Medicine and Health Sciences Commons^™

Intrinsically Disordered Proteins Play Diverse Roles In Cell Signaling, Sarah E. Bondos, A. Keith Dunker, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Signaling pathways allow cells to detect and respond to a wide variety of chemical (e.g. Ca2+ or chemokine proteins) and physical stimuli (e.g., sheer stress, light). Together, these pathways form an extensive communication network that regulates basic cell activities and coordinates the function of multiple cells or tissues. The process of cell signaling imposes many demands on the proteins that comprise these pathways, including the abilities to form active and inactive states, and to engage in multiple protein interactions. Furthermore, successful signaling often requires amplifying the signal, regulating or tuning the response to the signal, combining information sourced from multiple …

Would New Sars-Cov-2 Variants Change The War Against Covid-19?, Elrashdy M. Redwan, Fatma Elrashdy, Alaa A.A. Aljabali, Wagner Baetas-Da-Cruz, Debmalya Barh, Adam M. Brufsky, Sk. Sarif Hassan, Kenneth Lundstrom, Ángel Serrano-Aroca, Kazuo Takayama, Murtaza M. Tambuwala, Bruce D. Uhal, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The scientific, private, and industrial sectors use a wide variety of technological platforms available to achieve protection against SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), including vaccines. However, the virus evolves continually into new highly virulent variants, which might overcome the protection provided by vaccines and may re-expose the population to infections. Mass vaccinations should be continued in combination with more or less mandatory non-pharmaceutical interventions. Therefore, the key questions to be answered are: (i) How to identify the primary and secondary infections of SARS-CoV-2? (ii) Why are neutralizing antibodies not long-lasting in both cases of natural infections and post-vaccinations? …

Intrinsic Disorder In Bap1 And Its Association With Uveal Melanoma, Mak B. Djulbegovic, David J. Taylor, Vladimir N. Uversky, Anat Galor, Carol L. Shields, Carol L. Karp

Molecular Medicine Faculty Publications

Background: Specific subvariants of uveal melanoma (UM) are associated with increased rates of metastasis compared to other subvariants. BRCA1 (BReast CAncer gene 1)-associated protein-1 (BAP1) is encoded by a gene that has been linked to aggressive behavior in UM. Methods: We evaluated BAP1 for the presence of intrinsically disordered protein regions (IDPRs) and its protein–protein interactions (PPI). We evaluated specific sequence-based features of the BAP1 protein using a set of bioinformatic databases, predictors, and algorithms. Results: We show that BAP1’s structure contains extensive IDPRs as it is highly enriched in proline residues (the most disordered amino acid; p-value < 0.05), the average percent of predicted disordered residues (PPDR) was 57.34%, and contains 9 disorder-based binding sites (ie. molecular recognition features (MoRFs)). BAP1’s intrinsic disorder allows it to engage in a complex PPI network with at least 49 partners (p-value < 1.0 × 10−16). Conclusion: These findings show that BAP1 contains IDPRs and an intricate PPI network. Mutations in UM that are associated with the BAP1 gene may alter the function of the IDPRs embedded into its structure. These findings develop the understanding of UM and may provide a target for potential novel therapies to treat this aggressive neoplasm.

Limosilactobacillus Fermentum Strain 3872: Antibacterial And Immunoregulatory Properties And Synergy With Prebiotics Against Socially Significant Antibiotic-Resistant Infections Of Animals And Humans, Vyacheslav M. Abramov, Igor V. Kosarev, Andrey V. Machulin, Tatiana V. Priputnevich, Irina O. Chikileva, Eugenia I. Deryusheva, Tatiana N. Abashina, Almira D. Donetskova, Alexander N. Panin, Vyacheslav G. Melnikov, Natalia E. Suzina, Ilya N. Nikonov, Marina V. Selina, Valentin S. Khlebnikov, Vadim K. Sakulin, Raisa N. Vasilenko, Vladimir A. Samoilenko, Vladimir N. Uversky, Andrey V. Karlyshev

