Економічні напрями енергетичної безпеки Європейського Союзу

Interactions between proteins are orchestrated in a precise and timedependent manner, underlying cellular function. The binding affinity, defined as the strength of these interactions, is translated into physico-chemical terms in the dissociation constant (Kd), the latter being an experimental measure that determines whether an interaction will be formed in solution or not. Predicting binding affinity from structural models has been a matter of active research for more than 40 years because of its fundamental role in drug development. However, all available approaches are incapable of predicting the binding affinity of protein–protein complexes from coordinates alone. Here, we examine both theoretical and experimental limitations that complicate the derivation of structure–affinity relationships. Most work so far has concentrated on binary interactions. Systems of increased complexity are far from being understood. The main physico-chemical measure that relates to binding affinity is the buried surface area, but it does not hold for flexible complexes. For the latter, there must be a significant entropic contribution that will have to be approximated in the future. We foresee that any theoretical modelling of these interactions will have to follow an integrative approach considering the biology, chemistry and physics that underlie protein–protein recognition

Співвідношення категорій природного та позитивного права: сучасні погляди та концепції

В статье проведен анализ позитивных и негативных сторон естественно-правового и позитивного правопонимания и осуществлен поиск идеальной системы, объединяющий положительные моменты обеих концепций.In the article the analysis of positive and negative sides of absolute law and positive rights understanding is conducted and the search of the ideal system, uniting the positive moments of both conceptions, is carried out

Computational studies of semiflexible polymer translocation in nanopore systems

The translocation of double stranded DNA (dsDNA) through nanopore systems is a field with rich physics and many promising technological applications. Double stranded DNA is not fully flexible, and the translocation dynamics of semiflexible molecules are not very well understood. In this thesis, in a set of articles, several aspects of translocation with semiflexible polymers in various nanopore systems are explored using molecular dynamics simulations. We look at the effect of the capture process on the translocation dynamics of semiflexible chains for standard nanopores in detail. In collaboration with experiment, we use simulations to explore the dynamics of dsDNA in a nanofiltered nanopore device with potential applications in DNA sequencing technology. A secondary use for the nanofiltered nanopore device as an entropic cage for DNA is also examined. Simulations are used to obtain insight into the dynamics of molecules during the trapping phase

Вимоги СОТ для державного регулювання регіонального ринку сільськогосподарської продукції України

Державне регулювання України, як країни з перехідною ринковою економікою, повинно базуватися на основних положеннях та вимогах СОТ (Світової організації торгівлі). Україна вибрала курс Європейської інтеграції, тому її економіка повинна відповідати та працювати по принципах світового ринку. Мета досліджень: проаналізувати основні положення та вимоги Світової організації торгівлі, основні моменти державного регулювання ринку сільськогосподарської продукції, що відповідають принципам світового ринку і які повинні працювати в умовах України

Spatiotemporal variation of mammalian protein complex stoichiometries

Table reporting the summary of quantified complex members and their regulation. (XLSX 179 kb

Алгоритм проведення попередньої дегазації методом гравітаційного знещільнення вуглепородного масиву

Приводится алгоритм проведения предварительной дегазации при применении нового способа гравитационной разгрузки на угольных месторождениях Донбасса и Львовско-Волынского бассейнов. Среди главных эффектов, которые будут получены при внедрении способа – обеспечение безопасности работ на шахтах и промышленная добыча метана.The algorithm of realization of pre-degassing with using new way of gravitational unloading on coal fields of Donbas and Lviv-Volyn basins is given in this article. Guaranteeing of safety works in mines and industrial methane-mining are between main effects which will be got on conditions of application of this method

Guidelines for high dose chemotherapy and stem cell transplantation for systemic AL amyloidosis: EHA-ISA working group guidelines

AL amyloidosis is a systemic amyloidosis and is associated with an underlying plasma cell dyscrasia. High dose intravenous melphalan and autologous stem cell transplantation was developed for the treatment of AL amyloidosis in the early 1990s and was prompted by its success in multiple myeloma. This application has evolved significantly over the past three decades. These guidelines provide a comprehensive assessment of eligibility criteria, stem cell collection and mobilisation strategies and regimens, risk-adapted melphalan dosing, role for induction and consolidation therapies, specific supportive care management, long-term outcome with respect to survival, haematologic response and relapse and organ responses following stem cell transplantation. These guidelines are developed by the experts in the field on behalf of the stem cell transplant working group of the International Society of Amyloidosis (ISA) and European Haematology Association (EHA)

The combination of X-ray crystallography and cryo-electron microscopy provides insight into the overall architecture of the dodecameric Rvb1/Rvb2 complex

The Rvb1/Rvb2 complex is an essential component of many cellular pathways. The Rvb1/Rvb2 complex forms a dodecameric assembly where six copies of each subunit form two heterohexameric rings. However, due to conformational variability, the way the two rings pack together is still not fully understood. Here, we present the crystal structure and two cryo-electron microscopy reconstructions of the dodecameric, full-length Rvb1/Rvb2 complex, all showing that the interaction between the two heterohexameric rings is mediated through the Rvb1/Rvb2-specific domain II. Two conformations of the Rvb1/Rvb2 dodecamer are present in solution: a stretched conformation also present in the crystal, and a compact conformation. Novel asymmetric features observed in the reconstruction of the compact conformation provide additional insight into the plasticity of the Rvb1/Rvb2 complex

Autophagy activation can partially rescue proteasome dysfunction-mediated cardiac toxicity.

The ubiquitin-proteasome pathway and its functional interplay with other proteostatic and/or mitostatic modules are crucial for cell viability, especially in post-mitotic cells like cardiomyocytes, which are constantly exposed to proteotoxic, metabolic, and mechanical stress. Consistently, treatment of multiple myeloma patients with therapeutic proteasome inhibitors may induce cardiac failure; yet the effects promoted by heart-targeted proteasome dysfunction are not completely understood. We report here that heart-targeted proteasome knockdown in the fly experimental model results in increased proteome instability and defective mitostasis, leading to disrupted cardiac activity, systemic toxicity, and reduced longevity. These phenotypes were partially rescued by either heart targeted- or by dietary restriction-mediated activation of autophagy. Supportively, activation of autophagy by Rapamycin or Metformin administration in flies treated with proteasome inhibitors reduced proteome instability, partially restored mitochondrial function, mitigated cardiotoxicity, and improved flies' longevity. These findings suggest that autophagic inducers represent a novel promising intervention against proteasome inhibitor-induced cardiovascular complications