ZFIN ID: ZDB-LAB-030925-3
MacRae Lab
PI/Director: MacRae, Calum A.
Contact Person: Buys, Eva Plovie
Email: eplovie@partners.org
URL: http://macraelab.bwh.harvard.edu
Address: Cardiovascular Division Brigham and Women's Hospital Thorn 11 Rm1130 75 Francis Street Boston, MA 02115
Country: United States
Phone: 857-307-0302
Fax: 857-307-0300
Line Designation: bw

Show all 20 genomic features


Buys, Eva Plovie Administrative Staff

Lam, P.Y., Kutchukian, P., Anand, R., Imbriglio, J., Andrews, C., Padilla, H., Vohra, A., Lane, S., Parker, D.L., Taracido, I.C., Johns, D.G., Beerens, M., MacRae, C.A., Caldwell, J., Sorota, S., Asnani, A., Peterson, R.T. (2020) Cyp1 inhibition prevents doxorubicin-induced cardiomyopathy in a zebrafish heart failure model. Chembiochem : a European journal of chemical biology. 21(13):1905-1910
Ghazizadeh, Z., Kiviniemi, T.O., Olafsson, S., Plotnick, D., Beerens, M., Zhang, K., Gillon, L., Steinbaugh, M., Barrera, V., Ho Sui, S., Werdich, A.A., Kapur, S., Eranti, A., Gunn, J., Jalkanen, J., Airaksinen, J., Kleber, A.G., Hollmén, M., MacRae, C.A. (2019) A Metastable Atrial State Underlies The Primary Genetic Substrate for MYL4 Mutation-Associated Atrial Fibrillation. Circulation. 141(4):301-312
Moshal, K.S., Roder, K., Kabakov, A.Y., Werdich, A.A., Chiang, D.Y., Turan, N.N., Xie, A., Kim, T.Y., Cooper, L.L., Lu, Y., Zhong, M., Li, W., Terentyev, D., Choi, B.R., Karma, A., MacRae, C.A., Koren, G. (2019) LITAF Regulates Cardiac L-type Calcium Channels by Modulating NEDD4-1 Ubiquitin Ligase. Circulation. Genomic and precision medicine. 12(9):407-420
Mishra, S., Joshi, S., Ward, J.E., Buys, E.P., Mishra, D., Mishra, D., Morgado, I., Fisch, S., Lavatelli, F., Merlini, G., Dorbala, S., MacRae, C.A., Liao, R. (2019) Zebrafish model of amyloid light chain cardiotoxicity: regeneration vs degeneration. American journal of physiology. Heart and circulatory physiology. 316(5):H1158-H1166
Zhao, Y., Zhang, K., Sips, P., MacRae, C.A. (2019) Screening drugs for myocardial disease in vivo with zebrafish: an expert update. Expert opinion on drug discovery. 14(4):343-353
Morningstar, J., Lee, J., Hendry-Hofer, T., Witeof, A., Lyle, L.T., Knipp, G., MacRae, C.A., Boss, G.R., Peterson, R.T., Davisson, V.J., Gerszten, R.E., Bebarta, V.S., Mahon, S., Brenner, M., Nath, A.K. (2018) Intramuscular administration of hexachloroplatinate reverses cyanide-induced metabolic derangements and counteracts severe cyanide poisoning.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 1:81-92
Kithcart, A.P., MacRae, C.A. (2018) Zebrafish assay development for cardiovascular disease mechanism and drug discovery. Progress in Biophysics and Molecular Biology. 138:126-131
Sips, P.Y., Shi, X., Musso, G., Nath, A.K., Zhao, Y., Nielson, J., Morningstar, J., Kelly, A.E., Mikell, B., Buys, E., Bebarta, V., Rutter, J., Davisson, V.J., Mahon, S., Brenner, M., Boss, G.R., Peterson, R.T., Gerszten, R.E., MacRae, C.A. (2018) Identification of specific metabolic pathways as druggable targets regulating the sensitivity to cyanide poisoning. PLoS One. 13:e0193889
Natarajan, N., Abbas, Y., Bryant, D.M., Gonzalez-Rosa, J.M., Sharpe, M., Uygur, A., Cocco-Delgado, L.H., Ho, N.N., Gerard, N.P., Gerard, C.J., Macrae, C.A., Burns, C.E., Burns, C.G., Whited, J.L., Lee, R.T. (2018) Complement Receptor C5aR1 Plays an Evolutionarily Conserved Role in Successful Cardiac Regeneration. Circulation. 137(20):2152-2165
