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Background: The issue of judicial specialisation is one of the main concerns in the development of a judicial system. This study aims to analyse the function and legal basis ofspecialised courts among the member states of the European Union (EU) and in Ukraine. Methods: In the article, the authors used the following special legal methods: conceptual-legal, comparative-legal, formal-legal, and others. For example, the comparative-legal method helped the authors compare the features of specialised court practice in other countries and allowed them to identify how different countries regulate this issue at the legislative level. Results and Conclusions: This article argues that specialisation is driven by the need to improve the efficiency of justice and the need to apply in-depth specialist knowledge in a specific area of justice. Information and knowledge gained from the experience of different countries can be used as a basis for the implementation, adaptation, and development of relevant new provisions in Ukraine.

Microvillus inclusion disease (MVID) is a rare but fatal autosomal recessive congenital diarrheal disorder caused by MYO5B mutations. In 2013, we launched an open-access registry for MVID patients and their MYO5B mutations (www.mvid-central.org). Since then, additional unique MYO5B mutations have been identified in MVID patients, but also in non-MVID patients. Animal models have been generated that formally prove the causality between MYO5B and MVID. Importantly, mutations in two other genes, STXBP2 and STX3, have since been associated with variants of MVID, shedding new light on the pathogenesis of this congenital diarrheal disorder. Here, we review these additional genes and their mutations. Furthermore, we discuss recent data from cell studies that indicate that the three genes are functionally linked and, therefore, may constitute a common disease mechanism that unifies a subset of phenotypically linked congenital diarrheal disorders. We present new data based on patient material to support this. To congregate existing and future information on MVID geno-/phenotypes, we have updated and expanded the MVID registry to include all currently known MVID-associated gene mutations, their demonstrated or predicted functional consequences, and associated clinical information.

Cytokinetic abscission, the terminal step of cell division, crucially depends on the local constriction of ESCRT-III helices after cytoskeleton disassembly. While the microtubules of the intercellular bridge are cut by the ESCRT-associated enzyme Spastin, the mechanism that clears F-actin at the abscission site is unknown. Here we show that oxidation-mediated depolymerization of actin by the redox enzyme MICAL1 is key for ESCRT-III recruitment and successful abscission. MICAL1 is recruited to the abscission site by the Rab35 GTPase through a direct interaction with a flat three-helix domain found in MICAL1 C terminus. Mechanistically, in vitro assays on single actin filaments demonstrate that MICAL1 is activated by Rab35. Moreover, in our experimental conditions, MICAL1 does not act as a severing enzyme, as initially thought, but instead induces F-actin depolymerization from both ends. Our work reveals an unexpected role for oxidoreduction in triggering local actin depolymerization to control a fundamental step of cell division., Cytokinetic abscission relies on the local constriction after cytoskeleton disassembly, but it is not known how the actin filaments are disassembled. Here, the authors show that the redox enzyme MICAL1 is recruited by Rab35 and induces oxidation-mediated depolymerization of actin, which is required to recruit ESCRT-III and complete abscission.

