Digital Commons Network^™

Early Rescue Of Interneuron Disease Trajectory In Developmental Epilepsies, Ms Siehr, Jl Noebels

Faculty, Staff and Students Publications

The discovery of over 150 monogenic epilepsies and advances in early genetic diagnoses have launched a search for molecular strategies and developmental timetables to reverse or even prevent the course of these debilitating brain disorders. Orthologous rodent models of key disease genes are providing important examples of the range of targets, and serve as valuable test systems for perinatal therapeutic approaches. While gene-specific analyses of single rare 'orphan' diseases are each narrow in scope, they illuminate downstream pathways converging onto interneurons, and treatments that strengthen inhibition during cortical maturation may provide broad protection against these seemingly disparate gene errors. Several …

Efficacy Of Psychosocial Interventions In Inducing And Maintaining Alcohol Abstinence In Patients With Chronic Liver Disease: A Systematic Review, A Khan, A Tansel, Dl White, Wt Kayani, Wt Bano, J Lindsay, Hb El-Serag, F Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: We conducted a systematic review of efficacy of psychosocial interventions in inducing or maintaining alcohol abstinence in patients with chronic liver disease (CLD) and alcohol use disorder (AUD). METHODS: We performed structured keyword searches in PubMed, PsychINFO, and MEDLINE for original research articles that were published from January 1983 through November 2014 that evaluated the use of psychosocial interventions to induce or maintain alcohol abstinence in patients with CLD and AUD. RESULTS: We identified 13 eligible studies that comprised 1945 patients; 5 were randomized controlled trials (RCTs). Delivered therapies included motivational enhancement therapy, cognitive behavioral therapy (CBT), …

Eosinophilic Esophagitis In Children And Its Relationship With Parental Allergies: Texas Children's Hospital Experience, G Hiremath, D Byramji, A Pacheco, G Constantine, C Davis, R Shulman, A Olive

Faculty, Staff and Students Publications

BACKGROUND: Eosinophilic esophagitis (EoE) is an allergen-mediated, clinicopathological condition affecting all ages. The characteristics of children with EoE in the southwestern USA have not been fully described. Furthermore, very little is known about the relationship between parental allergies and risk of EoE in their offspring in this patient population. AIMS: To characterize children with EoE and to examine the relationship between prevalence of parental allergies and occurrence of EoE in their offspring at a single referral pediatric center in the southwestern USA. METHODS: Demographic and clinical information of 126 children (=18 years of age) with EoE was abstracted in a …

Glial Contributions To Neural Function And Disease, Mn Rasband

Faculty, Staff and Students Publications

The nervous system consists of neurons and glial cells. Neurons generate and propagate electrical and chemical signals, whereas glia function mainly to modulate neuron function and signaling. Just as there are many different kinds of neurons with different roles, there are also many types of glia that perform diverse functions. For example, glia make myelin; modulate synapse formation, function, and elimination; regulate blood flow and metabolism; and maintain ionic and water homeostasis to name only a few. Although proteomic approaches have been used extensively to understand neurons, the same cannot be said for glia. Importantly, like neurons, glial cells have …

Identification Of Novel Cyclic Lipopeptides From A Positional Scanning Combinatorial Library With Enhanced Antibacterial And Antibiofilm Activities, Nina Bionda, Renee M. Fleeman, César De La Fuente-Núñez, Maria C. Rodriguez, Fany Reffuveille, Lindsey N. Shaw, Irena Pastar, Stephen C Davis, Robert E W Hancock, Predrag Cudic

Molecular Biosciences Faculty Publications

Treating bacterial infections can be difficult due to innate or acquired resistance mechanisms, and the formation of biofilms. Cyclic lipopeptides derived from fusaricidin/LI-F natural products represent particularly attractive candidates for the development of new antibacterial and antibiofilm agents, with the potential to meet the challenge of bacterial resistance to antibiotics. A positional-scanning combinatorial approach was used to identify the amino acid residues responsible for driving antibacterial activity, and increase the potency of these cyclic lipopeptides. Screening against the antibiotic resistant ESKAPE pathogens revealed the importance of hydrophobic as well as positively charged amino acid residues for activity of this class …

First Described Case Of Group B Streptococcus Pelvic Abscess In A Patient With No Medical Comorbidities, Paul Tyan, Elias Abi-Khalil, Karthik Dwarki, Gaby N. Moawad

Obstetrics and Gynecology Faculty Publications

Background. Group B Streptococcus is an organism that commonly infects a wide range of hosts including infants in the first week of life, pregnant women, and older age adults as well as adults with underlying medical comorbidities.

