Introduction history and population genetics of intracontinental scotch broom ( Cytisus scoparius

Abstract Aim: Biological invasions at the intracontinental scale are poorly studied, and intracontinental invasions often remain cryptic. Here, we investigate the recent range expansion of scotch broom (Cytisus scoparius) into Norway and clarify whether the genetic patterns indicate natural spread or human introduction. Furthermore, we investigate whether plants were moved within the native range and how this influences invasion success. We also infer the level and structuring of genetic diversity within and between the putative native and introduced range. Location: Europe. Methods: We analysed the chloroplast sequence variation in 267 scotch broom samples from its northern expansion front and from its native range across Europe, including herbarium samples dating back to 1835. For 37 populations, we analysed variation in nuclear single‐nucleotide polymorphic markers to study gene flow and genetic diversity. Results: We identified 20 different haplotypes, which lacked spatial and temporal distribution patterns in the recent expansion range in Norway. They also mostly lacked patterns across the native European range of scotch broom. The genetic diversity of nuclear genomic SNP markers across populations in the introduced range was similar to that of populations in the native range, with limited differentiation among populations. Main conclusions: Scotch broom is alien to Norway and was introduced by humans on multiple occasions from diverse origins over a long period of time. High propagule pressure has probably maintained the high genetic diversity in the novel range through a combination of genetically diverse source populations and high gene flow among them. Within the native European range, our results suggest the presence of cryptic intraspecific admixture, most likely mediated by humans moving genotypes among the regions occupied by distinct native genotypes. Intracontinental invasions may easily go unnoticed and revealing these invasions and the factors driving them may be of great importance for the management of alien species.publishedVersio

Targeting tumour energy metabolism potentiates the cytotoxicity of 5-aminolevulinic acid photodynamic therapy

Background:Cancerous cells usually exhibit increased aerobic glycolysis, compared with normal tissue (the Warburg effect), making this pathway an attractive therapeutic target. Methods:Cell viability, cell number, clonogenic assay, reactive oxygen (ROS), ATP, and apoptosis were assayed in MCF-7 tumour cells and corresponding primary human mammary epithelial cells (HMEC). Results:Combining the glycolysis inhibitors 2-deoxyglucose (2DG; 180 mM) or lonidamine (300 μM) with 10 J cm-2 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) increases MCF-7 cytotoxicity (by 3.5-fold to 70% death after 24 h, and by 10-fold in 9-day clonogenic assays). However, glycolysis inhibition only slightly increases HMEC PDT cytotoxicity (between two-fold and three-fold to a maximum of 9% death after 24 h). The potentiation of PDT cytotoxicity only occurred if the glycolysis inhibitors were added after ALA incubation, as they inhibited intracellular accumulation of photosensitiser if coincubated with ALA. Conclusion:As 2DG and lonidamine are already used as cancer chemotherapeutic agents, our results are directly translatable to combination therapies with existing topical PD

Homology Modeling of Human c-Butyric Acid Transporters and the Binding of Pro-Drugs 5-Aminolevulinic Acid and Methyl Aminolevulinic Acid Used in Photodynamic Therapy

Photodynamic therapy (PDT) is a safe and effective method currently used in the treatment of skin cancer. In ALA-basedPDT, 5-aminolevulinic acid (ALA), or ALA esters, are used as pro-drugs to induce the formation of the potent photosensitizerprotoporphyrin IX (PpIX). Activation of PpIX by light causes the formation of reactive oxygen species (ROS) and toxicresponses. Studies have indicated that ALA and its methyl ester (MAL) are taken up into the cells via c-butyric acid (GABA)transporters (GATs). Uptake via GATs into peripheral sensory nerve endings may also account for one of the few adverseside effects of ALA-based PDT, namely pain. In the present study, homology models of the four human GAT subtypes wereconstructed using three x-ray crystal structures of the homologous leucine transporter (LeuT) as templates. Binding of thenative substrate GABA and the possible substrates ALA and MAL was investigated by molecular docking of the ligands intothe central putative substrate binding sites in the outward-occluded GAT models. Electrostatic potentials (ESPs) of theputative substrate translocation pathway of each subtype were calculated using the outward-open and inward-openhomology models. Our results suggested that ALA is a substrate of all four GATs and that MAL is a substrate of GAT-2, GAT-3and BGT-1. The ESP calculations indicated that differences likely exist in the entry pathway of the transporters (i.e. inoutward-open conformations). Such differences may be exploited for development of inhibitors that selectively targetspecific GAT subtypes and the homology models may hence provide tools for design of therapeutic inhibitors that can beused to reduce ALA-induced pain.<p><em>©</em>2013 Baglo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p