Colombo, S., de Sena-Tomás, C., George, V., Werdich, A.A., Kapur, S., MacRae, C.A., Targoff, K.L. (2017) nkx genes establish SHF cardiomyocyte progenitors at the arterial pole and pattern the venous pole through Isl1 repression. Development (Cambridge, England). 145(3)
Nath, A.K., Shi, X., Harrison, D.L., Morningstar, J.E., Mahon, S., Chan, A., Sips, P., Lee, J., MacRae, C.A., Boss, G.R., Brenner, M., Gerszten, R.E., Peterson, R.T. (2017) Cisplatin Analogs Confer Protection against Cyanide Poisoning. Cell chemical biology. 24(5):565-575.e4
Rider, S.A., Christian, H.C., Mullins, L.J., Howarth, A.R., MacRae, C.A., Mullins, J.J. (2017) Zebrafish mesonephric renin cells are functionally conserved and comprise of two distinct morphological populations. American journal of physiology. Renal physiology. 312(4):F778-F790
Kithcart, A., MacRae, C.A. (2017) Using Zebrafish for High-Throughput Screening of Novel Cardiovascular Drugs. JACC. Basic to translational science. 2:1-12
Santiago-Sim, T., Fang, X., Hennessy, M.L., Nalbach, S.V., DePalma, S.R., Lee, M.S., Greenway, S.C., McDonough, B., Hergenroeder, G.W., Patek, K.J., Colosimo, S.M., Qualmann, K.J., Hagan, J.P., Milewicz, D.M., MacRae, C.A., Dymecki, S.M., Seidman, C.E., Seidman, J.G., Kim, D.H. (2016) THSD1 (Thrombospondin Type 1 Domain Containing Protein 1) Mutation in the Pathogenesis of Intracranial Aneurysm and Subarachnoid Hemorrhage. Stroke. 47:3005-3013
Olabisi, O., Al-Romaih, K., Henderson, J., Tomar, R., Drummond, I., MacRae, C., Pollak, M. (2016) From man to fish: What can Zebrafish tell us about ApoL1 nephropathy?. Clinical nephrology. 86 (2016)(13):114-118
Wang, M., Sips, P., Khin, E., Rotival, M., Sun, X., Ahmed, R., Widjaja, A.A., Schafer, S., Yusoff, P., Choksi, P.K., Ko, N.S., Singh, M.K., Epstein, D., Guan, Y., Houštěk, J., Mracek, T., Nuskova, H., Mikell, B., Tan, J., Pesce, F., Kolar, F., Bottolo, L., Mancini, M., Hubner, N., Pravenec, M., Petretto, E., MacRae, C., Cook, S.A. (2016) Wars2 is a determinant of angiogenesis. Nature communications. 7:12061
Chelko, S.P., Asimaki, A., Andersen, P., Bedja, D., Amat-Alarcon, N., DeMazumder, D., Jasti, R., MacRae, C.A., Leber, R., Kleber, A.G., Saffitz, J.E., Judge, D.P. (2016) Central role for GSK3β in the pathogenesis of arrhythmogenic cardiomyopathy. JCI insight. 1(5)
Treggiari, D., Zoccatelli, G., Molesini, B., Degan, M., Rotino, G.L., Sala, T., Cavallini, C., MacRae, C.A., Minuz, P., Pandolfini, T. (2015) A cystine-knot miniprotein from tomato fruit inhibits endothelial cell migration and angiogenesis by affecting vascular endothelial growth factor receptor (VEGFR) activation and nitric oxide production. Molecular Nutrition & Food Research. 59(11):2255-66
MacRae, C.A., Peterson, R.T. (2015) Zebrafish as tools for drug discovery. Nature reviews. Drug discovery. 14(10):721-31
Musso, G., Mosimann, C., Panáková, D., Burger, A., Zhou, Y., Zon, L.I., MacRae, C.A. (2015) Generating and evaluating a ranked candidate gene list for potential vertebrate heart field regulators. Genomics Data. 6:199-201
