Recommender systems in antiviral drug discovery

Recommender systems (RSs), which underwent rapid development and had an enormous impact on e-commerce, have the potential to become useful tools for drug discovery. In this paper, we applied RS methods for the prediction of the antiviral activity class (active/inactive) for compounds extracted from ChEMBL. Two main RS approaches were applied: Collaborative filtering (Surprise implementation) and content-based filtering (sparse-group inductive matrix completion (SGIMC) method). The effectiveness of RS approaches was investigated for prediction of antiviral activity classes ("interactions") for compounds and viruses, for which some of their interactions with other viruses or compounds are known, and for prediction of interaction profiles for new compounds. Both approaches achieved relatively good prediction quality for binary classification of individual interactions and compound profiles, as quantified by cross-validation and external validation receiver operating characteristic (ROC) score >0.9. Thus, even simple recommender systems may serve as an effective tool in antiviral drug discovery

Reconstruction of Transcription Control Networks in Mollicutes by High-Throughput Identification of Promoters

Bacteria of the class Mollicutes have significantly reduced genomes and gene expression control systems. They are also efficient pathogens that can colonize a broad range of hosts including plants and animals. Despite their simplicity, Mollicutes demonstrate complex transcriptional responses to various conditions, which contradicts their reduction in gene expression regulation mechanisms. We analyzed the conservation and distribution of transcription regulators across the 50 Mollicutes species. The majority of the transcription factors regulate transport and metabolism, and there are four transcription factors that demonstrate significant conservation across the analyzed bacteria. These factors include repressors of chaperone HrcA, cell cycle regulator MraZ and two regulators with unclear function from the WhiA and YebC/PmpR families. We then used three representative species of the major clades of Mollicutes (Acholeplasma laidlawii, Spiroplasma melliferum and Mycoplasma gallisepticum) to perform promoters mapping and activity quantitation. We revealed that Mollicutes evolved towards a promoter architecture simplification that correlates with a diminishing role of transcription regulation and an increase in transcriptional noise. Using the identified operons structure and a comparative genomics approach, we reconstructed the transcription control networks for these three species. The organization of the networks reflects the adaptation of bacteria to specific conditions and hosts

Inclusive Education Importance and Problems for Students Social Integration

The article relevance. Modern concepts of education development, recognition of the uniqueness and self-worth of human individuality have led to the search for ways to socialize individuals with disabilities, to the development of new pedagogical strategies aimed at developing ideas of independent life for this category of the population. The research purpose is to study the features and identify ways to improve the quality of inclusive education. Research methods: as a research method, we used a questionnaire survey as a method of collecting primary information, which allows us to identify various aspects related to the problems of formation and perception of inclusive education by participants in the educational process. Research results: the article describes the peculiarity of the current stage of inclusive education development, analyzes the social mechanisms for improving the quality of inclusive education. The novelty and originality of the research lies in the fact that for the first time the correspondence of the existing model of inclusive education to the needs of a significant part of the educational process subjects was investigated. It is shown that, from the point of view of educational services’ consumers, a significant obstacle to improving the quality of inclusive education is the orientation of the education system on results, and not the educational process. It is revealed that the main functions of an inclusive school are educational, career-oriented, educational, and integrative. It is shown that relationships with teachers are a significant factor of psychological stress in inclusive classes. It is found that inclusive classes are sufficiently distanced from interaction with the local community. It is shown that teachers lack the skills of teamwork and confident behavior of the teacher in the presence of another adult in the classroom. It is revealed that the inclusive school is currently characterized by a high level of internal unity, but is not focused on external relations with the local community.  It is shown that parents, unlike students, note the creation of an accessible environment only for certain categories of children with disabilities (including children with musculoskeletal disorders), but not for children with sensory disorders (vision and hearing). Practical significance: the data Obtained in this work can be used in psychological research, pedagogical Sciences, age psychology, as well as for further theoretical development of this issu

Family Clustering of Viliuisk Encephalomyelitis in Traditional and New Geographic Regions

Transmission occurs through patient contact; human migration from disease-endemic villages leads to disease emergence in new communities

Relationships between the seasonal dynamics of soil fungi biomass and environmental factors in predominating forest types in the Bryansk woodlands (European Russia)

