Genetics and Genomics Commons^™

Rumen Fluid Metabolomics Analysis Associated With Feed Efficiency On Crossbred Steers, Virginia M. Artegoitia, Andrew P. Cassady, Ronald M. Lewis, Harvey C. Freetly

Department of Animal Science: Faculty Publications

The rumen has a central role in the efficiency of digestion in ruminants. To identify potential differences in rumen function that lead to differences in average daily gain (ADG), rumen fluid metabolomic analysis by LC-MS and multivariate/univariate statistical analysis were used to identify differences in rumen metabolites. Individual feed intake and body-weight was measured on 144 steers during 105 d on a high concentrate ration. Eight steers with the greatest ADG and 8 steers with the least-ADG with dry matter intake near the population average were selected. Blood and rumen fluid was collected from the 16 steers 26 d before …

Bcl11b And Combinatorial Resolution Of Cell Fate In The T-Cell Gene Regulatory Network., William J R Longabaugh, Weihua Zeng, Jingli A Zhang, Hiroyuki Hosokawa, Camden S Jansen, Long Li, Maile Romero-Wolf, Pentao Liu, Hao Yuan Kueh, Ali Mortazavi, Ellen V Rothenberg

Articles, Abstracts, and Reports

T-cell development from hematopoietic progenitors depends on multiple transcription factors, mobilized and modulated by intrathymic Notch signaling. Key aspects of T-cell specification network architecture have been illuminated through recent reports defining roles of transcription factors PU.1, GATA-3, and E2A, their interactions with Notch signaling, and roles of Runx1, TCF-1, and Hes1, providing bases for a comprehensively updated model of the T-cell specification gene regulatory network presented herein. However, the role of lineage commitment factor Bcl11b has been unclear. We use self-organizing maps on 63 RNA-seq datasets from normal and perturbed T-cell development to identify functional targets of Bcl11b during commitment …

Lichen Conservation In Eastern North America: Population Genomics, Climate Change, And Translocations, Jessica Allen

Dissertations, Theses, and Capstone Projects

Conservation biology is a scientific discipline that draws on methods from diverse fields to address specific conservation concerns and inform conservation actions. This field is overwhelmingly focused on charismatic animals and vascular plants, often ignoring other diverse and ecologically important groups. This trend is slowly changing in some ways; for example, increasing number of fungal species are being added to the IUCN Red-List. However, a strong taxonomic bias still exists. Here I contribute four research chapters to further the conservation of lichens, one group of frequently overlooked organisms. I address specific conservation concerns in eastern North America using modern methods. …

Naturally-Derived Molecular Ensembles In Medicine, Materials Science And Evolutionary Biology: An Interdisciplinary Study, Silvio Panettieri

Dissertations, Theses, and Capstone Projects

The first chapter will introduce the work carried out in collaboration with the Govind laboratory at CCNY. Our quest was set forth to investigate the intimate relationship lying between chronic inflammation and tumor development. For at least the last fifteen years much research has been conducted on this topic; yet, the level of complexity arising from exceedingly interwoven biochemical pathways in mammals has resulted in slow advancements in this field. This is why we resorted to a simple yet powerful immunogenetic model organism, the fruit fly Drosophila melanogaster, in combination with the administration of the most common anti-inflammatory drug, …

The Recycling Gtpase, Rab-10, Regulates Autophagy Flux In Caenorhabditis Elegans, Nicholas J. Palmisano

Dissertations, Theses, and Capstone Projects

Autophagy and endocytosis are two cellular pathways that are vital to cell growth and homeostasis. Autophagy is a dynamic and catabolic process involving the formation of a double-membrane vesicle called the autophagosome, which engulfs long-lived proteins and damaged organelles. Endocytosis involves the uptake of extracellular material into the cell through the formation of intracellular vesicles termed endosomes. Although both endocytosis and autophagy are interconnected processes, the extent to which endocytic proteins and/or compartments contribute to autophagy, and how these endocytic components do so, is still unknown. To improve our understanding of the connections that exist between autophagy and endocytosis, we …

Body Size Regulation Via Bmp Signaling In Caenorhabditis Elegans, Uday Madaan

Dissertations, Theses, and Capstone Projects

The body size of an organism can be a crucial determinant of access to nutrition, reproductive success and overall survival in the wild. However, how body size of an individual is determined is incompletely understood. Body size is a complex trait determined by multiple pathways and genes, making it difficult to understand the role of individual genes and pathways in determining overall size. In Caenorhabditis elegans, a homolog of Bone Morphogenetic Proteins (BMP) is a major regulator of body size; functional loss of DBL-1 leads to a small body size. Due to a drastic change in body size in dbl-1 …

