25 research outputs found

    Miller Early Childhood Sustained Home-visiting (MECSH) trial: design, method and sample description

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Home visiting programs comprising intensive and sustained visits by professionals (usually nurses) over the first two years of life show promise in promoting child health and family functioning, and ameliorating disadvantage. Australian evidence of the effectiveness of sustained nurse home visiting in early childhood is limited. This paper describes the method and cohort characteristics of the first Australian study of sustained home visiting commencing antenatally and continuing to child-age two years for at-risk mothers in a disadvantaged community (the Miller Early Childhood Sustained Home-visiting trial).</p> <p>Methods and design</p> <p>Mothers reporting risks for poorer parenting outcomes residing in an area of socioeconomic disadvantage were recruited between February 2003 and March 2005. Mothers randomised to the intervention group received a standardised program of nurse home visiting. Interviews and observations covering child, maternal, family and environmental issues were undertaken with mothers antenatally and at 1, 12 and 24 months postpartum. Standardised tests of child development and maternal-child interaction were undertaken at 18 and 30 months postpartum. Information from hospital and community heath records was also obtained.</p> <p>Discussion</p> <p>A total of 338 women were identified and invited to participate, and 208 were recruited to the study. Rates of active follow-up were 86% at 12 months, 74% at 24 months and 63% at 30 months postpartum. Participation in particular data points ranged from 66% at 1 month to 51% at 24 months postpartum. Rates of active follow-up and data point participation were not significantly different for the intervention or comparison group at any data point. Mothers who presented for antenatal care prior to 20 weeks pregnant, those with household income from full-time employment and those who reported being abused themselves as a child were more likely to be retained in the study. The Miller Early Childhood Sustained Home-visiting trial will provide Australian evidence of the effectiveness of sustained nurse home visiting for children at risk of poorer health and developmental outcomes.</p> <p>Trial registration</p> <p>ACTRN12608000473369</p

    The places parents go: understanding the breadth, scope, and experiences of activity spaces for parents

    Get PDF
    The final publication is available at Springer via https://doi.org/10.1007/s10708-015-9690-yNeighborhood environments are related to parenting behaviors, which in turn have a life-long effect on children’s health and well-being. Activity spaces, which measure individual routine patterns of movement, may be helpful in assessing how physical and social environments shape parenting. In this study we use qualitative data and GIS mapping from four California cities to examine parental activity spaces. Parents described a number of factors that shape their activity spaces including caregiving status, the age of their children, and income. Parental activity spaces also varied between times (weekends vs. weekdays) and places (adult-only vs. child-specific places). Knowing how to best capture and study parental activity spaces could identify mechanisms by which environmental factors influence parenting behaviors and child health

    Developmental Exposure to a Toxic Spill Compromises Long-Term Reproductive Performance in a Wild, Long-Lived Bird: The White Stork (Ciconia ciconia)

    Get PDF
