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

Optimal management of patients with ST-segment elevation myocardial infarction with delayed admission to the percutaneous coronary intervention center (more than 12 hours)

The success of myocardial infarction (MI) treatment largely depends on the timely delivery of quality health care, primarily on the blood flow restoration through the infarct-related artery. This review presents the results of several meta-analyzes and studies, including our own data, which indicate that delayed revascularization (>12 h from the onset) performed in patients with ST-segment elevation MI leads to an increase in the short- and long-term survival, a decrease in the incidence of cardiovascular events and severity of myocardial remodeling. For example, the analysis from the V. P. Polyakov Samara Regional Clinical Cardiological Dispensary showed the higher mortality rate in patients with ST-segment elevation MI admitted >12 hours from the onset, who received conservative treatment (7,9%) than in those with the invasive management (0,5%) (hazard ratio, 14,8; 95% confidence interval, 1,7- 124,7; P<0,05). However, at present, there is no complete clarity regarding the strategy of managing such patients. According to the current European Society of Cardiology guidelines on myocardial revascularization (2018), the class of recommendations reaches IIA, which means the conflicting data and/ or disagreement about usefulness/efficacy of a particular treatment method, but weight of evidence/opinion is in favor of usefulness/efficacy

Complex polyploid and hybrid species in an apomictic and sexual tropical forage grass group: genomic composition and evolution in Urochloa (Brachiaria) species

Background and Aims Diploid and polyploid Urochloa (including Brachiaria, Panicum and Megathyrsus species) C-4 tropical forage grasses originating from Africa are important for food security and the environment, often being planted in marginal lands worldwide. We aimed to characterize the nature of their genomes, the repetitive DNA and the genome composition of polyploids, leading to a model of the evolutionary pathways within the group including many apomictic species. Methods Some 362 forage grass accessions from international germplasm collections were studied, and ploidy was determined using an optimized flow cytometry method. Whole-genome survey sequencing and molecular cytogenetic analysis were used to identify chromosomes and genomes in Urochloa accessions belonging to the 'brizantha' and 'humidicola' agamic complexes and U. maxima. Key Results Genome structures are complex and variable, with multiple ploidies and genome compositions within the species, and no clear geographical patterns. Sequence analysis of nine diploid and polyploid accessions enabled identification of abundant genome-specific repetitive DNA motifs. In situ hybridization with a combination of repetitive DNA and genomic DNA probes identified evolutionary divergence and allowed us to discriminate the different genomes present in polyploids. Conclusions We suggest a new coherent nomenclature for the genomes present. We develop a model of evolution at the whole-genome level in diploid and polyploid accessions showing processes of grass evolution. We support the retention of narrow species concepts for Urochloa brizantha, U. decumbens and U. ruziziensis, and do not consider diploids and polyploids of single species as cytotypes. The results and model will be valuable in making rational choices of parents for new hybrids, assist in use of the germplasm for breeding and selection of Urochloa with improved sustainability and agronomic potential, and assist in measuring and conserving biodiversity in grasslands

Grass Diversity and Pasture Quality Baseline Assessement in Central Madagascar

Poaceae family contributes to Madagascar’s biodiversity hotspot with 217 of 541 grass species endemic to the island, although their forage value is unknown, at least in the scientific literature. Our research aims 1) to describe the diversity of native and endemic grasses thereby recognising the role of grass species diversity in forage and ecosystem management and 2) to provide new knowledge about pasture management based on the relationship between grazing capacity and productivity within experimental pastureland plots under different fire and grazing treatments. Our study seeks to provide information to inform improvements in livestock nutrition via grazing management of natural pastures in central Madagascar, specifically around the Ankafobe, Ibity and Itremo Protected Areas. Sampling in different grassy habitats was undertaken to develop a grass checklist and overview of grass diversity across the project sites. Further, in the communal and experimental pastures standardised grass surveys were carried out to compare grazing capacity and biomass productivity in the experimental pastures. Our regional survey recorded 123 Poaceae species during the first year: including 90% native species (of which 34% were endemic) and 10% introduced species. Thirty species, all C4 and belonging to PACMAD clade, are found within established pasture grasslands. Across communal pastures the most frequently recorded species and thus most frequently grazed are Loudetia simplex, Aristida rufescens, Panicum luridum, Schizachyrium sanguineum, Hyparrhenia rufa and Aristida tenuissima – these species are predominantly associated with fire. The grazing capacity baseline, at about 0.7 to 0.8 ha/zebu/year, is similar across all experimental sites that are also characterised by having a similar climate, acidic soils with low nitrogen and phosphorus, and., Annual biomass production appears to be driven by fire frequency: at both Itremo and Ankafobe, where fire is an annual occurrence, biomass yield is 2.4-2.9t/ha whereas at Ibity, where fire frequency is fire every 3-4 years, biomass productivity is 6.9t/ha. However, it is unclear how these productivity estimates relate to forage quality; the relationship will be the subject of future work

