[en] Anticoagulant rodenticides (ARs) are indiscriminate toxicants that threaten nontarget predatory and scavenger species through secondary poisoning. Accumulating evidence suggests that AR exposure may have disruptive sublethal consequences on individuals that can affect fitness. We evaluated AR-related effects on genome-wide expression patterns in a population of bobcats in southern California. We identify differential expression of genes involved in xenobiotic metabolism, endoplasmic reticulum stress response, epithelial integrity and both adaptive and innate immune function. Further, we find that differential expression of immune-related genes may be attributable to AR-related effects on leucocyte differentiation. Collectively, our results provide an unprecedented understanding of the sublethal effects of AR exposure on a wild carnivore. These findings highlight potential detrimental effects of ARs on a wide variety of species worldwide that may consume poisoned rodents and indicate the need to investigate gene expression effects of other toxicants added to natural environments by humans.
Disciplines :
Zoology
Author, co-author :
Fraser, Devaughn ✱
Mouton, Alice ✱; University of California, Los Angeles - UCLA > Department of Ecology and Evolutionary Biology
Serieys, Laurel E. K.
Cole, Steve
Carver, Scott
Vandewoude, Sue
Lappin, Michael
Riley, Seth P. D.
Wayne, Robert
✱ These authors have contributed equally to this work.
Language :
English
Title :
Genome-wide expression reveals multiple systemic effects associated with detection of anticoagulant poisons in bobcats (Lynx rufus).
Anders, S., Pyl, P. T., & Huber, W. (2014). HTSeq–a Python framework to work with high-throughput sequencing data. Bioinformatics, 31(2), 166–169.
Arlian, L. G., Morgan, M. S., Rapp, C. M., & Vyszenski-Moher, D. L. (1996). The development of protective immunity in canine scabies. Veterinary Parasitology, 62(1–2), 133–142. https://doi.org/10.1016/0304-4017(95)00854-3
Baert, K., Van Den Berge, K., Jansen, I., Gouwy, J., Croubels, S., & Casaer, J. (2015). Secundaire intoxicatie bij het gebruik van rodenticiden – Analyse van leverresiduen bij bunzing en steenmarter. Brussels, Rapporten van het Instituut voor Natuur- en Bosonderzoek, INBO.R.2015.9435187.
Baldwin, D. H., Spromberg, J. A., Collier, T. K., & Scholz, N. L. (2009). A fish of many scales: extrapolating sublethal pesticide exposures to the productivity of wild salmon populations. Ecological Applications, 19, 2004–2015. https://doi.org/10.1890/08-1891.1
Bartos, M., Dao, S., Douk, D., Falzone, S., Gumerlock, E., Hoekstra, S., … Ward, J. (2011). Use of anticoagulant rodenticides in single-family neighborhoods along an urban-wildland interface in California. Cities and the Environment, 4(1), 12.
Beier, P., Riley, S. P. D., & Sauvajot, R. M. (2010). Mountain lions (Puma concolor). In S. D. Gehrt, S. P. D. Riley & B. L. Cypher (Eds.), Urban carnivores: ecology, conflict, and conservation (pp. 141–156). Baltimore, MD: The Johns Hopkins University Press.
