Forward genetic analysis of Toll-like receptor responses in wild-derived mice reveals a novel antiinflammatory role for IRAK1BP1

Although inflammatory cytokines produced by activation of Toll-like receptors (TLRs) are essential for early host defense against infection, they also mediate a vast array of pathologies, including autoimmune disease, hypersensitivity reactions, and sepsis. Thus, numerous regulatory mechanisms exist in parallel with proinflammatory pathways to prevent excessive release of these potent effector molecules. We report elucidation of a novel regulatory function for interleukin receptor–associated kinase (IRAK)-1 binding protein 1 (IRAK1BP1, also known as SIMPL) through quantitative trait locus mapping of the TLR response in wild-derived mouse strains. This gene emerged as a negative regulator of TLR2-mediated interleukin (IL)-6 production in MOLF/Ei mice, which expressed IRAK1BP1 mRNA in an allele-specific manner when crossed with the C57BL/6J strain. Human peripheral blood mononuclear cells and primary macrophages from two other wild-derived mouse strains also induced IRAK1BP1 mRNA by 4 hours after stimulation with agonists of various TLRs. Examination of its effects on IL-6 and other cytokines demonstrated that IRAK1BP1 regulates transcription of a specific subset of TLR-responsive genes, producing an overall antiinflammatory profile. Our results reveal that IRAK1BP1 is a critical factor in preventing dangerous overproduction of proinflammatory cytokines by the innate immune system and in influencing the specificity of TLR responses. Furthermore, these results show that the genetic diversity of wild-derived mouse strains makes them a valuable model of important human gene functions that have been lost in some laboratory-inbred strains

Desenvolvimento de conteúdos de programas educativos de formação complementar para composição de professores na organização de serviços educativos de formação com deficiência