Genetic Associations With Lipoprotein Subfraction Measures Differ By Ethnicity In The Multi-Ethnic Study Of Atherosclerosis (Mesa), Zhe Wang, Ani Manichukal, David C. Goff, Samia Mora, Jose M. Ordovas, Nicholas M. Pajewski, Wendy S. Post, Jerome I. Rotter, Michele M. Sale, Stephanie A. Santorico, David Siscovick, Michael Y. Tsai, Donna K. Arnett, Stephen Rich, Alexis C. Frazier-Wood

Epidemiology and Environmental Health Faculty Publications

A recent genome-wide association study associated 62 single nucleotide polymorphisms (SNPs) from 43 genomic loci, with fasting lipoprotein subfractions in European–Americans (EAs) at genome-wide levels of significance across three independent samples. Whether these associations are consistent across ethnicities with a non-European ancestry is unknown. We analyzed 15 lipoprotein subfraction measures, on 1677 African–Americans (AAs), 1450 Hispanic–Americans (HAs), and 775 Chinese–Americans (CHN) participating in the multi-ethnic study of atherosclerosis (MESA). Genome-wide data were obtained using the Affymetrix 6.0 and Illumina HumanOmni chips. Linear regression models between genetic variables and lipoprotein subfractions were adjusted for age, gender, body mass index, smoking, study …

Swainsonine Biosynthesis Genes In Diverse Symbiotic And Pathogenic Fungi, Daniel Cook, Bruno G. G. Donzelli, Rebecca Creamer, Deana L. Baucom, Dale R. Gardner, Juan Pan, Neil Moore, Stuart B. Krasnoff, Jerzy W. Jaromczyk, Christopher L. Schardl

Plant Pathology Faculty Publications

Swainsonine—a cytotoxic fungal alkaloid and a potential cancer therapy drug—is produced by the insect pathogen and plant symbiont Metarhizium robertsii, the clover pathogen Slafractonia leguminicola, locoweed symbionts belonging to Alternaria sect. Undifilum, and a recently discovered morning glory symbiont belonging to order Chaetothyriales. Genome sequence analyses revealed that these fungi share orthologous gene clusters, designated “SWN,” which included a multifunctional swnKgene comprising predicted adenylylation and acyltransferase domains with their associated thiolation domains, a β-ketoacyl synthase domain, and two reductase domains. The role of swnK was demonstrated by inactivating it in M. robertsii through homologous …

Zinc Transporters Ybtx And Znuabc Are Required For The Virulence Of Yersinia Pestis In Bubonic And Pneumonic Plague In Mice, Alexander G. Bobrov, Olga Kirillina, Marina Y. Fosso, Jacqueline D. Fetherston, M. Clarke Miller, Tiva T. Vancleave, Joseph A. Burlison, William K. Arnold, Matthew B. Lawrenz, Sylvie Garneau-Tsodikova, Robert D. Perry

Microbiology, Immunology, and Molecular Genetics Faculty Publications

A number of bacterial pathogens require the ZnuABC Zinc (Zn²⁺) transporter and/or a second Zn²⁺ transport system to overcome Zn²⁺ sequestration by mammalian hosts. Previously we have shown that in addition to ZnuABC, Yersinia pestis possesses a second Zn²⁺ transporter that involves components of the yersiniabactin (Ybt), siderophore-dependent iron transport system. Synthesis of the Ybt siderophore and YbtX, a member of the major facilitator superfamily, are both critical components of the second Zn²⁺ transport system. Here we demonstrate that a ybtX znu double mutant is essentially avirulent in mouse models of bubonic and pneumonic …

Diverse Expression Patterns And Tumorigenic Role Of Neurotensin Signaling Components In Colorectal Cancer Cells, Ji Tae Kim, Heidi L. Weiss, B. Mark Evers

Markey Cancer Center Faculty Publications

Colorectal cancer (CRC), which is one of the most common malignancies worldwide, results from an accumulation of genetic and epigenetic modifications including DNA methylation. Neurotensin (NTS), a hormone localized to the gut and central nervous system, mediates its physiological and pathological effects, including growth stimulation for a variety of cancers, through three distinct NTS receptors (NTSRs). Most NTS functions are mediated through the high-affinity receptor NTSR1, and expression of NTSR1 is increased in many cancers including CRC. In this study, we investigated the expression profiles and cellular functions of the NTSRs, especially NTSR1, in CRC cells. We showed that expression …

Examination Of The Monoamine Oxidase A Gene Promoter On Motivation To Exercise And Levels Of Voluntary Physical Activity, Erin M. Kinney

Senior Theses

Purpose: The purpose of this study was to examine the genetic basis underlying voluntary exercise. Monoamine oxidase A (MAO-A) is an enzyme that acts on monoamine neurotransmitters, such as dopamine, to cause inactivation. There are several polymorphisms in the promoter region of the MAO-A gene, and these variations change transcriptional activity and the amount of MAO-A produced, leading to alterations in available dopamine levels. Interestingly, polymorphisms in MAO-A have been associated recently with physical activity level. This study sought to determine whether there is an association between motivation to exercise, levels of voluntary physical activity, and MAO-A gene polymorphisms.