Bevins, S. N., Carver, S., Boydston, E. E., Lyren, L. M., Alldredge, M., Logan, K. A., … Salman, M. (2012). Three pathogens in sympatric populations of pumas, bobcats, and domestic cats: implications for infectious disease transmission. PLoS ONE, 7(2), e31403. https://doi.org/10.1371/journal.pone.0031403
California Department of Pesticide Regulation (2013). Second generation anticoagulant rodenticide assessment Memorandum. http://www.cdpr.ca.gov/docs/registration/reevaluation/chemicals/brodifacoum_final_assess.pdf
Carver, S., Bevins, S. N., Lappin, M. R., Boydston, E. E., Lyren, L. M., Alldredge, M., …Fisher, R. N. (2016). Pathogen exposure varies widely among sympatric populations of wild and domestic felids across the United States. Ecological Applications, 26(2), 367–381. https://doi.org/10.1890/15-0445
Chan, Y. C., Valenti, D., Mansfield, A. O., & Stansby, G. (2000). Warfarin induced skin necrosis. The British Journal of Surgery, 87(3), 266–272. https://doi.org/10.1046/j.1365-2168.2000.01352.x
Christensen, T. K., Lassen, P., & Elmeros, M. (2012). High exposure rates of anticoagulant rodenticides in predatory bird species in intensively managed landscapes in Denmark. Archives of Environmental Contamination and Toxicology, 63(3), 437–444. https://doi.org/10.1007/s00244-012-9771-6
Cimino-Reale, G., Ferrario, D., Casati, B., Brustio, R., Diodovich, C., Collotta, A., … Gribaldo, L. (2008). Combined in utero and juvenile exposure of mice to arsenate and atrazine in drinking water modulates gene expression and clonogenicity of myeloid progenitors. Toxicology Letters, 180(1), 59–66. https://doi.org/10.1016/j.toxlet.2008.06.005
Cole, S. W., Hawkley, L. C., Arevalo, J. M., & Cacioppo, J. T. (2011). Transcript origin analysis identifies antigen-presenting cells as primary targets of socially regulated gene expression in leukocytes. Proceedings of the National Academy of Sciences of the United States of America, 108(7), 3080–3085. https://doi.org/10.1073/pnas.1014218108
Court, M. H. (2013). Feline drug metabolism and disposition: pharmacokinetic evidence for species differences and molecular mechanisms. The Veterinary Clinics of North America. Small Animal Practice, 43(5), 1039–1054. https://doi.org/10.1016/j.cvsm.2013.05.002
Cribb, A. E., Peyrou, M., Muruganandan, S., & Schneider, L. (2005). The endoplasmic reticulum in xenobiotic toxicity. Drug Metabolism Reviews, 37(3), 405–442. https://doi.org/10.1080/03602530500205135
Danziger, J. (2008). Vitamin K-dependent proteins, warfarin, and vascular calcification. Clinical Journal of the American Society of Nephrology, 3(5), 1504–1510. https://doi.org/10.2215/CJN.00770208
Davis, A. P., Grondin, C. J., Johnson, R. J., Sciaky, D., King, B. L., McMorran, R., … Mattingly, C. J. (2017). The comparative toxicogenomics database: update 2017. Nucleic Acids Research, 45(D1), 972–978. https://doi.org/10.1093/nar/gkw838
Dennis, G. C., & Gartrell, B. D. (2015). Nontarget mortality of New Zealand lesser short-tailed bats (Mystacina tuberculata) caused by diphacinone. Journal of Wildlife Diseases, 51(1), 177–186. https://doi.org/10.7589/2013-07-160
Dong, K. K., Damaghi, N., Picart, S. D., Markova, N. G., Obayashi, K., Okano, Y., … Yarosh, D. B. (2008). UV-induced DNA damage initiates release of MMP-1 in human skin. Experimental Dermatology, 17(12), 1037–1044. https://doi.org/10.1111/j.1600-0625.2008.00747.x
Dorshkind, K. (1990). Regulation of hemopoiesis by bone marrow stromal cells and their products. Annual Review of Immunology, 8(1), 111–137. https://doi.org/10.1146/annurev.iy.08.040190.000551
Eason, C. T., Murphy, E. C., Wright, G. R., & Spurr, E. B. (2001). Assessment of risks of brodifacoum to non-target birds and mammals in New Zealand. Ecotox: Ecological Modelling and Ecotoxicology, 11(1), 35–48.
El Asmar, M. S., Naoum, J. J., & Arbid, E. J. (2014). Vitamin k dependent proteins and the role of vitamin k2 in the modulation of vascular calcification: a review. Oman Medical Journal, 29(3), 172–177. https://doi.org/10.5001/omj.2014.44
Elias, P. M., Schmuth, M., Uchida, Y., Rice, R. H., Behne, M., Crumrine, D., … Holleran, W. M. (2002). Basis for the permeability barrier abnormality in lamellar ichthyosis. Experimental Dermatology, 11, 248–256. https://doi.org/10.1034/j.1600-0625.2001.110308.x
Elmeros, M., Christensen, T. K., & Lassen, P. (2011). Concentrations of anticoagulant rodenticides in stoats Mustela erminea and weasels Mustela nivalis from Denmark. Science of the Total Environment, 409, 2373–2378. https://doi.org/10.1016/j.scitotenv.2011.03.006
Esmon, C. T. (2005). The interactions between inflammation and coagulation. British Journal of Haematology, 131(4), 417–430. https://doi.org/10.1111/j.1365-2141.2005.05753.x
Faircloth, B. C., & Glenn, T. C. (2012). Not all sequence tags are created equal: designing and validating sequence identification tags robust to indels. PloS one, 7(8), e42543.
