Medicine and Health Sciences Commons^™

The Signal Peptide Of The Amyloid Precursor Protein Forms Amyloid-Like Aggregates And Enhances Aβ42 Aggregation, Kundlik Gadhave, Taniya Bhardwaj, Vladimir N. Uversky, Michele Vendruscolo, Rajanish Giri

Molecular Medicine Faculty Publications

Signal sequences are short peptides at the N terminus of proteins destined for the secretion pathway. Typically, after cleavage by peptidases, signal peptides are degraded by intra-membrane proteases. In some cases, however, signal peptides can be processed further and released into the endoplasmic reticulum, secretion pathways, or cytoplasm. The consequences of these processes remain unclear, in particular considering that dysregulated signal peptides could potentially aggregate and induce cytotoxicity. To investigate this problem, we study the signal peptide of the amyloid precursor protein (APP), which originates the Alzheimer’s β-amyloid (Aβ) peptide. Our results show that this signal peptide (residues 1–17 of …

Evolutionary Signatures Governing The Codon Usage Bias In Coronaviruses And Their Implications For Viruses Infecting Various Bat Species, Naveen Kumar, Rahul Kaushik, Chandana Tennakoon, Vladimir N. Uversky, Anamika Mishra, Richa Sood, Pratiksha Srivastava, Meghna Tripathi, Kam Y. J. Zhang, Sandeep Bhatia

Molecular Medicine Faculty Publications

Many viruses that cause serious diseases in humans and animals, including the betacoronaviruses (beta-CoVs), such as SARS-CoV, MERS-CoV, and the recently identified SARS-CoV-2, have natural reservoirs in bats. Because these viruses rely entirely on the host cellular machinery for survival, their evolution is likely to be guided by the link between the codon usage of the virus and that of its host. As a result, specific cellular microenvironments of the diverse hosts and/or host tissues imprint peculiar molecular signatures in virus genomes. Our study is aimed at deciphering some of these signatures. Using a variety of genetic methods we demonstrated …

Isolation And Characterization Of Human Colon Adenocarcinoma Stem-Like Cells Based On The Endogenous Expression Of The Stem Markers, Sergei A. Koshkin, Olga V. Anatskaya, Alexander E. Vinogradov, Vladimir N. Uversky, Guy W. Dayhoff Ii, Margarita A. Bystriakova, Valery A. Pospelov, Elena N. Tolkunova

Molecular Medicine Faculty Publications

Background: Cancer stem cells’ (CSCs) self-maintenance is regulated via the pluripotency pathways promoting the most aggressive tumor phenotype. This study aimed to use the activity of these pathways for the CSCs’ subpopulation enrichment and separating cells characterized by the OCT4 and SOX2 expression. Methods: To select and analyze CSCs, we used the SORE6x lentiviral reporter plasmid for viral transduction of colon adenocarcinoma cells. Additionally, we assessed cell chemoresistance, clonogenic, invasive and migratory activity and the data of mRNA-seq and intrinsic disorder predisposition protein analysis (IDPPA). Results: We obtained the line of CSC-like cells selected on the basis of the expression …

Structural Modeling Of The Treponema Pallidum Outer Membrane Protein Repertoire: A Road Map For Deconvolution Of Syphilis Pathogenesis And Development Of A Syphilis Vaccine, Kelly L. Hawley, Jairo M. Montezuma-Rusca, Kristina N. Delgado, Navreeta Singh, Vladimir N. Uversky, Melissa J. Caimano, Justin D. Radolf, Amit Luthra

Molecular Medicine Faculty Publications

Treponema pallidum, an obligate human pathogen, has an outer membrane (OM) whose physical properties, ultrastructure, and composition differ markedly from those of phylogenetically distant Gram-negative bacteria. We developed structural models for the outer membrane protein (OMP) repertoire (OMPeome) of T. pallidum Nichols using solved Gram-negative structures, computational tools, and small-angle X-ray scattering (SAXS) of selected recombinant periplasmic domains. The T. pallidum “OMPeome” harbors two “stand-alone” proteins (BamA and LptD) involved in OM biogenesis and four paralogous families involved in the influx/efflux of small molecules: 8-stranded β-barrels, long-chain-fatty-acid transporters (FadLs), OM factors (OMFs) for efflux pumps, and T. pallidum repeat proteins …

