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Targeting The Cerebrovasculature In Sepsis: A Focus On The Brain Microvascular Endothelium, Divine C. Nwafor 2023 West Virginia University

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 ...


Regulation Of Mhc Ii Trafficking And Expression By Host And Viral Factors, Alex Lac 2022 The University of Western Ontario

Regulation Of Mhc Ii Trafficking And Expression By Host And Viral Factors, Alex Lac

Electronic Thesis and Dissertation Repository

Antigen presentation by major histocompatibility complex class II (MHC II) to the adaptive immune system is crucial for mounting sterilizing immune responses. This central role has made antigen presentation a target for antagonism by many pathogens. Notably, infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) decrease MHC II expression in several immune cells. The mechanisms responsible for this suppression are unknown but involves either redirecting MHC II molecules away from the cell surface or inhibiting MHC II expression. To understand how pathogens manipulate intracellular MHC II trafficking, we first investigated the role of the Golgi trafficking regulator, ERC1, in ...


Mathematical Model Of Immune-Inflammatory Response In Covid-19 Patients, Quiyana M. Murphy 2022 Virginia Polytechnic Institute and State University

Mathematical Model Of Immune-Inflammatory Response In Covid-19 Patients, Quiyana M. Murphy

Biology and Medicine Through Mathematics Conference

No abstract provided.


Evaluation Of The Humoral/Fc-Mediated Immune Responses To An Adenovirus-26 Viral Vector/Gp140 Subunit Combined Vaccine Regimen As A Prophylactic Hiv-1, Nathan E. Adam 2022 Cedarville University

Evaluation Of The Humoral/Fc-Mediated Immune Responses To An Adenovirus-26 Viral Vector/Gp140 Subunit Combined Vaccine Regimen As A Prophylactic Hiv-1, Nathan E. Adam

Channels: Where Disciplines Meet

Background and Introduction: HIV is one of the most problematic pandemics to date, currently infecting upwards of 38 million people worldwide (“The Global HIV/AIDS Epidemic,” 2020). Although infection and mortality rates have generally decreased, current prophylactic (preventive) measures against HIV-1 acquisition have shown major weaknesses that could be remedied with a vaccine (Pitisuttuthum & Marovich, 2020). Manufacturing an effective, prophylactic HIV-1 vaccine, however, is not without challenges - namely design/selection of vaccine-delivered immunogens (antigens) and elicitation of proper immune responses to HIV-1 antigens (Ng’uni et al., 2020). Fortunately, despite past, unsuccessful research, studies within the past 10-15 years have begun to elucidate immune correlates of protection against HIV-1 acquisition, specifically IgG1/IgG3 antibody (Ab) production, as well as non-neutralizing, Fc-Mediated effector functions (Rerks-Ngarm et al., 2009). Excitingly, studies released in the last 3 years, which use Adenovirus serotype-26 (Ad26) vector (Custers et al., 2020) show promising signs that an effective HIV-1 vaccine could become a reality (Baden et al., 2020; Barouch et al., 2018). Thus, for this presentation, I hope to show that Johnson & Johnson’s two new Ad26-based vaccines (combined with booster vaccines) sufficiently elicit key immune correlates of protection to warrant an Ad26 vector-based regimen’s testing past Phase 1/2a clinical trials. Results ...


Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian Gilbert 2022 University of Arkansas, Fayetteville

Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian Gilbert

Animal Science Undergraduate Honors Theses

Lipoteichoic acid (LTA) is component of the cell wall of Gram-positive bacteria that stimulates inflammation during bacterial infection. However, few studies have investigated the in vivo immune response to LTA, and none of the in vivo studies done have been performed in birds. For this project, the pulp (a skin-derivative) of growing feathers (GFs) of chickens were used as a test site to investigate the in vivo effects of intradermally injected LTA. In Study 1, the pulp of 12 GFs of 11-week-old Light-brown Leghorn (LBL) males were injected with 10 μL of differing concentrations of LTA (0.1, 1.0 ...


