Medicine and Health Sciences Commons^™

Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: Ii. Unfolding Of The Monomeric Forms, Olga V. Stepanenko, Denis O. Roginski, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

In a family of monomeric odorant-binding proteins (OBPs), bovine OBP (bOBP), that lacks conserved disulfide bond found in other OBPs, occupies unique niche because of its ability to form domain-swapped dimers. In this study, we analyzed conformational stabilities of the recombinant bOBP and its monomeric variants, the bOBP-Gly121+ mutant containing an additional glycine residue after the residue 121 of the bOBP, and the GCC-bOBP mutant obtained from the bOBP-Gly121+ form by introduction of the Trp64Cys/His155Cys double mutation to restore the canonical disulfide bond. We also analyzed the effect of the natural ligand binding on the conformational stabilities of these bOBP …

Yersinia Pestis Caf1 Protein: Effect Of Sequence Polymorphism On Intrinsic Disorder Propensity, Serological Cross-Reactivity And Cross-Protectivity Of Isoforms, Pavel Kh. Kopylov, Mikhail E. Platonov, Vitaly G. Ablamunits, Tat’Yana I. Kombarova, Sergey A. Ivanov, Lidiya A. Kadnikova, Aleksey N. Somov, Svetlana V. Dentovskaya, Vladimir N. Uversky, Andrey P. Anisimov

Molecular Medicine Faculty Publications

Yersinia pestis Caf1 is a multifunctional protein responsible for antiphagocytic activity and is a key protective antigen. It is generally conserved between globally distributed Y. pestis strains, but Y. pestis subsp. microtus biovar caucasica strains circulating within populations of common voles in Georgia and Armenia were reported to carry a single substitution of alanine to serine. We investigated polymorphism of the Caf1 sequences among other Y. pestis subsp. microtus strains, which have a limited virulence in guinea pigs and in humans. Sequencing of caf1 genes from 119 Y. pestis strains belonging to different biovars within subsp. microtus showed that the …

Intrinsically Disordered Side Of The Zika Virus Proteome, Rajanish Giri, Deepak Kumar, Nitin Sharma, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Over the last few decades, concepts of protein intrinsic disorder have been implicated in different biological processes. Recent studies have suggested that intrinsically disordered proteins (IDPs) provide structural plasticity and functional diversity to viral proteins that are involved in rapid replication and immune evasion in host cells. In case of Zika virus, the roles of protein intrinsic disorder in mechanisms of pathogenesis are not completely understood. In this study, we have analyzed the prevalence of intrinsic disorder in Zika virus proteome (strain MR 766). Our analyses revealed that Zika virus polyprotein is enriched with intrinsically disordered protein regions (IDPRs) and …

Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: Ii. Unfolding Of The Monomeric Forms, Olga V. Stepanenko, Denis O. Roginskii, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

In a family of monomeric odorant-binding proteins (OBPs), bovine OBP (bOBP), that lacks conserved disulfide bond found in other OBPs, occupies unique niche because of its ability to form domain-swapped dimers. In this study, we analyzed conformational stabilities of the recombinant bOBP and its monomeric variants, the bOBP-Gly121+ mutant containing an additional glycine residue after the residue 121 of the bOBP, and the GCC-bOBP mutant obtained from the bOBP-Gly121+ form by introduction of the Trp64Cys/His155Cys double mutation to restore the canonical disulfide bond. We also analyzed the effect of the natural ligand binding on the conformational stabilities of these bOBP …

Compartmentalization And Functionality Of Nuclear Disorder: Intrinsic Disorder And Protein-Protein Interactions In Intra-Nuclear Compartments, Fanchi Meng, Insung Na, Lukasz Kurgan, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The cell nucleus contains a number of membrane-less organelles or intra-nuclear compartments. These compartments are dynamic structures representing liquid-droplet phases which are only slightly denser than the bulk intra-nuclear fluid. They possess different functions, have diverse morphologies, and are typically composed of RNA (or, in some cases, DNA) and proteins. We analyzed 3005 mouse proteins localized in specific intra-nuclear organelles, such as nucleolus, chromatin, Cajal bodies, nuclear speckles, promyelocytic leukemia (PML) nuclear bodies, nuclear lamina, nuclear pores, and perinuclear compartment and compared them with ~29,863 non-nuclear proteins from mouse proteome. Our analysis revealed that intrinsic disorder is enriched in the …

