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1. UV-filter pollution: current concerns and future prospects

Author

L.L.R. de Miranda, K.E. Harvey, S.C. Harvey, and A. Ahmed

Subjects
Pollution, Potential impact, Microplastics, Personal care, media_common.quotation_subject, Industrial production, UV filter, General Medicine, Management, Monitoring, Policy and Law, Cosmetics, Environmentally friendly, Environmental protection, Environmental science, General Environmental Science, media_common
Abstract

UV-filters are widely used in cosmetics and personal care products to protect users’ skin from redamage caused by ultraviolet (UV) radiation from the sun. Globally, an estimated 16,000 to 25,000 tonnes of products containing UV-filters were used in 2014 with modern consumption likely to be much higher. Beyond this use in cosmetics and personal care products, UV-filters are also widely used to provide UV-stability in industrial products such as paints and plastics. This review discusses the main routes by which UV-filters enter aquatic environments and summarises the conclusions of studies from the past 10 years that have investigated the effects of UV-filters on environmentally relevant species including corals, microalgae, fish, and marine mammals. Safety data regarding the potential impact of UV-filters on human health are also discussed. Finally, we explore the challenges surrounding UV-filter removal and research on more environmentally friendly alternatives to current UV-filters.

Published
2021
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2. Unusual DNA Structures : Proceedings of the First Gulf Shores Symposium, Held at Gulf Shores State Park Resort, April 6–8 1987, Sponsored by the Department of Biochemistry, Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, Alabama

Author

R.D. Wells, S.C. Harvey, R.D. Wells, and S.C. Harvey

Subjects
DNA--Structure--Congresses
Abstract

This book contains the papers which were presented at the First Gulf Shores Symposium on Unusual DNA Structures. The meeting was held April 6-8, 1987, in Gulf Shores, Alabama. Averitable explosion has taken place in recent years regarding our understanding of unusual DNA structures. This symposium was dedicated to enhancing our understanding of the biology and chemistry of these important structural features. The symposium was supported by funds provided by the Department of Biochemistry, University of Alabama at Birmingham, Schools of Medicine and Dentistry. We wish to express our app~eciationto Ms. Patti Guyton for her expert organizational skills and assistance in organizing the meeting and preparation of this book. Robert D. Wells and Stephen C. Harvey Department of Biochemistry Schools of Medicine and Dentistry University of Alabama at Birmingham Birmingham, Alabama 35294 VII VIII ;;C'Pete Dickie 1. Dave Wilson 20. 39. Paul Hagerman 58. Robert Shapiro 2. Wang-Ting Hsieh David Pettijohn 21. 40. Jacquelynn Larson 59. Angel Garcia 3. Hark Glover Hicaela Caserta 22. 41. Johanna Griffin 60. Richard Lavery 4. David Pulleyblank 23. Adam Jaworski 42. Jeremy Lee 61. Norma Wills 5. Robert Wells 24. Han Htun 43.

Published
2012

3. Contents Vol. 101, 2003

Author

N. Moreno-Mendoza, S. Aoyama, E. De Baere, M. Nakamura, M.H. Bogart, R.P. Teasdale, N.R. Bromage, Richard R. Behringer, D.K. Griffin, G.-C. Wu, N. Servel, Y.-H. Lee, V.A. Lance, M. Takase, Q. Yu, S.C. Harvey, P Penman, C. Santucciu, Annemiek Beverdam, Peter Koopman, Marilyn B. Renfree, T. Kobayashi, R. Campos-Ramos, Frank Grützner, L.-T. Sun, H. Merchant-Larios, V.R. Harley, Vincent R. Harley, J.-L. Du, M. Pannetier, J. Cocquet, A. Chesnel, M.T. Ezaz, C.-L. He, R.A. Veitia, S. Kuntz, C. Murdock, I. Grillier-Vuissoz, K. Matsui, J.A. Marchal, Sabine Kelly, Andrew J Pask, Stéphane Flament, L. Yue, N. Besnard, T. Taketo, X. Xia, A. Sánchez, Mónica Bullejos, C. Boonphakdee, R. Zhou, Eric Pailhoux, Kevin Christopher Knower, Y. Guo, H. Cheng, Jo Bowles, S. Tokunaga, M.J. Acosta, Marc Fellous, S. Takada, M. Gareil, H.W. Lau, C.-F. Chang, Y.-F.C. Lau, T. Wibbels, Y. Nagahama, K. Shibata, D. Chardard, Jennifer A. Marshall Graves, Y. Li, D.R. Carvalho-Silva, C. Cotinot, Kristy M. James, L.G. Kömüves, Dagmar Wilhelm, H. Kajiura-Kobayashi, and R. Díaz de la Guardia