Multi-Omic Systems Biological Analysis Of Host-Microbe Interactions, Piet Jones 2022 University of Tennessee, Knoxville

Multi-Omic Systems Biological Analysis Of Host-Microbe Interactions, Piet Jones

Doctoral Dissertations

Systems biology offers the opportunity to understand the complex mechanisms of various biological phenomena. The wealth of data that is produced, at an increasing rate, provides the potential to meet this opportunity. Here we take an applied approach to integrate multiple omic level data sources in order to generate biologically relevant hypotheses. We apply a novel analysis pipeline to model both, in concert, the microbial and transcriptomic signature from COVID-19 positive patients. We show patients may suffer from an increased microbial burden, with an increased pathogen potential. Gene expression evidence further shows patients may exhibit a compromised barrier immunity, owing ...


Macrophage Rac2 Promotes Suppression Of Germination During Aspergillus Fumigatus Infection, Chris D. Tanner 2022 Clemson University

Macrophage Rac2 Promotes Suppression Of Germination During Aspergillus Fumigatus Infection, Chris D. Tanner

All Theses

Aspergillus fumigatus is a fungus found ubiquitously in the environment including in the air we breathe. Though not a threat to most people, immunodeficient or immunosuppressed individuals are at risk for developing severe infection, including the life-threatening condition of invasive aspergillosis. The hematopoietic cell specific GTPase protein Rac2 is associated with major roles in innate immune defense. Currently Rac2 has been demonstrated to be crucial for survival against a variety of infections. Here, we use a rac2 null mutant zebrafish line and morpholino approaches to elucidate roles of Rac2 in mounting the macrophage host defense response against A. fumigatus infection ...


Structural Formation And Functionality Of The Spoiie Protein In Clostridium Difficile, Rachel Siebenmorgen 2022 University of Arkansas, Fayetteville

Structural Formation And Functionality Of The Spoiie Protein In Clostridium Difficile, Rachel Siebenmorgen

Biological Sciences Undergraduate Honors Theses

My research efforts were directed toward the structure and functionality of a protein, designated SpoIIE [11], which previously has been shown to regulate C. difficile peptide utilization in addition to sporulation and toxin release. The SpoIIE protein is found in all spore-forming gram-positive bacteria and is a crucial component in activation of transcription factors and septum formation thus affecting the regulation and timing of spore development [11,12]. A truncated form of the SpoIIE protein named SpoIIE∆TM was used in an effort to determine the structure of an important but uncharacterized linker domain of the protein. If the structure ...


Covid Susceptibility And Severity Correlation With The Ace2 Gene, Natalie Taylor 2022 University of Southern Maine

Covid Susceptibility And Severity Correlation With The Ace2 Gene, Natalie Taylor

Thinking Matters Symposium

A wide spectrum of susceptibility and severity of infection has been observed among COVID-19 patients. While some individuals remain unaffected by the Sars-Cov-2 virus, others have contracted the virus multiple times with varying levels of severity. This poster reviews some of the research demonstrating a link between the susceptibility of the Sars-Cov- 2 virus and the severity of infection, and a specific gene called ACE2. The ACE2 gene encodes an angiotensin-converting enzyme that acts as a functional receptor for the spike glycoprotein receptor binding domain of the coronavirus and severe acute respiratory syndrome coronaviruses. ACE2 presents numerous amino acid variants ...


