Immunology and Infectious Disease Commons^™

A Draft Of The Genome Of The Gulf Coast Tick, Amblyomma Maculatum, Jose M.C. Ribeiro, Natalia J. Bayona-Vásquez, Khemraj Budachetri, Deepak Kumar, Julia Catherine Frederick, Faizan Tahir, Brant C. Faircloth, Travis C. Glenn, Shahid Karim

Faculty Publications

The Gulf Coast tick, Amblyomma maculatum, inhabits the Southeastern states of the USA bordering the Gulf of Mexico, Mexico, and other Central and South American countries. More recently, its U.S. range has extended West to Arizona and Northeast to New York state and Connecticut. It is a vector of Rickettsia parkeri and Hepatozoon americanum. This tick species has become a model to study tick/Rickettsia interactions. To increase our knowledge of the basic biology of A. maculatum we report here a draft genome of this tick and an extensive functional classification of its proteome. The DNA from a single …

The Future Of Pandemics: Land Use Controls As Means Of Preventing Zoonotic Disease, Bailey Andree

Pace International Law Review

Zoonotic diseases are increasing in frequency as climate change worsens around the world, with the recent COVID-19 pandemic highlighting the inadequate mechanisms in place to counteract disease spread. This article reviews various zoonotic diseases and their patterns of spread, highlighting land use change as the key driver of disease to demonstrate the need for legal intervention. International land use law is a little-developed subsect of environmental law that holds the key to combating this disease spread, and this article proposes solutions through this legal lens. Land use techniques which may be used to combat disease spread include conservation laws, setback …

A Dynamical System Model Of Dengue Transmission For Rio De Janeiro, Brazil, Gregory Schmidt, Benjamin Whipple, Vinodh Chellamuthu, Xiaoxia Xie

Spora: A Journal of Biomathematics

The dengue virus is a serious concern in many parts of the world, including Brazil. As data indicates, a prominent vector for dengue is the mosquito Aedes aegypti. By using the dengue incidence records from the Brazilian SINAN database, we estimate the population of A. aegypti within the city of Rio de Janeiro. Using historical climate data for Rio de Janeiro and the computed population estimates, we extend an existing model for the population dynamics of mosquitoes to incorporate precipitation in aquatic stages of development for A. aegypti.

Targeting The Cerebrovasculature In Sepsis: A Focus On The Brain Microvascular Endothelium, Divine C. Nwafor

Graduate Theses, Dissertations, and Problem Reports

The blood-brain barrier (BBB) is a critical interface between the systemic circulation and the brain. It is a specialized multicellular unit composed of brain microvascular endothelial cells (BMECs), pericytes, a basement membrane, and astrocytic end foot processes. BMECs are a principal component of the BBB that provide the structural framework needed for the stringent transport of molecules into the brain. BMEC dysfunction permits the trafficking of neurotoxins from systemic circulation into the brain, which ultimately exacerbates BBB dysfunction and neuroinflammation. Studies have shown that BBB dysfunction is a key determinant of cognitive decline in sepsis. However, there are critical knowledge …

Antimalarial Chemoprophylaxis For Forest Goers In Southeast Asia: An Open-Label, Individually Randomised Controlled Trial, Rupam Tripura, Lorenz Von Seidlin, Siv Sovannaroth, Thomas J. Peto, James J. Callery, Meas Sokha, Mom Ean, Chhouen Heng, Franca Conradis-Jansen, Wanassanan Madmanee, Pimnara Peerawaranun, Naomi Waithira, Panarasri Khonputsa, Monnaphat Jongdeepaisal, Kulchada Pongsoipetch, Paphapisa Chotthanawathit, Ung Soviet, Christopher Pell, Jureeporn Duanguppama, Huy Rekol, Joel Tarning, Mallika Imwong, Mavuto Mukaka, Nicholas J. White, Arjen M. Dondorp, Richard J. Maude

H. W. Manter Laboratory Library Materials

Summary

Background

Malaria in the eastern Greater Mekong subregion has declined to historic lows. Countries in the Greater Mekong subregion are accelerating malaria elimination in the context of increasing antimalarial drug resistance. Infections are now increasingly concentrated in remote, forested foci. No intervention has yet shown satisfactory efficacy against forest-acquired malaria. The aim of this study was to assess the efficacy of malaria chemoprophylaxis among forest goers in Cambodia.