Looking At The Carcinogenicity Of Human Insulin Analogues Via The Intrinsic Disorder Prism, Elrashdy M. Redwan, Moustafa H. Linjawi, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Therapeutic insulin, in its native and biosynthetic forms as well as several currently available insulin analogues, continues to be the protein of most interest to researchers. From the time of its discovery to the development of modern insulin analogues, this important therapeutic protein has passed through several stages and product generations. Beside the well-known link between diabetes and cancer risk, the currently used therapeutic insulin analogues raised serious concerns due to their potential roles in cancer initiation and/or progression. It is possible that structural variations in some of the insulin analogues are responsible for the appearance of new oncogenic species …

Dancing Protein Clouds: The Strange Biology And Chaotic Physics Of Intrinsically Disordered Proteins, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Biologically active but floppy proteins represent a new reality of modern protein science. These intrinsically disordered proteins (IDPs) and hybrid proteins containing ordered and intrinsically disordered protein regions (IDPRs) constitute a noticeable part of any given proteome. Functionally, they complement ordered proteins, and their conformational flexibility and structural plasticity allow them to perform impossible tricks and be engaged in biological activities that are inaccessible to well folded proteins with their unique structures. The major goals of this minireview are to show that, despite their simplified amino acid sequences, IDPs/IDPRs are complex entities often resembling chaotic systems, are structurally and functionally …

Order, Disorder, And Everything In Between, Shelly Deforte, Vladimir N. Uversky

Molecular Medicine Faculty Publications

In addition to the “traditional” proteins characterized by the unique crystal-like structures needed for unique functions, it is increasingly recognized that many proteins or protein regions (collectively known as intrinsically disordered proteins (IDPs) and intrinsically disordered protein regions (IDPRs)), being biologically active, do not have a specific 3D-structure in their unbound states under physiological conditions. There are also subtler categories of disorder, such as conditional (or dormant) disorder and partial disorder. Both the ability of a protein/region to fold into a well-ordered functional unit or to stay intrinsically disordered but functional are encoded in the amino acid sequence. Structurally, IDPs/IDPRs …

Expression, Purification, And Characterization Of Interleukin-11 Orthologues, Andrei S. Sokolov, Alexei S. Kazakov, Valery V. Solovyev, Ramis G. Ismailov, Vladimir N. Uversky, Yulia S. Lapteva, Roman V. Mikhailov, Ekaterina V. Pavlova, Iana O. Terletskaya, Ludmila V. Ermolina, Sergei E. Permyakov, Eugene A. Permyakov, Eugene A. Permyakov

Molecular Medicine Faculty Publications

Interleukin-11 (IL-11) is a multifunctional cytokine implicated in several normal and pathological processes. The decoding of IL-11 function and development of IL-11-targeted drugs dictate the use of laboratory animals and need of the better understanding of species specificity of IL-11 signaling. Here, we present a method for the recombinant interleukin-11 (rIL-11) production from the important model animals, mouse and macaque. The purified mouse and macaque rIL-11 interact with extracellular domain of human IL-11 receptor subunit α and activate STAT3 signaling in HEK293 cells co-expressing human IL-11 receptors with efficacies resembling those of human rIL-11. Hence, the evolutionary divergence does not …

Rnd3 As A Novel Target To Ameliorate Microvascular Leakage, Jerome W. Breslin, Dayle A. Daines, Travis M. Doggett, Kristine H. Kurtz, Flavia M. Souza-Smith, Xun E. Zhang, Mack H. Wu, Sarah Y. Yuan

Molecular Pharmacology & Physiology Faculty Publications

Background: Microvascular leakage of plasma proteins is a hallmark of inflammation that leads to tissue dysfunction. There are no current therapeutic strategies to reduce microvascular permeability. The purpose of this study was to identify the role of Rnd3, an atypical Rho family GTPase, in the control of endothelial barrier integrity. The potential therapeutic benefit of Rnd3 protein delivery to ameliorate microvascular leakage was also investigated.

Methods and Results: Using immunofluorescence microscopy, Rnd3 was observed primarily in cytoplasmic areas around the nuclei of human umbilical vein endothelial cells. Permeability to fluorescein isothiocyanate–albumin and transendothelial electrical resistance of human umbilical vein endothelial …

Randomized, Placebo-Controlled Trial Evaluating The Safety Of One-Year Administration Of Green Tea Catechins, Nagi B. Kumar, Julio Pow-Sang, Philippe E. Spiess, Jong Park, Raoul Salup, Christopher R. Williams, Howard Parnes, Michael J. Schell

Urology Faculty Publications

Purpose: Although preclinical, epidemiological and prior clinical trial data suggest that green tea catechins (GTCs) may reduce prostate cancer (PCa) risk, several preclinical studies and case reports have reported liver toxicities and acute gastrointestinal bleeding. Based on these observations, regulatory bodies have required stringent inclusion criteria with frequent, excessive toxicity monitoring and early stopping rules in clinical trials. These requirements have impeded recruitment and retention of subjects in chemoprevention trials and subsequent progress in agent development efforts.

