Genetics and Genomics Commons^™

Transcriptome Analysis Of Listeria Monocytogenes Exposed To Biocide Stress Reveals A Multi-System Response Involving Cell Wall Synthesis, Sugar Uptake, And Motility, Aidan Casey, Edward M. Fox, Stephan Schmitz-Esser, Aidan Coffey, Olivia Mcauliffe, Kieran Jordan

Department of Biological Sciences Publications

Listeria monocytogenes is a virulent food-borne pathogen most often associated with the consumption of “ready-to-eat” foods. The organism is a common contaminant of food processing plants where it may persist for extended periods of time. A commonly used approach for the control of Listeria monocytogenes in the processing environment is the application of biocides such as quaternary ammonium compounds. In this study, the transcriptomic response of a persistent strain of L. monocytogenes (strain 6179) on exposure to a sub-lethal concentration of the quaternary ammonium compound benzethonium chloride (BZT) was assessed. Using RNA-Seq, gene expression levels were quantified by sequencing …

The Experience Of Having Primary Caregiving Responsibilities For An Adult Sibling With Down Syndrome, Patricia Sciscione

Seton Hall University Dissertations and Theses (ETDs)

Abstract

Background: The current generation of adults with Down syndrome is living longer and is likely to outlive their parents. Siblings have been identified as the likely future caregivers for adults with Down syndrome, yet little is known about what the experience is like for those who are currently caring for their siblings. It is necessary to gain an understanding of what the service needs are for this population in order to assist sibling caregivers.

Objectives: To explore and describe the experience of being an adult who is partially or fully involved with primary caregiving responsibilities for a sibling with …

Quantitative Field Testing Heterodera Glycines From Metagenomic Dna Samples Isolated Directly From Soil Under Agronomic Production., Yan Li, Gary W. Lawrence, Shien Lu, Clarissa Balbalian, Vincent P. Klink

CALS Publications

A quantitative PCR procedure targeting the Heterodera glycines ortholog of the Caenorhabditis elegans uncoordinated-78 gene was developed. The procedure estimated the quantity of H. glycines from metagenomic DNA samples isolated directly from field soil under agronomic production. The estimation of H. glycines quantity was determined in soil samples having other soil dwelling plant parasitic nematodes including Hoplolaimus, predatory nematodes including Mononchus, free-living nematodes and biomass. The methodology provides a framework for molecular diagnostics of nematodes from metagenomic DNA isolated directly from field soil.

Genome-Wide Methylation Analyses In Glioblastoma Multiforme, Rose K. Lai, Yanwen Chen, Xiaowei Guan, Darryl Nousome, Charu Sharma, Peter Canoll, Jeffrey Bruce, Andrew E. Sloan, Etty Cortes, Jean-Paul Vonsattel, Tao Su, Lissette Delgado-Cruzata, Irina Gurvich, Regina M. Santella, Quinn Ostrom, Annette Lee, Peter Gregersen, Jill Barnholtz-Sloan

Publications and Research

Few studies had investigated genome-wide methylation in glioblastoma multiforme (GBM). Our goals were to study differential methylation across the genome in gene promoters using an array-based method, as well as repetitive elements using surrogate global methylation markers. The discovery sample set for this study consisted of 54 GBM from Columbia University and Case Western Reserve University, and 24 brain controls from the New York Brain Bank. We assembled a validation dataset using methylation data of 162 TCGA GBM and 140 brain controls from dbGAP. HumanMethylation27 Analysis Bead-Chips (Illumina) were used to interrogate 26,486 informative CpG sites in both the discovery …

Gene And Protein Sequence Optimization For High-Level Production Of Fully Active And Aglycosylated Lysostaphin In Pichia Pastoris, Hongliang Zhao, Kristina Blazanovic, Yoonjoo Choi, Chris Bailey-Kellogg, Karl E. Griswold

Dartmouth Scholarship

Lysostaphin represents a promising therapeutic agent for the treatment of staphylococcal infections, in particular those of methicillin-resistant Staphylococcus aureus (MRSA). However, conventional expression systems for the enzyme suffer from various limitations, and there remains a need for an efficient and cost-effective production process to facilitate clinical translation and the development of nonmedical applications. While Pichia pastoris is widely used for high-level production of recombinant proteins, there are two major barriers to the production of lysostaphin in this industrially relevant host: lack of expression from the wild-type lysostaphin gene and aberrant glycosylation of the wild-type protein sequence. The first barrier can …