Case. Large pelvic abscess in a nonpregnant patient found to be caused by Group B Streptococcuswas treated successfully with IR guided drainage and antibiotics.

Conclusion. Though rare, GBS can still be a cause of invasive infection even in individuals who are nonpregnant and have no underlying comorbidities. Empiric antibiotic coverage for this organism should be kept in mind when treating an abscess.

Temperature-Dependent Gentamicin Resistance Of Francisella Tularensis Is Mediated By Uptake Modulation, Kathleen Loughman, Jesse Hall, Samantha Knowlton, Chandra S. Bakshi, Joseph Horzempa

NYMC Faculty Publications

Gentamicin (Gm) is an aminoglycoside commonly used to treat bacterial infections such as tularemia - the disease caused by Francisella tularensis. In addition to being pathogenic, F. tularensis is found in environmental niches such as soil where this bacterium likely encounters Gm producers (Micromonospora sp.). Here we show that F. tularensis exhibits increased resistance to Gm at ambient temperature (26°C) compared to mammalian body temperature (37°C). To evaluate whether F. tularensis was less permeable to Gm at 26°C, a fluorescent marker [Texas Red (Tr)] was conjugated with Gm, yielding Tr-Gm. Bacteria incubated at 26°C showed reduced fluorescence compared to those …

Changes In Cytoskeleton Proteins In Hsv-1 Infection Of J774a.1 Macrophage Phenotype, Riham Abbas Subahi

Browse all Theses and Dissertations

The cell cytoskeleton, a unique intracellular matrix found in all eukaryotes, is composed of three main protein structures, microtubules, microlaments and intermediate laments. The cytoskeleton maintains cell shape and internal structures providing mechanical support that facilitates intracellular transport (Parker et al., 2014). Many viruses such as the herpesviruses use the cytoskeleton system of the cell for infectivity (Henry Sum, M. S. 2015). HSV-1 utilizes the cell cytoskeleton in many steps of its life cycle from entry through assembly to egress (Lyman et al., 2008). During infection, HSV-1 viral proteins cause drastic changes and rearrangement of the cellular actin and cell …

Identification Of Protein-Protein Interactions Of Amyotrophic Lateral Sclerosis Associated Protein Tdp-43, Hanoor Sharma

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease caused by progressive degeneration of upper and lower motor neurons in the brain and spinal cord. Multiple mutations are found in some of the proteins associated with ALS, including superoxide dismutase (SOD1), fused in sarcoma (FUS) and trans-activation response DNA-binding protein (TDP-43). TDP-43 is a DNA and RNA binding protein, well conserved, and ubiquitously expressed in all tissues. TDP-43 resides in the nucleus and sometimes shuttles between nucleus and cytoplasm. Mutations in TDP-43 leads to mislocalization of TDP-43 to the cytosol where it was ubiqutinated and hyperphosphsorylated, ultimately leading to neuronal cell …

Lineage-Specific Differences In The Gp120 Inner Domain Layer 3 Of Human And Simian Immunodeficiency Viruses, Shilei Ding, Halima Medjahed, Jérémie Prévost, Mathieu Coutu, Shi-Hua Xiang, Andrés Finzi

Nebraska Center for Virology: Faculty Publications

Binding of HIV-1 and SIV gp120 exterior envelope glycoprotein to CD4 triggers conformational changes in gp120 that promote its interaction with one of the chemokine receptors, usually CCR5, ultimately leading to gp41-mediated virus-cell membrane fusion and entry. We previously described that topological Layers (Layer 1, Layer 2 and Layer 3) in the gp120 inner domain contribute to gp120-trimer association in the unliganded state but also help secure CD4 binding. Relative to Layer 1 of HIV-1 gp120, the SIVmac239 gp120 Layer 1 plays a more prominent role in maintaining gp120-trimer association but is minimally involved in promoting CD4 binding, which could …

Disseminated Cryptococcosis With Endobronchial Lesions, Kusha Davar, Arun Jose, Anne Cramer, Alexander Aldrich, Jillian S. Catalanotti

Medicine Faculty Posters and Presentations

No abstract provided.

Aeromonas Hydrophila In Amphibians: Harmless Bystander Or Opportunistic Pathogen, Zachary P. Rivas

Honors Undergraduate Theses

For several decades amphibian populations have been declining. Historically, the bacterium A. hydrophila (Ah) was hypothesized to be the causal factor in amphibian disease and population declines. However, with the discovery of a chytrid fungus, Batrachochytrium dendrobatidis (Bd) in 1998, which was identified on the skin of amphibians during documented mortality events, Ah research became of minor interest as focus shifted to Bd. Recent studies into the immunocompromising abilities of Bd, however, have opened new questions about its relationship with Ah and their combined effects on a host.