Guided by the results of the experimental work, the authors came to the conclusion that the use of the electronic educational and methodical complex in mathematics on the basis of modular qualification training technology is essential. The current stage in the development of educational systems is characterized by the emergence and practical introduction of inclusive education for children with disabilities in general education organizations. Inclusion in the educational process of children with disabilities is dictated not only by modern normative documents, but also by the social need for inclusive education. One of the conditions for the preparation of children with disabilities in the educational environment is the quality and special training of teachers who must possess certain knowledge and skills to work with children with disabilities. Therefore, this study aimed to address the problem of training teachers in additional vocational education to work with children with disabilities. We conducted a training experiment, in which the professors of the university participated. The purpose of the pilot work was to improve the quality of teacher training in additional professional education to create an inclusive educational environment in the university. The legislative concepts of the Russian Federation are justified. One of the priority directions for the education of children with mental retardation (intellectual disabilities) along with general education is to give them a real opportunity to obtain a profession. The requirements for the results of the development of the complementary education program for children reflect the set of individual, public and state needs. The article gives an example of the developed program of additional professional education for the teaching staff and gives an example of the subject matter of the taught modules. Applying the teacher's professional skills training technology in additional education, additional education courses have been developed for the teaching staff of the university. An example is given of the opening of a resource center at the K. Minin University, which allows solving the main tasks of vocational training for children with disabilities.Guiados por los resultados del trabajo experimental, los autores llegaron a la conclusión de que el uso del complejo educativo y metódico electrónico en matemáticas sobre la base de la tecnología de capacitación de calificación modular es esencial. La etapa actual en el desarrollo de los sistemas educativos se caracteriza por el surgimiento y la introducción en la práctica de la educación inclusiva de los niños con discapacidades en las organizaciones de educación general. La inclusión en el proceso educativo de los niños con discapacidades está dictada no solo por los documentos normativos modernos, sino también por la necesidad social de una educación inclusiva. Una de las condiciones para la preparación de niños con discapacidades en el entorno educativo es la calidad y la capacitación especial de los maestros que deben poseer ciertos conocimientos y habilidades para trabajar con niños con discapacidades. Por lo tanto, este estudio tuvo como objetivo abordar el problema de la capacitación de maestros en educación vocacional adicional para trabajar con niños discapacitados. Realizamos un experimento formativo, en el que participaron los profesores de la universidad. El propósito del trabajo piloto fue mejorar la calidad de la capacitación de los maestros en la educación profesional adicional para crear un ambiente educativo inclusivo en la universidad. Los conceptos a nivel legislativo de la Federación de Rusia están justificados. Una de las direcciones prioritarias para la educación de los niños con retraso mental (discapacidades intelectuales) junto con la educación general es brindarles una oportunidad real de obtener una profesión. Los requisitos para los resultados del desarrollo del programa de educación complementaria para niños reflejan el conjunto de necesidades individuales, públicas y estatales. El artículo da un ejemplo del programa desarrollado de educación profesional adicional para el personal docente y se da un ejemplo de la materia de los módulos enseñados. Aplicando la tecnología de formación de competencias profesionales del docente en la educación adicional, se han desarrollado cursos de educación adicionales para el personal docente de la universidad. Se da un ejemplo de la apertura de un centro de recursos en la Universidad K. Minin, que permite resolver las tareas principales de la formación profesional para niños con discapacidades.Guiados pelos resultados do trabalho experimental, os autores chegaram à conclusão de que o uso do complexo educacional e metódico eletrônico em matemática com base na tecnologia de treinamento modular de qualificação é essencial. O estágio atual no desenvolvimento de sistemas educacionais é caracterizado pelo surgimento e introdução prática da educação inclusiva para crianças com deficiência em organizações de educação geral. A inclusão no processo educacional das crianças com deficiência é ditada não apenas pelos documentos normativos modernos, mas também pela necessidade social de educação inclusiva. Uma das condições para a preparação de crianças com deficiência no ambiente educacional é a qualidade e treinamento especial de professores que devem possuir certos conhecimentos e habilidades para trabalhar com crianças com deficiência. Portanto, este estudo teve como objetivo abordar o problema da formação de professores em educação profissional adicional para trabalhar com crianças com deficiência. Realizamos um experimento de treinamento, no qual participaram os professores da universidade. O objetivo do trabalho piloto foi melhorar a qualidade da formação de professores em educação profissional adicional para criar um ambiente educacional inclusivo na universidade. Os conceitos legislativos da Federação Russa são justificados. Uma das direções prioritárias para a educação de crianças com retardo mental (deficiência intelectual), juntamente com a educação geral, é dar-lhes uma oportunidade real de obter uma profissão. Os requisitos para os resultados do desenvolvimento do programa de educação complementar para crianças refletem o conjunto de necessidades individuais, públicas e estatais. O artigo dá um exemplo do programa desenvolvido de formação profissional adicional para o corpo docente e dá um exemplo do assunto dos módulos ensinados. Aplicando a tecnologia de treinamento de habilidades profissionais do professor em educação adicional, foram desenvolvidos cursos de educação adicionais para o corpo docente da universidade. Um exemplo é dado da abertura de um centro de recursos na Universidade K. Minin, que permite resolver as principais tarefas de formação profissional para crianças com deficiência

Использование учебных видео-материалов в образовательном процессе высшего учебного заведения

This article is devoted to the creation and use of educational video clips in higher educational institutions. This article analyzes the results of studies on the impact of video content on listeners, which showed a large degree of positive impact, presents a theoretical analysis of the basics of developing video materials. The purpose of the article is to create a technology for developing instructional videos in a higher educational institution. The authors presented the experience of implementing video materials in the classroom on pedagogical disciplines. The stages of developing video materials were proposed, recommendations for creating video were highlighted, the conditions and tasks of using video materials in the educational process were substantiated. Experience allowed us to identify the possibilities of video materials in the modern learning process, which can significantly increase the effectiveness of the teaching activities of the teacher and increase the level of students' perception of the material.Este artículo está dedicado a la creación y uso de videoclips educativos en instituciones de educación superior. Este artículo analiza los resultados de estudios sobre el impacto del contenido de video en los oyentes, que mostraron un alto grado de impacto positivo, presenta un análisis teórico de los conceptos básicos del desarrollo de materiales de video. El propósito del artículo es crear una tecnología para desarrollar videos instructivos en una institución de educación superior. Los autores presentaron la experiencia de implementar materiales de video en el aula sobre disciplinas pedagógicas. Se propusieron las etapas de desarrollo de los materiales de video, se resaltaron las recomendaciones para la creación de video, se confirmaron las condiciones y las tareas de uso de materiales de video en el proceso educativo. La experiencia nos permitió identificar las posibilidades de los materiales de video en el proceso de aprendizaje moderno, lo que puede aumentar significativamente la efectividad de las actividades de enseñanza del maestro y aumentar el nivel de percepción del material por parte de los estudiantes.Данная статья посвящена вопросам создания и использования учебных видео-роликов в высших учебных заведениях. В данной статье проанализированы результаты исследований влияния видео-контента на слушателей, показавшие большую степень положительного воздействия, представлен теоретический анализ основ разработки видео-материалов. Цель статьи состоит в создании технологии разработки обучающего видео в условиях высшего образовательного учреждения. Авторами представлен опыт реализации видео-материалов на занятиях по педагогическим дисциплинам. Были предложены этапы разработки видео-материалов, выделены рекомендации к созданию видео, обоснованы условия и задачи использования видео-материалов в учебном процессе. Опыт позволил выявить возможности видео-материалов в современном процессе обучения, которые позволяют существенно повысить результативность обучающей деятельности преподавателя и увеличить уровень восприятия студентами материала