B Cell Tolerance In Health And Disease, Murali Gururajan, Vishal J. Sindhava, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B lymphocyte receptors are generated randomly during the bone marrow developmental phase of B cells. Hence, the B cell repertoire consists of both self and foreign antigen specificities necessitating specific tolerance mechanisms to eliminate self-reactive B cells. This review summarizes the major mechanisms of B cell tolerance, which include clonal deletion, anergy and receptor editing. In the bone marrow presentation of antigen in membrane bound form is more effective than soluble form and the role of dendritic cells in this process is discussed. Toll like receptor derived signals affect activation of B cells by certain ligands such as nucleic acids …

Direct-To-Consumer Genetic Testing In The College Classroom: Knowledge, Attitudes, And Concerns Of Introductory Biology Students, Nicanor Austriaco

Biology Faculty Publications

Pioneered by companies like 23andMe.com, deCODEme.com, and Navigenics.com, direct-to-consumer genetic testing refers to genetic tests that are marketed directly to consumers via television, print media, or the Internet. This kind of testing provides access to a customer’s genetic information without necessarily involving either a medical health care professional or a genetic counselor in the process. In recent years, a course offered to medical and graduate students at Stanford University has included an option for students to undergo personal genotyping, raising the possibility that direct-to-consumer genetic testing could also be incorporated into undergraduate biology courses to enhance student learning. In this …

Epicatechin Stimulates Mitochondrial Activity And Selectively Sensitizes Cancer Cells To Radiation, Hosam A. Elbaz, Icksoo Lee, Deborah A. Antwih, Jenney Liu, Maik Hüttemann, Steven P. Zielske

Center for Molecular Medicine and Genetics

Radiotherapy is the treatment of choice for solid tumors including pancreatic cancer, but the effectiveness of treatment is limited by radiation resistance. Resistance to chemotherapy or radiotherapy is associated with reduced mitochondrial respiration and drugs that stimulate mitochondrial respiration may decrease radiation resistance. The objectives of this study were to evaluate the potential of (-)-epicatechin to stimulate mitochondrial respiration in cancer cells and to selectively sensitize cancer cells to radiation. We investigated the natural compound (-)-epicatechin for effects on mitochondrial respiration and radiation resistance of pancreatic and glioblastoma cancer cells using a Clark type oxygen electrode, clonogenic survival assays, and …

Copy Number Variation In Chickens: A Review And Future Prospects, Xiaofei Wang, Shannon Byers

Biology Faculty Research

DNA sequence variations include nucleotide substitution, deletion, insertion, translocation and inversion. Deletion or insertion of a large DNA segment in the genome, referred to as copy number variation (CNV), has caught the attention of many researchers recently. It is believed that CNVs contribute significantly to genome variability, and thus contribute to phenotypic variability. In chickens, genome-wide surveys with array comparative genome hybridization (aCGH), SNP chip detection or whole genome sequencing have revealed a large number of CNVs. A large portion of chicken CNVs involves protein coding or regulatory sequences. A few CNVs have been demonstrated to be the determinant factors …

A Broadly Implementable Research Course In Phage Discovery And Genomics For First-Year Undergraduate Students, Tuajuanda C. Jordan, Sandra H. Burnett, Susan Carson, Steven M. Caruso

University Faculty Publications and Creative Works

Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been …

A Broadly Implementable Research Course In Phage Discovery And Genomics For First-Year Undergraduate Students, Tuajuanda C. Jordan, Sandra H. Burnett, Susan Carson, Steven M. Caruso

University Faculty Publications and Creative Works

Engaging large numbers of undergraduates in authentic scientific discovery is desirable but difficult to achieve. We have developed a general model in which faculty and teaching assistants from diverse academic institutions are trained to teach a research course for first-year undergraduate students focused on bacteriophage discovery and genomics. The course is situated within a broader scientific context aimed at understanding viral diversity, such that faculty and students are collaborators with established researchers in the field. The Howard Hughes Medical Institute (HHMI) Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES) course has been widely implemented and has been …