In this study, I explore the …

Giant Chloroviruses: Five Easy Questions, James L. Van Etten, David Dunigan

Nebraska Center for Virology: Faculty Publications

Chloroviruses are large, icosahedral, dsDNA-containing viruses that replicate in certain unicellular, chlorella-like green algae [1,2]. They exist in freshwater throughout the world with titers as high as thousands of plaque-forming units (PFU) per ml of indigenous water although titers are typically 1–100 PFU/ml. Titers fluctuate during the year with the highest titers typically occurring in the spring and late fall. Known chlorovirus hosts, which are normally symbionts and are often referred to as zoochlorellae, are associated with either the protozoan Paramecium bursaria (Fig 1A), the coelenterate Hydra viridis, or the heliozoan Acanthocystis turfacea. Zoochlorellae are resistant to viruses …

Genetic Barrier To Direct Acting Antivirals In Hcv Sequences Deposited In The European Databank, Dimas Alexandre Kliemann, Cristiane Valle Tovo, Ana Beatriz Gorini Da Veiga, André Luiz Machado, John T. West

Nebraska Center for Virology: Faculty Publications

Background & Aims: Development of resistance results from mutations in the viral genome, and the presence of selective drug pressure leads to the emergence of a resistant virus population. The aim of this study was to analyze the impact of genetic variability on the genetic barrier to drug resistance to DAAs.

Methods: The genetic barrier was quantified based on the number and type of nucleotide mutations required to impart resistance, considering full-length HCV NS3, NS5A and NS5B regions segregated by genotype into subtypes 1a, 1b, 2a, 2b and 3a. This study analyzed 789 NS3 sequences, 708 sequences and 536 NS5B …

Kaposi’S Sarcoma-Associated Herpesvirus Reduces Cellular Myeloid Differentiation Primary-Response Gene 88 (Myd88) Expression Via Modulation Of Its Rna, Amy Lingel, Erica Ehlers, Qianli Wang, Mingxia Cao, Charles Wood, Rongtuan Lin, Luwen Zhang

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) is a human gammaherpesvirus associated with several human malignancies. The replication and transcription activator (RTA) is necessary and sufficient for the switch from KSHV latency to lytic replication. Interleukin 1 (IL-1) is a major mediator for inflammation and plays an important role in both innate and adaptive immunity. Myeloid differentiation primary response gene 88 (MyD88) is an essential adaptor molecule for IL-1 as well as most Toll-like receptor signaling. In this study, we identified a novel mechanism by which KSHV interferes with host inflammation and immunity. KSHV RTA specifically reduces the steady-state protein levels of …

Nf45 And Nf90 Bind Hiv-1 Rna And Modulate Hiv Gene Expression, Yan Li, Michael Belshan

Nebraska Center for Virology: Faculty Publications

A previous proteomic screen in our laboratory identified nuclear factor 45 (NF45) and nuclear factor 90 (NF90) as potential cellular factors involved in human immunodeficiency virus type 1 (HIV-1) replication. Both are RNA binding proteins that regulate gene expression; and NF90 has been shown to regulate the expression of cyclin T1 which is required for Tat-dependent trans-activation of viral gene expression. In this study the roles of NF45 and NF90 in HIV replication were investigated through overexpression studies. Ectopic expression of either factor potentiated HIV infection, gene expression, and virus production. Deletion of the RNA binding domains of NF45 …

Mucosal Vaccination By Adenoviruses Displaying Reovirus Sigma 1, Eric A. Weaver, Zenaido T. Camacho, Matthew L. Hillestad, Catherine M. Crosby, Mallory A. Turner, Adam J. Guenzel, Hind J. Fadel, George T. Mercier, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We previously developed adenovirus serotype 5 (Ad5) vectors displaying the sigma 1 protein from reovirus as mucosal vaccines. Ad5-sigma retargets to JAM-1 and sialic acid, but had 40-fold reduced gene delivery when compared to Ad5. While weaker at transduction, Ad5-sigma generated stronger T cell responses than Ad5 when used for mucosal immunization. New Ad5- fiber-sigma vectors were generated here by varying the number of fiber β-spiral shaft repeats (R) fused between fiber tail and the sigma. Ad5 virions encoding R3, R14, and R20 chimeras were rescued. Increasing chimera length led to their decreasing encapsidation of these proteins in the virions. …

Adeno-Associated Virus-Vegf-165 Mediated Modification Of Adipose Derived Stem Cells For Cell Therapy, Upasana Niyogi

