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PRPF31-associated retinitis pigmentosa presents a fascinating enigma: some mutation carriers are blind, while others are asymptomatic. We identify the major molecular cause of this incomplete penetrance through three cardinal features: (1) there is population variation in the number (3 or 4) of a minisatellite repeat element (MSR1) adjacent to the PRPF31 core promoter; (2) in vitro, 3-copies of the MSR1 element can repress gene transcription by 50 to 115-fold; (3) the higher-expressing 4-copy allele is not observed among symptomatic PRPF31 mutation carriers and correlates with the rate of asymptomatic carriers in different populations. Thus, a linked transcriptional modifier decreases PRPF31 gene expression that leads to haploinsufficiency. This result, taken with other identified risk alleles, allows precise genetic counseling for the first time. We also demonstrate that across the human genome, the presence of MSR1 repeats in the promoters or first introns of genes is associated with greater population variability in gene expression indicating that copy number variation of MSR1s is a generic controller of gene expression and promises to provide new insights into our understanding of gene expression regulation.

Recently, carbon dots (CDs) have become one of the most sought nanomaterials for biological applications owing to their excellent fluorescence, chemical inertness and biocompatibility. This article depicts the generation of a fluorescent nano probe using CDs for viewing bone cracks and simultaneous drug delivery to the cracked or infected sites. Water soluble polyethylene glycol diamine capped CDs were conjugated with glutamic acid (GA), a calcium targeting ligand, and ciprofloxacin as an antibacterial model drug. Physicochemical characterizations, cytotoxicity evaluation, haemolysis and antibacterial activity studies of the synthesized probe and its ability to target onto bone are demonstrated. Our results indicate that there is significant scope in developing functionalized CDs as theranostic agents.

This article depicts a simple and novel approach to locate calcium deposits in bone using modified carbon dots (CDs) through fluorescence imaging. Amino-functionalized CDs along with glutamic acid, a naturally-occurring ligand for calcium ions, were conjugated onto hyaluronic acid using EDC chemistry. The ability of the probe to recognise Ca ions was demonstrated using polymer strips doped with Ca ions and freshly collected bones. The probe was found to bind more at bone cracks, reflecting its potential to locate micro-cracks in bone as well as to map Ca deposits. The bound portions can be visualized through a fluorescence microscope or by illumination by a UV source (365 nm). The components used to generate the probes, namely CD, glutamic acid and hyaluronic acid, are well known for their non-toxicity and biocompatibility. It appears, therefore, that the probe could be used for in vivo applications.