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Articles 2491 - 2520 of 14543
Full-Text Articles in Entire DC Network
Life Stressors And Immune Aging: Protective Effects Of Cognitive Reappraisal, Rebecca G. Reed, Steven R. Presnell, Ahmad Al-Attar, Charles T. Lutz, Suzanne C. Segerstrom
Life Stressors And Immune Aging: Protective Effects Of Cognitive Reappraisal, Rebecca G. Reed, Steven R. Presnell, Ahmad Al-Attar, Charles T. Lutz, Suzanne C. Segerstrom
Markey Cancer Center Faculty Publications
Stressful life events may accelerate aspects of immune aging, but habitual use of an adaptive emotion regulation strategy, cognitive reappraisal, may attenuate these effects. This study examined whether cognitive reappraisal moderates the associations between life stressor frequency and stressor desirability on aspects of immune aging, including late-differentiated CD8+ T and natural killer (NK) cells and inflammatory markers (IL-6, TNF-α, and CRP), both between and within people in a longitudinal sample of 149 older adults (mean age = 77.8, range: 64–92 years). Participants reported stressful life events, use of cognitive reappraisal, and provided blood semiannually for up to 5 years to …
Effect Of Temperature On The Microbiome Of A Laboratory-Reared Colony Of Haemaphysalis Longicornis Ticks, Brianna L. Mitchell
Effect Of Temperature On The Microbiome Of A Laboratory-Reared Colony Of Haemaphysalis Longicornis Ticks, Brianna L. Mitchell
Honors Theses
Haemaphysalis longicornis ticks are invasive to the United States with potential to transmit several tick-borne pathogens that are native to the United States. Based on existing locations of H. longicornis in its native regions in Asia, as well as its invasive populations that are established in the United States, several geographic range prediction models have been produced to help understand future range expansion and distribution of this invasive tick in North America. Unfortunately, these models do not all agree and there is uncertainty associated with the potential geographic range expansion of H. longicornis ticks in North America. Climate can affect …
Scientific Kenyon: Neuroscience Edition (Full Issue)
Scientific Kenyon: Neuroscience Edition (Full Issue)
Scientific Kenyon: The Neuroscience Edition
No abstract provided.
Investigating The Roles Of Lung Epithelial Stat3 In Therapeutically Inducible Resistance To Acute Bacterial Pneumonia., Vikram V. Kulkarni, Vikram V. Kulkarni
Investigating The Roles Of Lung Epithelial Stat3 In Therapeutically Inducible Resistance To Acute Bacterial Pneumonia., Vikram V. Kulkarni, Vikram V. Kulkarni
Dissertations and Theses (Open Access)
Investigating the roles of lung epithelial STAT3 in therapeutically inducible resistance to acute bacterial pneumonia.
Vikram Vitthal Kulkarni, M.S.
Advisory Professor: Scott Evans, MD.
The lung epithelium is a dynamic tissue capable of displaying structural and functional plasticity in response to pathogenic challenges. Our lab has demonstrated that it is possible to therapeutically exploit the lung epithelium’s versatility by inducing resistance to lethal pneumonias caused by viruses, bacteria and fungi. An inhaled combination of a TLR2/6 agonist and a TLR9 agonist (Pam2ODN) results in robust protection against otherwise lethal pneumonia caused by Pseudomonas aeruginosa. Pam2ODN-mediated protection requires key signaling …
The Cx3cl1-Cx3cr1 Chemokine Axis Contributes To Tumor Immune Evasion And Its Blockade Enhances Responses To Anti-Pd-1 Immunotherapy, Apoorvi Chaudhri
The Cx3cl1-Cx3cr1 Chemokine Axis Contributes To Tumor Immune Evasion And Its Blockade Enhances Responses To Anti-Pd-1 Immunotherapy, Apoorvi Chaudhri
Dissertations and Theses (Open Access)
CX3CL1 secreted in the tumor microenvironment serves as a chemoattractant playing a critical role in metastasis of CX3CR1 expressing cancer cells. While CX3CR1 can be expressed in both cancer and immune-inhibitory myeloid cells to facilitate their migration, the mechanisms employed by this axis on these cells to mediate immune suppression remain poorly understood. Here, we explore the immune evasion strategies implemented by this axis and find that it initiates a resistance program in cancer cells that results in 1) facilitation of tumor cell migration, 2) secretion of soluble mediators to generate a pro-metastatic niche, 3) secretion of mediators to attract …
Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance, Sonia A. Patel
Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance, Sonia A. Patel
Dissertations and Theses (Open Access)
Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Targeted therapeutic agents, such as epidermal-like growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) or monoclonal antibodies targeting vascular endothelial growth factor (VEGF/R), can effectively inhibit upregulated signaling pathways driving tumorigenesis in NSCLC and many other cancers. Unfortunately, however, resistance to such targeted therapies inevitably arise in most patients and can occur through a variety of resistance mechanisms including genomic alterations and upregulation of bypass pathways. Additionally, patients who have acquired resistance to these targeted agents typically have tumors characterized by an immunosuppressive tumor microenvironment and thus …
Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Nmn Li
Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Nmn Li
Dissertations and Theses (Open Access)
Trogocytosis is an active process that transfers surface material from targeted to effector cells. Using multiple in vivo tumor models and clinical data, we report that chimeric antigen receptor (CAR) activation in natural killer (NK) cells promoted the transfer of the CAR-cognate-antigen from tumor to NK cells, resulting in (1) lower tumor antigen density, thus impairing the ability of CAR-NK cells to engage with their targets, (2) induced self-recognition and continuous CAR-mediated engagement, resulting in fratricide of trogocytic antigen expressing NK cells (NKTROG+) and NK cell hyporesponsiveness. This phenomenon could be offset by a dual-CAR system incorporating both …
Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing
Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing
Dissertations and Theses (Open Access)
Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …
Hypoxia Activated Prodrug And Anti-Angiogenic Therapy Cooperate To Treat Pancreatic Cancer But Elicit Immune Suppressive G-Mdsc Infiltration, Arthur Liu
Dissertations and Theses (Open Access)
We previously showed that the hypoxia-activated prodrug TH-302 (Evofosfamide) reduces intratumoral hypoxia through a tissue remodeling process, initiates tumor vasculature reorganization, and sensitizes aggressive, spontaneous murine models of prostate cancer to immune checkpoint blockade (ICB). In a clinical trial testing the combination of TH-302 with cytotoxic T-lymphocyte-associated protein (CTLA-4) blockade (NCT03098160) a subset of metastatic, ICB refractory patients showed prolonged progression free survival. While these studies highlight hypoxia as therapeutically tractable, we lack a complete understanding of the contribution of the tumor vasculature to hypoxia reduction therapy, as well as the downstream consequences of hypoxia reduction on the cellular composition …
Preclinical Evaluation Of Immunomodulatory Effects Of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers, Pragya Sinha
Preclinical Evaluation Of Immunomodulatory Effects Of Aurora Kinase Inhibition In Human Papillomavirus Positive Cancers, Pragya Sinha
Dissertations and Theses (Open Access)
Human papillomavirus (HPV) is the causative agent of cervical cancer and some cancers of the penis, vulva, vagina, anus, and oropharynx. Current therapies for these cancers include a combination of surgery, radiotherapy, and chemotherapy that often results in permanent, life altering adverse effects. Immunotherapy is partially effective, but with significant recurrence and lower long-term survival. Importantly, there are no few biomarker-selective targeted therapies for these cancers. To address this unmet need, our collaborators conducted a large-scale drug screen and identified Aurora Kinase (AK) inhibitors as a unique class of reagents to induce selective apoptosis in HPV+, but not HPV- human …
A New Frontier For Fat: Dietary Palmitic Acid Induces Innate Immune Memory, Amy L. Seufert, Brooke A. Napier
A New Frontier For Fat: Dietary Palmitic Acid Induces Innate Immune Memory, Amy L. Seufert, Brooke A. Napier
Biology Faculty Publications and Presentations
Dietary saturated fats have recently been appreciated for their ability to modify innate immune cell function, including monocytes, macrophages, and neutrophils. Many dietary saturated fatty acids (SFAs) embark on a unique pathway through the lymphatics following digestion, and this makes them intriguing candidates for inflammatory regulation during homeostasis and disease. Specifically, palmitic acid (PA) and diets enriched in PA have recently been implicated in driving innate immune memory in mice. PA has been shown to induce long-lasting hyper-inflammatory capacity against secondary microbial stimuli in vitro and in vivo, and PA-enriched diets alter the developmental trajectory of stem cell progenitors in …
