Cell and Developmental Biology Commons^™

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 …

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 …

Seroprevalence Of Antibodies Against Kaposi's Sarcoma-Associated Herpesvirus Among Hiv-Negative People In China, Tiejun Zhang, Zhenqiu Liu, Jun Wang, Veenu Minhas, Charles Wood, Gary M. Clifford, Na He, Silvia Franceschi

Nebraska Center for Virology: Faculty Publications

Background: Little information on the prevalence of Kaposi’s sarcoma associated herpesvirus (KSHV) among HIV-negative individuals is available from Asia.

Methods: In the present study, we report findings from a new survey of KSHV in 983 HIV-negative male migrants from Shanghai and their combination with previous similar surveys of 600 female migrants, 600 female sex-workers (FSW), 1336 sexually transmitted infection (STI) clinic male patients, 439 intravenous drug-users (IVDU), and 226 men having sex with men (MSM) from China. KSHV-specific antibodies against latent and lytic antigens were assessed using Sf9 and BC3 monoclonal immunofluorescence assay. Age-adjusted prevalence ratios (PR) and 95% confidence …

Mutant Tdp-43 Does Not Impair Mitochondrial Bioenergetics In Vitro And In Viv, Hibiki Kawamata, Pablo Peixoto, Csaba Konrad, Gloria Palomo, Kirsten Bredvik, Meri Gerges, Federica Valsecchi, Leonard Petrucelli, John M. Ravits, Anatoly Starkov, Giovanni Manfredi

Publications and Research

Background: Mitochondrial dysfunction has been linked to the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Functional studies of mitochondrial bioenergetics have focused mostly on superoxide dismutase 1 (SOD1) mutants, and showed that mutant human SOD1 impairs mitochondrial oxidative phosphorylation, calcium homeostasis, and dynamics. However, recent reports have indicated that alterations in transactivation response element DNA-binding protein 43 (TDP-43) can also lead to defects of mitochondrial morphology and dynamics. Furthermore, it was proposed that TDP-43 mutations cause oxidative phosphorylation impairment associated with respiratory chain defects and that these effects were caused by mitochondrial localization of the mutant …

Characterization Of Neuronal Specific Responses To Induced Misfolded Protein Stress In Caenorhabditis Elegans, Claire Gormley

Senior Honors Projects, 2010-2019

Abstract

Misfolded protein stress has been associated with many types of disease,

including neurodegenerative disorders like Alzheimer’s, Parkinson’s and Huntington’s

disease. When a cell accumulates misfolded proteins in the endoplasmic reticulum,

misfolded protein stress occurs and the unfolded protein response (UPR) is triggered to

induce mechanisms that will allow the cell to either survive or undergo cell death. The

nascent polypeptide associated complex (NAC) is a co-translational chaperone and α/β

heterodimer that manages protein folding and localization, and protects against misfolded

protein stress; changes in NAC function have been linked to both neurodegeneration and

cancer. In these studies, I depleted …

Epigenetic Modifications Of Human Placenta Associated With Preterm Birth, Drissa Toure

Theses & Dissertations

Preterm birth is a complex multifactorial process. Despite the well-known role of the placenta in supporting the fetal development and maternal-fetal tolerance, the placental epigenetic modifications and preterm birth (PTB) remains poorly understood and under investigated. Various maternal and environment factors can influence epigenetic programming during fetal development to affect the functioning and structures of organs, including the placenta, which can lead to adverse pregnancy outcomes, including PTB. The understanding of the placental epigenetic alterations and maternal determinants associated with PTB are apparently indispensable for the development of actual diagnosis and methods of prevention and treatment of premature labor. The …

Characterization Of E-Cadherin Regulation In Response To Zeb1 Inhibition In Endometrial Cancer Cell Lines, Chidozie Paul Chukwu

Graduate School of Biomedical Sciences Theses and Dissertations

Epithelial to mesenchymal transition (EMT) is the process in which cells lose their epithelial structure during gastrulation. This process also affects the migration and movement of tumor cells and promotes invasion and metastases of endometrial carcinomas. Down-regulation of E-cadherin (CDH1) by transcription factors is the key target of EMT modulators and is achieved mainly by ZEB1 (zinc finger E-box binding homeobox 1). Current research looking at restoration of E-cadherin expression in vitro involves the use of small molecules such as histone deacetylase (HDAC) inhibitors and DNA methyltransferase inhibitors. Trichostatin A (TSA) and small interfering ribonucleic acid (siRNA) are tools that …

The Role Of The Expansion Segment 7 Of 25s Rrna During Oxidative Stress In Saccharomyces Cerevisiae, Ethan Gardner