Fedriani, J. M., Fuller, T. K., Sauvajot, R. M., & York, E. C. (2000). Competition and intraguild predation among three sympatric carnivores. Oecologia, 125(2), 258–270. https://doi.org/10.1007/s004420000448
Ferland, G. (2012). Vitamin K and the nervous system: an overview of its actions. Advances in Nutrition, 3(2), 204–212. https://doi.org/10.3945/an.111.001784
Filser, J. (2008). Ecotoxicology and ecosystems: Relevance, restrictions, research needs. Basic and Applied Ecology, 9(4), 333–336. https://doi.org/10.1016/j.baae.2007.08.009
Foster, A. M., Baliwag, J., Chen, C. S., Guzman, A. M., Stoll, S. W., Gudjonsson, J. E., … Johnston, A. (2014). IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin. Journal of Immunology, 192(12), 6053–6061. https://doi.org/10.4049/jimmunol.1301481
Foufelle, F., & Fromenty, B. (2016). Role of endoplasmic reticulum stress in drug-induced toxicity. Pharmacology Research & Perspectives, 4(1), e00211. https://doi.org/10.1002/prp2.211
Fournier-Chambrillon, C., Berny, P. J., Coiffier, O., Barbedienne, P., Dassé, B., Delas, G., … Fournier, P. (2004). Evidence of secondary poisoning of free-ranging riparian mustelids by anticoagulant rodenticides in France: implications for conservation of European mink (Mustela lutreola). Journal of Wildlife Diseases, 40(4), 688–695. https://doi.org/10.7589/0090-3558-40.4.688
Freeman, B. D., Zehnbauer, B. A., McGrath, S., Borecki, I., & Buchman, T. G. (2000). Cytochrome P450 polymorphisms are associated with reduced warfarin dose. Surgery, 128(2), 281–285. https://doi.org/10.1067/msy.2000.107283
Gabriel, M. W., Woods, L. W., Poppenga, R., Sweitzer, R. A., Thompson, C., Matthews, S. M., … Clifford, D. L. (2012). Anticoagulant rodenticides on our public and community lands: spatial distribution of exposure and poisoning of a rare forest carnivore. PLoS ONE, 7(7), e40163. https://doi.org/10.1371/journal.pone.0040163
Gabriel, M. W., Woods, L. W., Wengert, G. M., Stephenson, N., Higley, J. M., Thompson, C., … Sacks, B. N. (2015). Patterns of natural and human-caused mortality factors of a rare forest carnivore, the fisher (Pekania pennanti) in California. PLoS ONE, 10(11), e0140640. https://doi.org/10.1371/journal.pone.0140640
Gehrt, S. D., Riley, S. P., & Cypher, B. L. (Eds.). (2010). Urban carnivores: ecology, conflict, and conservation. Baltimore, MD: JHU Press.
Gill, R. J., & Raine, N. E. (2014). Chronic impairment of bumblebee natural foraging behaviour induced by sublethal pesticide exposure. Functional Ecology, 28(6), 1459–1471. https://doi.org/10.1111/1365-2435.12292
Hansen, K. D., Irizarry, R. A., & Wu, Z. (2012). Removing technical variability in RNA-seq data using conditional quantile normalization. Biostatistics, 13(2), 204–216. https://doi.org/10.1093/biostatistics/kxr054
Herman, M. L., Farasat, S., Steinbach, P. J., Wei, M. H., Toure, O., Fleckman, P., … Toro, J. R. (2009). Transglutaminase-1 gene mutations in autosomal recessive congenital ichthyosis: Summary of mutations (including 23 novel) and modeling of TGase-1. Human Mutation, 30(4), 537–547. https://doi.org/10.1002/humu.20952
Hsu, A. P., Sampaio, E. P., Khan, J., Calvo, K. R., Lemieux, J. E., Patel, S. Y., … Olivier, K. N. (2011). Mutations in GATA2 are associated with the autosomal dominant and sporadic monocytopenia and mycobacterial infection (MonoMAC) syndrome. Blood, 118, 2653–2655. https://doi.org/10.1182/blood-2011-05-356352
Huang, A. C., Elliott, J. E., Hindmarch, S., Lee, S. L., Maisonneuve, F., Bowes, V., … Martin, K. (2016). Increased rodenticide exposure rate and risk of toxicosis in barn owls (Tyto alba). Ecotox: Ecological Modelling and Ecotoxicology, 25(6), 1061–1071. https://doi.org/10.1007/s10646-016-1662-6