Subjects
Botany, Genetics, Zoology, Biology, Molecular Biology, Genetics (clinical)
Published
2003
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4. Subject Index Vol. 101, 2003

Author

Andrew J Pask, J.A. Marchal, Kevin Christopher Knower, Frank Grützner, D. Chardard, R.A. Veitia, H. Merchant-Larios, Jennifer A. Marshall Graves, C. Boonphakdee, N. Besnard, S. Aoyama, R. Díaz de la Guardia, N. Moreno-Mendoza, Kristy M. James, J.-L. Du, R. Campos-Ramos, M.J. Acosta, S. Takada, C.-L. He, T. Wibbels, J. Cocquet, Eric Pailhoux, X. Xia, K. Matsui, M. Nakamura, C. Cotinot, R.P. Teasdale, H. Cheng, N.R. Bromage, D.K. Griffin, R. Zhou, M. Gareil, Annemiek Beverdam, E. De Baere, H.W. Lau, Q. Yu, T. Taketo, Stéphane Flament, Jo Bowles, L. Yue, G.-C. Wu, Marc Fellous, Peter Koopman, N. Servel, Sabine Kelly, V.R. Harley, Vincent R. Harley, C. Santucciu, A. Chesnel, Marilyn B. Renfree, T. Kobayashi, Mónica Bullejos, C.-F. Chang, S. Kuntz, D.R. Carvalho-Silva, M.H. Bogart, Y.-F.C. Lau, Y. Guo, K. Shibata, Y. Li, A. Sánchez, Richard R. Behringer, L.-T. Sun, L.G. Kömüves, Dagmar Wilhelm, V.A. Lance, Y.-H. Lee, M. Takase, S. Tokunaga, H. Kajiura-Kobayashi, Y. Nagahama, M. Pannetier, S.C. Harvey, P Penman, M.T. Ezaz, C. Murdock, and I. Grillier-Vuissoz

Subjects
Index (economics), Statistics, Genetics, Subject (documents), Biology, Molecular Biology, Genetics (clinical)
Published
2003
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5. Contents Vol. 99, 2002