Molecular Medicine Faculty Publications

Limosilactobacillus fermentum strain 3872 (LF3872) was originally isolated from the breast milk of a healthy woman during lactation and the breastfeeding of a child. The high-quality genome sequencing of LF3872 was performed, and a gene encoding a unique bacteriocin was discovered. It was established that the bacteriocin produced by LF3872 (BLF3872) belongs to the family of cell-wall-degrading proteins that cause cell lysis. The antibacterial properties of LF3872 were studied using test cultures of antibiotic-resistant Gram-positive and Gram-negative pathogens. Gram-positive pathogens (Staphylococcus aureus strain 8325-4 and S. aureus strain IIE CI-SA 1246) were highly sensitive to the bacteriolytic action of LF3872. …

A Study On The Nature Of Sars-Cov-2 Using The Shell Disorder Models: Reproducibility, Evolution, Spread, And Attenuation, Gerard Kian-Meng Goh, A. Keith Dunker, James A. Foster, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The basic tenets of the shell disorder model (SDM) as applied to COVID-19 are that the harder outer shell of the virus shell (lower PID—percentage of intrinsic disorder—of the membrane protein M, PIDM) and higher flexibility of the inner shell (higher PID of the nucleocapsid protein N, PIDN) are correlated with the contagiousness and virulence, respectively. M protects the virion from the anti-microbial enzymes in the saliva and mucus. N disorder is associated with the rapid replication of the virus. SDM predictions are supported by two experimental observations. The first observation demonstrated lesser and greater presence of the Omicron particles …

Are The Functions Of Milk Exosomes Restricted To Their Protein Cargoes?, Elrashdy M. Redwan, Vladimir N. Uversky

Molecular Medicine Faculty Publications

No abstract provided.

The Aqueous Humor Proteome Is Intrinsically Disordered, Mak B. Djulbegovic, Vladimir N. Uversky

Molecular Medicine Faculty Publications

No abstract provided.

Bayesian Molecular Dating Analyses Combined With Mutational Profiling Suggest An Independent Origin And Evolution Of Sars-Cov-2 Omicron Ba.1 And Ba.2 Sub-Lineages, Naveen Kumar, Rahul Kaushik, Ashutosh Singh, Vladimir N. Uversky, Kam Y. J. Zhang, Upasana Sahu, Sandeep Bhatia, Aniket Sanyal

Molecular Medicine Faculty Publications

The ongoing evolution of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has resulted in the recent emergence of a highly divergent variant of concern (VOC) defined as Omicron or B.1.1.529. This VOC is of particular concern because it has the potential to evade most therapeutic antibodies and has undergone a sustained genetic evolution, resulting in the emergence of five distinct sub-lineages. However, the evolutionary dynamics of the initially identified Omicron BA.1 and BA.2 sub-lineages remain poorly understood. Herein, we combined Bayesian phylogenetic analysis, mutational profiling, and selection pressure analysis to track the virus’s genetic changes that drive the early evolutionary dynamics of …

Insights Into The Structural Properties Of Sars-Cov-2 Main Protease, Ibrahim Y. Akbaryak, Sule I. Caglayan, Lukasz Kurgan, Vladimir N. Uversky, Orkid Coskuner-Weber

Molecular Medicine Faculty Publications

SARS-CoV-2 is the infectious agent responsible for the coronavirus disease since 2019, which is the viral pneumonia pandemic worldwide. The structural knowledge on SARS-CoV-2 is rather limited. These limitations are also applicable to one of the most attractive drug targets of SARS-CoV-2 proteins – namely, main protease Mpro, also known as 3C-like protease (3CLpro). This protein is crucial for the processing of the viral polyproteins and plays crucial roles in interfering viral replication and transcription. In fact, although the crystal structure of this protein with an inhibitor was solved, Mpro conformational dynamics in aqueous solution is usually studied by molecular …

Bioinformatics-Based Characterization Of The Sequence Variability Of Zika Virus Polyprotein And Envelope Protein (E), Carlos Polanco, Vladimir N. Uversky, Alberto Huberman, Gilberto Vargas-Alarcón, Jorge Alberto Castañón González, Thomas Buhse, Enrique Hernández Lemus, Martha Rios Castro, Erika Jeannette López Oliva, Sergio Enrique Solís Nájera

Molecular Medicine Faculty Publications

Background: Zika virus, which is widely spread and infects humans through the bites of Aedes albopictus and Aedes aegypti female mosquitoes, represents a serious global health issue.