Methods

We conducted an open-label, individually randomized controlled trial in Cambodia, which recruited participants aged 16–65 years staying overnight in forests. Participants were randomly allocated 1:1 to antimalarial chemoprophylaxis, a 3-day …

Visualization And Characterization Of The Immunological Synapse Between Chlorotoxin Chimeric Antigen (Cltx-Car) Redirected T Cells And Targeted Glioblastoma Tumors, Arianna Livi

CMC Senior Theses

Chimeric Antigen Receptor T (CAR-T) cells have demonstrated anti-tumor activity against aggressive and invasive cancers such as glioblastoma (GBM); however, clinical response rates remain low in clinical trial studies. Tumor heterogeneity and tumor microenvironment conditions pose significant challenges for treatment of GBM, thus continuous optimization of CAR-T cell therapies and identification of novel, widely expressed, and highly specific GBM antigens are vital to better patient outcomes. A newly developed CAR-T cell construct incorporating chlorotoxin (CLTX) as the targeting domain exhibited broad GBM-targeting capabilities and elicited potent cytotoxic effects during preclinical studies and is currently being tested in a phase I …

Let Emerging Plant Diseases Be Predictable, Valeria Trivellone

MANTER: Journal of Parasite Biodiversity

A prevalent concept for colonization and evolution among plant pathogens and their hosts stems from a post-Darwinian paradigm rooted in the formalized assumption of “specialized parasitism.” Seminal studies on rust fungi of socioeconomic importance integrated such an evolutionary perspective driven by the assumption of strict coevolution among pathogens and their plant hosts. Following this fundamentally unfalsifiable assumption, theories regarding host-switching for parasites were dismissed. If colonization occurred, this process would depend upon the origin of specific and novel mutations that allow infections of previously unexploited hosts or host groups, the acquisition of a broader host range. After a specific mutation …

An Emerging Infectious Disease Surveillance Platform For The 21st Century, Eloy Ortiz, Alicia Juarrero

MANTER: Journal of Parasite Biodiversity

Current vector surveillance programs are insufficient for coping with the emerging infectious disease crisis. In particular, current practices do not deploy sufficient information technology (IT) tools to generate actionable insights that can inform interventions and contain and mitigate the spread of vector-borne diseases. VectorAnalytica has developed a highly configurable and adaptable IT platform that imports, harmonizes, and integrates a range of data sources. The state-of-the-art backend development allows users to fully appreciate and understand the complexity of infectious disease dynamics without having to resort to additional statistical and GIS software packages. The platform yields actionable insights into outbreak patterns of …

Taking Action: Turning Evolutionary Theory Into Preventive Policies, Orsolya Molnár, Marina Knickel, Christine Marizzi

MANTER: Journal of Parasite Biodiversity

The emerging infectious disease (EID) crisis has been challenging global health security for decades, dealing substantial damage to all socioeconomic landscapes. Control measures have failed to prevent or even mitigate damages from an accelerating wave of EIDs, leading to the emergence and devastation caused by the COVID-19 pandemic. In the wake of the pandemic, we must critically review our public health policies and approaches. Current health security measures are based on the evolutionary theorem of host-parasite coevolution, which falsely deems EIDs as rare and unpredictable. The DAMA protocol (Document, Assess, Monitor, Act) is nested in a novel evolutionary framework that …

The Stockholm Paradigm Explains The Dynamics Of Darwin’S Entangled Bank, Including Emerging Infectious Disease, Salvatore J. Agosta

MANTER: Journal of Parasite Biodiversity

Pathogens and their hosts are embedded within the larger biosphere, what Darwin called the “entangled bank.” Emerging infectious disease occurs when a parasite “switches” to a new host. Understanding the dynamics of emerging disease requires understanding the dynamics of host-switching, which requires a more general understanding of how the biosphere and its constituent members cope when conditions change. The Stockholm paradigm is an integrative evolutionary framework that describes how living systems cope with change by oscillating between exploiting and exploring the geographical and functional dimensions of their environments. It combines organismal capacity, ecological opportunity, and the repeated external perturbations to …

Anthelmintic Resistance In Sheep Across Ireland And The Uk: A Literature Review Of The In Vivo Versus In Vitro Methods, Megan Tumulty

SURE_J: Science Undergraduate Research Journal

Background: The animal welfare and production consequences of gastrointestinal nematode infections, namely Nematodirus battus, on sheep are compelling. The control of gastrointestinal infections has been heavily reliant on the administration of anthelmintics since their introduction into mainstream use in 1960. However, their frequent and often excessive use has resulted in anthelmintic resistance being reported extensively in several gastrointestinal nematode species. The prevalence of anthelmintic resistance as well as the increase in the number of cases of multiple-drug resistance in nematode populations now poses substantial hindrance on the viability of sheep production systems. However, despite the threat N. battus poses …

