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Automated Processing Of Metabolomics Data For Population-Scale Studies, Ethan Stancliffe Aug 2023

Automated Processing Of Metabolomics Data For Population-Scale Studies, Ethan Stancliffe

Arts & Sciences Graduate Student Theses and Dissertations

The growth of untargeted metabolomic profiling technology has prompted the upstart of many large cohort studies. Metabolomics serves as an informative complement to other more established ‘omics (e.g., genomics, transcriptomics, proteomics). As a younger discipline, however, experimental and computational workflows are non-standardized and at times inadequate for large-scale studies. Two primary limitations in analysis of untargeted metabolomics data are 1) the poor performance and scalability of the algorithms applied to detect metabolite signals from the raw LC/MS data and 2) inefficient and arduous metabolite identification, which is the process of determining the biochemical structures that correspond to the detected LC/MS …


Evaluation Of Different Stocking Densities On Fattening Performance, Slaughter, Carcass, Meat Quality Characteristics, And Fatty Acid Composition In New Zealand Rabbits, Büşra Yaranoğlu, Mustafa Hi̇lmi̇ Yaranoğlu, Sali̇ha Uysal, Adnan Adi̇l Hi̇şmi̇oğullari Aug 2023

Evaluation Of Different Stocking Densities On Fattening Performance, Slaughter, Carcass, Meat Quality Characteristics, And Fatty Acid Composition In New Zealand Rabbits, Büşra Yaranoğlu, Mustafa Hi̇lmi̇ Yaranoğlu, Sali̇ha Uysal, Adnan Adi̇l Hi̇şmi̇oğullari

Turkish Journal of Veterinary & Animal Sciences

The aim of the research was to investigate the effects of different stocking densities on fattening performance, slaughter, carcass, meat quality characteristics, and fatty acid composition in New Zealand rabbits raised in cage conditions and also determine the ideal housing frequency so that yields were not adversely affected. In the study, 36 New Zealand rabbits were used. After weaning, the fattening was started and rabbits were put into cages at different stocking densities as 1 rabbit/cage, 2 rabbits/cage, and 3 rabbits/ cage. The live weight of rabbits and feed consumption data were taken every week. At the end of 8 …


Comparison Of Bacterial Profile And Antibiotic Susceptibility Isolated From Surgical Site After Ventral Midline And Lateral Flank Approaches Of Ovariohysterectomy In Queens And Bitches, Ebru Karakaya Bi̇len, Serpi̇l Kahya Demi̇rbi̇lek, Öznur Yilmaz, Muhammet Ali̇ Karadağ, Havva Aner Aug 2023

Comparison Of Bacterial Profile And Antibiotic Susceptibility Isolated From Surgical Site After Ventral Midline And Lateral Flank Approaches Of Ovariohysterectomy In Queens And Bitches, Ebru Karakaya Bi̇len, Serpi̇l Kahya Demi̇rbi̇lek, Öznur Yilmaz, Muhammet Ali̇ Karadağ, Havva Aner

Turkish Journal of Veterinary & Animal Sciences

The aim of the study was to identify the bacterial profile and antimicrobial susceptibility from surgical site cultures in queens and bitches undergoing ovariohysterectomy via ventral midline and lateral flank approaches. Healthy 22 queens and 21 bitches were assigned randomly either ventral midline or lateral flank approach for routine ovariohysterectomy. Surgical site samples were collected before the surgery and on the 1$^{st}$, 2$^{nd}$ , and 3 $^{rd}$days after the surgery for microbiological analysis. A total of 70 different strains were isolated from 50 (29%) of 172 samples. In both queens and bitches the total number of bacteria isolated from the …


Determination Of Virulence Genes And Antibiotic Resistance Profiles Of Streptococcus Agalactiae Isolated From Buffalo Milk, Nevi̇n Tuzcu, Hasan Hüseyi̇n Hadi̇mli̇, Beatri̇z Padron Aug 2023