Carbon Quantum Dots' Effects On The Structure And Function Of Neurodegenerative And Non-Neurodegenerative Associated Proteins, Shima Masoudi Asil
Carbon Quantum Dots' Effects On The Structure And Function Of Neurodegenerative And Non-Neurodegenerative Associated Proteins, Shima Masoudi Asil
Open Access Theses & Dissertations
Protein folding is an important physical process in which the sequences of polypeptides fold into a three-dimensional biological active structure. Misfolding is the conversion of a protein molecule into a structure unlike the native form, and therefore misfolded proteins have a strong tendency to aggregate and make fibrils. Amyloid aggregation is constituted by misfolded amyloidogenic proteins. Neurodegenerative diseases, such as Alzheimer’s Disease (AD), stem from the abnormal accumulation of harmful proteins, including Amyloid-ß peptides, tau protein, and the presynaptic protein α-synuclein in the nervous system. Alzheimer's disease is the most common neurodegenerative disorder that causes memory and learning deficits and …
Sarcoidosis And Airway Disease After Immune Checkpoint Inhibitor Therapy: Case Study And Review Of The Literature, Felipe Soto, Luis F Torre-Sada, Frank E Mott, Sang T Kim, Roza Nurieva, Vickie R Shannon, Saadia A Faiz, Roberto F Casal, Mehmet Altan, Julie Lin, Ajay Sheshadri
Sarcoidosis And Airway Disease After Immune Checkpoint Inhibitor Therapy: Case Study And Review Of The Literature, Felipe Soto, Luis F Torre-Sada, Frank E Mott, Sang T Kim, Roza Nurieva, Vickie R Shannon, Saadia A Faiz, Roberto F Casal, Mehmet Altan, Julie Lin, Ajay Sheshadri
Faculty, Staff and Student Publications
Pulmonary toxicity from immune checkpoint inhibitor therapy is typically a severe and potentially fatal complication, but these observations are driven by the most common toxicity, pneumonitis. Rarer pulmonary immune related adverse events, like airway disease and sarcoidosis, may have a more benign course. In this case report, we present a patient in whom therapy with the PD-1 inhibitor pembrolizumab resulted in severe eosinophilic asthma and sarcoidosis. This is the first case showing that anti-IL-5 inhibition may be safe in patients who develop eosinophilic asthma after ICI therapy. We further show that sarcoidosis does not necessarily require treatment cessation. This case …
Targeting Pd-L2-Rgmb Overcomes Microbiome-Related Immunotherapy Resistance, Joon Seok Park, Francesca S Gazzaniga, Meng Wu, Amalia K Luthens, Jacob Gillis, Wen Zheng, Martin W Lafleur, Sarah B Johnson, Golnaz Morad, Elizabeth M Park, Yifan Zhou, Stephanie S Watowich, Jennifer A Wargo, Gordon J Freeman, Dennis L Kasper, Arlene H Sharpe
Targeting Pd-L2-Rgmb Overcomes Microbiome-Related Immunotherapy Resistance, Joon Seok Park, Francesca S Gazzaniga, Meng Wu, Amalia K Luthens, Jacob Gillis, Wen Zheng, Martin W Lafleur, Sarah B Johnson, Golnaz Morad, Elizabeth M Park, Yifan Zhou, Stephanie S Watowich, Jennifer A Wargo, Gordon J Freeman, Dennis L Kasper, Arlene H Sharpe
Faculty, Staff and Student Publications
The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors have been identified in mice1-6. Moreover, transplantation of faecal specimens from responders can improve the efficacy of anti-PD-1 therapy in patients with melanoma7,8. However, the increased efficacy from faecal transplants is variable and how gut bacteria promote anti-tumour immunity remains unclear. Here we show that the gut microbiome downregulates PD-L2 expression and its binding partner repulsive guidance molecule b (RGMb) to promote anti-tumour immunity and identify bacterial species that mediate this effect. PD-L1 and …
National Cancer Control Plan Of The Korea: Current Status And The Fourth Plan (2021-2025), Kyu-Tae Han, Jae Kwan Jun, Jeong-Soo Im
National Cancer Control Plan Of The Korea: Current Status And The Fourth Plan (2021-2025), Kyu-Tae Han, Jae Kwan Jun, Jeong-Soo Im
Faculty, Staff and Student Publications
Cancer management has become a major policy goal for the government of the Korea. As such, the government introduced the National Cancer Control Plan (NCCP) to reduce the individual and social burdens caused by cancer and to promote national health. During the past 25 years, 3 phases of the NCCP have been completed. During this time, the NCCP has changed significantly in all aspects of cancer control from prevention to survival. The targets for cancer control are increasing, and although some blind spots remain, new demands are emerging. The government initiated the fourth NCCP in March 2021, with the vision …