    Background/Objective: Exposure to environmental contaminants may result in reduced reproductive success and long- lasting population declines in vertebrates. Emerging data from laboratory studies on model species suggest that certain life- stages, such as development, should be of special concern. However, detailed investigations of long-term consequences of developmental exposure to environmental chemicals on breeding performance are currently lacking in wild populations of long-lived vertebrates. Here, we studied how the developmental exposure to a mine spill (Aznalco´ llar, SW Spain, April 1998) may affect fitness under natural conditions in a long-lived bird, the White Stork (Ciconia ciconia). Methodology: The reproductive performance of individually-banded storks that were or not developmentally exposed to the spill (i.e. hatched before or after the spill) was compared when these individuals were simultaneously breeding during the seven years after the spill occurred (1999–2005). Principal Findings: Female storks developmentally exposed to the spill experienced a premature breeding senescence compared with their non-developmentally exposed counterparts, doing so after departing from an unusually higher productivity in their early reproductive life (non-developmentally exposed females: 0.560.33SE fledglings/year at 3-yr old vs. 1.3860.31SE at 6–7 yr old; developmentally exposed females: 1.560.30SE fledglings/year at 3-yr old vs. 0.8660.25SE at 6– 7 yr old). Conclusions/Significance: Following life-history theory, we propose that costly sub-lethal effects reported in stork nestlings after low-level exposure to the spill-derived contaminants might play an important role in shaping this pattern of reproduction, with a clear potential impact on population dynamics. Overall, our study provides evidence that environmental disasters can have long-term, multigenerational consequences on wildlife, particularly when affecting developing individuals, and warns about the risk of widespread low-level contamination in realistic scenarios.Peer reviewe

    Expression of two barley proteinase inhibitors in tomato promotes endogenous defensive response and enhances resistance to Tuta absoluta

    Get PDF
    [EN] Background: For as long as 350 million years, plants and insects have coexisted and developed a set of relationships which affect both organisms at different levels. Plants have evolved various morphological and biochemical adaptations to cope with herbivores attacks. However, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) has become the major pest threatening tomato crops worldwide and without the appropriated management it can cause production losses between 80 to 100%. Results: The aim of this study was to investigate the in vivo effect of a serine proteinase inhibitor (BTI-CMe) and a cysteine proteinase inhibitor (Hv-CPI2) from barley on this insect and to examine the effect their expression has on tomato defensive response. We found that larvae fed on the double transgenic plants showed a notable reduction in weight. Moreover, only 56% of the larvae reached the adult stage. The emerged adults showed wings deformities and reduced fertility. We also investigated the effect of proteinase inhibitors ingestion on the insect digestive enzymes. Our results showed a decrease in larval trypsin activity. Transgenes expression had no harmful effect on Nesidiocoris tenuis (Reuter) (Heteroptera: Miridae), a predator of Tuta absoluta, despite transgenic tomato plants attracted the mirid. We also found that barley cystatin expression promoted plant defense by inducing the expression of the tomato