Matching Items (90)
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A coincidence reporter construct, consisting of the p21-promoter and two luciferase genes (Firefly and Renilla), was constructed for the screening of drugs that might inhibit Olig2's tumorigenic role in glioblastoma. The reporter construct was tested using an Olig2 inhibitor, HSP990, as well as short hairpin RNA targeting Olig2. Further confirmatory

A coincidence reporter construct, consisting of the p21-promoter and two luciferase genes (Firefly and Renilla), was constructed for the screening of drugs that might inhibit Olig2's tumorigenic role in glioblastoma. The reporter construct was tested using an Olig2 inhibitor, HSP990, as well as short hairpin RNA targeting Olig2. Further confirmatory analysis is needed before the reporter cell line is ready for high-throughput screening at the NIH and lead compound selection.
ContributorsCusimano, Joseph Michael (Author) / LaBaer, Joshua (Thesis director) / Mangone, Marco (Committee member) / Mehta, Shwetal (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
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Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths in females worldwide, accounting for 23% of all new cancer cases and 14% of all total cancer deaths in 2008. Five tumor-normal pairs of primary breast epithelial cells were treated for infinite proliferation by

Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer deaths in females worldwide, accounting for 23% of all new cancer cases and 14% of all total cancer deaths in 2008. Five tumor-normal pairs of primary breast epithelial cells were treated for infinite proliferation by using a ROCK inhibitor and mouse feeder cells. Methods: Raw paired-end, 100x coverage RNA-Seq data was aligned to the Human Reference Genome Version 19 using BWA and Tophat. Gene differential expression analysis was completed using Cufflinks and Cuffdiff. Interactive Genome Viewer was used for data visualization. Results: 15 genes were found to be down-regulated by at least one log-fold change in 4/5 of tumor samples. 75 genes were found to be down-regulated in 3/5 of our tumor samples by at least one log-fold change. 11 genes were found to be up-regulated in 4/5 of our tumor samples, and 68 genes were identified to be up-regulated in 3/5 of the tumor samples by at least one-fold change. Conclusion: Expression changes in genes such as AZGP1, AGER, ALG11, and S1007 suggest a disruption in the glycosylation pathway. No correlation was found between Cufflink's Her2 gene-expression and DAKO score classification.
ContributorsHernandez, Fernando (Author) / Anderson, Karen (Thesis director) / Mangone, Marco (Committee member) / Park, Jin (Committee member) / Barrett, The Honors College (Contributor) / Department of Information Systems (Contributor)
Created2013-05
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Description
miRNAs are short non-coding regulatory RNAs that have an important roles in a wide range of biological processes. Dysfunction of miRNA regulation has also been shown to occur in diseases such as cancer. Despite the widespread influence of miRNAs in these contexts, the vast majority of miRNA targets are poorly

miRNAs are short non-coding regulatory RNAs that have an important roles in a wide range of biological processes. Dysfunction of miRNA regulation has also been shown to occur in diseases such as cancer. Despite the widespread influence of miRNAs in these contexts, the vast majority of miRNA targets are poorly characterized. The aim of this research project was to gain a better understating of miRNA targeting by using the model organism C. elegans. In order to do this I adapted a novel high-throughput assay to detect miRNA targets for use with the C. elegans 3`UTRome. As a proof of principle I performed this assay on 96 C. elegans 3`UTRs using high-throughput techniques. The results revealed miRNA interactions with two predicted 3`UTR targets for the miRNA lin-4 and ten unpredicted targets. The results also corroborated previous findings that certain worm miRNAs require special modifications to be expressed in human cells.
ContributorsKotagama, Kasuen Indrajith Bandara (Author) / Mangone, Marco (Thesis director) / Anderson, Karen (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2013-12
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Description
Alternative polyadenylation (APA) is the biological mechanism in which the same gene can have multiple 3'untranslated region (3'UTR) isoforms due to the presence of multiple polyadenylation signal (PAS) elements within the pre mRNAs. Because APA produces mRNA transcripts that have different 3'UTR isoforms, certain transcripts may be subject to post-transcriptional

Alternative polyadenylation (APA) is the biological mechanism in which the same gene can have multiple 3'untranslated region (3'UTR) isoforms due to the presence of multiple polyadenylation signal (PAS) elements within the pre mRNAs. Because APA produces mRNA transcripts that have different 3'UTR isoforms, certain transcripts may be subject to post-transcriptional regulation by regulatory non-coding RNAs, such as microRNAs or RNA binding proteins defects of which have been implicated in diseases such as cancer. Despite the increasing level of information, functional understanding of the molecular mechanisms involved in transcription is still poorly understood, nor is it clear why APA is necessary at a cell or tissue-specific level. To address these questions I wanted to develop a set of sensor strain plasmids capable of detecting cleavage and polyadenylation in vivo, inject the complete sensor strain plasmid into C. elegans and prepare stable transgenic lines, and perform proof-of-principle RNAi feeding experiments targeting genes associated with the cleavage and polyadenylation complex machinery. I demonstrated that it was possible to create a plasmid capable of detecting cleavage and polyadenylation in C. elegans; however, issues arose during the RNAi assays indicating the sensor strain plasmid was not sensitive enough to the RNAi to effectively detect in the worms. Once the problems involved with sensitivity and variability in the RNAi effects are resolved, the plasmid would be able to better address questions regarding the functional understanding of molecular mechanisms involved in transcription termination.
ContributorsWilky, Henry Patrick (Author) / Mangone, Marco (Thesis director) / Newbern, Jason (Committee member) / Blazie, Stephen (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
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Description