Determination Of Virulence Genes And Antibiotic Resistance Profiles Of Streptococcus Agalactiae Isolated From Buffalo Milk, Nevi̇n Tuzcu, Hasan Hüseyi̇n Hadi̇mli̇, Beatri̇z Padron

Turkish Journal of Veterinary & Animal Sciences

Mastitis is a contagious disease that causes significant milk loss and serious economic damage in dairy animals. Streptococcus agalactiae causes clinical and subclinical mastitis in animals and infections in humans, especially adults, and newborns. This study aimed to confirm the identification of S. agalactiae isolates by PCR in buffalo milk; to determine the antibiotic resistance and virulence genes by multiplex PCR. The material of this study consisted of 30 (12%) S. agalactiae strains identified by phenotypic, biochemical, and PCR methods (rRNA-16S) from 250 isolates with bacterial growth from milk samples of buffaloes with mastitis. In addition, the Kirby-Bauer disc diffusion …


In Vitro Antimicrobial And Antibiofilm-Forming Activities Of Origanum Munzurense Plant Extract On Some Foodborne Gram-Negative Bacteria, Hali̇l Yalçin, Esra Zeybek, Oktay Özkan, Asim Kart Aug 2023

In Vitro Antimicrobial And Antibiofilm-Forming Activities Of Origanum Munzurense Plant Extract On Some Foodborne Gram-Negative Bacteria, Hali̇l Yalçin, Esra Zeybek, Oktay Özkan, Asim Kart

Turkish Journal of Veterinary & Animal Sciences

lants are an important source for the discovery of antimicrobial formulations due to the many biologically active components they contain. In this study, in vitro antimicrobial and antibiofilm forming activities of ethanolic extract of Origanum munzurense were investigated against some strains of foodborne pathogenic bacteria. To investigate the antimicrobial activity, the minimal inhibitory concentration values against the selected bacteria and antibiofilm-forming activity were tested with the liquid microdilution method and microplate method, respectively. MICs of Origanum munzurense extract against the bacteria tested are 32 mg/mL for Escherichia coli O157: H7 ATCC 35150, 32 mg/mL for Escherichia coli O157: H7 ATCC …


Immunological Monitoring In Hepatitis C Virus Controlled Human Infection Model, Naglaa H Shoukry, Andrea L Cox, Christopher M Walker Aug 2023

Immunological Monitoring In Hepatitis C Virus Controlled Human Infection Model, Naglaa H Shoukry, Andrea L Cox, Christopher M Walker

Faculty, Staff and Student Publications

Controlled human infection model trials for hepatitis C virus represent an important opportunity to identify correlates of protective immunity against a well-characterized inoculum of hepatitis C virus and how such responses are modified by vaccination. In this article, we discuss the approach to immunological monitoring during such trials, including a set of recommendations for optimal sampling schedule and preferred immunological assays to examine the different arms of the immune response. We recommend that this approach be adapted to different trial designs. Finally, we discuss how these studies can provide surrogate predictors of the success of candidate vaccines.


Mutation-Induced Changes In The Stability, B-Cell Epitope, And Antigenicity Of The Sars-Cov-2 Variant Spike Protein: A Comparative Computational Stud, Nira Meirita Wijayanti, Muhammad Hermawan Widyananda, Lailil Muflikhah, Nashi Widodo Aug 2023

Mutation-Induced Changes In The Stability, B-Cell Epitope, And Antigenicity Of The Sars-Cov-2 Variant Spike Protein: A Comparative Computational Stud, Nira Meirita Wijayanti, Muhammad Hermawan Widyananda, Lailil Muflikhah, Nashi Widodo

Karbala International Journal of Modern Science

The spike (S) protein is a major antigenicity site that targets neutralizing antibodies and drugs. The growing number of S protein mutations has become a severe problem for developing effective vaccines. Here, we investigated four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that were the most infectious and widespread during the COVID-19 pandemic to determine the trends and patterns of mutation-induced changes in the stability, B-cell epitope, and antigenicity of the SARS-CoV-2 S protein. The data showed that the Beta and Gamma variants had three mutations on the receptor-binding domain (RBD), which is the specific site on the S …


