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Identifying the Cytotoxic Effects of Mycobacteriophage Genes
A bacteriophage is a virus that infects and reproduces in bacteria. During productive infections—those that result in construction and release of infectious phage particles—key host cell metabolic processes are modified by the infecting phage and redirected toward making new phage particles. Protein-protein interactions are likely involved in this process. In this work, gene 80 of mycobacteriophage Vix, a gene cytotoxic to host strain Mycobacterium smegmatis, was studied. Our hypothesis was that an interaction between the Vix80 gene product and a host cell protein caused growth inhibition. Comparative analysis of the Vix80 protein sequence shows a conserved domain of unknown function 2786 (DUF2786) near the N-terminus. The Vix80 gene was dissected, and the N-terminal 66 residues, encompassing the entire DUF2786 domain, was found to be cytotoxic to M. smegmatis. DUF2786 was found to be homologous to a region of three M. smegmatis ORFs, two of which are related by alternate initiation points of the same sequence. Using in vitro protein pull-down and in vivo two-hybrid analyses, efforts are underway to look for possible interactions of Vix80 with itself and the three host proteins. As part of this process, different constructs of the Vix80 protein were expressed in Escherichia coli. We have determined that certain Vix80 constructs are also lethal to the E.coli host cell, while others permit growth, suggesting a conservation of cytotoxic function. Identifying the relevant phage and host gene products and understanding how phage exploit their host’s weaknesses could lead to new therapeutic options for many bacterial illnesses
How (Not?) to Make Diaminoacenaphthylene for Use in Preparing Carbonyl-Substituted Photochromes
The main goal of the Gillmore research group is to prepare derivatives of perimidinespirohexadienone (PSHD) photochromes to “gate” photoinduced charge transfer (PICT). Photochromes are molecules that can isomerize from their short wavelength form (SW) to their long wavelength form (LW) in the presence of ultraviolet light. PSHDs revert from LW to SW thermally. To act as photochromic photooxidants, effectively “gating” PICT, LW must be much more reducible than SW. Based on computationally predicted reduction potentials, carbonyl-substituted PSHDs are promising synthetic targets for achieving this goal. Previous experimental results show that it is not possible to add carbonyls to the photochrome bottom before coupling. Thus, it will be necessary to prepare an acenaphthylene-bottomed PSHD. This requires the synthesis of diaminoacenaphthylene. This seemingly simple molecule has proved very difficult to make. After ruling out the most straightforward syntheses and the use of protecting groups, we now detail our many failed synthetic attempts and some newly proposed synthetic routes we are currently investigating. This work was supported by the National Science Foundation under Career Grant CHE-0952768
Investigation of the Substrate Specificity of Farnesyltransferase and Geranylgeranyltransferase-I
The prenyltransferases farneysltransferase (FTase) and geranylgernayltransferase-I (GGTase-I) transfer 15-carbon and 20-carbon lipid groups, respectively, to a cysteine near the C-terminus of substrate proteins, targeting them to cellular membranes. Substrates of FTase and GGTase-I are involved in many cellular pathways, and inhibitors of the prenyltransferases are being investigated to treat diseases like cancer, parasitic infection, and progeria. In general, FTase and GGTase-I are thought to recognize a CaaX motif on substrate proteins. The CaaX motif is a cysteine residue followed by two “a” groups which are nonpolar amino acids and the “X” residue was thought to determine which enzyme recognizes it. Recent studies indicate that this model should be expanded. Therefore, I am studying the substrate specificity of the prenyltransferases FTase and GGTase-I using an in vitro peptide-based fluorescent assay. I have prepared 96-well plates with enzyme and various concentrations of substrate and measured the steady state kinetics as a function of time to refine sequence specificity of FTase and GGTase-I. This work will allow us to better predict prenyltransferase substrates in vivo and to better understand the modes of efficacy of prenyltranferase inhibitors
The Effect of Directing Groups and Various Substituents on Rhodium-Catalyzed Decarbonylation
The activation of carbon-carbon single bonds is difficult due to their nonpolar nature and kinetic stability. The ability to functionalize these bonds can lead to new methodologies valuable in synthetic pathways. Recently, a new method for decarbonylation of aryl ketones via rhodium catalysis has been developed. This study examines the carbon-carbon bond activation of compounds using nitrogen-directing groups. A palladium catalyzed carbon-carbon coupling reaction was utilized and improved upon for the purpose of creating a variety of starting materials. These species are being used to explore the mechanism of the rhodium-catalyzed decarbonylation reaction
Facebook: Friend or Foe for Self-Esteem and Happiness?
