subject:(MADD)

University of Toronto

1. Seetharaman, Ashwin. The Cloning and Characterization of MADD-4, A Novel Guidance Cue in C. elegans.

Degree: PhD, 2015, University of Toronto

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Directed cell migration is fundamental to the development of all multicellular organisms including humans. To investigate the molecular underpinnings of directed cell migration, our lab… (more)

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Directed cell migration is fundamental to the development of all multicellular organisms including humans. To investigate the molecular underpinnings of directed cell migration, our lab primarily exploits plasma membrane extensions called muscle arms, from the body wall muscles in the tiny nematode Caenorhabditis elegans. Through genetic screens for genes required for muscle arm extension, we found that the UNC-40/DCC netrin guidance receptor directs muscle arm extension to the midlines. Surprisingly, neither the UNC-6/netrin cue (the canonical ligand for UNC-40) nor other well-characterized guidance cues such as the slits, ephrins and semaphorins were found to be the primary cue for muscle arm extension. This suggested that muscle arms were likely responding to a novel guidance cue. In this thesis, I describe the cloning and characterization of MADD-4, a novel secreted cue that diffuses and attracts muscle arms and sensory axons along the dorsoventral axis in C. elegans. MADD-4 is a member of the non-enzymatic ADAMTSL family of proteins and is well conserved among animals. Very little is known about the biological role of any of MADD-4's orthologs. Together with Kevin Chan, I found that MADD-4's guidance function is dependent on an EVA-1-UNC-40 co-receptor complex. We found that MADD-4 interacts with both EVA-1 and UNC-40. Similarly, we found that EVA-1 and UNC-40 likely physically interact and this interaction is critical for the MADD-4 response. Furthermore, we found that the binding of EVA-1 to UNC-40 increases UNC-40's sensitivity to MADD-4. This enhanced sensitivity becomes especially meaningful within a field of other ligands capable of binding UNC-40 like UNC-6. In the absence of UNC-6, UNC-40's responsiveness to MADD-4 becomes less dependent on EVA-1. Hence, by regulating UNC-40's sensitivity to MADD-4, EVA-1 may increase the precision by which UNC-40-directed processes can reach MADD-4-expressing target cells. Collectively, the work discussed in this thesis recounts the first description of a novel guidance cue and its mechanism of action. Furthermore, since the biological role of any ADAMTSL family member outside of MADD-4 is largely unknown, it is very likely that my work on MADD-4 will broaden our understanding of the biological role of the ADAMTSL family of proteins.

2018-06-17 00:00:00

Advisors/Committee Members: Roy, Peter J, Molecular and Medical Genetics.

Subjects/Keywords: ADAMTSL; C. elegans; DCC; EVA-1; MADD-4; Netrin; 0758

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Seetharaman, A. (2015). The Cloning and Characterization of MADD-4, A Novel Guidance Cue in C. elegans. (Doctoral Dissertation). University of Toronto. Retrieved from http://hdl.handle.net/1807/94564

Chicago Manual of Style (16^th Edition):

Seetharaman, Ashwin. “The Cloning and Characterization of MADD-4, A Novel Guidance Cue in C. elegans.” 2015. Doctoral Dissertation, University of Toronto. Accessed March 08, 2021. http://hdl.handle.net/1807/94564.

MLA Handbook (7^th Edition):

Seetharaman, Ashwin. “The Cloning and Characterization of MADD-4, A Novel Guidance Cue in C. elegans.” 2015. Web. 08 Mar 2021.

Vancouver:

Seetharaman A. The Cloning and Characterization of MADD-4, A Novel Guidance Cue in C. elegans. [Internet] [Doctoral dissertation]. University of Toronto; 2015. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1807/94564.

Council of Science Editors:

Seetharaman A. The Cloning and Characterization of MADD-4, A Novel Guidance Cue in C. elegans. [Doctoral Dissertation]. University of Toronto; 2015. Available from: http://hdl.handle.net/1807/94564

The Ohio State University

2. Ceisler, Andrea Lynne. Mothers Against Drunk Drivers: three theoretical explanations for a contemporary rhetorical movement.

