93 research outputs found
Європейський суд з прав людини як гарант правового захисту людини в авіаційній діяльності України
Purpose: The effectiveness of human rights protection in the Council of Europe largely depends on activities of the European Court, which demonstrates high standards of justice, particularly in matters of human rights protection in the field of aviation activities. The article offers a critical assessment of Ukrainian national legislation in terms of its internal legal consistency and compliance with international legal acts. Methods: The methods of legal analysis are used to study court decisions in the aviation field; methods of comparative legal analysis, forecasting and dialectical - in the study of problems in the further improvement of Ukrainian legislation. Also in article applied the theory of legal comparative, approaches to applying the analogy of legal and law in process of making decisions on similar court cases. Results: The article deals with the analysis of the European Court of Human Rights jurisdiction on cases of protection of human rights in the field of aviation activities. Two groups of cases in which Ukraine is a defendant are identified: a) cases of international concern (in particular the Malaysia Airlines’ Boeing 777-200ER crash); b) cases of national character (citizens of Ukraine against the State of Ukraine). The author's position on deciding the cases in the field of aviation activities is based on the principles of respect for the European Convention on Human Rights, 1950. Discussion: The conclusion about the necessity of amending some national laws, taking into account the legal positions of the European Court (in particular, regarding the right of airlines workers to strike) is made, and the fact that the issues of States and airlines activities to respect human and civil rights in the field of aviation activities are covered by jurisdiction of the European Court of Human Rights and occupy an important place in its practice is indicated.Цель: Эффективность защиты прав человека в Совете Европы во многом зависит от деятельности именно Европейского Суда, который демонстрирует высокие стандарты осуществления правосудия, в том числе в вопросах защиты прав человека в сфере авиационной деятельности. В статье предлагается критический анализ украинского национального законодательства с точки зрения его внутренне-правовой согласованности и соответствия международно-правовым актам. Методы: В работе использованы методы юридического анализа судебных решений, сравнительно-правового анализа; методы прогнозирования и диалектический метод – при исследовании проблем дальнейшего усовершенствования украинского законодательства. В исследовании также использованы теория правовой компаративистики, подходы применения аналогий закона и права при вынесении решений по аналогичным судебным делам. Результаты: Осуществлен общий анализ судебной практики Европейского Суда по правам человека, касающейся рассмотрения дел о защите прав человека в сфере авиационной деятельности. Выделены две группы дел, ответчиком в которых выступает Украина, а именно: а) дела международного значения (в частности, по авиакатастрофе самолета Boeing 777-200ER компании Malaysia Airlines) б) дела национального характера (граждане Украины против государства Украина). Авторская позиция по решению судебных дел в сфере авиационной деятельности основывается на принципах соблюдения Конвенции о защите прав человека и основных свобод 1950 года. Обсуждение: Предлагается мнение о необходимости внесения изменений в национальные законы Украины с учетом правовых позиций Европейского Суда (в частности, по обеспечению права сотрудников авиакомпаний на забастовку), а также отстаивается позиция о том, что вопросы деятельности государств и авиакомпаний по соблюдению прав человека и гражданина в сфере авиационной деятельности подпадают под юрисдикцию Европейского Суда по правам человека и занимают важное место в его практике.Мета: Ефективність захисту прав людини в Раді Європи багато в чому залежить від діяльності саме Європейського суду, який демонструє високі стандарти здійснення правосуддя, зокрема, і у питаннях захисту прав людини у сфері авіаційної діяльності. В статті пропонується критичний аналіз українського національного законодавства з точки зору його внутрішньо-правової узгодженості та відповідності міжнародно-правовим актам. Методи: У работі використані методи юридичного аналізу судових рішень, порівняльно-правового аналізу; методи прогнозування й діалектичний метод – при дослідженні проблем подальшого вдосконалення українського законодавства. У дослідженні також використані теорія правової компаративістики, підходи застосування аналогій закону і права в ході прийняття рішень з аналогічних судових справ. Результати: Наведено загальний аналіз судової практики Європейського суду з прав людини щодо розгляду справ про захист прав людини у сфері авіаційної діяльності. Виділено дві групи справ, відповідачем в яких виступає Україна, а саме: а) справи міжнародного значення (зокрема, щодо авіакатастрофи літака Boeing 777-200ER компанії Malaysia Airlines); б) справи національного характеру (громадяни України проти держави Україна). Авторська позиція щодо вирішення судових справ у сфері авіаційної діяльності ґрунтується на принципах дотримання Конвенції про захист прав людини і основоположних свобод 1950 року. Обговорення: Робиться висновок про необхідність внесення змін до деяких національних законів з урахуванням правових позицій Європейського суду (зокрема, щодо забезпечення права працівників авіакомпаній на страйк), а також вказується, що питання діяльності держав та авіакомпаній щодо дотримання прав людини і громадянина у сфері авіаційної діяльності підпадають під юрисдикцію Європейського суду з прав людини та займають важливе місце в його практиці
