http://handle.tamu.edu/1969.1/3365 http://handle.tamu.edu/1969.1/85755 The Effects of Age at Infection and Gender on the Pathogenesis of Theiler’s Virus Induced Disease – A Model of Human Multiple Sclerosis Propst, Matthew Stephen Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS) affecting 1 in 2000 of the US population. Susceptibility to MS is influenced by environmental, gender, genetic and pathogenic factors. For instance, there is a higher incidence of MS in women than men (2:1) and that there is a sudden onset of the disease between the ages of 15 and 50, suggesting that gender, age and puberty alter the susceptibility to the disease. The etiology of MS is not known, and although viral infection is suspected to be an initiating event. Theiler’s murine encephalomyelitis virus (TMEV) infection in SJL mice causes a biphasic disease in which the chronic phase causes an inflammatory demyelinating disease of the CNS which closely resembles MS. In the current study we utilize TMEV to investigate the influence of both age and gender on disease progression in this viral model of human multiple sclerosis. Here, we tested the hypothesis that age and gender significantly affect the pathogenesis of Theiler’s virus-induced disease in which we showed that males displayed worse symptoms than females at later ages of inoculation. http://handle.tamu.edu/1969.1/85752 Contemporary Russian Women Authors: Rejecting Definition in Literary Rebellion Muff, Rebecca A. Russia’s women have had a difficult time finding a voice in literature until as recently as the 1980s. With this new voice, many women writers have countered the widespread gender assumptions inherent in patriarchal Russian culture. This essay explores how four contemporary Russian women authors— Ludmilla Petrushevskaya, Nina Sadur, Tatyana Tolstaya, and Ludmila Ulitskaya—challenge binary gender stereotypes, particularly those concerning women. Each author has uniquely rejected a prescribed definition of ‘woman’ in her prose, and together the four authors form a literary rebellion against stereotypical notions of femininity. http://handle.tamu.edu/1969.1/85750 Interferon-Stimulated Genes in the Pregnant Mouse Uterus Tilford, Sarah During pregnancy in the mouse, extensive communication takes place between the conceptus (embryo/fetus and associated extraembryonic membranes) and uterus. Our focus centers on the uterine response to the conceptus. In ruminants, the conceptus produces interferon tau that induces interferon stimulated genes (ISGs) which likely regulate uterine receptivity, conceptus implantation, and conceptus growth and development. Our hypothesis is that ISGs are similarly induced in uterus during pregnancy in the mouse. If ISGs have a critical role in pregnancy establishment and maintenance in mammals, it is important to identify these ISGs in order to address fertility issues in human medicine. In this research, in situ hybridization analysis of uteri during gestation in the mouse was conducted to understand cell specific expression of selected ISGs during pregnancy. Of the fifteen ISGs investigated, ten (Irf1, Irf2, Irf6, Irf7, Isg15, Oas2, Plscr1, Stat1, Rsad2, Tlr4) were found to be expressed in the uterus during pregnancy. http://handle.tamu.edu/1969.1/85749 Effect of Amino Acid Subsititution in Set1 on Histone H3 Methylation and Gene Silencing in Saaccharomyces Cerevisiae Chateau, Morgan Chromosomal DNA in our cells is wrapped around a histone protein octomer like thread on a spool, forming a structure called a nucleosome. Series of nucleosomes form the nuclear chromosomes found in all eukaryotic organisms. Modifications to histone proteins can change how accessible chromosomal DNA is to protein complexes that act on DNA. DNA sequences that are inaccessible are called silent chromatin and regions that can’t be transcribed are subject to “gene silencing.” Proper gene silencing is necessary for normal cell development and regulation. Incorrect or missing histone modifications can cause the loss of gene silencing and uncontrolled gene expression similar to the situation in cells of patients with cancer or leukemia. My project focuses on a histone modifying complex COMPASS. COMPASS is composed of eight proteins, one of which is the histone H3 methyltransferase Set1. There are seven Set1 homologs in yeast and over 60 Set1-like proteins in humans, including MLL, which is known to be associated with human leukemia. Previous studies have shown that Set1 and most COMPASS proteins are essential for gene silencing at the ribosomal DNA locus (rDNA) in yeast. The SET domain is the active site of the Set1 histone methyltransferase, where methyl groups are covalently attached to the fourth lysine residue (K4) of histone H3. My goal is to investigate the effect of six individual amino acid substitutions in the SET domain of Set1; Y967A, I972A, Y993A, H1017L, Y967F, and G951A, on histone H3 methylation and gene silencing. These altered Set1 proteins are being expressed in the yeast Saccharomyces cerevisiae. Using Western blots and marker genes, the effect of these mutations are compared to wild type Set1. My data show that there are defects in histone H3 methylation in the amino acid substitution variants of Set1. In five of the mutants there is a complete loss of H3K4 methylation. In the future, we will determine if these altered Set1 proteins are assembled into the COMPASS complex. By characterizing the catalytic domain of Set1 using amino acid substitution variants, we will acquire a better understanding of the related proteins in humans.