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  • 1. Portillo-Gonzalez, Rafael Antimicrobial Stewardship Education to Improve the Responsible Use of Antimicrobials in Dairy Cattle

    Doctor of Philosophy, The Ohio State University, 2024, Veterinary Preventive Medicine

    The majority of antimicrobials used in dairy production require a veterinarian's prescription; however, farmworkers make daily treatment decisions. Therefore, improving farmworkers' stewardship practices is a fundamental first step in the fight against antimicrobial resistance. This research project aimed to identify gaps in antimicrobial treatment practices between veterinarians and farmworkers, assess the level of agreement in their on-farm therapy options, and understand the barriers and drivers affecting their treatment decisions. Initially, we used a hierarchical survey with clinical case vignettes to understand current on-farm antimicrobial practices between veterinarians and farmworkers. Subsequently, we designed antimicrobial stewardship training to educate farmworkers on accurately identifying cows requiring treatment. Additionally, we quantified antimicrobial use (AMU) through farm treatment records (FTR) and empty drug containers (EDC) during a quasi-experimental study that included intervention and control farms in Ohio and California. Finally, trained farmworkers were individually interviewed using a semi-structured questionnaire, and the interviews were evaluated through thematic analysis. Results indicated that the overall agreement in AMU between veterinarians and farmworkers was generally weak across various disease severity levels. There was significant variation in AMU among the enrolled farms. No significant change in AMU was observed in the intervention farms after the educational training compared to the control farms. FTR underestimated the overall mean treatment incidence by 0.78 times compared to EDC, and the agreement level between them was moderate. Lastly, farmworkers identified six themes with one to three subthemes each. Animal welfare and job success were the primary drivers for improving on-farm AMU. However, they faced significant barriers, including knowledge deficiencies, time-supply constraints, and farm administration issues, whi (open full item for complete abstract)

    Committee: Gregory G. Habing (Advisor); Amanda M. Berrian (Committee Member); Thomas E. Wittum (Committee Member); Eric Gordon (Committee Member); Alia M. Dietsch (Committee Member) Subjects: Adult Education; Agriculture; Animal Diseases; Animal Sciences; Behavioral Sciences; Epidemiology; Public Health
  • 2. Khatiwada, Saroj Evaluation of reoviral arthritis in turkeys: roles of age and co-infection on disease outcome

    Master of Science, The Ohio State University, 2024, Animal Sciences

    Turkey arthritis reovirus (TARV) causes arthritic lameness affecting mostly market-age turkeys. Since 2011, TARV has caused significant economic losses in the turkey industry due to increased culling, reduced market weights, and decreased carcass quality, necessitating more effective control measures. Autogenous vaccine prevention strategies have been inefficacious partly due to a limited understanding of age-related susceptibility of turkeys to TARV. Moreover, nonpathogenic enteric reovirus are ubiquitously present in the intestinal tract, which might complicate the severity of turkey arthritis reovirus in commercial turkeys. Also, the interplay of enteric reovirus and arthritic reovirus during coinfection and how it alters the progression and severity of disease is not known. To begin addressing these questions, we investigated age-related host and gut microbiota responses to TARV infection in commercial turkeys derived from vaccinated breeder hens. Additional experiments investigated how coinfection of Specific Pathogen Free (SPF) turkeys with enteric reovirus and arthritic reovirus affects the progression and severity of disease. In our first study, poults with maternally derived antibodies were orally challenged with TARV O'Neil strain at 1-, 3-, and 7- weeks of age (WOA) and monitored for cloacal virus shedding, gastrocnemius tendon viral tropism, tendon inflammation, weight gain, and changes in gut microbiota. In the second study, SPF turkey poults were orally challenged with TERV MN1 at 1 day of age and TARV O'Neil at 8 days of age and euthanized at 1- and 4-weeks post-infection with TARV O'Neil. A transient TARV-induced weight gain reduction was evident in poults infected at 1- and 3- WOA during the first 3 weeks post-infection. Age-dependent variations in cloacal viral shedding, virus isolation from tendons, and tendon inflammation severity were also observed. There was significant dissimilarity in ileal and cecal bacterial communities between mock and (open full item for complete abstract)

    Committee: Scott P. Kenney (Committee Chair); Gireesh Rajashekara (Committee Co-Chair) Subjects: Animal Diseases; Virology
  • 3. Sarr, Omar Transformations in Rural Farming Communities: Ox-Plows, Mixed Farming Centers and Agricultural Production in The Gambia, c. 1960s-1970s

    Master of Arts (MA), Ohio University, 2024, History (Arts and Sciences)

    After the Second World War, Green Revolution techniques were introduced in West Africa to improve agricultural production and reduce poverty. Unlike in Asia and Latin American countries, the techniques in West Africa proved unsuccessful largely because of environmental and political hindrances. In recent years, few West African historians have shown interest in the region's agricultural history, especially during the early post-colonial period. The existing scholarship ignores the several agricultural programs introduced by, for instance, the Gambian government, whose aim was to enhance crop production and boost agricultural exports. Several agricultural schemes were introduced in the Gambia, but these projects appear to have exacerbated rural challenges, including gender inequality and landscape changes. Devastating droughts were also a common occurrence that worsened the situation. Disease outbreaks also devastated the livestock industry. To date, no study has examined why the ox-plows and Mixed Farming Centers of the 1960s and 1970s introduced in rural farming communities failed to yield the desired results. My project intends to investigate the impact of some of these projects, and the reasons for their failure. It also examines how environmental and climatic factors during this period contributed to the disruption of Gambian farming communities.