Ioannides, C. (2001). Xenobiotic Metabolism: An Overview. In C. Ioannides (Ed.), Enzyme systems that metabolise drugs and other xenobiotics (pp. 1–32). Chichester, UK: Wiley. https://doi.org/10.1002/0470846305
Irigoien, I., Sierra, B., & Arenas, C. (2012). ICGE: an R package for detecting relevant clusters and atypical units in gene expression. BMC Bioinformatics, 13(1), 30. https://doi.org/10.1186/1471-2105-13-30
Ishikawa, E. T., Chang, K. H., Nayak, R., Olsson, H. A., Ficker, A. M., Dunn, S. K., … Cancelas, J. A. (2013). Klf5 controls bone marrow homing of stem cells and progenitors through Rab5-mediated β1/β2-integrin trafficking. Nature Communications, 4, 1660. https://doi.org/10.1038/ncomms2645
Jiang, H., Jans, R., Xu, W., Rorke, E. A., Lin, C. Y., Chen, Y. W., … Eckert, R. L. (2010). Type I transglutaminase accumulation in the endoplasmic reticulum may be an underlying cause of autosomal recessive congenital ichthyosis. Journal of Biological Chemistry, 285(41), 31634–31646. https://doi.org/10.1074/jbc.M110.128645
Karlgren, M., Miura, S., & Ingelman-Sundberg, M. (2005). Novel extrahepatic cytochrome P450s. Toxicology and Applied Pharmacology, 207(2), 57–61. https://doi.org/10.1016/j.taap.2004.12.022
Kater, A. P., Peppelenbosch, M. P., Brandjes, D. P., & Lumbantobing, M. (2002). Dichotomal effect of the coumadin derivative warfarin on inflammatory signal transduction. Clinical and Diagnostic Laboratory Immunology, 9(6), 1396–1397.
Kawashima, H., Nakajima, Y., Matubara, Y., Nakanowatari, J., Fukuta, T., Mizuno, S., … Nakamura, T. (1997). Effects of vitamin K2 (menatetrenone) on atherosclerosis and blood coagulation in hypercholesterolemic rabbits. Japanese Journal of Pharmacology, 75(2), 135–143. https://doi.org/10.1254/jjp.75.135
Kelly, T. R., Poppenga, R. H., Woods, L. A., Hernandez, Y. Z., Boyce, W. M., Samaniego, F. J., … Johnson, C. K. (2014). Causes of mortality and unintentional poisoning in predatory and scavenging birds in California. Veterinary Record Open, 1(1), e000028. https://doi.org/10.1136/vropen-2014-000028
Kim, D., Pertea, G., Trapnell, C., Pimentel, H., Kelley, R., & Salzberg, S. L. (2013). TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biology, 14(4), R36. https://doi.org/10.1186/gb-2013-14-4-r36
Krueger, F. (2015). Trim Galore!: A wrapper tool around Cutadapt and FastQC to consistently apply quality and adapter trimming to FastQ files.
Langfelder, P., & Horvath, S. (2008). WGCNA: an R package for weighted correlation network analysis. BMC Bioinformatics, 9(1), 559. https://doi.org/10.1186/1471-2105-9-559
Langfelder, P., & Horvath, S. (2012). Fast R functions for robust correlations and hierarchical clustering. Journal of Statistical Software, 46(11), i11.
Lee, J. S., Ward, W. O., Liu, J., Ren, H., Vallanat, B., Delker, D., & Corton, J. C. (2011). Hepatic xenobiotic metabolizing enzyme and transporter gene expression through the life stages of the mouse. PLoS ONE, 6(9), e24381. https://doi.org/10.1371/journal.pone.0024381
Li, J., Lin, J. C., Wang, H., Peterson, J. W., Furie, B. C., Furie, B., … Rosenberg, P. A. (2003). Novel role of vitamin k in preventing oxidative injury to developing oligodendrocytes and neurons. Journal of Neuroscience, 23(13), 5816–5826.
Lynch, T., & Price, A. (2007). The effect of cytochrome P450 metabolism on drug response, interactions, and adverse effects. American Family Physician, 76, 391–396.
Malik, N. A., & Chughtai, A. S. (2003). The effects of lindane on rabbit hemopoietic system: an experimental study. International Journal of Pathology, 1, 39–41.