International audience

A lot of distinct features are typical for the formed conceptual approaches to the management of the competitive advantages. They do not only touch upon the conceptual apparatus but also upon the way the purposes are put, the theoretic-methodological and the practical base of the investigation process and the market analysis.But first of all the competitive advantages of an enterprise become the main link in the investigation of those advantages. Enterprise is a separate social-economic unit where certain goods are produced, services that may be realized thanks to the adequate system of management, strategies and competences of the development are provided.The essence of the competitive advantages is considered in the special economic literature from the view point of: the possibilities of leaving behind the rivals due to certain actions and factors; more rationalized use of different resources; certain value and competence in comparison with the competitors.The essence of the notion of competitive advantages we consider as the category inseparably connected and inter-conditioned with the notion of the theory of competition, namely: competitiveness, competitive ability, competitive stability, competitive position, competitive status, competitive strategy, and competitive potential.The essence of forming the strategy of competition lies in the inter-connection between the enterprise and its outer surrounding. Relevant outer surrounding is rather wide because it includes different social and economic factors, but the key aspect of the outer encirclement of the enterprise is the field it wages his competitive struggle in. The structure of this particular sphere greatly influences the definition of the rules of the competitive play as well as the potential strategies of the enterprise.Competitive advantages are not eternal; they are gained and kept only thanks to the constant improvement of the spheres of activity. The main directions in defending the competitive advantages may be monopolies at the market, patents, know-how, access to the sources of raw materials or communications. In defining the competitive advantages the organization should orient itself towards the consumers' demands and make sure these advantages are valuable for them.The aim of the system of managing the competitive advantages is to secure the integral index of the competitive advantages of the enterprise, to sustain the indices of those advantages on the level of the functional subsystems, thus attaining the optimal indices, but this is a local moment in comparison with the general purpose.The competitive advantages should be considered through the system of their types' classification, through the organizational connection of separate constituents and sources of forming the competitive advantages. As a result they all define the synergic effect in achieving success by the enterprise in the market encircling., В статье рассмотрены методологические подходы к формированию системы управления конкурентными преимуществами предприятия в контексте развития функций менеджмента. Определены факторы, влияющие на формирование конкурентных преимуществ, приведена структура системы конкурентных преимуществ предприятия с учетом динамизма внешней и внутренней среды предприятия., У статті розглянуто методологічні підходи до формування системи управління конкурентними перевагами підприємства в контексті розвитку функцій менеджменту. Визначено чинники, які впливають на формування конкурентних переваг, наведено структуру системи конкурентних переваг підприємства, що враховує динамізм внутрішнього та зовнішнього середовища підприємства.

Molecular motors such as myosins are allosteric enzymes that power essential motility functions in the cell and structural biology is an important tool to decipher how these motors work. Force is produced by myosins upon the actin-driven conformational changes that control the sequential release of the hydrolysis products of ATP (Pi followed by ADP). These conformational changes are amplified by a “lever arm” that includes the region of the motor known as the converter and the adjacent elongated light chain binding region. Analysis of four structural states of the motor provides a detailed understanding of the rearrangements and pathways of communication in the motor necessary for detachment from the actin track and repriming of the motor. However, the important part of the cycle in which force is produced remains enigmatic and awaits new high resolution structures. The value of a structural approach is particularly evident from the clues that have been provided from the structural states of the reverse myosin VI motor. Crystallographic structures have revealed that rearrangements within the converter subdomain occur which explains why this myosin can produce a large stroke in the opposite direction of all other myosins despite a very short lever arm. By providing detailed understanding of the motor rearrangements, structural biology will continue to reveal essential information to solve current enigma such as how actin promotes force production, how motors are tuned for specific cellular roles, or how motor/cargo interactions regulate myosin function in the cell.

International audience; Posttranslational geranylgeranylation of Rab GTPases is catalyzed by Rab geranylgeranyltransferase (RabGGTase), which consists of a catalytic alpha/beta heterodimer and an accessory Rab escort protein (REP). REP functions as a molecular chaperone that presents Rab proteins to the RabGGTase and after prenylation delivers them to their target membrane. Mutations in the REP-1 gene in humans lead to an X-chromosome-linked defect known as choroideremia, a progressive disease that inevitably culminates in complete blindness. Here we report in vitro assembly, purification, and crystallization of the monoprenylated Rab7GDP:REP-1 complex. X-Ray diffraction data for the REP-1:Rab7 complex were collected to 2.2-A resolution at the ESRF. The crystals belong to the orthorhombic space group P2(1)2(1)2 with unit-cell parameters a=64.3A, b=105.3A, c=132.6A. Preliminary structural analysis revealed the presence of one complex in the asymmetric unit. To understand the conformational changes in Rab protein on complex formation we also crystallized the GDP-bound form of Rab7 that diffracted to at least 1.8A on the in-house X-ray source.