Graduate School of Biomedical Sciences Theses and Dissertations

Translation is an essential process for protein expression in both eukaryotes and prokaryotes. Like any cellular process, translational factors are prone to damage when the cell is under stress. One common stressor that nearly all cells may experience is abnormal levels of reactive oxygen species (ROS). Damage caused by ROS has been associated with disease ranging from neurodegenerative impairments, to the aging process of cells. These oxygen radicals are capable of damaging a litany of molecules including nucleic acids, and molecular factors involved in translation. It has been shown that tRNA can be cleaved upon ROS-induced stress and these fragments …

Modeling 3d Retinogenesis In Mouse Embryonic Stem Cells Following Crispr-Mediated Crx Knockdown, Pooja Prasad

Dissertations, Masters Theses, Capstones, and Culminating Projects

An emerging technology known as three-dimensional (3D) tissue engineering has allowed scientists to mimic tissues found in vivo. Previous studies indicate that it is possible to differentiate dissociated mouse embryonic stem cells (mESCs) into 3D retinal tissues in vitro (Bertacchi, 2015; Eiraku, 2012). The newly differentiated retinal tissues are said to encompass all of the major components found in retinal tissues. The generation of in vitro 3D tissues holds great potential in terms of patient-specific disease modeling. Although various diseases have been well-studied in animal models, there are limitations with regards to patient-specificity. The generation of animal models to study …

Lymphoid Hematopoiesis And The Role Of B-Cells In Transgenic Mouse Model Of Sickle Cell Disease, Christina Cotte

University Scholar Projects

Sickle cell disease (SCD) has been shown to be associated with decreased baseline immunity and thus increased susceptibility to infection. I sought to discern possible causes of this by looking into the correlations between SCD and hematopoiesis, the immune system and the neuroendocrine system, and ultimately by conducting experiments surrounding the impaired immune system of SCD. These experiments focused on the potential causes and effects of the diminution of B-1a cells in the SCD spleen. Adoptive transfers, infections with Streptococcus pneumoniae, and histologic imaging were conducted to establish if the diminution of the B-1a cells in the SCD spleen …

Characterization Of Myod And Myf5 Double-Knockout Muscle Stem Cells During Muscle Development, Andreea Dinicu

University Scholar Projects

MyoD and Myf5 are transcription factors that regulate myogenesis by promoting satellite cell transcription. The two genes are known to display functional redundancy. Both genes are considered myogenic determination genes and are expressed in satellite cells. The fate of myogenic precursors in the absence of both MyoD and Myf5 remains largely unknown. We aimed to begin attaining this knowledge as part of this project. We utilized a CreLoxP system to control the expression of MyoD in mice lacking Myf5. MyoD was knocked out at embryonic day (E) 11.5 during myogenesis. Limbs were collected from experimental mice following tamoxifen injection. …

Proteomic Identification Of Histone Post-Translational Modifications Induced By Dna Double-Strand Breaks And Novel Proteins Involved In The Dna Damage Response, Pingping Wang

Dissertations and Theses (Open Access)

Inaccurate repair of DNA double-strand breaks (DSBs) can lead to DNA mutation and chromosome rearrangements, causing human diseases such as cancer. Although we know the basic mechanisms of DSB repair, the added complexities in the chromatin context are unclear. This is partially due to the lack of unbiased systems for identifying proteins and post-translational modifications (PTMs) involved in DSB repair. In this work, we established a novel method, termed DSB-ChAP-MS (Double Strand Break-Chromatin Affinity Purification with Mass Spectrometry), for the affinity purification of a sequence-specific single copy endogenous chromosomal locus containing a DSB, followed by the proteomic identification of enriched …

Non-Coding Rnas Identify The Intrinsic Molecular Subtypes Of Muscle-Invasive Bladder Cancer, Andrea E. Ochoa

Dissertations and Theses (Open Access)

NON-CODING RNAS IDENTIFY THE INTRINSIC MOLECULAR SUBTYPES OF MUSCLE-INVASIVE BLADDER CANCER

Andrea Elizabeth Ochoa, B.S.

Advisory Professors: David J. McConkey, Ph.D. and Joya Chandra, Ph.D.

There has been a recent explosion of genomics data in muscle-invasive bladder cancer (MIBC) to better understand the underlying biology of the disease that leads to the high amount of heterogeneity that is seen clinically. These studies have identified relatively stable intrinsic molecular subtypes of MIBC that show similarities to the basal and luminal subtypes of breast cancer. However, previous studies have primarily focused on protein-coding genes or DNA mutations/alterations.