McConnell, B. B., Ghaleb, A. M., Nandan, M. O., & Yang, V. W. (2007). The diverse functions of Krüppel-like factors 4 and 5 in epithelial biology and pathobiology. BioEssays, 29(6), 549–557. https://doi.org/10.1002/(ISSN)1521-1878
Medina, A., Ghaffari, A., Kilani, R. T., & Ghahary, A. (2007). The role of stratifin in fibroblast–keratinocyte interaction. Molecular and Cellular Biochemistry, 305(1–2), 255–264. https://doi.org/10.1007/s11010-007-9538-y
Meehan, B. M., & Beckwith, J. (2017). From protein folding to blood coagulation: menaquinone as a metabolic link between bacteria and mammals. In J. O. Gordeladze (Ed.), Vitamin K2-vital for health and wellbeing (pp. 257–279). Rijeka, Croatia: InTech.
Mikhail, M. W., & Abdel-Hamid, Y. M. (2007). Effect of warfarin anticoagulant rodenticide on the blood cell counts of Rattus norvegicus and Rattus rattus. Journal of the Egyptian Society of Parasitology, 37(3), 853–861.
Miller, G. P., Jones, D. R., Sullivan, S. Z., Mazur, A., Owen, S. N., Mitchell, N. C., … Moran, J. H. (2009). Assessing cytochrome P450 and UDP-glucuronosyltransferase contributions to warfarin metabolism in humans. Chemical Research in Toxicology, 22(7), 1239–1245. https://doi.org/10.1021/tx900031z
Miyazawa, K., & Aizawa, S. (2004). Vitamin K2 improves the hematopoietic supportive functions of bone marrow stromal cells in vitro: a possible mechanism of improvement of cytopenia for refractory anemia in response to vitamin K2 therapy. Stem Cells and Development, 13(5), 449–451. https://doi.org/10.1089/scd.2004.13.449
Moriarty, J. G., Riley, S. P., Serieys, L. E., Sikich, J. A., Schoonmaker, C. M., & Poppenga, R. H. (2012). Exposure of wildlife to anticoagulant rodenticides at Santa Monica Mountains National Recreation Area: From mountain lions to rodents. In 25th Vertebrate Pest Conference (March 5–8 2012), Monterey, CA, USA.
Naisbitt, D. J., Farrell, J., Chamberlain, P. J., Hopkins, J. E., Berry, N. G., Pirmohamed, M., & Park, B. K. (2005). Characterization of the T-cell response in a patient with phenindione hypersensitivity. Journal of Pharmacology and Experimental Therapeutics, 313(3), 1058–1065. https://doi.org/10.1124/jpet.105.083758
Nakagawa, K., Hirota, Y., Sawada, N., Yuge, N., Watanabe, M., Uchino, Y., … Okano, T. (2010). Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature, 468(7320), 117–121. https://doi.org/10.1038/nature09464
Noda, S., Asano, Y., Nishimura, S., Taniguchi, T., Fujiu, K., Manabe, I., … Takahashi, T. (2014). Simultaneous downregulation of KLF5 and Fli1 is a key feature underlying systemic sclerosis. Nature Communications, 5, 5797. https://doi.org/10.1038/ncomms6797
Nogeire, T. M., Lawler, J. J., Schumaker, N. H., Cypher, B. L., & Phillips, S. E. (2015). Land Use as a driver of patterns of rodenticide exposure in modeled kit fox populations. PLoS ONE, 10(8), e0133351. https://doi.org/10.1371/journal.pone.0133351
Nuutila, K., Siltanen, A., Peura, M., Bizik, J., Kaartinen, I., Kuokkanen, H., … Kankuri, E. (2012). Human skin transcriptome during superficial cutaneous wound healing. Wound Repair and Regeneration, 20(6), 830–839. https://doi.org/10.1111/j.1524-475X.2012.00831.x
Opal, S. M., & Esmon, C. T. (2002). Bench-to-bedside review: functional relationships between coagulation and the innate immune response and their respective roles in the pathogenesis of sepsis. Critical Care, 7(1), 23. https://doi.org/10.1186/cc1854
Orkin, S. H., & Zon, L. I. (2008). Hematopoiesis: an evolving paradigm for stem cell biology. Cell, 132(4), 631–644. https://doi.org/10.1016/j.cell.2008.01.025
Ozcan, A., Ware, K., Calomeni, E., Nadasdy, T., Forbes, R., Satoskar, A. A., … Brodsky, S. V. (2012). 5/6 Nephrectomy as a validated rat model mimicking human warfarin-related nephropathy. American Journal of Nephrology, 35(4), 356–364. https://doi.org/10.1159/000337918
