Proposing candidate genes under telomeric control based on cross-species position data.

In this paper, we present a comprehensive computational framework aimed at suggesting genes whose transcriptional regulation is likely to be influenced by their chromosomal position. This framework provides a user-friendly web interface, enabling researchers to explore the positional properties of all human genes and their orthologs across species, with a focus on their relation to the telomeres. Our approach involves multiple scoring methods, each adjustable by users, representing different features of the genes' positional variation across species. The resulting rankings can be combined to identify candidate genes that may be subject to position effects. Furthermore, the ranking can be tailored to a specific set of reference genes. We evaluate the method within the context of TPE-OLD, a mechanism where telomeres can exert a direct influence on gene expression across considerable genomic distances, and empower researchers to delve deeper into genes of interest, analyzing their position across species and estimating their susceptibility to position effects like TPE-OLD. We also provide simple enrichment analyses of user-provided gene lists in relation to top-ranking candidate genes.

γ-Cyclodextrin hydrogel for the sustained release of josamycin for potential ocular application.

Glaucoma is the leading cause of blindness worldwide. However, its surgical treatment, in particular via trabeculectomy, can be complicated by fibrosis. In current clinical practice, application of the drug, Mitomycin C, prevents or delays fibrosis, but can lead to additional side effects, such as bleb leakage and hypotony. Previous in silico drug screening and in vitro testing has identified the known antibiotic, josamycin, as a possible alternative antifibrotic medication with potentially fewer side effects. However, a suitable ocular delivery mechanism for the hydrophobic drug to the surgical site does not yet exist. Therefore, the focus of this paper is the development of an implantable drug delivery system for sustained delivery of josamycin after glaucoma surgery based on crosslinked γ-cyclodextrin. γ-Cyclodextrin is a commonly used solubilizer which was shown to complex with josamycin, drastically increasing the drug's solubility in aqueous solutions. A simple γ-cyclodextrin crosslinking method produced biocompatible hydrogels well-suited for implantation. The crosslinked γ - cyclodextrin retained the ability to form complexes with josamycin, resulting in a 4-fold higher drug loading efficiency when compared to linear dextran hydrogels, and prolonged drug release over 4 days.