Degree: MA, Communication, 1984, The Ohio State University

URL: http://rave.ohiolink.edu/etdc/view?acc_num=osu1134063991

Subjects/Keywords: MADD; DRUNK DRIVERS; Lightner

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ceisler, A. L. (1984). Mothers Against Drunk Drivers: three theoretical explanations for a contemporary rhetorical movement. (Masters Thesis). The Ohio State University. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=osu1134063991

Chicago Manual of Style (16^th Edition):

Ceisler, Andrea Lynne. “Mothers Against Drunk Drivers: three theoretical explanations for a contemporary rhetorical movement.” 1984. Masters Thesis, The Ohio State University. Accessed March 08, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=osu1134063991.

MLA Handbook (7^th Edition):

Ceisler, Andrea Lynne. “Mothers Against Drunk Drivers: three theoretical explanations for a contemporary rhetorical movement.” 1984. Web. 08 Mar 2021.

Vancouver:

Ceisler AL. Mothers Against Drunk Drivers: three theoretical explanations for a contemporary rhetorical movement. [Internet] [Masters thesis]. The Ohio State University; 1984. [cited 2021 Mar 08]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1134063991.

Council of Science Editors:

Ceisler AL. Mothers Against Drunk Drivers: three theoretical explanations for a contemporary rhetorical movement. [Masters Thesis]. The Ohio State University; 1984. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=osu1134063991

University of Georgia

3. Low, Walter Steven. Collective action and news report framing.

Degree: 2014, University of Georgia

URL: http://hdl.handle.net/10724/21892

► This study investigated the relationship between anti-drunk driving organizations, led by Mothers Against Drunk Driving and journalists who covered the drunk driving issue. A content… (more)

Subjects/Keywords: Framing; Social Movement Organizations; Collective Action Frames; MADD; Mothers Against Drunk Driving; Drunk Drivers; Print Journalism; Broadcast Journalism

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Low, W. S. (2014). Collective action and news report framing. (Thesis). University of Georgia. Retrieved from http://hdl.handle.net/10724/21892

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Low, Walter Steven. “Collective action and news report framing.” 2014. Thesis, University of Georgia. Accessed March 08, 2021. http://hdl.handle.net/10724/21892.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Low, Walter Steven. “Collective action and news report framing.” 2014. Web. 08 Mar 2021.

Vancouver:

Low WS. Collective action and news report framing. [Internet] [Thesis]. University of Georgia; 2014. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/10724/21892.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Low WS. Collective action and news report framing. [Thesis]. University of Georgia; 2014. Available from: http://hdl.handle.net/10724/21892

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

4. Ji, Tingting. Development of MegaTIC as a new tool for genome engineering and analysis of GABAA receptor localization mechanisms in Caenorhabditis elegans : Développement de MegaTIC comme un nouvel outil pour l'ingénierie du génome et analyse des mécanismes de localisation des récepteurs GABA dans Caenorhabditis elegans.

Degree: Docteur es, Génétique et neurobiologie, 2015, Université Pierre et Marie Curie – Paris VI

URL: http://www.theses.fr/2015PA066278

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Les stratégies d'ingénierie du génome par recombinaison homologue basées sur la technologie CRISPR/Cas-9 ont été largement utilisées pour modifier la séquence de gènes chez C.… (more)