Objective: The objective of the present study is to computationally characterize Zika virus polyproteins (UniProt Name: PRO_0000443018 [residues 1-3423], PRO_0000445659 [residues 1-3423] and PRO_0000435828 [residues 1-3419]) and their envelope proteins using their physico-chemical properties.

Methods: To achieve this, the Polarity Index Method (PIM) profile and the Protein Intrinsic Disorder Predisposition (PIDP) profile of 3 main groups of proteins were evaluated: structural proteins extracted from specific Databases, Zika virus polyproteins, and their envelope proteins …

Fight Fire With Fire: The Need For A Vaccine Based On Intrinsic Disorder And Structural Flexibility, Vladimir N. Uversky

Molecular Medicine Faculty Publications

The absence of advancement in finding efficient vaccines for several human viruses, such as hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), and herpes simplex viruses (HSVs) despite 30, 40, and even 60 years of research, respectively, is unnerving. Among objective reasons for such failure are the highly glycosylated nature of proteins used as primary vaccine targets against these viruses and the presence of neotopes and cryptotopes, as well as high mutation rates of the RNA viruses HCV and HIV-1 and the capability to establish latency by HSVs. However, the lack of success in utilization of the structure-based …

Specific S100 Proteins Bind Tumor Necrosis Factor And Inhibit Its Activity, Alexey S. Kazakov, Marina Y. Zemskova, Gleb K. Rystsov, Alisa A. Vologzhannikova, Eugenia I. Deryusheva, Victoria A. Rastrygina, Andrey S. Sokolov, Maria E. Permyakova, Ekaterina A. Litus, Vladimir N. Uversky, Eugene A. Permyakov, Sergei E. Permyakov

Molecular Medicine Faculty Publications

Tumor necrosis factor (TNF) inhibitors (anti-TNFs) represent a cornerstone of the treatment of various immune-mediated inflammatory diseases and are among the most commercially successful therapeutic agents. Knowledge of TNF binding partners is critical for identification of the factors able to affect clinical efficacy of the anti-TNFs. Here, we report that among eighteen representatives of the multifunctional S100 protein family, only S100A11, S100A12 and S100A13 interact with the soluble form of TNF (sTNF) in vitro. The lowest equilibrium dissociation constants (Kd) for the complexes with monomeric sTNF determined using surface plasmon resonance spectroscopy range from 2 nM to 28 nM. The …

Mechanism Of Phase Separation In Aqueous Two-Phase Systems, Amber R. Titus, Pedro P. Madeira, Luisa A. Ferreira, Vladimir Y. Chernyak, Vladimir N. Uversky, Boris Y. Zaslavsky

Molecular Medicine Faculty Publications

Liquid-liquid phase separation underlies the formation of membrane-less organelles inside living cells. The mechanism of this process can be examined using simple aqueous mixtures of two or more solutes, which are able to phase separate at specific concentration thresholds. This work presents the first experimental evidence that mesoscopic changes precede visually detected macroscopic phase separation in aqueous mixtures of two polymers and a single polymer and salt. Dynamic light scattering (DLS) analysis indicates the formation of mesoscopic polymer agglomerates in these systems. These agglomerates increase in size with increasing polymer concentrations prior to visual phase separation. Such mesoscopic changes are …

Stress, Coping, And Disease Awareness With Metabolic Disease Risk: A Longitudinal Cohort Study, Chelsea Anestal

Honors Undergraduate Theses

College students undergo stressors (e.g., potential financial strain, changes in workload or location), which may precipitate metabolic syndrome (MetS) risk associated with obesity and high blood pressure. Concerning rises in young adult obesity and type 2 diabetes, prompt study into MetS risk factor prevalence and awareness in youthful populations transitioning to new environments, such as college. This study assessed perceived stress, coping resources, and disease awareness differences in the first time on campus and final-year students associated with MetS risk factors (elevated body mass index (BMI) and blood pressure). We hypothesized lower stress perception, lower weight gain and blood …