Rider, S.A., Mullins, L.J., Verdon, R.F., MacRae, C.A., Mullins, J.J. (2015) Renin expression in developing zebrafish is associated with angiogenesis and requires the Notch pathway and endothelium. American journal of physiology. Renal physiology. 309(6):F531-9
Mosimann, C., Panáková, D., Werdich, A.A., Musso, G., Burger, A., Lawson, K.L., Carr, L.A., Nevis, K.R., Sabeh, M.K., Zhou, Y., Davidson, A.J., DiBiase, A., Burns, C.E., Burns, C.G., MacRae, C.A., Zon, L.I. (2015) Chamber identity programs drive early functional partitioning of the heart. Nature communications. 6:8146
Mahmoud, A.I., O'Meara, C.C., Gemberling, M., Zhao, L., Bryant, D.M., Zheng, R., Gannon, J.B., Cai, L., Choi, W.Y., Egnaczyk, G.F., Burns, C.E., Burns, C.G., MacRae, C.A., Poss, K.D., Lee, R.T. (2015) Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration. Developmental Cell. 34(4):387-99
Roder, K., Werdich, A.A., Li, W., Liu, M., Kim, T.Y., Organ-Darling, L.E., Moshal, K.S., Hwang, J.M., Lu, Y., Choi, B.R., MacRae, C.A., Koren, G. (2014) RING Finger Protein RNF207, a Novel Regulator of Cardiac Excitation. The Journal of biological chemistry. 289(49):33730-40
Deo, R.C., Musso, G., Tasan, M., Tang, P., Poon, A., Yuan, C., Felix, J.F., Vasan, R.S., Beroukhim, R., De Marco, T., Kwok, P.Y., MacRae, C.A., Roth, F.P. (2014) Prioritizing causal disease genes using unbiased genomic features. Genome biology. 15:534
Guan, J., Mishra, S., Qiu, Y., Shi, J., Trudeau, K., Las, G., Liesa, M., Shirihai, O.S., Connors, L.H., Seldin, D.C., Falk, R.H., MacRae, C.A., Liao, R. (2014) Lysosomal dysfunction and impaired autophagy underlie the pathogenesis of amyloidogenic light chain-mediated cardiotoxicity. EMBO Molecular Medicine. 6(11):1493-507
Kim, A.D., Melick, C.H., Clements, W.K., Stachura, D.L., Distel, M., Panáková, D., MacRae, C., Mork, L.A., Crump, J.G., Traver, D. (2014) Discrete Notch signaling requirements in the specification of hematopoietic stem cells. The EMBO journal. 33(20):2363-73
Asimaki, A., Kapoor, S., Plovie, E., Karin Arndt, A., Adams, E., Liu, Z., James, C.A., Judge, D.P., Calkins, H., Churko, J., Wu, J.C., MacRae, C.A., Kléber, A.G., Saffitz, J.E. (2014) Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy. Science Translational Medicine. 6:240ra74
Pieperhoff, S., Wilson, K.S., Baily, J., de Mora, K., Maqsood, S., Vass, S., Taylor, J., Del-Pozo, J., MacRae, C.A., Mullins, J.J., Denvir, M.A. (2014) Heart on a plate: histological and functional assessment of isolated adult zebrafish hearts maintained in culture. PLoS One. 9:e96771
Zhao, L., Borikova, A.L., Ben-Yair, R., Guner-Ataman, B., MacRae, C.A., Lee, R.T., Burns, C.G., and Burns, C.E. (2014) Notch signaling regulates cardiomyocyte proliferation during zebrafish heart regeneration. Proceedings of the National Academy of Sciences of the United States of America. 111(4):1403-1408
Becker, J.R., Chatterjee, S., Robinson, T.Y., Bennett, J.S., Panáková, D., Galindo, C.L., Zhong, L., Shin, J.T., Coy, S.M., Kelly, A.E., Roden, D.M., Lim, C.C., and MacRae, C.A. (2014) Differential activation of natriuretic peptide receptors modulates cardiomyocyte proliferation during development. Development (Cambridge, England). 141(2):335-345
Musso, G., Tasan, M., Mosimann, C., Beaver, J.E., Plovie, E., Carr, L.A., Chua, H.N., Dunham, J., Zuberi, K., Rodriguez, H., Morris, Q., Zon, L., Roth, F.P., and MacRae, C.A. (2014) Novel cardiovascular gene functions revealed via systematic phenotype prediction in zebrafish. Development (Cambridge, England). 141(1):224-235