Physician's Attitudes On Pulmonary Rehabilitation Following Covid-19: A Brief Perspective From A Developing Country, Ivan Cherrez-Ojeda, Emanuel Vanegas, Miguel Felix, María José Farfán Bajaña, Azza Sarfraz, Zouina Sarfraz, Genesis Camacho, Alanna Barrios-Ruiz, Jack Michel 2022 Universidad Espíritu Santo, Samborondón, Ecuador

Physician's Attitudes On Pulmonary Rehabilitation Following Covid-19: A Brief Perspective From A Developing Country, Ivan Cherrez-Ojeda, Emanuel Vanegas, Miguel Felix, María José Farfán Bajaña, Azza Sarfraz, Zouina Sarfraz, Genesis Camacho, Alanna Barrios-Ruiz, Jack Michel

Department of Paediatrics and Child Health

Despite the uncertainty about the follow up of COVID-19 survivors, there is a growing body of evidence supporting specific interventions including pulmonary rehabilitation, which may lead to a reduced hospital stay and improved overall respiratory function. The aim of this short report was to assess the attitudes toward pulmonary rehabilitation following COVID-19 among Ecuadorian physicians. A cross-sectional study was conducted, in which a 5-question survey was used to assess the level of agreement to specific statements with a 5-point Likert scale. Out of the 282 participants, 48.2% (n=136) were male, with a mean of 12.6 (SD=11 ...


Sars-Cov-2 Reveals That Chimeric Agents Are The Bioweapons Of The Future, Rachel Craig 2022 Liberty University

Sars-Cov-2 Reveals That Chimeric Agents Are The Bioweapons Of The Future, Rachel Craig

Senior Honors Theses

Bioweapons programs have existed since their development during the Cold War. These biowarfare programs initially utilized naturally occurring pathogens capable of infecting crops, livestock populations, and human populations. Anthrax is a widely exploited bioagent responsible for attacks ranging from the Germans’ deployment in World War I to the mailing of anthrax through the postal service in attempts on U.S. senators’ lives. With the development of genetic manipulations, the Soviet Union began modifying anthrax to resist detection and treatment. With the continued advancement of science and technology, a new bioagent has entered the scene – the man-made chimeric virus. Chimeric viruses ...


Meta-Analysis Of Transcriptomic Datasets For The Investigation Of Differential Expression In Hantavirus-Infected Human Tissue, John Krapohl 2022 Roseman University of Health Sciences

Meta-Analysis Of Transcriptomic Datasets For The Investigation Of Differential Expression In Hantavirus-Infected Human Tissue, John Krapohl

Annual Research Symposium

No abstract provided.


Transcriptomic Analysis Of Liver Indicates Novel Vaccine To Porcine Reproductive And Respiratory Virus Promotes Homeostasis In T-Cell And Inflammatory Immune Responses Compared To A Commercial Vaccine In Pigs, Damarius S. Fleming, Laura C. Miller, Jiuyi Li, Albert Van Geelen, Yongming Sang 2022 USDA, Agricultural Research Service

Transcriptomic Analysis Of Liver Indicates Novel Vaccine To Porcine Reproductive And Respiratory Virus Promotes Homeostasis In T-Cell And Inflammatory Immune Responses Compared To A Commercial Vaccine In Pigs, Damarius S. Fleming, Laura C. Miller, Jiuyi Li, Albert Van Geelen, Yongming Sang

Agricultural and Environmental Sciences Faculty Research

One of the largest impediments for commercial swine production is the presence of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a devastating RNA viral infection that is responsible for over $1 billion in loss in the U.S. annually. The challenge with combating PRRSV is a combination of the effect of an extraordinary rate of mutation, the ability to infect macrophages, and subversion of host immune response through a series of actions leading to both immunomodulation and immune evasion. Currently there are a handful of commercial vaccines on the market that have been shown to be effective against homologous infections ...


Wc1 And Tcr Interactions For Γδ T Cell Activation, Alexandria Gillespie 2022 University of Massachusetts Amherst

Wc1 And Tcr Interactions For Γδ T Cell Activation, Alexandria Gillespie

Doctoral Dissertations

Major subpopulations of gamma delta T cells within ruminant and pigs are defined by expression of WC1, a hybrid pattern recognition receptor/co-receptor to the T cell receptor (TCR). It is known that when WC1 is knocked down cells fail to respond. Showing that WC1 plays an active role in the stimulation of bovine gamma delta T cells. Here we explored the spatio-temporal dynamics of WC1 and TCR interaction using imaging flow cytometry and stochastic optical reconstruction microscopy. We found that in quiescent gamma delta T cells both WC1 and TCR existed in separate protein domains (protein islands) but after ...