Computational Model For Survey And Trend Analysis Of Patients With Endometriosis : A Decision Aid Tool For Ebm, Salvo Reina, Vito Reina, Franco Ameglio, Mauro Costa, Alessandro Fasciani

COBRA Preprint Series

Endometriosis is increasingly collecting worldwide attention due to its medical complexity and social impact. The European community has identified this as a “social disease”. A large amount of information comes from scientists, yet several aspects of this pathology and staging criteria need to be clearly defined on a suitable number of individuals. In fact, available studies on endometriosis are not easily comparable due to a lack of standardized criteria to collect patients’ informations and scarce definitions of symptoms. Currently, only retrospective surgical stadiation is used to measure pathology intensity, while the Evidence Based Medicine (EBM) requires shareable methods and correct …

Dysphagia And Disrupted Cranial Nerve Development In A Mouse Model Of Digeorge/22q11 Deletion Syndrome, Beverly A. Karpinski, Thomas M. Maynard, Matthew S. Fralish, Samar Nuwayhid, Irene Zohn, Sally Ann Moody, Anthony-Samuel Lamantia

Anatomy and Regenerative Biology Faculty Publications

We assessed feeding-related developmental anomalies in the LgDel mouse model of Chromosome 22q11 Deletion Syndrome (22q11DS), a common developmental disorder that frequently includes perinatal dysphagia - debilitating feeding, swallowing and nutrition difficulties from birth onward - within its phenotypic spectrum. LgDel pups gain significantly less weight during the first postnatal weeks, and have several signs of respiratory infections due to food aspiration. Most 22q11 genes are expressed in anlagen of craniofacial and brainstem regions critical for feeding and swallowing, and diminished expression in LgDel embryos apparently compromises development of these regions. Palate and jaw anomalies indicate divergent oro-facial morphogenesis. Altered …

Deletion Of Aif1 But Not Of Yca1/Mca1 Protects Saccharomyces Cerevisiae And Candida Albicans Cells From Caspofungin-Induced Programmed Cell Death, Nicanor Austriaco, Christopher Chin, Faith Donaghey, Kathrine Helming, Morgan Mccarthy, Stephen Rogers

Biology Faculty Publications

Caspofungin was the first member of a new class of antifungals called echinocandins to be approved by a drug regulatory authority. Like the other echinocandins, caspofungin blocks the synthesis of β(1,3)-D-glucan of the fungal cell wall by inhibiting the enzyme, β(1,3)-D-glucan synthase. Loss of β(1,3)-D-glucan leads to osmotic instability and cell death. However, the precise mechanism of cell death associated with the cytotoxicity of caspofungin was unclear. We now provide evidence that Saccharomyces cerevisiae cells cultured in media containing caspofungin manifest the classical hallmarks of programmed cell death (PCD) in yeast, including the generation of reactive oxygen species (ROS), the …

Inflammation Enhances Il-2 Driven Differentiation Of Cytolytic Cd4 T Cells, Aspen M. Workman, Ashley K. Jacobs, Alexander J. Vogel, Shirley Condon, Deborah M. Brown

Nebraska Center for Virology: Faculty Publications

Cytolytic CD4 T cells (CD4 CTL) have been identified in vivo in response to viral infections; however, the factors necessary for driving the cytolytic phenotype have not been fully elucidated. Our previously published work suggests IL-2 may be the master regulator of perforin-mediated cytotoxicity in CD4 effectors. To further dissect the role of IL-2 in CD4 CTL generation, T cell receptor transgenic mice deficient in the ability to produce IL-2 or the high affinity IL-2 receptor (IL-2Rα, CD25) were used. Increasing concentrations of IL-2 were necessary to drive perforin (Prf) expression and maximal cytotoxicity. Granzyme B (GrB) expression and killing …

Phylogeny And Population Genetics Of The Endangered Dwarf Bear-Poppy, Arctomecon Humilis Coville (Papaveraceae) Using Microsatellite Markers, Joshua Simpson

Dissertations, Theses, and Capstone Projects

The genus Arctomecon (Papaveraceae) is comprised of three narrowly endemic rare species that are largely restricted to gypsum soils of the eastern Mojave Desert. The small, remaining populations of these species have become increasingly isolated by urban development and habitat fragmentation. Arctomecon humilis is federally listed as endangered due to its limited distribution within a ~15 km radius of an actively expanding city. Organizations involved with land management and conservation have called for greater insight into the genetic variation and population structure of the remaining subpopulations as they make important decisions regarding where to focus their efforts and resources.