International audience; Posttranslational geranylgeranylation of Rab GTPases is catalyzed by Rab geranylgeranyltransferase (RabGGTase), which consists of a catalytic alpha/beta heterodimer and an accessory Rab escort protein (REP). REP functions as a molecular chaperone that presents Rab proteins to the RabGGTase and after prenylation delivers them to their target membrane. Mutations in the REP-1 gene in humans lead to an X-chromosome-linked defect known as choroideremia, a progressive disease that inevitably culminates in complete blindness. Here we report in vitro assembly, purification, and crystallization of the monoprenylated Rab7GDP:REP-1 complex. X-Ray diffraction data for the REP-1:Rab7 complex were collected to 2.2-A resolution at the ESRF. The crystals belong to the orthorhombic space group P2(1)2(1)2 with unit-cell parameters a=64.3A, b=105.3A, c=132.6A. Preliminary structural analysis revealed the presence of one complex in the asymmetric unit. To understand the conformational changes in Rab protein on complex formation we also crystallized the GDP-bound form of Rab7 that diffracted to at least 1.8A on the in-house X-ray source.

International audience; Posttranslational geranylgeranylation of Rab GTPases is catalyzed by Rab geranylgeranyltransferase (RabGGTase), which consists of a catalytic alpha/beta heterodimer and an accessory Rab escort protein (REP). REP functions as a molecular chaperone that presents Rab proteins to the RabGGTase and after prenylation delivers them to their target membrane. Mutations in the REP-1 gene in humans lead to an X-chromosome-linked defect known as choroideremia, a progressive disease that inevitably culminates in complete blindness. Here we report in vitro assembly, purification, and crystallization of the monoprenylated Rab7GDP:REP-1 complex. X-Ray diffraction data for the REP-1:Rab7 complex were collected to 2.2-A resolution at the ESRF. The crystals belong to the orthorhombic space group P2(1)2(1)2 with unit-cell parameters a=64.3A, b=105.3A, c=132.6A. Preliminary structural analysis revealed the presence of one complex in the asymmetric unit. To understand the conformational changes in Rab protein on complex formation we also crystallized the GDP-bound form of Rab7 that diffracted to at least 1.8A on the in-house X-ray source.

Members of the RabGDI/REP family serve as multifunctional regulators of the Rab family of GTP binding proteins. Mutations in members of this family, such as REP-1, lead to abnormalities, including progressive retinal degradation (choroideremia) in humans. The crystal structures of the REP-1 protein in complex with monoprenylated or C-terminally truncated Rab7 proteins revealed that Rab7 interacts with the Rab binding platform of REP-1 via an extended interface involving the Switch 1 and 2 regions. The C terminus of the REP-1 molecule functions as a mobile lid covering a conserved hydrophobic patch on the surface of REP-1 that in the complex coordinates the C terminus of Rab proteins. Using semisynthetic fluorescent Rab27A, we demonstrate that although Rab27A can be prenylated by REP-2, this reaction can be effectively inhibited by other Rab proteins, providing a possible explanation for the accumulation of unprenylated Rab27A in choroideremia.

Membrane Type 1 Matrix Metalloprotease (MT1-MMP) contributes to the invasive progression of breast cancers by degrading extracellular matrix tissues. Nucleoside diphosphate kinase, NME1/NM23-H1, has been identified as a metastasis suppressor; however, its contribution to local invasion in breast cancer is not known. Here, we report that NME1 is up-regulated in ductal carcinoma in situ (DCIS) as compared to normal breast epithelial tissues. NME1 levels drop in microinvasive and invasive components of breast tumor cells relative to synchronous DCIS foci. We find a strong anti-correlation between NME1 and plasma membrane MT1-MMP levels in the invasive components of breast tumors, particularly in aggressive histological grade III and triple-negative breast cancers. Knockout of NME1 accelerates the invasive transition of breast tumors in the intraductal xenograft model. At the mechanistic level, we find that MT1-MMP, NME1 and dynamin-2, a GTPase known to require GTP production by NME1 for its membrane fission activity in the endocytic pathway, interact in clathrin-coated vesicles at the plasma membrane. Loss of NME1 function increases MT1-MMP surface levels by inhibiting endocytic clearance. As a consequence, the ECM degradation and invasive potentials of breast cancer cells are enhanced. This study identifies the down-modulation of NME1 as a potent driver of the in situ-to invasive transition during breast cancer progression.