Author

H. Suzuki, R. Kunita, J.-N. Volff, R. Willemsen, A. von der Wense, S.B.A. Fonteles, A. Wolf, K. Saso, K. Sekiya, S.M. Gartler, I. Miura, S. Christin-Maitre, M. Ito, T. Tada, J.T. Lee, C.B. Moysés, D.J. Penman, W. Feichtinger, J. Bernardino-Sgherri, K. Sasaki, Y. Matsuda, S. Jakubiczka, C. Steinlein, M. Matsumura, A. Gal, W. Werner, S. Yamaguchi, D.K. Griffin, Y. Hasegawa, A.I. Shevchenko, A. Fernández Badillo, C.J. Brown, M. Fellous, M. Kuro-o, K. Kutsche, Y. Sabbagh, S. Kirsch, C.E. Schwartz, N. Brockdorff, G.A. Rappold, M. Ogata, T.V. Karamysheva, D.J. Paull, S.-S. Tan, P.G. Johnston, L.V. Pereira, J. Manzanilla Pupo, J.-Y. Lee, T. Ogata, A. Kuroiwa, D. Flagiello, P. Meinecke, K.D. Tsuchiya, L.L. Hall, M.F.Z. Daniel-Silva, T. Namikawa, A.D. Riggs, J.S. Masabanda, R. Campos-Ramos, H. Hameister, Julie Cocquet, C.E. Lopes, K. Abe, P. Muschke, F. Vialard, O.V. Anopriyenko, N.A. Mazurok, M. Schmid, S. Shetty, S. Mizuno, M. Tsudzuki, I. Yoshida, R. Visbal García, T. Kida, H.S. Tenenhouse, T. Hori, J.M.A. Turner, O. Nakabayashi, T. Sado, M. Harata, M. Gomez, E. Heard, O. Bartsch, Y. Fujinuki, H. Kiyosawa, M. Yoshino, Z. Webster, D. Zarkower, P. Wieacker, M. Teranishi, M. Alexiou, G.N. Filippova, C. Ikebe, Paul S. Burgoyne, M. Yamazaki, N. Arai, M. Monk, K. Tanaka, N.B. Rubtsov, S. Kim, Y. Watanabe, C. Gauthier, Y. Itoh, T.B. Nesterova, Y. Fukushima, L.F. de Almeida-Toledo, T. Nakamura, T. Yokomine, M. Adams, T. Kubota, P.J. Kirby, M. Schartl, H. Kimura, B.A. Oostra, I. Nanda, R. Wimmer, N. Okamoto, Y. Arakawa, N. Nakatsuji, E. Li, G.E. Herman, S. Sutou, Y. Goto, W. Schempp, S.C. Harvey, C. Nishida-Umehara, I.B. Van den Veyver, A. Akama, M.-L. Caparros, M. Krawczak, D.W. Burt, N. Takagi, H. Ohashi, Daniel Vaiman, R. Feil, I. Wieland, H.M. El-Hodiri, Y. Kuroda, H. Sasaki, S.M. Zakian, M. Tada, K. Akaba, M. Guggiari, L. Gerlach, L.-J. Ayling, M.N. Klöckner, F. Foresti, L.R. Vasques, B. Dutrillaux, T. Haaf, M. Okabe, R.E. Stevenson, J. Gécz, R.S. Hansen, S. Kohno, O.A. Ojarikre, T. Igarashi, N.V. Rubtsova, M. Sugimoto, M. Hemberger, S. Hatano, Y. Izumisawa, J.C. Chow, J.A.M. Graves, Reiner A. Veitia, J.B. Lawrence, Y. Ogawa, C.M. Watson, C.M. Disteche, A. Weber, K. Muroya, A. Ogawa, N.R. Bromage, B.R. Migeon, H. Ohtani, K. Wakui, Y. Ichikawa, J. Chaumeil, and I. Okamoto

Subjects
Botany, Genetics, Zoology, Biology, Molecular Biology, Genetics (clinical)
Published
2002
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6. Subject Index Vol. 99, 2002

