МЕТОДИЧНИЙ ПІДХІД ДО ОЦІНКИ РІВНЯ ФІНАНСОВОЇ БЕЗПЕКИ БУДІВЕЛЬНОГО ПІДПРИЄМСТВА

The article deals with the issues of assessing the level of a construction company financial security. It is determined that the specificity of the construction enterprises activity and their diverse financial relations system require the formation of an appropriate system for certain financial interests protection against existing and potential internal and external threats, that is reflected in the approaches to the definition of “enterprise financial security”. The system of an enterprise financial security is proposed and the existing methodical approaches to assessing the level of enterprise financial security are generalized. The methodical approach to assessing the level of construction company financial security on the example of JSC “Trust Zhytlobud-1” is developed, which allows to distinguish factors-indicators that influence that level, to rank them and to calculate the integral indicator of financial security, which determines its level. As a result of the assessment it was determined that Economic crisis in Ukraine 2013—2014 caused a fall in the level of JSC “Trust Zhytlobud-1” financial security, but the successful financial policy of the company management led to a substantial increase in the financial security level. The application of the proposed methodological approach to assessing the level of a construction company financial security will enable the enterprises management to respond in a timely manner to the deterioration of the economic entity financial condition as well as the negative trends that may develop in the course of the business entity’s activity.Исследован вопрос оценки уровня финансовой безопасности строительного предприятия. Установлено, что специфика деятельности строительных предприятий и наличие в них разнообразной системы финансовых отношений требует формирования соответствующей системы защиты определенных финансовых интересов от существующих и потенциальных угроз внутренней и внешней среды, что отражается в подходах к определению понятия «финансовая безопасность предприятия». Предложена система экономической безопасности предприятия и обобщены существующие методические подходы к оценке уровня финансовой безопасности предприятия. Разработан методический подход к оценке уровня финансовой безопасности строительного предприятия на примере АО «Трест Жилстрой-1», который позволяет выделить факторы-индикаторы, влияющие на уровень финансовой безопасности строительного предприятия, ранжировать их и вычислить интегральный показатель финансовой безопасности, по которому устанавливается ее уровень. В результате оценки установлено, что экономический кризис в Украине в 2013—2014 гг. обусловил падение уровня финансовой безопасности АО «Трест Жилстрой-1», но удачная финансовая политика руководства предприятия привела к повышению уровня финансовой безопасности к достаточно высокому. Использование предложенного методического подхода к оценке уровня финансовой безопасности строительного предприятия дает возможность для менеджмента предприятий вовремя среагировать на ухудшение финансового состояния субъекта хозяйствования и негативные тенденции, которые могут развиваться в процессе деятельности хозяйствующего субъекта.Досліджено питання оцінки рівня фінансової безпеки будівельного підприємства. Установлено, що специфіка діяльності будівельних підприємств і наявність у них різноманітної системи фінансових відносин вимагає формування  відповідної системи захисту певних фінансових інтересів від наявних і потенційних загроз внутрішнього і зовнішнього середовища, що відображається у підходах до визначення поняття «фінансова безпека підприємства». Запропоновано систему фінансової безпеки підприємства та узагальнено наявні методичні підходи до оцінки рівня фінансової безпеки підприємства. Розроблено методичний підхід до оцінки рівня фінансової безпеки будівельного підприємства на прикладі АТ «Трест Житлобуд-1», який дозволяє виокремити фактори-індикатори, що мають вплив на рівень фінансової безпеки будівельного підприємства, ранжирувати їх та обчислити інтегральний показник фінансової безпеки, за яким встановлюється її рівень. У результаті оцінки встановлено, що економічна криза в Україні у 2013—2014 роках зумовила падіння рівня фінансової безпеки АТ «Трест Житлобуд-1», але вдала фінансова політика керівництва підприємства призвела до підвищення рівня фінансової безпеки до достатньо високого. Використання запропонованого методичного підходу до оцінки рівня фінансової безпеки будівельного підприємства надасть можливість  менеджментові підприємств вчасно зреагувати на погіршення фінансового стану суб’єкта господарювання і негативні тенденції, що можуть розвиватися у процесі діяльності суб’єкта господарювання