Modern technologies in working with gifted students

Intellectual potential acts as a driving force of social and economic development of the modern state. In a high-tech society, there is a significant increase in interest in identifying and implementing the intellectual abilities of young people. The purpose of the article is to review the experience of using modern educational technologies in working with gifted students. The paper explores the implementation of innovative technologies, including games, projects, and collaborative learning technologies. The use of project and game technologies allows to develop the creative potential of students, to form an experience of research and creative activity, to activate cognitive interest by combining theory and practice. Modern educational technologies expand the opportunities for the formation and development of children's giftedness. Giftedness is a high level of development of any abilities. They are a special resource that forms the basis of the country's competitiveness and potential, which is updated as socially significant in the context of the analysis of fundamental documents in the field of education. Educational technologies allow not only to have a purposeful educational impact on students but also to create a variable, enriched, individualized educational environment that promotes the development of independence and self-learning ability

Самостоятельная работа студентов в профессиональных учебных заведениях

The reform of education in Russia has led to emergence of new learning pattern. Today, among numerous changes that have occurred in competence-based approach context, we note tendencies towards changes in teacher’s role in a student’s life, reduction in classroom hours and increase in the share of students’ independent work. In order to preserve and increase effectiveness of student learning, educational institutions should aim at finding new ways to use classroom hours to organize students' independent work. Insufficient knowledge of this topic actualizes the process of its further development. The purpose of our research was to verify the structure of independent work developed by the authors at a technical school in order to increase student training level. For this, the authors conducted an experiment in which two groups of second-year students of 25 people each took part. The results of the differentiated classification of two groups in the course "Engineering Graphics" were compared. The first group of students studied according to the structure available in the college, the second - with the help of the pattern developed by the authors. As a result, it was found that the second group has a higher level of training. The results of the experiment allowed us to conclude that the structure of independent work developed by the authors is very effective and its implementation will allow achieving positive results in students' competences development and in future graduates training.La reforma de la educación en Rusia ha llevado a la aparición de un nuevo patrón de aprendizaje. Hoy, entre los numerosos cambios que se han producido en el contexto del enfoque basado en la competencia, observamos tendencias hacia cambios en el papel del maestro en la vida de un estudiante, reducción en las horas de clase y aumento en la parte del trabajo independiente de los estudiantes. Para preservar y aumentar la efectividad del aprendizaje de los estudiantes, las instituciones educativas deben apuntar a encontrar nuevas formas de usar las horas de clase para organizar el trabajo independiente de los estudiantes. El conocimiento insuficiente de este tema actualiza el proceso de su desarrollo posterior. El propósito de nuestra investigación fue verificar la estructura del trabajo independiente desarrollado por los autores en una escuela técnica para aumentar el nivel de capacitación de los estudiantes. Para ello, los autores realizaron un experimento en el que participaron dos grupos de estudiantes de segundo año de 25 personas cada uno. Se compararon los resultados de la clasificación diferenciada de dos grupos en el curso "Gráficos de ingeniería". El primer grupo de estudiantes estudió de acuerdo con la estructura disponible en la universidad, el segundo, con la ayuda del patrón desarrollado por los autores. Como resultado, se encontró que el segundo grupo tiene un mayor nivel de entrenamiento. Los resultados del experimento nos permitieron concluir que la estructura del trabajo independiente desarrollado por los autores es muy efectiva y su implementación permitirá lograr resultados positivos en el desarrollo de competencias de los estudiantes y en la formación de futuros graduados.Реформа образования в России привела к появлению новой модели обучения. Сегодня среди многочисленных изменений, произошедших в контексте компетентностного подхода, мы отмечаем тенденции к изменению роли педагога в жизни студента, сокращению аудиторных часов и увеличению доли самостоятельной работы студентов. Чтобы сохранить и повысить эффективность обучения студентов, учебные заведения должны стремиться найти новые способы использования аудиторных часов для организации самостоятельной работы студентов. Недостаточная разработка этой темы актуализирует процесс ее дальнейшего развития. Целью нашего исследования была проверка структуры самостоятельной работы, разработанной авторами в техникуме с целью повышения уровня подготовки студентов. Для этого авторы провели эксперимент, в котором приняли участие две группы студентов второго курса по 25 человек в каждой. Результаты дифференцированной классификации двух групп по курсу «Инженерная графика» сравнивались. Первая группа студентов обучалась по структуре, имеющейся в колледже, вторая - по схеме, разработанной авторами. В результате выяснилось, что вторая группа имеет более высокий уровень подготовки. Результаты эксперимента позволили сделать вывод о том, что разработанная авторами структура самостоятельной работы имеет высокую результативность, а ее реализация позволит достичь положительных результатов в развитии компетенций студентов и в подготовке будущих выпускников