Methods: …

Noncanonical Alternative Polyadenylation Contributes To Gene Regulation In Response To Hypoxia, Laura De Lorenzo, Reed Sorenson, Julia Bailey-Serres, Arthur G. Hunt

Plant and Soil Sciences Faculty Publications

Stresses from various environmental challenges continually confront plants, and their responses are important for growth and survival. One molecular response to such challenges involves the alternative polyadenylation of mRNA. In plants, it is unclear how stress affects the production and fate of alternative mRNA isoforms. Using a genome-scale approach, we show that in Arabidopsis thaliana, hypoxia leads to increases in the number of mRNA isoforms with polyadenylated 3′ ends that map to 5′-untranslated regions (UTRs), introns, and protein-coding regions. RNAs with 3′ ends within protein-coding regions and introns were less stable than mRNAs that end at 3′-UTR poly(A) sites. …

The 'Pseudomonas Aeruginosa' Psl Polysaccharide Is A Social But Noncheatable Trait In Biofilms, Yasuhiko Irie, Aled E. Roberts, Kasper N. Kragh, Vernita D. Gordon, Jaime B. Hutchison, Rosalind J. Allen, Gavin Melaugh, Thomas Bjarnsholt, Stuart A. West, Stephen P. Diggle

Biology Faculty Publications

Extracellular polysaccharides are compounds secreted by microorganisms into the surrounding environment, and they are important for surface attachment and maintaining structural integrity within biofilms. The social nature of many extracellular polysaccharides remains unclear, and it has been suggested that they could function as either cooperative public goods or as traits that provide a competitive advantage. Here, we empirically tested the cooperative nature of the PSL polysaccharide, which is crucial for the formation of biofilms in Pseudomonas aeruginosa. We show that (i) PSL is not metabolically costly to produce; (ii) PSL provides populationlevel benefits in biofilms, for both growth and antibiotic …

Cancer Cell Redirection Biomarker Discovery Using A Mutual Information Approach, Kimberly Roche, F. Alex Feltus, Jang Pyo Park, Marie-May Coissieux, Chenyan Chang, Vera B.S. Chan, Mohamed Bentires-Alj, Brian W. Booth

Publications

Introducing tumor-derived cells into normal mammary stem cell niches at a sufficiently high ratio of normal to tumorous cells causes those tumor cells to undergo a change to normal mammary phenotype and yield normal mammary progeny. This phenomenon has been termed cancer cell redirection. We have developed an in vitro model that mimics in vivo redirection of cancer cells by the normal mammary microenvironment. Using the RNA profiling data from this cellular model, we examined high-level characteristics of the normal, redirected, and tumor transcriptomes and found the global expression profiles clearly distinguish the three expression states. To identify potential redirection …

A Comparison Of Nucleosome Organization In Drosophila Cell Lines, Rebecca L. Martin, John Maiorano, Greg J. Beitel, John F. Marko, Graham Mcvicker, Yvonne N. Fondufe-Mittendorf

Molecular and Cellular Biochemistry Faculty Publications

Changes in the distribution of nucleosomes along the genome influence chromatin structure and impact gene expression by modulating the accessibility of DNA to transcriptional machinery. However, the role of genome-wide nucleosome positioning in gene expression and in maintaining differentiated cell states remains poorly understood. Drosophila melanogastercell lines represent distinct tissue types and exhibit cell-type specific gene expression profiles. They thus could provide a useful tool for investigating cell-type specific nucleosome organization of an organism’s genome. To evaluate this possibility, we compared genome-wide nucleosome positioning and occupancy in five different Drosophila tissue-specific cell lines, and in reconstituted chromatin, and then …

The Santa Ana Speckled Dace (Rhinichthys Osculus): Phylogeography And Molecular Evolution Of The Mitochondrial Dna Control Region, James Jay Vanmeter