The purpose of this study is to explore Facebook’s role in social comparison, including the relationship between social media behavior and self-esteem, and the interaction of social media behavior and self-esteem in individualistic and collectivistic cultures. In a world that puts a high emphasis on connecting through Facebook, it is important to understand the role the site plays on one’s self-esteem and social comparison. We hypothesized that Facebook behaviors would be significantly related to Self Esteem and Happiness. We also hypothesized that students from individualistic cultures (USA) would rank lower on Self Esteem and Happiness than university students from collectivistic cultures (Morocco & Other). Internet surveys were administered in English to 90 USA university students, and 29 Moroccan university students. Regardless of culture, students are using Facebook to communicate, compare and connect with one other. The results indicate that students with high SE engage in more PSC and disapprove of NSC. Students with high SE are less like to worry about how others perceive them on Facebook and genuinely portray themselves on Facebook. These findings have important implications for understanding the impact of Facebook on the wellbeing of young adults. By observing the relationship between happiness, self-esteem, and Facebook, we can better understand the implications Facebook has on student’s views of themselves, their peers, and their overall happiness
Effective Childrearing of Young School-Aged Children: Evidence from College Enrolled Mothers
A large amount of research relates a mother’s education and child academic achievement, but little has focused on the timing of a mother’s college enrollment. Previous research (Estelle 2011) finds significant gains in children’s reading scores when a mother is enrolled in college during the child’s kindergarten year. The cause of those gains are unknown. This collaborative economic research project focuses on father involvement to determine if the presence of a father figure in the household affects child academic achievement. If so, and if father involvement also increases during a mother’s enrollment, we would consider fathers to be an important mechanism of the maternal enrollment benefit for children
Women\u27s Philanthropy: Why Knowing General Trends Is Not Enough
Although women have engaged in philanthropy for centuries, their personal contributions have often been masked because their donations were given in their husbands\u27 names. I argue that to fully understand a person’s actions, it is important to know the historical context in which they performed such actions because each historical time period has its own set of characteristics and challenges. By looking at the individual stories of women philanthropists, we can learn more about these women than from general trends. To support this claim, I looked at four general trends I saw expressed in women’s philanthropy: Influences from religion and education, the time in their lives when women donated, and the effects of societal gender norms on their philanthropy. I also used the life story of Mrs. Margaret Sage, a philanthropist during the Gilded Age who exemplified all four of these trends, as a basis for comparison against individual stories. Using archival resources located at the Joint Archives of Holland, I researched two women philanthropists, Mrs. Martha Kollen and Mrs. Elsa Prince, both local philanthropists born and raised in Holland, Michigan. In addition to seeing the extent to which these individual stories varied from general trends, I also examined the role culture plays in women’s philanthropy. Research by Stephen Post, a scholar of American ethics, has found that much of twentieth-century philanthropy was “disinterested benevolence.” This kind of benevolence was used to express one’s faith in the form of Christian love. Using these two local women, I looked to see if being from Holland, a city with a distinct Christian culture, resulted in philanthropy such as the one mentioned above. I found it does to an extent; therefore, culture is also important to keep in mind when thinking about women’s philanthropy, as leaving it out can prevent one from seeing the whole story
Visualizing Piers Plowman
The complex narrative structure of Piers Plowman, a fourteenth-century, visionary poem attributed to William Langland and surviving in three versions, provides a struggle for both students approaching the poem for the first time and scholars who have been studying the poem for years. Often the poem is divided into passus, meaning steps, and sometimes split into two sections, the Visio and the Vita. These divisions are based on manuscript markings, but scholars disagree about their validity. Another way to break apart the poem, one that doesn’t rely on manuscript markings that may or may not be a result of scribal corruption, is into the dreams and dreams within dreams of the narrator. A further complication of working with the poem is that the narrative itself is discontinuous and defies attempts to summarize it. The goal of my project was to examine shapes scholars have used to define the narrative structure of Piers Plowman in order to come up with a way to visualize the poem without denying its complexity. I worked with a future project in mind of the creation of a digital tool to help students and scholars alike explore the poem
Changing Methods, Changing Libraries: Making Digital Literacy Accessible for Undergraduate Researchers
This project was supported by The Andrew W. Mellon Foundation Scholars Program in the Arts & Humanities at Hope College
Revolution in Tunisia: A Historical Analysis of the Uprisings that Began the Arab Spring
Tunisia was the first country to have a revolution in the Arab Spring of 2010. The history of Tunisia serves to explain how and why the uprisings came about. Tunisia, as it has developed through the 20th and 21st centuries, was and is engaged in a struggle between the traditional and the modern. This is clear in the various contributing factors that led to the revolution. Those factors include a restrictive, authoritarian, and corrupt government, an educated populace, the desire of the Tunisian people to choose their own government, and poor economic conditions. Religion also played a role in the revolution. After Tunisia gained its independence in 1956, its leaders Habib Bourguiba and Zine El Abidine Ben Ali set out to secularize Tunisia. Religion essentially became excluded from the public sphere. Many Tunisians in 2010 called for the revival of Islam in the public domain. The Islam they called for in their government, though, was not a radical and oppressive Islam, but a pluralistic and accepting one. Tunisians rose up against their government in 2010 because of the varied tensions that had developed over the years between the interior and coastal regions, the modern and the traditional, the secular and the religious, and the wealthy and the poor