The Devil You Know And The Devil You Don’T: Current Status And Challenges Of Bovine Tuberculosis Eradication In The United States, Daniel J. O'Brien, Tyler C. Thacker, Liliana C.M. Salvador, Anthony G. Duffiney, Suelee Robbe‑Austerman, Mark S. Camacho, Jason E. Lombard, Mitchell V. Palmer Aug 2023

The Devil You Know And The Devil You Don’T: Current Status And Challenges Of Bovine Tuberculosis Eradication In The United States, Daniel J. O'Brien, Tyler C. Thacker, Liliana C.M. Salvador, Anthony G. Duffiney, Suelee Robbe‑Austerman, Mark S. Camacho, Jason E. Lombard, Mitchell V. Palmer

United States Department of Agriculture Wildlife Services: Staff Publications

Having entered into its second century, the eradication program for bovine tuberculosis (bTB, caused by Mycobacterium bovis) in the United States of America occupies a position both enviable and daunting. Excepting four counties in Michigan comprising only 6109 km2 (0.06% of US land area) classified as Modified Accredited, as of April 2022 the entire country was considered Accredited Free of bTB by the US Department of Agriculture for cattle and bison. On the surface, the now well-described circumstances of endemic bTB in Michigan, where white-tailed deer (Odocoileus virginianus) serve as a free-ranging wildlife maintenance host, may appear to be …


Dna Methylation Networks Underlying Mammalian Traits, Amin Haghani Aug 2023

Dna Methylation Networks Underlying Mammalian Traits, Amin Haghani

Department of Animal Science: Faculty Publications

INTRODUCTION: Comparative epigenomics is an emerging field that combines epigenetic signatures with phylogenetic relationships to elucidate species characteristics such as maximum life span. For this study, we generated cytosine DNA methylation (DNAm) profiles (n = 15,456) from 348mammalian species using amethylation array platform that targets highly conserved cytosines.

RATIONALE: Nature has evolved mammalian species of greatly differing life spans. To resolve the relationship ofDNAmwith maximum life span and phylogeny, we performed a largescale cross-species unsupervised analysis. Comparative studies in many species enables the identification of epigenetic correlates of maximum life span and other traits.

RESULTS: We …


Understanding And Quantifying Bioaerosol Fate Within The Aerobiological Pathway: Physical Transport, Environmental Decay, And Mitigation, Sean Kinahan Aug 2023

Understanding And Quantifying Bioaerosol Fate Within The Aerobiological Pathway: Physical Transport, Environmental Decay, And Mitigation, Sean Kinahan

Theses & Dissertations

The recent COVID-19 pandemic has highlighted the need for better tools to understand and characterize phases of the aerobiological pathway, a model for understanding how infectious bioaerosols are sourced, generated, transported, deposit, and affect human health. This dissertation presents validation of methodologies for studying transport of airborne biological agents and variations on their consequences, especially focusing on their physical and chemical fate. Chapter 1 focuses on a parallel comparison of two methods of aging bioaerosols in real-world outdoor environments with complex sunlight, atmospheric chemistry, and pollutants. Both capture on microfibers and the use of Goldberg rotating drums to keep a …


Genome-Scale Methylation Analysis In Blood And Tumor Identifies Immune Profile, Age Acceleration, And Dna Methylation Alterations Associated With Bladder Cancer Outcomes, Ji-Qing Chen Aug 2023

Genome-Scale Methylation Analysis In Blood And Tumor Identifies Immune Profile, Age Acceleration, And Dna Methylation Alterations Associated With Bladder Cancer Outcomes, Ji-Qing Chen

Dartmouth College Ph.D Dissertations

Bladder cancer patients receive frequent screening due to the high tumor recurrence rate (more than 60%). Nowadays, the conventional monitoring method relies on cystoscopy which is highly invasive and increases patient morbidity and burden to the health care system with frequent follow-up. As a result, it is urgent to explore novel markers related to the outcomes of bladder cancer. Immune profiles have been associated with cancer outcomes and may have the potential to be biomarkers for outcomes management. However, little work has been conducted to investigate the associations of immune cell profiles with bladder cancer outcomes. Here, I utilized the …