Engineered pavements cover a large fraction of cities and offer significant potential for urban heat island mitigation. Though rapidly increasing research efforts have been devoted to the study of pavement materials, thermal interactions between buildings and the ambient environment are mostly neglected. In this study, numerical models featuring a realistic

Engineered pavements cover a large fraction of cities and offer significant potential for urban heat island mitigation. Though rapidly increasing research efforts have been devoted to the study of pavement materials, thermal interactions between buildings and the ambient environment are mostly neglected. In this study, numerical models featuring a realistic representation of building-environment thermal interactions, were applied to quantify the effect of pavements on the urban thermal environment at multiple scales. It was found that performance of pavements inside the canyon was largely determined by the canyon geometry. In a high-density residential area, modifying pavements had insignificant effect on the wall temperature and building energy consumption. At a regional scale, various pavement types were also found to have a limited cooling effect on land surface temperature and 2-m air temperature for metropolitan Phoenix. In the context of global climate change, the effect of pavement was evaluated in terms of the equivalent CO2 emission. Equivalent CO2 emission offset by reflective pavements in urban canyons was only about 13.9e46.6% of that without building canopies, depending on the canyon geometry. This study revealed the importance of building-environment thermal interactions in determining thermal conditions inside the urban canopy.

ContributorsYang, Jiachuan (Author) / Wang, Zhi-Hua (Author) / Kaloush, Kamil (Author) / Dylla, Heather (Author)
Created2016-08-22
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Description
A study was conducted to assess the effects of generational status on various measures of stigmatization, acculturative stress, and perceived social and interpersonal threat within the Mexican heritage population in the Southwest. The role of the fear of stigma by association, regardless of actual experiences of stigmatization, was investigated, including

A study was conducted to assess the effects of generational status on various measures of stigmatization, acculturative stress, and perceived social and interpersonal threat within the Mexican heritage population in the Southwest. The role of the fear of stigma by association, regardless of actual experiences of stigmatization, was investigated, including its relationships with acculturative stress, perceived threat, and social distancing. Exploratory analyses indicated that first generation Mexican Americans differed significantly from second generation Mexican Americans on the perception of Mexican nationals as ingroup members, the fear of stigma by association by Americans, and levels of acculturative stress. Additional analyses indicated that Mexican Americans with one parent born in Mexico and one in the United States held opinions and attitudes most similar to second generation Mexican Americans. Results from path analyses indicated that first-generation Mexican Americans were more likely than second-generation Mexican Americans to both see Mexican nationals as ingroup members and to be afraid of being stigmatized for their perceived association with them. Further, seeing Mexican nationals as in-group members resulted in less social distancing and lower perceived threat, but fear of stigma by association lead to greater perceived threat and greater acculturative stress. Implications for within- and between-group relations and research on stigma by association are discussed.
ContributorsBoyd, Brenna Margaret (Author) / Knight, George P (Thesis advisor) / Kwan, Sau (Committee member) / Neuberg, Steven (Committee member) / Arizona State University (Publisher)
Created2010
Description
In eukaryotes, most messenger RNA precursors (pre-mRNA) undergo extensive processing, leading to the cleavage of the transcript followed by the addition of a poly(A) tail. This process is executed by a large complex known as the Cleavage and Polyadenylation Complex (CPC). Its central subcomplex, the Cleavage and Polyadenylation Specificity Factor

