Life Sciences Commons^™

Integrative Genomic And Transcriptomic Analysis For Pinpointing Recurrent Alterations Of Plant Homeodomain Genes And Their Clinical Significance In Breast Cancer, Huimei Yu, Yuanyuan Jiang, Lanxin Liu, Wenqi Shan, Xiaofang Chu, Zhe Yang, Zeng-Quan Yang

Oncology Faculty Publications

A wide range of the epigenetic effectors that regulate chromatin modification, gene expression, genomic stability, and DNA repair contain structurally conserved domains called plant homeodomain (PHD) fingers. Alternations of several PHD finger-containing proteins (PHFs) due to genomic amplification, mutations, deletions, and translocations have been linked directly to various types of cancer. However, little is known about the genomic landscape and the clinical significance of PHFs in breast cancer. Hence, we performed a large-scale genomic and transcriptomic analysis of 98 PHF genes in breast cancer using TCGA and METABRIC datasets and correlated the recurrent alterations with clinicopathological features and survival of …

Cullin-4 Regulates Wingless And Jnk Signaling-Mediated Cell Death In The Drosophila Eye., Meghana Tare, Ankita Sarkar, Shimpi Bedi, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

In all multicellular organisms, the fundamental processes of cell proliferation and cell death are crucial for growth regulation during organogenesis. Strict regulation of cell death is important to maintain tissue homeostasis by affecting processes like regulation of cell number, and elimination of unwanted/unfit cells. The developing Drosophila eye is a versatile model to study patterning and growth, where complex signaling pathways regulate growth and cell survival. However, the molecular mechanisms underlying regulation of these processes is not fully understood. In a gain-of-function screen, we found that misexpression of cullin-4 (cul-4), an ubiquitin ligase, can rescue reduced eye mutant phenotypes. Previously, …

Novel Models Of Visual Topographic Map Alignment In The Superior Colliculus., Ruben A Tikidji-Hamburyan, Tarek A El-Ghazawi, Jason W. Triplett

Pediatrics Faculty Publications

The establishment of precise neuronal connectivity during development is critical for sensing the external environment and informing appropriate behavioral responses. In the visual system, many connections are organized topographically, which preserves the spatial order of the visual scene. The superior colliculus (SC) is a midbrain nucleus that integrates visual inputs from the retina and primary visual cortex (V1) to regulate goal-directed eye movements. In the SC, topographically organized inputs from the retina and V1 must be aligned to facilitate integration. Previously, we showed that retinal input instructs the alignment of V1 inputs in the SC in a manner dependent on …

A Machine Learning Approach For Using The Postmortem Skin Microbiome To Estimate The Postmortem Interval, Hunter R. Johnson, Donovan D. Trinidad, Stephania Guzman, Zenab Khan, James V. Parziale, Jennifer M. Debruyn, Nathan H. Lents

Publications and Research

Research on the human microbiome, the microbiota that live in, on, and around the human person, has revolutionized our understanding of the complex interactions between microbial life and human health and disease. The microbiome may also provide a valuable tool in forensic death investigations by helping to reveal the postmortem interval (PMI) of a decedent that is discovered after an unknown amount of time since death. Current methods of estimating PMI for cadavers discovered in uncontrolled, unstudied environments have substantial limitations, some of which may be overcome through the use of microbial indicators. In this project, we sampled the microbiomes …

Comparative Genomic Analysis Of Two Serotype 1/2b Listeria Monocytogenes Isolates From Analogous Environmental Niches Demonstrates The Influence Of Hypervariable Hotspots In Defining Pathogenesis, Aidan Casey, Kieran Jordan, Aidan Coffey, Edward M. Fox, Olivia Mcauliffe

Department of Biological Sciences Publications

The vast majority of clinical human listeriosis cases are caused by serotype 1/2a, 1/2b, 1/2c, and 4b isolates of Listeria monocytogenes. The ability of L. monocytogenes to establish a systemic listeriosis infection within a host organism relies on a combination of genes that are involved in cell recognition, internalization, evasion of host defenses, and in vitro survival and growth. Recently, whole genome sequencing and comparative genomic analysis have proven to be powerful tools for the identification of these virulence-associated genes in L. monocytogenes. In this study, two serotype 1/2b strains of L. monocytogenes with analogous isolation sources, but …

