RNApredator: fast accessibility-based prediction of sRNA targets

Bacterial genomes encode a plethora of small RNAs (sRNAs), which are heterogeneous in size, structure and function. Most sRNAs act as post-transcriptional regulators by means of specific base pairing interactions with the 5′-untranslated region of mRNA transcripts, thereby modifying the stability of the target transcript and/or its ability to be translated. Here, we present RNApredator, a web server for the prediction of sRNA targets. The user can choose from a set of over 2155 genomes and plasmids from 1183 bacterial species. RNApredator then uses a dynamic programming approach, RNAplex, to compute putative targets. Compared to web servers with a similar task, RNApredator takes the accessibility of the target during the target search into account, improving the specificity of the predictions. Furthermore, enrichment in Gene Ontology terms, cellular pathways as well as changes in accessibilities along the target sequence can be done in fully automated post-processing steps. The predictive performance of the underlying dynamic programming approach RNAplex is similar to that of more complex methods, but needs at least three orders of magnitude less time to complete. RNApredator is available at http://rna.tbi.univie.ac.at/RNApredator

The long noncoding RNA mimi scaffolds neuronal granules to maintain nervous system maturity

RNA binding proteins and messenger RNAs (mRNAs) assemble into ribonucleoprotein granules that regulate mRNA trafficking, local translation, and turnover. The dysregulation of RNA-protein condensation disturbs synaptic plas-ticity and neuron survival and has been widely associated with human neurological disease. Neuronal granules are thought to condense around particular proteins that dictate the identity and composition of each granule type. Here, we show in Drosophila that a previously uncharacterized long noncoding RNA, mimi, is required to scaffold large neuronal granules in the adult nervous system. Neuronal ELAV-like proteins directly bind mimi and mediate granule assembly, while Staufen maintains condensate integrity. mimi granules contain mRNAs and proteins involved in synaptic processes; granule loss in mimi mutant flies impairs nervous system maturity and neuropeptide-mediated signaling and causes phenotypes of neurodegeneration. Our work reports an architectural RNA for a neuronal granule and provides a handle to interrogate functions of a condensate independently of those of its constituent proteins

The RNA workbench: best practices for RNA and high-throughput sequencing bioinformatics in Galaxy

RNA-based regulation has become a major research topic in molecular biology. The analysis of epigenetic and expression data is therefore incomplete if RNA-based regulation is not taken into account. Thus, it is increasingly important but not yet standard to combine RNA-centric data and analysis tools with other types of experimental data such as RNA-seq or ChIP-seq. Here, we present the RNA workbench, a comprehensive set of analysis tools and consolidated workflows that enable the researcher to combine these two worlds. Based on the Galaxy framework the workbench guarantees simple access, easy extension, flexible adaption to personal and security needs, and sophisticated analyses that are independent of command-line knowledge. Currently, it includes more than 50 bioinformatics tools that are dedicated to different research areas of RNA biology including RNA structure analysis, RNA alignment, RNA annotation, RNA-protein interaction, ribosome profiling, RNA-seq analysis and RNA target prediction. The workbench is developed and maintained by experts in RNA bioinformatics and the Galaxy framework. Together with the growing community evolving around this workbench, we are committed to keep the workbench up-to-date for future standards and needs, providing researchers with a reliable and robust framework for RNA data analysis. Availability: The RNA workbench is available at https://github.com/bgruening/galaxy-rna-workbench

The RNA workbench: Best practices for RNA and high-throughput sequencing bioinformatics in Galaxy

