СТАН ТА ТЕНДЕНЦІЇ МІЖБЮДЖЕТНОГО РЕГУЛЮВАННЯ В УКРАЇНІ В УМОВАХ ФІСКАЛЬНОЇ ДЕЦЕНТРАЛІЗАЦІЇ

A balanced socio-economic development of any country is closely related to the efficiency of the system of intergovernmental relations, which should be aimed at optimizing the process of fiscal decentralization and clear definition of the powers of local government. Interbudgetary regulation in Ukraine reflects processes of the national and political importance and is of great importance in the composition of intergovernmental fiscal relations, which priority is growing in terms of decentralization reforms. Purpose. The main objectives of this study are: to summarize a complex task that is resolved in the process of budgetary control; to analyze the dynamics of revenues of the consolidated budget of Ukraine in 2007-2016 and the proportion of own local revenues in GDP; to distinguish formation features of Ukrainian local budgets by region; to analyze volumes of local budgets per capita in terms of area; to highlight the leverage rate of local budgets; to analyze the share of interbudget transfers in total local budgets. Results. The study is a synthesis of the complex challenges that must be resolved in the process of budgetary control, such as: balancing the budget; foster the interest of local governments in the maximum revenue mobilization; reallocation of existing budgetary resources, taking into account local features. The dynamics of the revenues of the consolidated budget of Ukraine in 2007-2016 was analyzed and concluded that the proportion of own local revenues in GDP tended to decrease with a simultaneous increase in the share of the interbudget transfers from the state budget. Abovementioned resulted in the ensuring of a stable share of local budgets in the GDP structure (at 14-15%). As a result of the intergovernmental fiscal decentralization reform by the results of 2016 the share of own revenues of local budgets Ukraine in GDP rose to 7.2%, or 1.1% compared to 2015 with a simultaneous decrease in the interbudget transfers share from the state budget to 8.2% (0.6% compared to 2015). Analyzed the share interbudget transfers in total local budgets, which for a long period tended to increase (from 47.2% in 2007 to 53.4% in 2016), which is contrary to the basic principles of fiscal decentralization. Conclusion. Grounded features of Ukrainian local budget revenues by region and proved that the unevenness of income between regions of Ukraine are often equivalent to the level of industrial production. Analyzed volumes of local budgets per capita in terms of area. Presented the list of influence instruments on local budgets indexes of incomes, including the increase in the minimum wage, inflation, continuing reform of the budget system in the direction of fiscal decentralization and transfer volumes.Представлен комплекс задач, который должен решаться в процессе межбюджетного регулирования, проанализирована динамика доходной части сводного бюджета Украины в 2007-2016 гг. и удельный вес собственных доходов местных бюджетов в структуре ВВП, выделены особенности формирования доходов местных бюджетов Украины по регионам. Проанализированы объемы доходов местных бюджетов на душу населения в разрезе территорий, освещены рычаги влияния на показатель доходов местных бюджетов, проведен анализ удельного веса межбюджетных трансфертов в общей структуре местных бюджетов.Узагальнено комплекс завдань, що має вирішуватись у процесі міжбюджетного регулювання, проаналізовано динаміку дохідної частини зведеного бюджету України у 2007–2016 рр. та питому вагу власних доходів місцевих бюджетів в структурі ВВП, виокремлено особливості формування доходів місцевих бюджетів України за регіонами. Проаналізовано обсяги доходів місцевих бюджетів на душу населення у розрізі територій, висвітлено важелі впливу на показник доходів місцевих бюджетів, здійснено аналіз питомої ваги міжбюджетних трансфертів у загальній структурі місцевих бюджетів

Thermal inactivation and conformational lock studies on glucose oxidase

In this study, the dissociative thermal inactivation and conformational lock theories are applied for the homodimeric enzyme glucose oxidase (GOD) in order to analyze its structure. For this purpose, the rate of activity reduction of glucose oxidase is studied at various temperatures using b-D-glucose as the substrate by incubation of enzyme at various temperatures in the wide range between 40 and 70 �C using UV–Vis spectrophotometry. It was observed that in the two ranges of temperatures, the enzyme has two different forms. In relatively low temperatures, the enzyme is in its dimeric state and has normal activity. In high temperatures, the activity almost disappears and it aggregates. The above achievements are confirmed by dynamic light scattering. The experimental parameter ‘‘n’’ as the obvious number of conformational locks at the dimer interface of glucose oxidase is obtained by kinetic data, and the value is near to two. To confirm the above results, the X-ray crystallography structure of the enzyme, GOD (pdb, 1gal), was also studied. The secondary and tertiary structures of the enzyme to track the thermal inactivation were studied by circular dichroism and fluorescence spectroscopy, respectively. We proposed a mechanism model for thermal inactivation of GOD based on the absence of the monomeric form of the enzyme by circular dichroism and fluorescence spectroscopy

