ОРГАНІЗАЦІЙНА МОДЕЛЬ ПОЛЬСЬКИХ КООПЕРАТИВНИХ БАНКІВ В ПОСТ-КРИЗОВОМУ РЕГУЛЯТОРНОМУ СЕРЕДОВИЩІ

Even though the Polish cooperative banks were affected by the global crisis only indirectly, yet after the crisis their condition has begun to deteriorate. This was the result of numerous changes taking place within the macroeconomic and regulatory environment. This paper is to define the impact of crucial post-crisis regulations passed by the EU – CRDIV/CRR package, the directives on DGS and BRR – on the directions in which the organizational model of domestic cooperative banking should evolve.CRDIV/CRR is a regulatory package implementing the provisions of Basel III (Third Capital Agreement, Basel III). As part of the package, changes were made in two main areas determining banks’ security: the first one is capital adequacy, the second – liquidity and liquidity risk. Implementation of the provisions of the CRD IV/CRR package regarding banks' capital base policy into the Polish legal regime began in mid-2015 on the back of the act on macro-prudential supervision of the financial system and crisis management in the financial system dated 5 August 2015.Directive 2014/49/EU of the European Parliament and of the Council concerning Deposit Guarantee Schemes (DGS) essentially increases the protection of depositors' savings and one of its main provisions is harmonizing the methods of financing deposit-guarantee schemes ex ante. The Directive of the European Parliament and Council 2014/59/EU (BRRD) defines the principles of establishing national recovery and resolution mechanisms. The DGS and BRR Directives were introduced into the Polish legal regime by means of the act on the bank guarantee fund, deposit guarantee scheme and resolution of 10 June 2016.Based on an analysis of the impact of selected EU and national post-crisis regulations on the cooperative banking sector in Poland, two final conclusions were reached. First and foremost, in the hitherto existing regulatory environment imposing additional burdens on all banks, privileges were foreseen mainly for Institutional Protection Schemes (IPSs) members, while in the new legal regime the proportionality rule was applied to a limited extent. Secondly, due to the privileges arising from existing regulations, the evolution of the organizational model of Poland’s cooperative banking sector towards IPS seems to be inevitable.Несмотря на то, что польские кооперативные банки пострадали от глобального кризиса лишь частично, но после кризиса их состояние ухудшалось. Это стало результатом многочисленных изменений, происходящих в рамках макроэкономического и регуляторной среды.На основании анализа влияния отдельных посткризисных правил ЕС и национальных посткризисных мер на кооперативный банковский сектор в Польше было достигнуто двух окончательных выводов. Прежде всего, в существующем в настоящее время регуляторной среде, создает дополнительное бремя для всех банков, льготы предусматривались в основном для членов институциональных схем защиты (ИПС), тогда как в новом правовом режиме применялось ограничение пропорциональности. Во-вторых, из-за привилегии, вытекающие из существующих правил, эволюция организационной модели кооперативного банковского сектора Польши в IPS, кажется, неизбежна.Незважаючи на те, що польські кооперативні банки постраждали від глобальної кризи лише частково, але після кризи їх стан погіршувався. Це стало результатом численних змін, що відбуваються в рамках макроекономічного та регуляторного середовища. Цей документ визначає вплив вирішальних посткризових правил, прийнятих у пакеті ЄС - CRDIV / CRR, директиви щодо DGS та BRR - щодо напрямків розвитку організаційної моделі вітчизняного кооперативного банкінгу.CRDIV / CRR є регуляторним пакетом, який реалізує положення Базель III (Третя столична угода, Базель III). У рамках пакету були внесені зміни у двох основних сферах, що визначають безпеку банків: перша - достатність капіталу, друга - ризик ліквідності та ліквідності. Реалізація положень пакету CRD IV / CRR щодо політики розрахункової бази капіталу у польському правовому режимі розпочалася в середині 2015 року на тлі акту про макропруденційний нагляд за фінансовою системою та врегулювання кризових ситуацій у фінансовій системі від 5 серпня 2015 року.Директива 2014/49 / ЄС Європейського Парламенту та Ради щодо схем гарантування вкладів (ДГС) суттєво підвищує захист заощаджень вкладників, і одним із основних положень є гармонізація методів фінансування схем гарантування депозитів ex ante. Директива Європейського Парламенту та Ради 2014/59 / ЄС (BRRD) визначає принципи створення національних механізмів відновлення та регулювання.  Директиви DGS та BRR були введені в правовий режим Польщі шляхом акту Банківського гарантійного фонду, схеми гарантування вкладів та постанови від 10 червня 2016 року.На підставі аналізу впливу окремих посткризових правил ЄС та національних посткризових заходів на кооперативний банківський сектор у Польщі було досягнуто двох остаточних висновків. Перш за все, в існуючому в даний час регуляторному середовищі, що створює додатковий тягар для всіх банків, пільги передбачалися в основному для членів Інституціональних схем захисту (ІПС), тоді як в новому правовому режимі застосовувалося обмеження пропорційності. По-друге, через привілеї, що випливають з існуючих правил, еволюція організаційної моделі кооперативного банківського сектора Польщі до IPS, здається, неминуча

