Genetics and Genomics Commons^™

Expanding Mouse-Adapted Yamagata-Like Influenza B Viruses In Eggs Enhances In Vivo Lethality In Balb/C Mice, Matthew J. Pekarek, Erika M. Petro-Turnquist, Adam Rubrum, Richard J. Webby, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Despite the yearly global impact of influenza B viruses (IBVs), limited host range has been a hurdle to developing a readily accessible small animal disease model for vaccine studies. Mouseadapting IBV can produce highly pathogenic viruses through serial lung passaging in mice. Previous studies have highlighted amino acid changes throughout the viral genome correlating with increased pathogenicity, but no consensus mutations have been determined. We aimed to show that growth system can play a role in mouse-adapted IBV lethality. Two Yamagata-lineage IBVs were serially passaged 10 times in mouse lungs before expansion in embryonated eggs or Madin–Darby canine kidney cells …

Reduction Of Plasmid Vector Backbone Length Enhances Reporter Gene Expression, Carly Boye, Sezgi Arpag, Michael Francis, Scott Declemente, Aislin West, Richard Heller, Anna Bulysheva

Electrical & Computer Engineering Faculty Publications

Gene therapy has a wide range of applications for various types of pathologies. Viral methods of gene delivery provide high levels of gene expression but have various safety concerns. Non-viral methods are largely known to provide lower levels of expression. We aim to address this issue by using plasmid DNA with smaller backbones to increase gene expression levels when delivered using non-viral methods. In this study we compare gene expression levels between two vectors with firefly luciferase encoding gene insert using liposome complexes and gene electrotransfer as delivery methods. A 2-fold reduction in plasmid vector backbone size, disproportionately enhanced gene …

Genetic Variants Associated With Circulating Liver Injury Markers In Mexican Americans, A Population At Risk For Non-Alcoholic Fatty Liver Disease, Caroline M Sabotta, Suet-Ying Kwan, Lauren E Petty, Jennifer E Below, Aron Joon, Peng Wei, Susan P Fisher-Hoch, Joseph B Mccormick, Laura Beretta

Faculty, Staff and Student Publications

Objective: Mexican Americans are disproportionally affected by non-alcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma. Noninvasive means to identify those in this population at high risk for these diseases are urgently needed. Approach: The Cameron County Hispanic Cohort (CCHC) is a population-based cohort with high rates of obesity (51%), type 2 diabetes (28%) and NAFLD (49%). In a subgroup of 564 CCHC subjects, we evaluated 339 genetic variants previously reported to be associated with liver injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in United Kingdom and Japanese cohorts. Results: Association was confirmed for 86 variants. Among …

Robust Meta-Analysis For Large-Scale Genomic Experiments Based On An Empirical Approach, Sinjini Sikdar

Mathematics & Statistics Faculty Publications

BACKGROUND: Recent high-throughput technologies have opened avenues for simultaneous analyses of thousands of genes. With the availability of a multitude of public databases, one can easily access multiple genomic study results where each study comprises of significance testing results of thousands of genes. Researchers currently tend to combine this genomic information from these multiple studies in the form of a meta-analysis. As the number of genes involved is very large, the classical meta-analysis approaches need to be updated to acknowledge this large-scale aspect of the data.

METHODS: In this article, we discuss how application of standard theoretical null distributional assumptions …

Determinants Of Virus Variation, Evolution, And Host Adaptation, Katherine Latourrette, Hernan Garcia-Ruiz

Nebraska Center for Virology: Faculty Publications

Virus evolution is the change in the genetic structure of a viral population over time and results in the emergence of new viral variants, strains, and species with novel biological properties, including adaptation to new hosts. There are host, vector, environmental, and viral factors that contribute to virus evolution. To achieve or fine tune compatibility and successfully establish infection, viruses adapt to a particular host species or to a group of species. However, some viruses are better able to adapt to diverse hosts, vectors, and environments. Viruses generate genetic diversity through mutation, reassortment, and recombination. Plant viruses are exposed to …

Immunogenicity And Protective Efficacy Of A Recombinant Pichinde Viral-Vectored Vaccine Expressing Influenza Virus Hemagglutinin Antigen In Pigs, Sushmita Kumari, Jayeshbhai Chaudhari, Qinfeng Huang, Phillip Gauger, Marcelo Nunes De Almeida, Yuying Liang, Hinh Ly, Hiep Vu