Parasites Versus Predation: The Role Of Chronic And Acute Parasite Exposure In Infection Risk And Anti-Predator Behavior, Delaney Farrell Aug 2023

Parasites Versus Predation: The Role Of Chronic And Acute Parasite Exposure In Infection Risk And Anti-Predator Behavior, Delaney Farrell

All HCAS Student Capstones, Theses, and Dissertations

Parasites with complex, multi-host lifecycles often engage in host behavior manipulation to increase transmission between successive hosts. In intermediate fish hosts, previous research has measured increased frequency of conspicuous behaviors, decreased swimming performance, and reduced antipredator behavior, which would collectively increase the fish’s risk of predation. In ecosystems where this type of parasite increased trophic transmission (PITT) occurs, parasites can play a substantial role in food webs. In this study, I investigate how chronic versus acute exposure to the trematode Euhaplorchis sp. A. affects the antipredator behavior of the Gulf killifish Fundulus grandis. Using a fully crossed design, I …


Investigating Transcriptional Anomalies During Persistence In Chlamydia Trachomatis, Nathan D. Hatch Aug 2023

Investigating Transcriptional Anomalies During Persistence In Chlamydia Trachomatis, Nathan D. Hatch

Theses & Dissertations

Chlamydia trachomatis (Ctr) is the leading cause of bacterial sexually transmitted infections. Ctr, a Gram-negative, obligate intracellular bacterium, develops within a membrane-bound vacuole termed an inclusion. This protective, nutrient rich, intracellular environment has allowed Ctr to undergo extensive reductive evolution – resulting in a streamlined genome of approximately 1 Mbp and the loss or fragmentation of several biosynthetic pathways, including the ability to synthesize tryptophan (Trp) de novo. During infection, the host immune system releases the cytokine IFNγ. Upon binding to a host cell, IFNγ stimulates the expression of indoleamine-2,3-dioxygenase, an enzyme capable of catabolizing cytosolic Trp, thereby starving …


Cytokine Profiles In Peruvian Pinnipeds And Their Relationships With Environmental Stressors, Mykenzee L. Munaco Aug 2023

Cytokine Profiles In Peruvian Pinnipeds And Their Relationships With Environmental Stressors, Mykenzee L. Munaco

All HCAS Student Capstones, Theses, and Dissertations

Large colonies of two vulnerable, sympatric pinniped species, Peruvian fur seals (Arctocephalus australis Peruvian subpopulation; PFS) and South American sea lions (Otaria byronia; SASL), reside and reproduce in Punta San Juan, Peru (PSJ) where they are exposed to stressors such as environmental contaminants and El Niño-Southern Oscillation (ENSO) events. Cytokine concentrations can be indicative of an animal’s health and immune function by allowing for immunoresponse characterization as Th1 or Th2 dominant. Utilizing an archived pinniped plasma collection of samples from 2009-2019 (n=148), 13 cytokines were analyzed in PFS and SASL: GM-CSF, IFN-γ, KC-like, MCP-1, TNF-α, IL-2, IL-6, …


Real-World Experience Of Patients With Multiple Myeloma Receiving Ide-Cel After A Prior Bcma-Targeted Therapy, Christopher J Ferreri, Michelle A T Hildebrandt, Hamza Hashmi, Leyla O Shune, Joseph P Mcguirk, Douglas W Sborov, Charlotte B Wagner, M Hakan Kocoglu, Aaron Rapoport, Shebli Atrash, Peter M Voorhees, Jack Khouri, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, Larry D Anderson, Gary Simmons, James A Davis, Nilesh Kalariya, Lauren C Peres, Yi Lin, Murali Janakiram, Omar Nadeem, Melissa Alsina, Frederick L Locke, Surbhi Sidana, Doris K Hansen, Krina K Patel, Omar Alexis Castaneda Puglianini Aug 2023

