MicroRNAs (miRNAs) are a class of small RNA molecules that regulate expression of specific mRNA targets. They can be released from cells, often encapsulated within extracellular vesicles (EVs), and ...therefore have the potential to mediate intercellular communication. It has been suggested that certain miRNAs may be selectively exported, although the mechanism has yet to be identified. Manipulation of the miRNA content of EVs will be important for future therapeutic applications. We therefore wished to assess which endogenous miRNAs are enriched in EVs and how effectively an overexpressed miRNA would be exported.
Small RNA libraries from HEK293T cells and vesicles before or after transfection with a vector for miR-146a overexpression were analysed by deep sequencing. A subset of miRNAs was found to be enriched in EVs; pathway analysis of their predicted target genes suggests a potential role in regulation of endocytosis. RT-qPCR in additional cell types and analysis of publicly available data revealed that many of these miRNAs tend to be widely preferentially exported. Whilst overexpressed miR-146a was highly enriched both in transfected cells and their EVs, the cellular:EV ratios of endogenous miRNAs were not grossly altered. MiR-451 was consistently the most highly exported miRNA in many different cell types. Intriguingly, Argonaute2 (Ago2) is required for miR-451 maturation and knock out of Ago2 has been shown to decrease expression of other preferentially exported miRNAs (eg miR-150 and miR-142-3p).
The global expression data provided by deep sequencing confirms that specific miRNAs are enriched in EVs released by HEK293T cells. Observation of similar patterns in a range of cell types suggests that a common mechanism for selective miRNA export may exist.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Striding explores the modernization process by outlining the economics of agriculture, growth theories of economic development, and problems with growth.During the last century, policy makers and the ...public acquired a considerable interest in economics. As a result, this heightened awareness enhanced the well-being of society.In 1969, the Nobel Foundation initiated the new prize category of economic sciences and started awarding the prize annually. At the forefront of their field, prize winners have introduced many innovative ideas. Moreover, an evaluation of their ideas reveals valuable nuggets to enrich the professional lives of non-economists.Drawing on publications written by the Laureates, Striding with Economic Giants presents the essence of their thoughts in easy-to-understand concepts for the business and academic communities. This book is perfect for business executives, public policy makers, and economics students.It describes logic and experimental frameworks in mathematics, econometrics, behavior modeling, and game theory. Next, Striding presents microeconomic contributions, including production theory, theory of institutions, fundamental ideas of markets, and consumerism. Then, it reviews financial theory in capital markets, portfolio choice, and asset pricing.The book spotlights contributions to the rule of law, public administration, and political science. It also highlights a growing understanding of human capital by tracing demographic trends and describing health, education, minority, and labor economics. Enhancements to macroeconomic theory are featured in economic mechanisms and cycles, managing the economy, and policy making.Striding explores the modernization process by outlining the economics of agriculture, growth theories of economic development, and problems with growth. It illustrates contributions to international economics in trade, finance, and global public policy. Finally, the book showcases contributions to social justice in social equality, income redistribution, and climate change.
This review paper serves to describe the composition and activity of a biologically active carbon (BAC) biofilm used in water purification. An analysis of several physical–chemical, biochemical and ...microbiological methods (indicators) used to characterize the BAC biofilm's composition and activity is provided. As well, the ability of the biofilm to remove and biodegrade waterborne organic substances and pollutants will be reviewed, with context to other industrial processes such as pre-ozonation and post-membrane filtration. Strategies to control the growth of the BAC biofilm, such as varying the nutrient loading rate, manipulating influent DO and pH levels, altering the frequency of BAC filter backwashing and applying oxidative disinfection, will be described in detail along with their respective process control challenges.
This reading of Wordworth's poetry by leading critic David Simpson centres on its almost obsessive representation of spectral forms and images of death in life. Wordsworth is reacting, Simpson ...argues, to the massive changes in the condition of England and the modern world at the turn of the century: mass warfare; the increased scope of machine-driven labour and urbanisation; and the expanding power of commodity form in rendering economic and social exchange more and more abstract, more and more distant from human agency and control. Reading Wordsworth alongside Marx and Derrida, Simpson examines the genesis of an attitude of concern which exemplifies the predicament of modern subjectivity as it faces suffering and distress.