Innate Lymphoid Cells And Covid-19 Severity In Sars-Cov-2 Infection, Noah J. Silverstein, Yetao Wang, Claudia Carbone, Ann Dauphin, Jeremy Luban 2022 University of Massachusetts Medical School

Innate Lymphoid Cells And Covid-19 Severity In Sars-Cov-2 Infection, Noah J. Silverstein, Yetao Wang, Claudia Carbone, Ann Dauphin, Jeremy Luban

COVID-19 Publications by UMass Chan Authors

Background: Risk of severe COVID-19 increases with age, is greater in males, and is associated with lymphopenia, but not with higher burden of SARS-CoV-2. It is unknown whether effects of age and sex on abundance of specific lymphoid subsets explain these correlations.

Methods: Multiple regression was used to determine the relationship between abundance of specific blood lymphoid cell types, age, sex, requirement for hospitalization, duration of hospitalization, and elevation of blood markers of systemic inflammation, in adults hospitalized for severe COVID-19 (n=40), treated for COVID-19 as outpatients (n=51), and in uninfected controls (n=86), as well as in ...


Implementation Of A Drive-Through Covid-19 Mass Vaccination Site: Experiences From Louvax–Broadbent In Louisville, Kentucky, Ruth Carrico, Sarah Beth Hartlage, Valenchia Brown MSN, APRN, FNP-C, Sarah M. Bishop, Luanne Didelot, William Hayden, Beverly Williams Coleman, Sarah Tan, Delanor Manson, Kellie Kane, Dawn Balcom, Paul Kern 2022 Norton Infectious Diseases Institute

Implementation Of A Drive-Through Covid-19 Mass Vaccination Site: Experiences From Louvax–Broadbent In Louisville, Kentucky, Ruth Carrico, Sarah Beth Hartlage, Valenchia Brown Msn, Aprn, Fnp-C, Sarah M. Bishop, Luanne Didelot, William Hayden, Beverly Williams Coleman, Sarah Tan, Delanor Manson, Kellie Kane, Dawn Balcom, Paul Kern

The University of Louisville Journal of Respiratory Infections

Background: Response to the COVID-19 pandemic has required innovative approaches to vaccination, including methods to rapidly and safely immunize communities. A major challenge to such a response involved access to untapped healthcare worker resources. The Louisville, Kentucky, response involved the use of a large volunteer workforce to supplement local public health employees in planning and implementing a large-scale drive-through vaccination event. The objective of this manuscript was to outline processes involved in training a mass immunization workforce and implementating a large-scale COVID-19 community vaccination.

Approach: Competency-based and standardized training was provided for every volunteer before working their shift. Volunteers worked ...


Capsaicinoids From Capsicum Annuum As An Alternative Fabh Inhibitor Of Mycobacterium Tuberculosis: In Silico Study, Gabriella Chandrakirana Krisnamurti, Dewi Ratih Tirto Sari, Yohanes Bare 2021 Biotechnology Program, School of Bioresources and Technology, King Mongkut’s University of Technology Thonburi, Bang Khun Thian 10150, Thailand

Capsaicinoids From Capsicum Annuum As An Alternative Fabh Inhibitor Of Mycobacterium Tuberculosis: In Silico Study, Gabriella Chandrakirana Krisnamurti, Dewi Ratih Tirto Sari, Yohanes Bare

Makara Journal of Science

The number of tuberculosis (TB) cases worldwide reached 1.5 million in 2018; thus, TB is considered a deadly disease. TB is caused by Mycobacterium tuberculosis and involves lipid synthesis. Considering the importance of lipid metabolism in bacteria, FabH may be an essential protein target for repressing lipid synthesis. Capsaicinoids from Capsicum annuum demonstrate potent antibacterial activity. This study predicted the ability of capsaicinoid compounds to inhibit FabH. In silico analysis was performed by retrieving the structure of FabH from PDB and those of selected capsaicinoid derivatives from PubChem. The compounds were docked using AutoDock Vina in PyRx 0.8 ...