Park, C. S., Shen, Y., Lewis, A., & Lacorazza, H. D. (2016). Role of the reprogramming factor KLF4 in blood formation. Journal of Leukocyte Biology, 99(5), 673–685. https://doi.org/10.1189/jlb.1RU1215-539R
Pasquet, M., Bellanné-Chantelot, C., Tavitian, S., Prade, N., Beaupain, B., LaRochelle, O., … Poirel, H. A. (2013). High frequency of GATA2 mutations in patients with mild chronic neutropenia evolving to MonoMac syndrome, myelodysplasia, and acute myeloid leukemia. Blood, 121(5), 822–829. https://doi.org/10.1182/blood-2012-08-447367
Pence, D. B., Matthews III, F. D., & Windberg, L. A. (1982). Notoedric mange in the bobcat, Felis rufus, from south Texas. Journal of Wildlife Diseases, 18(1), 47–50. https://doi.org/10.7589/0090-3558-18.1.47
Pence, D. B., Tewes, M. E., Shindle, D. B., & Dunn, D. M. (1995). Notoedric mange in an ocelot (Felis pardalis) from southern Texas. Journal of Wildlife Diseases, 31(4), 558–561. https://doi.org/10.7589/0090-3558-31.4.558
Penner, L. R., & Parke, W. N. (1954). Notoedric mange in the bobcat, Lynx rufus. Journal of Mammalogy, 35(3), 458–459.
Petterino, C., & Paolo, B. (2001). Toxicology of various anticoagulant rodenticides in animals. Veterinary and Human Toxicology, 43(6), 353–360.
Popov, A., Belij, S., Subota, V., Zolotarevski, L., Mirkov, I., Kataranovski, D., & Kataranovski, M. (2013). Oral warfarin affects peripheral blood leukocyte IL-6 and TNF α production in rats. Journal of Immunotoxicology, 10(1), 17–24. https://doi.org/10.3109/1547691X.2012.684159
Powell, N. D., Sloan, E. K., Bailey, M. T., Arevalo, J. M., Miller, G. E., Chen, E., … Cole, S. W. (2013). Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis. Proceedings of the National Academy of Sciences of the United States of America, 110(41), 16574–16579. https://doi.org/10.1073/pnas.1310655110
Rahman, M. M., Lecchi, C., Fraquelli, C., Sartorelli, P., & Ceciliani, F. (2010). Acute phase protein response in Alpine ibex with sarcoptic mange. Veterinary Parasitology, 168(3), 293–298. https://doi.org/10.1016/j.vetpar.2009.12.001
Rattner, B. A., Lazarus, R. S., Elliott, J. E., Shore, R. F., & van den Brink, N. (2014). Adverse outcome pathway and risks of anticoagulant rodenticides to predatory wildlife. Environmental Science and Technology, 48(15), 8433–8445. https://doi.org/10.1021/es501740n
Reimand, J., Arak, T., Adler, P., Kolberg, L., Reisberg, S., Peterson, H., & Vilo, J. (2016). g: Profiler—a web server for functional interpretation of gene lists (2016 update). Nucleic acids Research, 44, W83–W89. https://doi.org/10.1093/nar/gkw199
Riley, S. P. D., Boydston, E. E., Crooks, K. R., & Lyren, L. M. (2010). Bobcats (Lynx rufus). In S. D. Gehrt, S. P. D. Riley & B. Cypher (Eds.), Urban carnivores: ecology, conflict, and conservation (pp. 120–138). Baltimore, MD: Johns Hopkins University Press.
Riley, S. P. D., Bromley, C., Poppenga, R. H., Uzal, F. A., Whited, L., & Sauvajot, R. M. (2007). Anticoagulant exposure and notoedric mange in bobcats and mountain lions in urban southern California. The Journal of Wildlife Management, 71(6), 1874–1884. https://doi.org/10.2193/2005-615
Riley, S. P. D., Sauvajot, R. M., Fuller, T. K., York, E. C., Kamradt, D. A., Bromley, C., & Wayne, R. K. (2003). Effects of urbanization and habitat fragmentation on bobcats and coyotes in southern California. Conservation Biology, 17(2), 566–576. https://doi.org/10.1046/j.1523-1739.2003.01458.x
Riley, S. P. D., Serieys, L. E. K., & Moriarty, J. G. (2015). Infectious disease and contaminants in urban wildlife: unseen and often overlooked threats. In B. McCleery, C. Moorman & N. Peterson (Eds.), Urban wildlife science: theory and practice (pp. 175–215). Boston, MA: Elsevier Press.