The Fate Of Icd-1 During Misfolded Protein Induced Apoptosis In Caenorhabditis Elegans, Kyle H. Perez

Senior Honors Projects, 2010-2019

Severe misfolded protein stress initiates cellular responses that often result in the death of the affected cell, typically by apoptosis. An essential aspect of apoptosis is caspase-mediated cleavage of proteins that, once cleaved, further propagate death. One heterodimeric structure putatively targeted in this process in the nascent polypeptide-associated complex (NAC), a translational chaperone thought to help prevent misfolded protein stress in the ER. The purpose of this investigation was to determine whether the beta subunit of the NAC in C. elegans (ICD-1) is cleaved during the induction of apoptosis, with the hypothesis that ICD-1 is cleaved during stressed-induced apoptosis to …

A Bioinformatics Methodology For The Annotation And Analysis Of Sperm Chromatin Remodeling Proteins In Sequenced Drosophila Species, Zain A. Alvi

Seton Hall University Dissertations and Theses (ETDs)

Spermatogenesis is the process by which mature functional spermatozoa are formed, and is initiated in the stem cell niche of the testes. During the post-meiotic stage of spermatogenesis, spermiogenesis, transition proteins facilitate the transformation of chromatin from a histone-based nucleosome structure to a protamine-based nucleosome structure. This study is aimed at analyzing genomic, transcript, and protein sequences of transition proteins in 13 sequenced Drosophila species. The Drosophila melanogaster spermatid specific transition protein-like protein (Tpl^94D) was used as the reference sequence in this study. An extensive bioinformatics approach was employed in establishing the Tpl^94D orthologs. We identified …

Dna Polymerase Zeta-Dependent Mutagenesis: Molecular Specificity, Extent Of Error-Prone Synthesis, And The Role Of Dntp Pools, Olga V. Kochenova

Theses & Dissertations

Despite multiple DNA repair pathways, DNA lesions can escape repair and compromise normal chromosomal replication, leading to genome instability. Cells utilize specialized low-fidelity Translesion Synthesis (TLS) DNA polymerases to bypass lesions and rescue arrested replication forks. TLS is a highly conserved two-step process that involves insertion of a nucleotide opposite a lesion and extension of the resulting aberrant primer terminus. The first step can be performed by both replicative and TLS DNA polymerases and, because of non-instructive DNA lesions, often results in a nucleotide misincorporation. The second step is almost exclusively catalyzed by DNA polymerase ζ …

Improved Genome-Scale Multitarget Virtual Screening Via A Novel Collaborative Filtering Approach To Cold-Start Problem, Hansaim Lim, Paul Gray, Lei Xie, Aleksandar Poleksic

Publications and Research

Conventional one-drug-one-gene approach has been of limited success in modern drug discovery. Polypharmacology, which focuses on searching for multi-targeted drugs to perturb disease-causing networks instead of designing selective ligands to target individual proteins, has emerged as a new drug discovery paradigm. Although many methods for single-target virtual screening have been developed to improve the efficiency of drug discovery, few of these algorithms are designed for polypharmacology. Here, we present a novel theoretical framework and a corresponding algorithm for genome-scale multitarget virtual screening based on the one-class collaborative filtering technique. Our method overcomes the sparseness of the protein-chemical interaction data by …

Biophysical And Functional Characterization Of Rhesus Macaque Igg Subclasses, Austin W. Boesch, Nana Yaw Osei-Owusu, Andrew R. Crowley, Thach H. Chu, Ying Chan, Joshua Weiner, Pranay Bharadwaj, Rufus Hards, Mark Adamo, Scott Gerber, Sarah Cocklin, Joern Schmitz, Adam Miles, Joshua Eckman, Aaron J. Belli, Keith Reimann, Margaret E. Ackerman

Dartmouth Scholarship

Antibodies raised in Indian rhesus macaques [Macaca mulatta (MM)] in many preclinical vaccine studies are often evaluated in vitro for titer, antigen-recognition breadth, neu- tralization potency, and/or effector function, and in vivo for potential associations with protection. However, despite reliance on this key animal model in translation of promising candidate vaccines for evaluation in first in man studies, little is known about the proper- ties of MM immunoglobulin G (IgG) subclasses and how they may compare to human IgG subclasses. Here, we evaluate the binding of MM IgG1, IgG2, IgG3, and IgG4 to human Fc gamma receptors (FcγR) and their …