Multilevel Factors Associated With Length Of Stay For Neonatal Abstinence Syndrome In Florida’S Nicus: 2010–2015, Chinyere N. Reid, Tara R. Foti, Alfred K. Mbah, Mark L. Hudak, Maya Balakrishnan, Russell S. Kirby, Roneé E. Wilson, William M. Sappenfield

College of Public Health Faculty Publications

To investigate potential factors influencing initial length of hospital stay (LOS) for infants with neonatal abstinence syndrome (NAS) in Florida. The study population included 2984 term, singleton live births in 33 Florida hospitals. We used hierarchical linear modeling to evaluate the association of community, hospital, and individual factors with LOS. The average LOS of infants diagnosed with NAS varied significantly across hospitals. Individual-level factors associated with increased LOS for NAS included event year (P < 0.001), gestational age at birth (P < 0.001), maternal age (P = 0.002), maternal race and ethnicity (P < 0.001), maternal education (P = 0.032), and prenatal care adequacy (P < 0.001). Average annual hospital NAS volume (P = 0.022) was a significant hospital factor. NAS varies widely across hospitals in Florida. In addition to focusing on treatment regimens, to reduce LOS, public health and quality improvement initiatives should identify and adopt strategies that can minimize the prevalence and impact of these contributing factors.

Nutrition Risk And Validation Of An Hiv Disease-Specific Nutrition Screening Tool In Ghana, Lauri Wright, Maxwell Bisala Konlan, Laurene Boateng, James B. Epps

Mental Health Law & Policy Faculty Publications

Objectives: The objectives of this study were to assess the nutritional status and the most commonly reported nutrition-related factors contributing to nutritional risk in people living with HIV/AIDS (PLWHA) in Ghana and the specificity and sensitivity of the Rapid Nutrition Screening for HIV disease tool (RNS-H) in this population.

Design: A cross-sectional design was utilised. Patients were screened for nutritional status during a one-week period by clinic nurses using the RNS-H. Results were compared with a comprehensive nutritional assessment by a dietitian.

Setting: The research was conducted in a public health clinic at the University of Ghana Hospital, Legon.

Subjects: …

Possible Transmission Flow Of Sars-Cov-2 Based On Ace2 Features, Sk Sarif Hassan, Shinjini Ghosh, Diksha Attrish, Pabitra Pal Choudhury, Alaa A A Aljabali, Bruce D Uhal, Kenneth Lundstrom, Nima Rezaei, Vladimir N Uversky, Murat Seyran, Damiano Pizzol, Parise Adadi, Antonio Soares, Tarek Mohamed Abd El-Aziz, Ramesh Kandimalla, Murtaza M Tambuwala, Gajendra Kumar Azad, Samendra P Sherchan, Wagner Baetas-Da-Cruz, Kazuo Takayama, Ángel Serrano-Aroca, Gaurav Chauhan, Giorgio Palu, Adam M Brufsky

All publications

Angiotensin-converting enzyme 2 (ACE2) is the cellular receptor for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that is engendering the severe coronavirus disease 2019 (COVID-19) pandemic. The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 binds to the three sub-domains viz. amino acids (aa) 22-42, aa 79-84, and aa 330-393 of ACE2 on human cells to initiate entry. It was reported earlier that the receptor utilization capacity of ACE2 proteins from different species, such as cats, chimpanzees, dogs, and cattle, are different. A comprehensive analysis of ACE2 receptors of nineteen species was carried out in this study, and the …

Addressing Health Disparities In The Rural United States: Advocacy As Caregiving Among Community Health Workers And Promotores De Salud, Ryan I Logan, Heide Castañeda

All publications

Rural populations in the United States are faced with a variety of health disparities that complicate access to care. Community health workers (CHWs) and their Spanish-speaking counterparts, promotores de salud, are well-equipped to address rural health access issues, provide education, and ultimately assuage these disparities. In this article, we compare community health workers in the states of Indiana and Texas, based on the results of two separate research studies, in order to (1) investigate the unique role of CHWs in rural communities and (2) understand how their advocacy efforts represent a central form of caregiving. Drawing on ethnographic, qualitative data—including …

Disproportionate Impact Of Covid-19 Pandemic On Racial And Ethnic Minorities, Brad Boserup, Mark Mckenney, Adel Elkbuli

All publications

Background: Health disparities are prevalent in many areas of medicine. We aimed to investigate the impact of the COVID-19 pandemic on racial/ethnic groups in the United States (US) and to assess the effects of social distancing, social vulnerability metrics, and medical disparities.