RNA-based regulation has become a major research topic in molecular biology. The analysis of epigenetic and expression data is therefore incomplete if RNA-based regulation is not taken into account. Thus, it is increasingly important but not yet standard to combine RNA-centric data and analysis tools with other types of experimental data such as RNA-seq or ChIP-seq. Here, we present the RNA workbench, a comprehensive set of analysis tools and consolidated workflows that enable the researcher to combine these two worlds. Based on the Galaxy framework the workbench guarantees simple access, easy extension, flexible adaption to personal and security needs, and sophisticated analyses that are independent of command-line knowledge. Currently, it includes more than 50 bioinformatics tools that are dedicated to different research areas of RNA biology including RNA structure analysis, RNA alignment, RNA annotation, RNA-protein interaction, ribosome profiling, RNA-seq analysis and RNA target prediction. The workbench is developed and maintained by experts in RNA bioinformatics and the Galaxy framework. Together with the growing community evolving around this workbench, we are committed to keep the workbench up-to-date for future standards and needs, providing researchers with a reliable and robust framework for RNA data analysis

Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion

Mesenchymal stem cells (MSC) are under investigation as a therapy for a variety of disorders. Although animal models show long term regenerative and immunomodulatory effects of MSC, the fate of MSC after infusion remains to be elucidated. In the present study the localization and viability of MSC was examined by isolation and re-culture of intravenously infused MSC. C57BL/6 MSC (500,000) constitutively expressing DsRed-fluorescent protein and radioactively labeled with Cr-51 were infused via the tail vein in wild-type C57BL/6 mice. After 5 min, 1, 24, or 72 h, mice were sacrificed and blood, lungs, liver, spleen, kidneys, and bone marrow removed. One hour after MSC infusion the majority of Cr-51 was found in the lungs, whereas after 24 h Cr-51 was mainly found in the liver. Tissue cultures demonstrated that viable donor MSC were present in the lungs up to 24 h after infusion, after which they disappeared. No viable MSC were found in the other organs examined at any time. The induction of ischemia-reperfusion injury in the liver did not trigger the migration of viable MSC to the liver. These results demonstrate that MSC are short-lived after i.v. infusion and that viable MSC do not pass the lungs. Cell debris may be transported to the liver. Long term immunomodulatory and regenerative effects of infused MSC must therefore be mediated via other cell types

Are mesenchymal stromal cells immune cells?

Mesenchymal stromal cells (MSCs) are considered to be promising agents for the treatment of immunological disease. Although originally identified as precursor cells for mesenchymal lineages, in vitro studies have demonstrated that MSCs possess diverse immune regulatory capacities. Pre-clinical models have shown beneficial effects of MSCs in multiple immunological diseases and a number of phase 1/2 clinical trials carried out so far have reported signs of immune modulation after MSC infusion. These data indicate that MSCs play a central role in the immune response. This raises the academic question whether MSCs are immune cells or whether they are tissue precursor cells with immunoregulatory capacity. Correct understanding of the immunological properties and origin of MSCs will aid in the appropriate and safe use of the cells for clinical therapy. In this review the whole spectrum of immunological properties of MSCs is discussed with the aim of determining the position of MSCs in the immune system

Careers in context: An international study of career goals as mesostructure between societies' career-related human potential and proactive career behaviour

Careers exist in a societal context that offers both constraints and opportunities for career actors. Whereas most studies focus on proximal individual and/or organisational-level variables, we provide insights into how career goals and behaviours are understood and embedded in the more distal societal context. More specifically, we operationalise societal context using the career-related human potential composite and aim to understand if and why career goals and behaviours vary between countries. Drawing on a model of career structuration and using multilevel mediation modelling, we draw on a survey of 17,986 employees from 27 countries, covering nine of GLOBE's 10 cultural clusters, and national statistical data to examine the relationship between societal context (macrostructure building the career-opportunity structure) and actors' career goals (career mesostructure) and career behaviour (actions). We show that societal context in terms of societies' career-related human potential composite is negatively associated with the importance given to financial achievements as a specific career mesostructure in a society that is positively related to individuals' proactive career behaviour. Our career mesostructure fully mediates the relationship between societal context and individuals' proactive career behaviour. In this way, we expand career theory's scope beyond occupation- and organisation-related factors

Future Perspectives of Bone Tissue Engineering with Special Emphasis on Extracellular Vesicles

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