Huang, C.J., Wilson, V., Pennings, S., MacRae, C.A., and Mullins, J. (2013) Sequential effects of spadetail, one-eyed pinhead and no tail on midline convergence of nephric primordia during zebrafish embryogenesis. Developmental Biology. 384(2):290-300
Icli, B., Wara, A.K., Moslehi, J., Sun, X., Plovie, E., Cahill, M., Marchini, J.F., Schissler, A., Padera, R.F., Shi, J., Cheng, H.W., Raghuram, S., Arany, Z., Liao, R., Croce, K., MacRae, C.A., and Feinberg, M.W. (2013) MicroRNA-26a Regulates Pathological And Physiological Angiogenesis by Targeting BMP/SMAD1 Signaling. Circulation research. 113(11):1231-41
Guan, J., Mishra, S., Shi, J., Plovie, E., Qiu, Y., Cao, X., Gianni, D., Jiang, B., Del Monte, F., Connors, L.H., Seldin, D.C., Lavatelli, F., Rognoni, P., Palladini, G., Merlini, G., Falk, R.H., Semigran, M.J., Dec, G.W., MacRae, C.A., and Liao, R. (2013) Stanniocalcin1 is a key mediator of amyloidogenic light chain induced cardiotoxicity. Basic Research in Cardiology. 108(5):378
Arndt, A.K., Schafer, S., Drenckhahn, J.D., Sabeh, M.K., Plovie, E.R., Caliebe, A., Klopocki, E., Musso, G., Werdich, A.A., Kalwa, H., Heinig, M., Padera, R.F., Wassilew, K., Bluhm, J., Harnack, C., Martitz, J., Barton, P.J., Greutmann, M., Berger, F., Hubner, N., Siebert, R., Kramer, H.H., Cook, S.A., MacRae, C.A., and Klaassen, S. (2013) Fine Mapping of the 1p36 Deletion Syndrome Identifies Mutation of PRDM16 as a Cause of Cardiomyopathy. American journal of human genetics. 93(1):67-77
Mishra, S., Guan, J., Plovie, E., Seldin, D.C., Connors, L.H., Merlini, G., Falk, R.H., MacRae, C.A., and Liao, R. (2013) Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish. American journal of physiology. Heart and circulatory physiology. 305(1):H95-H103
Kolpa, H.J., Peal, D.S., Lynch, S.N., Giokas, A.C., Ghatak, S., Misra, S., Norris, R.A., MacRae, C.A., Markwald, R.R., Ellinor, P., Bischoff, J., and Milan, D.J. (2013) miR-21 represses Pdcd4 during cardiac valvulogenesis. Development (Cambridge, England). 140(10):2172-80
MacRae, C.A. (2013) Recent advances in in vivo screening for antiarrhythmic drugs. Expert opinion on drug discovery. 8(2):131-141
Jin, S., Sarkar, K.S., Jin, Y.N., Liu, Y., Kokel, D., Van Ham, T.J., Roberts, L.D., Gerszten, R.E., MacRae, C.A., and Peterson, R.T. (2013) An In Vivo Zebrafish Screen Identifies Organophosphate Antidotes with Diverse Mechanisms of Action. Journal of Biomolecular Screening. 18(1):108-115
Peterson, R.T., and MacRae, C.A. (2013) Changing the Scale and Efficiency of Chemical Warfare Countermeasure Discovery Using the Zebrafish. Drug Discovery Today: Disease Models. 10(1):e37–e42
Werdich, A.A., Brzezinski, A., Jeyaraj, D., Ficker, E., Wan, X., McDermott, B.M., Sabeh, M.K., MacRae, C.A., and Rosenbaum, D.S. (2012) The zebrafish as a novel animal model to study the molecular mechanisms of mechano-electrical feedback in the heart. Progress in Biophysics and Molecular Biology. 110(2-3):154-165
Rider, S.A., Tucker, C.S., Del-Pozo, J., Rose, K.N., MacRae, C.A., Bailey, M.A., and Mullins, J.J. (2012) Techniques for the in vivo assessment of cardio-renal function in zebrafish (Danio rerio) larvae. The Journal of physiology. 590(8):1803-1809