The …

Validation Of Predicted Mrna Splicing Mutations Using High-Throughput Transcriptome Data, Coby Viner, Stephanie Dorman, Ben Shirley, Peter Rogan

Biochemistry Publications

Interpretation of variants present in complete genomes or exomes reveals numerous sequence changes, only a fraction of which are likely to be pathogenic. Mutations have been traditionally inferred from allele frequencies and inheritance patterns in such data. Variants predicted to alter mRNA splicing can be validated by manual inspection of transcriptome sequencing data, however this approach is intractable for large datasets. These abnormal mRNA splicing patterns are characterized by reads demonstrating either exon skipping, cryptic splice site use, and high levels of intron inclusion, or combinations of these properties. We present, Veridical, an in silico method for the automatic validation …

Trip/Nopo E3 Ubiquitin Ligase Promotes Ubiquitylation Of Dna Polymerase Η, Heather A. Wallace, Julie A. Merkle, Michael C. Yu, Taloa G. Berg, Ethan Lee, Giovanni Bosco, Laura A. Lee

Dartmouth Scholarship

We previously identified a Drosophila maternal effect-lethal mutant named ‘no poles’ (nopo). Embryos from nopo females undergo mitotic arrest with barrel-shaped, acentrosomal spindles during the rapid cycles of syncytial embryogenesis because of activation of a Chk2-mediated DNA checkpoint. NOPO is the Drosophila homolog of human TNF receptor associated factor (TRAF)-interacting protein (TRIP), which has been implicated in TNF signaling. NOPO and TRIP contain RING domains closely resembling those of known E3 ubiquitin ligases. We herein sought to elucidate the mechanism by which TRIP/NOPO promotes genomic stability by performing a yeast two-hybrid screen to identify potential substrates/interactors. We identified members of …

Measuring Radiation Exposure In Human Blood Using Gene Expression, Krystal Naranjo, Melissa Bentley, Harsha Konery, Matthew Coleman

STAR Program Research Presentations

Mammalian cells are known to express genes that are associated with repairing damaged DNA. The transcript CDKN1A is one of several cell cycle regulator genes expressed in response to cell damage by ionizing radiation (IR). In this study, male and female lymphocytes; previously exposed ex vivo to IR, were used to demonstrate linear gene expression responses that may vary between genders. We used qRT-PCR to generate response curves for CDKN1A. No differences were identified for the endogenous control gene GAPDH. CDKN1A expression demonstrated average fold changes well above three fold for three of the four healthy patient donors at 24 …

Finding Fault?: Exploring Legal Duties To Return Incidental Findings In Genomic Research, Elizabeth R. Pike, Karen H. Rothenberg, Benjamin E. Berkman

Faculty Scholarship

The use of whole genome sequencing in biomedical research is expected to produce dramatic advances in human health. The increasing use of this powerful, data-rich new technology in research, however, will inevitably give rise to incidental findings (IFs), findings with individual health or reproductive significance that are beyond the aims of the particular research, and the related questions of whether and to what extent researchers have an ethical obligation to return IFs. Many have concluded that researchers have an ethical obligation to return some findings in some circumstances, but have provided vague or context-dependent approaches to determining which IFs must …

Horses As Sources Of Proprietary Information: Commercialization, Conservation, And Compensation Pursuant To The Convention On Biological Diversity, Haley Mcclory, Stanley Kowalski

Law Faculty Scholarship

Horses indigenous to East and Southeast (E/SE) Asia, including native, landrace, feral, and wild populations, embody valuable genetic diversity. Conservation efforts for animals have largely been driven by humane altruism, with little consideration for the information value of genomes. Yet, if horses are viewed as archives of information as well as objects of affection, their conservation shifts to a market-based paradigm. Horse genetic resources (GR) likely contain significant value to the lucrative global horse industry, including veterinary applications such as diagnostics, therapeutics, genetic markers, gene therapies, and cloning technologies. As biotechnology becomes increasingly sophisticated, mining of horse GR will accelerate, …