Multipolar second-harmonic generation from high-Q quasi-BIC states in subwavelength resonators

We put forward the multipolar model whichcaptures the physics behind linear and nonlinear responsedriven by high-quality (high-Q) supercavity modes in sub-wavelength particles. We show that the formation ofsuch trapped states associated with bound states in thecontinuum (quasi-BIC) can be understood through multi-polar transformations of coupled leaky modes. The quasi-BIC state appears with increasing the order of the domi-nating multipole, where dipolar losses are completely sup-pressed. The efficient optical coupling to this state in theAlGaAs nanodisk is implemented via azimuthally polarizedbeam illumination matching its multipolar origin. Weestablish a one-to-one correspondence between the stan-dard phenomenological non-Hermitian coupled-modetheory and multipolar models. The derived multipolarcomposition of the generated second-harmonic radiationfrom the AlGaAs nanodisk is then validated with full-wavenumerical simulations. Back-action of the second-harmonicradiation onto the fundamental frequency is taken into ac-count in the coupled nonlinear model with pump depletion.A hybrid metal-dielectric nanoantenna is proposed toaugment the conversion efficiency up to tens of per cent dueto increasing quality factors of the involved resonant states.Ourfindings delineate novel promising strategies in thedesign of functional elements for nonlinear nanophotonics applications

Constitutive interferon signaling maintains critical threshold of MLKL expression to license necroptosis

Interferons (IFNs) are critical determinants in immune-competence and autoimmunity, and are endogenously regulated by a low-level constitutive feedback loop. However, little is known about the functions and origins of constitutive IFN. Recently, lipopolysaccharide (LPS)-induced IFN was implicated as a driver of necroptosis, a necrotic form of cell death downstream of receptor-interacting protein (RIP) kinase activation and executed by mixed lineage kinase like-domain (MLKL) protein. We found that the pre-established IFN status of the cell, instead of LPS-induced IFN, is critical for the early initiation of necroptosis in macrophages. This pre-established IFN signature stems from cytosolic DNA sensing via cGAS/STING, and maintains the expression of MLKL and one or more unknown effectors above a critical threshold to allow for MLKL oligomerization and cell death. Finally, we found that elevated IFN-signaling in systemic lupus erythematosus (SLE) augments necroptosis, providing a link between pathological IFN and tissue damage during autoimmunity

The Alternating Access Transport Mechanism in LacY

Lactose permease of Escherichia coli (LacY) is highly dynamic, and sugar binding causes closing of a large inward-facing cavity with opening of a wide outward-facing hydrophilic cavity. Therefore, lactose/H+ symport via LacY very likely involves a global conformational change that allows alternating access of single sugar- and H+-binding sites to either side of the membrane. Here, in honor of Stephan H. White’s seventieth birthday, we review in camera the various biochemical/biophysical approaches that provide experimental evidence for the alternating access mechanism