Uptake epithelia behave in a cell-centric and not systems homeostatic manner in response to zinc depletion and supplementation.

Much remains to be understood about systemic regulation of zinc uptake in vertebrates, and adequate zinc status is far from always achieved in animals or human. In addition to absorbing zinc from the diet, fish are able to take up zinc directly from the water with the gills. This provides an elegant system to study zinc uptake, how it relates to zinc status, and the expression of genes for proteins involved in zinc acquisition.

Dynamic transcriptomic profiles of zebrafish gills in response to zinc supplementation.

Background: Dietary zinc supplementation may help to promote growth, boost the immune system, protect against diabetes, and aid recovery from diarrhoea. We exploited the zebrafish (Danio rerio) gill as a unique vertebrate ion transporting epithelium model to study the time-dependent regulatory networks of gene-expression leading to homeostatic control during zinc supplementation. This organ forms a conduit for zinc uptake whilst exhibiting conservation of zinc trafficking components.

Dynamic transcriptomic profiles of zebrafish gills in response to zinc depletion.

Background: Zinc deficiency is detrimental to organisms, highlighting its role as an essential micronutrient contributing to numerous biological processes. To investigate the underlying molecular events invoked by zinc depletion we performed a temporal analysis of transcriptome changes observed within the zebrafish gill. This tissue represents a model system for studying ion absorption across polarised epithelial cells as it provides a major pathway for fish to acquire zinc directly from water whilst sharing a conserved zinc transporting system with mammals.

ABCG2-associated resistance to Hoechst 33342 and topotecan in a murine cell model with constitutive expression of side population characteristics.

Drug resistant tumor "side-populations," enriched in cancer stem cells and identified by reduced accumulation of Hoechst 33342 under ABCG2-mediated efflux, may compromise therapeutic outcome. Side-population cells have predicted resistance to minor groove ligands, including the DNA topoisomerase I poison topotecan. We have used a stable Hoechst 33342-resistant murine L cell system (HoeR415) to study resistance patterns, removing the need for SP isolation before microarray analysis of gene expression and the tracking of cell cycle dynamics and cytotoxicity.

Zinc-controlled gene expression by metal-regulatory transcription factor 1 (MTF1) in a model vertebrate, the zebrafish.

There is a growing appreciation for the diverse roles of zinc as a signalling substance in biological systems. Zinc signalling is brought about by changes in intracellular concentrations of labile Zn(2+), resulting in both genomic and non-genomic effects. The genomic responses are largely mediated by MTF1 (metal-regulatory transcription factor 1), which binds to MREs (metal-response elements) in the 5' regulatory region of genes in response to zinc.

Regulation of ZIP and ZnT zinc transporters in zebrafish gill: zinc repression of ZIP10 transcription by an intronic MRE cluster.

Resolving the mechanisms underlying the temporal and spatial profile of zinc transporter expression in response to zinc availability is key to understanding zinc homeostasis. The mRNA expression of seven zinc transporters was studied in zebrafish gills when treated with zinc deficiency/excess over a 14-day period. Of these, ZnT1, ZnT5, ZIP3, and ZIP10 were differentially expressed in response to changed zinc status.

Autofluorescence in eleocytes of some earthworm species.

Immunocompetent cells of earthworms, coelomocytes, comprise adherent amoebocytes and granular eleocytes (chloragocytes). Both cell populations can be expelled via dorsal pores of adult earthworms by exposure to an electric current (4.5 V) for 1 min.

The phylogeny of teleost ZIP and ZnT zinc transporters and their tissue specific expression and response to zinc in zebrafish.

In contrast to mammals, zinc transporter genes remain largely uncharacterised in teleosts. Teleost zinc transporter genes were data-mined and phylogenetically assigned to mammalian orthologues. For the first time in animals, the tissue-distribution and mRNA expression response to zinc for most zinc transporter genes was tested in zebrafish.

Changes in erythropoiesis in hereditary hemochromatosis are not mediated by HFE expression in nucleated red cells.

Background And Objectives: The HFE protein interacts with the transferrin receptor (TfR) to regulate cellular iron uptake. Nucleated erythroid cells have the highest number of TfR and the greatest iron uptake. The aim of this study was to investigate whether erythroid iron uptake is directly affected by HFE mutations.

A mathematical model for the in vitro kinetics of the anti-cancer agent topotecan.

In this paper a compartmental modelling approach is applied to provide a mathematical description of the activity of the anti-cancer agent topotecan, and delivery to its nuclear DNA target following administration. The activity of topotecan in defined buffers is first modelled using a linear two compartment model that then forms the basis of a cell based model for drug activity in live cell experiments. An identifiability analysis is performed before parameter estimation to ensure that the model output (i.