Abstract
microRNAs (miRNAs) are short (∼23nt) single-stranded non-coding RNAs that act as potent post-transcriptional gene expression regulators. Information about miRNA expression and distribution ...across cell types and tissues is crucial to the understanding of their function and for their translational use as biomarkers or therapeutic targets. DIANA-miTED is the most comprehensive and systematic collection of miRNA expression values derived from the analysis of 15 183 raw human small RNA-Seq (sRNA-Seq) datasets from the Sequence Read Archive (SRA) and The Cancer Genome Atlas (TCGA). Metadata quality maximizes the utility of expression atlases, therefore we manually curated SRA and TCGA-derived information to deliver a comprehensive and standardized set, incorporating in total 199 tissues, 82 anatomical sublocations, 267 cell lines and 261 diseases. miTED offers rich instant visualizations of the expression and sample distributions of requested data across variables, as well as study-wide diagrams and graphs enabling efficient content exploration. Queries also generate links towards state-of-the-art miRNA functional resources, deeming miTED an ideal starting point for expression retrieval, exploration, comparison, and downstream analysis, without requiring bioinformatics support or expertise. DIANA-miTED is freely available at http://www.microrna.gr/mited.
microRNAs (miRNAs) are short non-coding RNA species, which act as potent gene expression regulators. Accurate identification of miRNA targets is crucial to understanding their function. Currently, ...hundreds of thousands of miRNA:gene interactions have been experimentally identified. However, this wealth of information is fragmented and hidden in thousands of manuscripts and raw next-generation sequencing data sets. DIANA-TarBase was initially released in 2006 and it was the first database aiming to catalog published experimentally validated miRNA:gene interactions. DIANA-TarBase v7.0 (http://www.microrna.gr/tarbase) aims to provide for the first time hundreds of thousands of high-quality manually curated experimentally validated miRNA:gene interactions, enhanced with detailed meta-data. DIANA-TarBase v7.0 enables users to easily identify positive or negative experimental results, the utilized experimental methodology, experimental conditions including cell/tissue type and treatment. The new interface provides also advanced information ranging from the binding site location, as identified experimentally as well as in silico, to the primer sequences used for cloning experiments. More than half a million miRNA:gene interactions have been curated from published experiments on 356 different cell types from 24 species, corresponding to 9- to 250-fold more entries than any other relevant database. DIANA-TarBase v7.0 is freely available.
Diabetic foot ulceration (DFU) is a devastating complication of diabetes whose pathogenesis remains incompletely understood. Here, we profile 174,962 single cells from the foot, forearm, and ...peripheral blood mononuclear cells using single-cell RNA sequencing. Our analysis shows enrichment of a unique population of fibroblasts overexpressing MMP1, MMP3, MMP11, HIF1A, CHI3L1, and TNFAIP6 and increased M1 macrophage polarization in the DFU patients with healing wounds. Further, analysis of spatially separated samples from the same patient and spatial transcriptomics reveal preferential localization of these healing associated fibroblasts toward the wound bed as compared to the wound edge or unwounded skin. Spatial transcriptomics also validates our findings of higher abundance of M1 macrophages in healers and M2 macrophages in non-healers. Our analysis provides deep insights into the wound healing microenvironment, identifying cell types that could be critical in promoting DFU healing, and may inform novel therapeutic approaches for DFU treatment.
As the relevant literature and the number of experiments increase at a super linear rate, databases that curate and collect experimentally verified microRNA (miRNA) targets have gradually emerged. ...These databases attempt to provide efficient access to this wealth of experimental data, which is scattered in thousands of manuscripts. Aim of TarBase 6.0 (http://www.microrna.gr/tarbase) is to face this challenge by providing a significant increase of available miRNA targets derived from all contemporary experimental techniques (gene specific and high-throughput), while incorporating a powerful set of tools in a user-friendly interface. TarBase 6.0 hosts detailed information for each miRNA-gene interaction, ranging from miRNA- and gene-related facts to information specific to their interaction, the experimental validation methodologies and their outcomes. All database entries are enriched with function-related data, as well as general information derived from external databases such as UniProt, Ensembl and RefSeq. DIANA microT miRNA target prediction scores and the relevant prediction details are available for each interaction. TarBase 6.0 hosts the largest collection of manually curated experimentally validated miRNA-gene interactions (more than 65 000 targets), presenting a 16.5-175-fold increase over other available manually curated databases.