Investigating The Role Of Cnag_05113 In The Carnitine Biosynthesis Pathway In Cryptococcus Neoformans., Jasmine Meltzer, Rodrigo Catalan-Hurtado, Perry Kezh, Kerry Smith
Investigating The Role Of Cnag_05113 In The Carnitine Biosynthesis Pathway In Cryptococcus Neoformans., Jasmine Meltzer, Rodrigo Catalan-Hurtado, Perry Kezh, Kerry Smith
Honors College Theses
Cryptococcus neoformans, the leading cause of fungal meningitis, is a fungal pathogen that causes severe infection of the central nervous system in patients with compromised immune systems, typically caused by HIV/AIDS. C. neoformans infections are present in developed countries including the United States, but most fatalities occur in sub-Saharan Africa where antiretroviral therapy, the treatment for HIV/AIDS, is less accessible. Current treatments for severe cryptococcal infections are extensive and outdated. There is a critical need for an improved understanding of the fungus and new targeted therapies. Our goal is to identify metabolic pathways important to the survival of C. …
Translational Studies Using The Malt1 Inhibitor (S)-Mepazine To Induce Treg Fragility And Potentiate Immune Checkpoint Therapy In Cancer, Mauro Di Pilato, Yun Gao, Yi Sun, Amina Fu, Carina Grass, Thomas Seeholzer, Regina Feederle, Irina Mazo, Samuel W Kazer, Kevin Litchfield, Ulrich H Von Andrian, Thorsten R Mempel, Russell W Jenkins, Daniel Krappmann, Peter Keller
Translational Studies Using The Malt1 Inhibitor (S)-Mepazine To Induce Treg Fragility And Potentiate Immune Checkpoint Therapy In Cancer, Mauro Di Pilato, Yun Gao, Yi Sun, Amina Fu, Carina Grass, Thomas Seeholzer, Regina Feederle, Irina Mazo, Samuel W Kazer, Kevin Litchfield, Ulrich H Von Andrian, Thorsten R Mempel, Russell W Jenkins, Daniel Krappmann, Peter Keller
Faculty, Staff and Student Publications
Introduction
Regulatory T cells (Tregs) play a critical role in the maintenance of immune homeostasis but also protect tumors from immune-mediated growth control or rejection and pose a significant barrier to effective immunotherapy. Inhibition of MALT1 paracaspase activity can selectively reprogram immune-suppressive Tregs in the tumor microenvironment to adopt a proinflammatory fragile state, which offers an opportunity to impede tumor growth and enhance the efficacy of immune checkpoint therapy (ICT).
Methods
We performed preclinical studies with the orally available allosteric MALT1 inhibitor (S)-mepazine as a single-agent and in combination with anti-programmed cell death protein 1 (PD-1) ICT to …
Establishment Of A Transgenic Human Angiotensin Converting Enzyme-2 Hamster Infection Model For The Evaluation Of Therapeutics Against Severe Acute Respiratory Syndrome Coronavirus 2, Scott A. Gibson
All Graduate Theses and Dissertations, Spring 1920 to Summer 2023
The virus SARS-CoV-2 emerged in late 2019 and has gone on to spread throughout the global population. The virus is still the cause of a healthcare crisis two years after being identified. Viral infection in humans leads to the development of the disease COVID-19. A complex disease that can result in a wide variety of outcomes for infected individuals. In the majority of individuals, COVID-19 will manifest as either an asymptomatic disease state or a mild to moderate disease state that is resolved in approximately one week. In some infected patients COVID-19 will manifest with the rapid onset of severe …
Evaluating Methods For Pathogen Spillover Detection And Forecasting In Desert Bighorn Sheep (Ovis Canadensis Nelsoni), Grete E. Wilson-Henjum
Evaluating Methods For Pathogen Spillover Detection And Forecasting In Desert Bighorn Sheep (Ovis Canadensis Nelsoni), Grete E. Wilson-Henjum
All Graduate Theses and Dissertations, Spring 1920 to Summer 2023
Managers mitigate the effects of disease on wildlife populations by detecting outbreaks and predicting disease transmission. Bighorn sheep (Ovis canadensis) populations face threat from the introduced pathogen Mycoplasma ovipneumoniae (M. ovipneumoniae). In the eastern Mojave Desert, managers detect pathogen outbreaks in desert bighorn (O. c. nelsoni) through aerial population surveys, which produce irregular and coarse population information. Furthermore, managers model the risk of M. ovipneumoniae transmission amongst desert bighorn populations, however these models assume that desert bighorn space use is unchanging across years. Here, I evaluate methods used by managers to detect disease outbreaks …