Author

K. Abe, S. Yamaguchi, H. Ohashi, J.M.A. Turner, M. Tsudzuki, D.K. Griffin, M. Tada, K. Tanaka, M. Hemberger, Y. Fujinuki, C.J. Brown, Y. Watanabe, A. Weber, M. Fellous, S. Hatano, Y. Izumisawa, A. Gal, R. Wimmer, J.C. Chow, K. Muroya, J.A.M. Graves, Reiner A. Veitia, R.E. Stevenson, A.D. Riggs, J. Gécz, R.S. Hansen, Y. Arakawa, N. Arai, T. Sado, Y. Hasegawa, L.-J. Ayling, Y. Itoh, M. Adams, T. Kubota, C.M. Disteche, L.V. Pereira, N. Okamoto, M. Yoshino, I. Nanda, L.F. de Almeida-Toledo, K. Saso, T. Yokomine, J.-N. Volff, F. Foresti, M. Schartl, K. Akaba, M. Ogata, D.J. Paull, S.-S. Tan, J. Manzanilla Pupo, Y. Fukushima, D. Zarkower, M.N. Klöckner, C.E. Schwartz, N. Brockdorff, O.A. Ojarikre, N. Nakatsuji, S. Sutou, G.N. Filippova, N.B. Rubtsov, J.B. Lawrence, Y. Sabbagh, S. Kim, C. Gauthier, J.T. Lee, H. Sasaki, N.R. Bromage, S. Kirsch, C.B. Moysés, M. Ito, L.L. Hall, P.J. Kirby, Y. Goto, C. Nishida-Umehara, T. Tada, D.J. Penman, Y. Ogawa, J.S. Masabanda, I. Wieland, B.A. Oostra, S.M. Gartler, M.F.Z. Daniel-Silva, T. Namikawa, Julie Cocquet, M. Guggiari, L. Gerlach, F. Vialard, C. Ikebe, Z. Webster, S.C. Harvey, A. Fernández Badillo, H.M. El-Hodiri, H. Hameister, P. Wieacker, G.E. Herman, T. Ogata, O.V. Anopriyenko, M. Monk, T. Igarashi, N.V. Rubtsova, M. Sugimoto, W. Feichtinger, J. Bernardino-Sgherri, M. Matsumura, R. Willemsen, S. Mizuno, D. Flagiello, Y. Kuroda, J.-Y. Lee, R. Visbal García, R. Feil, S. Jakubiczka, S.M. Zakian, N.A. Mazurok, S. Shetty, R. Kunita, N. Takagi, Daniel Vaiman, A. von der Wense, A. Akama, H.S. Tenenhouse, M. Alexiou, H. Suzuki, T. Hori, T. Kida, G.A. Rappold, B. Dutrillaux, L.R. Vasques, W. Werner, T.B. Nesterova, A.I. Shevchenko, E. Li, W. Schempp, T. Haaf, M. Okabe, M. Kuro-o, S. Kohno, S.B.A. Fonteles, A. Wolf, I. Miura, I.B. Van den Veyver, M. Krawczak, M. Harata, K. Sekiya, M. Gomez, E. Heard, T.V. Karamysheva, S. Christin-Maitre, A. Kuroiwa, C.E. Lopes, K. Kutsche, P. Muschke, M. Schmid, I. Yoshida, O. Nakabayashi, O. Bartsch, K. Sasaki, Y. Matsuda, P.G. Johnston, C. Steinlein, Y. Ichikawa, J. Chaumeil, I. Okamoto, B.R. Migeon, H. Ohtani, K. Wakui, C.M. Watson, A. Ogawa, H. Kiyosawa, M. Teranishi, Paul S. Burgoyne, M. Yamazaki, P. Meinecke, K.D. Tsuchiya, R. Campos-Ramos, T. Nakamura, H. Kimura, M.-L. Caparros, and D.W. Burt

Subjects
Index (economics), Statistics, Genetics, Subject (documents), Biology, Molecular Biology, Genetics (clinical)
Published
2002
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7. Werner Schmid, 1930–2002