Methods: A cross-sectional study was conducted utilizing data from the COVID-19 Tracking Project and the Centers for Disease Control and Prevention (CDC). Demographic data were obtained from the US Census Bureau, social vulnerability data were obtained from the CDC, social distancing data were obtained from Unacast, and medical disparities data from the Center for Medicare and Medicaid Services. …

Cognition In Health And Disease: Two Mouse Model Studies, Heather Lynn Mahoney

USF Tampa Graduate Theses and Dissertations

Cognitive and circadian dysfunction are common aspects of neuropsychiatric disease that are often overlooked in disease models and treatment strategies. In this work, we first evaluated the potential for cognitive enhancement in healthy adult mice by targeting a kinase involved in regulation of the molecular circadian clock. We then developed and characterized a model of neuropsychiatric disease that could present a target for rescuing circadian and cognitive deficits using this treatment.

Time-of-day effects have been noted in a wide variety of cognitive behavioral tests, and perturbation of circadian rhythms impairs hippocampus-dependent learning and memory. We first asked whether casein kinase …

Quantifying The Impact Of Chronic Stress On Racial Disparities In Cardiovascular Disease, Nnadozie Emechebe

USF Tampa Graduate Theses and Dissertations

Background: Despite declining mortality in cardiovascular diseases (CVD), racial disparities between non-Hispanic Blacks (NHB) and to non-Hispanic Whites (NHW) persist. Although the prevalence of traditional risk factors of CVD such as hypertension, is higher in NHB compared to NHW, adjusting for this difference does not eliminate the disparity completely. This suggests other factors might explain the persisting disparities. Thus, the purpose of this dissertation is to quantify the impact of chronic stress in explaining the racial disparities in cardiovascular diseases (CVD). This dissertation contains three studies that addressed the following Specific Aims: Specific aims: 1) To create and assess the …

Hearing Aid Acclimatization In The Context Of Central Gain Mechanisms, Peter J. Hutchison

USF Tampa Graduate Theses and Dissertations

The primary goals of this dissertation were to 1) identify markers of central gain in the auditory system following short-term acoustic attenuation via earplugging and acoustic enhancement via sound generators, and 2) determine if acoustic enhancement is effective in modulating central gain in older adults with age-related hearing loss, and if so, to what extent. Additionally, a further goal of this dissertation was to explore the possibility that central gain is related hearing aid acclimatization. The results described in Chapter 2 are further evidence that altering acoustic input to the peripheral auditory system modulates central auditory plasticity and is evident …

Spatial And Temporal Determinants Associated With Eastern Equine Encephalitis Virus Activity In Florida, Kristi M. Miley

USF Tampa Graduate Theses and Dissertations

Eastern Equine Encephalitis virus (EEEV) is considered the most pathogenic mosquito-borne illness in the United States. Human mortality has been estimated to range between 35 to 75%, with horses experiencing mortality rates greater than 90%. A large number of EEEV cases occur in Florida. Though we have come a long way since the first human infection was identified in the 1930s, there is still much to learn regarding the virus’s ability to maintain transmission year-round in Florida. Phylogenic studies support that Florida may serve as the geographic reservoir for EEEV. This research investigated spatiotemporal and ecological variables associated with risk …