    Committee: Assan Sarr (Advisor); Paul Milazzo (Committee Member); Katherine Jellison (Committee Member) Subjects: African History; Agriculture; Animal Diseases; Gender; Technology
  • 4. Agustini, Dyah Modic Changes in Dogs with Intervertebral Disc Disease

    Master of Science, The Ohio State University, 2024, Comparative Biomedical Sciences

    Modic changes (MC) are signs of vertebral pathology visible on magnetic resonance (MR) images that have been associated with low back pain (LBP) and disc degeneration in people. Multiple breeds of dogs also develop MCs and coincidental back pain. However, the association between breed, MC, and spinal pathologies has yet to be fully elucidated. This study aimed to identify the prevalence of MC that occur spontaneously in the lumbar vertebral column of dogs diagnosed with intervertebral disc disease (IVDD) and examine their association with demographic criteria and the disc width index (DWI). Medical records and lumbar vertebral column MR images were examined from 104 dogs (831 intervertebral disc spaces and adjacent vertebrae), which were divided into three groups: chondrodystrophic dogs (CD; n= 54) and non-chondrodystrophic dogs (NCD; n= 30) with IVDD as the primary diagnosis, and control dogs (n= 20) with other spinal diseases as their primary diagnosis. Results demonstrate increasing age and a diagnosis of IVDD were significantly associated with MC in dogs (p< 0.001 and p= 0.0062, respectively). In CD dogs with IVDD, Type 2 MC were most prevalent, whereas, in NCD dogs, Type 3 MC were the most prevalent type. Type 2 MC were distributed nearly equally across the lumbar vertebral column, while Type 3 MC were primarily detected at the level of L7-S1. This study demonstrated that MC developed spontaneously in dogs, are common in dogs diagnosed with IVDD, and the type observed varies by breed. Further research is needed to understand the pathogenesis of MC; however, the increased presence of Type 2 MC in CD dogs, similar to what is found in people with disc degeneration, suggests that CD dogs could serve as models for MC in people.

    Committee: Sarah Moore (Advisor); Benjamin Walter (Committee Member); Devina Purmessur (Committee Member); Nina Kieves (Committee Member) Subjects: Animal Diseases; Medical Imaging; Medicine; Neurology
  • 5. Bugybayeva, Dina Evaluation of surface coated versus entrapped mannose-chitosan nanoparticle based intranasal inactivated vaccine against influenza A virus in swine

    Master of Science, The Ohio State University, 2023, Animal Sciences

    Intranasal vaccination has important implications for generation of vaccine-induced cross protective immunity against mucosal infections, including influenza A virus (IAV). In this study, intranasal delivery of an adjuvanted nanoparticulate vaccine platform was developed and characterized. The whole inactivated swine influenza virus (OH10-H1N2) and STING-activating ADU-S100 adjuvant was either surface adsorbed or entrapped in mannose-chitosan nanoparticles (m-Chit-NPs). The m-Chit-NPs were optimized by studying NPs size distribution, zeta potential and cytotoxicity. A cross protective study was performed using a heterologous challenge infection in vaccinates using CA09-H1N1 IAV in specific-pathogen-free (SPF) pigs following prime-boost vaccination. Samples from animals were evaluated for viral loads in the nose, antibody as well as innate and adaptive cellular immune responses both at systemic and respiratory tract. Physical characterization of m-Chit NPs showed that these particles are suitable for mucosal vaccination with zeta potential ≥ +15 mV, polydispersity index of <0.5, size diameter of around 350nm and 1:9 antigen (Ag)/NPs mass ratio for both loading methods with 75% cell viability. Animal study results show that m-Chit-NP intranasal vaccination induced cross reactive secretory IgA antibodies in both upper and lower airways exceeding those in FluSureXP™ - a commercial swine influenza virus vaccine. Between mucosal vaccine groups, the Ag entrapped vaccine induced higher virus specific neutralizing activity in serum, whereas surface adsorbed vaccine induced high virus neutralization and hemagglutination inhibition (HAI) activity in bronchoalveolar lavage (BAL) fluid. Mucosal vaccination induced high gamma interferon and IL-17A secreting cytotoxic T lymphocytes and T-helper/memory cells both systematically and in tracheobronchial lymph nodes, especially pronounced in Ag and adjuvant entrapped vaccinates. Viral replication was reduced substantially in the nose (open full item for complete abstract)

    Committee: Renukaradhya Gourapura Dr. (Advisor); Scott Kenney Dr. (Committee Member); Anastasia Vlasova Dr. (Committee Member) Subjects: Animal Diseases; Animal Sciences; Immunology
  • 6. Sisler, Jonathan In vivo Neuroprotective Effects of Cannabis sativa in Models of Parkinson's Disease