Knowing The Biosphere: Documentation, Specimens, Archives, And Names Reveal Environmental Change And Emerging Pathogens, Eric P. Hoberg, Valeria Trivellone, Joseph A. Cook, Jonathan L. Dunnum, Walter A. Boeger, Daniel R. Brooks, Salvatore J. Agosta, Jocelyn P. Colella

MANTER: Journal of Parasite Biodiversity

One Health programs and trajectories are now the apparent standard for exploring the occurrence and distribution of emerging pathogens and disease. By definition, One Health has been characterized as a broadly inclusive, collaborative, and transdisciplinary approach with connectivity across local to global scales, which integrates the medical and veterinary community to recognize health outcomes emerging at the environmental nexus for people, animals, plants, and their shared landscapes. One Health has been an incomplete model, conceptually and operationally, focused on reactive and response-based foundations, to limit the impact of emerging pathogens and emerging infectious diseases and, as such, lacks a powerful …

Regional Characteristics And Spatiotemporal Differentiation Of The Prevalence Of Hand, Foot, And Mouth Disease In Xinjiang, China, Ma Chen, Wang Hongwei, Xie Ling, Yi Suyan, Tan Bo

Regional Sustainability

Climate change is expected to threaten the developing countries the most. Nepal is considered one of the five countries most vulnerable to climate change in the world. The mountainous area such as Rasuwa District in Nepal is more vulnerable due to complex topography, human activity (tourism), and climate change. In this context, we carried out this study to assess the climate change and its impact on agriculture production as well as people’s perceptions on the impact of climate change. The long-term (1980–2014) observed climate data (temperature and precipitation) and field-based survey data on people’s perceptions were analyzed. Mann-Kendall trend test …

The Evolutionary Dynamics Of Infectious Diseases On An Unstable Planet: Insights From Modeling The Stockholm Paradigm, Angie T.C. Souza, Sabrina B.L. Araujo, Walter A. Boeger

MANTER: Journal of Parasite Biodiversity

Emerging infectious diseases (EIDs) are, besides a question of food safety and public health, an ecological and evolutionary issue. The recognition of this condition combined with the accumulation of evidence that pathogens are not specialists in their original hosts evidences the need for understanding how the dynamics of interaction between pathogens and hosts occurs. The Stockholm Paradigm (SP) provides the theoretical fundaments to understand the dynamics of diseases and design proactive measures to avoid the emergence and reemergence of infectious diseases. In this review, we revisit the models that evaluate several aspects of the proposed dynamics of the SP, including …

Selection Pressure On Surface Exposed Virus Proteins, Sareh Bagherichimeh

Electronic Thesis and Dissertation Repository

Viral infection requires the interaction between virus surface-exposed (SE) proteins and host cell receptors. This can result in an “arms race” that is assumed to drive accelerated rates of evolution, and some well known examples of diversifying selection involve surface pro- teins (HIV-1 env, influenza hemagglutinin). We conducted a systematic analysis to determine whether this is truly a distinctive feature of SE virus proteins, in comparison to non-SE proteins encoded by the same genomes.

We obtained reference and all neighbour genomes of 52 human viruses from the NCBI Viral Genomes database. The coding sequences (CDS) of each genome extracted by …

Alternative Precautionary Measures Yielding Lower C. Diff Infection Rates In Healthcare Facilities, Matthew Kramer

Symposium of Student Scholars

Background: An international healthcare concern is the persistent spread of Clostridium difficile, a Gram-positive spore forming bacterium that is responsible for the most common hospital-acquired infection, amongst patients.

Objective: A systematic review was performed to summarize evidence that the interventions utilized in healthcare facilities which indicate a patient’s precautionary status are insufficient, outdated, and commonly lead to infection in neighboring patient rooms. Databases such as PubMed, NCBI, Google Scholar, and APHA’s Medical Care were searched, covering the period from 2017-2022. Studies were included if their focus concentrated on C. diff and the precautionary measures taken by employees at healthcare …

Doxorubicin-Induced Cardiotoxicity Is Mediated By Neutrophils Through Release Of Neutrophil Elastase, Anchit Bhagat

