Юридичний зміст та ознаки фінансово-правової санкції

У статті проведено аналіз теоретичних засад поняття фінансово-правової відповідальності та її складового елементу - фінансово-правової санкції. Автор досліджує наукові думки щодо понять «фінансово-правові санкції», «економічні санкції», «штрафні санкції», «штраф», «пеня» тощо; розглядає функції фінансово-правових санкцій з урахування засад загальної теорії права та фінансового права, зокрема, та виокремлює найхарактерніші ознаки фінансово-правової санкції. Ключові слова: фінансово-правова відповідальність, фінансово-правова санкція, ознаки фінансово-правової санкції.В статье проведен анализ теоретических основ понятия финансово-правовой ответственности и ее составляющего элемента - финансово-правовой санкции. Автор исследует существующие научные взгляды на понятия «финансово-правовая санкция», «экономическая санкция», «штрафная санкция», «штраф» и т.д.; рассматривает функции финансово-правовых санкций с позиций общей теории права и финансового права, в частности, и выделяет наиболее характерные признаки финансово-правовой санкции. Ключевые слова: финансово-правовая ответственность, финансово-правовая санкция, признаки финансово-правовой санкции.This article deals with the analysis of theoretical background of the notion in the sphere of both financial and law responsibility and its structural element - the financial and law sanction. The author researches the real scientific ideas as to the notions «financial and law sanction», «fine». The author also analyses the functions of financial and law sanctions including as the basement of common law theory so as financial law in particular. His special task is to analyses the most characteristic determinants of financial and law sanction. Key words: financial and law responsibility; financial and law sanction; signs of financial and law sanction

Boundaries Around the 'Well-Informed' Patient: The Contribution of Schutz to Inform Nurses' Interactions

Aim. The aim of this paper is to explore the operation of two different types of knowledge in health care and the position of the nurse to assist in the confluence of knowledge to develop the well-informed patient. Background. If patients are to be active participants in their care they require useful information. Interactions in contemporary health care mostly involve 'medico-scientific' knowledge, that refers to the 'science' of patients' conditions, as opposed to 'everyday' knowledge, which refers to information that can assist patients in lifestyle matters relating to their condition. Theoretical perspective. This paper draws on the work of the 'well-informed citizen' as proposed by Schutz in the analysis of two patient case studies of practices in the acute care setting of the hospital. Method. Data collection was undertaken through fieldwork, incorporating participant observation and discussions with patients in general medical/surgical areas. Results. Two patient case studies representative of the findings are analysed. Analysis identifies the predominant use of 'medico-scientific' knowledge to the detriment of 'everyday' knowledge during interactions between patients and all health professionals. Conclusions. There is predisposition in the acute context to interact in 'medico-scientific' knowledge as opposed to 'everyday' knowledge that does not facilitate a comprehensive understanding by patients of how they can best manage their lifestyle. Relevance to clinical practice. Using the notion of Schutz's 'well-informed' citizen this study identifies strategies for nursing staff to capture and explore the development of 'everyday' knowledge that can assist patients to become more informed and improve their health management

Loss of Pten promotes angiogenesis and enhanced vegfaa expression in zebrafish

Angiogenesis, the emergence of vessels from an existing vascular network, is pathologically associated with tumor progression and is of great interest for therapeutic intervention. PTEN is a frequently mutated tumor suppressor and has been linked to the progression of many types of tumors, including hemangiosarcomas in zebrafish. Here, we report that mutant zebrafish embryos lacking functional Pten exhibit enhanced angiogenesis, accompanied by elevated levels of phosphorylated Akt (pAkt). Inhibition of phosphoinositide 3-kinase (PI3K) by LY294002 treatment and application of sunitinib, a widely used anti-angiogenic compound, suppressed enhanced angiogenesis in Pten mutants. Vegfaa has a crucial role in angiogenesis and vegfaa expression was upregulated in embryos lacking functional Pten. Interestingly, vegfaa expression was also upregulated in hemangiosarcomas from haploinsufficient adult zebrafish Pten mutants. Elevated vegfaa expression in mutant embryos lacking functional Pten was suppressed by LY294002. Surprisingly, sunitinib treatment dramatically enhanced vegfaa expression in Pten mutant embryos, which might account for tumor relapse in human patients who are treated with sunitinib. Combined treatment with suboptimal concentrations of sunitinib and LY294002 rescued enhanced angiogenesis in pten mutant embryos without the dramatic increase in vegfaa expression, suggesting a new approach for therapeutic intervention in VEGFR-signaling-dependent tumors