endogenous wound inducible Proteinase inhibitor 2 (Pin2) gene, increasing the production of glandular trichomes and altering the emission of volatile organic compounds. Conclusion: Our results demonstrate the usefulness of the co-expression of different proteinase inhibitors for the enhancement of plant resistance to Tuta absoluta.This work was partly supported by grants BIO2013-40747-R and AGL2014-55616-C3 from the Spanish Ministry of Economy and Competitiveness (MINECO)Hamza, R.; Pérez-Hedo, M.; Urbaneja, A.; Rambla Nebot, JL.; Granell Richart, A.; Gaddour, K.; Beltran Porter, JP.... (2018). Expression of two barley proteinase inhibitors in tomato promotes endogenous defensive response and enhances resistance to Tuta absoluta. BMC Plant Biology. 18. https://doi.org/10.1186/s12870-018-1240-6S18Oerke EC. Crop losses to pests. J Agric Sci. 2005;144(01):31.Jouanin L, Bonadé-Bottino M, Girard C, Morrot G, Giband M. Transgenic plants for insect resistance. Plant Sci. 1998;131(1):1–11.Markwick NP, Docherty LC, Phung MM, Lester MT, Murray C, Yao JL, Mitra DS, Cohen D, Beuning LL, Kutty-Amma S, et al. Transgenic tobacco and apple plants expressing biotin-binding proteins are resistant to two cosmopolitan insect pests, potato tuber moth and lightbrown apple moth, respectively. Transgenic Res. 2003;12(6):671–81.Koiwa H, Bressan RA, Hasegawa PM. Regulation of protease inhibitors and plant defense. Trends Plant Sci. 1997;2(10):379–84.Ryan CA. Protease inhibitors in plants: genes for improving defenses against insects and pathogens. Annu Rev Phytopathol. 1990;28(1):425–49.Abdeen A, Virgos A, Olivella E, Villanueva J, Aviles X, Gabarra R, Prat S. Multiple insect resistance in transgenic tomato plants over-expressing two families of plant proteinase inhibitors. Plant Mol Biol. 2005;57(2):189–202.Quilis J, López-García B, Meynard D, Guiderdoni E, San Segundo B. Inducible expression of a fusion gene encoding two proteinase inhibitors leads to insect and pathogen resistance in transgenic rice. Plant Biotechnol J. 2014;12(3):367–77.Smigocki AC, Ivic-Haymes S, Li H, Savic J. Pest protection conferred by a Beta vulgaris serine proteinase inhibitor gene. PLoS One. 2013;8(2):e57303.Mazumdar-Leighton S, Broadway RM. Transcriptional induction of diverse midgut trypsins in larval Agrotis ipsilon and Helicoverpa zea feeding on the soybean trypsin inhibitor. Insect Biochem Mol Biol. 2001;31(6–7):645–57.Oppert B, Morgan TD, Hartzer K, Kramer KJ. Compensatory proteolytic responses to dietary proteinase inhibitors in the red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae). Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 2005;140(1):53–8.Broadway RM. Dietary regulation of serine proteinases that are resistant to serine proteinase inhibitors. J Insect Physiol. 1997;43(9):855–74.Zhu-Salzman K, Koiwa H, Salzman R, Shade R, Ahn JE. Cowpea bruchid Callosobruchus maculatus uses a three-component strategy to overcome a plant defensive cysteine protease inhibitor. Insect Mol Biol. 2003;12(2):135–45.Oppert B, Morgan TD, Hartzer K, Lenarcic B, Galesa K, Brzin J, Turk V, Yoza K, Ohtsubo K, Kramer KJ. Effects of proteinase inhibitors on digestive proteinases and growth of the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae). Comparative biochemistry and physiology Toxicology & pharmacology : CBP. 2003;134(4):481–90.Duan X, Li X, Xue Q, Abo-El-Saad M, Xu D, Wu R. Transgenic rice plants harboring an introduced potato proteinase inhibitor II gene are insect resistant. Nat Biotechnol. 1996;14(4):494–8.Pompermayer P, Lopes AR, Terra WR, Parra JRP, Falco MC, Silva-Filho MC. Effects of soybean proteinase inhibitor on development, survival and reproductive potential of the sugarcane borer, Diatraea saccharalis. Entomologia Experimentalis et Applicata. 