Real-World Experience Of Patients With Multiple Myeloma Receiving Ide-Cel After A Prior Bcma-Targeted Therapy, Christopher J Ferreri, Michelle A T Hildebrandt, Hamza Hashmi, Leyla O Shune, Joseph P Mcguirk, Douglas W Sborov, Charlotte B Wagner, M Hakan Kocoglu, Aaron Rapoport, Shebli Atrash, Peter M Voorhees, Jack Khouri, Danai Dima, Aimaz Afrough, Gurbakhash Kaur, Larry D Anderson, Gary Simmons, James A Davis, Nilesh Kalariya, Lauren C Peres, Yi Lin, Murali Janakiram, Omar Nadeem, Melissa Alsina, Frederick L Locke, Surbhi Sidana, Doris K Hansen, Krina K Patel, Omar Alexis Castaneda Puglianini

Faculty, Staff and Student Publications

Most patients with multiple myeloma experience disease relapse after treatment with a B-cell maturation antigen-targeted therapy (BCMA-TT), and data describing outcomes for patients treated with sequential BCMA-TT are limited. We analyzed clinical outcomes for patients infused with standard-of-care idecabtagene vicleucel, an anti-BCMA chimeric antigen receptor (CAR) T-cell therapy, at 11 US medical centers. A total of 50 patients with prior BCMA-TT exposure (38 antibody-drug conjugate, 7 bispecific, 5 CAR T) and 153 patients with no prior BCMA-TT were infused with ide-cel, with a median follow-up duration of 4.5 and 6.0 months, respectively. Safety outcomes between cohorts were comparable. The prior …


Nutritional Strategies To Reduce Salmonella Enteritidis Infections In Laying Hens: Prebiotic, Probiotic, And Precision Biotics, Ishab Poudel Aug 2023

Nutritional Strategies To Reduce Salmonella Enteritidis Infections In Laying Hens: Prebiotic, Probiotic, And Precision Biotics, Ishab Poudel

Theses and Dissertations

Salmonella Enteritidis (SE) infections in laying hens is a significant cause of foodborne illness linked to the consumption of contaminated eggs. This dissertation encompasses novel strategies aimed to explore appropriate in-vitro and in-vivo models to evaluate the effects of these novel strategies to reduce SE in laying hens. Firstly, we investigated the potential probiotics, prebiotics, and essential oil combinations to reduce SE in-vitro. The results showed that probiotics and prebiotics are equally effective to reduce SE. In subsequent studies, we evaluated the role of vaccination history on cecal microbiota and SE infections with various doses of oral SE challenge. …


Advancing Poultry Nutrition Through Statistical Strategies To Reduce Experimental Variation And Novel Protease Enzyme Research, Caleb Morgan Marshall Aug 2023

Advancing Poultry Nutrition Through Statistical Strategies To Reduce Experimental Variation And Novel Protease Enzyme Research, Caleb Morgan Marshall

Theses and Dissertations

Increasingly, nutritionists are challenged to optimize broiler genetic capacity, while considering varying ingredient qualities and pricing, to meet production goals and profitability. Due to scale and cost, university and private research is often used by nutritionists to help make these decisions; thus, requiring these facilities to detect small, incremental improvements. In Chapters 1 and 2, processing data from several nutrition research trials were utilized to evaluate the impact of processing personnel, sample size, and unit of analysis on the detection of dietary differences. By accounting for potential variability between personnel (as a covariant) and selecting an adequate sample size for …


Use Of Comparative Genomics And In Vitro Screening Approach To Identify Vaccine Candidates For The Food-Borne Pathogen Campylobacter Jejuni, Sabin Poudel Aug 2023

Use Of Comparative Genomics And In Vitro Screening Approach To Identify Vaccine Candidates For The Food-Borne Pathogen Campylobacter Jejuni, Sabin Poudel

