Medicine and Health Sciences Commons^™

Human-Bat Interactions In A Disease Emergence Hotspot: Implications For Human Health And Bat Conservation, Reilly Tempest Jackson

Graduate Theses and Dissertations

Bats are an ecologically important taxon that can host zoonotic pathogens. Globally, many bat species are synanthropic and live closely with humans, often roosting in man-made structures. The spatial overlap between humans and bats creates opportunities for human-bat contact, which can lead to human exposure to bat-borne pathogens and conflicts that cause bat mortality. Despite this risk, little is known about the drivers and characteristics of these human-bat interactions in buildings and work is needed to understand this aspect of the wildlife-urban interface. In Chapter I, I present a literature review that identifies the geographic and taxonomic trends in reported …

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

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.

Starch Granule And Crystalline Structures With Relation To Enzyme Digestibility, Ana Isabel Gonzalez Conde

Graduate Theses and Dissertations

Porous starch produced by enzyme hydrolysis has attracted much attention for its adsorption and delivery properties. Porous starch has been successfully prepared from A-type starch, but not from B-type and C-type starches, which is partly attributed to the surface and crystalline structure. The present study aimed to characterize the role of the crystalline structure and the structure-function relationship impacting the susceptibility of starch with different crystalline polymorphs to amylase digestion. The starches were subjected to chemical modification (acid hydrolysis or surface gelatinization), physical modification (heat-moisture treatment, HMT, or high-pressure processing, HPP) or their combinations prior to amylase digestion, and the …

Unveiling The Ancestral Function Of A Neuroendocrine Regulator, Pou-I/Pit1: Insights From Gene Expression Analysis In The Sea Anemone Nematostella Vectensis, Miguel Agostinho Pina Da Silva

Graduate Theses and Dissertations

Cnidaria (i.e., sea anemones, jellyfish, corals) and Bilateria (i.e., vertebrates, sea stars, fruit flies), are sister groups that diverged around 600 million years ago. Despite the long evolutionary time, many cellular differentiation mechanisms, cell types, tissues and behaviors are conserved. Such as neurons, mechanosensory hair cells, feeding behaviors, peristaltic movements, and sleep. Recent advances in genomics, molecular biology and microscopy have fueled an increased interest in understanding cnidarian nervous and neuroendocrine systems. Understanding the developmental mechanisms and the mode of operation of Cnidarian nervous systems helps to reconstruct the ancestral nervous system of the last common ancestor of Cnidaria and …

Isolation Of Drug-Sensitive Eimeria Species From Wild Turkey Feces And Development Of A Model Bioshuttle Program For Eimeria Meleagrimitis For Domestic Turkeys, Maria Carolina Trujillo Peralta

Graduate Theses and Dissertations

The objective of this thesis was to determine the anticoccidial profile of Eimeria spp. derived from wild turkeys. These drug-sensitive Eimeria spp. have potential to be used as vaccine candidates to control coccidiosis in commercial turkeys. Chapter two consists of a brief literature review focused on coccidiosis in turkeys. Chapter three addresses the methodologies utilized to isolate, recover, and speciate Eimeria recovered from wild turkey feces in the eastern two-thirds of the United States. From this, we successfully obtained single oocyst-derived stocks for E. meleagrimitis, E. dispersa, E. meleagridis, E. gallopavonis, and E. adenoeides. Chapter four describes the experiment conducted …

Optimization Of Clostridium Septicum Antigen Production And Evaluation Of Vaccine Administration Parameters For A Candidate Bacterin-Toxoid To Prevent Dermatitis In Commercial Turkeys, Aaron Forga

Graduate Theses and Dissertations

The objective of this thesis was to optimize the hemolytic activity of two isolates of Clostridium septicum to evaluate if hemolytic titer of C. septicum antigen at time of formalin inactivation corresponded to increased serum antibody titer to the C. septicum alpha-toxin of turkeys immunized with an experimental formalin inactivated bacterin-toxoid vaccine. Chapter 1 provides a brief overview of the thesis. Chapter 2 consists of a literature review focused on clostridial dermatitis, specifically C. septicum-associated dermatitis (cellulitis) that affects commercial turkeys. Chapter 3 outlines our attempts to optimize an experimental autogenous bacterin-toxoid vaccine as a potential strategy to mitigate clostridial …

Differential Impacts Of Hhv-6a Versus Hhv-6b Infection In Differentiated Human Neural Stem Cells, Elham Bahramian