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Les stratégies d'ingénierie du génome par recombinaison homologue basées sur la technologie CRISPR/Cas-9 ont été largement utilisées pour modifier la séquence de gènes chez C. elegans. Cependant, l'efficacité de sélection des animaux modifiés nécessite d'être améliorée. Nous avons développé un nouveau marqueur, le gène miniSOG, qui permet la contre-sélection des animaux non modifiés et que nous avons intégré dans une cassette de double sélection. Les animaux contenant la cassette HySOG sont d'abord sélectionnés pour leur résistance à un antibiotique, l'hygromycine B. HySOG est ensuite excisée et les modifications sont insérées au locus cible. Les souches recombinantes résistent à une exposition à la lumière bleue, qui tue les vers exprimant le gène miniSOG. Nous montrons que la méganucléase I-SceI peut être utilisée pour exciser HySOG et pour introduire des modifications dans la lignée germinale avec la même efficacité que la technologie CRISPR/Cas-9.Des technologies d'ingénierie du génome ont été utilisées pour étiqueter la sous-unité des GABAAR UNC-49 et pour analyser le rôle de MADD-4/Punctin, UNC-40/DCC et NLG-1/neurologine sur l'agrégation synaptique des GABAAR à la jonction neuromusculaire GABAergique. Nous montrons que MADD-4, une protéine de la matrice extracellulaire sécrétée par les motoneurones, est un nouveau ligand de NLG-1 et de UNC-40 et constitue un organisateur synaptique antérograde des synapses GABAergiques. D'abord, l'isoforme courte de MADD-4, MADD-4B, lie directement NLG-1 et assure sa localisation à la membrane post-synaptique. Ensuite, MADD-4B lie, recrute et active probablement le récepteur UNC-40, qui renforce l'interaction des GABAAR avec NLG-1.

CRISPR/Cas-9-based techniques have been widely used to engineer any gene in C. elegans by homologous recombination. However, the selective efficacy of engineered animals needs to be expanded. We have developed miniSOG as a counter-selection marker in a dual selection strategy. Animals containing the dual selection cassette HySOG are firstly selected by the resistance to the antibiotic hygromycin B. HySOG is then excised and customized gene modifications are inserted into target sites. Recombinant strains are selected based on the resistance to blue light exposure, which otherwise kills miniSOG expressing worms. We demonstrate that meganuclease I-SceI can be used to excise HySOG and to introduce gene modifications in C. elegans germline as efficiently as CRISPR/Cas-9. Genome-engineering techniques have been used to tag the GABAAR subunit UNC-49 with RFP and to analyze the role of MADD-4/Punctin, UNC-40/DCC and NLG-1/neuroligin on GABAARs clustering at GABAergic NMJs. We showed that MADD-4/Punctin, an extracellular matrix protein secreted by GABAergic neurons, is a new ligand of NLG-1/neuroligin and of UNC-40/DCC and functions as a central anterograde organizer of GABAergic synapses. First, the short isoform of MADD-4, MADD-4B directly binds NLG-1/neuroligin and localizes it in the post-synaptic membrane of GABAergic synapses. Second, MADD-4B…

Advisors/Committee Members: Bessereau, Jean-Louis (thesis director).

Subjects/Keywords: MiniSOG; Méganucléase I-SceI; Conversion génique; NLG-1/neuroligin; MADD-4/Punctin; L'agrégation synaptique des GABAAR; MiniSOG; Genome; 576.5

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ji, T. (2015). Development of MegaTIC as a new tool for genome engineering and analysis of GABAA receptor localization mechanisms in Caenorhabditis elegans : Développement de MegaTIC comme un nouvel outil pour l'ingénierie du génome et analyse des mécanismes de localisation des récepteurs GABA dans Caenorhabditis elegans. (Doctoral Dissertation). Université Pierre et Marie Curie – Paris VI. Retrieved from http://www.theses.fr/2015PA066278

Chicago Manual of Style (16^th Edition):

Ji, Tingting. “Development of MegaTIC as a new tool for genome engineering and analysis of GABAA receptor localization mechanisms in Caenorhabditis elegans : Développement de MegaTIC comme un nouvel outil pour l'ingénierie du génome et analyse des mécanismes de localisation des récepteurs GABA dans Caenorhabditis elegans.” 2015. Doctoral Dissertation, Université Pierre et Marie Curie – Paris VI. Accessed March 08, 2021. http://www.theses.fr/2015PA066278.

MLA Handbook (7^th Edition):

Ji, Tingting. “Development of MegaTIC as a new tool for genome engineering and analysis of GABAA receptor localization mechanisms in Caenorhabditis elegans : Développement de MegaTIC comme un nouvel outil pour l'ingénierie du génome et analyse des mécanismes de localisation des récepteurs GABA dans Caenorhabditis elegans.” 2015. Web. 08 Mar 2021.

