout Russia to manage cardiovascular diseases. On the basis of N.V. Sklifosovsky Research Institute for Emergency Medicine in Moscow, a center was created, which received the status of the head RVC. A comprehensive analysis of its work has not yet been carried out.Aim of study. To assess the main performance indicators and development directions of the head RVC based on the analysis of data for 2012–2019.Results. Analysis of the data obtained showed that by 2019 the flow of patient admissions increased 2.3-fold. At the same time, the use of the hospital bed fund does not exceed 100%, and the use of the intensive care bed fund has increased to 123%. A significant proportion of patients come with not field-specific diagnosis. The mortality, which is the main indicator of the quality of treatment in patients treated at the RVC, remained within 2.33–3%, which turned out to be 3 times lower in similar patients treated in other departments of the Institute.Discussion. Against the background of a constant increase in the number of hospitalizations, resusci-tation provision turned out to be insufficient when the number of hospital beds corre-sponded to the flow of admissions. The general lack of intensive care beds in the center and the lack of specialized intensive care for the department of vascular surgery forces the use of other intensive care units of the Institute. The admission of patients with other (not specific for RVC) diagnosis to the vascular center reduces the volume of highly specialized care for specialized patients.Conclusion. The analysis of the performance indicators of the head regional vascular center on the basis of N.V. Sklifosovsky Research Institute for Emergency Medicine, identified the need to expand the resuscitation bed fund in the existing departments of the center and organize specialized resuscitation for patients of the vascular surgery department. Also, the lack of intensive care beds is aggravated by a large flow of non-core admissions. Their reduction with the existing structure will provide significant savings in resources and will increase the number of treated profile patients and improve the quality of highly specialized care.Введение. Для борьбы с сердечно-сосудистыми заболеваниями была создана сеть региональных сосудистых центров (РСЦ) по всей территории России. На базе Московского Научно-исследовательского института скорой помощи им. Н.В. Склифосовского был создан центр, получивший статус головного РСЦ. Комплексного анализа его работы до настоящего времени не проводилось.Цель. Оценить основные показатели работы и направления развития головного РСЦ на основании анализа данных за 2012–2019 годы.Результаты. Анализ полученных данных показал, что к 2019 году поток поступлений пациентов увеличился в 2,3 раза. При этом использование госпитального коечного фонда не превышает 100%, а использование коечного фонда реанимации возросло до 123%. Значительная часть пациентов обращается с непрофильными диагнозами. Основной показатель качества лечения — летальность, у пациентов, пролеченных в РСЦ, оставался в пределах 2,33–3%, что оказалось в 3 раза ниже, чем у аналогичных пациентов, пролеченных в других отделениях Института.Обсуждение. На фоне постоянного увеличения числа госпитализаций реанимационная обеспеченность оказалась недостаточной при соответствии числа госпитальных коек потоку поступлений. Общий недостаток реанимационных коек в центре и отсутствие профильной реанимации для отделения сосудистой хирургии вынуждает использовать непрофильные реанимации Института. Поступление в сосудистый центр непрофильных больных сокращает объем оказания высокоспециализированной помощи профильным пациентам.Вывод. Анализ показателей работы головного регионального сосудистого центра на базе НИИ СП им. Н.В. Склифосовского выявил необходимость расширения реанимационного коечного фонда в существующих отделениях центра и организации специализированной реанимации для пациентов отделения сосудистой хирургии. Также недостаток реанимационных коек усугубляется большим потоком непрофильных поступлений. Их снижение при существующей структуре обеспечит значительную экономию ресурсов и позволит увеличить число пролеченных профильных пациентов и повысить качество оказания высокоспециализированной помощи

Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.