Effect Of Maternal Age On Recombination Rate In Drosophila Melanogaster, Christopher Schimmoeller

Honors Projects

Recombination is vital because it adds genetic diversity to a species and has the potential to influence fitness, the relative reproductive success of an organism in passing genes to the next generation (Roeder, 1997). Multiple aspects of recombination have been studied, including its mechanisms of production and the role of recombination events in evolution (Hudson & Kaplan, 1985). In this study we examined how maternal age affects the rate of recombination. Our hypothesis states that recombination rate is positively correlated with maternal age. If this is true we would expect to see recombination rate, in progeny, increase as the parental …

Dna Methylation Signatures Of Chronic Low-Grade Inflammation Are Associated With Complex Diseases, Symen Ligthart, Carola Marzi, Stella Aslibekyan, Michael M. Mendelson, Karen N. Conneely, Toshiko Tanaka, Elena Colicino, Lindsay L. Waite, Roby Joehanes, Weihua Guan, Jennifer A. Brody, Cathy Elks, Riccardo Marioni, Min A. Jhun, Golareh Agha, Jan Bressler, Cavin K. Ward-Caviness, Brian H. Chen, Tianxiao Huan, Kelly Bakulski, Elias L. Salfati, Whi-Empc Investigators, Giovanni Fiorito, Charge Epigenetics Of Coronary Heart Disease, Simone Wahl, Katharina Schramm, Jin Sha, Dena G. Hernandez, Allan C. Just, Jennifer A. Smith, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Background: Chronic low-grade inflammation reflects a subclinical immune response implicated in the pathogenesis of complex diseases. Identifying genetic loci where DNA methylation is associated with chronic low-grade inflammation may reveal novel pathways or therapeutic targets for inflammation.

Results: We performed a meta-analysis of epigenome-wide association studies (EWAS) of serum C-reactive protein (CRP), which is a sensitive marker of low-grade inflammation, in a large European population (n = 8863) and trans-ethnic replication in African Americans (n = 4111). We found differential methylation at 218 CpG sites to be associated with CRP (P < 1.15 × 10^–7) in the discovery panel …

Allelic Variation In Cxcl16 Determines Cd3+ T Lymphocyte Susceptibility To Equine Arteritis Virus Infection And Establishment Of Long-Term Carrier State In The Stallion, Sanjay Sarkar, Ernest Bailey, Yun Young Go, R. Frank Cook, Ted Kalbfleisch, John E. Eberth, R. Lakshman Chelvarajan, Kathleen M. Shuck, Sergey Artiushin, Peter J. Timoney, Udeni B. R. Balasuriya

Maxwell H. Gluck Equine Research Center Faculty Publications

Equine arteritis virus (EAV) is the causative agent of equine viral arteritis (EVA), a respiratory, systemic, and reproductive disease of horses and other equid species. Following natural infection, 10–70% of the infected stallions can become persistently infected and continue to shed EAV in their semen for periods ranging from several months to life. Recently, we reported that some stallions possess a subpopulation(s) of CD3⁺ T lymphocytes that are susceptible to in vitro EAV infection and that this phenotypic trait is associated with long-term carrier status following exposure to the virus. In contrast, stallions not possessing the CD3⁺ T …

Control Of Gene Expression By Rna Binding Protein Action On Alternative Translation Initiation Sites, Angela Re, Levi Waldron, Alessandro Quattrone

Publications and Research

Transcript levels do not faithfully predict protein levels, due to post-transcriptional regulation of gene expression mediated by RNA binding proteins (RBPs) and non-coding RNAs. We developed a multivariate linear regression model integrating RBP levels and predicted RBP-mRNA regulatory interactions from matched transcript and protein datasets. RBPs significantly improved the accuracy in predicting protein abundance of a portion of the total modeled mRNAs in three panels of tissues and cells and for different methods employed in the detection of mRNA and protein. The presence of upstream translation initiation sites (uTISs) at the mRNA 5' untranslated regions was strongly associated with improvement …