Evaluation Of Aging And Genetic Mutation Variants On Tauopathy, Amber M. Tetlow

USF Tampa Graduate Theses and Dissertations

Alzheimer’s disease (AD) is characterized by amyloid β plaques and neurofibrillary tau tangles (NFTs). While research has demonstrated amyloid pathology occurs prior to tau pathology, or tauopathy, tau has proven to be more toxic. Tauopathy is associated with cognitive declines and neurodegeneration. These findings have highlighted the importance of further understanding tauopathy. In the progression of tauopathy, there is an observable immune response that can be measured by glial cells such as microglia. Activated microglia are known to exacerbate tauopathy rather than reducing the pathology. Research has indicated that with increased age there is an increased risk for AD-related tauopathy …

The Effect Of Hope On The Relationship Between Personal And Disease Characteristics And Anxiety And Depression In Adolescents And Young Adults With Cancer, Sharon B. Mcneil

USF Tampa Graduate Theses and Dissertations

Adolescents and young adults (AYAs) with cancer face physical, psychosocial, emotional, and developmental challenges that are unique to their age group. In facing the crisis of a cancer diagnosis, both social support and hope have been shown to be tools utilized by some AYAs. However, AYAs have higher rates of anxiety and depression than in older adults which may have an effect on their levels of hope.

This cross-sectional study examined the mechanistic effects of hope on the relationship between personal characteristics of age, gender, and social support, the disease characteristics of type of cancer and length of time since …

Impact Assessment Of Full And Partial Stay-At-Home Orders, Face Mask Usage, And Contact Tracing: An Agent-Based Simulation Study Of Covid-19 For An Urban Region, Hanisha Tatapudi, Rachita Das, Tapas K Das

All publications

Purpose: Social intervention strategies to mitigate COVID-19 are examined using an agent-based simulation model. Outbreak in a large urban region, Miami-Dade County, Florida, USA is used as a case study. Results are intended to serve as a planning guide for decision makers.

Methods: The simulation model mimics daily social mixing behavior of the susceptible and infected generating the spread. Data representing demographics of the region, virus epidemiology, and social interventions shapes model behavior. Results include daily values of infected, reported, hospitalized, and dead.

Results: Results show that early implementation of complete stay-at-home order is effective in flattening and reversing the …

Immune Modulation As A Therapeutic Target In An Α-Synuclein Model Of Parkinson’S Disease, Meena Subhashini Subbarayan

USF Tampa Graduate Theses and Dissertations

Parkinson’s disease (PD) is the second most common neurodegenerative disorder affecting about 1.5 million people in the United States with more than 60,000 people diagnosed each year. It is classically characterized by four major symptoms: tremor, postural instability, stiffness in joints, and slow movement (bradykinesia). Pathologically PD is characterized by up to 70% loss of dopaminergic neurons in substantia nigra pars compacta (SNpc) of midbrain and accumulation of presynaptic protein called α-synuclein (α-syn) within dopaminergic neurons that extend to the striatum. This disrupts the nigrostriatal pathway leading to the motor symptoms seen in PD patients. Microglia, the innate immune cells …

Longitudinal Examination Of A Dual-Factor Model Of Mental Health: Academic Adjustment And Stability Of Group Membership In High School Students In Academically Accelerated Curricula, Letty Langton Dileo

USF Tampa Graduate Theses and Dissertations

Middle adolescence (ages 14 to 18 years old) has been associated with declines in both psychopathology and subjective well-being (SWB). This study examined a dual-factor model (DFM) of mental health, which conceptualizes complete mental health as including both low levels of psychopathology and high levels of SWB, across three time points, each 9-12 months apart, in a sample of 328 9th grade students enrolled in accelerated coursework. This study aimed to determine (1) the stability of students’ mental health status over time, (2) the role of psychopathology versus SWB for students who changed mental health status, and (3) the relationship …

Physician Self-Efficacy And Risk-Taking Attitudes As Determinants Of Upcoding And Downcoding Errors: An Empirical Investigation, Samantha J. Champagnie

USF Tampa Graduate Theses and Dissertations

Physicians across the United States are burdened with the pressure of accurate coding while trying to maintain quality patient care. Despite the economic importance of coding accuracy, investigators have not reached consensus on the factors that contribute to coding errors. This study fills this gap by investigating physician characteristics that explain the variation in physician coding accuracy, specifically evaluation and management upcoding and downcoding errors. An electronic survey was distributed to 325 physicians that measured physicians’ attitudes towards risk and coding self-efficacy. Regression analysis found physicians with low self-efficacy had more conservative coding behaviors, resulting in higher incidences of downcoding. …