A 250 plastome phylogeny of the grass family (Poaceae): topological support under different data partitions

The systematics of grasses has advanced through applications of plastome phylogenomics, although studies have been largely limited to subfamilies or other subgroups of Poaceae. Here we present a plastome phylogenomic analysis of 250 complete plastomes (179 genera) sampled from 44 of the 52 tribes of Poaceae. Plastome sequences were determined from high throughput sequencing libraries and the assemblies represent over 28.7 Mbases of sequence data. Phylogenetic signal was characterized in 14 partitions, including (1) complete plastomes; (2) protein coding regions; (3) noncoding regions; and (4) three loci commonly used in single and multi-gene studies of grasses. Each of the four main partitions was further refined, alternatively including or excluding positively selected codons and also the gaps introduced by the alignment. All 76 protein coding plastome loci were found to be predominantly under purifying selection, but specific codons were found to be under positive selection in 65 loci. The loci that have been widely used in multi-gene phylogenetic studies had among the highest proportions of positively selected codons, suggesting caution in the interpretation of these earlier results. Plastome phylogenomic analyses confirmed the backbone topology for Poaceae with maximum bootstrap support (BP). Among the 14 analyses, 82 clades out of 309 resolved were maximally supported in all trees. Analyses of newly sequenced plastomes were in agreement with current classifications. Five of seven partitions in which alignment gaps were removed retrieved Panicoideae as sister to the remaining PACMAD subfamilies. Alternative topologies were recovered in trees from partitions that included alignment gaps. This suggests that ambiguities in aligning these uncertain regions might introduce a false signal. Resolution of these and other critical branch points in the phylogeny of Poaceae will help to better understand the selective forces that drove the radiation of the BOP and PACMAD clades comprising more than 99.9% of grass diversity

Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification

Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly. We now demonstrate synergistic interactions of spineless and CG5017 in pathways controlling oxidative stress response and long-term memory formation in Drosophila melanogaster. Oxidative stress was induced by low doses of X-ray irradiation of flies carrying hypomorphic mutation of spineless, mutation of CG5017, and their combination. To determine the sensitivity of these mutants to pharmacological modifiers of the irradiation effect, we irradiated flies growing on standard medium supplemented by radiosensitizer furazidin and radioprotector serotonin. The effects of irradiation were investigated by analyzing leg and antenna morphological structures and by using real-time PCR to measure mRNA expression levels for spineless, Cyp6g1 and Gst-theta genes. We also examined long-term memory in these mutants using conditioned courtship suppression paradigm. Our results show that the interaction of spineless and CG5017 is important for regulation of morphogenesis, long-term memory formation, and detoxification during oxidative stress. Since spineless and CG5017 are evolutionary conserved, these results must be considered when evaluating the risk of combining similar mutations in other organisms, including humans