Multispecies RNA tomography reveals regulators of hematopoietic stem cell birth in the embryonic aorta

The defined location of a stem cell within a niche regulates its fate, behavior and molecular identity via a complex extrinsic regulation far from being fully elucidated yet. To explore the molecular characteristics and key components of the aortic microenvironment, where the first hematopoietic stem cells (HSCs) are generated during development, we performed genome-wide RNA tomography sequencing on zebrafish, chicken, mouse and human embryos. The resulting anterior-posterior and dorsal-ventral transcriptional maps provided a powerful resource for exploring genes and regulatory pathways active in the aortic microenvironment. By performing inter-species comparative RNA-seq analyses and functional assays, we explored the complexity of the aortic microenvironment landscape and the fine-tuning of various factors interplaying to control HSC generation both in time and space in vivo, including the ligand-receptor couple ADM-RAMP2 and SVEP1. Understanding the regulatory function of the local environment will pave the way for improved stem cell production in vitro and clinical cell therapy

NFATc2 is a necessary mediator of calcineurin-dependent cardiac hypertrophy and heart failure.

One major intracellular signaling pathway involved in heart failure employs the phosphatase calcineurin and its downstream transcriptional effector nuclear factor of activated T-cells (NFAT). In vivo evidence for the involvement of NFAT factors in heart failure development is still ill defined. Here we reveal that nfatc2 transcripts outnumber those from other nfat genes in the unstimulated heart by severalfold. Transgenic mice with activated calcineurin in the postnatal myocardium crossbred with nfatc2-null mice revealed a significant abrogation of calcineurin-provoked cardiac growth, indicating that NFATc2 plays an important role downstream of calcineurin and validates the original hypothesis that calcineurin mediates myocyte hypertrophy through activation of NFAT transcription factors. In the absence of NFATc2, a clear protection against the geometrical, functional, and molecular deterioration of the myocardium following biomechanical stress was also evident. In contrast, physiological cardiac enlargement in response to voluntary exercise training was not affected in nfatc2-null mice. Combined, these results reveal a major role for the NFATc2 transcription factor in pathological cardiac remodeling and heart failure

Mecp2 regulates tnfa during zebrafish embryonic development and acute inflammation

Mutations in MECP2 cause Rett syndrome, a severe neurological disorder with autism-like features. Duplication of MECP2 also causes severe neuropathology. Both diseases display immunological abnormalities that suggest a role for MECP2 in controlling immune and inflammatory responses. Here, we used mecp2-null zebrafish to study the potential function of Mecp2 as an immunological regulator. Mecp2 deficiency resulted in an increase in neutrophil infiltration and upregulated expression of the pro- and anti-inflammatory cytokines Il1b and Il10 as a secondary response to disturbances in tissue homeostasis. By contrast, expression of the proinflammatory cytokine tumor necrosis factor alpha (Tnfa) was consistently downregulated in mecp2-null animals during development, representing the earliest developmental phenotype described for MECP2 deficiency to date. Expression of tnfa was unresponsive to inflammatory stimulation, and was partially restored by re-expression of functional mecp2. Thus, Mecp2 is required for tnfa expression during zebrafish development and inflammation. Finally, RNA sequencing of mecp2-null embryos revealed dysregulated processes predictive for Rett syndrome phenotypes