A Review Of American College Campus Tobacco Or Smoke Free Policies: A Case Study Of A Large Urban University, Sarah E. Powell

USF Tampa Graduate Theses and Dissertations

Objective: A year after a tobacco free policy was passed, the University of South Florida (USF) was interested in the overall policy opinions and efficacy. To assess this a project was completed that included a survey and geospatial data. The survey measured tobacco policy enforcement behavior and a geographic information system (GIS) mapped tobacco policy violation. This project introduces an evaluation process that can efficiently assess an institutions tobacco-free policy. Methods: Using a cross-sectional survey sent to students, faculty, and staff, understanding of policy and resources, tobacco use observations, stage of change regarding policy enforcement, self-efficacy to enforce, and perceived …

Covid-19 And Quantitative Literacy: Focusing On Probability, Michael A. Lewis

Numeracy

The COVID-19 pandemic is arguably the worst crisis the world has faced, so far, in this new century. We haven’t seen a pandemic like this since the 1918 Flu at the beginning of the last century, and, as of this writing, there appears to be no end in sight. What those of us who’re focused on quantitative methods have noticed, in addition to the many people dying, becoming ill, and losing their livelihoods, is the importance of quantitative literacy to an understanding of what’s going on. That’s what this article is about. Specifically, it’s about how the COVID-19 pandemic is …

On The Importance Of Context: Examining The Applicability Of Infertility Insurance Mandates In The United States Using A Mixed-Methods Study Design, Nathanael B. Stanley

USF Tampa Graduate Theses and Dissertations

Accessibility of infertility services is disproportionately experienced in the United States. Although there exist state-based health insurance mandates for infertility services, these mandates contain language that disqualify people from using them. In order to better understand why these mandates are not able to reduce the financial burden and bridge the income disparity for using infertility services, the purpose of this study is to add context to the applicability of these insurance mandates through qualitative and quantitative inquiry. Using the Glass and McAtee model of risk regulators as an operational paradigm, this research explores the role of environmental context, or “place”, …

Functional Gait Asymmetries Achieved Through Modeling And Understanding The Interaction Of Multiple Gait Modulations, Fatemeh Rasouli

USF Tampa Graduate Theses and Dissertations

Walking is an important determinant of human functionality. Gait disabilities affect millions of people worldwide every year. Investigating the science of walking advances recovery techniques and assistive devices for gait rehabilitation. A functional gait promotes productivity, independence, and quality of life. Human gait, like any other moving mechanism, is a dynamic system. Understanding and analyzing the dynamic aspects of gait improves the recovery methods to fundamentally affect and interact with lower limbs.

This dissertation aims to fill the gaps in mechanical simulations of gait and dynamic analysis of rehabilitation techniques. The solutions consider kinematic, kinetic, and spatiotemporal parameters of gait …

Untreated Stroke As Collateral Damage Of Covid-19: "Time Is Brain" Versus "Stay At Home"., David Z. Rose, W. Scott Burgin, Swetha Renati

All publications

For decades, neurologists have been advocating that anyone with acute focal deficits report immediately to the closest hospital's emergency room. Major advancements in the hyperacute diagnosis and treatment of stroke have justified our call-to-action slogan of "Time is Brain"-faster therapy leads to superior outcomes. However, this mantra has been recently usurped by the catchphrase "Stay at Home" during the coronavirus disease 2019 (COVID-19) pandemic. Fewer patients are presenting to hospitals with acute stroke; our census is down. Presumably the etiology of this phenomenon is either strict "social distancing" that some people may misperceive to exclude even emergent situations, or fears …

Ssh1 Impedes P62/Sqstm1 Flux And Tau Clearance Independent Of Cofilin Activation, Cenxiao Fang