    Master of Science (MS), Ohio University, 2023, Food and Nutrition Sciences (Health Sciences and Professions)

    Neurodegenerative diseases (NDs) are a broad range of disorders characterized by the chronic and progressive degeneration of neurons and synaptic connections of the nervous system. After Alzheimer's disease (AD), Parkinson's disease (PD) is the most common ND. PD affects ~0.3% of the general population and accounts for an estimated $15.5 billion in medical and non-medical costs each year. PD is a movement disorder characterized by the gradual loss of gross and fine motor control, impaired speech, dyskinesias, postural instability, and a resulting decrease in quality of life. As the disease progresses, interrupted sleep, depression, and cognitive impairment may also arise. Clinically, these symptoms have been associated with the loss of dopamine (DA) production due to the progressive degeneration of dopaminergic neurons of the substantia nigra pars compacta (SNc) region of the midbrain. Another hallmark of PD is the presence of insoluble inclusions called Lewy bodies in neurons due to the pathological aggregation of a protein called α-synuclein. The molecular mechanisms governing the aggregation of α-synuclein and formation of Lewy bodies are not well understood. Emerging research suggests that excitotoxicity, oxidative stress, and neuroinflammation may be important factors in the α-synuclein aggregation-mediated formation of Lewy bodies and associated loss of dopaminergic neurons, and therefore may serve as promising therapeutic targets for PD. The current pharmaceutical therapies available for PD are only effective in providing short-term management of symptoms and are unable to slow the progression of the disease. Furthermore, these treatments have been associated with many adverse side effects, limiting patient compliance and long-term effectiveness. Natural products such as plants, fungi, and microbes have played a pivotal role in pharmaceutical drug discovery for a variety of pathologies. More recently, molecules derived from natural products have been exten (open full item for complete abstract)

    Committee: Dhiraj Vattem PhD (Advisor); Vatsala Maitin PhD (Committee Member); Robert Brannan PhD (Committee Member) Subjects: Aging; Animal Diseases; Food Science; Health; Health Sciences; Medicine; Neurology; Neurosciences; Nutrition; Pharmacology
  • 7. Chishaka, Passmore INDIGENOUS KNOWLEDGE AND CLIMATE CHANGE: LESSONS FROM THE LOWVELD IN ZIMBABWE, 1930-PRESENT

    PHD, Kent State University, 2023, College of Arts and Sciences / Department of History

    Based on a critical reading of colonial archives and extensive use of oral sources, this dissertation argues that indigenous custodians of the landscape in semi-arid regions of the Zimbabwean Lowveld have a longstanding experience of harnessing their environmental literacy and detailed knowledge of nature to combat climate change. Starting with colonial encounters and contested boundaries of knowledge in Southern Rhodesia (present day Zimbabwe) since the early twentieth century, I demonstrate that oral traditions survived the onslaught of colonialism and offered new generations ways of responding to climate change. I use empirical examples to demonstrate that indigenous knowledge systems (IKS) have been obscured under the veneer of colonial historiography, hence, the importance of recovering African cultural achievements and indigenous agency to the historical record. This dissertation examines the adoption of various coping strategies and sustainable agricultural practices initiated by indigenous people to promote climate smart agriculture and identifies the factors that influence adoption of certain adaptive practices. Water has been a central and defining factor of Africa's development trajectory. A growing body of literature has demonstrated that agricultural yields have been declining in developing countries, including Zimbabwe, due to the impacts of climate change. Indigenous experiences, conceptions and perceptions have played a vital role in the adoption of climate-smart agricultural practices. Indigenous farmers are at peace with modernity and modernization, but in the absence of modern technologies and state support, they have been going back to traditional forms of development. The interrelated objectives of climate change mitigation, adaptation and food security were simultaneously sustained through the hybrid integration of indigenous and modern farming practices in agricultural production and sustainable development planning. Indigenous knowledge sys (open full item for complete abstract)

    Committee: Timothy Scarnecchia (Advisor) Subjects: African History; Agriculture; Animal Diseases; Environmental Management; Environmental Philosophy; Environmental Studies; Evolution and Development; Folklore; Forestry; Gender; History; Land Use Planning; Livestock; Religion; Spirituality; Sustainability; Water Resource Management
  • 8. Gammariello, Corienne Milk and blood composition during subclinical mastitis