IQGAP1 and IQGAP2 are Reciprocally Altered in Hepatocellular Carcinoma

<p>Abstract</p> <p>Background</p> <p>IQGAP1 and IQGAP2 are homologous members of the IQGAP family of scaffold proteins. Accumulating evidence implicates IQGAPs in tumorigenesis. We recently reported that IQGAP2 deficiency leads to the development of hepatocellular carcinoma (HCC) in mice. In the current study we extend these findings, and investigate IQGAP1 and IQGAP2 expression in human HCC.</p> <p>Methods</p> <p>IQGAP1 and IQGAP2 protein expression was assessed by Western blotting and immunohistochemistry. IQGAP mRNA was measured by quantitative RT-PCR. The methylation status of the <it>Iqgap2 </it>promoter was determined by pyrosequencing of bisulfite-treated genomic DNA.</p> <p>Results</p> <p>IQGAP1 and IQGAP2 expression was reciprocally altered in 6/6 liver cancer cell lines. Similarly, immunohistochemical staining of 82 HCC samples showed that IQGAP2 protein expression was reduced in 64/82 (78.0%), while IQGAP1 was present in 69/82 (84.1%). No IQGAP1 staining was detected in 23/28 (82.1%) normal livers, 4/4 (100.0%) hepatic adenomas and 23/23 (100.0%) cirrhosis cases, while IQGAP2 was increased in 22/28 (78.6%), 4/4 (100.0%) and 23/23 (100.0%), respectively. Although the <it>Iqgap2 </it>promoter was not hypermethylated in HCC at any of the 25 CpG sites studied (N = 17), IQGAP2 mRNA levels were significantly lower in HCC specimens (N = 23) than normal livers (N = 6).</p> <p>Conclusions</p> <p>We conclude that increased IQGAP1 and/or decreased IQGAP2 contribute to the pathogenesis of human HCC. Furthermore, downregulation of IQGAP2 in HCC occurs independently of hypermethylation of the <it>Iqgap2 </it>promoter. Immunostaining of IQGAP1 and IQGAP2 may aid in the diagnosis of HCC, and their pharmacologic modulation may represent a novel therapeutic strategy for the treatment of liver cancer.</p

Expression of Regulatory Platelet MicroRNAs in Patients with Sickle Cell Disease

Background: Increased platelet activation in sickle cell disease (SCD) contributes to a state of hypercoagulability and confers a risk of thromboembolic complications. The role for post-transcriptional regulation of the platelet transcriptome by microRNAs (miRNAs) in SCD has not been previously explored. This is the first study to determine whether platelets from SCD exhibit an altered miRNA expression profile. Methods and Findings: We analyzed the expression of miRNAs isolated from platelets from a primary cohort (SCD = 19, controls = 10) and a validation cohort (SCD = 7, controls = 7) by hybridizing to the Agilent miRNA microarrays. A dramatic difference in miRNA expression profiles between patients and controls was noted in both cohorts separately. A total of 40 differentially expressed platelet miRNAs were identified as common in both cohorts (p-value 0.05, fold change>2) with 24 miRNAs downregulated. Interestingly, 14 of the 24 downregulated miRNAs were members of three families - miR-329, miR-376 and miR-154 - which localized to the epigenetically regulated, maternally imprinted chromosome 14q32 region. We validated the downregulated miRNAs, miR-376a and miR-409-3p, and an upregulated miR-1225-3p using qRT-PCR. Over-expression of the miR-1225-3p in the Meg01 cells was followed by mRNA expression profiling to identify mRNA targets. This resulted in significant transcriptional repression of 1605 transcripts. A combinatorial approach using Meg01 mRNA expression profiles following miR-1225-3p overexpression, a computational prediction analysis of miRNA target sequences and a previously published set of differentially expressed platelet transcripts from SCD patients, identified three novel platelet mRNA targets: PBXIP1, PLAGL2 and PHF20L1. Conclusions: We have identified significant differences in functionally active platelet miRNAs in patients with SCD as compared to controls. These data provide an important inventory of differentially expressed miRNAs in SCD patients and an experimental framework for future studies of miRNAs as regulators of biological pathways in platelets. © 2013 Jain et al

Proteome changes in platelets activated by arachidonic acid, collagen, and thrombin

<p>Abstract</p> <p>Background</p> <p>Platelets are small anucleated blood particles that play a key role in the control of bleeding. Platelets need to be activated to perform their functions and participate in hemostasis. The process of activation is accompanied by vast protein reorganization and posttranslational modifications. The goal of this study was to identify changes in proteins in platelets activated by different agonists. Platelets were activated by three different agonists - arachidonic acid, collagen, and thrombin. 2D SDS-PAGE (pI 4-7) was used to separate platelet proteins. Proteomes of activated and resting platelets were compared with each other by Progenesis SameSpots statistical software; and proteins were identified by nanoLC-MS/MS.</p> <p>Results</p> <p>190 spots were found to be significantly different. Of these, 180 spots were successfully identified and correspond to 144 different proteins. Five proteins were found that had not previously been identified in platelets: protein CDV3 homolog, protein ETHE1, protein LZIC, FGFR1 oncogene partner 2, and guanine nucleotide-binding protein subunit beta-5. Using spot expression profile analysis, we found two proteins (WD repeat-containing protein 1 and mitochondrial glycerol-3-phosphate dehydrogenase) that may be part of thrombin specific activation or signal transduction pathway(s).</p> <p>Conclusions</p> <p>Our results, characterizing the differences within proteins in both activated (by various agonists) and resting platelets, can thus contribute to the basic knowledge of platelets and to the understanding of the function and development of new antiplatelet drugs.</p