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Doxorubicin (Dox) is one of the most effective chemotherapy agents that is used for the treatment of childhood cancer. Unfortunately Dox treatment can cause damage to the heart. Indeed, childhood cancer survivors are at a higher risk of developing a cardiovascular disease at an earlier age. The mechanisms by which Dox causes acute and late cardiotoxicity are not completely understood. One understudied area in Dox-induced cardiotoxicity is the contribution of inflammation and innate immune cells, in particular neutrophils. Recognizing that neutrophils have been implicated in a number of heart diseases, we evaluated the role of neutrophils in Dox-induced cardiotoxicity. Here, …

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

A Novel Transmembrane Ligand Inhibits T Cell Receptor Activation, Yujie Ye

Doctoral Dissertations

T lymphocytes (T cells) play essential roles in the adaptive immune system. Each mature T cell expresses one type of functional T cell receptor (TCR). The TCR recognizes antigens bound to the major histocompatibility complex (MHC) in antigen presenting cells. The resulting stimulation signal crosses the transmembrane domain of TCR and initiates downstream signaling cascades. The human immune system relies on TCRs to recognize a variety of pathogens. Normally, TCR can distinguish the self-antigens from pathogenic antigens. However, dysfunction or aberrant expression of TCRs causes different inflammatory and autoimmune diseases, which afflict millions of people annually (Chapter I). Current treatments …

Danio Rerio: A Past, Present, And Future Hallmark For Immunological Studies, Michael Solomon Chembars Jr.

Senior Honors Theses

An emerging species that is slowly gaining reputation as a common model organism is Danio rerio. Due to its similarities to our own immune response and its general ease of use, hundreds of studies have been conducted which have increased our understanding of how chemicals or pathogens can affect both our own health, and the health of the environment.

This study aims to briefly describe a brief history of D. rerio, as well as discuss key experiments that have been performed using D. rerio. A comparison will also be made between the human and zebrafish immune responses, and …

A Field Synopsis, Systematic Review, And Meta-Analyses Of Cophylogenetic Studies: What Is Affecting Congruence Between Phylogenies?, Valeria Trivellone, Bernd Panassiti

MANTER: Journal of Parasite Biodiversity

We conducted a field synopsis and systematic meta-analysis of studies that carried out cophylogenetic analyses using algorithms and available software. We evaluated the influence of three factors—namely, cophylogenetic method, association, and ecosystem type—on the outcome of the analyses, that is, the degree of congruence between phylogenies of interacting species.

The published papers were identified using 4 different databases and 13 keywords; we included all studies for which statistical approaches to compare phylogenies (cophylogenetic analyses) of interacting lineages were used. After the initial screening, 296 studies were selected to extract response variable (outcome of the cophylogenetic analyses, i.e., congruent, incongruent, or …

Modeling The Impact Of Hospitalization On The Death Rate Of An Ebola Outbreak, Erin N. Bodine, Jana V. Turner

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

The Stockholm Paradigm: Lessons For The Emerging Infectious Disease Crisis, Daniel R. Brooks, Walter A. Boeger, Eric P. Hoberg

MANTER: Journal of Parasite Biodiversity

The emerging infectious disease (EID) crisis represents an immediate existential threat to modern humanity. Current policies aimed at coping with the EID crisis are ineffective and unsustainably expensive. They have failed because they are based on a scientific paradigm that produced the parasite paradox. The Stockholm paradigm (SP) resolves the paradox by integrating four elements of evolutionary biology: ecological fitting, sloppy fitness space, coevolution, and responses to environmental perturbations. It explains why and how the EID crisis occurs and is expanding and what happens after an EID emerges that sets the stage for future EIDs. The SP provides a number …

The Dama Protocol, An Introduction: Finding Pathogens Before They Find Us, Eric P. Hoberg, Walter A. Boeger, Orsolya Molnár, Gábor Földvári, Scott Gardner, Alicia Juarrero, Vitaliy A. Kharchenko, Eloy Ortiz, Valeria Trivellone, Daniel R. Brooks

MANTER: Journal of Parasite Biodiversity

Globally, humanity is coming to recognize the magnitude of the interactive crisis for emerging infectious disease (EID). Strategies for coping with EID have been largely in the form of reactive measures for crisis response. The DAMA protocol (Document, Assess, Monitor, Act), the operational policy extension of the Stockholm paradigm, constitutes a preventive/proactive dimension to those efforts. DAMA is aimed at focusing and extending human and material resources devoted to coping with the accelerating wave of EID. DAMA is integrative, combining efforts to strategically document the distribution of complex pathogen and host assemblages in the biosphere in the context of dynamic …

