Extracellular Vesicles:Novel Opportunities to Understand and Detect Neoplastic Diseases

With a size range from 30 to 1000 nm, extracellular vesicles (EVs) are one of the smallest cell components able to transport biologically active molecules. They mediate intercellular communications and play a fundamental role in the maintenance of tissue homeostasis and pathogenesis in several types of diseases. In particular, EVs actively contribute to cancer initiation and progression, and there is emerging understanding of their role in creation of the metastatic niche. This fact underlies the recent exponential growth in EV research, which has improved our understanding of their specific roles in disease and their potential applications in diagnosis and therapy. EVs and their biomolecular cargo reflect the state of the diseased donor cells, and can be detected in body fluids and exploited as biomarkers in cancer and other diseases. Relatively few studies have been published on EVs in the veterinary field. This review provides an overview of the features and biology of EVs as well as recent developments in EV research including techniques for isolation and analysis, and will address the way in which the EVs released by diseased tissues can be studied and exploited in the field of veterinary pathology. Uniquely, this review emphasizes the important contribution that pathologists can make to the field of EV research: pathologists can help EV scientists in studying and confirming the role of EVs and their molecular cargo in diseased tissues and as biomarkers in liquid biopsies

Економіко-правове забезпечення формування та реалізації соціальної політики держави, регіону, міста

У статті визначено потребу послідовного правового забезпечення формування та реалізації соціальної політики в багаторівневій системі управління. Обґрунтовано зміст та особливості соціальної політики залежно від рівня управління. Сформульовано пропозиції з удосконалення соціальної політики держави та її регіонів, виконано їх правову регламентацію

Проблеми оцінки якості індустріального розвитку соціально-економічної системи України

Розглянуті особливості процесу системної трансформації індустріального базису соціально-економічної системи України в умовах соціальної поляризації світового суспільства. Доведено існування дихотомії типу базису економіки України: індустріального в межах національної підсистеми та доіндустріального в межах світової соціально-економічної системи. Ключові слова: трансформація, система, промисловість, якість.Рассмотрены особенности процесса системной трансформации индустриального базиса социально-экономической системы Украины в условиях социальной поляризации мирового сообщества. Доказано существование дихотомии базиса экономики Украины: индустриального в рамках национальной подсистемы и доиндустриальной в рамках мировой социально-экономической системы. Ключевые слова: трансформация, система, промышленность, качество.Features of process of system transformation of industrial basis of social and economic system of Ukraine in the conditions of social polarisation of the world community are considered. Existence of a dichotomy of basis of economy of Ukraine is proved: industrial within the limits of a national subsystem and befor industrial in frames of world social and economic system. Key words: transformation, system, industry, quality

Пленум Наукової ради«Українська мова» Українська лексикографія та лексикологія: проблеми, завдання

10–11 листопада 2011року у Ніжинському державному університеты імені Миколи Гоголя відбувся Пленум Наукової ради “Українська мова” Інституту української мови НАН України на тему “Українська лексикографія та лексикологія: проблеми, завдання”

Immune stimuli shape the small non-coding transcriptome of extracellular vesicles released by dendritic cells

Molecular Technology and Informatics for Personalised Medicine and Healt

Immune stimuli shape the small non-coding transcriptome of extracellular vesicles released by dendritic cells

Molecular Technology and Informatics for Personalised Medicine and Healt

Picornavirus security proteins promote the release of extracellular vesicle enclosed viruses via the modulation of host kinases