In eukaryotes, most messenger RNA precursors (pre-mRNA) undergo extensive processing, leading to the cleavage of the transcript followed by the addition of a poly(A) tail. This process is executed by a large complex known as the Cleavage and Polyadenylation Complex (CPC). Its central subcomplex, the Cleavage and Polyadenylation Specificity Factor (CPSF) complex is responsible for recognizing a short hexameric element AAUAAA located at the 3’end in the nascent mRNA molecule and catalyzing the pre-mRNA cleavage. In the round nematode C. elegans, the cleavage reaction is executed by a subunit of this complex named CPSF3, a highly conserved RNA endonuclease. While the crystal structure of its human ortholog CPSF73 has been recently identified, we still do not understand the molecular mechanisms and sequence specificity used by this protein to induce cleavage, which in turn would help to understand how this process is executed in detail. Additionally, we do not understand in additional factors are needed for this process. In order to address these issues, we performed a comparative analysis of the CPSF3 protein in higher eukaryotes to identify conserved functional domains. The overall percent identities for members of the CPSF complex range from 33.68% to 56.49%, suggesting that the human and C. elegans orthologs retain a high level of conservation. CPSF73 is the protein with the overall highest percent identity of the CPSF complex, with its active site-containing domain possessing 74.60% identity with CPSF3. Additionally, we gathered and expressed using a bacterial expression system CPSF3 and a mutant, which is unable to perform the cleavage reaction, and developed an in vitro cleavage assay to test whether CPSF3 activity is necessary and sufficient to induce nascent mRNA cleavage. This project establishes tools to better understand how CPSF3 functions within the CPC and sheds light on the biology surrounding the transcription process as a whole.
ContributorsGallante, Christina (Author) / Mangone, Marco (Thesis director) / Sharma, Shalini (Committee member) / Hrach, Heather (Committee member) / School of Life Sciences (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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The successful reduction of CO2 and protons by a light-induced cobalt porphyrin/cytb562 hybrid metalloenzyme in water is reported. Incorporation of the porphyrin into a protein scaffold results in increases in CO and H2 production over naked porphyrin. Rational point mutations to the CoPPIX binding site of cytb562 modulate production,

The successful reduction of CO2 and protons by a light-induced cobalt porphyrin/cytb562 hybrid metalloenzyme in water is reported. Incorporation of the porphyrin into a protein scaffold results in increases in CO and H2 production over naked porphyrin. Rational point mutations to the CoPPIX binding site of cytb562 modulate production, indicating possible further improvements in catalytic activity.
ContributorsGwerder, Noah D (Author) / Ghirlanda, Giovanna (Thesis director) / Williams, Peter (Committee member) / Mangone, Marco (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
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People generally struggle with making good decisions for their well-being (Hershfield, 2019; Hershfield & Bartels, 2018). One reason for this might be that people struggle with connecting to their future selves. Prior research suggests that future self-connectedness predicts better decisions. This study examined if feeling more positive or negative helps

People generally struggle with making good decisions for their well-being (Hershfield, 2019; Hershfield & Bartels, 2018). One reason for this might be that people struggle with connecting to their future selves. Prior research suggests that future self-connectedness predicts better decisions. This study examined if feeling more positive or negative helps people connect more to their future self and if this, in turn, helps people make better decisions. Participants read a scenario in which they are presented with two decisions, one having a short-term benefit/long-term cost and the other having a short-term cost/long-term benefit. Either neutral affect framing, positive affect framing, or negative affect framing was emphasized in the scenario depending on the condition. Our study did not find that positive affect framing and negative affect framing enhanced future self-connectedness. Neither did we find that positive affect framing and negative affect framing influenced decision-making.

ContributorsDe La Torre, Annabel (Author) / Shiota, Michelle N. (Thesis director) / Corbin, William (Committee member) / Kwan, Sau (Committee member) / Pages, Erika (Committee member) / Department of Psychology (Contributor) / School of International Letters and Cultures (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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The Beck Depression Inventory II (BDI-II) and the Patient Health Questionnaire 9 (PHQ-9) are highly valid depressive testing tools used to measure the symptom profile of depression globally and in South Asia, respectively (Steer et al., 1998; Kroenke et al, 2001). Even though the South Asian population comprises only 23%

The Beck Depression Inventory II (BDI-II) and the Patient Health Questionnaire 9 (PHQ-9) are highly valid depressive testing tools used to measure the symptom profile of depression globally and in South Asia, respectively (Steer et al., 1998; Kroenke et al, 2001). Even though the South Asian population comprises only 23% of the world’s population, it represents one-fifth of the world’s mental health disorders (Ogbo et al., 2018). Although this population is highly affected by mental disorders, there is a lack of culturally relevant research on specific subsections of the South Asian population.

As such, the goal of this study is to investigate the differences in the symptom profile of depression in native and immigrant South Asian populations. We investigated the role of collective self-esteem and perceived discrimination on mental health.
For the purpose of this study, participants were asked a series of questions about their depressive symptoms, self-esteem and perceived discrimination using various depressive screening measures, a self-esteem scale, and a perceived discrimination scale.

We found that immigrants demonstrated higher depressive symptoms than Native South Asians as immigration was viewed as a stressor. First-generation and second-generation South Asian immigrants identified equally with somatic and psychological symptoms. These symptoms were positively correlated with perceived discrimination, and collective self-esteem was shown to increase the likelihood of these symptoms.

This being said, the results from this study may be generalized only to South Asian immigrants who come from highly educated and high-income households. Since seeking professional help and being aware of one’s mental health is vital for wellbeing, the results from this study may spark the interest in an open communication about mental health within the South Asian immigrant community as well as aid in the restructuring of a highly reliable and valid measurement to be specific to a culture.

ContributorsSwaminathan, Manasa (Co-author) / Murthy, Nithara (Co-author) / Vogel, Joanne (Thesis director) / Kwan, Sau (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05