The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve ...the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for ≥3 months. The new classification lists the most common conditions of peripheral neuropathic pain: trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neuralgia, and painful radiculopathy. Conditions of central neuropathic pain include pain caused by spinal cord or brain injury, poststroke pain, and pain associated with multiple sclerosis. Diseases not explicitly mentioned in the classification are captured in residual categories of ICD-11. Conditions of chronic neuropathic pain are either insufficiently defined or missing in the current version of the ICD, despite their prevalence and clinical importance. We provide the short definitions of diagnostic entities for which we submitted more detailed content models to the WHO. Definitions and content models were established in collaboration with the Classification Committee of the IASP's Neuropathic Pain Special Interest Group (NeuPSIG). Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document this public health need and the therapeutic challenges related to chronic neuropathic pain.
Summary Background Treatment of multiple sclerosis with natalizumab is complicated by rare occurrence of progressive multifocal leukoencephalopathy (PML). Between July, 2006, and November, 2009, ...there were 28 cases of confirmed PML in patients with multiple sclerosis treated with natalizumab. Assessment of these clinical cases will help to inform future therapeutic judgments and improve the outcomes for patients. Recent developments The risk of PML increases with duration of exposure to natalizumab over the first 3 years of treatment. No new cases occurred during the first two years of natalizumab marketing but, by the end of November, 2009, 28 cases had been confirmed, of which eight were fatal. The median treatment duration to onset of symptoms was 25 months (range 6–80 months). The presenting symptoms most commonly included changes in cognition, personality, and motor performance, but several cases had seizures as the first clinical event. Although PML has developed in patients without any previous use of disease-modifying therapies for multiple sclerosis, previous therapy with immunosuppressants might increase risk. Clinical diagnosis by use of MRI and detection of JC virus in the CSF was established in all but one case. Management of PML has routinely used plasma exchange (PLEX) or immunoabsorption to hasten clearance of natalizumab and shorten the period in which natalizumab remains active (usually several months). Exacerbation of symptoms and enlargement of lesions on MRI have occurred within a few days to a few weeks after PLEX, indicative of immune reconstitution inflammatory syndrome (IRIS). This syndrome seems to be more common and more severe in patients with natalizumab-associated PML than it is in patients with HIV-associated PML. Where next? Diagnosis of natalizumab-associated PML requires optimised clinical vigilance, reliable and sensitive PCR testing of the JC virus, and broadened criteria for recognition of PML lesions by use of MRI, including contrast enhancement. Optimising the management of IRIS reactions will be needed to improve outcomes. Predictive markers for patients at risk for PML must be sought. It is crucial to monitor the risk incurred during use of natalizumab beyond 3 years.
The term endothelial progenitor cells (EPCs) is currently used to refer to cell populations which are quite dissimilar in terms of biological properties. This study provides a detailed molecular ...fingerprint for two EPC subtypes: early EPCs (eEPCs) and outgrowth endothelial cells (OECs).
Human blood-derived eEPCs and OECs were characterised by using genome-wide transcriptional profiling, 2D protein electrophoresis, and electron microscopy. Comparative analysis at the transcript and protein level included monocytes and mature endothelial cells as reference cell types.
Our data show that eEPCs and OECs have strikingly different gene expression signatures. Many highly expressed transcripts in eEPCs are haematopoietic specific (RUNX1, WAS, LYN) with links to immunity and inflammation (TLRs, CD14, HLAs), whereas many transcripts involved in vascular development and angiogenesis-related signalling pathways (Tie2, eNOS, Ephrins) are highly expressed in OECs. Comparative analysis with monocytes and mature endothelial cells clusters eEPCs with monocytes, while OECs segment with endothelial cells. Similarly, proteomic analysis revealed that 90% of spots identified by 2-D gel analysis are common between OECs and endothelial cells while eEPCs share 77% with monocytes. In line with the expression pattern of caveolins and cadherins identified by microarray analysis, ultrastructural evaluation highlighted the presence of caveolae and adherens junctions only in OECs.
This study provides evidence that eEPCs are haematopoietic cells with a molecular phenotype linked to monocytes; whereas OECs exhibit commitment to the endothelial lineage. These findings indicate that OECs might be an attractive cell candidate for inducing therapeutic angiogenesis, while eEPC should be used with caution because of their monocytic nature.
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