There is emerging evidence implicating …

Understanding The Mechanism Of Genomic Instability During Replicative Aging In Budding Yeast, Sangita Pal

Dissertations and Theses (Open Access)

Aging brings a gradual decline in molecular fidelity and biological functionality, resulting in age related phenotypes and diseases. Despite continued efforts to uncover the conserved aging pathways among eukaryotes, exact molecular causes of aging are still poorly understood. One of the most important hallmarks of aging is increased genomic instability. However, there remains much ambiguity as to the cause. I am studying the replicative life span (RLS) of the genetically tractable model organism Saccharomyces cerevisiae, or budding yeast using the innovative “mother enrichment program” as the method to isolate unparalleled numbers of aged yeast cells to investigate the molecular changes …

Lysine Residues Of Interferon Regulatory Factor 7 Affect The Replication And Transcription Activatormediated Lytic Replication Of Kaposi’S Sarcomaassociated Herpesvirus/Human Herpesvirus 8, Tianzheng Zhang, Ying Wang, Li Zhang, Bin Liu, Jinhui Xie, Charles Wood, Jinzhong Wang

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) infection goes through latent and lytic phases, which are controlled by the viral replication and transcription activator (RTA). Upon KSHV infection, the host responds by suppressing RTA-activated lytic gene expression through interferon regulatory factor 7 (IRF-7), a key regulator of host innate immune response. Lysine residues are potential sites for post-translational modification of IRF-7, and were suggested to be critical for its activity. In this study, we analysed the 15 lysine residues for their effects on IRF-7 function by site-directed mutagenesis. We found that some mutations affect the ability of IRF-7 to activate interferon (IFN)-a1 and …

C-Myc’S Role On Methylation Of The Gata-2 Gene In Non-Small Cell Lung Carcinoma, Jonathan D. Hajduk

Student Scholar Showcase

Lung cancer accounts for more deaths per year than any other form of cancer, resulting in a total of 158,000 deaths per year in the U.S. Non-small cell lung cancer (NSCLC) is diagnosed in greater than 224,000 Americans every year. Methylation and subsequent downregulation of certain genes has been directly linked to the uncontrolled growth of NSCLC cells. Natural killer (NK) cells are key innate immune cells responsible for apoptosis of cells with incorrect genetic code. It is believed that one component of uncontrolled NSCLC growth is due to the NK cells’ inability to detect errors within NSCLC cells. Perhaps …

Identifying Regulators From Multiple Types Of Biological Data In Cancer, Brittany Baur

Dissertations (1934 -)

Cancer genomes accumulate alterations that promote cancer cell proliferation and survival. Structural, genetic and epigenetic alterations that have a selective advantage for tumorigenesis affect key regulatory genes and microRNAs that in turn regulate the expression of many target genes. The goal of this dissertation is to leverage the alteration-rich landscape of cancer genomes to detect key regulatory genes and microRNAs. To this end, we designed a feature selection algorithm to identify DNA methylation signals around a gene that would highly predict its expression. We found that genes whose expression could be predicted by DNA methylation accurately were enriched in Gene …

Whole Transcriptome Comparison Between Multipotent Adult Stem Cells (Mascs) And Two Families Of Mesenchymal Stem Cells (Mscs), Jessica C. Black, Drew Cumming, Andra Sullivan, Wei-Hua Huang, Paul A. Lucas

NYMC Faculty Posters

No abstract provided.

Coccolithoviruses: A Review Of Cross-Kingdom Genomic Thievery And Metabolic Thuggery, Jozef I. Nissimov, António Pagarete, Fangrui Ma, Sean Cody, David D. Dunigan, Susan A. Kimmance, Michael J. Allen

Nebraska Center for Virology: Faculty Publications

Coccolithoviruses (Phycodnaviridae) infect and lyse the most ubiquitous and successful coccolithophorid in modern oceans, Emiliania huxleyi. So far, the genomes of 13 of these giant lytic viruses (i.e., Emiliania huxleyi viruses—EhVs) have been sequenced, assembled, and annotated. Here, we performed an in-depth comparison of their genomes to try and contextualize the ecological and evolutionary traits of these viruses. The genomes of these EhVs have from 444 to 548 coding sequences (CDSs). Presence/absence analysis of CDSs identified putative genes with particular ecological significance, namely sialidase, phosphate permease, and sphingolipid biosynthesis. The viruses clustered into distinct clades, based on their DNA polymerase …

