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

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

Contrasted histories of organelle and nuclear genomes underlying physiological diversification in a grass species: Intraspecific dispersal of C4 physiology

C 4 photosynthesis evolved multiple times independently in angiosperms, but most origins are relatively old so that the early events linked to photosynthetic diversification are blurred. The grass Alloteropsis semialata is an exception, as this species encompasses C 4 and non-C 4 populations. Using phylogenomics and population genomics, we infer the history of dispersal and secondary gene flow before, during and after photosynthetic divergence in A. semialata. We further analyse the genome composition of individuals with varied ploidy levels to establish the origins of polyploids in this species. Detailed organelle phylogenies indicate limited seed dispersal within the mountainous region of origin and the emergence of a C 4 lineage after dispersal to warmer areas of lower elevation. Nuclear genome analyses highlight repeated secondary gene flow. In particular, the nuclear genome associated with the C 4 phenotype was swept into a distantly related maternal lineage probably via unidirectional pollen flow. Multiple intraspecific allopolyploidy events mediated additional secondary genetic exchanges between photosynthetic types. Overall, our results show that limited dispersal and isolation allowed lineage divergence, with photosynthetic innovation happening after migration to new environments, and pollen-mediated gene flow led to the rapid spread of the derived C 4 physiology away from its region of origin.This study was funded by the European Research Council (grant no. ERC-2014-STG-638333), the Royal Society (grant no. RGF\EA\181050) and has benefited from ‘Investissements d'Avenir' grants managed by the Agence Nationale de la Recherche (CEBA, ref. ANR-10-LABX-25-01 and TULIP, ref. ANR-10-LABX-41). Edinburgh Genomics, which contributed to the sequencing, is partly supported through core grants from the NERC (grant no. R8/H10/ 56), MRC (grant no. MR/K001744/1) and BBSRC (grant no. BB/ J004243/1). P.A.C. is funded by a Royal Society University Research Fellowship (grant no. URF\R\180022).Abstract 1. Introduction 2. Materials and methods (a) Sampling, sequencing and data filtering (b) Genome sizing and carbon isotope analyses (c) Assembly of organelle genomes and molecular dating (d) Phylogenetic analyses of the nuclear genome (e) Genetic structure (f) Genome composition 3. Results (a) Genome sizes (b) Time-calibrated organelle phylogenies (c) Nuclear phylogeny (d) Population structure and genome composition 4. Discussion (a) Limited seed dispersal in the region of origin (b) Widespread pollen flow and sweep of the C4 nuclear genome (c) Recurrent hybridization and polyploidization 5. Concluding remarks Data accessibility Authors' contributions Competing interests Funding Acknowledgements Footnote

Botanical Monography in the Anthropocene

Unprecedented changes in the Earth's biota are prompting urgent efforts to describe and conserve plant diversity. For centuries, botanical monographs — comprehensive systematic treatments of a family or genus — have been the gold standard for disseminating scientific information to accelerate research. The lack of a monograph compounds the risk that undiscovered species become extinct before they can be studied and conserved. Progress towards estimating the Tree of Life and digital information resources now bring even the most ambitious monographs within reach. Here, we recommend best practices to complete monographs urgently, especially for tropical plant groups under imminent threat or with expected socioeconomic benefits. We also highlight the renewed relevance and potential impact of monographies for the understanding, sustainable use, and conservation of biodiversity.Fil: Grace, Olwen M.. Royal Botanic Gardens, Kew; Reino UnidoFil: Pérez-Escobar, Oscar A.. Royal Botanic Gardens, Kew; Reino UnidoFil: Lucas, Eve J.. Royal Botanic Gardens, Kew; Reino UnidoFil: Vorontsova, Maria S.. Royal Botanic Gardens, Kew; Reino UnidoFil: Lewis, Gwilym P.. Royal Botanic Gardens, Kew; Reino UnidoFil: Walker, Barnaby E.. Royal Botanic Gardens, Kew; Reino UnidoFil: Lohmann, Lúcia G.. Universidade de Sao Paulo; BrasilFil: Knapp, Sandra. Natural History Museum; Reino UnidoFil: Wilkie, Peter. Royal Botanic Gardens; Reino UnidoFil: Sarkinen, Tiina. Royal Botanic Gardens; Reino UnidoFil: Darbyshire, Iain. Royal Botanic Gardens; Reino UnidoFil: Lughadha, Eimear Nic. Royal Botanic Gardens; Reino UnidoFil: Monro, Alexandre. Royal Botanic Gardens; Reino UnidoFil: Woudstra, Yannick. Universidad de Copenhagen; Dinamarca. Royal Botanic Gardens; Reino UnidoFil: Demissew, Sebsebe. Addis Ababa University; EtiopíaFil: Muasya, A. Muthama. University Of Cape Town; SudáfricaFil: Díaz, Sandra Myrna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Baker, William J.. Royal Botanic Gardens, Kew; Reino UnidoFil: Antonelli, Alexandre. University of Oxford; Reino Unido. University Goteborg; Sueci