Atypical E2Fs inhibit tumor angiogenesis

Atypical E2F transcription factors (E2F7 and E2F8) function as key regulators of cell cycle progression and their inactivation leads to spontaneous cancer formation in mice. However, the mechanism of the tumor suppressor functions of E2F7/8 remain obscure. In this study we discovered that atypical E2Fs control tumor angiogenesis, one of the hallmarks of cancer. We genetically inactivated atypical E2Fs in epithelial and mesenchymal neoplasm and analyzed blood vessel formation in three different animal models of cancer. Tumor formation was either induced by application of 7,12-Dimethylbenz(a)anthracene/12-O-Tetradecanoylphorbol-13-acetate or by Myc/Ras overexpression. To our surprise, atypical E2Fs suppressed tumor angiogenesis in all three cancer models, which is in a sharp contrast to previous findings showing that atypical E2Fs promote angiogenesis during fetal development in mice and zebrafish. Real-time imaging in zebrafish displayed that fluorescent-labeled blood vessels showed enhanced intratumoral branching in xenografted E2f7/8-deficient neoplasms compared with E2f7/8-proficient neoplasms. DLL4 expression, a key negative inhibitor of vascular branching, was decreased in E2f7/8-deficient neoplastic cells, indicating that E2F7/8 might inhibit intratumoral vessel branching via induction of DLL4

E2F7 and E2F8 promote angiogenesis through transcriptional activation of VEGFA in cooperation with HIF1

The E2F family of transcription factors plays an important role in controlling cell-cycle progression. While this is their best-known function, we report here novel functions for the newest members of the E2F family, E2F7 and E2F8 (E2F7/8). We show that simultaneous deletion of E2F7/8 in zebrafish and mice leads to severe vascular defects during embryonic development. Using a panel of transgenic zebrafish with fluorescent-labelled blood vessels, we demonstrate that E2F7/8 are essential for proper formation of blood vessels. Despite their classification as transcriptional repressors, we provide evidence for a molecular mechanism through which E2F7/8 activate the transcription of the vascular endothelial growth factor A (VEGFA), a key factor in guiding angiogenesis. We show that E2F7/8 directly bind and stimulate the VEGFA promoter independent of canonical E2F binding elements. Instead, E2F7/8 form a transcriptional complex with the hypoxia inducible factor 1 (HIF1) to stimulate VEGFA promoter activity. These results uncover an unexpected link between E2F7/8 and the HIF1-VEGFA pathway providing a molecular mechanism by which E2F7/8 control angiogenesis

Atypical E2Fs inhibit tumor angiogenesis

Atypical E2F transcription factors (E2F7 and E2F8) function as key regulators of cell cycle progression and their inactivation leads to spontaneous cancer formation in mice. However, the mechanism of the tumor suppressor functions of E2F7/8 remain obscure. In this study we discovered that atypical E2Fs control tumor angiogenesis, one of the hallmarks of cancer. We genetically inactivated atypical E2Fs in epithelial and mesenchymal neoplasm and analyzed blood vessel formation in three different animal models of cancer. Tumor formation was either induced by application of 7,12-Dimethylbenz(a) anthracene/12-O-Tetradecanoylphorbol-13-acetate or by Myc/Ras overexpression. To our surprise, atypical E2Fs suppressed tumor angiogenesis in all three cancer models, which is in a sharp contrast to previous findings showing that atypical E2Fs promote angiogenesis during fetal development in mice and zebrafish. Real-time imaging in zebrafish displayed that fluorescent-labeled blood vessels showed enhanced intratumoral branching in xenografted E2f7/8-deficient neoplasms compared with E2f7/8-proficient neoplasms. DLL4 expression, a key negative inhibitor of vascular branching, was decreased in E2f7/8-deficient neoplastic cells, indicating that E2F7/8 might inhibit intratumoral vessel branching via induction of DLL4