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015). limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research, 43(7), e47. https://doi.org/10.1093/nar/gkv007
Robinson, M. D., & Oshlack, A. (2010). A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biology, 11, R25. https://doi.org/10.1186/gb-2010-11-3-r25
Russell, L. J., DiGiovanna, J. J., Rogers, G. R., Steinert, P. M., Hashem, N., Compton, J. G., & Bale, S. J. (1995). Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis. Nature Genetics, 9, 279–283. https://doi.org/10.1038/ng0395-279
Rutkevich, L. A., & Williams, D. B. (2012). Vitamin K epoxide reductase contributes to protein disulfide formation and redox homeostasis within the endoplasmic reticulum. Molecular Biology of the Cell, 23(11), 2017–2027. https://doi.org/10.1091/mbc.E12-02-0102
Sada, E., Abe, Y., Ohba, R., Tachikawa, Y., Nagasawa, E., Shiratsuchi, M., & Takayanagi, R. (2010). Vitamin K2 modulates differentiation and apoptosis of both myeloid and erythroid lineages. European Journal of Haematology, 85(6), 538–548. https://doi.org/10.1111/j.1600-0609.2010.01530.x
Sánchez-Barbudo, I. S., Camarero, P. R., & Mateo, R. (2012). Primary and secondary poisoning by anticoagulant rodenticides of non-target animals in Spain. Science of the Total Environment, 420, 280–288. https://doi.org/10.1016/j.scitotenv.2012.01.028
Santadino, M., Coviella, C., & Momo, F. (2014). Glyphosate sublethal effects on the population dynamics of the earthworm Eisenia fetida (Savigny, 1826). Water, Air, & Soil Pollution, 225(12), 2207. https://doi.org/10.1007/s11270-014-2207-3
Sato, S., Fujimoto, M., Hasegawa, M., & Takehara, K. (2004). Altered blood B lymphocyte homeostasis in systemic sclerosis: expanded naive B cells and diminished but activated memory B cells. Arthritis and Rheumatism, 50(6), 1918–1927. https://doi.org/10.1002/(ISSN)1529-0131
Schoeters, G. E. R., Vander Plaetse, F., Leppens, H., & Van Den Heuvel, R. (1995). Haemopoietic and osteogenic toxicity testing in vitro using murine bone marrow cultures. Toxicology in Vitro, 9(4), 421–428. https://doi.org/10.1016/0887-2333(95)00034-6
Segre, J. A., Bauer, C., & Fuchs, E. (1999). Klf4 is a transcription factor required for establishing the barrier function of the skin. Nature Genetetics, 22(4), 356–360.
Serieys, L. E., Armenta, T. C., Moriarty, J. G., Boydston, E. E., Lyren, L. M., Poppenga, R. H., … Riley, S. P. (2015). Anticoagulant rodenticides in urban bobcats: exposure, risk factors and potential effects based on a 16-year study. Ecotoxicology, 24(4), 844–862. https://doi.org/10.1007/s10646-015-1429-5
Serieys, L. E., Lea, A. J., Epeldegui, M., Armenta, T. C., Moriarty, J., VandeWoude, S., … Uittenbogaart, C. H. (2018). Urbanization and anticoagulant poisons promote immune dysfunction in bobcats. Proceedings of the Royal Society of London B, 285(1871), 20172533.
Serieys, L. E. K., Lea, A., Pollinger, J. P., Riley, S. P. D., & Wayne, R. K. (2015). Disease and urbanization drive temporal and spatial genetic changes among bobcat populations in an urban, fragmented landscape. Evolutionary Applications, 8, 75–92. https://doi.org/10.1111/eva.12226
Shahrin, N. H., Diakiw, S., Dent, L. A., Brown, A. L., & D'Andrea, R. J. (2016). Conditional knockout mice demonstrate function of Klf5 as a myeloid transcription factor. Blood, 128(1), 55–59. https://doi.org/10.1182/blood-2015-12-684514
Shearer, M. J., & Newman, P. (2008). Metabolism and cell biology of vitamin K. Thrombosis and Haemostasis, 100(4), 530–547.