Hnrnpa2 Is A Novel Histone Acetyltransferase That Mediates Mitochondrial Stress-Induced Nuclear Gene Expression, Manti Guha, Satish Srinivasan, Kip Guja, Edison Mejia, Miguel Garcia-Diaz, F. Brad Johnson, Gordon Ruthel, Brett A. Kaufman, Eric F. Rappaport, M. Rebecca Glineburg, Ji-Kang Fang, Andres J. Klein-Szanto, Hiroshi Nakagawa, Jeelan Basha, Tapas Kundu, Narayan G. Avadhani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Reduced mitochondrial DNA copy number, mitochondrial DNA mutations or disruption of electron transfer chain complexes induce mitochondria-to-nucleus retrograde signaling, which induces global change in nuclear gene expression ultimately contributing to various human pathologies including cancer. Recent studies suggest that these mitochondrial changes cause transcriptional reprogramming of nuclear genes although the mechanism of this cross talk remains unclear. Here, we provide evidence that mitochondria-to-nucleus retrograde signaling regulates chromatin acetylation and alters nuclear gene expression through the heterogeneous ribonucleoprotein A2 (hnRNAP2). These processes are reversed when mitochondrial DNA content is restored to near normal cell levels. We show that the mitochondrial stress-induced …

Functional Significance Of Branch Points In Mirtrons, Britton A. Strickland

Honors Theses

MicroRNAs are a heterogeneous group of small regulatory RNAs generated by many pathways. Mirtrons (miR) are a class of microRNAs produced by splicing, and some mirtrons contain a 3’ tail located downstream from the self-complementary hairpin. During RNA splicing, a loop-like “lariat” intermediate structure is created when the 5’ end of the RNA is attached to an adenine called the branch point. The goal of this project is to uncover the contribution of branch point location to the processing of tailed mirtrons into functional gene regulators. This project approaches this issue from two directions. First, branch points were identified by …

Reexamining Chronic Toxoplasma Gondii Infection: Surprising Activity For A "Dormant" Parasite, Anthony P. Sinai, Elizabeth A. Watts, Animesh Dhara, Robert D. Murphy, Matthew S. Gentry, Abhijit R. Patwardhan

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Purpose of Review

Despite over a third of the world’s population being chronically infected with Toxoplasma gondii, little is known about this largely asymptomatic phase of infection. This stage is mediated in vivo by bradyzoites within tissue cysts. The absence of overt symptoms has been attributed to the dormancy of bradyzoites. In this review, we reexamine the conventional view of chronic toxoplasmosis in light of emerging evidence challenging both the nature of dormancy and the consequences of infection in the CNS.

Recent Findings

New and emerging data reveal a previously unrecognized level of physiological and replicative capacity of bradyzoites …

Determining The Impacts Of Environmental Contaminants To Zebra Mussels Using Genetic Biomarkers, Nicklaus James Neureuther

Theses and Dissertations

ABSTRACT

DETERMINING THE IMPACTS OF ENVIRONMENTAL CONTAMINANTS TO ZEBRA MUSSELS USING GENETIC BIOMARKERS

by

Nicklaus James Neureuther

The University of Wisconsin-Milwaukee, 2016

Under the Supervision of Professor Rebecca Klaper, PhD

Persistent legacy contaminants and emerging chemicals of concern continue to be a threat to the function and health in the Great Lakes Areas of Concern (AOCs). While chemical monitoring programs traditionally sample water and sediment, these studies can only provide information of the type and level of contamination within an (AOC). This being said, information on the biological impacts to the biota are needed to measure impairments of chemical exposure, …

Strategies For Enriching Variant Coverage In Candidate Disease Loci On A Multiethnic Genotyping Array, Stephanie Bien, Genevieve L. Wojcik, Niha Zubair, Christopher Gignoux, Alicia R. Martin, Lisa W. Martin, Page Study Investigators

Medicine Faculty Publications

Investigating genetic architecture of complex traits in ancestrally diverse populations is imperative to understand the etiology of disease. However, the current paucity of genetic research in people of African and Latin American ancestry, Hispanic and indigenous peoples in the United States is likely to exacerbate existing health disparities for many common diseases. The Population Architecture using Genomics and Epidemiology, Phase II (PAGE II), Study was initiated in 2013 by the National Human Genome Research Institute to expand our understanding of complex trait loci in ethnically diverse and well characterized study populations. To meet this goal, the Multi-Ethnic Genotyping Array (MEGA) …