USF Tampa Graduate Theses and Dissertations

Accumulation of toxic protein assemblies and damaged mitochondria are key features of neurodegenerative diseases, which arise in large part from clearance defects in the autophagy-lysosome system. The autophagy cargo receptor p62/SQSTM1 plays a major role in the clearance of ubiquitinated cargo through Ser403 phosphorylation by multiple kinases. However, no phosphatase is known to physiologically dephosphorylate p62 on this activating residue. RNAi-mediated knockdown and overexpression experiments using genetically encoded fluorescent reporters and defined mutant constructs in cell lines, primary neurons, and brains show that SSH1, the canonical cofilin phosphatase, mediates the dephosphorylation of phospho-Ser403-p62, thereby impairing p62 flux and phospho-tau clearance. …

The Impact Of Myeloid-Mediated Co-Stimulation And Immunosuppression On The Anti-Tumor Efficacy Of Adoptive T Cell Therapy, Pasquale Patrick Innamarato

USF Tampa Graduate Theses and Dissertations

Adoptive T cell therapy (ACT) in combination with lymphodepleting chemotherapy is an effective strategy to induce the eradication of tumors, providing long-term regression in cancer patients. However, only a minority of patients that receive ACT with tumor infiltrating lymphocytes (TILs) exhibit durable benefit. Thus, there is an urgent need to define strategies that potentiate anti-tumor activity conducted by adoptively transferred T cells. In these studies, we aimed to identify novel strategies to enhance the therapeutic efficacy of ACT. Accordingly, we describe the disparate roles of myeloid cells in the context of ACT characterized by the augmentation of TIL proliferation in …

From R0 To The Herd: A Review Of The Rules Of Contagion, By Adam Kucharski, Nathan D. Grawe

Numeracy

Adam Kucharski. 2020. The Rules of Contagion: Why Things Spread--and Why They Stop; (London: Profile Books, Ltd.). Hardback ISBN 978-17-88-16019-3. E-book ISBN 978-17-82-83430-4.

Kucharski's well-timed Rules of Contagion provides an introduction to the mathematical and epidemiological principles behind contagious phenomenon. While the author's primary expertise stems from work on biological epidemics, the book points to examples from a wide range of fields including finance, psychology, computer science, and criminology. As such, selections of the book could be used by faculty in a wide range of classes to show how our recent experience with a viral epidemic might add to …

Factors In The Probability Of Covid-19 Transmission In University Classrooms, Charles Connor

Numeracy

University students and faculty members need an effective strategy to evaluate and reduce the probability that an individual will become infected with COVID-19 as a result of classroom interactions. Models are developed here that consider the probability an individual will become infected as a function of: prevalence of the disease in the university community, number of students in class, number of class meetings, and transmission rate in the classroom given the presence of an infected individual. Absolute probabilities that an individual will become infected in a classroom environment cannot be calculated because some of these factors have unknown values. Nevertheless, …

Effects Of The 340b Drug Pricing Program On Hospitals’ Prescribing Behavior, Patient Mix, And Quality Of Care, Yilu Dong

USF Tampa Graduate Theses and Dissertations

In 1992, Congress created the 340B Drug Pricing Program that requires drug manufacturers to provide outpatient drugs to participating hospitals with substantial discounts. Although the intent of the program is to allow covered entities to increase access to care for more vulnerable patients, hospitals are not required by law to pass on the discounts. Therefore, a concern is that hospitals might over-prescribe. This dissertation includes three chapters to study the effects of the 340B program on hospitals’ behavior changes:

Chapter 1 uses state aggregate hospital service spending data from the Centers for Medicare and Medicaid Services (CMS) to study the …

In Post-Extubated Patients What Are The Preferred Methods Of Communication During Their Experience Of Endotracheal Intubation With Mechanical Ventilation, Lanette Dumas

USF Tampa Graduate Theses and Dissertations

To date, communication between mechanically intubated patients and nurses is laden with negative psychological and physiological impacts. Research has focused more on what patients want to communicate, and how nurses communicate with intubated patients. There is limited research identifying the communication methods preferred by these patients. The purpose of this study was to identify communication preferences of mechanically intubated patients using a phenomenological approach.

Semi-structured interviews were conducted with participants in their hospital rooms. The interview questions focused on the period of mechanical intubation when the participants were unable to speak. A total of 27 participants were interviewed at a …