Electronic Theses, Projects, and Dissertations

The purpose of this genetic study of the Santa Ana Speckled Dace Rhinichthys osculus was three-fold. The first goal was to characterize the molecular structure of the mtDNA control region of R. osculus. An 1143 base-pair region of the mitochondrial DNA genome, which included the complete control region was sequenced for all individuals. Analysis of the sequence data revealed that the molecular structure of the speckled dace control region was similar to the molecular structure described for other vertebrate taxa. The speckled dace control region contains three major domains, which vary in base frequency as well as in the frequency …

Variation In Dna Methylation Is Not Consistently Reflected By Sociality In Hymenoptera, Karl M. Glastad, Samuel V. Arsenault, Kim L. Vertacnik, Scott M. Geib, Sasha Kay, Bryan N. Danforth, Sandra M. Rehan, Catherine R. Linnen, Sarah D. Kocher, Brendan G. Hunt

Biology Faculty Publications

Changes in gene regulation that underlie phenotypic evolution can be encoded directly in the DNA sequence or mediated by chromatin modifications such as DNA methylation. It has been hypothesized that the evolution of eusocial division of labor is associated with enhanced gene regulatory potential, which may include expansions in DNA methylation in the genomes of Hymenoptera (bees, ants, wasps, and sawflies). Recently, this hypothesis garnered support from analyses of a commonly used metric to estimate DNA methylation in silico, CpG content. Here, we test this hypothesis using direct, nucleotide-level measures of DNA methylation across nine species of Hymenoptera. In doing …

C/D-Box Snornas Form Methylating And Non-Methylating Ribonucleoprotein Complexes: Old Dogs Show New Tricks, Marina Falaleeva, Justin R. Welden, Marilyn J. Duncan, Stefan Stamm

Molecular and Cellular Biochemistry Faculty Publications

C/D box snoRNAs (SNORDs) are an abundantly expressed class of short, non‐coding RNAs that have been long known to perform 2′‐O‐methylation of rRNAs. However, approximately half of human SNORDs have no predictable rRNA targets, and numerous SNORDs have been associated with diseases that show no defects in rRNAs, among them Prader‐Willi syndrome, Duplication 15q syndrome and cancer. This apparent discrepancy has been addressed by recent studies showing that SNORDs can act to regulate pre‐mRNA alternative splicing, mRNA abundance, activate enzymes, and be processed into shorter ncRNAs resembling miRNAs and piRNAs. Furthermore, recent biochemical studies have shown that a given SNORD …

Genome- And Cd4+ T-Cell Methylome-Wide Association Study Of Circulating Trimethylamine-N-Oxide In The Genetics Of Lipid Lowering Drugs And Diet Network (Goldn), Stella Aslibekyan, Marguerite R. Irvin, Bertha A. Hidalgo, Rodney T. Perry, Elias J. Jeyarajah, Erwin Garcia, Irina Shalaurova, Paul N. Hopkins, Michael A. Province, Hemant K. Tiwari, Jose M. Ordovas, Devin M. Absher, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Trimethylamine-N-oxide (TMAO), an atherogenic metabolite species, has emerged as a possible new risk factor for cardiovascular disease. Animal studies have shown that circulating TMAO levels are regulated by genetic and environmental factors. However, large-scale human studies have failed to replicate the observed genetic associations, and epigenetic factors such as DNA methylation have never been examined in relation to TMAO levels.

Methods and results: We used data from the family-based Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) to investigate the heritable determinants of plasma TMAO in humans. TMAO was not associated with other plasma markers of cardiovascular disease, …

Modulation Of Bax And Mtor For Cancer Therapeutics., Rui Li, Chunyong Ding, Jun Zhang, Maohua Xie, Dongkyoo Park, Ye Ding, Guo Chen, Guojing Zhang, Melissa Gilbert-Ross, Wei Zhou, Adam I Marcus, Shi-Yong Sun, Zhuo G Chen, Gabriel L Sica, Suresh S Ramalingam, Andrew T Magis, Haian Fu, Fadlo R Khuri, Walter J Curran, Taofeek K Owonikoko, Dong M Shin, Jia Zhou, Xingming Deng

Articles, Abstracts, and Reports

A rationale exists for pharmacologic manipulation of the serine (S)184 phosphorylation site of the proapoptotic Bcl2 family member Bax as an anticancer strategy. Here, we report the refinement of the Bax agonist SMBA1 to generate CYD-2-11, which has characteristics of a suitable clinical lead compound. CYD-2-11 targeted the structural pocket proximal to S184 in the C-terminal region of Bax, directly activating its proapoptotic activity by inducing a conformational change enabling formation of Bax homooligomers in mitochondrial membranes. In murine models of small-cell and non-small cell lung cancers, including patient-derived xenograft and the genetically engineered mutant KRAS-driven lung cancer models, CYD-2-11 …