Homogeneity And Heterogeneity As Situational Properties: Producing – And Moving Beyond? – Race In Post-Genomic Science, J. K. Shim, K. W. Darling, M. D. Lappe, Laura Katherine Thomson, Sandra Soo-Jin Lee, R. A. Hiatt, S. L. Ackerman

Sociology

In this article, we explore current thinking and practices around the logics of difference in gene–environment interaction research in the post-genomic era. We find that scientists conducting gene–environment interaction research continue to invoke well-worn notions of racial difference and diversity, but use them strategically to try to examine other kinds of etiologically significant differences among populations. Scientists do this by seeing populations not as inherently homogeneous or heterogeneous, but rather by actively working to produce homogeneity along some dimensions and heterogeneity along others in their study populations. Thus we argue that homogeneity and heterogeneity are situational properties – properties that …

Relationships Between The Weedy (Amaranthaceae) And The Grain Amaranths [Abstract], Kiel D. Kielinski, Felix Jimenez, Eric N. Jellen, Peter J. Maughan, Scott M. Smith, Donald B. Pratt

Faculty Publications

No abstract provided.

Prioritizing Protein Complexes Implicated In Human Diseases By Network Optimization., Yong Chen, Thibault Jacquemin, Shuyan Zhang, Rui Jiang

College of Science & Mathematics Departmental Research

BACKGROUND: The detection of associations between protein complexes and human inherited diseases is of great importance in understanding mechanisms of diseases. Dysfunctions of a protein complex are usually defined by its member disturbance and consequently result in certain diseases. Although individual disease proteins have been widely predicted, computational methods are still absent for systematically investigating disease-related protein complexes.

RESULTS: We propose a method, MAXCOM, for the prioritization of candidate protein complexes. MAXCOM performs a maximum information flow algorithm to optimize relationships between a query disease and candidate protein complexes through a heterogeneous network that is constructed by combining protein-protein interactions …

Integrated Omics Study Delineates The Dynamics Of Lipid Droplets In Rhodococcus Opacus Pd630., Yong Chen, Yunfeng Ding, Li Yang, Jinhai Yu, Guiming Liu, Xumin Wang, Shuyan Zhang, Dan Yu, Lai Song, Hangxiao Zhang, Congyan Zhang, Linhe Huo, Chaoxing Huo, Yang Wang, Yalan Du, Huina Zhang, Peng Zhang, Huimin Na, Shimeng Xu, Yaxin Zhu, Zhensheng Xie, Tong He, Yue Zhang, Guoliang Wang, Zhonghua Fan, Fuquan Yang, Honglei Liu, Xiaowo Wang, Xuegong Zhang, Michael Q Zhang, Yanda Li, Alexander Steinbüchel, Toyoshi Fujimoto, Simon Cichello, Jun Yu, Pingsheng Liu

College of Science & Mathematics Departmental Research

Rhodococcus opacus strain PD630 (R. opacus PD630), is an oleaginous bacterium, and also is one of few prokaryotic organisms that contain lipid droplets (LDs). LD is an important organelle for lipid storage but also intercellular communication regarding energy metabolism, and yet is a poorly understood cellular organelle. To understand the dynamics of LD using a simple model organism, we conducted a series of comprehensive omics studies of R. opacus PD630 including complete genome, transcriptome and proteome analysis. The genome of R. opacus PD630 encodes 8947 genes that are significantly enriched in the lipid transport, synthesis and metabolic, indicating a super …

Complete Genome Sequence Of Anabaena Variabilis Atcc 29413, Teresa Thiel, Brenda Pratte, Jinshun Zhong, Lynne Goodwin, Alex Copeland, Susan Lucas, Cliff Han, Sam Pitluck, Miriam Land, Nikos Kyrpides, Tanja Woyke

