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003 OCoLC;

005 20141212075947.0;

006 m d ;

007 cr bn|||||||||;

008 120124s2011 ncua ob 000 0 eng d;

035 a| (Sirsi) o773723371;

035 a| (OCoLC)773723371;

040 a| EREc| EREd| EREd| UtOrBLW;

049 a| EREE;

090 a| QP801.N48;

100 1 a| Smith, Michael A.q| (Michael Alfred),d| 1940-=| ^A55278;

245 10 a| Effects of nicotine on Caenorhabditis elegans survival, reproduction, and gene expressions :b| development of an invertebrate animal model for drugs of abuse /c| by Michael A. Smith.;

260 a| [Greenville, N.C.] :b| East Carolina University,c| 2011.;

300 a| 101 pages :b| illustrations (some color), digital, PDF file;

336 a| text2| rdacontent;

337 a| computer2| rdamedia;

338 a| online resource2| rdacarrier;

538 a| System requirements: Adobe Reader.;

538 a| Mode of access: World Wide Web.;

502 b| M.S.c| East Carolina Universityd| 2011.;

500 a| Presented to the faculty of the Department of Biology.;

500 a| Advisor: Xiaoping Pan.;

500 a| Title from PDF t.p. (viewed Jan. 31, 2012).;

520 3 a| Although much is known about the addictive effects of nicotine, the molecular mechanisms of nicotine-induced effects remain largely unclear. Specifically, little is known about the effects of nicotine on gene expression, including gene expression controlled by miRNAs. miRNAs may play a key role in regulating gene expression in response to nicotine exposure due to the fact that expression profiles of the miRNAs will be altered. These effects on gene expression may be associated with long-term use and the "addictive" behavior that is often exhibited with use of nicotine. Our goals are to explore the toxicity of nicotine on Caenorhabditis elegans (C. elegans), including survival, reproduction, and gene expression and to develop C. elegans as a model organism to assess the toxicity of various xenobiotics. We hypothesize that 1) Nicotine affects survival and reproduction of C. elegans; 2) The expression of several important genes, including the genes coding for the nicotinic acetylcholine receptor and for oxidative stress response, will be affected by nicotine exposure; and 3) The expression of miRNA genes will be changed and related to the selected protein coding gene expression. In survival trials, we tested a range of doses to obtain a 24- hour dose-response data. The 24-hour lethal dose-20 (LD20) in C. elegans corresponds to dose of ~3.16 ppm (19.5 uM) of nicotine. A reproduction study revealed that even at low nicotine exposure levels, egg-laying is affected. Using qRT-PCR, we found that the expression of several egg-laying and oxidative stress related genes were altered by nicotine, which may be regulated by miRNAs. We were able to analytically determine that the expression patterns of the selected protein coding genes were dose-related. In the miRNA assay, we analyzed the expression of four miRNAs (Cel-mir-70, Cel-mir-58, Cel-mir-790, Cel-mir-253.), which were selected by in-silico prediction of miRNAs that potentially target our protein-coding genes of interest. We found that individual miRNA expression profiles varied among the different concentrations, indicating that the nicotine concentration induces a differential miRNA expression. At 3.16 ppm, where the protein-coding genes are the most active, miRNAs are also up-regulated indicating there is a complex system of regulation based on more than one miRNA, many miRNAs may target the same gene. Therefore, we believe that miRNAs may play a key role in controlling protein-coding gene expression. The understanding of this relationship between the toxicant (nicotine) and its effects on miRNAs and their targeted genes will lead to a greater understanding of mechanisms of nicotine-related addiction.;

504 a| Includes bibliographical references.;

650 0 a| Caenorhabditis elegans.=| ^A627930;

650 0 a| Nicotine addiction.=| ^A652385;

650 0 a| Gene expression.=| ^A6250;

650 0 a| RNA.=| ^A4131;

650 0 a| Animal models in research.=| ^A146732;

653 a| Biology;

653 a| Biochemistry;

700 1 a| Pan, Xiaopingc| (Professor of biology),e| degree supervisor.=| ^A1443924;