Author

Z. Liu, H. Starke, C.L. Li, A. Rupprecht, S.L. Ewart, L. Fröhlich, R. Tomasini, D. Gallagher, N. Gmachl, N. Ghaffari-Tabrizi, N.A. Jenkins, T. Leeb, M. Grosz, S. Izraeli, H. Akutsu, C. Steinlein, I. Eisenberg, C. Drögemüller, M. Satoh, W. Engel, I.M. Adham, D.J. Gilbert, K. Ying, H.P. Klinger, Y. Ma, N. Coleman, J. Nowak, T. Yagi, R.L. Prueitt, A. Bernheim, N.B. Atkin, H. Kikuchi, R. Tang, M. Bina, L. Ziercher, T. Osada, N. Dusetti, J. Taylor, E. Antoniou, E.I. Pares-Matos, C. Knorr, D.R. Beier, A. Kuechler, H. Chen, T. Haaf, Y. Mao, W. Feichtinger, D.B. Zimonjic, A. Heller, S.K. Swanson, D.K. Griffin, P. Quignon, B. Bjerkehagen, M. Muenke, M. Shibazaki, N.G. Copeland, H. Kuiper, J.C. Phillips, G. Cao, E. Nacheva, L.A. Azizi Samir, H.-U.G. Weier, M.-G. Mattei, M. Wills-Karp, H. Hochner, D.C. Shing, T.P. Yang, H. Cheng, R. Shamsadin, A.M. Simckes, E. Roessler, D.M. Shubitowski, K. Mrasek, R. Fries, B. Lanske, I. Artner, M.-J. Pébusque, S. Kollers, C.A. Morley-Jacob, A. Dutra, S. Mitrani-Rosenbaum, N. Kleiter, R.A. White, P. Coullin, F. Micci, I. Roberts, A.R. Zinn, N.C. Popescu, S. Heim, R. Yanagimachi, F. Galibert, A. Weise, A. Srisodsai, C. Auffray, S.C. Harvey, B. Brenig, I. Kirsch, X. Ni, Selena Davis, C. Ji, C.L. Keck-Waggoner, B. Perbal, Z.H. Shan, J. Young, Y. Xie, B. Hong, T. Niimi, H. Kaiser, S. Fukushige, D.J. Penman, L.A.P. Carrasco, R.I. Barnes, W.H. Brooks, N.R. Bromage, J. Masabanda, J.-L. Iovanna, G.A. Rohrer, O. Distl, S.G. Rak, M. Schmid, Y. Shiratori, K. Kratochwil, M. Sadeh, H. Kusakabe, U. Claussen, M. Jiang, M.R. Teixeira, Z. Argov, T. Liehr, R. Zoorob, W.H. Reeves, J. Womack, J.D. Karkera, S. Kimura, J.-C. Dagorn, and L. Guo

Subjects
Psychoanalysis, Genetics, Biology, Molecular Biology, Genetics (clinical)
Published
2002
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8. Brief Gene Mapping Reports A / B / C / D / E / F / G

Author

Y. Mao, M. Grosz, S. Izraeli, J.D. Karkera, S. Kimura, I.M. Adham, A.R. Zinn, Y. Ma, T. Yagi, T. Haaf, S. Mitrani-Rosenbaum, N. Coleman, N. Ghaffari-Tabrizi, J. Taylor, J. Nowak, A. Srisodsai, W. Feichtinger, J.-L. Iovanna, C.L. Li, A. Rupprecht, N.A. Jenkins, P. Coullin, M. Muenke, Selena Davis, C. Ji, D.B. Zimonjic, A. Heller, J. Masabanda, J.-C. Dagorn, Y. Xie, B. Hong, H. Kuiper, R.I. Barnes, W.H. Brooks, A.M. Simckes, T. Leeb, D.J. Gilbert, I. Eisenberg, D.M. Shubitowski, R. Fries, B. Lanske, R. Zoorob, G. Cao, W.H. Reeves, M. Satoh, E. Roessler, S.G. Rak, W. Engel, H. Akutsu, L. Guo, H. Kusakabe, S.K. Swanson, D.R. Beier, K. Mrasek, N. Dusetti, M. Shibazaki, C. Steinlein, L. Fröhlich, S.L. Ewart, H. Starke, S. Kollers, C.A. Morley-Jacob, B. Bjerkehagen, N. Kleiter, R.A. White, T.P. Yang, T. Niimi, L.A.P. Carrasco, H. Kikuchi, A. Weise, M. Jiang, R. Tomasini, M.R. Teixeira, L.A. Azizi Samir, C. Auffray, A. Kuechler, H. Cheng, S. Heim, H.-U.G. Weier, M.-J. Pébusque, Z. Liu, S.C. Harvey, D. Gallagher, J.C. Phillips, F. Micci, H. Hochner, N. Gmachl, X. Ni, M.-G. Mattei, A. Dutra, E. Nacheva, C. Drögemüller, R.L. Prueitt, J. Womack, Z.H. Shan, N.C. Popescu, R. Tang, H. Kaiser, G.A. Rohrer, N.G. Copeland, O. Distl, N.R. Bromage, M. Schmid, A. Bernheim, K. Kratochwil, F. Galibert, M. Bina, R. Shamsadin, B. Brenig, Y. Shiratori, E. Antoniou, H. Chen, R. Yanagimachi, M. Sadeh, S. Fukushige, U. Claussen, I. Kirsch, N.B. Atkin, B. Perbal, C.L. Keck-Waggoner, H.P. Klinger, T. Osada, E.I. Pares-Matos, J. Young, C. Knorr, D.J. Penman, K. Ying, L. Ziercher, P. Quignon, M. Wills-Karp, I. Artner, I. Roberts, D.K. Griffin, T. Liehr, D.C. Shing, and Z. Argov