Graduate Theses and Dissertations

Within the family Herpesviridae, sub-family β-herpesvirinae, and genus Roseolovirus, there areonly three human herpesviruses that have been described: HHV-6A, HHV-6B, and HHV-7. Initially, HHV-6A and HHV-6B were considered as two variants of the same virus (i.e., HHV6). Despite high overall genetic sequence identity (~90%), HHV-6A and HHV-6B are now recognized as two distinct viruses. Sequence divergence (e.g., >30%) in key coding regions and significant differences in physiological and biochemical profiles (e.g., use of different receptors for viral entry) underscores the conclusion that HHV-6A and HHV-6B are distinct viruses of the β-herpesvirinae. Despite these viruses being implicated as causative agents in …

Identification Of Possible Vectors For Histomoniasis In Turkeys On Commercial Farms In Arkansas And Oklahoma, Treva Dillon

Graduate Theses and Dissertations

Histomonas meleagridis, is a parasitic protozoan, commonly found in the gallinaceous species of birds and is the causative agent of Blackhead disease. The cecal worm, known as Heteraskis gallinarum, acts as a vector in the spread of H. meleagridis in gallinaceous birds. H. meleagridis develops inside the cecal worm and in its eggs which allows H. meleagridis a method to survive in the environment. Blackhead disease causes high mortality rates in both chickens and turkeys; however, turkeys are noted to have a higher mortality rate compared to chickens. Molecular diagnostic testing such as PCR has been developed by creating primers …

Discrete Choice Experiments In Agricultural And Food Economics: Two Essays On Information Provision Modalities, Uncertainty Adjustment, And Hypothetical Bias, Monsoïa Arsène Juste Agossadou

Graduate Theses and Dissertations

Stated discrete choice experiments are extensively used in applied economics to study preferences and valuation for new products, as well as costs and benefits of new policies and programs. Moreover, information provision experiments widely use the method to examine information effects on different outcomes. This thesis explores two methodological issues in discrete choice experiments: (i) information provision modalities and (ii) hypothetical bias. The first study examines the effect of information modality by testing the effect of using combined text script and audio clip (treatment) versus only text script (control) to convey information in discrete choice experiments. Specifically, the study elicits …

The Effects Of Physical Function And Genetics On Cognition And Blood Biomarkers In Individuals At-Risk For Alzheimer’S Disease And Related Dementias, Joshua Louis Gills

Graduate Theses and Dissertations

Alzheimer’s disease and related dementia (ADRD) rates are expected to triple by the year 2050. Early detection and specific mitigation efforts are warranted to blunt the alarming rate. Physical function (PF) declines with age, but higher physical function is associated with better cognitive functioning in middle-to- older age individuals. Moreover, greater physical activity (PA) is associated with better global cognition; however, Apoliporotein e4 carriers may not gain the same benefits with exercise. Additionally, plasma phosphorylated tau 217 (p-tau217) has been identified as a novel diagnostic ADRD biomarker which needs further research to examine associations with risk factors. Therefore, the aims …

Intestinal Microbiota Analysis Of Broiler Chickens Under Necrotic Enteritis Challenge And Tributyrin Supplementation, Taylor Nicole Mckinney

Graduate Theses and Dissertations

Poultry is a staple protein source for most of the planet. Until recently, antibiotic growth promoters (AGPs) were used to prevent illnesses in commercial chicken production. Currently, this is not possible due to regulations and consumer concern, but without such a preventative, diseases like necrotic enteritis (NE) have reemerged, posing a threat to bird health, and ultimately, our food source. Necrotic enteritis is a severe gastrointestinal disease caused by the gram-positive pathogen, Clostridium perfringens. Clinical features of this disease are diarrhea, intestinal lesions, and death, with a high transmission rate. In a subclinical form, growth performance is diminished and is …

Bacterial Chondronecrosis With Osteomyelitis In Broilers: Genomics, Phylogenomics, And Methods To Detect Specific Pathogens During Outbreaks., Abdulkarim Abdulaziz A. Shwani

Graduate Theses and Dissertations

Lameness is a major issue in animal welfare and the broiler industry. Bacterial chondronecrosis with osteomyelitis (BCO) is one of the main causes of lameness. Many staphylococcal species, including Staphylococcus agnetis isolate 908, have been isolated from the bones and blood of lame broilers at the University of Arkansas. Staphylococcus agnetis is a coagulase-variable, Gram-positive bacterial species that has been previously associated with subclinical or mild clinical cases of mastitis in dairy cattle. The annotated complete genome of hypervirulent strain 908 was published at NCBI. In this study, it has been compared to nine genomes we assembled for hypervirulent isolates …