Being the crucial part of the forest soil's microbial pool, soil fungi in general and mycorrhizal fungi in particular are an important study object when it comes to forest ecosystems sustainability and preservation. Thus, the study of ectomycorrhizal fungi has been carried out in the Bryanskiy Les State Nature Biosphere Reserve, located in the south-eastern part of the Bryansk woodlands (European Russia). Forest types featured in the study are the local predominating types, namely green-moss-fructiculose pine forests and polydominant deciduous broadleaved nemoral-herbaceous forests with spruce. This study was aimed to assess seasonal dynamics of soil fungi' biomass overall and ectomycorrhizal fungi in particular over the course of the 2017 vegetation period (May – November) and its dependence on biotic and abiotic environmental factors, such as soil water content, temperature and vegetation. The vegetation period was divided into three periods of observation, namely an early (May – July), middle (July – September) and late (September – November) one. The method used to assess the fungal biomass was direct microscopic observation using the fluorescein diacetate staining. In order to estimate the ectomycorrhizal fungi biomass separately, trenching and in-growth mesh bags were employed. The obtained results suggest that the soil fungi biomass steadily increases over the vegetation period in both studied forest types. This is mostly affected by the forest type, available water amount and seasonal changes, while the temperature's impact is less pronounced. On average, the soil fungi biomass was higher in broadleaved forests than in pine forests (2.288 mg C × g-1 soil vs. 1.672 mg C × g-1 soil, respectively), with non-ectomycorrhizal component having comparable biomass. The dynamics of biomass differed in the two forest types. However, noticeable differences (p < 0.1) between the two forest types have only been recorded during the July – September period. The biomass of ectomycorrhizal fungi is smaller than the biomass of non-mycorrhizal fungi, but at the same time it is less affected by changes in moisture. Besides that, the study has shown that the forest litter characteristics can greatly affect the dynamics of the fungal biomass

Inclusive Education Importance and Problems for Students Social Integration

The article relevance. Modern concepts of education development, recognition of the uniqueness and self-worth of human individuality have led to the search for ways to socialize individuals with disabilities, to the development of new pedagogical strategies aimed at developing ideas of independent life for this category of the population. The research purpose is to study the features and identify ways to improve the quality of inclusive education. Research methods: as a research method, we used a questionnaire survey as a method of collecting primary information, which allows us to identify various aspects related to the problems of formation and perception of inclusive education by participants in the educational process. Research results: the article describes the peculiarity of the current stage of inclusive education development, analyzes the social mechanisms for improving the quality of inclusive education. The novelty and originality of the research lies in the fact that for the first time the correspondence of the existing model of inclusive education to the needs of a significant part of the educational process subjects was investigated. It is shown that, from the point of view of educational services’ consumers, a significant obstacle to improving the quality of inclusive education is the orientation of the education system on results, and not the educational process. It is revealed that the main functions of an inclusive school are educational, career-oriented, educational, and integrative. It is shown that relationships with teachers are a significant factor of psychological stress in inclusive classes. It is found that inclusive classes are sufficiently distanced from interaction with the local community. It is shown that teachers lack the skills of teamwork and confident behavior of the teacher in the presence of another adult in the classroom. It is revealed that the inclusive school is currently characterized by a high level of internal unity, but is not focused on external relations with the local community.  It is shown that parents, unlike students, note the creation of an accessible environment only for certain categories of children with disabilities (including children with musculoskeletal disorders), but not for children with sensory disorders (vision and hearing). Practical significance: the data Obtained in this work can be used in psychological research, pedagogical Sciences, age psychology, as well as for further theoretical development of this issueRelevancia del artículo. Los conceptos modernos de desarrollo educativo, el reconocimiento de la singularidad y la autoestima de la individualidad humana han llevado a la búsqueda de formas de socializar a las personas con discapacidad, al desarrollo de nuevas estrategias pedagógicas destinadas a desarrollar ideas de vida independiente para esta categoría de la población. . El propósito de la investigación es estudiar las características e identificar formas de mejorar la calidad de la educación inclusiva. Métodos de investigación: como método de investigación, utilizamos una encuesta cuestionario como método de recolección de información primaria, que nos permite identificar diversos aspectos relacionados con los problemas de formación y percepción de la educación inclusiva por parte de los participantes en el proceso educativo. Resultados de la investigación: el artículo describe la peculiaridad de la etapa actual de desarrollo de la educación inclusiva, analiza los mecanismos sociales para mejorar la calidad de la educación inclusiva. La novedad y originalidad de la investigación radica en que por primera vez se investigó la correspondencia del modelo existente de educación inclusiva con las necesidades de una parte significativa de los sujetos del proceso educativo. Se muestra que, desde el punto de vista de los consumidores de los servicios educativos, un obstáculo importante para mejorar la calidad de la educación inclusiva es la orientación del sistema educativo a los resultados y no al proceso educativo. Se revela que las principales funciones de una escuela inclusiva son educativas, vocacionales, educativas e integradoras. Se demuestra que las relaciones con los profesores son un factor significativo de estrés psicológico en las clases inclusivas. Se encuentra que las clases inclusivas están suficientemente alejadas de la interacción con la comunidad local. Se demuestra que los profesores carecen de las habilidades de trabajo en equipo y del comportamiento confiado del profesor en presencia de otro adulto en el aula. Se revela que la escuela inclusiva se caracteriza actualmente por un alto nivel de unidad interna, pero no está enfocada a las relaciones externas con la comunidad local. Se muestra que los padres, a diferencia de los estudiantes, notan la creación de un entorno accesible solo para ciertas categorías de niños con discapacidades (incluidos los niños con trastornos musculoesqueléticos), pero no para los niños con trastornos sensoriales (visión y audición). Importancia práctica: los datos obtenidos en este trabajo pueden ser utilizados en investigación psicológica, ciencias pedagógicas, psicología de la edad, así como para un mayor desarrollo teórico de este tema

