G-quadruplex structures within the 3' UTR of LINE-1 elements stimulate retrotransposition

Long interspersed nuclear elements (LINEs) are ubiquitous transposable elements in higher eukaryotes that have a significant role in shaping genomes, owing to their abundance. Here we report that guanine-rich sequences in the 3' untranslated regions (UTRs) of hominoid-specific LINE-1 elements are coupled with retrotransposon speciation and contribute to retrotransposition through the formation of G-quadruplex (G4) structures. We demonstrate that stabilization of the G4 motif of a human-specific LINE-1 element by small-molecule ligands stimulates retrotransposition.S.B. is a Wellcome Trust Senior Investigator (grant 099232/z/12/z). The Balasubramanian group is supported by European Research Council Advanced Grant 339778, and receives core (C14303/A17197) and program (C9681/A18618) funding from Cancer Research UK

The Impact of Logistics on Marketing Margin in the Philippine Agricultural Sector

The logistics industry is a fundamental aspect of fulfilling the supply chain in agriculture. Agricultural farmers in the Philippines often use the services of middlemen to transact on their behalf since these intermediaries possess better information, and engaging in logistics affects the marketing margin in the process. Frequently, logistics costs cause marketing margin to increase, leading to high farm-retail prices of agricultural goods. This paper examines if the existence of middlemen improves farmers' wages even with the additional logistics costs incurred. The variables' secondary data were all gathered from the Philippine Statistics Authority, and its annual frequency spanned the period of 1995 to 2019. Using Ordinary Least Squares (OLS) regression analysis procedure and diagnostic tests prove that logistics cost negatively affects marketing margin while farmers' wages have a positive relationship. The findings of this study address the presence of a longer supply chain, asymmetric information, technology, storage and facilities, and added logistics costs in agricultural transactions. Although middlemen have greater market power than the farmers, these mediators are still affected by the changes in the logistics costs since it is unavoidable for them to reduce the price due to the need to competitively sell the commodities

Expanding the druggable space of the LSD1/CoREST epigenetic target: New potential binding regions for drug-like molecules, peptides, protein partners, and chromatin

Lysine specific demethylase-1 (LSD1/KDM1A) in complex with its corepressor protein CoREST is a promising target for epigenetic drugs. No therapeutic that targets LSD1/CoREST, however, has been reported to date. Recently, extended molecular dynamics (MD) simulations indicated that LSD1/CoREST nanoscale clamp dynamics is regulated by substrate binding and highlighted key hinge points of this large-scale motion as well as the relevance of local residue dynamics. Prompted by the urgent need for new molecular probes and inhibitors to understand LSD1/CoREST interactions with small-molecules, peptides, protein partners, and chromatin, we undertake here a configurational ensemble approach to expand LSD1/CoREST druggability. The independent algorithms FTMap and SiteMap and our newly developed Druggable Site Visualizer (DSV) software tool were used to predict and inspect favorable binding sites. We find that the hinge points revealed by MD simulations at the SANT2/Tower interface, at the SWIRM/AOD interface, and at the AOD/Tower interface are new targets for the discovery of molecular probes to block association of LSD1/CoREST with chromatin or protein partners. A fourth region was also predicted from simulated configurational ensembles and was experimentally validated to have strong binding propensity. The observation that this prediction would be prevented when using only the X-ray structures available (including the X-ray structure bound to the same peptide) underscores the relevance of protein dynamics in protein interactions. A fifth region was highlighted corresponding to a small pocket on the AOD domain. This study sets the basis for future virtual screening campaigns targeting the five novel regions reported herein and for the design of LSD1/CoREST mutants to probe LSD1/CoREST binding with chromatin and various protein partners