Poop! There It Is! Anti-Germinants And Biological Variables As Modulators Of Clostridioides Difficile Infection (Cdi), Jacqueline Renee Phan
Poop! There It Is! Anti-Germinants And Biological Variables As Modulators Of Clostridioides Difficile Infection (Cdi), Jacqueline Renee Phan
UNLV Theses, Dissertations, Professional Papers, and Capstones
Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea. Due to its insidious nature, the Centers for Disease Control and Prevention (CDC) has declared CDI an urgent threat. A key characteristic of C. difficile is its ability to form dormant spores that act as the infectious vehicles for disease. In the gut, spores recognize bile salts to germinate into toxin-producing cells.Dysbiosis of the gut microbiome is a key factor in allowing the C. difficile spores to germinate. Normal gut microbiota naturally protects from CDI. However, biological variables such as diet and sex have been found to modulate to …
Sting Agonist-Loaded Mesoporous Manganese-Silica Nanoparticles For Vaccine Applications, Cheng Xu, Hannah E Dobson, Mengjie Yu, Wang Gong, Xiaoqi Sun, Kyung Soo Park, Andrew Kennedy, Xingwu Zhou, Jin Xu, Yao Xu, Andrew W Tai, Yu Leo Lei, James J Moon
Sting Agonist-Loaded Mesoporous Manganese-Silica Nanoparticles For Vaccine Applications, Cheng Xu, Hannah E Dobson, Mengjie Yu, Wang Gong, Xiaoqi Sun, Kyung Soo Park, Andrew Kennedy, Xingwu Zhou, Jin Xu, Yao Xu, Andrew W Tai, Yu Leo Lei, James J Moon
Faculty, Staff and Student Publications
Cyclic dinucleotides (CDNs), as one type of Stimulator of Interferon Genes (STING) pathway agonist, have shown promising results for eliciting immune responses against cancer and viral infection. However, the suboptimal drug-like properties of conventional CDNs, including their short in vivo half-life and poor cellular permeability, compromise their therapeutic efficacy. In this study, we have developed a manganese-silica nanoplatform (MnOx@HMSN) that enhances the adjuvant effects of CDN by achieving synergy with Mn2+ for vaccination against cancer and SARS-CoV-2. MnOx@HMSN with large mesopores were efficiently co-loaded with CDN and peptide/protein antigens. MnOx@HMSN(CDA) amplified the activation of the STING pathway and enhanced the …
Identification Of A Role Beyond Iron Acquisition For Yersiniabactin During Yersinia Pestis Infection., Sarah Price
Identification Of A Role Beyond Iron Acquisition For Yersiniabactin During Yersinia Pestis Infection., Sarah Price
Electronic Theses and Dissertations
Yersinia pestis is a Gram-negative re-emerging bacterial pathogen that is responsible for bubonic, septicemic, and pneumonic plague. Y. pestis and other bacteria require transition metals, such as iron, zinc, and manganese, to maintain intermediary metabolism, transcriptional regulation, and virulence. To inhibit infection, eukaryotic organisms have developed distinct mechanisms, called nutritional immunity, to sequester these important nutrients from invading bacteria. For pathogens to colonize the vertebrate host, they have evolved dedicated acquisition systems for transition metals. During infection, Y. pestis overcomes iron limitation by secreting the siderophore yersiniabactin. Additionally, Y. pestis requires zinc for infection and utilizes high affinity transporters to …
Transmission And The Evolution Of Diseases Caused By Chlamydia Trachomatis, Sars-Cov-2, And Plasmodium Species., Nathan Steffens
Transmission And The Evolution Of Diseases Caused By Chlamydia Trachomatis, Sars-Cov-2, And Plasmodium Species., Nathan Steffens
Electronic Theses and Dissertations
Principles of natural selection have proven valuable for explaining why pathogens cause the diseases that they do. In theory, the evolved level of host exploitation should reflect how dependent a pathogen is on host health for transmission. This dependency is shaped by transmission mode and transmission opportunity, which should therefore be predictors of disease manifestations. In this dissertation, I apply these principles to investigations of depression in Chlamydia trachomatis and virulence of SARS-COV-2 and Plasmodium species. This dissertation has five chapters. In chapter I, I describe the theoretical foundation of my dissertation research. I also briefly introduce each study system. …
Landscape Genetics Of The Gulf Coast Tick, Amblyomma Maculatum, Sara Simmons Benham
Landscape Genetics Of The Gulf Coast Tick, Amblyomma Maculatum, Sara Simmons Benham