Experimental Design: We conducted a placebo-controlled, randomized clinical trial of Polyphenon E® (PolyE®), a proprietary mixture of decaffeinated GTCs, containing 400 mg (−)-epigallocatechin-3-gallate …

Nutrition Resources For Football Players In Division I Institutions: The Athletic Trainer's Perspective And Role, Giovanna Marie Giannini

Honors Undergraduate Theses

Background: The importance of nutrition on athletic performance is evident. Athletic trainers (ATs), nutritionists/RDs, strength and conditioning specialists (SCSs), and other athletic department personnel may be available to student-athletes and can be solicited for nutrition advice. Multiple studies have found that although some universities have a sports nutritionist on staff, student-athletes approached an AT most often for nutrition advice rather than an SCS, nutritionist or other person. ATs have the necessary education to provide proper nutrition information to student-athletes; however, it is not the primary role of an AT.

Objective: The purpose of this study was to examine the quantity, …

Therapy Options For Winged Scapula Patients: A Literature Review, Samantha L. Normand

Honors Undergraduate Theses

Winged scapula is a condition characterized by lateral or medial protrusion of the scapula caused by nerve damage leading to muscular paralysis. The purpose of this systematic review of literature is to evaluate the current research literature related to the effectiveness of therapy options for winged scapula. Eleven peer reviewed English language research articles published from 1998 to present were included for evaluation. Study results revealed positive therapeutic outcomes for physical therapy and scapular bracing. Results also showed positive outcomes for the use of transcutaneous electrical nerve stimulation and acupuncture for the treatment of nerve related conditions similar to winged …

The Integration Of Mobile Technology To Lower The Risk Of Developing Cervical Cancer In Hiv Positive Women, Tugce Kinik

Dissertations, Master's Theses and Master's Reports

Cervical cancer is the most common cancer in HIV positive women in the world [1]. According to epidemiologists, HPV infection alone will not initiate cervical cancer [2]. In addition to high risk HPV types, smoking, long term hormonal contraceptive use, high parity, HIV/AIDS infection, sexual activity before 20 years of age, multiple sexual partners, exposure to sexually transmitted disease, and family history of cervical cancer are other reasons to turn an HPV infection to the cervical cancer [3]. With the increasing global population, cervical cancer cases are expected to increase 46% until 2030 [4]. Effective prevention and control efforts will …

Does Shifting Gender Norms On The Community Level Lead To Increased Hiv Services Uptake?, Project Soar

HIV and AIDS

Project SOAR and partners are building on an ongoing National Institute of Mental Health–funded randomized controlled trial being conducted in South Africa—Community Mobilization for Treatment as Prevention. Specifically, the study aims to strengthen and expand the gender content of the intervention to engage both women and men in critically examining gender norms and power inequalities. This brief presents the particularly timely study that will address a key question in the field as to how gender norms may operate to affect HIV service utilization. Building the evidence base in this area is vital for improving care outcomes as well as creating …

Estimating The Costs Of Providing Voluntary Medical Male Circumcision In South Africa, Project Soar

HIV and AIDS

The South African government introduced voluntary medical male circumcision (VMMC) as an HIV-prevention intervention in 2010, based on the compelling evidence that VMMC reduces men’s risk of becoming HIV infected by approximately 60 percent. To inform strategic planning for continued scale-up of its VMMC program and better understand cost drivers and cost variances across provinces, the South African National Department of Health in 2014 requested estimates of the unit cost of VMMC and the level of current spending for VMMC demand creation. The results of this study provide a comprehensive analysis of the unit cost of providing VMMC in South …

Caring Minds, University Of Texas Health Science Center At Houston School Of Nursing

Caring Minds

No abstract provided.

2015 6a Minnesota State High School Prep Bowl, Joe Steinert

Master of Arts in Sport Management

The Minnesota State High School League (MSHSL) is in charge of all high school athletics in the state of Minnesota. The MSHSL is in charge of putting on tournaments and championship games for all high school sports. This paper focuses on the 2015 high school football championship game for section 6A. Within this paper are seven chapters about the MSHSL and the 6A championship game called the Prep Bowl. The seven chapters are history of the MSHSL, introduction to the 2015 Prep Bowl game, a marketing plan around the 6A Prep Bowl game, proper ways to retain high end coaches, …

