This paper surveys the variables controlling the lattice structure and charge in macroscopic Coulombic crystals made from electrically charged, millimeter-sized polymer objects (spheres, cubes, and cylinders). Mechanical agitation of these objects inside planar, bounded containers caused them to charge electrically through contact electrification, and to selfassemble. The processes of electrification and self-assembly, and the characteristics of the assemblies, depended on the type of motion used for agitation, on the type of materials used for the objects and the dish, on the size and shape of the objects and the dish, and on the number of objects. Each of the three different materials in the system (of the dish and of the two types of spheres) influenced the electrification. Three classes of structures formed by self-assembly, depending on the experimental conditions: two-dimensional lattices, onedimensional chains, and zero-dimensional 'rosettes'. The lattices were characterized by their structure (disordered, square, rhombic, or hexagonal) and by the electrical charges of individual objects; the whole lattices were approximately electrically neutral. The lattices observed in this study were qualitatively different from ionic crystals; the charge of objects had practically continuous values which changed during agitation and self-assembly, and depended on experimental conditions which included the lattice structure itself. The relationship between charge and structure led to the coexistence of regions with different lattice structures within the same assembly, and to transformations between different lattice structures during agitation.2
Post-transcriptional RNA modifications (PTxMs) present in small RNA species, specifically circulating extracellular RNAs, were recently identified as clinically relevant readouts, often more indicative of disease severity than the classical up and down changes in their copy number alone. While identification of PTxMs requires multiple and complex sample preparation steps, microgram-range amounts of RNA, followed by expensive and protracted bioinformatics analyses, the clinically relevant information is usually a yes/no for a particular genetic variant(s), and an up/down answer for relevant biomarkers. We have previously shown that molecular beacons (MBs) can identify specific nucleic acid sequences with picomolar sensitivity and single nucleotide specificity by exploiting the target-dependent change in their electrophoretic mobility profile. We now present a method for direct identification of miRNAs and isomiRs in cells and extracellular vesicles using gel electrophoresis, without the need for RNA isolation and purification. The detection is based on discreet changes in the hydrodynamic surface profile, the overall size, charge and charge distribution of the MB-target hybrid. Furthermore, using an RNA tertiary structure prediction algorithm (iFoldRNA) and a custom molecular dynamics simulation (DMD), we designed modified MBs specific for m6A-modified nucleotides in target RNA sequences. The sample preparation method coupled to the software package affords the design of specific MBs and sensitive, multiplex-type detection of targets in a wide variety of biofluids and cells, in a simple mix and read approach.
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