Latexin Inactivation Enhances Survival And Long-Term Engraftment Of Hematopoietic Stem Cells And Expands The Entire Hematopoietic System In Mice, Yi Liu, Cuiping Zhang, Zhenyu Li, Chi Wang, Jianhang Jia, Tianyan Gao, Gerhard C. Hildebrandt, Daohong Zhou, Subbarao Bondada, Peng Ji, Daret K. St. Clair, Jinze Liu, Chang-Guo Zhan, Hartmut Geiger, Shuxia Wang, Ying Liang

Toxicology and Cancer Biology Faculty Publications

Natural genetic diversity offers an important yet largely untapped resource to decipher the molecular mechanisms regulating hematopoietic stem cell (HSC) function. Latexin (Lxn) is a negative stem cell regulatory gene identified on the basis of genetic diversity. By using an Lxn knockout mouse model, we found that Lxn inactivation in vivo led to the physiological expansion of the entire hematopoietic hierarchy. Loss of Lxn enhanced the competitive repopulation capacity and survival of HSCs in a cell-intrinsic manner. Gene profiling of Lxn-null HSCs showed altered expression of genes enriched in cell-matrix and cell-cell interactions. Thrombospondin 1 (Thbs1 …

Molecular Regulation Of Stem Cell Behavior During Tissue Repair And Cancer Formation, Nestor J. Oviedo

Science Seminar Series

Oviedo will be presenting his work on identifying the mechanisms of adult stem cell fate determination based on their topographical location in the adult body. Understanding stem cell fate determination is crucial because tissue repair and neoplastic growth are greater in anterior than in posterior regions of adult animals. Despite its critical implications for stem cell biology, carcinogenesis and regenerative medicine, this physiological phenomenon has remained overlooked. Recent findings from his group provide intriguing evidence implying DNA repair mechanisms and cellular signaling through post-translational modifications regulate stem cell fate decision depending on their topographical location in the adult body. We …

Effect Of Cigarette Smoke Exposure And Mutant Kras Overexpression On Pancreatic Cell Proliferation, Howard P. Glauert, R. Scott Elliott, Sung Gu Han, Mark Athey, Eun Young Lee, C. Gary Gairola

Pharmacology and Nutritional Sciences Faculty Publications

Pancreatic cancer is the fourth leading cause of cancer‑associated mortality. The major risk factor for pancreatic cancer is cigarette smoking. Kras mutations are commonly observed in human pancreatic cancers. The present study examined the hypothesis that exposure to cigarette smoke and overexpression of a mutant Kras gene in the pancreas affects pancreatic cell proliferation in mice. Mice overexpressing the mutant Kras gene (KRas^G12D) in the pancreas as well as wild‑type mice were exposed to environmental tobacco smoke for 2 weeks. Overexpression of mutant Kras increased cell proliferation in pancreatic ductal, acinar and islet cells. Notably, cigarette smoke exposure …

The Mirnaome Of Catharanthus Roseus: Identification, Expression Analysis, And Potential Roles Of Micrornas In Regulation Of Terpenoid Indole Alkaloid Biosynthesis, Ethan M. Shen, Sanjay Kumar Singh, Jayadri S. Ghosh, Barunava Patra, Priyanka Paul, Ling Yuan, Sitakanta Pattanaik

Plant and Soil Sciences Faculty Publications

MicroRNAs (miRNAs) regulate numerous crucial biological processes in plants. However, information is limited on their involvement in the biosynthesis of specialized metabolites in plants, including Catharanthus roseus that produces a number of pharmaceutically valuable, bioactive terpenoid indole alkaloids (TIAs). Using small RNA-sequencing, we identified 181 conserved and 173 novel miRNAs (cro-miRNAs) in C. roseus seedlings. Genome-wide expression analysis revealed that a set of cro-miRNAs are differentially regulated in response to methyl jasmonate (MeJA). In silico target prediction identified 519 potential cro-miRNA targets that include several auxin response factors (ARFs). The presence of cleaved transcripts of miRNA-targeted ARFs in C. roseus …

Sumo Regulates The Activity Of Smoothened And Costal-2 In Drosophila Hedgehog Signaling, Jie Zhang, Yajuan Liu, Kai Jiang, Jianhang Jia

Markey Cancer Center Faculty Publications

In Hedgehog (Hh) signaling, the GPCR-family protein Smoothened (Smo) acts as a signal transducer that is regulated by phosphorylation and ubiquitination, which ultimately change the cell surface accumulation of Smo. However, it is not clear whether Smo is regulated by other post-translational modifications, such as sumoylation. Here, we demonstrate that knockdown of the small ubiquitin-related modifier (SUMO) pathway components Ubc9 (a SUMO-conjugating enzyme E2), PIAS (a SUMO-protein ligase E3), and Smt3 (the SUMO isoform in Drosophila) by RNAi prevents Smo accumulation and alters Smo activity in the wing. We further show that Hh-induced-sumoylation stabilizes Smo, whereas desumoylation by Ulp1 …