Vancouver:

Ji T. Development of MegaTIC as a new tool for genome engineering and analysis of GABAA receptor localization mechanisms in Caenorhabditis elegans : Développement de MegaTIC comme un nouvel outil pour l'ingénierie du génome et analyse des mécanismes de localisation des récepteurs GABA dans Caenorhabditis elegans. [Internet] [Doctoral dissertation]. Université Pierre et Marie Curie – Paris VI; 2015. [cited 2021 Mar 08]. Available from: http://www.theses.fr/2015PA066278.

Council of Science Editors:

Ji T. Development of MegaTIC as a new tool for genome engineering and analysis of GABAA receptor localization mechanisms in Caenorhabditis elegans : Développement de MegaTIC comme un nouvel outil pour l'ingénierie du génome et analyse des mécanismes de localisation des récepteurs GABA dans Caenorhabditis elegans. [Doctoral Dissertation]. Université Pierre et Marie Curie – Paris VI; 2015. Available from: http://www.theses.fr/2015PA066278

University of Pennsylvania

5. Song, Yuanquan. Cellular and Molecular Analyses of Neural and Synaptic Development in Zebrafish.

Degree: 2009, University of Pennsylvania

URL: https://repository.upenn.edu/edissertations/297

► Proper function of the nervous system requires the precise wiring of neuronal circuitry, which is established during development via mechanisms that guide cells to establish… (more)

Subjects/Keywords: zebrafish; synaptogenesis; fucosylation; notch; etfdh; madd; Developmental Neuroscience; Molecular and Cellular Neuroscience

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Song, Y. (2009). Cellular and Molecular Analyses of Neural and Synaptic Development in Zebrafish. (Thesis). University of Pennsylvania. Retrieved from https://repository.upenn.edu/edissertations/297

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Song, Yuanquan. “Cellular and Molecular Analyses of Neural and Synaptic Development in Zebrafish.” 2009. Thesis, University of Pennsylvania. Accessed March 08, 2021. https://repository.upenn.edu/edissertations/297.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Song, Yuanquan. “Cellular and Molecular Analyses of Neural and Synaptic Development in Zebrafish.” 2009. Web. 08 Mar 2021.

Vancouver:

Song Y. Cellular and Molecular Analyses of Neural and Synaptic Development in Zebrafish. [Internet] [Thesis]. University of Pennsylvania; 2009. [cited 2021 Mar 08]. Available from: https://repository.upenn.edu/edissertations/297.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Song Y. Cellular and Molecular Analyses of Neural and Synaptic Development in Zebrafish. [Thesis]. University of Pennsylvania; 2009. Available from: https://repository.upenn.edu/edissertations/297

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of New Mexico

6. Medina, Una E. MADD MESSAGE EFFECTS: A TWELVE-YEAR RANDOMIZED TRIAL.

Degree: Department of Communication and Journalism, 2010, University of New Mexico

URL: http://hdl.handle.net/1928/12395

► One out of three Americans undergoes drunk-driving crashes; 23% result in death. To deter DWIs (Driving While under Influence), MADD (Mothers Against Drunk Drivers) created… (more)

▼ One out of three Americans undergoes drunk-driving crashes; 23% result in death. To deter DWIs (Driving While under Influence), MADD (Mothers Against Drunk Drivers) created VIPs (Victim Impact Panels) where victims impact offenders with gory stories, photos, and threats of punishments and loss of freedom, hoping this message will deter DWIs. It is remarkable that although the VIP message is considered a primary DWI intervention, yet no studies have investigated VIP message effects. VIP message effects, their persistence and decay, are chronicled here over the course of 12 years. This study extends an empirical investigation of VIPs, conducted by Woodall, Delaney, Rogers, and Wheeler (2007) (n = 833) during 1994-1996. At 2 years, these researchers found MADD VIP participants' recidivism rates were 30% higher than their DWI School comparison group, trending toward significance at p = .0583. This study supports those results as significant at 12 years. As an extension, it investigates whether reactance theory explains VIP message effects failure. Reactance theory research, a subset of message effects research, explains how emotional, confrontational, and threatening messages induce psychological reactance in the mind of the message receiver, who then seeks to preserve his or her sense of freedom by behaving contrarily (Brehm, 1966). Hierarchically intensifying effects of these theoretical reactance antecedents are studied here in an unusual manner, as they occur in vivo, in real life. The same intervention was observed to have different effects depending on prior conditions and demographics. The emotional high-threat, high-confrontation MADD VIP message coincided with significantly shorter time to recidivism (p = .009, d = 1.64) and significantly higher number of subsequent arrests (p < .0001, d = 1.64) among recent prior offenders, and those with no priors under age 30 (p = .01, d = 0.35). Younger offenders may be associated with more iconoclastic behavior than older offenders (Beirness & Simpson, 1997; Greenberg, 2005; NHTSA, 2008), partially explaining the under-30 age effect. This study furthers persuasive message design as a science and suggests a message-based approach to intervention analysis. There was no effect when MADD VIP was analyzed simply as an intervention. However, there were highly significant effect sizes when the same MADD VIP intervention was analyzed as a message. This study concludes by offering MADD VIP best practice recommendations. Advisors/Committee Members: Woodall, W. Gill, Schuetz, Janice, Rivera, Mario A., McDermott, Virginia, Delaney, Harold.