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

Концептуальные основы региональной образовательной политики

У монографії висвітлено концептуальні засади регіональної освітньої політики, об’єктивовані в теоретичному описі основних підходів, принципів, умов реалізації концепції навчання впродовж життя як чинника регіональної розвитку. Проаналізовано основні передумови розроблення концепції освіти впродовж життя у світі та соціально-економічні результати її упровадження. Викладено особливості та специфіку освіти впродовж життя, освіти дорослих як її складової в умовах регіонального розвитку (національний і зарубіжний досвід). Охарактеризовано психологічні особливості розвитку особистості в дорослому віці, а також професійного становлення особистості на різних етапах дорослості. Висвітлено роль неформальної освіти дорослих як чинника розвитку регіонів, що навчаються, а також механізми розроблення та реалізації концепції міста, регіону, що навчається. Інтерпретовано результати соціологічного дослідження культурно-освітніх потреб жителів Запорізької обл. та рівня їх задоволеності.The monograph describes the conceptual foundations of regional educational policy, objectified in the theoretical description of the main approaches, principles, conditions to implement the lifelong learning concept as a factor of regional development. The basic prerequisites for the development of lifelong learning concept in the world and the socio-economic results of its implementation are analyzed. The peculiarities and specifics of lifelong learning, education of adults as a part of it in the conditions of regional development (national and foreign experience) are described. The psychological peculiarities of personality development in adulthood as well as professional development of personality at different stages of adolescence are characterized. The role of non-formal adults education as a factor of learning regions development as well as mechanisms of the city development and implementation of the concept is highlighted. The results of sociological research of cultural and educationalneeds of Zaporizhzhya region's residents and their level of satisfaction are interpreted.В монографии освещены концептуальные основы региональной образовательной политики, объективированные в теоретическом описании основных подходов, принципов, условий реализации концепции непрерывного обучения как фактора регионального развития. Проанализированы основные предпосылки для разработки концепции обучения на протяжении всей жизни в мире и социально-экономических результатов ее реализации. Описаны особенности и специфика обучения на протяжении всей жизни, образования взрослых как его составляющей в условиях регионального развития (национальный и зарубежный опыт). Охарактеризованы психологические особенности развития личности во взрослом возрасте, а также профессиональное развитие личности на разных этапах подросткового возраста. Освещена роль неформального образования взрослых как фактора развития обучающихся регионов, а также механизмы разработки и реализации концепции обучающихся городов

High Mutability of the Tumor Suppressor Genes RASSF1 and RBSP3 (CTDSPL) in Cancer

BACKGROUND:Many different genetic alterations are observed in cancer cells. Individual cancer genes display point mutations such as base changes, insertions and deletions that initiate and promote cancer growth and spread. Somatic hypermutation is a powerful mechanism for generation of different mutations. It was shown previously that somatic hypermutability of proto-oncogenes can induce development of lymphomas. METHODOLOGY/PRINCIPAL FINDINGS:We found an exceptionally high incidence of single-base mutations in the tumor suppressor genes RASSF1 and RBSP3 (CTDSPL) both located in 3p21.3 regions, LUCA and AP20 respectively. These regions contain clusters of tumor suppressor genes involved in multiple cancer types such as lung, kidney, breast, cervical, head and neck, nasopharyngeal, prostate and other carcinomas. Altogether in 144 sequenced RASSF1A clones (exons 1-2), 129 mutations were detected (mutation frequency, MF = 0.23 per 100 bp) and in 98 clones of exons 3-5 we found 146 mutations (MF = 0.29). In 85 sequenced RBSP3 clones, 89 mutations were found (MF = 0.10). The mutations were not cytidine-specific, as would be expected from alterations generated by AID/APOBEC family enzymes, and appeared de novo during cell proliferation. They diminished the ability of corresponding transgenes to suppress cell and tumor growth implying a loss of function. These high levels of somatic mutations were found both in cancer biopsies and cancer cell lines. CONCLUSIONS/SIGNIFICANCE:This is the first report of high frequencies of somatic mutations in RASSF1 and RBSP3 in different cancers suggesting it may underlay the mutator phenotype of cancer. Somatic hypermutations in tumor suppressor genes involved in major human malignancies offer a novel insight in cancer development, progression and spread

Coding SNPs analysis highlights genetic relationships and evolution pattern in eggplant complexes