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Chronic wounds have become a major clinical and economic burden in our society. New approaches that accelerate wound healing are desperately needed. Angiogenesis and vascularization play a critical role in healing. One of the essential angiogenic factors that promote the formation of vascular beds is vascular endothelial growth factor (VEGF). Moreover, adipose-derived stem cells (ASC), through their regeneration and differentiation properties, may promote healing when transplanted into a wound bed. I have proposed to develop a novel organotypic wound model to facilitate the study of wound healing process. I hypothesize that administration of genetically-modified ASC secreting VEGF via an adeno-associated …

Antibody-Mediated Immunity To Vibrio Cholerae At Epithelial Surfaces, Kara Jeanette Levinson

Legacy Theses & Dissertations (2009 - 2024)

Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, has an estimated worldwide disease burden in the millions and remains a significant public health threat. Immunity to V. cholerae is primarily antibody-mediated and though V. cholerae colonization evokes a mucosal immune response, it is the secretory IgA (SIgA) antibodies produced against bacterial surface antigens, specifically lipopolysaccharide (LPS) that confer protective immunity. SIgA antibodies are thought to function by inhibiting colonization by cross-linking and agglutination of pathogens, thereby limiting access to the epithelium, a process known as immune exclusion. Recent studies in other enteric pathogens have demonstrated that SIgA …

Recapitulating Cross-Species Transmission Of Sivcpz To Humans Using Humanized-Blt Mice, Zhe Yuan, Guobin Kang, Fangrui Ma, Wuxun Lu, Wenjin Fan, Christine M. Fennessey, Brandon F. Keele, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

The origins of HIV-1 have been widely accepted to be the consequence of simian immunodeficiency viruses from wild chimpanzees (SIVcpz) crossing over to humans. However, there has not been any in vivo study of SIVcpz infection of humans. Also, it remains largely unknown why only specific SIVcpz strains have achieved cross-species transmission and what transmission risk might exist for those SIVcpz strains that have not been found to infect humans. Closing this knowledge gap is essential for better understanding cross-species transmission and predicting the likelihood of additional cross-species transmissions of SIV into humans. Here we show hu-BLT mice are susceptible …

High Glucose Induces Reactivation Of Latent Kaposi’S Sarcoma-Associated Herpesvirus, Fengchun Ye, Yan Zeng, Jingfeng Sha, Tiffany Jones, Kurt Kuhne, Charles Wood, Shou-Jiang Gao

Nebraska Center for Virology: Faculty Publications

High prevalence of Kaposi’s sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological condition of diabetes contributes to KS development. We found elevated levels of viral lytic gene expression when Kaposi’s sarcoma-associated herpesvirus (KSHV) infected cells were cultured in high glucose medium. To demonstrate the association between high glucose and KSHV replication, we xeno29

grafted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high …

Persistent Low-Level Replication Of Sivδnef Drives Maturation Of Antibody And Cd8 T Cell Responses To Induce Protective Immunity Against Vaginal Siv Infection, Sama Adnan, R. Keith Reeves, Jacqueline Gillis, Fay E. Wong, Yi Yu, Jeremy V. Camp, Qingsheng Li, Michelle Connole, Yuan Li, Michael Piatak Jr., Jeffrey D. Lifson, Wenjun Li, Brandon F. Keele, Pamela A. Kozlowski, Ronald C. Desrosiers, Ashley T. Haase, R. Paul Johnson

Nebraska Center for Virology: Faculty Publications

Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef …

Flaviviruses As A Cause Of Undifferentiated Fever In Sindh Province, Pakistan: A Preliminary Report, Erum Khan, Joveria Q. Farooqi, Kelli L. Barr, Dhani Prakoso, Amna Nasir, Akbar Kanji, Sadia Shakoor, Faisal Riaz Malik, Rumina Hasan, John A. Lednicky

Department of Pathology and Laboratory Medicine

Arboviral diseases are expanding worldwide, yet global surveillance is often limited due to diplomatic and cultural barriers between nations. With human encroachment into new habitats, mosquito-borne viruses are also invading new areas. The actual prevalence of expanding arboviruses is unknown in Pakistan due to inappropriate diagnosis and poor testing for arboviral diseases. The primary objective of this study was to document evidence of flavivirus infections as the cause of undifferentiated fever in Pakistan. Through a cooperative effort between the USA and Pakistan, patient exposure to dengue virus (DENV), West Nile virus (WNV), and Japanese encephalitis virus (JEV) was examined in …

The Expression Of Aryl Hydrocarbon Receptor In Raw 264.7 Macrophages In The Presence Of Socs1 Peptide And Socs3 Peptide Mimetic And Cells Infected With Hsv-1, Maher Salem Alwethaynani