Nebraska Center for Virology: Faculty Publications

Influenza A virus of swine (IAV-S) is an economically important swine pathogen. The IAV-S hemagglutinin (HA) surface protein is the main target for vaccine development. In this study, we evaluated the feasibility of using the recombinant tri-segmented Pichinde virus (rPICV) as a viral vector to deliver HA antigen to protect pigs against IAV-S challenge. Four groups of weaned pigs (T01–T04) were included in the study. T01 was injected with PBS to serve as a non-vaccinated control. T02 was inoculated with rPICV expressing green fluorescence protein (rPICV-GFP). T03 was vaccinated with rPICV expressing the HA antigen of the IAV-S H3N2 strain …

Comparison Of Multiple Imputation Algorithms And Verification Using Whole-Genome Sequencing In The Cmuh Genetic Biobank, Ting-Yuan Liu, Chih-Fan Lin, Hsing-Tsung Wu, Ya-Lun Wu, Yu-Chia Chen, Chi-Chou Liao, Yu-Pao Chou, Dysan Chao, Hsing-Fang Lu, Ya-Sian Chang, Jan-Gowth Chang, Kai-Cheng Hsu, Fuu‑Jen Tsai

BioMedicine

A genome-wide association study (GWAS) can be conducted to systematically analyze the contributions of genetic factors to a wide variety of complex diseases. Nevertheless, existing GWASs have provided highly ethnic specific data. Accordingly, to provide data specific to Taiwan, we established a large-scale genetic database in a single medical institution at the China Medical University Hospital. With current technological limitations, microarray analysis can detect only a limited number of single-nucleotide polymorphisms (SNPs) with a minor allele frequency of >1%. Nevertheless, imputation represents a useful alternative means of expanding data. In this study, we compared four imputation algorithms in terms of …

Interleukin-10 Suppression Enhances T-Cell Antitumor Immunity And Responses To Checkpoint Blockade In Chronic Lymphocytic Leukemia., J R Rivas, Y Liu, S S Alhakeem, J M Eckenrode, F Marti, J P Collard, Y Zhang, K A Shaaban, N Muthusamy, G C Hildebrandt, L Chen, J S Thorson, M Leggas, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

T-cell dysfunction is a hallmark of B-cell Chronic Lymphocytic Leukemia (CLL), where CLL cells downregulate T-cell responses through regulatory molecules including programmed death ligand-1 (PD-L1) and Interleukin-10 (IL-10). Immune checkpoint blockade (ICB) aims to restore T-cell function by preventing the ligation of inhibitory receptors like PD-1. However, most CLL patients do not respond well to this therapy. Thus, we investigated whether IL-10 suppression could enhance antitumor T-cell activity and responses to ICB. Since CLL IL-10 expression depends on Sp1, we utilized a novel, better tolerated analogue of the Sp1 inhibitor mithramycin (MTM

The Role Of The Filifactor Alocis Hypothetical Protein Fa519 In Oxidative Stress Resistance, Ezinne Rebecca Aja

Loma Linda University Electronic Theses, Dissertations & Projects

Filifactor alocis, a fastidious, Gram-positive, obligate anaerobic bacterium, is a newly appreciated member of the periodontal community, which is now proposed to be a diagnostic indicator of periodontal disease. Its pathogenic characteristics are highlighted by its ability to survive in the oxidative-stress rich environment of the periodontal pocket and to significantly alter the microbial community dynamics by forming biofilms and interacting with several oral bacteria. Currently, there is incomplete information on the pathogenic mechanism(s) and a possible dynamic functional role of F. alocis in the dysbiotic microbial community. Because the stress response of this bacterium to the oxidative environment …

Global Gene Expression Analysis Of Systemic Sclerosis Myofibroblasts Demonstrates A Marked Increase In The Expression Of Multiple Nbpf Genes, Giuseppina Abignano, Heidi Hermes, Sonsoles Piera-Velazquez, Sankar Addya, Francesco Del Galdo, Sergio A. Jimenez