[EN] Brinjal (Solanum melongena), scarlet (S. aethiopicum) and gboma (S. macrocarpon) eggplants are three Old World domesticates. The genomic DNA of a collection of accessions belonging to the three cultivated species, along with a representation of various wild relatives, was characterized for the presence of single nucleotide polymorphisms (SNPs) using a genotype-by-sequencing approach. A total of 210 million useful reads were produced and were successfully aligned to the reference eggplant genome sequence. Out of the 75,399 polymorphic sites identified among the 76 entries in study, 12,859 were associated with coding sequence. A genetic relationships analysis, supported by the output of the FastSTRUCTURE software, identified four major sub-groups as present in the germplasm panel. The first of these clustered S. aethiopicum with its wild ancestor S. anguivi; the second, S. melongena, its wild progenitor S. insanum, and its relatives S. incanum, S. lichtensteinii and S. linneanum; the third, S. macrocarpon and its wild ancestor S. dasyphyllum; and the fourth, the New World species S. sisymbriifolium, S. torvum and S. elaeagnifolium. By applying a hierarchical FastSTRUCTURE analysis on partitioned data, it was also possible to resolve the ambiguous membership of the accessions of S. campylacanthum, S. violaceum, S. lidii, S. vespertilio and S. tomentsum, as well as to genetically differentiate the three species of New World Origin. A principal coordinates analysis performed both on the entire germplasm panel and also separately on the entries belonging to sub-groups revealed a clear separation among species, although not between each of the domesticates and their respective wild ancestors. There was no clear differentiation between either distinct cultivar groups or different geographical provenance. Adopting various approaches to analyze SNP variation provided support for interpretation of results. The genotyping-by-sequencing approach showed to be highly efficient for both quantifying genetic diversity and establishing genetic relationships among and within cultivated eggplants and their wild relatives. The relevance of these results to the evolution of eggplants, as well as to their genetic improvement, is discussed.This work has been funded in part by European Unions Horizon 2020 Research and Innovation Programme under grant agreement No 677379 (G2P-SOL project: Linking genetic resources, genomes and phenotypes of Solanaceous crops) and by Spanish Ministerio de Economia, Industria y Competitividad and Fondo Europeo de Desarrollo Regional (grant AGL2015-64755-R from MINECO/FEDER). Funding has also been received from the initiative "Adapting Agriculture to Climate Change: Collecting, Protecting and Preparing Crop Wild Relatives", which is supported by the Government of Norway. This last project is managed by the Global Crop Diversity Trust with the Millennium Seed Bank of the Royal Botanic Gardens, Kew and implemented in partnership with national and international gene banks and plant breeding institutes around the world. For further information see the project website:http://www.cwrdiversity.org/. Pietro Gramazio is grateful to Universitat Politecnica de Valencia for a pre-doctoral (Programa FPI de la UPV-Subprograma 1/2013 call) contract. Mariola Plazas is grateful to Spanish Ministerio de Economia, Industria y Competitividad for a post-doctoral grant within the Santiago Grisolia Programme (FCJI-2015-24835). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Acquadro, A.; Barchi, L.; Gramazio, P.; Portis, E.; Vilanova Navarro, S.; Comino, C.; Plazas Ávila, MDLO.... (2017). Coding SNPs analysis highlights genetic relationships and evolution pattern in eggplant complexes. PLoS ONE. 12(7). https://doi.org/10.1371/journal.pone.0180774Se018077412

Madagascar’s extraordinary biodiversity: Threats and opportunities

Madagascar's unique biota is heavily affected by human activity and is under intense threat. Here, we review the current state of knowledge on the conservation status of Madagascar's terrestrial and freshwater biodiversity by presenting data and analyses on documented and predicted species-level conservation statuses, the most prevalent and relevant threats, ex situ collections and programs, and the coverage and comprehensiveness of protected areas. The existing terrestrial protected area network in Madagascar covers 10.4% of its land area and includes at least part of the range of the majority of described native species of vertebrates with known distributions (97.1% of freshwater fishes, amphibians, reptiles, birds, and mammals combined) and plants (67.7%). The overall figures are higher for threatened species (97.7% of threatened vertebrates and 79.6% of threatened plants occurring within at least one protected area). International Union for Conservation of Nature (IUCN) Red List assessments and Bayesian neural network analyses for plants identify overexploitation of biological resources and unsustainable agriculture as themost prominent threats to biodiversity. We highlight five opportunities for action at multiple levels to ensure that conservation and ecological restoration objectives, programs, and activities take account of complex underlying and interacting factors and produce tangible benefits for the biodiversity and people of Madagascar

Spider-Venom Peptides as Therapeutics

Spiders are the most successful venomous animals and the most abundant terrestrial predators. Their remarkable success is due in large part to their ingenious exploitation of silk and the evolution of pharmacologically complex venoms that ensure rapid subjugation of prey. Most spider venoms are dominated by disulfide-rich peptides that typically have high affinity and specificity for particular subtypes of ion channels and receptors. Spider venoms are conservatively predicted to contain more than 10 million bioactive peptides, making them a valuable resource for drug discovery. Here we review the structure and pharmacology of spider-venom peptides that are being used as leads for the development of therapeutics against a wide range of pathophysiological conditions including cardiovascular disorders, chronic pain, inflammation, and erectile dysfunction