Theses and Dissertations

Campylobacteriosis is a leading foodborne illness worldwide, primarily caused by Campylobacter jejuni (C. jejuni) which is associated with poultry consumption. The emergence of antibiotic resistance has emphasized the need for alternative strategies to control C. jejuni colonization in poultry. To assess the prevalence of C. jejuni in poultry, 270 cloacal swab samples were collected from broilers raised under No-Antibiotics Ever system. Among these samples, 16.3% were identified as C. jejuni positive. Notably, these isolates exhibited a diverse range of virulence factors and antimicrobial resistance genes, with 61.36% of isolates showing hyper-motile and 20.45% demonstrating multidrug resistance. Following isolation, whole genome …


Evaluating The Role Of The Bovine Vaginal Microbiome In Neonatal And Maternal Health Outcomes, Riley D. Messman Aug 2023

Evaluating The Role Of The Bovine Vaginal Microbiome In Neonatal And Maternal Health Outcomes, Riley D. Messman

Theses and Dissertations

The dam vaginal microbiota is the first major microbial inoculating community within the neonate. The composition of the dam vaginal microbiota has implications in calf commensal microbiota development. Alterations of the dam microbial community prior to parturition could alter inoculating communities and immune responses in both the dam and calf. Thus, authors aimed to elucidate the microbial community composition of the bovine dam vaginal and calf nasal microbiota post-partum after utilizing betadine lavages (BL). The dam vaginal and calf nasal microbial communities and immune responses were evaluated at 0-, 15-, 30- and 60-day post-partum. Microbiota composition of the dam haircoat, …


Evaluating The Immunogenicity Of Colonization Proteins Of S. Pneumoniae For Identification Of Vaccine Candidates, Isidora Fereday Aug 2023

Evaluating The Immunogenicity Of Colonization Proteins Of S. Pneumoniae For Identification Of Vaccine Candidates, Isidora Fereday

Theses and Dissertations

Streptococcus pneumoniae is typically an asymptomatic colonizer of the upper respiratory tract but can cause invasive disease in susceptible populations. Pneumococcal vaccines which are currently in use have failed to significantly reduce colonization by S. pneumoniae. To control invasive pneumococcal disease, novel strategies must be utilized. One such strategy is to reduce or eradicate colonization by pneumococcus. Supplementary vaccination with pneumococcal proteins important for colonization could serve to prime the immune system against these targets. This study serves as an initial step towards identification of crucial pneumococcal colonization proteins which may previously have been uncharacterized. Assessing the immune reactivity …


The Development Of Fetal Immunity From In Utero To Shortly After Birth And Complications That Can Arise From Improper Functioning, Marlee Curnutt Aug 2023

The Development Of Fetal Immunity From In Utero To Shortly After Birth And Complications That Can Arise From Improper Functioning, Marlee Curnutt

Masters Projects

The development of the immune system in humans is highly complex and requires precise timing which is still debated today. Research has shown IL-10 and T-regulatory cells play a significant role in the proper development of the immune system from in utero continuing into months after birth. These components and various cytokines continue to be guiding factors supplemented by the mother via placenta and breastfeeding. The dysregulation of immune development can have detrimental effects on the infant and may lead to autoimmune disorders. In this paper, we aim to further understand the development of the immune system from fetal to …


Cancer: The Burden Of Treatments Eased By Recent Developments In The Field: A Review Of The Literature, Zachary J. Seim Aug 2023

Cancer: The Burden Of Treatments Eased By Recent Developments In The Field: A Review Of The Literature, Zachary J. Seim

Masters Projects

Cancer is a very prevalent disease that has affected most of the population. Treatment options that have been used for decades are beginning to be outcompeted by newer developments in the field. Newer developments allow a more specific response to cancers that have proven to be very difficult for traditional treatment. Immune specific treatments also give the ability to specifically target areas affected by the cancer, to reduce potential risk of systemic damage and autoimmunity. Developing cancer treatments that are highly specific brings forth a new age of medicine, hoping to prolong the life expectancy of those affected with cancers, …


Distinct Roles For Ltα3 And Ltα1Β2 Produced By B Cells Contribute To Their Multi-Faceted Impact On Ileitis, Emma Claire Erlich Aug 2023