Kimmel Cancer Center Faculty Papers

Myofibroblasts are the key effector cells responsible for the exaggerated tissue fibrosis in Systemic Sclerosis (SSc). Despite their importance to SSc pathogenesis, the specific transcriptome of SSc myofibroblasts has not been described. The purpose of this study was to identify transcriptome differences between SSc myofibroblasts and non-myofibroblastic cells. Alpha smooth muscle actin (α-SMA) expressing myofibroblasts and α-SMA negative cells were isolated employing laser capture microdissection from dermal cell cultures from four patients with diffuse SSc of recent onset. Total mRNA was extracted from both cell populations, amplified and analyzed employing microarrays. Results for specific genes were validated by Western blots …

Chemotherapy-Induced Cognitive Impairment: Focus On The Intersection Of Oxidative Stress And Tnfα., Nicole G Rummel, Luksana Chaiswing, Subbarao Bondada, Daret K St Clair, D Allan Butterfield

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Chemotherapy-induced cognitive impairment (CICI) has been observed in a large fraction of cancer survivors. Although many of the chemotherapeutic drugs do not cross the blood-brain barrier, following treatment, the structure and function of the brain are altered and cognitive dysfunction occurs in a significant number of cancer survivors. The means by which CICI occurs is becoming better understood, but there still remain unsolved questions of the mechanisms involved. The hypotheses to explain CICI are numerous. More than 50% of FDA-approved cancer chemotherapy agents are associated with reactive oxygen species (ROS) that lead to oxidative stress and activate a myriad of …

Effects Of Hormone Replacement Therapy (Hrt) On Gene Expression In The Amyloid Processing Pathway Of Ovariectomized Rhesus Macaque Females Under An Obesogenic Diet, Megan Ball

University Honors Theses

Estrogens rapidly decline at the onset of menopause, putting women at higher risk of osteoporosis, obesity, and neurodegenerative diseases, including Alzheimer’s disease (AD). Estradiol hormone therapies (HT) have been suggested to limit these negative effects on women, with controversial findings as to their effectiveness. A study at OHSU recently found differentially expressed genes (DEGs) using RNAseq between ovariectomized/hysterectomized (OvH) old (range = 19.4–23.2 years) female rhesus macaques on HT and those on a placebo on chronic western style diet (WSD). The DEGs identified in the amyloid processing pathway of the amygdala were selected for validation using RT-qPCR because β-amyloid peptide …

Determining Effective Drug Concentrations For Selection And Counterselection Genetics In Drosophila Melanogaster, Nick Matinyan, Yezabel Gonzalez, Herman A Dierick, Koen J T Venken

Faculty, Staff and Students Publications

We recently integrated into fly genetics a set of four selection and two counterselection markers and their corresponding drugs that can be used individually or in combination. These markers eliminate the need to visually screen progeny. Before using these markers in new genetic backgrounds, effective selection/counterselection concentrations should be established for each marker/drug combination. This protocol describes how to set up, perform, and analyze a drug titration curve to determine the effective selection/counterselection drug concentrations for their corresponding markers. For complete details on the use and execution of this protocol, please refer to Matinyan et al., 2021.

Multiplexed Drug-Based Selection And Counterselection Genetic Manipulations In Drosophila, Nick Matinyan, Mansi S Karkhanis, Yezabel Gonzalez, Antrix Jain, Alexander Saltzman, Anna Malovannaya, Alejandro Sarrion-Perdigones, Herman A Dierick, Koen J T Venken

Faculty, Staff and Students Publications

The power of Drosophila melanogaster as a model system relies on tractable germline genetic manipulations. Despite Drosophila's expansive genetics toolbox, such manipulations are still accomplished one change at a time and depend predominantly on phenotypic screening. We describe a drug-based genetic platform consisting of four selection and two counterselection markers, eliminating the need to screen for modified progeny. These markers work reliably individually or in combination to produce specific genetic outcomes. We demonstrate three example applications of multiplexed drug-based genetics by generating (1) transgenic animals, expressing both components of binary overexpression systems in a single transgenesis step; (2) dual selectable …

Assesment Of Antibiotic Resistant Gene Expression In Clinical Isolates Of Pseudomonas Aeruginosa, Dustin Esmond