High-Affinity, Neutralizing Antibodies To Sars-Cov-2 Can Be Made Without T Follicular Helper Cells, Jennifer S. Chen, Gowthaman Uthaman, Craig B. Wilen, Stephanie C. Eisenbarth 2021 Yale University

High-Affinity, Neutralizing Antibodies To Sars-Cov-2 Can Be Made Without T Follicular Helper Cells, Jennifer S. Chen, Gowthaman Uthaman, Craig B. Wilen, Stephanie C. Eisenbarth

COVID-19 Publications by UMass Chan Authors

T follicular helper (Tfh) cells are the conventional drivers of protective, germinal center (GC)-based antiviral antibody responses. However, loss of Tfh cells and GCs has been observed in patients with severe COVID-19. As T cell-B cell interactions and immunoglobulin class switching still occur in these patients, non-canonical pathways of antibody production may be operative during SARS-CoV-2 infection. We found that both Tfh-dependent and -independent antibodies were induced against SARS-CoV-2 infection, SARS-CoV-2 vaccination, and influenza A virus infection. Even though Tfh-independent antibodies to SARS-CoV-2 had evidence of reduced somatic hypermutation, they were still high-affinity, durable, and reactive against diverse spike-derived ...


Moraxella Species Associated With Infectious Bovine Keratoconjunctivitis: Detection, Characterization, And Immunity, Matthew M. Hille 2021 University of Wyoming & University of Nebraska-Lincoln

Moraxella Species Associated With Infectious Bovine Keratoconjunctivitis: Detection, Characterization, And Immunity, Matthew M. Hille

Dissertations & Theses in Veterinary and Biomedical Science

Infectious bovine keratoconjunctivitis (IBK) represents the most common ocular disease of cattle. Moraxella bovis (M. bovis) is the only bacteria proven to cause IBK under experimental conditions. A closely related bacteria, Moraxella bovoculi (M. bovoculi) is cultured from IBK lesions more frequently than M. bovis, and is suspected to cause IBK, although a causal relationship between M. bovoculi and IBK has not been confirmed experimentally. Two distinct genotypes were recently characterized in M. bovoculi based on whole genome sequencing. Genotype 1 M. bovoculi appears to represent a potential pathogen whereas genotype 2 M. bovoculi appears to represent a nonpathogenic normal ...


Determinants Of Precocious B-Cell Aging In European Adolescents Living With Perinatally Acquired Hiv-1 After Over 10 Years Of Suppressive Therapy [Preprint], Alessandra Ruggiero, Katherine Luzuriaga, Paolo Palma 2021 University of Verona

Determinants Of Precocious B-Cell Aging In European Adolescents Living With Perinatally Acquired Hiv-1 After Over 10 Years Of Suppressive Therapy [Preprint], Alessandra Ruggiero, Katherine Luzuriaga, Paolo Palma

UMass Chan Medical School Faculty Publications

HIV infection results in a state of chronic immune activation leading to premature immune aging, B-cells dysfunction, that persists despite prolonged virological suppression. In this scenario, adolescence living with perinatally acquired HIV (PHIV), deserve a peculiar attention since potentially exposed for their entire life to chronic immune activation. Here we identified determinants of precocious aging B cells in 40 PHIV undergoing suppressive antiretroviral therapy (ART) for median 13.5 years. All individuals started ART by 2nd year of life and achieved virus suppression within the 1st year of ART, with majority of patient maintaining suppression until analysis and 5/40 ...


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