Shrestha, B., Reed, J. M., Starks, P. T., Kaufman, G. E., Goldstone, J. V., Roelke, M. E., … Frank, L. G. (2011). Evolution of a major drug metabolizing enzyme defect in the domestic cat and other felidae: phylogenetic timing and the role of hypercarnivory. PLoS ONE, 6(3), e18046. https://doi.org/10.1371/journal.pone.0018046
Storey, J., Bass, A., Dabney, A., & Robinson, D. (2015). qvalue: Q-value estimation for false discovery rate control. R package version 2.6.0
Suttie, J. W. (2009). Vitamin K in health and disease. Boca Raton, FL: CRC Press. https://doi.org/10.1201/9781420005110
Tabb, M. M., Sun, A., Zhou, C., Grün, F., Errandi, J., Romero, K., … Forman, B. M. (2003). Vitamin K2 regulation of bone homeostasis is mediated by the steroid and xenobiotic receptor SXR. The Journal of Biological Chemistry, 278(45), 43919–43927. https://doi.org/10.1074/jbc.M303136200
Tetreault, M. P., Weinblatt, D., Shaverdashvili, K., Yang, Y., & Katz, J. P. (2016). KLF4 transcriptionally activates non-canonical WNT5A to control epithelial stratification. Scientific Reports, 6, 26130. https://doi.org/10.1038/srep26130
Thacher, S. M., & Rice, R. H. (1985). Keratinocyte-specific transglutaminase of cultured human epidermal cells: relation to cross-linked envelope formation and terminal differentiation. Cell, 40, 685–695. https://doi.org/10.1016/0092-8674(85)90217-X
Thompson, C., Sweitzer, R., Gabriel, M., Purcell, K., Barrett, R., & Poppenga, R. (2014). Impacts of rodenticide and insecticide toxicants from marijuana cultivation sites on fisher survival rates in the Sierra National Forest, California. Conservation Letters, 7(2), 91–102. https://doi.org/10.1111/conl.12038
Tsai, F. Y., & Orkin, S. H. (1997). Transcription factor GATA-2 is required for proliferation/survival of early hematopoietic cells and mast cell formation, but not for erythroid and myeloid terminal differentiation. Blood, 89(10), 3636–3643.
van Beusekom, C. D. (2015). Feline hepatic biotransformation and transport mechanisms. Doctoral dissertation, Utrecht University, Utrecht, the Netherlands.
Wadelius, M., Sörlin, K., Wallerman, O., Karlsson, J., Yue, Q. Y., Magnusson, P. K. E., … Melhus, H. (2004). Warfarin sensitivity related to CYP2C9, CYP3A5, ABCB1 (MDR1) and other factors. The Pharmacogenomics Journal, 4(1), 40–48. https://doi.org/10.1038/sj.tpj.6500220
Walton, S. F. (2010). The immunology of susceptibility and resistance to scabies. Parasite Immunology, 32(8), 532–540.
Ware, K. M., Feinstein, D. L., Rubinstein, I., Weinberg, G., Rovin, B. H., Hebert, L., … Brodsky, S. V. (2015). Brodifacoum induces early hemoglobinuria and late hematuria in rats: novel rapid biomarkers of poisoning. American Journal of Nephrology, 41(4–5), 392–399. https://doi.org/10.1159/000433568
Yates, A., Akanni, W., Amode, M. R., Barrell, D., Billis, K., Carvalho-Silva, D., … Girón, C. G. (2016). Ensembl 2016. Nucleic Acids Research, 44(D1), D710–D716. https://doi.org/10.1093/nar/gkv1157
Zanger, U. M., & Schwab, M. (2013). Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacology & Therapeutics, 138(1), 103–141. https://doi.org/10.1016/j.pharmthera.2012.12.007
Zhang, B., & Horvath, S. (2005). A general framework for weighted gene co-expression network analysis. Statistical Applications in Genetics and Molecular Biology, 4(1).
Zhu, L., Qu, K., Xia, B., Sun, X., & Chen, B. (2016). Transcriptomic response to water accommodated fraction of crude oil exposure in the gill of Japanese flounder, Paralichthys olivaceus. Marine Pollution Bulletin, 106(1), 283–291. https://doi.org/10.1016/j.marpolbul.2015.12.022