Biology Theses

Increasing prevalence of nosocomial infections by antimicrobial resistant pathogens resulting in higher mortality rates and financial burden is of great concern. Pseudomonas aeruginosa represents one of six highly virulent “ESKAPE” pathogens that exhibit considerable intrinsic drug resistance as well as mechanisms for acquiring further resistance. As many of these mechanisms are regulated through gene expression, we sought to identify regulatory strategies and patterns at play in 23 clinical isolates collected from Baku, Azerbaijan and Tyler, Texas, USA. Real-time quantitative polymerase chain reaction was performed on six gene targets implicated in resistance and contrasted with antibiotic phenotypes. We found AmpC cephalosporinase …

Exome Sequence Association Study Of Levels And Longitudinal Change Of Cardiovascular Risk Factor Phenotypes In European Americans And African Americans From The Atherosclerosis Risk In Communities Study, Elena V Feofanova, Elise Lim, Han Chen, Minjae Lee, Ching-Ti Liu, L Adrienne Cupples, Eric Boerwinkle

Faculty, Staff and Student Publications

Cardiovascular disease (CVD) is responsible for 31% of all deaths worldwide. Among CVD risk factors are age, race, increased systolic blood pressure (BP), and dyslipidemia. Both BP and blood lipids levels change with age, with a dose-dependent relationship between the cumulative exposure to hyperlipidemia and the risk of CVD. We performed an exome sequence association study using longitudinal data with up to 7805 European Americans (EAs) and 3171 African Americans (AAs) from the Atherosclerosis Risk in Communities (ARIC) study. We assessed associations of common (minor allele frequency > 5%) nonsynonymous and splice-site variants and gene-based sets of rare variants with levels …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

The Sulfur Microbial Diet And Risk Of Colorectal Cancer By Molecular Subtypes And Intratumoral Microbial Species In Adult Men, Daniel R. Sikavi, Long H. Nguyen, Koichiro Haruki, Tomotaka Ugai, Wenjie Ma, Dong D. Wang, Kelsey N. Thompson, Yan Yan, Tobyn Branck, Jeremy E. Wilkinson, Naohiko Akimoto, Rong Zhong, Mai Chan Lau, Kosuke Mima, Keisuke Kosumi, Teppei Morikawa, Eric B. Rimm, Wendy S. Garrett, Jacques Izard, Yin Cao, Mingyang Song, Curtis Huttenhower, Shuji Ogino, Andrew T. Chan

Department of Food Science and Technology: Faculty Publications

Introduction: We recently described the sulfur microbial diet, a pattern of intake associated with increased gut sulfur-metabolizing bacteria and incidence of distal colorectal cancer (CRC). We assessed whether this risk differed by CRC molecular subtypes or presence of intratumoral microbes involved in CRC pathogenesis (Fusobacterium nucleatum and Bifidobacterium spp.).

Methods: We performed Cox proportional hazards modeling to examine the association between the sulfur microbial diet and incidence of overall and distal CRC by molecular and microbial subtype in the Health Professionals Follow-Up Study (1986-2012).

Results: We documented 1,264 incident CRC cases among 48,246 men, approximately 40% …

Transcriptional Milestones In Dictyostelium Development, Mariko Katoh-Kurasawa, Karin Hrovatin, Shigenori Hirose, Amanda Webb, Hsing-I Ho, Blaž Zupan, Gad Shaulsky

Faculty, Staff and Students Publications

Dictyostelium development begins with single-cell starvation and ends with multicellular fruiting bodies. Developmental morphogenesis is accompanied by sweeping transcriptional changes, encompassing nearly half of the 13,000 genes in the genome. We performed time-series RNA-sequencing analyses of the wild type and 20 mutants to explore the relationships between transcription and morphogenesis. These strains show developmental arrest at different stages, accelerated development, or atypical morphologies. Considering eight major morphological transitions, we identified 1371 milestone genes whose expression changes sharply between consecutive transitions. We also identified 1099 genes as members of 21 regulons, which are groups of genes that remain coordinately regulated despite …

Rnase Κ Promotes Robust Pirna Production By Generating 2',3'-Cyclic Phosphate-Containing Precursors, Megumi Shigematsu, Takuya Kawamura, Keisuke Morichika, Natsuko Izumi, Takashi Kiuchi, Shozo Honda, Venetia Pliatsika, Ryuma Matsubara, Isidore Rigoutsos, Susumu Katsuma, Yukihide Tomari, Yohei Kirino