Covid-19 And Diabetes, Radhika Desai

Honors Undergraduate Theses

Patients with Type 2 Diabetes (T2D) have been found to have increased mortality and morbidity for COVID-19 and are at higher risk for severe disease once infected with COVID-19. Clearly, there exists a relationship between T2D and COVID-19 that requires more attention. In order to understand the mechanisms by which T2D contributes to more severe COVID-19 disease, attention was turned to extracellular vesicles (EVs). It was speculated that viral RNA components of the COVID-19 virus may have originated from circulating EVs that came from infected cells and use a Trojan Exosome method to infect host cells. It is necessary to …

Regenerating Agroecosystems By Overcoming Human Exceptionalism In Designing For Increased Equity Of Benefits From Ecoservices, Ali Loker, Charles A. Francis

Department of Agronomy and Horticulture: Faculty Publications

Our commentary explores three critical issues related to ecosystem services. First is how ecoservices are currently designed and implemented primarily for human benefit without concern for how these impact other species. We conclude that awareness of this imbalance is the first step toward meaningful change. Second we observe that human exceptionalism guides most decisions, and ask whether we can overcome this mind-set to embrace ecoregeneration and design of resilient and mutually beneficial agroecosystems. Our attitude toward the challenge and moving toward greater humility about human roles that guide management decisions in the ecosystem is a requisite for change. Third we …

Healing With Feeling: Addressing Substance Abuse In Teens During The Covid-19 Pandemic, Gisselle Amaya, Xunashy Lopez, Gabby Olumilua, Mbange Palle, Kendra Williams

DC Health and Academic Prep Program (DC HAPP)

In recent years, substance abuse among teenagers has steadily increased since the beginning of the Covid-19 pandemic in 2020. Teen substance abuse related deaths have only continued to rise since then; with nationwide substance abuse related deaths being 1,146 in 2021, a sharp increase from the 954 deaths in 2020 (UCLA health, 2022). Teen substance abuse is determined by many factors, such as mental health, home/school environment, etc. In order to cope with these difficult emotions, teenagers turn to drug use to numb the feeling. Studies have shown that art based therapy and afterschool programs are effective in mitigating the …

Suppressing Depression: Raising Awareness For Depression In Teens, David Whittington, Hiwot Ayalew, Kierra Jones, Oscar Colindres

DC Health and Academic Prep Program (DC HAPP)

About 13.3% of the U.S. population aged 12 to 17 has been diagnosed with at least one major depressive episode [1]. 14.3% of the DC population suffers from diagnosed depression [8]. It is important to note that most people with depression don’t seek clinical help. Many factors lead to depression among teens and adults including poverty, unemployment, lack of access to health care, and genetics. DC is one of the most segregated places in the U.S. Employment rates, wages, parks, and museums are deeply segregated resources within different wards. Wards 5, 7, and 8 have the highest rates of depression …

Adenoviral-Vectored Centralized Consensus Hemagglutinin Vaccine Provides Broad Protection Against H2 Influenza A Virus, Erika M. Petro-Turnquist, Brianna L. Bullard, Matthew J. Pekarek, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Several influenza pandemics have occurred in the past century, one of which emerged in 1957 from a zoonotic transmission of H2N2 from an avian reservoir into humans. This pandemic caused 2–4 million deaths and circulated until 1968. Since the disappearance of H2N2 from human populations, there has been waning immunity against H2, and this subtype is not currently incorporated into seasonal vaccines. However, H2 influenza remains a pandemic threat due to consistent circulation in avian reservoirs. Here, we describe a method of pandemic preparedness by creating an adenoviral-vectored centralized consensus vaccine design against human H2 influenza. We also assessed the …

The Application Of The Skin Virome For Human Identification, Ema H. Graham, Jennifer Clarke, Samodha Fernando, Joshua Herr, Michael Adamowicz