Louis Pasteur Signature Saying: Science Brings Men Closer To God Bicentenary Year: 200 Years After His Birth, Alan L. Gillen, Justin A. Ambrose

Faculty Publications and Presentations

This year (2022) marks the bicentenary birth (December 27, 1822) of Louis Pasteur. He has a global reputation. His contributions can be seen in our homes, in the "pasteurized" products derived from one of his discoveries and in disease prevention. It was in his discovery of gently heating beverages and food for what we today call pasteurization that he first said: “Man's first look at the universe discovers only variety, diversity, multiplicity of phenomena. Let this gaze be enlightened by science — by science which brings man closer to God — and simplicity and unity shine everywhere.” Louis Pasteur (Vallery-Radot, …

Comparison Of The Humoral Immune Response Following Both Bacterial Challenge And Rnai Of Major Factors On Proliferation Of Bartonella Quintana In The Human Louse, Jake Zina

Masters Theses

Human body lice, Pediculus humanus humanus, and head lice, Pediculus humanus capitis, have been hematophagous ectoparasites of humans for thousands of years. Despite being ecotypes, only body lice are known to transmit bacterial diseases to humans, and it appears that lower humoral and cellular immune responses allow body lice to possess a higher vector competence. We previously observed that the transcription level of the defensin 1 gene was up-regulated only in head lice following oral challenge of Bartonella quintana, a causative agent of trench fever, and also that body lice excreted more viable B. quintana in their …

The 3p Framework: A Comprehensive Approach To Coping With The Emerging Infectious Disease Crisis, Orsolya Molnár, Eric Hoberg, Valeria Trivellone, Gábor Földvári, Daniel R. Brooks

MANTER: Journal of Parasite Biodiversity

The COVID-19 pandemic is the latest example of the profound socioeconomic impact of the emerging infectious disease (EID) crisis. Current health security measures are based on a failed evolutionary paradigm that presumes EID is rare and cannot be predicted because emergence requires the prior evolution of novel genetic capacities for colonizing a new host. Consequently, crisis response through preparation for previously emerged diseases and palliation following outbreaks have been the only health security options, which have become unsustainably expensive and unsuccessful. The Stockholm paradigm (SP) is an alternative evolutionary framework that suggests host changes are the result of changing conditions …

Chemical Biology Approaches For Tracking And Manipulation Of Macrophage Phenotypes, Javier A. Mas Rosario

Doctoral Dissertations

Macrophages are white blood cells of the innate immune system that have the ability to change phenotypically depending on the stimuli present in their surroundings through a process commonly referred to as polarization. Macrophage phenotypes broadly range from pro-inflammatory, anti-tumor (M1) to immune-suppressing (M2). Of particular interest to this work, breast cancer progression and metastasis rely on the presence of M2-like tumor-associated macrophages (TAMs). While many studies have shown the involvement of macrophages in tumor progression and metastasis, there remains a need to further explore these interactions and the polarization process, including tracking of macrophage subtypes. Toward this end, I …

Using The Embl-Ebi Clustal Omega Tool To Calculate Diversity Of Heavy Chain Phage-Display Libraries, Michael Bodri, Shane A. Webb

Georgia Journal of Science

Here we show that traditional Sanger sequencing combined with analysis tools available from the European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), specifically EMBOSS Transeq and Clustal Omega, is extremely effective in the analysis of naïve phage display antibody libraries for the determination of library size and diversity. The free tools are easy to use and require little manipulation of reads by hand, allowing analysis to be performed on a standard personal computer. Utilization of this technique has applicability to researchers with limited access to deep sequencing. The primary drawback to this analysis methodology is that antibodies with particular molecular or …

Whole Genome Sequencing Of Moraxella Bovis Strains From North America Reveals Two Genotypes With Different Genetic Determinants, Emily L. Wynn, Matthew M. Hille, John Dustin Loy, Gennie Schuller, Kristen L. Kuhn, Aaron M. Dickey, James L. Bono, Michael L. Clawson

Papers in Veterinary and Biomedical Science

Background: Moraxella bovis and Moraxella bovoculi both associate with infectious bovine keratoconjunctivitis (IBK), an economically significant and painful ocular disease that affects cattle worldwide. There are two genotypes of M. bovoculi (genotypes 1 and 2) that differ in their gene content and potential virulence factors, although neither have been experimentally shown to cause IBK. M. bovis is a causative IBK agent, however, not all strains carry a complete assortment of known virulence factors. The goals of this study were to determine the population structure and depth of M. bovis genomic diversity, and to compare core and accessory genes and …