Computational Medicine Center Faculty Papers

In animal germlines, PIWI proteins and the associated PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposons. Here we report the extensive sequence and quantitative correlations between 2′,3′-cyclic phosphate-containing RNAs (cP-RNAs), identified using cP-RNA-seq, and piRNAs in the Bombyx germ cell line and mouse testes. The cP-RNAs containing 5′-phosphate (P-cP-RNAs) identified by P-cP-RNA-seq harbor highly consistent 5′-end positions as the piRNAs and are loaded onto PIWI protein, suggesting their direct utilization as piRNA precursors. We identified Bombyx RNase Kappa (BmRNase κ) as a mitochondria-associated endoribonuclease which produces cP-RNAs during piRNA biogenesis. BmRNase κ-depletion elevated transposon levels and disrupted a piRNA-mediated …

Predicting Synchronized Gene Coexpression Patterns From Fibration Symmetries In Gene Regulatory Networks In Bacteria, Ian Leifer, Mishael Sánchez‑Pérez, Cecilia Ishida, Hernán A. Makse

Publications and Research

Background: Gene regulatory networks coordinate the expression of genes across physiological states and ensure a synchronized expression of genes in cellular subsystems, critical for the coherent functioning of cells. Here we address the question whether it is possible to predict gene synchronization from network structure alone. We have recently shown that synchronized gene expression can be predicted from symmetries in the gene regulatory networks described by the concept of symmetry fibrations. We showed that symmetry fibrations partition the genes into groups called fibers based on the symmetries of their ’input trees’, the set of paths in the network through which …

Novel Scalable And Simplified System To Generate Microglia-Containing Cerebral Organoids From Human Induced Pluripotent Stem Cells, Brittany Bodnar, Yongang Zhang, Jinbiao Liu, Yuan Lin, Peng Wang, Zhengyu Wei, Sami Saribas, Yuanjun Zhu, Fang Li, Xu Wang, Wenli Yang, Qingsheng Li, Wen-Zhe Ho, Wenhui Hu

Nebraska Center for Virology: Faculty Publications

Human cerebral organoid (CO) is a three-dimensional (3D) cell culture system that recapitulates the developing human brain. While CO has proved an invaluable tool for studying neurological disorders in a more clinically relevant matter, there have still been several shortcomings including CO variability and reproducibility as well as lack of or underrepresentation of certain cell types typically found in the brain. As the technology to generate COs has continued to improve, more efficient and streamlined protocols have addressed some of these issues. Here we present a novel scalable and simplified system to generate microglia-containing CO (MCO). We characterize the cell …

Gene Therapy Knockdown Of Hippo Signaling Induces Cardiomyocyte Renewal In Pigs After Myocardial Infarction, Shijie Liu, Ke Li, Leonardo Wagner Florencio, Li Tang, Todd R Heallen, John P Leach, Yidan Wang, Francisco Grisanti, James T Willerson, Emerson C Perin, Sui Zhang, James F Martin

Faculty, Staff and Students Publications

Human heart failure, a leading cause of death worldwide, is a prominent example of a chronic disease that may result from poor cell renewal. The Hippo signaling pathway is an inhibitory kinase cascade that represses adult heart muscle cell (cardiomyocyte) proliferation and renewal after myocardial infarction in genetically modified mice. Here, we investigated an adeno-associated virus 9 (AAV9)–based gene therapy to locally knock down the Hippo pathway gene Salvador (Sav) in border zone cardiomyocytes in a pig model of ischemia/reperfusion-induced myocardial infarction. Two weeks after myocardial infarction, when pigs had left ventricular systolic dysfunction, we administered AAV9-Sav …

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021, Iujhs Full Issue

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences

Synphilin-1 And Its Effects On Pathogenesis Of Parkinson’S Disease, Mirghani Mohamed

Honors Scholar Theses

Parkinson's Disease (PD) is a progressive neurodegenerative and movement disorder primarily caused by the degradation of dopaminergic neurons. Known markers of neurodegeneration in PD are Lewy Bodies, which are fibrillar aggregates that are found in the brains of PD patients. Lewy Bodies can accumulate from specific mutations in the SNCA gene that codes for alpha-synuclein, a protein enriched in presynaptic neurons. A mutated SNCA gene can cause conformational aggregates of alpha-synuclein to form toxic species mediating neuronal death. Research into alpha-synuclein has led to the discovery of a binding partner known as synphilin-1 that is also found in protein aggregates …