Ncaa Men's Ice Hockey Championship, Lindsay A. Currie

Master of Arts in Sport Management

This emphasis of this capstone is the NCAA Men's Division I Frozen Four ice hockey championship tournament. For the sake of this paper, aside from the risk management plan in chapter five, the paper's concentration is the 2015 Frozen Four in Boston, Massachusetts. This paper focuses on all areas of executing a National Collegiate Athletic Association Championship event. The areas are organized into chapters relating to overall sport management. Chapter One focuses on the NCAA as an organization and the event history. Chapter Two discusses the Frozen Four as an event and discusses the financial figures related to hosting the …

The Division I Ncaa Wrestling Championships, Ryan Degeeter

Master of Arts in Sport Management

The effects of the International Olympic Committee's decision to remove wrestling from the Olympic rotation are undeniable. In addition to exposing the then fragile state of wrestling, on a worldwide level, the "coming together" and rebuilding has led to many new positive changes as well as possibilities for more changes at the collegiate level, NCAA, in the United States. The NCAA, and NCAA wrestling in particular, is very adept to change and so a change of this stature would not be unheard of. The NCAA Division I Individual Wrestling Championships is already quite successful and this capstone looks into the …

The Little League World Series, Richard W. White

Master of Arts in Sport Management

This is a comprehensive study assessing Little League Baseball and the Little League World Series. Founded in 1939, Little League Baseball has become the world's largest organized youth sports program. In the span of 60 years, Little League Baseball has grown from three teams to nearly 200,000 teams, covering all 50 U.S. states and more than 80 countries. Despite being a non-profit organization, Little League Baseball must still place a high priority on generating revenue. The more revenue Little League Baseball can produce, the more affordable they can make programs to participants. Keeping these program costs low will aid in …

Ymca Healthy Kids Day, Leanna L. Curry-Larson

Master of Arts in Sport Management

An organizational event has the objective of emphasizing company directives and consumer needs. A clear vision of company objectives gives relevance to the event while consumer needs defines the purpose. This paper examined the detailed components needed by the Young Men's Christian Association (YMCA) to host the annual free Healthy Kids Day (HKD) event. Healthy Kids Day is a promotional tool for YMCA wellness programs. The one-day event's purpose is to create awareness for community members regarding the predisposed health risks and then offer viable and affordable solutions. Community participation can be hindered by costs associated with the event. Eliminating …

2017 Nhl Winter Classic, Melissa A. Dalum

Master of Arts in Sport Management

This thesis paper examined one of the National Hockey League's (NHL) premier events, the Winter Classic, in preparation of their 2017 game. In an effort to set guidelines and objectives in pursuit of growing the NHL brand, this comprehensive report reviewed the detailed positioning of this product extension through the marketing of nostalgic memories of early hockey traditions. Taking place in Minneapolis, MN, the Winter Classic is a regular season hockey game played in an open-air stadium on New Year's Day. The uniqueness of this event is developed herein through an examination of the marketing mix to help define its …

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. …

A Lost Tribe In The City: Health Status And Needs Of African Asylum Seekers And Refugees In Hong Kong, William Chi Wai Wong, Sealing Cheng, Eleanor Holroyd, Julie Chen, Kelley Ann Loper, Lynn Tran, Heidi Yin Hai Miu

School of Nursing & Midwifery, East Africa

Background: Hong Kong’s resistance to be a signatory of the 1951 Geneva Convention and lack of domestic policies in this area has resulted in restrictions on access to healthcare amongst asylum seekers and refugees (ASRs). Using social determinants of health framework this study sought to identify health practices, problems and needs of African ASRs in Hong Kong.

Methods: A cross-sectional survey comprising of six domains including health status, health-seeking behaviour and social experience targeted at adult African ASRs in Hong Kong was conducted through three local non-governmental organisations between February and April 2013. Outpatient care and inpatient care in the …

Cutaneous Human Papillomavirus Infection And Development Of Subsequent Squamous Cell Carcinoma Of The Skin, Shalaka S. Hampras, Rhianna A. Reed, Spencer Bezalel, Michael Cameron, Basil Cherpelis, Neil Fenske, Vernon K. Sondak, Jane Messina, Massimo Tommasino, Tarik Gheit, Dana E. Rollison

Pathology and Cell Biology Faculty Publications

The role of cutaneous human papillomavirus (HPV) infection in the development of subsequent cutaneous squamous cell carcinoma (SCC) is unknown. Pathologically confirmed cases of SCC () enrolled in a previously conducted case-control study were included in a retrospective cohort study to examine the association of cutaneous HPV at the time of SCC diagnosis with the risk of subsequent SCC development. Data on HPV seropositivity, HPV DNA in eyebrow hairs (EB) and SCC tumors were available from the parent study. Incidence of subsequent SCC was estimated using person-years of follow up. Cox Proportional Hazards ratios were estimated to evaluate the associations …