Sighting acute myocardial infarction through platelet gene expression

© 2019, The Author(s). Acute myocardial infarction is primarily due to coronary atherosclerotic plaque rupture and subsequent thrombus formation. Platelets play a key role in the genesis and progression of both atherosclerosis and thrombosis. Since platelets are anuclear cells that inherit their mRNA from megakaryocyte precursors and maintain it unchanged during their life span, gene expression profiling at the time of an acute myocardial infarction provides information concerning the platelet gene expression preceding the coronary event. In ST-segment elevation myocardial infarction (STEMI), a gene-by-gene analysis of the platelet gene expression identified five differentially expressed genes: FKBP5, S100P, SAMSN1, CLEC4E and S100A12. The logistic regression model used to combine the gene expression in a STEMI vs healthy donors score showed an AUC of 0.95. The same five differentially expressed genes were externally validated using platelet gene expression data from patients with coronary atherosclerosis but without thrombosis. Platelet gene expression profile highlights five genes able to identify STEMI patients and to discriminate them in the background of atherosclerosis. Consequently, early signals of an imminent acute myocardial infarction are likely to be found by platelet gene expression profiling before the infarction occurs

Investigation of Variation in Gene Expression Profiling of Human Blood by Extended Principle Component Analysis

BACKGROUND: Human peripheral blood is a promising material for biomedical research. However, various kinds of biological and technological factors result in a large degree of variation in blood gene expression profiles. METHODOLOGY/PRINCIPAL FINDINGS: Human peripheral blood samples were drawn from healthy volunteers and analysed using the Human Genome U133Plus2 Microarray. We applied a novel approach using the Principle Component Analysis and Eigen-R(2) methods to dissect the overall variation of blood gene expression profiles with respect to the interested biological and technological factors. The results indicated that the predominating sources of the variation could be traced to the individual heterogeneity of the relative proportions of different blood cell types (leukocyte subsets and erythrocytes). The physiological factors like age, gender and BMI were demonstrated to be associated with 5.3% to 9.2% of the total variation in the blood gene expression profiles. We investigated the gene expression profiles of samples from the same donors but with different levels of RNA quality. Although the proportion of variation associated to the RNA Integrity Number was mild (2.1%), the significant impact of RNA quality on the expression of individual genes was observed. CONCLUSIONS: By characterizing the major sources of variation in blood gene expression profiles, such variability can be minimized by modifications to study designs. Increasing sample size, balancing confounding factors between study groups, using rigorous selection criteria for sample quality, and well controlled experimental processes will significantly improve the accuracy and reproducibility of blood transcriptome study

Proteomic and Phospho-Proteomic Profile of Human Platelets in Basal, Resting State: Insights into Integrin Signaling

During atherogenesis and vascular inflammation quiescent platelets are activated to increase the surface expression and ligand affinity of the integrin αIIbβ3 via inside-out signaling. Diverse signals such as thrombin, ADP and epinephrine transduce signals through their respective GPCRs to activate protein kinases that ultimately lead to the phosphorylation of the cytoplasmic tail of the integrin αIIbβ3 and augment its function. The signaling pathways that transmit signals from the GPCR to the cytosolic domain of the integrin are not well defined. In an effort to better understand these pathways, we employed a combination of proteomic profiling and computational analyses of isolated human platelets. We analyzed ten independent human samples and identified a total of 1507 unique proteins in platelets. This is the most comprehensive platelet proteome assembled to date and includes 190 membrane-associated and 262 phosphorylated proteins, which were identified via independent proteomic and phospho-proteomic profiling. We used this proteomic dataset to create a platelet protein-protein interaction (PPI) network and applied novel contextual information about the phosphorylation step to introduce limited directionality in the PPI graph. This newly developed contextual PPI network computationally recapitulated an integrin signaling pathway. Most importantly, our approach not only provided insights into the mechanism of integrin αIIbβ3 activation in resting platelets but also provides an improved model for analysis and discovery of PPI dynamics and signaling pathways in the future

Massive-Scale RNA-Seq Analysis of Non Ribosomal Transcriptome in Human Trisomy 21

Hybridization- and tag-based technologies have been successfully used in Down syndrome to identify genes involved in various aspects of the pathogenesis. However, these technologies suffer from several limits and drawbacks and, to date, information about rare, even though relevant, RNA species such as long and small non-coding RNAs, is completely missing. Indeed, none of published works has still described the whole transcriptional landscape of Down syndrome. Although the recent advances in high-throughput RNA sequencing have revealed the complexity of transcriptomes, most of them rely on polyA enrichment protocols, able to detect only a small fraction of total RNA content. On the opposite end, massive-scale RNA sequencing on rRNA-depleted samples allows the survey of the complete set of coding and non-coding RNA species, now emerging as novel contributors to pathogenic mechanisms. Hence, in this work we analysed for the first time the complete transcriptome of human trisomic endothelial progenitor cells to an unprecedented level of resolution and sensitivity by RNA-sequencing. Our analysis allowed us to detect differential expression of even low expressed genes crucial for the pathogenesis, to disclose novel regions of active transcription outside yet annotated loci, and to investigate a plethora of non-polyadenilated long as well as short non coding RNAs. Novel splice isoforms for a large subset of crucial genes, and novel extended untranslated regions for known genes—possibly novel miRNA targets or regulatory sites for gene transcription—were also identified in this study. Coupling the rRNA depletion of samples, followed by high-throughput RNA-sequencing, to the easy availability of these cells renders this approach very feasible for transcriptome studies, offering the possibility of investigating in-depth blood-related pathological features of Down syndrome, as well as other genetic disorders