    Master of Science, The Ohio State University, 2023, Animal Sciences

    Mastitis induces losses in milk yield and undesirable changes in milk composition. The mechanisms behind reduced milk production during mastitis remains unknown. Two studies were conducted to investigate the effects of sterile inflammation on mammary gland metabolism via changes in milk and venous blood composition. In the first study, one udder half of each primiparous Holstein cow (n = 4) in mid-lactation was infused with oyster glycogen; the other control udder half with saline. Cows were milked in tie stalls every 8 h for 5 d. Udder half milk samples were collected for analysis. Results showed milk of oyster glycogen udder halves had an increased and sustained recruitment of immune cells, increased concentrations of protein, and decreased concentrations of lactose compared to control udder halves. There were no detectable changes in fat concentrations or milk yield between udder half treatments. In the second study, primiparous Holstein cows (n = 4) were fitted with venous catheters in the left and right subcutaneous abdominal veins. Two billion cfu of formalin-fixed Staph. aureus were subsequently infused into one udder halve (FX-STAPH) of each cow; the other udder half was infused with saline (SAL). After FX-STAPH challenge, blood sampling commenced every 2.6 h till the end of the study and blood samples were analyzed using a portable blood analyzer (iStat Alinity) while plasma samples were stored for wet lab chemistry. Milk of FX-STAPH udder halves had an increased and sustained SCS, increased concentrations of protein, and decreased concentrations of lactose compared to control udder halves. Milk of FX-STAPH udder halves had increased concentrations of lactate compared to SAL udder halves. There were no changes in fat concentrations or milk yield between udder half treatments in the second study. Venous blood of FX-STAPH udder halves had marginally greater saturated and partial pressures of oxygen, greater anion gap values, and concentrations of glucose, but (open full item for complete abstract)

    Committee: Benjamin Enger (Advisor); Alejandro Relling (Committee Member); Anja Sipka (Committee Member) Subjects: Animal Diseases; Animal Sciences; Animals
  • 9. McBride, Dillon Dissemination, Outbreak, and Zoonotic Transmission Risk of Influenza A Viruses in Exhibition Swine at the Human-Animal Interface

    Doctor of Philosophy, The Ohio State University, 2023, Comparative Biomedical Sciences

    Swine are a critical host species for influenza A virus (IAV) due to the public health risk posed by zoonotic transmission, which can result in pandemic IAV generation. Exhibition swine, raised by youth to be shown at agricultural fairs and livestock exhibitions, have been the primary source of zoonotic IAV infections in people in the USA. The structure of “jackpot” shows is distinct from county fairs, and they allow contact and comingling of numerous pigs from separate and unique locales year-round. To evaluate the role of this show network in IAV dissemination, we collected samples from 17,009 pigs attending 350 national, state, and local swine during 2016–2018. Jackpot shows had 4.3-fold higher odds of detecting at least one influenza-positive pig compared to county fairs. However, when influenza was detected at a county fair, almost half of pigs tested positive, clarifying why zoonotic infections occur primarily at county fairs. The IAV genotypes detected within the jackpot show network within a given year are the same genotypes detected at county fairs during those years. Because these jackpot shows occur in the early spring and summer, before peak county fair season in the Midwest, there is a clear pathway for IAV at these shows to seed the IAVs in county fairs that transmit from pigs to people. Next, we investigated how once IAV is introduced, the duration of these county fairs influences the high IAV prevalence in swine, which drives zoonotic transmission. We longitudinally sampled every pig daily for the full duration of 16 county fairs during 2014–2015 (39,768 nasal wipes from 6,768 pigs). We found that shortening duration drastically reduces IAV prevalence in exhibition swine at county fairs. Additionally, we found further evidence that altering the arrival procedures can substantially slow the potential IAV outbreak growth at these fairs further reducing zoonotic risk. Finally, we investigated the exposure and neutralizing protection of the human exhibit (open full item for complete abstract)

    Committee: Andrew Bowman (Advisor); Andréia Arruda (Committee Member); Jacob Yount (Committee Member); Laura Pomeroy (Committee Member); Eben Kenah (Committee Member) Subjects: Animal Diseases; Epidemiology; Health Sciences; Public Health; Virology
  • 10. Snowden, Christine Advancing the Knowledge of Ohio's Pork Producers through an Education Program focused on Foreign Animal Disease Preparedness.

    Master of Science, The Ohio State University, 2023, Food, Agricultural and Biological Engineering

    Two studies were completed to address the knowledge gaps that Ohio pork producers face if presented with a foreign animal disease. A foreign animal disease that would lead to mass depopulation and disposal of infected swine mortalities. To create the training program needed to fill the knowledge gaps the present studies worked with the Ohio Department of Agriculture (ODA) and the United States Department of Agriculture (USDA) to get the materials that had been created for a foreign animal disease outbreak in swine. These materials are titled Ohio ASF and CSF Emergency Response Plan. The plan was created for the state's regulatory officials and needed to be transformed into what the producers and other key personnel needed to know. Once the materials were secured the present studies worked using the principles of the revised Bloom's Taxonomy to create the curriculum. From there the learning outcomes were outlined and work was done to create the learning modules to support the outcomes. The curriculum consisted of five teaching modules delivered in person, a training manual, a hands-on program, and a pre- and post- assessment. The first study was a pilot program that took place on August 8th and 9th 2022. The audience was regulatory officials from across the state of Ohio who took part in this pilot program at Ohio State's Wooster Campus. There were 9 participants total for this training. For this study the program was stretched over two days because the goal was to have the classroom experience and equipment demonstrations in one day and all the hands-on experiences the next day. The agenda layout chronologically for the first day was a pre-assessment, in-person teaching of the 5 learning modules and demonstration of the equipment. The second day consisted of the participants being in-charge of setting up all the water-based foam equipment, depopulation of 20, 300lbs gilt, and coordination of those 20 carcasses being disposed of via grinding composting. The partic (open full item for complete abstract)