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Macrophages play a crucial role for our immune system and protect our body from infection. Suppressor of cytokine signaling (SOCS) proteins negatively regulate cytokine receptor and TLRs. The aryl hydrocarbon receptor (AhR) also performs an important role in immunity. This study investigated the changes in expression of AhR in RAW 264.7 macrophage cells after the addition of SOCS1 and SOCS3 peptide mimetics and also examined AhR expression in RAW 264.7 macrophage cells before and after the addition of HSV-1 RAW 264.7 murine macrophage cell lines which are from male BALB/c mice were used in this study. The addition of the …

The Expression Of Major Histocompatibility Class I And Major Histocompatibility Class Ii On Macrophages In The Presence Of Aryl Hydrocarbon Antagonist (Ch-223191), Caitlin Wilson

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Macrophages are crucial for ridding the body of debris and foreign cells. The aryl hydrocarbon receptor (AhR) also plays a critical role in immunity. This study examined the effect of the AhR on the expression of major histocompatiability complex class I (MHCI) and MHC class II (MHCII) in two murine macrophage cell lines. This study used Raw264.7 and J774A.1 murine macrophage cell lines. The Raw264.7 cells are from male BALB/c mice while the J774A.1 cells are from female BALB/cN mice. The addition of the AhR anatagonist CH-223191 (AhRa) showed that the AhR does not significantly impact MHCI expression. However, MHCII …

Molecular And Biochemical Signaling Underlying Arabidopsis-Bacterial/Virus/Fungal Interactions, Mohamed H. El-Shetehy

Theses and Dissertations--Plant Pathology

Systemic acquired resistance (SAR) is a form of inducible defense response triggered upon localized infection that confers broad-spectrum disease resistance against secondary infections. Several factors are known to regulate SAR and these include phenolic phytohormone salicylic acid (SA), phosphorylated sugar glycerol-3-phosphate (G3P), and dicarboxylic acid azelaic acid (AzA). This study evaluated a role for free radicals nitric oxide (NO) and reactive oxygen species (ROS) in SAR. Normal accumulation of both NO and ROS was required for normal SAR and mutations preventing NO/ROS accumulation and/or biosynthesis compromised SAR. A role for NO and ROS was further established using pharmacological approaches. Notably, …

Endosymbiotic Bacteria In The Bed Bug, Cimex Lectularius L. (Hemiptera: Cimicidae), Mark H. Goodman

Theses and Dissertations--Entomology

The return of bed bugs to prominence as an urban pest has precipitated an emphatic research response from the scientific community in an effort to better understand their biology and management. However, not all aspects of bed bug biology have received equal attention. The role of symbiotic bacteria in the normal function and biology of insects is often underappreciated, and this is true of bed bugs. Bed bugs have two main endosymbiotic bacteria, a Wolbachia species and a poorly-characterized gamma-proteobacterium referred to as BLS. However, their interactions with the host are poorly understood. I explored various aspects of these symbionts …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

Frequency And Etiology Of Community-Acquired Bloodstream Infection In Hospitalized Febrile Children, Tufail Soomro, Shiyam Sunder Tikmani, Sumera Aziz Ali

Community Health Sciences

Background: Blood stream infection is a serious problem that needs immediate attention and treatment. We aim to identify the frequency of common organisms in blood culture of febrile pediatric patients so that empirical antibiotic therapy can be started timely.
Methods: This cross-sectional study was conducted in pediatric ward Civil Hospital Sukkur from 1st May 2013 to 31st October 2014. Children of both genders who are between the age of one month to 15 years admitted to the pediatric ward with a fever of > 38.0 c and with a history of fever ˃ two days and whose blood culture has been …

Cell Viability, Cytoskeleton Organization And Cytokines Secretion Of Raw 264.7 Macrophages Exposed To Gram-Negative Bacterial Components, Ali Awadh Alshehri

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Macrophages play an important role in innate immunity by controlling cellular responses. In this study, the effects of gram-negative bacterial components (Flagellin, lipoprotein, lipopolysaccharides (LPS), outer membrane proteins-A (OMP-A) and peptidoglycan) were determined on cell viability, morphology, cytoskeletal filament and cytokines secretion of murine RAW 264.7 macrophages at 24 hours. The effect of LPS, flagellin and peptidoglycan from gram negative bacteria on viability murine RAW 264.7 macrophages were evaluated using different concentrations (1, 5 and 10 µg/ml). Cells stimulated with LPS displayed ~ 2-fold decrease (P=0.001) in cell viability compared to control cells at 24 hours whereas cells stimulated with …