Outcomes of sepsis: a new look at old problems

Infections represent a common health problem in people at any age. Usually, a local reaction develops in response to the infection, and intensive treatment is not required. However, sometimes the response to infection is inadequate and may lead to organ dysfunction; such condition is defined as septic state. The pathophysiology of sepsis is multifactorial, and the immune system is directly involved in development of pathological processes accompanying septic conditions. Dysregulatory disorders in sepsis may be observed, in particular, those affecting immune system and, immediately, innate immunity, which presents the first line of immune defense. Currently, neutrophilic granulocytes are considered important players in development and maintenance of inflammatory processes, which is due to their ability to produce various inflammatory mediators. At the same time, at different stages of pathogenesis, immune factors and mechanisms act both as a generating factors and effectors of damage reactions, as well as the main components of the defense responses. Uncontrolled release of endogenous inflammatory mediators induced by microorganisms, and lack of damagelimiting mechanisms mutually synergize when promoting the organ dysfunction. Hence, dysfunction of the immune system may develop and deepen upon any inappropriate strategy of response to distinct infectious pathogen. The aim of our study was to assess the spectrum of microorganisms, levels of neutrophilic extracellular traps (NVL), PAD4, IL-6, IL-8 and their correlations in the patients with sepsis and septic shock, depending on the outcome of the disease. The study included 44 patients with sepsis and septic shock, and 20 apparently healthy donors. Peripheral blood samples were taken from the ulnar vein serially in dynamics, from the moment of diagnosis to clinical outcome. Microbiological and immunological studies have been carried out. The obtained data were processed with “SPSS Statistic 23.0” software. Development of septic conditions was found to be accompanied by a significant changes in the levels of studied immunological parameters (NLV, IL-6, IL-8 and PAD4). Toxicity of lysosomal enzymes and oxygen metabolites present in neutrophilic extracellular traps leads to endothelial damage, appearance of focal intravascular inflammation, which, along with damaging effects of microorganisms and their toxins, leads to development of organ failure and onset. High burden   of these factors is most likely to cause lethal outcomes

A mechanism for the inhibition of DNA-PK-mediated DNA sensing by a virus

The innate immune system is critical in the response to infection by pathogens and it is activated by pattern recognition receptors (PRRs) binding to pathogen associated molecular patterns (PAMPs). During viral infection, the direct recognition of the viral nucleic acids, such as the genomes of DNA viruses, is very important for activation of innate immunity. Recently, DNA-dependent protein kinase (DNA-PK), a heterotrimeric complex consisting of the Ku70/Ku80 heterodimer and the catalytic subunit DNA-PKcs was identified as a cytoplasmic PRR for DNA that is important for the innate immune response to intracellular DNA and DNA virus infection. Here we show that vaccinia virus (VACV) has evolved to inhibit this function of DNA-PK by expression of a highly conserved protein called C16, which was known to contribute to virulence but by an unknown mechanism. Data presented show that C16 binds directly to the Ku heterodimer and thereby inhibits the innate immune response to DNA in fibroblasts, characterised by the decreased production of cytokines and chemokines. Mechanistically, C16 acts by blocking DNA-PK binding to DNA, which correlates with reduced DNA-PK-dependent DNA sensing. The C-terminal region of C16 is sufficient for binding Ku and this activity is conserved in the variola virus (VARV) orthologue of C16. In contrast, deletion of 5 amino acids in this domain is enough to knockout this function from the attenuated vaccine strain modified vaccinia virus Ankara (MVA). In vivo a VACV mutant lacking C16 induced higher levels of cytokines and chemokines early after infection compared to control viruses, confirming the role of this virulence factor in attenuating the innate immune response. Overall this study describes the inhibition of DNA-PK-dependent DNA sensing by a poxvirus protein, adding to the evidence that DNA-PK is a critical component of innate immunity to DNA viruses

Characterization analysis and polymorphism detection of the porcine Myd88 gene

The myeloid differentiation primary response protein 88 (Myd88) is an essential adaptor protein, which mediates in all Toll-like receptor (TLR) members signal transduction, except for TLR3. In this study, the 4464 bp genomic sequence of porcine Myd88 was first isolated, whereupon tissue distribution, chromosome mapping and single nucleotide polymorphism (SNP) were analyzed. Our results revealed that porcine Myd88 gene, which was located at chromosome 13 linked with marker S0288 (distance = 40 cR; LOD = 8.66), was widely expressed in all the examined tissues. There were 16 potential SNPs in the isolated genome fragment. SNP 797T/C in the first intron was studied, with no significant association being found between the genotype and immune traits in pigs (p > 0.05). The porcine Myd88 protein contained both the death domain (DD) and the Toll/IL-1 receptor domain (TIR). Leu residues, essential for its structure, were the most abundant encountered in the DD. The TIR contained two conserved motifs which may play important roles in the Myd88 function

Ovarian follicular cells have innate immune capabilities that modulate their endocrine function

Oestrogens are pivotal in ovarian follicular growth, development and function, with fundamental roles in steroidogenesis, nurturing the oocyte and ovulation. Infections with bacteria such as Escherichia coli cause infertility in mammals at least in part by perturbing ovarian follicle function, characterised by suppression of oestradiol production. Ovarian follicle granulosa cells produce oestradiol by aromatisation of androstenedione from the theca cells, under the regulation of gonadotrophins such as FSH. Many of the effects of E. coli are mediated by its surface molecule lipopolysaccharide (LPS) binding to the Toll-like receptor-4 (TLR4), CD14, MD-2 receptor complex on immune cells, but immune cells are not present inside ovarian follicles. The present study tested the hypothesis that granulosa cells express the TLR4 complex and LPS directly perturbs their secretion of oestradiol. Granulosa cells from recruited or dominant follicles are exposed to LPS in vivo and when they were cultured in the absence of immune cell contamination in vitro they produced less oestradiol when challenged with LPS, although theca cell androstenedione production was unchanged. The suppression of oestradiol production by LPS was associated with down-regulation of transcripts for aromatase in granulosa cells, and did not affect cell survival. Furthermore, these cells expressed TLR4, CD14 and MD-2 transcripts throughout the key stages of follicle growth and development. It appears that granulosa cells have an immune capability to detect bacterial infection, which perturbs follicle steroidogenesis, and this is a likely mechanism by which ovarian follicle growth and function is perturbed during bacterial infection