Biology Department Faculty Works

Anabaena variabilis ATCC 29413 is a filamentous, heterocyst-forming cyanobacterium that has served as a model organism, with an extensive literature extending over 40 years. The strain has three distinct nitrogenases that function under different environmental conditions and is capable of photoautotrophic growth in the light and true heterotrophic growth in the dark using fructose as both carbon and energy source. While this strain was first isolated in 1964 in Mississippi and named Anabaena flos-aquae MSU A-37, it clusters phylogenetically with cyanobacteria of the genus Nostoc. The strain is a moderate thermophile, growing well at approximately 40° C. Here we provide …

Set-Based Tests For Genetic Association In Longitudinal Studies, Zihuai He, Min Zhang, Seunggeun Lee, Jennifer A. Smith, Xiuqing Guo, Walter Palmas, Sharon L.R. Kardia, Ana V. Diez Roux, Bhramar Mukherjee

The University of Michigan Department of Biostatistics Working Paper Series

Genetic association studies with longitudinal markers of chronic diseases (e.g., blood pressure, body mass index) provide a valuable opportunity to explore how genetic variants affect traits over time by utilizing the full trajectory of longitudinal outcomes. Since these traits are likely influenced by the joint effect of multiple variants in a gene, a joint analysis of these variants considering linkage disequilibrium (LD) may help to explain additional phenotypic variation. In this article, we propose a longitudinal genetic random field model (LGRF), to test the association between a phenotype measured repeatedly during the course of an observational study and a set …

Using Phylogenetically-Informed Annotation (Pia) To Search For Light-Interacting Genes In Transcriptomes From Non-Model Organisms, Daniel I. Speiser, M. Sabrina Pankey, Alexander K. Zaharoff, Barbara A. Battelle, Heather D. Bracken-Grissom, Jesse W. Breinholt, Seth M. Bybee, Thomas W. Cronin, Anders Garm, Annie R. Lindgren, Nipam H. Patel, Megan L. Porter, Meredith E. Protas, Anja S. Rivera, Jeanne M. Serb, Kirk S. Zigler, Keith A. Crandall, Todd H. Oakley

Collected Faculty Scholarship

Background: Tools for high throughput sequencing and de novo assembly make the analysis of transcriptomes (i.e. the suite of genes expressed in a tissue) feasible for almost any organism. Yet a challenge for biologists is that it can be difficult to assign identities to gene sequences, especially from non-model organisms. Phylogenetic analyses are one useful method for assigning identities to these sequences, but such methods tend to be time-consuming because of the need to re-calculate trees for every gene of interest and each time a new data set is analyzed. In response, we employed existing tools for phylogenetic analysis to …

High Prevalence Of Early Childhood Infection By Kshv In A Minority Population In China, Yifei Cao, Veenu Minhas, Xiaohua Tan, Jin Huang, Baodong Wang, Meiyi Zhu, Yuan Gao, Tingting Zhao, Lei Yang, Charles Wood

Nebraska Center for Virology: Faculty Publications

In China, KSHV seroprevalence varies considerably among different regions and ethnicities. But in Xinjiang province, located in the northwestern China, there is a very high seroprevalence of KSHV in adults of Kazak and Ughur ethnicities. However, KSHV prevalence in children and the risk factors associated with the acquisition of infection are currently not known. The aim of this study was to investigate the prevalence of KSHV infection, identify associated socio-economic or behavioral risk factors and the humoral immune response among children in this population. This is a cross-sectional study (N=178) to screen children and their caregivers from Xinjiang for total …

Frequency-Dependent Mate Selection In The Guppy (Poeciliidae: Poecilia Reticulata), Andre Porter, Jack Frankel

Department of Biology Faculty Publications

Heterogeneity within a population enhances its long-term survival. A fundamental method of maintaining population heterogeneity is the retention of rare or uncommon phenotypes by selective mating strategies. Employing two color morphs, red tuxedo and red, of the guppy (Poecilia reticulata, Poeciliidae), this study was designed to investigate whether P. reticulata females would preferentially seek out heterogeneous groupings of males exhibiting two color morphs. Adult female guppies were exposed simultaneously to two groups of males (n=10); one comprised of only the tuxedo color morph (n=5) and the other of both color morphs (n=5). For the latter group, the ratio of males …