Discrete Mutations In Colorectal Cancer Correlate With Defined Microbial Communities In The Tumor Microenvironment, Michael B. Burns, Emmanuel Montassier, Juan Abrahante, Timothy K. Starr, Dan Knights, Ran Blekhman

Biology: Faculty Publications and Other Works

Variation in the gut microbiome has been linked to colorectal cancer (CRC), as well as to host genetics. However, we do not know whether genetic mutations in CRC tumors interact with the structure and composition of the microbial communities surrounding the tumors, and if so, whether changes in the microbiome can be used as a predictor for tumor mutational status. Here, we characterized the association between CRC tumor mutational landscape and its proximal microbial communities by performing whole exome sequencing and microbiome profiling in tumors and normal colorectal tissue samples from the same patient. We find a significant association between …

Improving And Elucidating Factors Regulating Black Walnut (Juglans Nigra L.) Clonal Propagation, Micah E. Stevens

Open Access Dissertations

Black walnut (Juglans nigra L.) is a fine hardwood tree species native to the central hardwood region of the United States. High-quality black walnut timber is highly desirable. Traded in both regional and global markets, it has been used for veneer, and the manufacture of high-end products such as cabinets, furniture, and gunstocks. As a result of its high economic value, black walnut has been commercially cultivated for many years, and breeding programs have generated superior timber genotypes with improved marketable traits. Once elite genotypes were developed, it was quickly recognized that black walnut was recalcitrant to clonal propagation …

Exploration Of Dna Transfer In The Nyc Subway, Sannia K. Tauqeer

Student Theses

The ability to detect “touch” DNA has complicated the interpretation of DNA profiles in the field of forensics because it leads to the introduction of the concept of DNA transfer, persistence and background into casework. This project is geared towards understanding DNA transfer in the NYC subways and has relevance in groping and attempted sexual assault cases, where garments are submitted as evidence. The study involved 10 volunteers who were asked to wear a clean jacket during their trips on the subway for one week and the DNA from these jackets was collected, extracted, quantified, amplified and typed. The results …

Characterization Of Vesicular Monoamine Transporter 2 And Its Role In Parkinson's Disease Pathogenesis Using Drosophila, Antonio Joel Tito Jr., Sheng Zhang

Dissertations & Theses (Open Access)

Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by the selective loss of the dopaminergic neurons in the Substantia nigra pars compacta region of the brain. PD is also the most common neurodegenerative disorder and the second most common movement disorder. PD patients exhibit the cardinal symptoms, including tremor of the extremities, rigidity, slowness of movement, and postural instability, after 70-80% of DA neurons degenerate. It is, therefore, imperative to elucidate the underlying mechanisms involved in the selective degeneration of DA neurons. Although increasing numbers of PD genes have been identified, why these largely widely expressed genes induce …

Genetic Study Of Carotenoids In Maize Grain (Zea Mays L.), Oscar Rafael Espejel Venado

Open Access Theses

Pro-Vitamin A (proVA) carotenoids, which are converted into retinol (Vitamin A) in the human body, have been the subject of human nutrition studies and are a target for biofortification of staple crops. Historically, β-carotene has been the principal target for enhancing levels of proVA, yet there is recent interest in enhancing the proVA carotenoid β-cryptoxanthin. Studies have shown that β-cryptoxanthin has excellent bioavailability, and its use in maize may be nearly as effective as β-carotene in providing retinol. The primary aim of this study was to gain a better understanding of the genetic control of levels of β-cryptoxanthin, conversion of …

Cohesion Without Cohesins In Drosophila Meiosis, Avik Mukherjee

Doctoral Dissertations

Meiosis is essential for sexual reproduction. The proper segregation of chromosomes in meiosis requires multiple functions of a multi-subunit protein complex known as cohesin. Cohesin forms a ring around duplicated sister chromatids and prevents them from separating prematurely. In Drosophila, mitotic cohesin is composed of four subunits: SMC1 and SMC3 and SCC1/RAD21 and SCC3/SA and are required for mitotic cohesion. However, RAD21 is dispensable for meiotic cohesion and although SMC1 and SMC3 are present on meiotic centromeres and on synapsed chromosome arms, as expected, their functions in meiosis remain poorly characterized. Moreover, unlike in other eukaryotes in which screens for …