Subjects/Keywords: Victim Impact panels; MADD; message effects; randomized trial; effect size; drunk driving; DWI; efficacy trial; method problems; methodological problems; communication theory; theory building; rhetorical analysis; triangulation; drunk driving; interventions; covariates; ANOVA; ANCOVA; survival analysis; message context; message content; message function; message intensity; message frequency; message metrics; message pathos; pathos; message decay; decay rate; message decay rate; intent to persuade; persuasion; confrontation; shame; shaming; public shaming; public censure; forewarning; perceived threat; reactance theory; assumptions; sampling error; recruitment error; non-adherence to condition; random assignment error; factorial design; operationalization; theory construct operationalization; methods informed by literature; methodological symbiosis; questionnaire reliability and validity; secondary data sources; public arrest record; public data; covariate operationalization; reactance constructs; content analysis; theme analysis; prior arrest; censored cases; QSR N6; SPSS; Excel; limitations; under-identification; attrition; population attrition; bimodal distribution; dichotomous variables; data splitting; discretizing data; time to recidivism; subsequent arrests; emotional change; emotion score; outliers; reactance antecedent; message dose; message dosage; treatment fidelity; assess treatment fidelity; predictor variables; controlling variables; demographic covariate; demographic predictor; confirmation bias; data bias; interaction effect; treatment effect; message design; fear appeal; message strength; anger; survival analysis; time dependence; mixed methods; study design; message standardization; internal validity; hard data; hard end-point data; marginal sample size; observed variables; intervening factors; intervening variables; sample size; in vivo; hierarchy of effects; emotional threat; older offenders; young offenders; intervention analysis; message-based approach; best practices; DWI intervention; DWI treatment; prior conditions; iconoclast; Drunks Against MADD Mothers; resistance; message design science

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Medina, U. E. (2010). MADD MESSAGE EFFECTS: A TWELVE-YEAR RANDOMIZED TRIAL. (Doctoral Dissertation). University of New Mexico. Retrieved from http://hdl.handle.net/1928/12395

Chicago Manual of Style (16^th Edition):

Medina, Una E. “MADD MESSAGE EFFECTS: A TWELVE-YEAR RANDOMIZED TRIAL.” 2010. Doctoral Dissertation, University of New Mexico. Accessed March 08, 2021. http://hdl.handle.net/1928/12395.

MLA Handbook (7^th Edition):

Medina, Una E. “MADD MESSAGE EFFECTS: A TWELVE-YEAR RANDOMIZED TRIAL.” 2010. Web. 08 Mar 2021.

Vancouver:

Medina UE. MADD MESSAGE EFFECTS: A TWELVE-YEAR RANDOMIZED TRIAL. [Internet] [Doctoral dissertation]. University of New Mexico; 2010. [cited 2021 Mar 08]. Available from: http://hdl.handle.net/1928/12395.

Council of Science Editors:

Medina UE. MADD MESSAGE EFFECTS: A TWELVE-YEAR RANDOMIZED TRIAL. [Doctoral Dissertation]. University of New Mexico; 2010. Available from: http://hdl.handle.net/1928/12395

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