710 2 a| East Carolina University.b| Department of Biology.=| ^A637467;

856 40 z| Access via ScholarShipu| http://hdl.handle.net/10342/3713;

949 o| jgml;

994 a| C0b| ERE;

596 a| 1 4;

998 a| 2677546;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 2677546-1001l| JNETm| JOYNERr| Ys| Yt| JNE3ETDu| 1/24/2012x| ETDz| JERESOURCE;

999 a| CLICK ON WEB ADDRESSw| ASISc| 1i| 2677546-2001l| HSLELECm| HSLr| Ys| Yt| HEETDu| 1/24/2012x| ETDz| HERESOURCE;

Effects of nicotine on Caenorhabditis elegans survival, reproduction, and gene expressions : development of an invertebrate animal model for drugs of abuse / by Michael A. Smith.

Author/creator	Smith, Michael A., 1940-
Other author	Pan, Xiaoping (Professor of biology), degree supervisor.
Other author	East Carolina University. Department of Biology.
Format	Theses and dissertations
Publication Info	[Greenville, N.C.] : East Carolina University, 2011.
Description	101 pages : illustrations (some color), digital, PDF file
Supplemental Content	Access via ScholarShip
Subjects	Caenorhabditis elegans. Nicotine addiction. Gene expression. RNA. Animal models in research.

Summary	Although much is known about the addictive effects of nicotine, the molecular mechanisms of nicotine-induced effects remain largely unclear. Specifically, little is known about the effects of nicotine on gene expression, including gene expression controlled by miRNAs. miRNAs may play a key role in regulating gene expression in response to nicotine exposure due to the fact that expression profiles of the miRNAs will be altered. These effects on gene expression may be associated with long-term use and the "addictive" behavior that is often exhibited with use of nicotine. Our goals are to explore the toxicity of nicotine on Caenorhabditis elegans (C. elegans), including survival, reproduction, and gene expression and to develop C. elegans as a model organism to assess the toxicity of various xenobiotics. We hypothesize that 1) Nicotine affects survival and reproduction of C. elegans; 2) The expression of several important genes, including the genes coding for the nicotinic acetylcholine receptor and for oxidative stress response, will be affected by nicotine exposure; and 3) The expression of miRNA genes will be changed and related to the selected protein coding gene expression. In survival trials, we tested a range of doses to obtain a 24- hour dose-response data. The 24-hour lethal dose-20 (LD20) in C. elegans corresponds to dose of ~3.16 ppm (19.5 uM) of nicotine. A reproduction study revealed that even at low nicotine exposure levels, egg-laying is affected. Using qRT-PCR, we found that the expression of several egg-laying and oxidative stress related genes were altered by nicotine, which may be regulated by miRNAs. We were able to analytically determine that the expression patterns of the selected protein coding genes were dose-related. In the miRNA assay, we analyzed the expression of four miRNAs (Cel-mir-70, Cel-mir-58, Cel-mir-790, Cel-mir-253.), which were selected by in-silico prediction of miRNAs that potentially target our protein-coding genes of interest. We found that individual miRNA expression profiles varied among the different concentrations, indicating that the nicotine concentration induces a differential miRNA expression. At 3.16 ppm, where the protein-coding genes are the most active, miRNAs are also up-regulated indicating there is a complex system of regulation based on more than one miRNA, many miRNAs may target the same gene. Therefore, we believe that miRNAs may play a key role in controlling protein-coding gene expression. The understanding of this relationship between the toxicant (nicotine) and its effects on miRNAs and their targeted genes will lead to a greater understanding of mechanisms of nicotine-related addiction.
General note	Presented to the faculty of the Department of Biology.
General note	Advisor: Xiaoping Pan.
General note	Title from PDF t.p. (viewed Jan. 31, 2012).
Dissertation note	M.S. East Carolina University 2011.
Bibliography note	Includes bibliographical references.
Technical details	System requirements: Adobe Reader.
Technical details	Mode of access: World Wide Web.

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Effects of nicotine on Caenorhabditis elegans survival, reproduction, and gene expressions : development of an invertebrate animal model for drugs of abuse / by Michael A. Smith.

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