Subjects
Genetics, Gene mapping, Biology, Molecular Biology, Genetics (clinical)
Published
2002
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10. Serial testing in Parkinson's dementia: A case study

Author

M.L. Russell and S.C. Harvey

Subjects
medicine.medical_specialty, Psychiatry and Mental health, Clinical Psychology, Physical medicine and rehabilitation, Neuropsychology and Physiological Psychology, business.industry, Medicine, Dementia, General Medicine, business, medicine.disease
Published
1998
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12. Comparison of free energy surfaces for extended-atom and all-atom models of n-butane

Author

S.C. Harvey and C.D. Bell

Subjects
Internal energy, Anharmonicity, General Engineering, Butane, Dihedral angle, Energy minimization, Molecular physics, chemistry.chemical_compound, Molecular dynamics, chemistry, Physical chemistry, Physical and Theoretical Chemistry, Entropy (energy dispersal), Umbrella sampling
Abstract

The dependence of conformational energy on the central torsion angle of butane (phi) has been examined for an all-atom and for an extended-atom model, using molecular dynamics (MD). Conformational space was sampled with a special umbrella sampling potential that optimizes sampling statistics. Although the shapes of the free energy surfaces of the two models are similar, there are substantial differences in the dependence of entropy on phi. Anharmonic effects make important contributions to the entropy in the extended-atom model. In the extended atom model, the dependence of internal energy on phi is quite different when determined by MD than when determined by energy minimization, suggesting that potential function parameters that have been refined by energy minimization may not always be suitable for MD simulations.

Published
1986
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13. Failure of chronic denervation to alter the sensitivity of the rat diaphragm to local anaesthetics of quinidine

Author

H. P. Rang and S.C. Harvey

Subjects
Quinidine, Male, Diaphragm, Dibucaine, Action Potentials, Tetrodotoxin, Pharmacology, In Vitro Techniques, chemistry.chemical_compound, Procaine, medicine, Animals, Anesthetics, Local, Denervation, Chemistry, Sodium channel, Muscles, Electric Stimulation, Rats, Drug Mechanisms, Halothane, Acetylcholine, medicine.drug
Abstract

1 The actions of procaine, nupercaine and quinidine on the membrane resting and action potentials of the normal and chronically denervated rat diaphragm were studied in vitro. 2 The degree of suppression of the rate of rise of the action potential by any of the drugs was the same in denervated as in normal muscle. 3 The degree of suppression of the rate of rise of the action potential by procaine in denervated muscle was about the same in the presence and absence of tetrodotoxin. 4 Three possible interpretations of the lack of effect of denervation on the response to these drugs are discussed: (a) In the sodium channel, the structural alteration that confers resistance to tetrodotoxin is quite limited and does not affect groups which interact with local anaesthetics. (b) Local anaesthetics are non-selective in their binding so that alteration in membrane structure around the channel has little influence on the efficiency of the local anaesthetic. (c) Denervation may affect the outer surface of the membrane, where acetylcholine and tetrodotoxin act, more than the intracellular surface, where local anaesthetics appear to act. 5 The slope of the log concentration-effect line for quinidine was steeper than that for procaine or nupercaine.