Selective Changes of GABAA Channel Subunit mRNAs in the Hippocampus and Orbitofrontal Cortex but not in Prefrontal Cortex of Human Alcoholics
Alcohol dependence is a common chronic relapsing disorder. The development of alcohol dependence has been associated with changes in brain GABAA channel-mediated neurotransmission and plasticity. We have examined mRNA expression of the GABAA channel subunit genes in three brain regions in individuals with or without alcohol dependence using quantitative real-time PCR assay. The levels of selective GABAA channel subunit mRNAs were altered in specific brain regions in alcoholic subjects. Significant increase in the α1, α4, α5, β1, and γ1 subunit mRNAs in the hippocampal dentate gyrus region, and decrease in the β2 and δ subunit mRNAs in the orbitofrontal cortex were identified whereas no changes in the dorsolateral prefrontal cortex were detected. The data increase our understanding of the role of GABAA channels in the development of alcohol dependence
Morphine Exacerbates HIV-1 Tat-Induced Cytokine Production in Astrocytes through Convergent Effects on [Ca2+]i, NF-κB Trafficking and Transcription
Astroglia are key cellular sites where opiate drug signals converge with the proinflammatory effects of HIV-1 Tat signals to exacerbate HIV encephalitis. Despite this understanding, the molecular sites of convergence driving opiate-accelerated neuropathogenesis have not been deciphered. We therefore explored potential points of interaction between the signaling pathways initiated by HIV-1 Tat and opioids in striatal astrocytes. Profiling studies screening 152 transcription factors indicated that the nuclear factor-kappa B (NF-κB) subunit, c-Rel, was a likely candidate for Tat or Tat plus opiate-induced increases in cytokine and chemokine production by astrocytes. Pretreatment with the NF-κB inhibitor parthenolide provided evidence that Tat±morphine-induced release of MCP-1, IL-6 and TNF-α by astrocytes is NF-κB dependent. The nuclear export inhibitor, leptomycin B, blocked the nucleocytoplasmic shuttling of NF-κB; causing p65 (RelA) accumulation in the nucleus, and significantly attenuated cytokine production in Tat±morphine exposed astrocytes. Similarly, chelating intracellular calcium ([Ca2+]i) blocked Tat±morphine-evoked MCP-1 and IL-6 release, while artificially increasing the concentration of extracellular Ca2+ reversed this effect. Taken together, these results demonstrate that: 1) exposure to Tat±morphine is sufficient to activate NF-κB and cytokine production, 2) the release of MCP-1 and IL-6 by Tat±morphine are highly Ca2+-dependent, while TNF-α appears to be less affected by the changes in [Ca2+]i, and 3) in the presence of Tat, exposure to opiates augments Tat-induced NF-κB activation and cytokine release through a Ca2+-dependent pathway
Эпидемиологическая характеристика парвовирусной В19 инфекции у детей с гематологическими заболеваниями
ДЕТИ, СЛУЖБЫ ОХРАНЫ ЗДОРОВЬЯКРОВИ БОЛЕЗНИПАРВОВИРУСНЫЕ ИНФЕКЦИИЭПИДЕМИОЛОГИ
Opioid precursor protein isoform is targeted to the cell nuclei in the human brain
Background: Neuropeptide precursors are traditionally viewed as proteins giving rise to small neuropeptide molecules. Prodynorphin (PDYN) is the precursor protein to dynorphins, endogenous ligands for the kappa-opioid receptor. Alternative mRNA splicing of neuropeptide genes may regulate cell- and tissue-specific neuropeptide expression and produce novel protein isoforms. We here searched for novel PDYN mRNA and their protein product in the human brain. Methods: Novel PDYN transcripts were identified using nested PCR amplification of oligo(dT) selected full-length capped mRNA. Gene expression was analyzed by qRT-PCR, PDYN protein by western blotting and confocal imaging, dynorphin peptides by radioimmunoassay. Neuronal nuclei were isolated using fluorescence activated nuclei sorting (FANS) from postmortem human striatal tissue. lmmunofluorescence staining and con focal microscopy was performed for human caudate nucleus. Results: Two novel human PDYN mRNA splicing variants were identified. Expression of one of them was confined to the striatum where its levels constituted up to 30% of total PDYN mRNA. This transcript may be translated into ASP-PDYN protein lacking 13 N-terminal amino acids, a fragment of signal peptide (SP). Delta SP-PDYN was not processed to mature dynorphins and surprisingly, was targeted to the cell nuclei in a model cellular system. The endogenous PDYN protein was identified in the cell nuclei in human striatum by western blotting of isolated neuronal nuclei, and by confocal imaging. Conclusions and general significance: High levels of alternatively spliced Delta SP-PDYN mRNA and nuclear localization of PDYN protein suggests a nuclear function for this isoform of the opioid peptide precursor in human striatum. (C) 2016 Elsevier B.V. All rights reserved