2001;99(1):79–85.Alfonso-Rubí J, Ortego F, Castañera P, Carbonero P, Díaz I. Transgenic expression of trypsin inhibitor CMe from barley in indica and japonica rice, confers resistance to the rice weevil Sitophilus oryzae. Transgenic Res. 2003;12(1):23–31.Altpeter F, Diaz I, Mc Auslane H, Gaddour K, Carbonero P, Vasil IK. Increased insect resistance in transgenic wheat stably expressing trypsin inhibitor CMe. Mol Breed. 1999;5(1):53–63.Martinez M, Cambra I, Carrillo L, Diaz-Mendoza M, Diaz I. Characterization of the entire cystatin gene family in barley and their target cathepsin L-like cysteine-proteases, partners in the hordein mobilization during seed germination. Plant Physiol. 2009;151(3):1531–45.FAOSTAT: Food and Organization of the United Nations, statistics division. 2017.Mueller LA, Lankhorst RK, Tanksley SD, Giovannoni JJ, White R, Vrebalov J, Fei Z, van Eck J, Buels R, Mills AA, et al. A snapshot of the emerging tomato genome sequence. The Plant Genome. 2009;2(1):78–92.Ellul P, Garcia-Sogo B, Pineda B, Rios G, Roig L, Moreno V. The ploidy level of transgenic plants in agrobacterium-mediated transformation of tomato cotyledons (Lycopersicon esculentum L. mill.) is genotype and procedure dependent. Theor Appl Genet. 2003;106(2):231–8.Pino LE, Lombardi-Crestana S, Azevedo MS, Scotton DC, Borgo L, Quecini V, Figueira A, Peres LE. The Rg1 allele as a valuable tool for genetic transformation of the tomato'Micro-Tom'model system. Plant Methods. 2010;6(1):23.Sharma MK, Solanke AU, Jani D, Singh Y, Sharma AK. A simple and efficient agrobacterium-mediated procedure for transformation of tomato. J Biosci. 2009;34(3):423–33.van Eck J, Kirk DD, Walmsley AM. Tomato (Lycopersicum esculentum). Agrobacterium Protocols. 2006:459–74.Dan Y, Yan H, Munyikwa T, Dong J, Zhang Y, Armstrong CL. MicroTom—a high-throughput model transformation system for functional genomics. Plant Cell Rep. 2006;25(5):432–41.Pearce G, Strydom D, Johnson S, Ryan CA. A polypeptide from tomato leaves induces wound-inducible proteinase inhibitor proteins. Science. 1991;253(5022):895–9.Farmer EE, Ryan CA. Interplant communication: airborne methyl jasmonate induces synthesis of proteinase inhibitors in plant leaves. Proc Natl Acad Sci. 1990;87(19):7713–6.Bosch M, Wright LP, Gershenzon J, Wasternack C, Hause B, Schaller A, Stintzi A. Jasmonic acid and its precursor 12-oxophytodienoic acid control different aspects of constitutive and induced herbivore defenses in tomato. Plant Physiol. 2014;166(1):396–410.Christensen SA, Nemchenko A, Borrego E, Murray I, Sobhy IS, Bosak L, DeBlasio S, Erb M, Robert CA, Vaughn KA. The maize lipoxygenase, ZmLOX10, mediates green leaf volatile, jasmonate and herbivore-induced plant volatile production for defense against insect attack. Plant J. 2013;74(1):59–73.Boughton AJ, Hoover K, Felton GW. Methyl jasmonate application induces increased densities of glandular trichomes on tomato, Lycopersicon esculentum. J Chem Ecol. 2005;31(9):2211–6.Li L, Zhao Y, McCaig BC, Wingerd BA, Wang J, Whalon ME, Pichersky E, Howe GA. The tomato homolog of CORONATINE-INSENSITIVE1 is required for the maternal control of seed maturation, jasmonate-signaled defense responses, and glandular trichome development. Plant Cell. 2004;16(1):126–43.Peiffer M, Tooker JF, Luthe DS, Felton GW. Plants on early alert: glandular trichomes as sensors for insect herbivores. New Phytol. 2009;184(3):644–56.Bryant J, Green TR, Gurusaddaiah T, Ryan CA. Proteinase inhibitor II from potatoes: isolation and characterization of its protomer components. Biochemistry. 