Downstream and Intermediate Interactions of Synovial Sarcoma-Associated Fusion Oncoproteins and Their Implication for Targeted Therapy

Synovial sarcoma (SS), an aggressive type of soft tissue tumor, occurs mostly in adolescents and young adults. The origin and molecular mechanism of the development of SS remain only partially known. Over 90% of SS cases are characterized by the t(X;18)(p11.2;q11.2) translocation, which results mainly in the formation of SS18-SSX1 or SS18-SSX2 fusion genes. In recent years, several reports describing direct and indirect interactions of SS18-SSX1/SSX2 oncoproteins have been published. These reports suggest that the fusion proteins particularly affect the cell growth, cell proliferation, TP53 pathway, and chromatin remodeling mechanisms, contributing to SS oncogenesis. Additional research efforts are required to fully explore the protein-protein interactions of SS18-SSX oncoproteins and the pathways that are regulated by these partnerships for the development of effective targeted therapy

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Molecular Characterization and Patient Outcome of Melanoma Nodal Metastases and an Unknown Primary Site

Background Melanoma of unknown primary site (MUP) is not a completely understood entity with nodal metastases as the most common first clinical manifestation. The aim of this multicentric study was to assess frequency and type of oncogenic BRAF/NRAS/KIT mutations in MUP with clinically detected nodal metastases in relation to clinicopathologic features and outcome. Materials and Methods We analyzed series of 103 MUP patients (period: 1992-2010) after therapeutic lymphadenectomy (LND): 40 axillary, 47 groin, 16 cervical, none treated with BRAF inhibitors. We performed molecular characterization of BRAF/NRAS/KIT mutational status in nodal metastases using direct sequencing of respective coding sequences. Median follow-up time was 53 months. Results BRAF mutations were detected in 55 cases (53 %) (51 V600E, 93 %; 4 others, 7 %), and mutually exclusive NRAS mutations were found in 14 cases (14 %) (7 p.Q61R, 4 p.Q61K, 2 p.Q61H, 1 p.Q13R). We have not detected any mutations in KIT. The 5-year overall survival (OS) was 34 %; median was 24 months. We have not found significant correlation between mutational status (BRAF/NRAS) and OS; however, for BRAF or NRAS mutated melanomas we observed significantly shorter disease-free survival (DFS) when compared with wild-type melanoma patients (p = .04; 5-year DFS, 18 vs 19 vs 31 %, respectively). The most important factor influencing OS was number of metastatic lymph nodes >1 (p = .03). Conclusions Our large study on molecular characterization of MUP with nodal metastases showed that MUPs had molecular features similar to sporadic non-chronic-sun-damaged melanomas. BRAF/NRAS mutational status had negative impact on DFS in this group of patients. These observations might have potential implication for molecular-targeted therapy in MUPs