microRNAs (miRNAs) are central regulators of gene expression. They are actively studied for their involvement in numerous physiological and pathological conditions but also as diagnostic biomarkers ...or promising therapeutic targets. The increased complexity of the miRNA interactomes hinders straightforward interpretation of miRNA expression differences between states and conditions. To this end, functional analysis web servers process and combine experimental and in silico data, enabling researchers to uncover targeted pathways and transcriptional mechanisms that are hidden within numerous interactions and vast expression datasets. DIANA-tools ( www.microrna.gr ) is a web server hosting state-of-the-art utilities and databases for miRNA functional investigation. Available utilities cover a wide scope of different needs and research scenarios, rendering DIANA website a one-stop-shop for miRNA analyses. The most commonly utilized databases and algorithms include DIANA-microT-CDS, DIANA-TarBase v7.0, DIANA-lncBase v2.0, DIANA-miRGen v3.0, DIANA-miRPath v3.0, and DIANA-mirExTra v2.0.In the presented protocol, we will utilize different online tools in order to explore miRNA functions and to identify probable targets of interest for downstream analyses and wet lab experiments. The combined use of different applications from the DIANA suite can shed light to numerous different aspects of miRNA regulation and regulatory function, without the necessity for extensive bioinformatics expertise or computational infrastructure.
α-Synuclein (αSyn) is the major gene linked to sporadic Parkinson’s disease (PD), whereas the G209A (p.A53T) αSyn mutation causes a familial form of PD characterized by early onset and a generally ...severe phenotype, including nonmotor manifestations. Here we generated de novo induced pluripotent stem cells (iPSCs) from patients harboring the p.A53T mutation and developed a robust model that captures PD pathogenic processes under basal conditions. iPSC-derived mutant neurons displayed novel disease-relevant phenotypes, including protein aggregation, compromised neuritic outgrowth, and contorted or fragmented axons with swollen varicosities containing αSyn and Tau. The identified neuropathological features closely resembled those in brains of p.A53T patients. Small molecules targeting αSyn reverted the degenerative phenotype under both basal and induced stress conditions, indicating a treatment strategy for PD and other synucleinopathies. Furthermore, mutant neurons showed disrupted synaptic connectivity and widespread transcriptional alterations in genes involved in synaptic signaling, a number of which have been previously linked to mental disorders, raising intriguing implications for potentially converging disease mechanisms.
In this article we present a simulated annealing based algorithm for the determination of optimal ship routes through the minimization of a cost function defined as a weighted sum of the time of ...voyage and the voyage comfort (safety is taken into account too). This cost function is dependent on the wind speed and its direction as well as on the wave height and its direction. The constructed algorithm at the beginning discretizes an initial route and then optimizes it by considering small deviations, which are accepted or rejected by utilizing the simulated annealing technique. Using calculus of variations, we prove a key theorem which tremendously accelerates the convergence of the proposed algorithm. For an illustration of the advantages of the constructed method, both computational and real experiments have been carried out which are presented and discussed.
Abstract Multirotor UAVs have become an essential tool in a wider range of applications, including among others disaster management, and search and rescue (SAR) operations. Typically, these systems ...operate outdoors, with their guidance and positioning being based primarily on GPS. This work is focused on the design and optimization of a multirotor UAV specifically tailored for indoor SAR applications, where GPS signal is unavailable, and obstacles are prevalent. The design incorporates a lightweight frame structure, in order to increase the UAV’s payload capability. This is necessary, since the UAV requires multiple obstacle recognition and avoidance sensors, as well as thermal and optical cameras, to successfully accomplish its mission objectives in a GPS-denied environment. Towards this goal, various trade studies were conducted including different motor/propeller configurations and airframe FEM analyses. The aerodynamic performance of the UAV is evaluated also, using dedicated CFD analyses that incorporate the effect of propellers. Lastly, a prototype of the designed configuration is produced using additive manufacturing methods and initial flight tests of the UAV are performed.
Abstract In the recent years a rapid increase of multirotor UAVs in the commercial market is observed resulting in a large number of motor/propeller concepts and thrust architectures. The limited ...availability of data for the aerodynamic performance of the motor/propeller system often leads to a non-optimal operation on multirotor UAVs design points. Since experimental investigations are both cost- and time-demanding, the accurate CFD modeling of UAV propellers is crucial and highly supportive in the early design phases of multirotor UAVs. In the current study, a CFD framework is employed for the performance investigation of a small-scale three-blade propeller on a lightweight micro quadrotor UAV, designed for indoor search and rescue operations. More specifically, two widely implemented methods for propeller modeling are examined, namely the Multiple Reference Frame (MRF) and the Sliding Mesh (SM). Several operating points are investigated, corresponding to different propeller rotating speeds (RPM) and Reynolds numbers. The accuracy of each method is evaluated by comparing the CFD results with those obtained from literature experimental data. Finally, the uncertainty of the computational methods is quantified through Richardson’s extrapolation method.
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