Mung Bean nuclease mapping of RNAs 3' end

A method is described that allows an accurate mapping of 3' ends of RNAs. In this method a labeled DNA probe, containing the presumed 3' end of the RNA under analysis is allowed to anneals to the RNA itself. Mung-bean nuclease is then used to digest single strands of both RNA and DNA. Electrophoretic fractionation of "protected" undigested, labeled DNA is than performed using a sequence reaction of a known DNA as length marker. This procedure was applied to the analysis of both a polyA RNA (Interleukin 10 mRNA) and non polyA RNAs (sea urchin 18S and 26S rRNAs). This method might be potentially relevant for the evaluation of the role of posttrascriptional control of IL-10 in the pathogenesis of the immune and inflammatory mediated diseases associated to ageing. This might allow to develop new strategies to approach to the diagnosis and therapy of age related diseases

The DIANA-mirExTra Web Server: From Gene Expression Data to MicroRNA Function

Background: High-throughput gene expression experiments are widely used to identify the role of genes involved in biological conditions of interest. MicroRNAs (miRNA) are regulatory molecules that have been functionally associated with several developmental programs and their deregulation with diverse diseases including cancer. Methodology/Principal Findings: Although miRNA expression levels may not be routinely measured in high-throughput experiments, a possible involvement of miRNAs in the deregulation of gene expression can be computationally predicted and quantified through analysis of overrepresented motifs in the deregulated genes 39 untranslated region (39UTR) sequences. Here, we introduce a user-friendly web-server, DIANA-mirExTra (www.microrna.gr/mirextra) that allows the comparison of frequencies of miRNA associated motifs between sets of genes that can lead to the identification of miRNAs responsible for the deregulation of large numbers of genes. To this end, we have investigated different approaches and measures, and have practically implemented them on experimental data. Conclusions/Significance: On several datasets of miRNA overexpression and repression experiments, our proposed approaches have successfully identified the deregulated miRNA. Beyond the prediction of miRNAs responsible for the deregulation of transcripts, the web-server provides extensive links to DIANA-mirPath, a functional analysis tool incorporating miRNA targets in biological pathways. Additionally, in case information about miRNA expression changes i

Accurate microRNA Target Prediction Using Detailed Binding Site Accessibility and Machine Learning on Proteomics Data

MicroRNAs (miRNAs) are a class of small regulatory genes regulating gene expression by targeting messenger RNA. Though computational methods for miRNA target prediction are the prevailing means to analyze their function, they still miss a large fraction of the targeted genes and additionally predict a large number of false positives. Here we introduce a novel algorithm called DIANA-microT-ANN which combines multiple novel target site features through an artificial neural network (ANN) and is trained using recently published high-throughput data measuring the change of protein levels after miRNA overexpression, providing positive and negative targeting examples. The features characterizing each miRNA recognition element include binding structure, conservation level, and a specific profile of structural accessibility. The ANN is trained to integrate the features of each recognition element along the 3′untranslated region into a targeting score, reproducing the relative repression fold change of the protein. Tested on two different sets the algorithm outperforms other widely used algorithms and also predicts a significant number of unique and reliable targets not predicted by the other methods. For 542 human miRNAs DIANA-microT-ANN predicts 120000 targets not provided by TargetScan 5.0. The algorithm is freely available at http://microrna.gr/microT-ANN

Systemic Corticosteroids in Asthma : A Call to Action From World Allergy Organization and Respiratory Effectiveness Group

Acknowledgments This manuscript was endorsed by the World Allergy Organization and the Respiratory Effectiveness Group. Editorial support was funded by AstraZeneca and was provided by Katherine Hardy, PhD of Helios Medical Communications, Oxford, Oxfordshire, UK Funding This manuscript was funded by a grant from AstraZeneca. The authors retained full control. AstraZeneca provided a review for scientific accuracy and did not participate in the content development.Peer reviewedPublisher PD

Open innovation in the power & energy sector: Bringing together government policies, companies’ interests, and academic essence

The Power and Energy (P&E) sector needs to respond to several challenges fostering investments in research and development. According to the Open Innovation (OI) paradigm, key stakeholders like utilities, vendors, laboratories, universities etc. should take advantage of external knowledge to improve their innovation performance. Several studies have demonstrated that firms adopting the OI paradigm are more likely to innovate. Despite the interest of P&E firms in enhancing their innovation capabilities, surprisingly few articles (usually case studies) described the implementation of the OI paradigm in P&E firms. This article fills the gap by identifying the key drivers that encourage a firm in the P&E sector to embrace the OI paradigm. The authors adopt a hybrid research approach collecting evidence from the literature and through a multiple case-study analysis involving seven British firms and universities operating in the P&E industry. As the drivers of OI have mutual influence, this article describes them with a fuzzy cognitive map. Finally, the authors identify appropriated policies to enhance the OI adoption and, consequently, the sustainability of innovation in the P&E sector. A salient research agenda closes the paper

Accurate microRNA target prediction correlates with protein repression levels

MicroRNAs are small endogenously expressed non-coding RNA molecules that regulate target gene expression through translation repression or messenger RNA degradation. MicroRNA regulation is performed through pairing of the microRNA to sites in the messenger RNA of protein coding genes. Since experimental identification of miRNA target genes poses difficulties, computational microRNA target prediction is one of the key means in deciphering the role of microRNAs in development and diseas

EAACI Biologicals Guidelines-Recommendations for severe asthma

Severe asthma imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include selection of a certain biological (as they all target overlapping disease phenotypes), the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness. The EAACI Guidelines on the use of biologicals in severe asthma follow the GRADE approach in formulating recommendations for each biological and each outcome. In addition, a management algorithm for the use of biologicals in the clinic is proposed, together with future approaches and research priorities.Peer reviewe

Exploring definitions and predictors of severe asthma clinical remission post-biologic in adults

Peer reviewe

Characterization of patients in the International Severe Asthma Registry with high steroid exposure who did or did not initiate biologic therapy

Peer reviewedPostprin

Next-generation care pathways for allergic rhinitis and asthma multimorbidity:a model for multimorbid non-communicable diseases-Meeting Report (Part 1)

International audienceIn all societies, the burden and cost of allergic and chronic respiratory diseases are increasing rapidly. Most economies are struggling to deliver modern health care effectively. There is a need to support the transformation of the health care system for integrated care with organizational health literacy. MASK (Mobile Airways Sentinel NetworK) (1), a new development of the ARIA (Allergic Rhinitis and its Impact on Asthma) initiative, and POLLAR (Impact of Air POLLution on Asthma and Rhinitis, EIT Health) (2), in collaboration with professional and patient organizations in the field of allergy and airway diseases, are proposing real-life integrated care pathways (ICPs) (3)-centred around the patient with rhinitis and using mHealth monitoring of environmental exposure (4).An expert meeting took place at the Pasteur Institute in Paris, December 3, 2018. The aim was to discuss next-generation care pathways: (I) Patient participation, health literacy and self-care through technology-assisted “patient activation”; (II) Implementation of care pathways by pharmacists and (III) Next-generation guidelines assessing the recommendations of GRADE guidelines in rhinitis and asthma using real-world evidence (RWE) assessed by mobile technology.The EU (5) and global political agendas are of great importance in supporting health care transformation. MASK has been recognized by DG Santé as a Good Practice (6) in the field of digitally-enabled, integrated, person-centred care.The one-day meeting objectives were clear (Figure 1). The meeting was followed by a workshop. The present paper reports the background of the two-day meeting