Genome Sequence Of A Virulent African Swine Fever Virus Isolated In 2020 From A Domestic Pig In Northern Vietnam, Quang Lam Truong, Thi Lan Nguyen, Thi Hoa Nguyen, Jishu Shi, Hiep Lai Xuan Vu, Thi Lan Huong Lai, Van Giap Nguyen

Nebraska Center for Virology: Faculty Publications

This study reports the genome sequence of an isolated African swine fever (ASF) virus (VNUA-ASFV-05L1/HaNam) obtained at the fourth passage on pulmonary alveolar macrophages. The virus was isolated during a typical acute ASF outbreak in pigs in a northern province of Vietnam in 2020.

The Immune Microenvironment And Relation To Outcome In Patients With Advanced Breast Cancer Treated With Docetaxel With Or Without Gemcitabine, Elisabeth S. Stovgaard, Karama Asleh, Nazia Riaz, Samuel Leung, Dongxia Gao, Lise B. Nielsen, Anne-Vibeke Lænkholm, Eva Balslev, Maj-Britt Jensen, Dorte Nielsen, Torsten O. Nielsen

Centre for Regenerative Medicine & Stem Cell Research

Preclinical studies suggest that some effects of conventional chemotherapy, and in particular, gemcitabine, are mediated through enhanced antitumor immune responses. The objective of this study was to use material from a randomized clinical trial to evaluate whether patients with preexisting immune infiltrates responded better to treatment with gemcitabine + docetaxel (GD) compared to docetaxel alone. Formalin fixed, paraffin-embedded breast cancer tissues from SBG0102 phase 3 trial patients randomly assigned to treatment with GD or docetaxel were used. Immunohistochemical staining for CD8, FOXP3, LAG3, PD-1, PD-L1 and CD163 was performed. Tumor infiltrating lymphocytes (TILs) and tumor associated macrophages were evaluated. Prespecified …

The Effects Of Mapk Signaling On The Development Of Cerebellar Granule Cells, Kerry Morgan

Honors Scholar Theses

The granule cells are the most abundant neuronal type in the human brain. Rapid proliferation of granule cell progenitors results in dramatic expansion and folding of the cerebellar cortex during postnatal development. Mis-regulation of this proliferation process causes medulloblastoma, the most prevalent childhood brain tumor. In the developing cerebellum, granule cells are derived from Atoh1-expressing cells, which arise from the upper rhombic lip (the interface between the roof plate and neuroepithelium). In addition to granule cells, the Atoh1 lineage also gives rise to different types of neurons including cerebellar nuclei neurons. In the current study, I have investigated the …

Codon Bias Can Determine Sorting Of A Potassium Channel Protein, Anja J. Engel, Marina Kithil, Markus Langhans, Oliver Rauh, Matea Cartolano, James L. Van Etten, Anna Moroni, Gerhard Thiel

Nebraska Center for Virology: Faculty Publications

Due to the redundancy of the genetic code most amino acids are encoded by multiple synonymous codons. It has been proposed that a biased frequency of synonymous codons can affect the function of proteins by modulating distinct steps in transcription, translation and folding. Here, we use two similar prototype K⁺ channels as model systems to examine whether codon choice has an impact on protein sorting. By monitoring transient expression of GFP-tagged channels in mammalian cells, we find that one of the two channels is sorted in a codon and cell cycle-dependent manner either to mitochondria or the secretory pathway. …

Molecular And Genetic Studies Of Robo2 Transcriptional Regulation In The Central Nervous System Of Drosophila Melanogaster, Muna Abdal Rahim Abdal Rhida

Graduate Theses and Dissertations

Drosophila Robo2 axon guidance receptor is a member of the evolutionarily conserved Roundabout (Robo) protein family that is involved in directing axons that cross the midline to the other side of the animal body. Robo2 roles mainly depend on two factors: The functional domains of the Robo2 protein, which is extensively studied, and the dynamic transcription of robo2 in various subsets of cells throughout embryogenesis which is not fully understood. Thus, knowing robo2 enhancers that transcriptionally regulate robo2 during embryogenesis is significant. To investigate robo2 potential enhancers, we screened 17 transgenic lines of Drosophila that were generated by Janelia Research …