1976;15(16):3418–24.Johnson R, Narvaez J, An G, Ryan C. Expression of proteinase inhibitors I and II in transgenic tobacco plants: effects on natural defense against Manduca sexta larvae. Proc Natl Acad Sci. 1989;86(24):9871–5.Klopfenstein NB, Allen KK, Avila FJ, Heuchelin SA, Martinez J, Carman RC, Hall RB, Hart ER, McNabb HS. Proteinase inhibitor II gene in transgenic poplar: chemical and biological assays. Biomass Bioenergy. 1997;12(4):299–311.Dicke M, Takabayashi J, Posthumus MA, Schütte C, Krips OE. Plant—Phytoseiid interactions mediated by herbivore-induced plant volatiles: variation in production of cues and in responses of predatory mites. Exp Appl Acarol. 1998;22(6):311–33.Turlings T, Loughrin JH, Mccall PJ, Röse U, Lewis WJ, Tumlinson JH. How caterpillar-damaged plants protect themselves by attracting parasitic wasps. Proc Natl Acad Sci. 1995;92(10):4169–74.Levin DA. The role of trichomes in plant defense. Q Rev Biol. 1973;48(1, Part 1):3–15.Traw BM, Dawson TE. Differential induction of trichomes by three herbivores of black mustard. Oecologia. 2002;131(4):526–32.Handley R, Ekbom B, Ågren J. Variation in trichome density and resistance against a specialist insect herbivore in natural populations of Arabidopsis thaliana. Ecological Entomology. 2005;30(3):284–92.Valverde P, Fornoni J, NÚÑez-Farfán J. Defensive role of leaf trichomes in resistance to herbivorous insects in Datura stramonium. J Evol Biol. 2001;14(3):424–32.Elle E, Hare J. Environmentally induced variation in floral traits affects the mating system in Datura wrightii. Funct Ecol. 2002;16(1):79–88.Agrawal AA. Benefits and costs of induced plant defense for Lepidium virginicum (Brassicaceae). Ecology. 2000;81(7):1804–13.Dalin P, Björkman C. Adult beetle grazing induces willow trichome defence against subsequent larval feeding. Oecologia. 2003;134(1):112–8.Campos MR, Biondi A, Adiga A, Guedes RN, Desneux N. From the western Palaearctic region to beyond: Tuta absoluta 10 years after invading Europe. J Pest Sci. 2017:1–10.Desneux N, Wajnberg E, Wyckhuys KA, Burgio G, Arpaia S, Narváez-Vasquez CA, González-Cabrera J, Ruescas DC, Tabone E, Frandon J. Biological invasion of European tomato crops by Tuta absoluta: ecology, geographic expansion and prospects for biological control. J Pest Sci. 2010;83(3):197–215.Urbaneja A, Montón H, Mollá O. Suitability of the tomato borer Tuta absoluta as prey for Macrolophus pygmaeus and Nesidiocoris tenuis. J Appl Entomol. 2009;133(4):292–6.Pérez-Hedo M, Urbaneja A. Prospects for predatory mirid bugs as biocontrol agents of aphids in sweet peppers. J Pest Sci. 2015;88(1):65–73.Hewitt E. The composition of the nutrient solution. Sand and water culture methods used in the study of plant Nutrition. 1966:187–246.Karimi M, Inzé D, Depicker A. GATEWAY™ vectors for agrobacterium-mediated plant transformation. Trends Plant Sci. 2002;7(5):193–5.Martín-Trillo M, Grandío EG, Serra F, Marcel F, Rodríguez-Buey ML, Schmitz G, Theres K, Bendahmane A, Dopazo H, Cubas P. Role of tomato BRANCHED1-like genes in the control of shoot branching. Plant J. 2011;67(4):701–14.Vargas C. Observations on the bionomics and natural enemies of the tomato moth, Gnorimoschema absoluta (Meyrick)(Lep. Gelechiidae). Idesia. 1970;1:75–110.Mollá O, Biondi A, Alonso-Valiente M, Urbaneja A. A comparative life history study of two mirid bugs preying on Tuta absoluta and Ephestia kuehniella eggs on tomato crops: implications for biological control. BioControl. 2014;59(2):175–83.Abbot C. Solar variation and the weather. Science (New York, NY). 1925;62(1605):307.Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72(1–2):248–54.Bouagga S, Urbaneja A, Rambla JL, Granell A, Pérez-Hedo M. Orius laevigatus strengthens its role as a biological control agent by inducing plant defenses. J Pest Sci. 2017:1–10.Hilder VA, Gatehouse AM, Sheerman SE, Barker RF, Boulter D. A novel mechanism of insect resistance engineered into tobacco. Nature. 1987;330(6144):160–3.Saikia K, Kalita J, Saikia PK. Biology and life cycle generations of common crow–Euploea core core Cramer (Lepidoptera: Danainae) on Hemidesmus indica host plant. Int J NeBIO. 2010;1(3):28–37.Srinivasan A, Giri AP, Gupta VS. Structural and functional diversities in lepidopteran serine proteases. Cellular & molecular biology letters. 2006;11(1):132.Tamhane VA, Chougule NP, Giri AP, Dixit AR, Sainani MN, Gupta VS. In vivo and in vitro effect of Capsicum annum proteinase inhibitors on Helicoverpa armigera gut proteinases. Biochimica et Biophysica Acta (BBA)-General Subjects. 2005;1722(2):156–67.Telang M, Srinivasan A, Patankar A, Harsulkar A, Joshi V, Damle A, Deshpande V, Sainani M, Ranjekar P, Gupta G. Bitter gourd proteinase inhibitors: potential growth inhibitors of Helicoverpa armigera and Spodoptera litura. Phytochemistry. 2003;63(6):643–52.Damle MS, Giri AP, Sainani MN, Gupta VS. Higher accumulation of proteinase inhibitors in flowers than leaves and fruits as a possible basis for differential feeding preference of Helicoverpa armigera on tomato (Lycopersicon esculentum mill, cv. Dhanashree). Phytochemistry. 2005;66(22):2659–67.De Leo F, Bonadé-Bottino MA, Ceci LR, Gallerani R, Jouanin L. Opposite effects on spodoptera littoralis larvae of high expression level of a trypsin proteinase inhibitor in transgenic plants. Plant Physiol. 1998;118(3):997–1004.Rahbé Y, Ferrasson E, Rabesona H, Quillien L. Toxicity to the pea aphid Acyrthosiphon pisum of anti-chymotrypsin isoforms and fragments of Bowman–Birk protease inhibitors from pea seeds. Insect Biochem Mol Biol. 2003;33(3):299–306.Luo M, Ding L-W, Ge Z-J, Wang Z-Y, Hu B-L, Yang X-B, Sun Q-Y, Xu Z-F. The characterization of SaPIN2b, a plant trichome-localized proteinase inhibitor from Solanum americanum. Int J Mol Sci. 2012;13(11):15162–76.Dalin P, Ågren J, Björkman C, Huttunen P, Kärkkäinen K. Leaf trichome formation and plant resistance to herbivory. In: Dordrecht SA, editor. Induced plant resistance to herbivory. Netherlands: Springer; 2008. p. 89–105.Gonzáles WL, Negritto MA, Suárez LH, Gianoli E. Induction of glandular and non-glandular trichomes by damage in leaves of Madia sativa under contrasting water regimes. Acta Oecol. 2008;33(1):128–32.Luo M, Wang Z, Li H, Xia K-F, Cai Y, Xu Z-F. Overexpression of a weed (Solanum americanum) proteinase inhibitor in transgenic tobacco results in increased glandular trichome density and enhanced resistance to Helicoverpa armigera and Spodoptera litura. Int J Mol Sci. 2009;10(4):1896–910.Björkman C, Dalin P, Ahrné K. Leaf trichome responses to herbivory in willows: induction, relaxation and costs. New Phytol. 2008;179(1):176–84.Duffey S. Plant glandular trichomes: their partial role in defence against insects. Insects and the plant surface. London: Edward Arnold; 1986. p. 151–72.James DG. Further field evaluation of synthetic herbivore-induced plan volatiles as attractants for beneficial insects. J Chem Ecol. 2005;31(3):481–95.Naselli M, Zappalà L, Gugliuzzo A, Garzia GT, Biondi A, Rapisarda C, Cincotta F, Condurso C, Verzera A, Siscaro G. Olfactory response of the zoophytophagous mirid Nesidiocoris tenuis to tomato and alternative host plants. Arthropod Plant Interact. 