Nebraska Center for Virology: Faculty Publications

The use of skin virome offers a unique approach for human identification purposes in instances where a viable and statistically relevant human DNA profile is unavailable. The skin virome may act as an alternative DNA profile and/or an additional form of probative genetic material. To date, no study has attempted to investigate the human virome over a time series across various physical locations of the body to identify its diagnostic potential as a tool for human identification. For this study, we set out to evaluate the stability, diversity, and individualization of the human skin virome. An additional goal was to …

I’M Not A Tragedy: Speaking Up About Ableist Microaggressions, Kasandra Marguerite Colwell

Communication Senior Capstones

Have you heard of ableist microaggressions? Let me tell you about them, as someone who has experienced them. I have a bi-lateral dislocating knee condition that I was born with. I can walk, but sometimes I need additional stability or reduction of pain while getting around, in which case I tend to use a cane. I have had many othering interactions while using a mobility aid in public, whether that be a knee brace, a cane, or crutches. While it often seemed the stranger didn’t mean any harm, the question is how many invasive questions and comments from strangers can …

Incidence And Potential Co-Morbidities In Facial Pigmentary Demarcation Lines In Indian Populations, Lakkireddygari Sujana, Savitha L. Beergouder, Alekhya Rallapalli, Sujatha Alla, Prasanthi Chidipudi

Engineering Management & Systems Engineering Faculty Publications

Background: The most noticeable part of human body is face. The obvious boundaries on the skin known as Pigmentary Demarcation Lines (PDL) found over face and have clear borders of abrupt transition between more hyper-pigmented skin and areas of normal skin pigmentation due to differences in melanocyte distribution that may be influenced by multiple factors. Facial pigmentary demarcation lines (PDL) directly reflect on patient’s physical appearance and self-image as they may contribute to dysmorphism and even central to depressive illness in susceptible individuals posing cosmetic concern for the patient and a challenge for dermatologist. Therefore, it is important for early …

Effectiveness Of Stricter Vaccine Mandates In Public Schools And Childcare Centers, Anna Ferentinos

Emerging Writers

Vaccines have been a controversial and frequently discussed topic the last two years due to the COVID-19 pandemic. The amount of readily available information on the internet - accurate or not – has led to many theories and opinions on whether to vaccinate and why, or why not. This article discusses these theories, as well as the benefits and consequences of vaccine mandates, with the help of examples from other countries. The author argues that a federal vaccine mandate should be implemented in the United States of America so as to encourage parents to protect children through scheduled immunizations.

The Effectiveness Of An Aprn-Led Pain Service On Patient Satisfaction Scores: A Retrospective Analysis, Maripatricia Welz-Bosna

West Chester University Doctoral Projects

Abstract

This quality improvement (QI) project examined if the implementation of an Advanced Practice Registered Nurse (APRN) led consult pain service, was able to improve patient satisfaction measured on the HCAHPS and Press Ganey pain satisfaction scores. A one-way ANOVA analysis was used to examine if mean outcome scores varied at a statistically significant level (p<.05) by year (2018, 2019, 2020). Bonferroni Post Hoc tests reflecting How Often Staff Talk About Pain by year using the dependent variable Top Box Score, indicated that the mean score for year 2020 (M=74.10, SD=17.45) was significantly higher than year 2018 (M=63.22). The mean score for year 2019 (M=64.62, SD=22.80) did not differ significantly from the other two years. Bivariate analysis indicated that Press Ganey Scores reflecting Staff Talk About Pain Treatment did not vary significantly by year, F(2, 445) = .41, p=.66. Results from this QI project and the effectiveness of an APRN-led pain service on patient satisfaction scores are inconclusive, and further research is needed. Pain is complex, and a patient's satisfaction with pain is never straightforward. The effectiveness of an APRN-led pain service on patient satisfaction remains under-researched and in need of more methodological evaluation. APRNs need to focus on multidimensional validated outcome measures, which can measure our effectiveness in the management of patients with pain.