Biological Sciences Theses & Dissertations
Connectivity among populations helps to maintain genetic diversity, population stability, and resilience. The Gulf Coast tick, Amblyomma maculatum, is a vector of the pathogen Rickettsia parkeri. Persistence of tick populations with high rates of R. parkeri infection poses health risks to humans and animals. Mitochondrial haplotypes were characterized by sequencing a fragment of the mitochondrial 16S rRNA gene. A comparative study of A. maculatum and Amblyomma americanum was conducted to identify similar and unique patterns between the species within the same region. Next, I compared A. maculatum sites across three different regions of the United States. This work …
The Antioxidant Content Of Wong Lo Kat Tea, Valerie Kwong
The Antioxidant Content Of Wong Lo Kat Tea, Valerie Kwong
Theses, Dissertations and Culminating Projects
Wong Lo Kat (or Wanglaoji in Mandarin) is a popular soft drink containing herbal tea that is often used as a Chinese folk remedy for mild ailments. The herbs included in the drink are the following: Chinese Mesona, White Frangipani, Microcos, Chrysanthemum, Japanese Honeysuckle, Heal All, and Chinese Licorice. While there is research on the individual plants, there is limited information on the combined mixture of the herbs included in the Wong Lo Kat drink, particularly in published English literature. Antioxidant content for the individual herbs and a combined mixture of equal parts of each herb was tested using the …
The Interconnected Roles Of Residues N189, E168, And S220 In M. Tuberculosis Indole-3-Glycerol Phosphate Synthase Catalysis, Erik Domlija
The Interconnected Roles Of Residues N189, E168, And S220 In M. Tuberculosis Indole-3-Glycerol Phosphate Synthase Catalysis, Erik Domlija
Theses, Dissertations and Culminating Projects
Tuberculosis (TB) is an infectious disease caused by the bacteria Mycobacterium tuberculosis that primarily attacks the lungs. Drug resistance for M. tuberculosis is emerging and therefore new drug targets need to be identified. One way to target TB is through the inhibition of the tryptophan biosynthetic pathway of M. tuberculosis since production of tryptophan is essential for the replication of M. tuberculosis. The enzyme Indole-3-glycerol phosphate synthase (MtIGPS) was chosen as a potential drug target due to its role in tryptophan biosynthesis. Residue N189 interacts with active site residues E168 and S220. It is inferred from previous studies done with …
Fulfilling Koch’S Postulates And Evaluation Of Different Administration Routes In Poults Challenged With Streptococcus Gallolyticus, Latasha Gray
Graduate Theses and Dissertations
Streptococcus gallolyticus (SG) is a Gram-positive found as commensal gut flora in animals and humans. SG has been associated with acute mortality in poults 2 to 3 weeks of age, with lesions mainly consisting of splenomegaly, hepatomegaly, and pericarditis. The objective of this thesis was to reproduce disease in poults caused by SG recovered from clinical field isolates and evaluate different routes of administration. Three field isolates from geographically disparate areas in Arkansas and Missouri were used for the experiments contained in this thesis. Antibiotic sensitives of the three field isolates revealed sensitivity to penicillin as well as a wide …
Evaluation Of The Effect Of Enterococcus Cecorum Exposure During Late Embryogenesis On Systemic Disease And Early Performance In Broiler Chickens, Marcela Arango
Graduate Theses and Dissertations
The objective of this thesis was to investigate the effects of Enterococcus cecorum (EC) administration into the amnion at day 18 of embryogenesis on performance and septicemia development in broiler chickens. Chapter I consists of a brief overview of the thesis. Chapter II provides a literature review on EC-related disease in broiler chickens and methods to isolate, detect, and differentiate between commensal and pathogenic strains of EC. Chapter III consists of a study conducted to determine if different EC strains isolated from field cases that exhibited septicemia and high mortality impacted hatchability, livability, organ colonization, and early performance in broiler …
An Ecological Perspective Of American Rodent-Borne Orthohantavirus Surveillance, Nathaniel Mull
An Ecological Perspective Of American Rodent-Borne Orthohantavirus Surveillance, Nathaniel Mull
Graduate Theses and Dissertations