Localization of a bacterial group II intron-encoded protein in human cells

Group II introns are mobile retroelements that self-splice from precursor RNAs to form ribonucleoparticles (RNP), which can invade new specific genomic DNA sites. This specificity can be reprogrammed, for insertion into any desired DNA site, making these introns useful tools for bacterial genetic engineering. However, previous studies have suggested that these elements may function inefficiently in eukaryotes. We investigated the subcellular distribution, in cultured human cells, of the protein encoded by the group II intron RmInt1 (IEP) and several mutants. We created fusions with yellow fluorescent protein (YFP) and with a FLAG epitope. We found that the IEP was localized in the nucleus and nucleolus of the cells. Remarkably, it also accumulated at the periphery of the nuclear matrix. We were also able to identify spliced lariat intron RNA, which co-immunoprecipitated with the IEP, suggesting that functional RmInt1 RNPs can be assembled in cultured human cells.This work was supported by research grants CSD 2009–0006 from the Consolider-Ingenio, BIO2011-24401 and BIO2014-51953-P from the Spanish Ministerio de Economía y Competitividad all including ERDF (European Regional Development Funds). We thank Dr. Antonio Barrientos Durán for technical advice. MRC was supported by an FPI Ph.D grant. J.L.G.P´s laboratory is supported by CICE-FEDER-P09-CTS-4980, CICE-FEDER-P12-CTS-2256, Plan Nacional de I+D+I 2008–2011 and 2013–2016 (FIS-FEDER-PI11/01489 and FIS-FEDER-PI14/02152), PCIN-2014-115-ERA-NET NEURON II, the European Research Council (ERC-Consolidator ERC-STG-2012-233764) and by an International Early Career Scientist grant from the Howard Hughes Medical Institute (IECS-55007420).Peer Reviewe

Statistical Inference of In Vivo Properties of Human DNA Methyltransferases from Double-Stranded Methylation Patterns

DNA methyltransferases establish methylation patterns in cells and transmit these patterns over cell generations, thereby influencing each cell's epigenetic states. Three primary DNA methyltransferases have been identified in mammals: DNMT1, DNMT3A and DNMT3B. Extensive in vitro studies have investigated key properties of these enzymes, namely their substrate specificity and processivity. Here we study these properties in vivo, by applying novel statistical analysis methods to double-stranded DNA methylation patterns collected using hairpin-bisulfite PCR. Our analysis fits a novel Hidden Markov Model (HMM) to the observed data, allowing for potential bisulfite conversion errors, and yields statistical estimates of parameters that quantify enzyme processivity and substrate specificity. We apply this model to methylation patterns established in vivo at three loci in humans: two densely methylated inactive X (Xi)-linked loci ( and ), and an autosomal locus (), where methylation densities are tissue-specific but moderate. We find strong evidence for a high level of processivity of DNMT1 at and , with the mean association tract length being a few hundred base pairs. Regardless of tissue types, methylation patterns at are dominated by DNMT1 maintenance events, similar to the two Xi-linked loci, but are insufficiently informative regarding processivity to draw any conclusions about processivity at that locus. At all three loci we find that DNMT1 shows a strong preference for adding methyl groups to hemi-methylated CpG sites over unmethylated sites. The data at all three loci also suggest low (possibly 0) association of the de novo methyltransferases, the DNMT3s, and are consequently uninformative about processivity or preference of these enzymes. We also extend our HMM to reanalyze published data on mouse DNMT1 activities in vitro. The results suggest shorter association tracts (and hence weaker processivity), and much longer non-association tracts than human DNMT1 in vivo

Structure Analysis of Entamoeba histolytica DNMT2 (EhMeth)

In eukaryotes, DNA methylation is an important epigenetic modification that is generally involved in gene regulation. Methyltransferases (MTases) of the DNMT2 family have been shown to have a dual substrate specificity acting on DNA as well as on three specific tRNAs (tRNAAsp, tRNAVal, tRNAGly). Entamoeba histolytica is a major human pathogen, and expresses a single DNA MTase (EhMeth) that belongs to the DNMT2 family and shows high homology to the human enzyme as well as to the bacterial DNA MTase M.HhaI. The molecular basis for the recognition of the substrate tRNAs and discrimination of non-cognate tRNAs is unknown. Here we present the crystal structure of the cytosine-5-methyltransferase EhMeth at a resolution of 2.15 Å, in complex with its reaction product S-adenosyl-L-homocysteine, revealing all parts of a DNMT2 MTase, including the active site loop. Mobility shift assays show that in vitro the full length tRNA is required for stable complex formation with EhMeth