Conformation Effects of CpG Methylation on Single-Stranded DNA Oligonucleotides: Analysis of the Opioid Peptide Dynorphin-Coding Sequences
Single-stranded DNA (ssDNA) is characterized by high conformational flexibility that allows these molecules to adopt a variety of conformations. Here we used native polyacrylamide gel electrophoresis (PAGE), circular dichroism (CD) spectroscopy and nuclear magnetic resonance (NMR) spectroscopy to show that cytosine methylation at CpG sites affects the conformational flexibility of short ssDNA molecules. The CpG containing 37-nucleotide PDYN (prodynorphin) fragments were used as model molecules. The presence of secondary DNA structures was evident from differences in oligonucleotide mobilities on PAGE, from CD spectra, and from formation of A-T, G-C, and non-canonical G-T base pairs observed by NMR spectroscopy. The oligonucleotides displayed secondary structures at 4°C, and some also at 37°C. Methylation at CpG sites prompted sequence-dependent formation of novel conformations, or shifted the equilibrium between different existing ssDNA conformations. The effects of methylation on gel mobility and base pairing were comparable in strength to the effects induced by point mutations in the DNA sequences. The conformational effects of methylation may be relevant for epigenetic regulatory events in a chromatin context, including DNA-protein or DNA-DNA recognition in the course of gene transcription, and DNA replication and recombination when double-stranded DNA is unwinded to ssDNA
Neuroadaptations in Human Chronic Alcoholics: Dysregulation of the NF-κB System
Anna Ökvist is with Karolinska Institute, Sofia Johansson is with Karolinska Institute, Alexander Kuzmin is with Karolinska Institute, Igor Bazov is with Karolinska Institute, Roxana Merino-Martinez is with Karolinska Institute, Igor Ponomarev is with UT Austin, R. Dayne Mayfield is with UT Austin, R. Adron Harris is with UT Austin, Donna Sheedy is with University of Sydney, Therese Garrick is with University of Sydney, Clive Harper is with University of Sydney, Yasmin L. Hurd is with Mount Sinai School of Medicine, Lars Terenius is with Karolinska Institute, Tomas J. Ekström is with Karolinska Institute, Georgy Bakalkin is with Karolinska Institute and Uppsala University, Tatjana Yakovleva is with Karolinska Institute and Uppsala University.Background -- Alcohol dependence and associated cognitive impairments apparently result from neuroadaptations to chronic alcohol consumption involving changes in expression of multiple genes. Here we investigated whether transcription factors of Nuclear Factor-kappaB (NF-κB) family, controlling neuronal plasticity and neurodegeneration, are involved in these adaptations in human chronic alcoholics. Methods and Findings -- Analysis of DNA-binding of NF-κB (p65/p50 heterodimer) and the p50 homodimer as well as NF-κB proteins and mRNAs was performed in postmortem human brain samples from 15 chronic alcoholics and 15 control subjects. The prefrontal cortex involved in alcohol dependence and cognition was analyzed and the motor cortex was studied for comparison. The p50 homodimer was identified as dominant κB binding factor in analyzed tissues. NF-κB and p50 homodimer DNA-binding was downregulated, levels of p65 (RELA) mRNA were attenuated, and the stoichiometry of p65/p50 proteins and respective mRNAs was altered in the prefrontal cortex of alcoholics. Comparison of a number of p50 homodimer/NF-κB target DNA sites, κB elements in 479 genes, down- or upregulated in alcoholics demonstrated that genes with κB elements were generally upregulated in alcoholics. No significant differences between alcoholics and controls were observed in the motor cortex. Conclusions -- We suggest that cycles of alcohol intoxication/withdrawal, which may initially activate NF-κB, when repeated over years downregulate RELA expression and NF-κB and p50 homodimer DNA-binding. Downregulation of the dominant p50 homodimer, a potent inhibitor of gene transcription apparently resulted in derepression of κB regulated genes. Alterations in expression of p50 homodimer/NF-κB regulated genes may contribute to neuroplastic adaptation underlying alcoholism.This work was supported by grants from the AFA Forsäkring to AK, YLH, TJE and GB, the Research Foundation of the Swedish Alcohol Retail Monopoly (SRA) and Karolinska Institutet to AK, TJE and GB, and the Swedish Science Research Council and the Swedish National Drug Policy Coordinator to GB. The Australian Brain Donor Programs NSW Tissue Resource Centre was supported by The University of Sydney, National Health and Medical Research Council of Australia, Neuroscience Institute of Schizophrenia and Allied Disorders, National Institute of Alcohol Abuse and Alcoholism and NSW Department of Health.Waggoner Center for Alcohol and Addiction Researc
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