Orthohantaviruses are a global group of viruses found primarily in rodents, though several viruses have also been found in shrews and moles. Many rodent-borne orthohantaviruses are capable of causing one of several diseases in humans, and the mortality associated with these diseases ranges from < 0.1% - 50% depending on the specific etiological virus. In North and South America, orthohantavirus research was ignited by an outbreak of severe disease in the Four Corners region of the United States in 1993. However, despite the discovery of over 20 orthohantaviruses in the Americas, our understanding of orthohantavirus ecology and virus-host dynamics in this region is still limited, and orthohantavirus surveillance is generally restricted in scope to select regions and small portions of host distributional ranges. In Chapter I, I present a literature review on the current understanding of American rodent-borne orthohantavirus ecology. This review focused on under-studied orthohantaviruses, addressing gaps in knowledge by extrapolating information from well-studied orthohantaviruses, general rodent ecology, and occassionally from Eurasian orthohantavirus-host ecology. There were several key conclusions generated from this review that warrant further research: 1) the large number of putative orthohantaviruses and gaps in orthohantavirus evolution necessitate further surveillance and characterization, 2) orthohantavirus traits differ and are more generalizable based on host taxonomy rather than geography, and 3) orthohantavirus host species are disproportionately found in grasslands and disturbed habitats. In Chapter II, I present a prioritized list of rodent species to target for orthohantavirus surveillance based on predictive modeling using machine learning. Probable orthohantavirus hosts were predicted based on traits of known orthohantavirus hosts using two different types of evidence: RT-PCR and virus isolation. Predicted host distributions were also mapped to identify geographic hotspots to spatially guide future surveillance efforts. In Chapter III, I present a framework for understanding and predicting orthohantavirus traits based on reservoir host phylogeny, as opposed to the traditional geographic dichotomy used to group orthohantaviruses. This framework establishes three distinct orthohantavirus groups: murid-borne orthohantaviruses, arvicoline-borne orthohantaviruses, and non-arvicoline cricetid-borne orthohantaviruses, which differ in several key traits, including the human disease they cause, transmission routes, and virus-host fidelity. In Chapter IV, I compare rodent communities and orthohantavirus prevalence among grassland management regimes. Sites that were periodically burned had high rodent diversity and a high proportion of grassland species. However, rodent seroprevalence for orthohantavirus was also highest in burned sites, representing a trade-off in habitat management outcomes. The high seroprevalence in burned sites is likely due to the robust populations supported by the high quality habitat resulting from prescribed burning. In Chapters V and VI, I describe Ozark virus and Sager Creek virus, two novel orthohantaviruses discovered from specimens collected during Chapter IV. Both chapters report full genome sequences of the respective viruses and compare both nucleotide and protein phylogenies with related orthohantaviruses. Additionally in Chapter VI, I support the genetic analyses with molecular and ecological characterizations, including seasonal fluctuations in host abundance, correlates of prevalence, evidence of virus shedding, and information on host cell susceptibility to Sager Creek virus.
Optimal R&D Investment In The Management Of Invasive Species, William Haden Chomphosy, Dale T. Manning, Stephanie A. Shwiff, Stephan Weiler
Optimal R&D Investment In The Management Of Invasive Species, William Haden Chomphosy, Dale T. Manning, Stephanie A. Shwiff, Stephan Weiler
United States Department of Agriculture Wildlife Services: Staff Publications
Invasive alien species (IAS) threaten world biodiversity, ecosystem services, and economic welfare. While existing literature has characterized the optimal control of an established IAS, it has not considered how research and development (R&D) into new removal methods or technologies can affect management decisions and costs over time. R&D can lower the costs of control in a management plan and creates an intertemporal trade-off between quick but costly control and gradual but cheaper removal over time. In this paper, we develop and solve a continuous time dynamic optimization model to study how investment in R&D influences the optimal control of an …