Xenobiotic-induced activation of human aryl hydrocarbon receptor target genes in Drosophila is mediated by the epigenetic chromatin modifiers

Aryl hydrocarbon receptor (AHR) is the key transcription factor that controls animal development and various adaptive processes. The AHR\u27s target genes are involved in biodegradation of endogenous and exogenous toxins, regulation of immune response, organogenesis, and neurogenesis. Ligand binding is important for the activation of the AHR signaling pathway. Invertebrate AHR homologs are activated by endogenous ligands whereas vertebrate AHR can be activated by both endogenous and exogenous ligands (xenobiotics). Several studies using mammalian cultured cells have demonstrated that transcription of the AHR target genes can be activated by exogenous AHR ligands, but little is known about the effects of AHR in a living organism. Here, we examined the effects of human AHR and its ligands using transgenic Drosophila lines with an inducible human AhR gene. We found that exogenous AHR ligands can increase as well as decrease the transcription levels of the AHR target genes, including genes that control proliferation, motility, polarization, and programmed cell death. This suggests that AHR activation may affect the expression of gene networks that could be critical for cancer progression and metastasis. Importantly, we found that AHR target genes are also controlled by the enzymes that modify chromatin structure, in particular components of the epigenetic Polycomb Repressive complexes 1 and 2. Since exogenous AHR ligands (alternatively - xenobiotics) and small molecule inhibitors of epigenetic modifiers are often used as pharmaceutical anticancer drugs, our findings may have significant implications in designing new combinations of therapeutic treatments for oncological diseases. © Akishina et al

Fungus Metarhizium robertsii and neurotoxic insecticide affect gut immunity and microbiota in Colorado potato beetles

Fungal infections and toxicoses caused by insecticides may alter microbial communities and immune responses in the insect gut. We investigated the effects of Metarhizium robertsii fungus and avermectins on the midgut physiology of Colorado potato beetle larvae. We analyzed changes in the bacterial community, immunity- and stress-related gene expression, reactive oxygen species (ROS) production, and detoxification enzyme activity in response to topical infection with the M. robertsii fungus, oral administration of avermectins, and a combination of the two treatments. Avermectin treatment led to a reduction in microbiota diversity and an enhancement in the abundance of enterobacteria, and these changes were followed by the downregulation of Stat and Hsp90, upregulation of transcription factors for the Toll and IMD pathways and activation of detoxification enzymes. Fungal infection also led to a decrease in microbiota diversity, although the changes in community structure were not significant, except for the enhancement of Serratia. Fungal infection decreased the production of ROS but did not affect the gene expression of the immune pathways. In the combined treatment, fungal infection inhibited the activation of detoxification enzymes and prevented the downregulation of the JAK-STAT pathway caused by avermectins. The results of this study suggest that fungal infection modulates physiological responses to avermectins and that fungal infection may increase avermectin toxicosis by blocking detoxification enzymes in the gut

Luminescent silica mesoparticles for protein transduction

Unlike silica nanoparticles, the potential of silica mesoparticles (SMPs) (i.e. particles of submicron size) for biological applications in particular the in vitro (let alone in vivo) cellular delivery of biological cargo has so far not been sufficiently studied. Here we examine the potential of luminescent (namely, octahedral molybdenum cluster doped) SMPs synthesised by a simple one-pot reaction for the labelling of cells and for protein transduction into larynx carcinoma (Hep-2) cells using GFP as a model protein. Our data demonstrates that the SMPs internalise into the cells within half an hour. This results in cells that detectably luminesce via conventional methods. In addition, the particles are non-toxic both in darkness and upon photo-irradiation. The SMPs were modified to allow their functionalisation by a protein, which then delivered the protein (GFP) efficiently into the cells. Thus, the luminescent SMPs offer a cheap and trackable alternative to existing materials for cellular internalisation of proteins, such as the HIV TAT protein and commercial protein delivery agents (e.g. Pierce™)

Comparative analysis of the immune response of the wax moth Galleria mellonella after infection with the fungi Cordyceps militaris and Metarhizium robertsii

Entomopathogenic fungi form different strategies of interaction with their insect hosts. The influence of funga

Wild type and mutant antenna and leg in flies in normal conditions and following irradiation.

<p>Simultaneous combination of mutations at both <i>ss</i> and <i>CG5017</i> loci increases sensitivity to even low doses of X-ray radiation (1 and 10 R), which is manifested as an increase in the mutant phenotype (photographs within the red frame).</p

Wild type and mutant leg and antenna phenotypes.

<p>Micrographs show the normal morphology of the tarsal structures of the wild type <i>Canton S</i>, <i>ss^a40ahm</i> and <i>milkah-1</i> flies. Antennal structures of the <i>milkah-1</i> mutant flies do not show any difference from the wild type. The distal segment of the antenna – the arista - of the <i>ss^a40ahm</i> flies presents a certain thickening of the proximal end. The arista of the <i>ss^a40ahmmilkah-1</i> hybrid flies suffered homeotic transformation into an unsegmented tarsus. The tarsal structures of the <i>ss^a40ahmmilkah-1</i> hybrids show altered segment fusion.</p

Dynamics of acquisition and retention of conditioned courtship suppression in mutant males.

<p>Males from wild type <i>Canton S</i> (A-B), <i>milkah-1</i> (C–D), <i>ss^a40a</i> (E–F) and <i>ss^a40amilkah-1</i> (G–H) lines were tested. (A, C, E, G) – of tested males. (B, D, F, H) – of tested males. On the X-axis: time following training, in days; on the Y axis: – courtship index, – learning index, standard units. Open columns – of naive males, hatched columns – () of trained males. Each point represents 20 males. ** - or significantly lower than for wild type (two-sided randomization test, ) in similar condition; - in a test immediately following training or in a deferred test, significantly lower than the CI of naive males (two-sided randomization test, ); - in the delayed test significantly lower than in test immediately following training (two-sided randomization test,.</p

Effect of X-rays and pharmacological agents on Cyp6g1, GST-theta (CG1681) and ss mRNA expression.

<p>The relative level of expression of mRNA was measured using real-time PCR. A, B, C – level of mRNA expressed in <i>Canton S</i>, <i>ss^a40a</i> and <i>ss^aSc</i> flies respectively. As a control, we used RNA from flies, which have not been exposed to radiation (cont.). F, 5-HT – level of mRNA expressed in flies, grown on medium with added furazidin (F) and 5-hydroxytryptamine (5-HT), respectively; R – radiation dose in Roentgens; 1-10R, level of expressed mRNA of the genes under study in flies irradiated with a dose of 1-10 R. F1-10R, 5-HT1-10R – level of expressed mRNA of the genes under study in flies grown on medium with added F or 5-HT and radiated with 1-10 R, respectively. The bars show the level of mRNA expression. The error bars represent the standard error of the mean of triplicate experiments. * - P<0.05, compared to control group, - P<0.05, compared to F or 5-HT group.</p