Keywords: Patient Satisfaction, Pain, HCAHPS, Advanced Practice Registered Nurse (APRN), Effectiveness

Hypothermic Patient Warming In A Pediatric Emergency Department, Daniel Bileth

West Chester University Doctoral Projects

Hypothermia has been associated with increased morbidity and mortality in adults and increased mortality in children. Unplanned hypothermia increases adverse outcomes in patients, including increased blood loss, increased risk for blood transfusion, decreased oxygenation to major organs, and decreased immune response (Beedle et al., 2017; Brozanski et al., 2020; Erdoğan et al., 2019; Granum et al., 2019). Collaboration with Emergency Department (ED) physician leadership, clinical educators, and trauma leadership determined the need for a formal warming procedure. The purpose of this project was to implement a clinical warming algorithm for pediatric patients within the ED who had a temperature of …

Can It Heal And Hurt?: Survivors Of Sexual Assault Share The Benefits And Challenges Of Sexual Assault Support Group Participation, Brittni Gettys

West Chester University Doctoral Projects

Research exploring the relationships among trauma survivors is largely non-existent. This study aimed to explore the effects of relationships among individuals with a shared experience of sexual trauma within the group therapeutic context of sexual assault support groups. This study sought to examine the potential buffering and supportive effects of social support between sexual assault survivors, while also exploring the potential negative effects of shared trauma that may occur from the potentially triggering nature of seeking support from other sexual assault survivors. These complex dynamics were explored through examining the relationships and experiences of sexual assault survivors who have attended …

The Impact Of The Mandatory Phab Accreditation Process On Environmental Health Programs At Local Health Districts In Ohio, Wesley Vins

West Chester University Doctoral Projects

Ohio has 112 local health districts and in 2013 these health districts were mandated by state law to achieve national accreditation by July of 2020 from the Public Health Accreditation Board (PHAB) that was established in 2011. To understand the impact on local health districts of the state policy approach, thirteen question paper surveys were mailed to the Environmental Health Directors at all Ohio health districts in May of 2022 and the results were analyzed.

A survey response rate of 54.5% was achieved and the Directors reported that on average they experienced 76-100 annual hours due to accreditation, as did …

Clinical Cell Therapy Guidelines For Neurorestoration (Ianr/Canr 2017), Hongyun Huang, Wise Young, Lin Chen, Shiqing Feng, Ziad M. Zoubi, Hari Shanker Sharma, Hooshang Saberi, Gustavo A. Moviglia, Xijing He, Dafin F. Muresanu, Alok Sharma, Ali Otom, Russell J. Andrews, Adeeb Al-Zoubi, Andrey S. Bryukhovetskiy, Elena R. Chernykh, Krystyna Domańska-Janik, Emad Jafar, W. Eustace Johnson, Ying Li, Daqing Li, Zuo Luan, Gengsheng Mao, Ashok K. Shetty, Dario Siniscalco, Stephen Skaper, Tiansheng Sun, Yunliang Wang, Lars Wiklund, Qun Xue, Si-Wei You, Zuncheng Zheng, Milan R. Dimitrijevic, W. S. Masri, Paul R. Sanberg

Neurosurgery and Brain Repair Faculty Publications

Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version “Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)”. The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and …

The Prevalence Of Substance Abuse Within The Nursing Profession, Kaylie Paige Cox

Senior Honors Theses and Projects

No abstract provided.

Variability In Antimicrobial Properties Of Multifloral Honey In Southwestern Virginia, Isabella Jessee

Undergraduate Honors Theses

The antimicrobial properties of multifloral honey have been utilized for centuries in wound healing, as well as for infection treatment and prevention. The chemical properties from the nectar source, enzymes produced by the bee, as well as the digestive activity of the microorganisms in the bee gut all contribute to the antimicrobial activity of honey. Honeybee (Apis mellifera, the western or European Honeybee) farms in four locations across southwestern Virginia (Fincastle, Covington, Troutville, and Martinsville) were visited in the fall of 2021 to collect honey (fall and spring), worker bees, and pollen pellets. Disk diffusion assays were used …