ИЗУЧЕНИЕ ПРОЦЕССА СООСАЖДЕНИЯ МЫШЬЯКА И СУРЬМЫ ПРИ ОТДЕЛЕНИИ МАКРОКОЛИЧЕСТВ ЖЕЛЕЗА, ХРОМА В ВИДЕ Na3FeF6, Na3CrF6

Theoretical and experimental studies were carried out for the first time in order to determine the mechanism of co-precipitation of arsenic and antimony during their separation from the macro-quantities of iron and chromium in the form of Na3FeF6 and Na3CrF6 sediments. It was found that the application of Dubinin-Radushkevich adsorption isotherm gives the most accurate description of the process. The average free energy of adsorption for As and Sb is 9.6 and 9.7 kJ/mol respectively. Co-precipitation of analytes in the micropores of precipitates occurred as a result of the chemical (ion-exchange) reaction. The possibility of inhibiting this process by introducing a different amount of complexing agent (hydrofluoric acid) was studied. The addition of HF led to the formation of more coarse crystalline precipitates with lower specific surface area and porosity. For the accurate ICP-AES determination of analytes (As, Sb) the molar ratio of precipitating agent / complexing agent (NaF / HF) ≈ 1 should be strictly observed. According to the developed procedure, state standard samples of steels and nickel-based precision alloys were prepared for ICP-AES determination of As and Sb contents. The difference between the found and certified content of analytes did not exceed the permitted deviations given in the corresponding Russian state standards. The ICP-AES method of simultaneous determination of As and Sb contents after their preliminary separation from the main components is recommended for the analysis of materials with high content of Fe and Cr.Keywords: sorption, co-precipitation, determination of arsenic and antimony, inductively coupled plasma atomic emission spectroscopy (ICP-AES), adsorption isotherms, fluorides, matrix componentsDOI: http://dx.doi.org/10.15826/analitika.2017.21.3.001 A.V. Maiorova1, S.Yu. Melchakov1,2, T.G. Okuneva2 , K.A. Vorontsova1, M.A. Mashkovtsev21Institute of Metallurgy of Ural Branch of Russian Academy of Sciences,101 Amundsena st., Yekaterinburg, 620016, Russian Federation2Ural Federal University, 19 Mira st., Yekaterinburg, 620002, Russian FederationВпервые проведены теоретические и экспериментальные исследования с целью определения механизма соосаждения мышьяка и сурьмы при отделении от макроколичеств железа, хрома в виде Na3FeF6, Na3CrF6. Установлено, что использование изотермы адсорбции Дубинина-Радушкевича приводит к наиболее точному описанию процесса. Средняя свободная энергия адсорбции для As и Sb принимает значения 9.6 и 9.7 кДж/моль соответственно. Соосаждение в микропорах осадков происходит в результате химической (ионообменной) реакции. Изучена возможность ингибирования процесса с помощью введения разного количества комплексообразующего агента – фтороводородной кислоты. Ее использование приводит к получению более крупнокристаллических осадков с меньшей удельной поверхностью и пористостью. Для точного ИСП-АЭС определения аналитов необходимо строгое соблюдение мольного соотношения осадитель/комплексообразующий агент (NaF/HF) ≈ 1. По разработанной процедуре к ИСП-АЭС определению содержания As и Sb были подготовлены ГСО состава стали и сплавов прецизионного типа на никелевой основе. Разница между найденным и аттестованным их содержанием не превышает нормативов, приведенных в соответствующих ГОСТах.  ИСП-АЭС методика одновременного определения содержания As и Sb с предварительным отделением основных компонентов рекомендована для анализа материалов с высоким содержанием Fe и Cr.Ключевые слова: адсорбция, соосаждение, определение мышьяка и сурьмы, атомно-эмиссионная спектрометрия с индуктивно связанной плазмой (ИСП-АЭС), изотермы адсорбции, фториды, матричные компонентыDOI: http://dx.doi.org/10.15826/analitika.2017.21.3.00

Hemocoagulation Activity of Sulfur-Containing Pinane-Type Terpenoids

© 2017, Springer Science+Business Media, LLC. A series of pinane-type sulfides and sulfoxides were synthesized from (1S)-(–)-β-pinene. Their hemocoagulation activity in vitro on human blood plasma was studied. All tested compounds exhibited antiaggregation and anticoagulation activity. The most water-soluble sulfoxide with a mercaptoacetic acid moiety inhibited spontaneous platelet aggregation and that induced by collagen and arachidonic acid and also reduced the coagulation activity of human blood plasma. The hemocoagulation activity was due to selective inhibition of platelet receptors, decreased yield of thrombocytic microvesicles, and suppression of their activity

Smallholder Zebu and Forage Production Development in Central Madagascar

Poverty in the Central Highlands of Madagascar is partly driven by inefficient exploitation of native forages and poor livestock nutrition. Zebus are of importance as cultural symbols, but this tradition has grown disconnected from agricultural policy. This project is working with three central highland communities near the protected areas of Itremo, Ibity and Ankafobe, to boost rangeland productivity and trial management methods which will support key forage grasses and improve livestock nutrition. A severe nitrogen deficiency compounded by extremely acidic soil conditions and low phosphorus is observed across the three sites. The lowest grazing capacity of an estimated 0.7 livestock unit per hectare and biomass production of 1600 kg/ha is observed at Ankafobe, the highest elevation windy site with fires that are almost annual. Low production is due to acidic soils with a lack of phosphorus as well as likely iron toxicity. The project works with 90 households owning a total 150 female zebu, 1-5 per household. The project initiated 3 demonstration farms to show the planting of sorghum for silage, harvesting of the native grasses for hay, and building a secure barn meeting at least minimum animal care standards, using local materials to protect the livestock from the weather and theft which is sadly perceived to be common. In the first year the project produced the highest yields in the most remote and fertile site of Itremo, with 365 kg of sorghum silage from 0.5 ha and 165 kg of Brachiaria hay from 0.5 ha. Five households based in the milk producing region of eastern Ibity have completed new barns. Fifty percent of households at Ibity successfully fed silage and hay to their zebu for the first time. Madagascar remains famous for subsistence farming and rural poverty with a long-term decline in livestock, but substantial opportunity nevertheless exists for integrated crop and livestock production, alongside the protection of biodiversity in nearby forests