Distinct Roles For Ltα3 And Ltα1Β2 Produced By B Cells Contribute To Their Multi-Faceted Impact On Ileitis, Emma Claire Erlich

Arts & Sciences Graduate Student Theses and Dissertations

Crohn’s disease, one of the most common forms of inflammatory bowel disease, is marked by local intestinal inflammation. However, pathology in CD patients is not strictly limited to the gastrointestinal system, and almost 50% of CD patients exhibit extraintestinal manifestations of disease. Many, though not all, of these systemic pathologies are linked to intestinal inflammation and, thus, resolution of local gastrointestinal disease also ameliorates systemic disease. How the connection between local and systemic inflammation is mediated is not well understand, nor is why only some patients exhibit these extraintestinal manifestations of disease. Blocking dissemination of inflammatory signals generated in the …


Traf3-Ewsr1 Signaling Axis Acts As A Checkpoint On Germinal Center Responses, Yanchuan Li, Lele Zhu, Chun-Jung Ko, Jin-Young Yang, Hongjiao Wang, Ganiraju Manyam, Jing Wang, Xuhong Cheng, Shuli Zhao, Zuliang Jie Aug 2023

Traf3-Ewsr1 Signaling Axis Acts As A Checkpoint On Germinal Center Responses, Yanchuan Li, Lele Zhu, Chun-Jung Ko, Jin-Young Yang, Hongjiao Wang, Ganiraju Manyam, Jing Wang, Xuhong Cheng, Shuli Zhao, Zuliang Jie

Faculty, Staff and Student Publications

The formation of germinal centers (GCs) is crucial for humoral immunity and vaccine efficacy. Constant stimulation through microbiota drives the formation of constitutive GCs in Peyer's patches (PPs), which generate B cells that produce antibodies against gut antigens derived from commensal bacteria and infectious pathogens. However, the molecular mechanism that regulates this persistent process is poorly understood. We report that Ewing Sarcoma Breakpoint Region 1 (EWSR1) is a brake to constitutive GC generation and immunoglobulin G (IgG) production in PPs, vaccination-induced GC formation, and IgG responses. Mechanistically, EWSR1 suppresses Bcl6 upregulation after antigen encounter, thereby negatively regulating induced GC B …


Roles Of Type I Interferon Signaling In Drug Resistant Mycobacterium Tuberculosis Infection, Suhas Bobba Aug 2023

Roles Of Type I Interferon Signaling In Drug Resistant Mycobacterium Tuberculosis Infection, Suhas Bobba

Arts & Sciences Graduate Student Theses and Dissertations

Tuberculosis (TB) is a global health threat, with 10 million people developing active TB disease and a million deaths attributed to TB annually. Emergence of drug resistance in Mycobacterium tuberculosis (Mtb), the causative agent of TB, has led to half a million cases of drug resistant (DR) TB annually. Further, clinical reports suggest dysregulation and suppression of immune responses in DR TB patients as compared with DS TB patients. However, we do not understand how acquisition of drug resistance-conferring mutations can drive broad and systemic differences in immune responses of DR TB patients. We found that rpoB-H445Y a specific DR …


Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke Aug 2023

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …


Multiphasic Molecular Mechanisms Regulate Expression Of Interleukin 1Β, As Well As Other Immediate-Early Genes, In Monocytes And Macrophages, David Macar Aug 2023

Multiphasic Molecular Mechanisms Regulate Expression Of Interleukin 1Β, As Well As Other Immediate-Early Genes, In Monocytes And Macrophages, David Macar

Electronic Theses and Dissertations

Interleukin 1β (IL-1β), an important cytokine in both health and disease, functions as a major proinflammatory mediator of pathological challenges, including involvement in the cytokine storm associated with Macrophage Activation Syndrome, Hemophagocytic Lymphohistiocytosis and the severe secondary effects of SARS-CoV-2 infection. Therapeutic approaches to limiting the effects of IL-1β protein have focused either on specific protein neutralization before release from activated macrophages (by general metabolic inhibitors and inflammasome inhibition) or after release by ligand and receptor obstruction (e.g., Canakinumab, Anakinra and Rilonacept). Although these approaches are efficacious, they inhibit steps after gene expression. Since a single gene expresses …