Histomonosis In Turkeys – Factors Influencing Transmission, Pathogenesis, And The Search For Prophylactic Or Therapeutic Compounds, Thainá Landim De Barros

Graduate Theses and Dissertations

The incidence of histomonosis has been increasing in poultry since the ban of prophylactic and therapeutic compounds. Histomonosis is caused by the protozoa Histomonas meleagridis. The objective of this dissertation was to investigate factors impacting the pathogenesis and transmission of histomonosis and to evaluate compounds that could potentially prevent or reduce the severity of histomonosis in turkeys. In the first study, the effect of sodium chlorate and sodium nitrate on reducing histomonads growth was tested in vitro and added to a basal turkey diet. A decrease in the growth of histomonads in vitro was observed, but no in vivo effect …

Investigating Molecular Mechanisms Behind Bacterial Chondronecrosis With Osteomyelitis (Bco) Pathogenesis In Modern Broilers, Alison Ramser

Graduate Theses and Dissertations

Bacterial chondronecrosis with osteomyelitis (BCO), a leading cause of lameness in broiler chickens, is characterized by infection, inflammation, and bone attrition. There are currently no effective treatments and positive diagnosis is only possible through necropsy evaluations. Lameness is also a rising animal welfare and economic concern, making prevention and detection of BCO all the more critical. These challenges are exacerbated by a lack of mechanistic understanding of BCO’s etiology. The question I asked during my dissertation was how bacteria induce bone attrition in BCO pathology. My research has shown that mitochondrial dysfunction is characteristic of BCO conditions along with autophagy …

Examining The Effects Of Oral Contraceptive Use On Thermoregulation, Whitley C. Atkins

Graduate Theses and Dissertations

Purpose: The purpose of this investigation was to evaluate the effects of combined (estradiol and progestin) monophasic oral contraceptive pill (OCP) use on thermoregulation. Further, we sought to evaluate OCP use on acute rehydration post-exercise in the heat using recommended rehydration guidelines. Methods: Twelve healthy, aerobically trained (VO2peak = 47.8 ± 4.7 mL/kg/min), long term female oral contraceptive users completed a familiarization trial and two experimental days separated by ≥ 7 days. The two experimental trials were identical except for the hormone dosing phase. One trial was completed during the third week of active pill dosing (ACT) and one during …

Efficacy Of Multivitamin-Mineral Supplementation On Measures Of Anxiety, Depression, Self-Esteem, Dysregulation, And Perceived Stress In Young Adults, Courtney Gorden

Graduate Theses and Dissertations

Mental health in the United States is at an all-time low with 21% of adults 18+ suffering from depression or anxiety. When compared with other categories, emerging adults (18-25 years old) have the highest prevalence of mental health disorders at 30%. Young adults face an inordinate amount of stress given the COVID-19 pandemic, being in a unique developmental stage, experiencing new relationships, and transitioning from high school to their professional lives. Vitamins and minerals have roles in neurobiochemistry and have been investigated for effects on mental health with mixed results. Few studies factor in the unique emerging adult developmental stage …

Evaluation Of The Effect Of A Lippia Organoides Essential Oil Extract On Clostridium Perfringens Proliferation In Vitro And Necrotic Enteritis In Broiler Chickens, Makenly E. Coles

Graduate Theses and Dissertations

The purpose of the present research was to assess the effects of essential oils derived from the plant Lippia organoides on performance parameters, intestinal integrity, and necrotic enteritis (NE) in broiler chickens. To do this, a previously established challenge model for NE was utilized which included challenging with Salmonella Typhimurium on day 0, Eimeria maxima on day 18, and Clostridium perfringens on days 22 and 23. Treatment groups included a 1) non-challenged, negative control, 2) challenged control, and 3) challenged, Lippia origanoides (37ppm in the diet). Group 1 (negative control) had significantly (P < 0.05) higher body weight gain from d8-25 and d0-25 compared to both challenged groups. Feed intake was significantly different for all three groups (P < 0.05) at 8-25 days and 0-25 days with group 1 having the highest feed intake for both time periods. Total mortality was greater in the positive control when compared to both the negative and treatment groups. NE lesion scores were significantly different between all groups with the positive control having the highest mean lesion scores and the negative control having a mean lesion score of 0. The positive control group had the highest FITC-d amounts detected in the sera, being statistically higher than both the treatment group and negative group which were both statistically different from each other. At the present inclusion rate for the essential oil (37 ppm), there was an overall reduction in the negative impact from the NE infection. Further studies should be conducted to reach more significant conclusions.