    Committee: Michael Cressman (Advisor); Steven Moeller (Committee Member); Andrew Bowman (Committee Member); Kelly George (Committee Member) Subjects: Agriculture; Animal Diseases; Animal Sciences; Animals
  • 11. McGovern, Kate Research Strategies for Prophylaxis of Enterococcal Spondylitis in Broilers

    Master of Science, The Ohio State University, 2022, Animal Sciences

    Enterococcal spondylitis (ES) is a clinical syndrome caused by improper colonization of Enterococcus cecorum in the free thoracic vertebra (FTV) and adjacent notarium or synsacrum. Enterococcal spondylitis is a devastating disease that results in lameness which can lead to lowered feed efficiency, decreased weight gain, and mortality. Because of the relatively recent discovery and recognition of the pathogenesis for ES, research models are still under development. Induction of ES through E. cecorum bacterial translocation, which occurs when the intestinal barriers are damaged or weakened by stressors like pathogens, heat, dietary ingredients, etc. may accurately represent production setting conditions. Some diet additives that have been known to have antinutritional effects and cause intestinal barrier damage include rye high in non-starch polysaccharides (NSPs), animal-based proteins, and poor-quality soybean meals (pqSBM). These ingredients may be able to induce translocation of E. cecorum in broilers and lead to cases of ES. Enterococcus cecorum is a normal component of gastrointestinal flora of chickens and has been found to make up the majority of enterococcal and streptococcal flora in older birds. Since E. cecorum is part of normal gastrointestinal (GI) tract, finding methods to prevent translocation to other areas of the body can be challenging. Thus, promoting and maintaining the intestinal barrier is integral. Probiotics have been documented to influence gut barrier integrity via increased tight junction gene expression. Since the gut barrier prevents transfer of potential pathogens like E. cecorum into the blood stream and probiotics have been shown to increase gut barrier integrity, probiotics may be able to prevent instances of ES. Two separate experiments were conducted, a series of 4 in vitro assays were used to determine the effects of two commercial Bacillus sp. probiotics, GutCare® and Ecobiol® on growth of known pathogenic strains of E. cecorum (open full item for complete abstract)

    Committee: Lisa Bielke (Advisor); Sara Mastellar (Committee Member); Shelia Jacobi (Committee Member) Subjects: Agriculture; Animal Diseases; Animal Sciences
  • 12. Paazig, Josie Fungal and Bacterial Populations on Clemmys guttata and Chrysemys picta in Clark County, Ohio, and Kinosternon steindachneri and Virginia valeriae in Lafayette County, Mississippi

    Bachelor of Science, Wittenberg University, 2022, Biology

    Recently fungal communities have been observed on wetland and freshwater reptiles in the United States including Ophidiomycosis, or Snake Fungal Disease. Examination of fungal and bacterial communities present on spotted and painted turtles (Chrysemys picta) in Clark County, Ohio was done following the discovery of potential necrosis on spotted turtles (Clemmys guttata). The presence of a specific pathogenic fungal population may account for the decline in population of spotted turtles. Additional analysis of fungal and bacterial populations in common mud turtles (Kinosternon steindachneri) and smooth earthsnakes (Virginia valeriae) in Lafayette County, Mississippi was also conducted. The bacterial and fungal communities found on the snake and turtle populations may be found to be similar between the species and further exploration and research should be done to determine which communities are present in these wetland habitats.

    Committee: Richard Phillips (Advisor); Billy Davis (Committee Member); Kunal Chatterjee (Committee Member) Subjects: Animal Diseases; Animal Sciences; Animals; Biology; Environmental Science; Environmental Studies; Pathology; Zoology
  • 13. Zhang, Jun Development and Validation of Novel Polymer-based DNA Delivery Systems for Effective and Affordable Non-viral Gene Therapies

    Doctor of Philosophy, Case Western Reserve University, 0, Macromolecular Science and Engineering

    Gene therapy is a highly promising disease treatment and prevention strategy through addition, inhibition, editing, or functional replacement of a gene, aiming to address the root cause of a disease. One critical issue in gene therapy is effective delivery of the therapeutic DNA into target cells through a viral or non-viral vector. About 70 % of vectors in clinical trials are recombinant viral vectors. The commonly used viral vectors, such as lentivirus and rAAV, are highly efficient in carrying DNA into many cell types and enable long-term expression of the cargo gene. However, viral vectors are of limited gene carrying capacities and very difficult and extremely costly to produce in therapeutic quantities, and they induce immune responses and often carry long-term cancer risks. These serious caveats associated with viral vectors are largely absent for non-viral vectors. However, non-viral vectors have their own shortcomings, one of which is the very poor cell entry by naked non-viral DNA vectors, necessitating the assistance of a DNA delivery agent. My research focuses on developing effective and adjustable polyethylenimine (PEI)-based DNA delivery agents for in vitro and validating their performance in vivo for future applications in gene therapy. PEIs are inexpensive and have shown good DNA delivery capacities in vitro. I first utilized GFP reporter plasmid DNAs and muscular and neuronal cell lines to identify the most promising PEI forms, then I subjected the select PEIs to systematic optimizations using the same cell culture systems. Finally, I applied the optimized PEIs, in comparison with a popular commercial DNA delivery agent, to deliver a few therapeutic genes carried on naked plasmid DNA vectors into cultured cells in vitro or into muscle or brain tissues in mice. The results show that the optimized PEIs are highly effective and significantly superior to the commercial reagent, especially in in vivo experiments, demonstrating the huge potential of our o (open full item for complete abstract)