Becker, J.R., Robinson, T.Y., Sachidanandan, C., Kelly, A.E., Coy, S., Peterson, R.T., and MacRae, C.A. (2012) In vivo natriuretic peptide reporter assay identifies chemical modifiers of hypertrophic cardiomyopathy signaling. Cardiovascular research. 93(3):463-470
Peterson, R.T., and MacRae, C.A. (2012) Systematic Approaches to Toxicology in the Zebrafish. Annual Review of Pharmacology and Toxicology. 52:433-53
Wythe, J.D., Jurynec, M.J., Urness, L.D., Jones, C.A., Sabeh, M.K., Werdich, A.A., Sato, M., Yost, H.J., Grunwald, D.J., MacRae, C.A., and Li, D.Y. (2011) Hadp1, a newly identified pleckstrin homology domain protein, is required for cardiac contractility in zebrafish. Disease models & mechanisms. 4(5):607-21
Wang, J., Panáková, D., Kikuchi, K., Holdway, J.E., Gemberling, M., Burris, J.S., Singh, S.P., Dickson, A.L., Lin, Y.F., Sabeh, M.K., Werdich, A.A., Yelon, D., MacRae, C.A., and Poss, K.D. (2011) The regenerative capacity of zebrafish reverses cardiac failure caused by genetic cardiomyocyte depletion. Development (Cambridge, England). 138(16):3421-30
Becker, J.R., Deo, R.C., Werdich, A.A., Panàkovà, D., Coy, S., and MacRae, C.A. (2011) Human cardiomyopathy mutations induce myocyte hyperplasia and activate hypertrophic pathways during cardiogenesis in zebrafish. Disease models & mechanisms. 4(3):400-410
Deo, R.C., and MacRae, C.A. (2011) The zebrafish:scalable in vivo modeling for systems biology. Wiley Interdisciplinary Reviews. Systems Biology and Medicine. 3(3):335-46
Sogah, V.M., Serluca, F.C., Fishman, M.C., Yelon, D.L., MacRae, C.A., and Mably, J.D. (2010) Distinct troponin C isoform requirements in cardiac and skeletal muscle. Developmental dynamics : an official publication of the American Association of Anatomists. 239(11):3115-3123
Panáková, D., Werdich, A.A., and MacRae, C.A. (2010) Wnt11 patterns a myocardial electrical gradient through regulation of the L-type Ca(2+) channel. Nature. 466(7308):874-878
Shin, J.T., Pomerantsev, E.V., Mably, J.D., and MacRae, C.A. (2010) High-resolution cardiovascular function confirms functional orthology of myocardial contractility pathways in zebrafish. Physiological Genomics. 42(2):300-309
MacRae, C.A. (2010) Cardiac Arrhythmia: In vivo screening in the zebrafish to overcome complexity in drug discovery. Expert opinion on drug discovery. 5(7):619-632
Lamont, R.E., Vu, W., Carter, A.D., Serluca, F.C., MacRae, C.A., and Childs, S.J. (2010) Hedgehog signaling via angiopoietin1 is required for developmental vascular stability. Mechanisms of Development. 127(3-4):159-168
Kikuchi, K., Holdway, J.E., Werdich, A.A., Anderson, R.M., Fang, Y., Egnaczyk, G.F., Evans, T., MacRae, C.A., Stainier, D.Y., and Poss, K.D. (2010) Primary contribution to zebrafish heart regeneration by gata4(+) cardiomyocytes. Nature. 464(7288):601-605
Kokel, D., Bryan, J., Laggner, C., White, R., Cheung, C.Y., Mateus, R., Healey, D., Kim, S., Werdich, A.A., Haggarty, S.J., MacRae, C.A., Shoichet, B., and Peterson, R.T. (2010) Rapid behavior-based identification of neuroactive small molecules in the zebrafish. Nature Chemical Biology. 6(3):231-237
Peal, D.S., Burns, C.G., MacRae, C.A., and Milan, D. (2009) Chondroitin sulfate expression is required for cardiac atrioventricular canal formation. Developmental dynamics : an official publication of the American Association of Anatomists. 238(12):3103-3110