Dissecting Epigenetic Silencing Complexity in the Mouse Lung Cancer Suppressor Gene Cadm1

Disease-oriented functional analysis of epigenetic factors and their regulatory mechanisms in aberrant silencing is a prerequisite for better diagnostics and therapy. Yet, the precise mechanisms are still unclear and complex, involving the interplay of several effectors including nucleosome positioning, DNA methylation, histone variants and histone modifications. We investigated the epigenetic silencing complexity in the tumor suppressor gene Cadm1 in mouse lung cancer progenitor cell lines, exhibiting promoter hypermethylation associated with transcriptional repression, but mostly unresponsive to demethylating drug treatments. After predicting nucleosome positions and transcription factor binding sites along the Cadm1 promoter, we carried out single-molecule mapping with DNA methyltransferase M.SssI, which revealed in silent promoters high nucleosome occupancy and occlusion of transcription factor binding sites. Furthermore, M.SssI maps of promoters varied within and among the different lung cancer cell lines. Chromatin analysis with micrococcal nuclease also indicated variations in nucleosome positioning to have implications in the binding of transcription factors near nucleosome borders. Chromatin immunoprecipitation showed that histone variants (H2A.Z and H3.3), and opposing histone modification marks (H3K4me3 and H3K27me3) all colocalized in the same nucleosome positions that is reminiscent of epigenetic plasticity in embryonic stem cells. Altogether, epigenetic silencing complexity in the promoter region of Cadm1 is not only defined by DNA hypermethylation, but high nucleosome occupancy, altered nucleosome positioning, and ‘bivalent’ histone modifications, also likely contributed in the transcriptional repression of this gene in the lung cancer cells. Our results will help define therapeutic intervention strategies using epigenetic drugs in lung cancer

Transcriptome Characterization by RNA-seq Unravels the Mechanisms of Butyrate-Induced Epigenomic Regulation in Bovine Cells

Short-chain fatty acids (SCFAs), especially butyrate, affect cell differentiation, proliferation, and motility. Butyrate also induces cell cycle arrest and apoptosis through its inhibition of histone deacetylases (HDACs). In addition, butyrate is a potent inducer of histone hyper-acetylation in cells. Therefore, this SCFA provides an excellent in vitro model for studying the epigenomic regulation of gene expression induced by histone acetylation. In this study, we analyzed the differential in vitro expression of genes induced by butyrate in bovine epithelial cells by using deep RNA-sequencing technology (RNA-seq). The number of sequences read, ranging from 57,303,693 to 78,933,744, were generated per sample. Approximately 11,408 genes were significantly impacted by butyrate, with a false discovery rate (FDR) <0.05. The predominant cellular processes affected by butyrate included cell morphological changes, cell cycle arrest, and apoptosis. Our results provided insight into the transcriptome alterations induced by butyrate, which will undoubtedly facilitate our understanding of the molecular mechanisms underlying butyrate-induced epigenomic regulation in bovine cells

Redox Modulation at Work: Natural Phytoprotective Polysulfanes From Alliums Based on Redox-Active Sulfur

Purpose of review: This article provides a brief overview of natural phytoprotective products of allium with a special focus on the therapeutic potential of diallyl polysulfanes from garlic, their molecular targets and their fate in the living organisms. A comprehensive overview of antimicrobial and anticancer properties of published literature is presented for the reader to understand the effective concentrations of polysulfanes and their sensitivity towards different human pathogenic microbes, fungi, and cancer cell lines. Recent findings: The article finds polysulfanes potentials as new generation novel antibiotics and chemo preventive agent. The effective dose rates of polysulfanes for antimicrobial properties are in the range of 0.5–40 mg/L and for anticancer 20–100 μM. The molecular targets for these redox modulators are mainly cellular thiols as well as inhibition and/or activation of certain cellular proteins in cancer cell lines. Summary: Antimicrobial and anticancer activities of polysulfanes published in the literature indicate that with further development, they could be promising candidates for cancer prevention due to their selectivity towards abnormal cells