    Committee: Qingzhong Kong (Advisor) Subjects: Animal Diseases; Biochemistry; Biology; Biomedical Engineering; Biomedical Research; Cellular Biology; Developmental Biology; Engineering; Environmental Health; Health; Health Sciences; Immunology; Materials Science; Medicine; Molecular Biology; Molecules; Nanoscience; Nanotechnology; Neurobiology; Neurology; Neurosciences; Organic Chemistry; Pharmaceuticals; Pharmacy Sciences; Polymer Chemistry; Polymers; Public Health; Therapy; Toxicology; Virology
  • 14. Daruwalla, Anahita Understanding Carotenoid and Retinoid Biochemical Diversity using Novel Archaeal and Eukaryotic Model Systems

    Doctor of Philosophy, Case Western Reserve University, 2021, Pharmacology

    Carotenoid cleaving dioxygenases (CCD) are a group of proteins involved in oxidative cleavage of carotenoids and non-carotenoids using a non-heme iron center. Previous studies on structure and function of CCD in plants, cyanobacteria as well animals show these are typically regio- and stereo-specific for substrate cleavage. Some are also known to show double bond isomerization similar to the visual cycle isomerase RPE65. However, it is still unclear as to how certain members of this family evolved to function distinctly. More so, dearth of knowledge on CCDs in archaea makes it implausible to link their evolutionary divergence. Recent phylogenetic studies propose that eukaryotes have emerged from archaea, favoring a two-domain tree of life model with Archaea and Bacteria. Probing into the cleavage mechanism of CCDs in archaea would provide valuable insight into the evolution of these proteins. In an attempt to bridge this gap, we characterized a putative oxygenase from an archaeon, Candidatus Nitrosotalea devanaterra (NdCCD), with a close evolutionary relationship to metazoan CCDs. The structure of NdCCCD in complex with its apocarotenoid product displays similarity to RPE65 and helps discern the active site determinants for cleavage. RDH5, an 11-cis-retinol dehydrogenase present in the retinal pigment epithelium (RPE) of the eye retina catalyzes oxidation of 11-cis-retinol to 11- retinaldehyde, thus regenerating the visual chromophore. In humans, mutations in RDH5 are predominantly associated with fundus albipunctatus, characterized by presence of white flecks in the retina and delayed rod adaptation impairing night vision. However, a subset of patients also develops macular atrophy or cone dystrophy. Rdh5-/- mice do not recapitulate human phenotype and exhibit delayed dark adaptation only after prolonged bleaching. We characterized a new domestic cat model with a loss of function missense mutation in RDH5 that results in atrophy of its area centralis region (equ (open full item for complete abstract)

    Committee: Philip Kiser (Advisor); Jason Mears (Committee Chair); Johannes Von Lintig (Committee Member); Youwei Zhang (Committee Member); Paul Park (Committee Member) Subjects: Animal Diseases; Biochemistry; Molecular Biology
  • 15. Keller, Emma The Contribution of IFNα-Stimulated Immune Cell Populations to B6.NbA2 Lupus-like Disease

    Doctor of Philosophy, Case Western Reserve University, 2021, Molecular Medicine

    Systemic Lupus Erythematosus (SLE) is an autoimmune disease that can present with in a variety of ways, often with chronic inflammation, pain, and fatigue. Unfortunately, the extreme variety of symptoms with which SLE patients present has proven to be a barrier for the successful development of targeted treatments, with only a select few therapies progressing through clinical trials. Interferon α (IFNα) is one of the main cytokines elevated in a majority of SLE patients [1]. IFNα has been also shown to be important for disease development in animal models, however how IFNα is contributing to disease pathogenesis via the direct stimulation of specific immune cells such as B cells, T cells, and myeloid cells remains largely unknown. My research shows that IFNα stimulation of B cells leads to increased B cell activation, increased germinal center B cell survival, increased populations of antibody producing cells, and auto-antibodies. This research also shows that IFNα stimulation of T cells leads to a reduction in CD8+ FoxP3+ Tcregs. Additionally, IFNα stimulation of myeloid cells was found to lead to a decrease in marginal zone macrophages and myeloid-derived suppressor cells that normally provide tolerance. Finally, my research highlights that the action of IFNα is directly tied to the ability of apoptotic pathways to signal correctly. In summary, these findings provide critical insight into the progression of SLE, in addition to identifying new potential therapeutic targets.

