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RESEARCH I REPORTS <br /> Fish reared in the highest microplastic concentra- 10.W.C.Leggett,E.Deblois,Neth.J.Sea Res.32,119-134 25.G.Sundblad,U.Bergstrom,A.Sandstrom,P.Eklov,ICES J. <br /> lions were significantly smaller(8.35±0.07 min) (1994). Mar.Sci.71,672-680(2014). <br /> than fish reared in average concentrations(8.89± 11. K.M.Bailey,E.D.Houde,Adv.Mar.Biol.25,1-83(1989). 26.L.Ljunggren et al.,ICES J.Mar.Sci.67,1587-1595(2010). <br /> 12. 0.M.Lonnstedt,M.I.McCormick,M.G.Meekan, <br /> 0.12 mm)or than those without exposure to mi- M.C.0.Ferrari,D.P.Chivers,Proc.Biol.Sci.279,2091-2098 ACKNOWLEDGMENTS <br /> croplastics(9.17±0.1 mm).There was also a sig- (2012). This study was financially supported by Uppsala University- <br /> nificant difference in the number of ingested 13. F.Noren,KIMO Sweden(2007). Campus Gotland and the Swedish Research Council <br /> microplastic particles between the three treat 14. F.Noren,K.Noren,K.Magnusson,tans.Vastra GOtaland Rapp. Vetenskapsr5det.All work reported herein was conducted in <br /> 52(2014). accordance with the guidelines for the care and use of animals in <br /> ments(2 factor ANOVA:F2,45=79.24,P<0.0001; 15. D.-H.Chae,I.-S.Kim,S.-K.Kim,Y.K.Song,W.J.Shim,Arch, research of the Swedish Board of Agriculture with approval by the <br /> Fig. 3C; N= 20). Larvae from the high micro- Environ.Contam.Toxicol.69,269-278(2015). Uppsala University Ethics Committee.We thank A.Nissling, <br /> plastics treatment had consumed an average of 16.A.L.Andrady,M.A.Neal,Philos.Trans.R.Soc.London B Riol. J.Sundin,G.Rosenqvist,M.Cunha,I.Wallin,R.Gydemo,and <br /> Sci.364,1977-1984(2009). L.Vallin for logistic support and A.Roswald,I.Lonnstedt,and <br /> 7.15 ± 1.2 polystyrene particles, with stomachs 17. K.Mattsson et al.,Environ.Sci.Technol.49,553-561 M.McCormick for comments and statistical advice.The data <br /> containing solely plastic particles. In contrast, (2015). reported in this paper are archived at the research database at <br /> fish from the average microplastics treatment 18. T.Cedervall,L.-A.Hansson,M.Lard,B.Frahm,S.Linse, Uppsala University and are also included in the online <br /> consumed 1.4 ± 0.35 plastic particles but also PLOS ONE 7,e32254(2012). supplementary materials. <br /> 19. Materials and methods are available as supplementary <br /> consumed the food source(Anemia sp.nauplii) materials on Science online. <br /> that was available at similar concentrations across 20.J.W.Treasurer,Environ.Biol.Fishes 8,3-16(1983). SUPPLEMENTARY MATERIALS <br /> all three treatments.Fish that were reared in water 21. B.R.Smith,D.T.Blumstein,Behay.Ecol.19,448-455 www,sciencemag.org/content/352/6290/1213/suppl/DC1 <br /> (2008). Materials and Methods <br /> that contained no microplastics only had Anemia 22.0.M.Lonnstedt,M.I.McCormick,D.P.Chivers, <br /> sp. nauplii in their stomachs (Fig. 3, E to J). M.C.0.Ferrari,J.Anim.Ecol.83,1178-1185(2014). Figs.Si and S2 <br /> References(27-35) <br /> These results suggest that newly hatched larvae 23.D.L.Dixson,P.L.Munday,G.P.Jones,Ecol.Lett.13,68-75 VD <br /> favor microplastic particles over the more na- <br /> (2010). 16 November 2015;accepted 21 April 2016 0 <br /> 24.C.M.Rachman et al.,Sci.Rep.5,14340(2015). 10.1126/science.aad8828 N <br /> tural food source of free-swimming zooplankton. N <br /> Other aquatic organisms have been found to a) <br /> both passively and actively ingest plastic waste <br /> ti <br /> (8,24).Here it appears that larvae preferentially CELL REPROGRAMMING <br /> feed on plastic particles. o <br /> Our results suggest that environmentally o <br /> relevant concentrations of microplastic particles Conversion of human fibroblasts o" <br /> operate both chemically and physically on the ms <br /> early life stages of perch.Not only are crucial ' a) <br /> behaviors such as activity and feeding affected, into functional cardiomyocytes y 0 <br /> but innate responses to olfactory threat cues are ' <br /> impaired.Such loss of predator-avoidance