A Machine Learning Classifier Trained On Cancer Transcriptomes Detects Nf1 Inactivation Signal In Glioblastoma, Gregory P. Way, Robert J. Allaway, Stephanie J. J. Bouley, Camilo E. Fadul, Yolanda Sanchez, Casey Greene

Dartmouth Scholarship

We have identified molecules that exhibit synthetic lethality in cells with loss of the neurofibromin 1 (NF1) tumor suppressor gene. However, recognizing tumors that have inactivation of the NF1 tumor suppressor function is challenging because the loss may occur via mechanisms that do not involve mutation of the genomic locus. Degradation of the NF1 protein, independent of NF1 mutation status, phenocopies inactivating mutations to drive tumors in human glioma cell lines. NF1 inactivation may alter the transcriptional landscape of a tumor and allow a machine learning classifier to detect which tumors will benefit from synthetic lethal molecules. We …

The Molecular Basis Of Talin2'S High Affinity Toward Β1-Integrin, Yaxia Yuan, Liqing Li, Yanyan Zhu, Lei Qi, Latifeh Azizi, Vesa P. Hytönen, Chang-Guo Zhan, Cai Huang

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Talin interacts with β-integrin tails and actin to control integrin activation, thus regulating focal adhesion dynamics and cell migration. There are two talin genes, Tln1 and Tln2, which encode talin1 and talin2, and it is generally believed that talin2 functions redundantly with talin1. However, we show here that talin2 has a higher affinity to β1-integrin tails than talin1. Mutation of talin2 S339 to leucine, which can cause Fifth Finger Camptodactyly, a human genetic disease, completely disrupted its binding to β–integrin tails. Also, substitution of talin1 C336 with Ser enhanced the affinity of talin1, whereas substitution of talin2 S339 with …

Post-Transcriptional Regulation Of The Drosophila Anterior Determinant, Bicoid, John Mclaughlin

Dissertations, Theses, and Capstone Projects

In a wide variety of biological contexts, messenger RNA (mRNA) is known to have a complex and dynamic life cycle. In particular, the localization and translational control of mRNA are essential for proper development in eukaryotes. The fly Drosophila melanogaster is an excellent model for studying these processes. During D. melanogaster oogenesis, several mRNAs are trafficked and localized within the developing egg chamber, and regulated at the translational level to enable embryo patterning. One such mRNA, bicoid, is localized at the anterior of the oocyte and translated in the early embryo, where its encoded protein directs formation of the fly's …

Environmental Changes Turn On The Sinorhizobium Melitloti Exor-Exos/Chvi (Rsi) Host Invasion Switch, Shari N. Walcott

Dissertations, Theses, and Capstone Projects

The free-living Gram-negative soil bacterium, Sinorhizobium meliloti, must switch into its host-invading form in order to infect the root hairs of the host plant, alfalfa (Medicago sativa), and establish a nitrogen-fixing symbiosis. The activation of the switch is believed to occur inside the infection chamber that is formed by curling of the root hairs. It is not fully understood what signals in the environment of the root hairs trigger and infection chamber S. meliloti to switch into a host-invading form since these signals were not extensively examined until now. This switch can be observed directly, due to …

Transcriptional And Post-Transcriptional Regulation Of Histone Variant H2a.Z During Sea Urchin Development, Mihai Hajdu

Dissertations, Theses, and Capstone Projects

Histone variant H2A.Z promotes chromatin accessibility at transcriptional regulatory elements and is developmentally regulated in metazoans. We characterize the transcriptional and post-transcriptional regulation of H2A.Z in the purple sea urchin Strongylocentrotus purpuratus. H2A.Z depletion by antisense translation-blocking morpholino oligonucleotides during early development causes developmental collapse, in agreement with its previously demonstrated general role in transcriptional multipotency. During H2A.Z peak expression in 24-h embryos, endogenous H2A.Z 3’ UTR sequences stabilize GFP mRNAs relative to those with SV40 3’ UTR sequences, although the 3’UTR of H2A.Z does not determine the spatial distribution of H2A.Z transcripts during embryonic and postembryonic development. We …

The Subject Librarian Newsletter, Biology, Spring 2017, Sandy Avila

Libraries' Newsletters

No abstract provided.