    Committee: Trine Jorgensen PhD (Advisor); William Baldwin MD PhD (Committee Chair); Ganes Sen PhD (Committee Member); Christine O'Connor PhD (Committee Member); Howard Smith MD (Committee Member) Subjects: Animal Diseases; Health Sciences; Immunology; Molecular Biology
  • 16. Kathayat, Dipak Discovery of Novel Antibacterial Agents against Avian Pathogenic Escherichia coli (APEC): Identification of Molecular Targets, Assessing Impact on Gut Microbiome and Evaluating Potential as Antibiotic Adjuvants

    Doctor of Philosophy, The Ohio State University, 2021, Comparative and Veterinary Medicine

    Avian pathogenic E. coli (APEC), an extra-intestinal pathogenic E. coli (ExPEC), is one of the most common bacterial pathogens affecting poultry, including broilers, layers, breeders, turkeys and many other avian species. It causes high morbidity and mortality (up to 20%), decrease in production and increase in condemnation of carcasses (up to 43%) during slaughter, thus resulting in substantial economic losses to the poultry industry worldwide. Recent reports have suggested APEC as a source of human extra-intestinal infections, including urinary tract infections and sometimes meningitis. Further, APEC is also considered as a source of antibiotic resistance genes (ARGs) to human pathogens. Therefore, APEC is a pathogen of significant importance to both animal and human health. Currently, antibiotics are commonly used to control APEC infections; however, the increasing emergence of resistance to antibiotics and FDA (Food and Drug Administration) restrictions on using antibiotics in food-producing animals necessitate the development of new and effective antibacterials that can circumvent the resistance problem. Antibacterials targeting the outer membrane (OM) of bacteria can evade the problem of resistance in Gram-negative bacteria such as APEC. To this end, we discovered and evaluated small molecule (SM) growth inhibitors (GIs) and antimicrobial peptides (AMPs) affecting OM of APEC. We uncovered their antibacterial targets in the OM of APEC and assessed their impact on gut microbiome. We further demonstrated the potential of GIs as adjuvants to current antibiotics, including one of the last-resort antibiotics, colistin. A total of 11 GIs (GI1 – GI11) with bactericidal activity against APEC were identified through high throughput screening of pre-selected enriched small molecule library. Eight GIs that were effective and showed low toxicity in vitro in cultured epithelial and macrophage cells, red blood cells, and in vivo in wax moth (Galleria mellonella) larva mode (open full item for complete abstract)

    Committee: Gireesh Rajashekara (Advisor); James Fuchs (Committee Member); Vlasova Anastasia (Committee Member); Hale Vanessa (Committee Member) Subjects: Animal Diseases; Bioinformatics; Microbiology; Molecular Biology; Molecules; Pharmaceuticals; Therapy
  • 17. Fronczek, Kylie Modulation of thigmotaxis and locomotor activity in larval Danio rerio by the M1 muscarinic agonist CDD-0102A and the positive allosteric modulator BQCA.

    Master of Science (MS), University of Toledo, 2020, Pharmaceutical Sciences (Pharmacology/Toxicology)

    The behavioral studies revealed that the M1 muscarinic agonist CDD-0102A and the M1 receptor PAM BQCA produced significant changes in thigmotaxis in larval zebrafish. Increased levels of thigmotaxis may reflect an increase in repetitive behaviors. When anxious, repetitive behaviors generally increase. These compounds were predicted to decrease repetitive behaviors such as thigmotaxis in times associated with anxiety (dark times). CDD-0102A and BQCA both decreased thigmotaxis during the dark times when compared to the control.

    Committee: William Messer (Committee Co-Chair); Frederick Williams (Committee Co-Chair); Steven Peseckis (Committee Member) Subjects: Animal Diseases; Animal Sciences; Animals; Aquatic Sciences; Behavioral Sciences; Behaviorial Sciences; Biology; Biomedical Research; Pharmacology; Toxicology
  • 18. Lee, Elijah Trends in Bat Activity and Occupancy in Yellowstone National Park

    Master of Science (MS), Ohio University, 2020, Biological Sciences (Arts and Sciences)

    There are inherent challenges to monitoring bat populations in the Rocky Mountain West of North America, due in part to the apparent scarcity of large hibernacula that facilitate population assessments via abundance counts, and to the expansive, difficult or impassable terrain that can thwart data-collection efforts. The use of bioacoustic monitoring equipment and techniques provides a viable option to overcome these challenges and to provide much needed and otherwise sparse population ecology data. The studies within the following chapters employ various acoustic monitoring strategies with the goals of providing baseline data on bat populations in Yellowstone National Park, comparing two popular acoustic survey frameworks, and tracking changes in bat activity patterns following habitat disturbance caused by wildfire. In an effort to provide baseline data on bat populations in Yellowstone, I deployed 32 ultrasonic acoustic bat detectors for single-season occupancy analysis coupled with per-night activity level assessments over the summer of 2018. This project design focused on identifying habitat characteristics that explain current distributions in occupancy and loci of activity. Habitats were selected for consideration based on their documented use by bats for foraging, roosting, and as water sources, and were represented on two spatial scales. This analysis produced results for habitat associations that were diverse and species-specific, emphasizing the disparate strategies and habitat requirements represented within the Yellowstone bat population at large. To compare the results of mobile acoustic transect and point station survey frameworks, I performed 12 acoustic transects in the summer of 2018. The resultant data was compared to a subset of sites deployed for the occupancy and analysis study selected for their proximity to transect routes. I found that point stations recorded significantly more bats and documented greater species richness than mobile (open full item for complete abstract)