Published
1974

14. DURATION OF THE CYCLE OF THE SEMINIFEROUS EPITHELIUM OF NORMAL, HYPOPHYSECTOMIZED AND HYPOPHYSECTOMIZED-HORMONE TREATED ALBINO RATS

Author

Yves Clermont and S.C. Harvey

Subjects
Male, medicine.medical_specialty, Hypophysectomy, Cell division, Physiology, medicine.medical_treatment, Biology, Tritium, Chorionic Gonadotropin, chemistry.chemical_compound, Endocrinology, Internal medicine, Testis, medicine, Humans, Spermatogenic epithelium, Pharmacology, Research, Spermatozoa, Epithelium, Hormones, Rats, medicine.anatomical_structure, Germ Cells, Seminiferous Epithelium, chemistry, Thymidine, Cell Division, Gonadotropins, Hormone
Published
1965

15. Genetic variation associated with Alpha-synuclein pathology in Caenorhabditis elegans

Author

Yiru A. Wang, Wageningen University, J.E. Kammenga, M.G. Sterken, and S.C. Harvey

Subjects
education.field_of_study, Pathology, medicine.medical_specialty, ved/biology, Transgene, ved/biology.organism_classification_rank.species, Population, Biology, PE&RC, Genetic architecture, Proteotoxicity, Genetic variation, Expression quantitative trait loci, medicine, Life Science, Allele, Laboratory of Nematology, Model organism, education, Laboratorium voor Nematologie
Abstract

Neurodegenerative diseases (NGDs), such as Alzheimer’s diseases (AD) and Parkinson’s diseases (PD), are characterized by progressive degeneration in the human nervous system. The effect of variants harboured in genetic background on diseases onset and progression has been identified in studies with either humans or other model organisms. The nematode C. elegans is one of the powerful models in which to study human complex diseases studies, e.g. NGDs,due to the high level of conservation of gene functions compared to humans. Researches with C. elegans largely relies on a single worm genotype – the laboratory N2 strain – limiting the ability to explore how naturally varying alleles alter pathological mechanisms in NGDs. Hence we focused on a C. elegans model of α-synuclein, of which aggregate formation (i.e. Lewy body) isthe pathologicalhallmarkof PD, and introduced five more different genetic backgrounds into this model. Life history phenotypic traits, including shortened lifespan, development delay, pumping arrest, and so on, together with the microarray-based gene expression analysis indicate that α-synuclein transgene effects vary greatly depending on the genetic background. Functional enrichment analysis reveals that the background genes which significantly responded to the α-synuclein-effect link to the developmental arrest, metabolic, and cellular repair mechanisms. Moreover, we also identified variable accumulated both protein aggregation and lipid contents in different genetic backgrounds. These results together suggest natural genetic variation appears to affect α-synuclein aggregation and proteotoxicity resulting in a variety of disease phenotypic outcomes. Furthermore, we performed eQTL mapping in the newly constructed panel of NL5901xSCH4856 recombinant inbred lines (RILs) harbouring the α-synuclein introgression. By detectable expression levels of the parental (N2&CB4856) genotypes of the RILs population, both cis- and trans-effects of variants were identified, which provides insight into the underlying genetic architecture of transcriptional phenotype in response to introgressed α-synuclein. Overall, these together highlights the importance of C. elegans' variable genetic backgrounds in human α-synuclein pathology studies. Especially, genetic variants present differential alterations in global gene expression in response to α-synuclein and/or proteotoxicity, which could not be readily observed in the N2 background. Despite still having inherent limitations, it is essential to consider the influence of natural variation in genetic background on the disease onset and progressing mechanism.

Published
2019

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