Investigating How Sterol Transport Affects Survival Of The Pathogenic Fungus Cryptococcus Neoformans In Host-Like Conditions, Hau Lam Choy Aug 2023

Investigating How Sterol Transport Affects Survival Of The Pathogenic Fungus Cryptococcus Neoformans In Host-Like Conditions, Hau Lam Choy

Arts & Sciences Graduate Student Theses and Dissertations

Cryptococcus neoformans is an opportunistic fungal pathogen that has an enormous impact on global health and is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. With a mortality rate of 10-75%, cryptococcal meningitis results in over 100,000 deaths per year, comprising 18% of all AIDS-related deaths worldwide. These numbers emphasize the need to understand the basic biology and pathogenesis of this fungus. During infection, spores or desiccated yeast cells are inhaled, resulting in primary pulmonary infection. In immunocompetent hosts, these infections are asymptomatic and are either quickly cleared or remain latent. In immunocompromised patients, …


Safety And Efficacy Of Immune Checkpoint Inhibitors In Patients With Cancer And Viral Hepatitis: The Md Anderson Cancer Center Experience, Mirella Nardo, Bulent Yilmaz, Blessie Elizabeth Nelson, Harrys A Torres, Lan Sun Wang, Bruno Palma Granwehr, Juhee Song, Hanna R F Dalla Pria, Van A Trinh, Isabella C Glitza Oliva, Sapna P Patel, Nizar M Tannir, Ahmed Omar Kaseb, Mehmet Altan, Sunyoung S Lee, Ethan Miller, Hao Zhang, Bettzy A Stephen, Aung Naing Aug 2023

Safety And Efficacy Of Immune Checkpoint Inhibitors In Patients With Cancer And Viral Hepatitis: The Md Anderson Cancer Center Experience, Mirella Nardo, Bulent Yilmaz, Blessie Elizabeth Nelson, Harrys A Torres, Lan Sun Wang, Bruno Palma Granwehr, Juhee Song, Hanna R F Dalla Pria, Van A Trinh, Isabella C Glitza Oliva, Sapna P Patel, Nizar M Tannir, Ahmed Omar Kaseb, Mehmet Altan, Sunyoung S Lee, Ethan Miller, Hao Zhang, Bettzy A Stephen, Aung Naing

Faculty, Staff and Student Publications

Background: Despite the clinical benefit of immune checkpoint inhibitors (ICIs), patients with a viral hepatitis have been excluded from clinical trials because of safety concerns. The purpose of this study was to determine the incidence rate of adverse events (AEs) in patients with viral hepatitis who received ICIs for cancer treatment.

Materials and methods: We conducted a retrospective study in patients with cancer and concurrent hepatitis B or C, who had undergone treatment with ICI at MD Anderson Cancer Center from January 1, 2010 to December 31, 2019.

Results: Of the 1076 patients screened, we identified 33 with concurrent hepatitis. …


Sensing The Rhizosphere: Microbial Transcriptome Responses To Root Exudates And Redox-Active Metabolites, Ankita Bhattacharyya Aug 2023

Sensing The Rhizosphere: Microbial Transcriptome Responses To Root Exudates And Redox-Active Metabolites, Ankita Bhattacharyya

Dissertations

The term “rhizosphere” describes the dynamic interface between plant roots and soil influenced by root exudates. It is a hotspot of microbial activity, plant-microbe, and microbe-microbe interactions. Distinct variations in bacterial diversity are thought to be driven by plant root exudates. However, the molecular details of these processes still remain unclear.

I addressed this gap by focusing on two strains, Pseudomonas synxantha 2-79 and Burkholderia lata 383, representing diverse groups of Gammaproteobacteria comprised of species with environmental, agricultural, and medical significance. In the first part of this project, we used a combination of metabolomics and RNA-seq to characterize transcriptome responses …