behav- small molecules rn <br /> ai <br /> iors greatly increased predator-induced mortal- <br /> ity rates of larvae. ,,� 1 i,z scu <br /> -" <br /> Increases in microplasticpollution in the Bal- Nan Cao, Yu Huang, Jiashun Zheng,4'5C.Ian Spencer,'Yu Zhang, Ji-Dong Fu, <br /> p Baoming Nie,1'2 Min Xie,i'2 Mingliang Zhang,"'2 Haixia Wang,i'2 Tianhua Ma,1'2 <br /> tic Sea and marked recruitment declines of the a <br /> coastal keystone species(e.g.,perch and pike) <br /> Tao Xu,1'2 Guilai Shi,i'2 Deepak Srivastava,i'3'4*Sheng Dingi'2*-f <br /> have recently been observed(25).It has been sug- 5 <br /> Bested that population decline is related to feed- Reprogramming somatic fibroblasts into alternative lineages would provide a promising o <br /> ing in the juvenile stage,where resource deficits source of cells for regenerative therapy.However,transdifferentiating human cells into specific t <br /> may have led to increased mortality (26). Our homogeneous,functional cell types is challenging.Here we show that cardiomyocyte-like ,) I <br /> study suggests a potential driver for the observed cells can be generated by treating human fibroblasts with a combination of nine compounds o <br /> decreased recruitment rate and increased mor- that we term 9C.The chemically induced cardiomyocyte-like cells uniformly contracted and c <br /> tality.If early life-history stages of other species resembled human cardiomyocytes in their transcriptome,epigenetic,and electrophysiological c <br /> are similarly affected by microplastics,and this properties.9C treatment of human fibroblasts resulted in a more open-chromatin A <br /> translates to increased mortality rates,the effects conformation at key heart developmental genes,enabling their promoters and enhancers to <br /> on aquatic ecosystems could be profound.Our bind effectors of major cardiogenic signals.When transplanted into infarcted mouse hearts, <br /> findings highlight ecologically important and pre- 9C-treated fibroblasts were efficiently converted to chemically induced cardiomyocyte-like <br /> viously underappreciated effects of microplastic cells.This pharmacological approach to lineage-specific reprogramming may have many <br /> particles that enter marine ecosystems and em- important therapeutic implications after further optimization to generate mature cardiac cells. <br /> phasize the need for new management strat- <br /> egies to control the release of microplastic waste dvances in reprogramming enable the fate over genetic methods:They are convenient to use, <br /> products. of a cell to be changed,with potential appli- can be efficiently delivered into cells,provide <br /> cations for regenerative therapy.Cardio- <br /> REFERENCES AND NOTES myocyte(CM)-like cells can be reprogrammed <br /> 1. "Plastics-the Facts 2013;'Plastics Europe,Belgiumfrom somatic fibroblasts by overexpression 'Gladstone Institute of Cardiovascular Disease,San <br /> (2013). Francisco,CA 94158,USA. Department of Pharmaceutical <br /> 2. R.C.Thompson et al.,Science 304,838(2004). of cardiac genes in vitro(1-6)and in vivo(5,7-10). Chemistry,University of California-San Francisco,San <br /> 3. M.A.Browne et al.,Proc.Biol.Sci.282,20142929(2015). However,efficiently transdifferentiating human Francisco,CA 94158,USA.°Department of Pediatrics, <br /> 4. C.J.Moore,Environ.Res.108,131-139(2008). noncardiac cells into highly functional CMs has University of California-San Francisco,San Francisco,CA <br /> 5. A.L.Andrady,Mar.Pollut Bull.62,1596-1605(2011), remained a major challenge(1,4,6).In contrast to 94158,USA.4Department of Biochemistry and Biophysics, <br /> 6. 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R.Sussarellu et al.,Proc.Natl.Acad.Sci.U.S.A.113, fibroblast)in the absence of target cell type-specific *These authors contributed equally to this work.tCorresponding <br /> 2430-2435(2016). proteins.Small molecules have certain advantages author.Email:sheng.ding@gladstone.ucsf.edu <br /> 1216 3 JUNE 2016•VOL 352 ISSUE 6290 sciencemag.org SCIENCE <br />