Implementing An Exercise Referral Scheme For Promoting Physical Activity In University Mental Health Care, Bryce Daniels

Graduate Theses and Dissertations

Introduction. Mental health symptoms and conditions are prevalent and increasing on college campuses with anxiety and depression having the highest increases in prevalence. Many college students are also physically inactive which is problematic as physical activity benefits mental health. Exercise referral schemes (ERS) can promote physical activity, though no studies have investigated the implementation of an ERS within a college counseling center. Purpose. The purpose of this dissertation was to investigate the implementation of an ERS for promoting physical activity in university mental health care. Methods. Study 1 used a qualitative descriptive design of 14 certified counselors to explore perceptions …

A Mixed Methods Approach To Context Specific Curriculum Design For Very Small And Small Strawberry Growers In The Southeastern United States, Thomas A. Yeargin

Graduate Theses and Dissertations

Outbreaks of foodborne illness due to fresh produce are a continued threat to both the publichealth and the economy in the United States. Though there are many factors which influence the perpetuation of foodborne pathogens, the inability of the food industry to curtail this issue indicates systemic failure of interventions aimed at improving food safety practices. In this dissertation, we detail the efforts made over the past few decades to provide training to food producers and food handlers as well as recommendations that have been made for improvement based on these studies. By borrowing from more advanced fields of study …

The Effects Of Metronomic And Maximum-Tolerated Dose Chemotherapy In Colorectal Cancer Angiogenesis: A Combined Approach Using Endoscopic Diffuse Reflectance Spectroscopy And Mrna Expression, Ariel Isaac Mundo Ortiz

Graduate Theses and Dissertations

Colorectal cancer (CRC) continues to be one of the most incident and deadliest types of cancer worldwide. Chemotherapy has proven effective to reduce tumor burden for CRC patients, but there are several disadvantages associated with the use of mainstay maximtolerated dose (MTD) chemotherapeutic strategies. Metronomic chemotherapy (MET) has been developed as an alternative that addresses the shortcomings of maximum-tolerated dose chemotherapy but so far its effectiveness as a neoadjuvant strategy for CRC has not been explored.

This dissertation uses a combined optics and molecular biology approach (using diffuse reflectance spectroscopy and mRNA expression) to study the changes in angiogenesis and …

Investigation Of Histomoniasis Prevention In Poultry, Lesleigh Beer

Graduate Theses and Dissertations

Histomonas meleagridis is the etiological agent of histomoniasis, also commonly known as blackhead disease. This protozoal disease of poultry is detrimental to turkeys with flock mortalities often reaching 80-100%, although other gallinaceous birds are susceptible. Since the voluntary removal of nitarsone in 2015, the poultry industry is suffering with no approved prophylactics, therapeutics, or vaccines for this disease. The objectives of this dissertation were to evaluate multiple methods for prevention or control of histomoniasis, including dietary chemoprophylaxis and vaccination. Specifically, this research evaluated quinine as a chemoprophylactic candidate (Chapter 3) or live-attenuated H. meleagridis as vaccine candidates (Chapter 4) in …

Effects Of Localized Oxygen Production By Electrolysis On The First-Generation Glucose Sensor Response, Nandita Halder

Graduate Theses and Dissertations

Glucose sensors are very important for detecting blood glucose both in vitro and in vivo. First-generation glucose biosensors were based on the glucose oxidase (GOx) enzyme using molecular oxygen as the electron acceptor and therefore oxygen dependent. Unfortunately for in-vivo work, oxygen in the body is variable and limited. Alternative approaches to overcome the oxygen dependency came with their own limitations. The widely used and commercially available ex-vivo glucose test strip uses a mediator in place of oxygen to free it from oxygen dependency. The mediator-based technology, in most cases cannot be transferred to in vivo applications due to the …

Evaluation Of Two Neonatal Challenge Models For Broiler Chickens And Their Effects On Early Performance Parameters, Callie Selby

Graduate Theses and Dissertations

Formaldehyde fumigation in poultry hatch cabinets has been utilized for sanitation of hatching eggs for over a century. Formaldehyde is utilized to minimize pathogenic microbes on the surface of the egg as well as the microbial bloom during the hatching process. While formaldehyde is effective, its use is regulated in the United States and Europe due to its carcinogenic nature. Formaldehyde has been shown to damage the cuticle of the egg, cause embryonic death, and damage the epithelial lining of the respiratory tract of freshly hatched chicks, predisposing them for respiratory infection. Alternatives for formaldehyde fumigation must be identified and …

Nanomaterial-Based Biosensors For Detection Of Salmonella Typhimurium And Avian Influenza Virus H5n1 In Poultry, Xinge Xi