Mitochondrial mutations associated with cardiac angina

Aim: Cardiac angina is a disease in which discomfort or retrosternal pain may occur. Atherosclerosis of coronary arteries is one of the main risk factors for cardiac angina. The aim of the investigation was to analyze the association of 11 mitochondrial genome mutations with cardiac angina. In our preliminary studies an association of these mutations with atherosclerosis, a risk factor for cardiac angina, was found.Methods: We used samples of white blood cells collected from 192 patients with cardiac angina and 201 conventionally healthy study participants. DNA from blood leukocyte samples was isolated using a phenol-chloroform method. DNA amplicons containing the investigated regions of 11 mitochondrial genome mutations (m.12315G&gt;A, m.652delG, m.5178C&gt;A, m.14459G&gt;A, m.3336T&gt;C, 652insG, m.3256C&gt;T, m.1555A&gt;G, m.15059G&gt;A, m.13513G&gt;A, m.14846G&gt;A) were pyrosequenced. The heteroplasmy level of mitochondrial DNA (mtDNA) mutations was analyzed using a method developed by our laboratory on the basis of pyrosequencing technology.Results: According to the obtained data, three mitochondrial mutations of human genome correlated with cardiac angina. A positive correlation was observed for mutation m.14459G&gt;A (P ≤ 0.05). One single nucleotide substitution m.5178C&gt;A (P ≤ 0.1) had a trend for positive correlation. A negative correlation for mutation m.15059G&gt;A with cardiac angina (P ≤ 0.05) was found.Conclusion: MtDNA mutations m.14459G&gt;A and m.5178C&gt;A can be used for evaluation the predisposition of individuals to atherosclerotic lesions. At the same time, mitochondrial genome mutation m.15059G&gt;A may be used for gene therapy of atherosclerosis

Multiomic Profiling Identified EGF Receptor Signaling as a Potential Inhibitor of Type I Interferon Response in Models of Oncolytic Therapy by Vesicular Stomatitis Virus

Cancer cell lines responded differentially to type I interferon treatment in models of oncolytic therapy using vesicular stomatitis virus (VSV). Two opposite cases were considered in this study, glioblastoma DBTRG-05MG and osteosarcoma HOS cell lines exhibiting resistance and sensitivity to VSV after the treatment, respectively. Type I interferon responses were compared for these cell lines by integrative analysis of the transcriptome, proteome, and RNA editome to identify molecular factors determining differential effects observed. Adenosine-to-inosine RNA editing was equally induced in both cell lines. However, transcriptome analysis showed that the number of differentially expressed genes was much higher in DBTRG-05MG with a specific enrichment in inflammatory proteins. Further, it was found that two genes, EGFR and HER2, were overexpressed in HOS cells compared with DBTRG-05MG, supporting recent reports that EGF receptor signaling attenuates interferon responses via HER2 co-receptor activity. Accordingly, combined treatment of cells with EGF receptor inhibitors such as gefitinib and type I interferon increases the resistance of sensitive cell lines to VSV. Moreover, sensitive cell lines had increased levels of HER2 protein compared with non-sensitive DBTRG-05MG. Presumably, the level of this protein expression in tumor cells might be a predictive biomarker of their resistance to oncolytic viral therapy