    Committee: Joseph Johnson (Advisor); Viorel Popescu (Committee Member); Willem Roosenburg (Committee Member) Subjects: Animal Diseases; Animal Sciences; Animals; Biology; Climate Change; Conservation; Ecology; Environmental Management; Environmental Science; Environmental Studies; Wildlife Conservation; Wildlife Management
  • 19. Reese, Daysia Surveillance for Multi-Drug Resistant Salmonella enterica Serovar Heidelberg in Livestock Markets

    Master of Public Health, The Ohio State University, 2020, Public Health

    Salmonella enterica serovar Heidelberg causes severe illness in humans and animals. It is recognized as the twelfth most reported serovar causing human salmonellosis and the fifth most reported serovar in cattle. Multi-drug resistant (MDR) Salmonella ser. Heidelberg is emerging as a pathogen that increases the likelihood of treatment complications and hospitalization. A recent multistate outbreak of multi-drug resistant Salmonella ser. Heidelberg was attributed to direct contact with dairy bull calves. Dairy bull calves are typically sold from the dairy farm within the first five days of birth for veal products. Transportation to livestock markets can increase the risk of infection in immunocompromised calves. Livestock markets can also serve as a point in the veal production system where calves may be exposed to MDR Salmonella ser. Heidelberg. Therefore, the primary objective of this study was to assess the prevalence of MDR Salmonella ser. Heidelberg in the environment of livestock markets. The secondary objective was to determine the prevalence of MDR Salmonella spp. for other virulent serovars. Ten livestock markets in Ohio and fourteen livestock markets in Wisconsin were sampled twice between April and November. Four environmental samples using boot swabs were taken at each livestock market during the first and second round of sampling. Sampling locations included the loading dock, a common alleyway traveled by calves from the loading dock to the holding pen, and two of the most frequently used holding pens or containing the largest number of calves at the time of sampling. Samples were sent to the Wisconsin Veterinary Diagnostic Lab for culture and serotype identification. Salmonella was recovered from 97.4% (186/191) of environmental samples. Among 191 samples, the most common serogroups identified were E1 (44%, 84/191), C1(22%, 42/191), and B (21.5%, 41/191). Isolates identified as Serogroup B, Serogroup C2, Serogroup D1 were selected for serotyping. Seven ( (open full item for complete abstract)

    Committee: Gregory Habing DVM, MS, PhD (Advisor); Andréia Arruda DVM, MS, PhD (Committee Member); Laura Pomeroy PhD (Committee Member) Subjects: Animal Diseases; Public Health
  • 20. Briggs, Whitney Evaluation and optimization of quantitative analysis methods for Clostridium perfringens detection in broiler intestinal samples to use with necrotic enteritis challenge models

    Master of Science, The Ohio State University, 2020, Animal Sciences

    Necrotic enteritis (NE) is a multifactorial disease caused by Clostridium perfringens. A way to examine treatments on NE is through methods like body weight gain or lesion scores. Quantification of C. perfringens could be additional measurement. In experiment 3.1, four published extraction protocols, and a new protocol were compared to determine which would be ideal for extracting bacterial DNA. After extraction, DNA concentrations were measured with quality assessed, and a qPCR standard curve was established for each protocol. For Protocols 1 to 5, mean DNA yields and A260/280/A260/230 ratios were 459.02μg/g and 2.18/1.26, 989.66μg/g and 2.07/2.06, 110.71μg/g and 1.58/0.89, 437.03μg/g and 2.07/1.93 and 1,794.90μg/g and 1.91/1.42, respectively. Amplification efficiency percentages and standard curve regression coefficient values for Protocols 1 to 5 were 84.69%/1.00, 79.76%/0.99, 100.30%/1.00, 80.93%/0.99 and 95.76%/0.99, respectively. There was extensive variation in DNA quantity, quality, and PCR efficiency, highlighting challenges of DNA extraction from intestinal samples. Protocol 2 was identified as ideal based on DNA quantity and quality, and low standard deviations between qPCR samples. Experiments 4.1 and 4.2 compared qPCR and direct plating of fecal, ileal and cecal samples for C. perfringens quantification. In experiment 4.1, two groups were compared; an un-inoculated control and an inoculated group, while in experiment 4.2, the two groups compared were an un-inoculated control, fed a corn-based diet and an inoculated rye-based diet group. For quantifying C. perfringens, qPCR and two recently developed selective agar types were compared, with results analyzed by ANOVA factorials and Tukey's Honestly Significant Difference test. All methods were further evaluated using relative standard deviation of CFU/g percentage (RSD%) values. In experiment 4.1, quantification method was a significant variable (p<0.05), with significant differences between qPCR and C. p (open full item for complete abstract)

    Committee: Lisa Bielke (Advisor); Thaddeus Ezeji (Committee Member); Zhongtang Yu (Committee Member) Subjects: Animal Diseases; Microbiology; Molecular Biology