Graduate Theses and Dissertations

This research focused on developing biosensing method and biosensing device for rapid detection of pathogens in poultry: Salmonella Typhimurium and avian influenza virus H5N1. The first part of the dissertation reports an original research on the development of a portable biosensing device for Salmonella detection. The device was designed and constructed based on a previously developed optical biosensing method, using immuno-magnetic nanoparticles to specifically capture target bacteria, and immuno-quantum dot beads to label the target bacteria for fluorescence detection. All the actions of sample mixing, magnetic separation, and fluorescence detection were controlled automatically in a disposable microfluidic chip in the …

Experimental And Analysis Of Electromagnetic Characterization Of Biological And Non-Biological Materials In Microwave, Millimeter-Wave, And Terahertz Frequency Bands, Nagma Vohra

Graduate Theses and Dissertations

The goal of this research is to characterize the electromagnetic properties of biological and non-biological materials at terahertz (THz), millimeter-wave, and microwave frequency bands. The biological specimens are measured using the THz imaging and spectroscopy system, whereas the non-biological materials are measured using the microwave and millimeter-wave free-space system. These facilities are located in the Engineering Research Center at the University of Arkansas. The THz imaging system (TPS 3000) uses a Ti-Sapphire laser directed on the photoconductive antennas to generate a THz time domain pulse. Upon using the Fourier Transform, the spectrum of the pulsed THz signal includes frequencies from …

A Time-Course Characterization Of Muscle Function And Mitochondrial Markers During Colorectal Cancer-Induced Cachexia In Tumor-Bearing Male Mice, Ana Cabrera Ayuso

Graduate Theses and Dissertations

Cachexia is a multisystemic and multifactorial syndrome prevalent in cancer patients. It is clinically defined by involuntary loss of >5% weight in a six-month window, despite nutritional interventions. A negative energy balance characterizes cancer cachexia (CC), it is associated with weakness and fatigue in skeletal muscle. Impaired muscle function is associated with lower quality of life in cancer patients. Defects in mitochondrial function are strongly associated with muscle wasting. This study explored muscular contractile function and mitochondrial quality control (MQC) markers in soleus, gastrocnemius, and tibialis anterior (TA) muscles of C26-induced male tumor-bearing mice during a 25-day time course. It …

Directed Genome Evolution To Identify Genes For Macrophage Survival By Staphylococcus Agnetis, Sonali Lakshika Anne Lenaduwe Lokuge

Graduate Theses and Dissertations

Bacterial Chondronecrosis with Osteomyelitis (BCO) is a debilitating infection that negatively impacts animal welfare and costs the broiler industry billions of dollars annually. We have previously isolated Staphylococcus agnetis 908 from BCO samples obtained from broilers at the University of Arkansas research farm. This isolate can induce BCO lameness at greater than 50% in broilers exposed to the pathogen in drinking water. We found that S. agnetis 908 is capable of surviving and escaping macrophages compared to a closely related cattle isolate,1379. Through Directed Genome Evolution (DGE) we identified that this difference is at least partially associated with an alanine …

The Balance Of Excitation And Inhibition And Its Influence On Cortical States And Rett Syndrome, Jingwen Li

Graduate Theses and Dissertations

Our brain consists of billions of neurons, properly coordinating to process information and realize brain functions. Among them, there are two types of neurons: excitatory neurons and inhibitory neurons. The firing of excitatory neurons increases the membrane potential of downstream neurons, and thus excites other neurons to fire. The firing of inhibitory neurons, in contrast, decreases the membrane potential of downstream neurons, and thus inhibits other neurons to fire. The interplay of excitatory and inhibitory neurons shape the spiking activity in the population. Thus, the `balance of excitation and inhibition' plays an important role in cortical processing and brain functions. …

Biochemical Characterization Of Small Molecule Inhibitor Binding On A Ras Related Gtpase And Its Effector Interactions, Djamali Muhoza

Graduate Theses and Dissertations

The Ras superfamily of GTPases has 167 proteins that are involved in various cellular processes such as proliferation, transformation, migration, and inhibition of cell death. Mutations, abnormal expression, and function of these proteins are observed in many diseases, including several forms of cancer. Even though these GTPases were among the first discovered oncogenes, no successful Ras drug candidate has successfully passed clinical trials. Drugs targeting these proteins have failed mainly because of the complexity of their regulation, their high affinity to GTP, and their structure’s dynamic nature. Recently, novel promising targeting approaches have renewed interest in the Ras drug discovery …