Whole Genome Sequencing As A Tool For Identifying Phenotypic Properties And Underlying Genetic Mechanisms In Staphylococcus Pseudintermedius, Matthew C. Riley

Doctoral Dissertations

Staphylococcus pseudintermedius is a Gram-positive bacterial opportunistic pathogen commonly associated with dermal infections in canines, but capable of causing serious disease in other species. Reports of human infections caused by S. pseudintermedius along with an increase in resistance to multiple antibiotics highlights the importance of this organism. Whole genome sequencing can allow large scale investigation of genetic mechanisms underlying phenotypic properties that contribute to the expansion of successful S. pseudintermedius clonal lineages.

The increase in multidrug and methicillin-resistant S. pseudintermedius (MRSP) may result from horizontal transfer of genetic material between bacterial isolates, yet is thought to be rare in Staphylococci …

Tetrameric Photosystem I: From Initial Discovery And Characterization In Chroococcidiopsis Sp. Ts-821 To Exploration Of Its Distribution And Understanding Of Its Significance In Cyanobacteria, Meng Li

Doctoral Dissertations

Photosystem I (PSI) forms trimeric complexes in most characterized cyanobacteria. We had reported the tetrameric form of PSI in the unicellular cyanobacterium, Chroococcidiopsis sp. TS-821 (TS-821). Using Cryo-EM, a 3D model of the PSI tetramer structure at 11.5 [Angstrom] resolution was obtained and a 2D map within the membrane plane of at 6.1 [Angstrom]. In contrast to the three-fold symmetry in trimeric PSI crystal structure from T. elongatus, two different inter-monomer interactions involving PsaLs are found in the PSI tetramer. Phylogenetic analysis based on PsaL protein sequences shows that TS-821 is closely related to heterocyst-forming cyanobacteria. Additionally, this tetrameric …

Punctuated Evolution Within A Eurythermic Genus (Mesenchytraeus) Of Segmented Worms: Genetic Modification Of The Glacier Ice Worm F1f0 Atp Synthase, Shirley A. Lang

Graduate School of Biomedical Sciences Theses and Dissertations

Segmented worms (Annelida) are among the most successful animal inhabitants of extreme environments worldwide. An unusual group of Mesenchytraeus worms endemic to the Pacific Northwest of North America occupy geographically proximal ecozones ranging from low elevation temperate rainforests to high altitude glaciers. Along this altitudinal transect, Mesenchytraeus representatives from disparate habitat types were collected and subjected to deep mitochondrial and nuclear phylogenetic analyses. Evidence presented here employing modern bioinformatic analyses (i.e., maximum likelihood, Bayesian inference, multi-species coalescent) supports a Mesenchytraeus “explosion” in the upper Miocene (5-10 million years ago) that gave rise to ice, snow and terrestrial worms, derived from …

Consensus Paper: Cerebellar Development., K Leto, M Arancillo, Ebe Becker, A Chiang, Et Al.

Faculty Publications

The development of the mammalian cerebellum is orchestrated by both cell-autonomous programs and inductive environmental influences. Here, we describe the main processes of cerebellar ontogenesis, highlighting the neurogenic strategies used by developing progenitors, the genetic programs involved in cell fate specification, the progressive changes of structural organization, and some of the better-known abnormalities associated with developmental disorders of the cerebellum.

A Population Genetics Study Of Discula Destructiva, The Causal Agent Of Dogwood Anthracnose, Kristie Lynn Mantooth

Masters Theses

Flowering dogwood (Cornus florida L.) is prized as an ornamental and contributes millions of dollars to the economy through tourism and sales each year. Dogwood anthracnose, caused by Discula destructiva Redlin, was observed in the late 1970s on the east and west coasts of the United States and by 1991 had quickly spread throughout much of the native ranges of C. florida and C. nuttalli. The objectives of this study were to investigate the genetic diversity and population structure of D. destructiva using simple sequence repeats (SSRs), and to test the cross-transferability of these markers to other Discula …