Following severe or chronic liver injury, adult ductal cells (cholangiocytes) contribute to regeneration by restoring both hepatocytes and cholangiocytes. We recently showed that ductal cells clonally expand as self-renewing liver organoids that retain their differentiation capacity into both hepatocytes and ductal cells. However, the molecular mechanisms by which adult ductal-committed cells acquire cellular plasticity, initiate organoids and regenerate the damaged tissue remain largely unknown. Here, we describe that ductal cells undergo a transient, genome-wide, remodelling of their transcriptome and epigenome during organoid initiation and in vivo following tissue damage. TET1-mediated hydroxymethylation licences differentiated ductal cells to initiate organoids and activate the regenerative programme through the transcriptional regulation of stem-cell genes and regenerative pathways including the YAP-Hippo signalling. Our results argue in favour of the remodelling of genomic methylome/hydroxymethylome landscapes as a general mechanism by which differentiated cells exit a committed state in response to tissue damage.RCUK Cancer Research UK ERC H2020 Wellcome Trus

Parametric Oscillations of a Thermal Field During Explosive Crystallization of Amorphous Films

Изучены тепловые процессы, происходящие при взрывной кристаллизации аморфных пленок, напыленных на подложку. Представлены результаты численного моделирования параметрических колебаний теплового поля в системе «фазовая граница – подложка». Рассмотрены стационарный и волновой режимы возбуждения горячих центров кристаллизации в аморфной фазе. Расчеты выполнены для аморфной пленки германия. Установлены основные физические факторы, определяющие амплитудно-частотные свойства данного процесса: толщина пленки, температура подложки и скорость фазовой границы кристаллизации. Указаны примеры возникновения резонансных ситуаций. Рассмотрены колебания параметрической системы, которая испытывает внешнее воздействие в режиме биений. Для этой системы по-строен трехмерный фазовый портрет, демонстрирующий ее динамические свойства. При наличии спектра частот структура фазовых траекторий в основном аналогична варианту колебаний на одной частоте.The thermal processes occurring during explosive crystallization of amorphous films deposited on a substrate are studied. The results of numerical modeling of parametric oscillations of a thermal field in the “phase boundary – substrate” system are presented. The stationary and wave modes of hot crystallization centers in the amorphous phase are considered. The calculations are performed for an amorphous germanium film. The main physical factors determining the amplitude and frequency properties of this process are established: film thickness, substrate temperature, and crystallization phase boundary rate. Examples of the resonant situation occurrence are indicated. The parametric system oscillations, which has external influence in the beating mode, are considered. A three-dimensional phase portrait is constructed for this system, demonstrating its dynamic properties. In the presence of a frequency spectrum, the structure of phase trace is basically similar to the variant of oscillations at one frequency

Session 17 Ecophysiology

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The effect of tilorone on the cytoimmunological parameters of induced sputum and on the frequency of asthma exacerbations caused by respiratory viral infection

The abilities of tilorone to modulate an inflammatory response in acute respiratory viral infections (ARVI) and proofs of its clinical efficacy were the basis for investigating the effect of tilorone (Amixin) on the cytoimmunological parameters of induced sputum and on the frequency of asthma exacerbations caused by respiratory viral infection in children.Objective: to evaluate the clinical course of the disease and the cellular composition and immunological indices of induced sputum in children with an asthma exacerbation in the presence of the acute respiratory disease on addition of Amixin to standard basic therapy. Thirty children aged 7 to 16 years with an asthma exacerbation in the presence of ARVI were examined. Pharyngeal and nasal swabs were tested by PCR forrespiratory viruses; externalrespiratory function was determined before and after a pharmacological test; and nasal secretions and induced sputum were also cytologically investigated. A follow-up group (n=19) received treatment with Amixin according to the regimen.The predominant inflammatory phenotype in children with an asthma exacerbation in the presence of ARVI was ascertained to be neutrophilic (53.9%). Pathogen identification revealed rhinovirus in two-thirds of cases. Addition of tilorone (Amixin) to standard basic therapy for an asthma exacerbation caused by ARVI declined the number of recurrent ARVIs over the next 6 weeks; the number of bacterial complications did reduce that of asthma exacerbations if the latter occurred. The children treated with Amixin showed elevated levels of macrophages, reduced concentrations of eosinophils and IL-8, IL-1β in the induced sputum, and improved spirometric parameters reflecting permeability at the level of small and medium-sized bronchi