DNA damage signaling in response to double-strand breaks during mitosis

Dividing cells can sense DNA damage and initiate a primary response, but repair isn’t completed until the cells enter G1

Structure specific recognition protein-1 (SSRP1) is an elongated homodimer that binds histones

The histone chaperone complex facilitates chromatin transcription (FACT) plays important roles in DNA repair, replication, and transcription. In the formation of this complex, structure-specific recognition protein-1 (SSRP1) heterodimerizes with suppressor of Ty 16 (SPT16). SSRP1 also has SPT16-independent functions, but how SSRP1 functions alone remains elusive. Here, using analytical ultracentrifugation (AUC) and small-angle X-ray scattering (SAXS) techniques, we characterized human SSRP1 and that from the amoeba Dictyostelium discoideum and show that both orthologs form an elongated homodimer in solution. We found that substitutions in the SSRP1 pleckstrin homology domain known to bind SPT16 also disrupt SSRP1 homodimerization. Moreover, AUC and SAXS analyses revealed that SSRP1 homodimerization and heterodimerization with SPT16 (resulting in FACT) involve the same SSRP1 surface, namely, the PH2 region, and that the FACT complex contains only one molecule of SSRP1. These observations suggest that SSRP1 homo- and heterodimerization might be mutually exclusive. Moreover, isothermal titration calorimetry analyses disclosed that SSRP1 binds both histones H2A-H2B and H3-H4 and that disruption of SSRP1 homodimerization decreases its histone-binding affinity. Together, our results provide evidence for regulation of SSRP1 by homodimerization and suggest a potential role for homodimerization in facilitating SPT16-independent functions of SSRP1

Implementación de un enfoque diferenciado a la organización del aprendizaje a distancia

The widespread practice and results of the introduction of distance learning in several countries prove its economic efficiency. In this article, the authors consider the possibilities and advantages of using a differentiated approach in the practice of distance learning at a university. The article describes the pedagogical experience of structuring distance learning in the form of a new educational model - a block-modular system used by teachers in the practice of higher education. The authors argue that such structuring ensures the integrity of the perception and presentation of educational material, contributes to a better mastery of the discipline, provides the ability to build personal educational trajectories of students and identifies the following principles: flexibility, individualization, modularity, differentiated form of control..La práctica generalizada y los resultados de la introducción del aprendizaje a distancia en varios países demuestran su eficiencia económica. En este artículo, los autores consideran las posibilidades y ventajas de utilizar un enfoque diferenciado en la práctica del aprendizaje a distancia en una universidad. El artículo describe la experiencia pedagógica de estructurar el aprendizaje a distancia en forma de un nuevo modelo educativo: un sistema modular de bloques utilizado por los docentes en la práctica de la educación superior. Los autores sostienen que dicha estructuración garantiza la integridad de la percepción y la presentación del material educativo, contribuye a un mejor dominio dela disciplina, proporciona la capacidad de construir trayectorias educativas personales de los estudiantes e identifica los siguientes principios: flexibilidad, individualización, modularidad, diferenciación forma de control

Implementation of a Differentiated Approach to the Organization of Distance Learning

The widespread practice and results of the introduction of distance learning in several countries prove its economic efficiency. In this article, the authors consider the possibilities and advantages of using a differentiated approach in the practice of distance learning at a university. The article describes the pedagogical experience of structuring distance learning in the form of a new educational model - a block-modular system used by teachers in the practice of higher education. The authors argue that such structuring ensures the integrity of the perception and presentation of educational material, contributes to a better mastery of the discipline, provides the ability to build personal educational trajectories of students and identifies the following principles: flexibility, individualization, modularity, differentiated form of control.

Training of teachers for teaching in the conditions of distance education

An effective distance learning form should use detailed and particularly careful planning of the educational process. The organization of distance learning should have clear objectives and goals regarding the conditions of the educational process. Communication and interactive technologies, effective feedback between the student and the teacher are of great importance in distance education. The use of a modular system in distance education makes it possible to improve its quality control. The success of distance education depends on the level of motivation of students in acquiring new knowledge and skills. To improve the effectiveness of quality control in distance education, the level of training of teachers and their ability to motivate students to educational activities is important. A modern teacher should be able to use modern information and pedagogical technologies and constantly improve the level of his professional competence

PALB2 chromatin recruitment restores homologous recombination in BRCA1-deficient cells depleted of 53BP1

Abstract: Loss of functional BRCA1 protein leads to defects in DNA double-strand break (DSB) repair by homologous recombination (HR) and renders cells hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibitors used to treat BRCA1/2-deficient cancers. However, upon chronic treatment of BRCA1-mutant cells with PARP inhibitors, resistant clones can arise via several mechanisms, including loss of 53BP1 or its downstream co-factors. Defects in the 53BP1 axis partially restore the ability of a BRCA1-deficient cell to form RAD51 filaments at resected DSBs in a PALB2- and BRCA2-dependent manner, and thereby repair DSBs by HR. Here we show that depleting 53BP1 in BRCA1-null cells restores PALB2 accrual at resected DSBs. Moreover, we demonstrate that PALB2 DSB recruitment in BRCA1/53BP1-deficient cells is mediated by an interaction between PALB2’s chromatin associated motif (ChAM) and the nucleosome acidic patch region, which in 53BP1-expressing cells is bound by 53BP1’s ubiquitin-directed recruitment (UDR) domain

Результаты многоцентрового нерандомизированного несравнительного исследования эффективности и безопасности левофлоксацина при внебольничной пневмонии среднетяжелого течения

The article shows results of Russian multi-center trial of efficacy and safety of levofloxacin in moderate community-acquired pneumonia (CAP) patients took place from October, 2001, to November, 2002, at Moscow, Nizhny Novgorod, Samara, Ekaterinburg, Chelyabinsk, Tyumen and Irkutsk. The trial involved 77 patients (37 females and 40 males with the average age of 40.8±14.4 yrs) admitted to a hospital with the CAP. Levofloxacin was given in a standard dose of 500 meg once a day, the average length of the treatment was 9.2 days. The clinical efficacy of the single-therapy with levofloxacin was 98.7%. Adverse effects were noted in 4 cases (nausea was in 4 patients and headache was in 1 patient). The therapy was abolished in 1 case due to the adverse effects.В статье представлены результаты российского многоцентрового исследования по оценке эффективности и безопасности левофлоксацина в лечении больных среднетяжелой внебольничной пневмонией (ВП), проходившего с октября 2001 по ноябрь 2002 г. в Москве, Нижнем Новгороде, Самаре, Екатеринбурге, Челябинске, Тюмени и Иркутске. В исследование были включены 77 пациентов (37 женщин и 40 мужчин; средний возраст составил 40,8±14,4 года), госпитализированных по поводу ВП. Левофлоксацин назначался в стандартной дозе 500 мг 1 раза в сутки внутрь, средняя продолжительность терапии составила 9,2 дня. Клиническая эффективность монотерапии левофлоксацином составила 98,7%. Нежелательные явления при приеме антибиотика были отмечены в 4 случаях (у 3 пациентов тошнота, у 1 головная боль), в одном случае из-за развития нежелательных явлений прием левофлоксацина был прекращен