Milan, D.J., Kim, A.M., Winterfield, J.R., Jones, I.L., Pfeufer, A., Sanna, S., Arking, D.E., Amsterdam, A.H., Sabeh, K.M., Mably, J.D., Rosenbaum, D.S., Peterson, R.T., Chakravarti, A., Kääb, S., Roden, D.M., and MacRae, C.A. (2009) Drug-Sensitized Zebrafish Screen Identifies Multiple Genes, Including GINS3, as Regulators of Myocardial Repolarization. Circulation. 120(7):553-559
Yeh, J.R., Munson, K.M., Chao, Y.L., Peterson, Q.P., MacRae, C.A., and Peterson, R.T. (2008) AML1-ETO reprograms hematopoietic cell fate by downregulating scl expression. Development (Cambridge, England). 135(2):401-410
Heuser, A., Plovie, E.R., Ellinor, P.T., Grossmann, K.S., Shin, J.T., Wichter, T., Basson, C.T., Lerman, B.B., Sasse-Klaassen, S., Thierfelder, L., MacRae, C.A., and Gerull, B. (2006) Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy. American journal of human genetics. 79(6):1081-1088
Milan, D.J., Jones, I.L., Ellinor, P.T., and MacRae, C.A. (2006) In vivo recording of adult zebrafish electrocardiogram and assessment of drug-induced QT prolongation. American journal of physiology. Heart and circulatory physiology. 291(1):H269-H273
Burns, C.G., and MacRae, C.A. (2006) Purification of hearts from zebrafish embryos. Biotechniques. 40(3):274, 276, 278
Milan, D.J., Giokas, A.C., Serluca, F.C., Peterson, R.T., and MacRae, C.A. (2006) Notch1b and neuregulin are required for specification of central cardiac conduction tissue. Development (Cambridge, England). 133(6):1125-1132
Burns, C.G., Milan, D.J., Grande, E.J., Rottbauer, W., MacRae, C.A., and Fishman, M.C. (2005) High-throughput assay for small molecules that modulate zebrafish embryonic heart rate. Nature Chemical Biology. 1(5):263-264
Shin, J.T., Priest, J.R., Ovcharenko, I., Ronco, A., Moore, R.K., Burns, C.G., and MacRae, C.A. (2005) Human-zebrafish non-coding conserved elements act in vivo to regulate transcription. Nucleic acids research. 33(17):5437-45
Schonberger, J., Wang, L., Shin, J.T., Kim, S.D., Depreux, F.F., Zhu, H., Zon, L., Pizard, A., Kim, J.B., MacRae, C.A., Mungall, A.J., Seidman, J.G., and Seidman, C.E. (2005) Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss. Nature Genetics. 37(4):418-422
Friedrich, E.B., Liu, E., Sinha, S., Cook, S., Milstone, D.S., MacRae, C.A., Mariotti, M., Kuhlencordt, P.J., Force, T., Rosenzweig, A., St-Arnaud, R., Dedhar, S., and Gerszten, R.E. (2004) Integrin-linked kinase regulates endothelial cell survival and vascular development. Molecular and cellular biology. 24(18):8134-8144
Peterson, R.T., Shaw, S.Y., Peterson, T.A., Milan, D.J., Zhong, T.P., Schreiber, S.L., MacRae, C.A., and Fishman, M.C. (2004) Chemical suppression of a genetic mutation in a zebrafish model of aortic coarctation. Nat. Biotechnol.. 22(5):595-599
MacRae, C.A. and Peterson, R.T. (2003) Zebrafish-based small molecule discovery. Chemistry & Biology. 10(10):901-908
Milan, D.J., Peterson, T.A., Ruskin, J.N., Peterson, R.T., and MacRae, C.A. (2003) Drugs that induce repolarization abnormalities cause bradycardia in zebrafish. Circulation. 107(10):1355-1358
MacRae, C.A. and Fishman, M.C. (2002) Zebrafish: the complete cardiovascular compendium. Cold Spring Harbor symposia on quantitative biology. 67:301-307