2017;11(2):121–31.Tholl D. Biosynthesis and biological functions of terpenoids in plants. Advances in Biochemical Engineering and Biotechnology. 2015;148:63-106.Lange BM, Rujan T, Martin W, Croteau R. Isoprenoid biosynthesis: the evolution of two ancient and distinct pathways across genomes. Proc Natl Acad Sci. 2000;97(24):13172–7.Dudareva N, Klempien A, Muhlemann JK, Kaplan I. Biosynthesis, function and metabolic engineering of plant volatile organic compounds. New Phytol. 2013;198(1):16–32.Razal RA, Ellis S, Singh S, Lewis NG, Towers GHN. Nitrogen recycling in phenylpropanoid metabolism. Phytochemistry. 1996;41(1):31–5.Effmert U, Große J, Röse US, Ehrig F, Kägi R, Piechulla B. Volatile composition, emission pattern, and localization of floral scent emission in Mirabilis jalapa (Nyctaginaceae). Am J Bot. 2005;92(1):2–12.Guterman I, Masci T, Chen X, Negre F, Pichersky E, Dudareva N, Weiss D, Vainstein A. Generation of phenylpropanoid pathway-derived volatiles in transgenic plants: rose alcohol acetyltransferase produces phenylethyl acetate and benzyl acetate in petunia flowers. Plant Mol Biol. 2006;60(4):555–63.Vogel JT, Tan B-C, McCarty DR, Klee HJ. The carotenoid cleavage dioxygenase 1 enzyme has broad substrate specificity, cleaving multiple carotenoids at two different bond positions. J Biol Chem. 2008;283(17):11364–73.Colquhoun TA, Kim JY, Wedde AE, Levin LA, Schmitt KC, Schuurink RC, Clark DG. PhMYB4 fine-tunes the floral volatile signature of petunia×hybrida through PhC4H. J Exp Bot. 2011;62(3):1133–43.Kolosova N, Gorenstein N, Kish CM, Dudareva N. Regulation of circadian methyl benzoate emission in diurnally and nocturnally emitting plants. Plant Cell. 2001;13(10):2333–47.Maeda H, Shasany AK, Schnepp J, Orlova I, Taguchi G, Cooper BR, Rhodes D, Pichersky E, Dudareva N. RNAi suppression of arogenate dehydratase1 reveals that phenylalanine is synthesized predominantly via the arogenate pathway in petunia petals. Plant Cell. 2010;22(3):832–49.Lerdau M, Gray D. Ecology and evolution of light-dependent and light-independent phytogenic volatile organic carbon. New Phytol. 2003;157(2):199–211.Martin DM, Gershenzon J, Bohlmann J. Induction of volatile terpene biosynthesis and diurnal emission by methyl jasmonate in foliage of Norway spruce. Plant Physiol. 2003;132(3):1586–99.van Doorn WG, Woltering EJ. Physiology and molecular biology of petal senescence. J Exp Bot. 2008;59(3):453–80

    BRAFV600E-mutated serrated colorectal neoplasia drives transcriptional activation of cholesterol metabolism

    No full text
    BRAF mutations occur early in serrated colorectal cancers, but their long-term influence on tissue homeostasis is poorly characterized. We investigated the impact of short-term (3 days) and long-term (6 months) expression of Braf V600E in the intestinal tissue of an inducible mouse model. We show that Braf V600E perturbs the homeostasis of intestinal epithelial cells, with impaired differentiation of enterocytes emerging after prolonged expression of the oncogene. Moreover, Braf V600E leads to a persistent transcriptional reprogramming with enrichment of numerous gene signatures indicative of proliferation and tumorigenesis, and signatures suggestive of metabolic rewiring. We focused on the top-ranking cholesterol biosynthesis signature and confirmed its increased expression in human serrated lesions. Functionally, the cholesterol lowering drug atorvastatin prevents the establishment of intestinal crypt hyperplasia in Braf V600E-mutant mice. Overall, our work unveils the long-term impact of Braf V600E expression in intestinal tissue and suggests that colorectal cancers with mutations in BRAF might be prevented by statins
    corecore