The discovery that extracellular vesicles (EVs) serve as carriers of virus particles calls for a reevaluation of the release strategies of non-enveloped viruses. Little is currently known about the molecular mechanisms that determine the release and composition of EVs produced by virus-infected cells, as well as conservation of these mechanisms among viruses. We previously described an important role for the Leader protein of the picornavirus encephalomyocarditis virus (EMCV) in the induction of virus-carrying EV subsets with distinct molecular and physical properties. EMCV L acts as a 'viral security protein' by suppressing host antiviral stress and type-I interferon (IFN) responses. Here, we tested the ability of functionally related picornavirus proteins of Theilers murine encephalitis virus (TMEV L), Saffold virus (SAFV L), and coxsackievirus B3 (CVB3 2Apro), to rescue EV and EV-enclosed virus release when introduced in Leader-deficient EMCV. We show that all viral security proteins tested were able to promote virus packaging in EVs, but that only the expression of EMCV L and CVB3 2Apro increased overall EV production. We provide evidence that one of the main antiviral pathways counteracted by this class of picornaviral proteins, i.e. the inhibition of PKR-mediated stress responses, affected EV and EV-enclosed virus release during infection. Moreover, we show that the enhanced capacity of the viral proteins EMCV L and CVB3 2Apro to promote EV-enclosed virus release is linked to their ability to simultaneously promote the activation of the stress kinase P38 MAPK. Taken together, we demonstrate that cellular stress pathways involving the kinases PKR and P38 are modulated by the activity of non-structural viral proteins to increase the release EV-enclosed viruses during picornavirus infections. These data shed new light on the molecular regulation of EV production in response to virus infection

Intracellular localisation and extracellular release of Y RNA and Y RNA binding proteins

Cells can communicate via the release and uptake of extracellular vesicles (EVs), which are nano-sized membrane vesicles that can transfer protein and RNA cargo between cells. EVs contain microRNAs and various other types of non-coding RNA, of which Y RNA is among the most abundant types. Studies on how RNAs and their binding proteins are sorted into EVs have mainly focused on comparing intracellular (cytoplasmic) levels of these RNAs to the extracellular levels in EVs. Besides overall transcriptional levels that may regulate sorting of RNAs into EVs, the process may also be driven by local intracellular changes in RNA/RBP concentrations. Changes in extracellular Y RNA have been linked to cancer and cardiovascular diseases. Although the loading of RNA cargo into EVs is generally thought to be influenced by cellular stimuli and regulated by RNA binding proteins (RBP), little is known about Y RNA shuttling into EVs. We previously reported that immune stimulation alters the levels of Y RNA in EVs independently of cytosolic Y RNA levels. This suggests that Y RNA binding proteins, and/or changes in the local Y RNA concentration at EV biogenesis sites, may affect Y RNA incorporation into EVs. Here, we investigated the subcellular distribution of Y RNA and Y RNA binding proteins in activated and non-activated THP1 macrophages. We demonstrate that Y RNA and its main binding protein Ro60 abundantly co-fractionate in organelles involved in EV biogenesis and in EVs. Cellular activation led to an increase in Y RNA concentration at EV biogenesis sites and this correlated with increased EV-associated levels of Y RNA and Ro60. These results suggest that Y RNA incorporation into EVs may be controlled by local intracellular changes in the concentration of Y RNA and their protein binding partners

CDC6:A novel canine tumour biomarker detected in circulating extracellular vesicles

Circulating nucleic acids and extracellular vesicles (EV) represent novel biomarkers to diagnose cancer. The non-invasive nature of these so-called liquid biopsies provides an attractive alternative to tissue biopsy-based cancer diagnostics. This study aimed to investigate if circulating cell cycle-related E2F target transcripts can be used to diagnose tumours in canine tumour patients with different types of tumours. Furthermore, we assessed if these mRNAs are localised within circulating EV. We isolated total RNA from the plasma of 20 canine tumour patients and 20 healthy controls. Four E2F target genes (CDC6, DHFR, H2AFZ and ATAD2) were selected based on the analysis of published data of tumour samples available in public databases. We performed reverse transcription and quantitative real-time PCR to analyse the plasma levels of selected E2F target transcripts. All four E2F target transcripts were detectable in the plasma of canine tumour patients. CDC6 mRNA levels were significantly higher in the plasma of canine tumour patients compared to healthy controls. A subset of canine tumour patient and healthy control plasma samples (n = 7) were subjected to size exclusion chromatography in order to validate association of the E2F target transcripts to circulating EV. For CDC6, EV analysis enhanced their detectability compared to total plasma analysis. In conclusion, our study reveals circulating CDC6 as a promising non-invasive biomarker to diagnose canine tumours

Natural T-cell ligands that are created by genetic variants can be transferred between cells by extracellular vesicles

Immunobiology of allogeneic stem cell transplantation and immunotherapy of hematological disease