Matching Items (89)
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The devastating 2014 Ebola virus outbreak in Western Africa demonstrated the lack of therapeutic approaches available for the virus. Although monoclonal antibodies (mAb) and other molecules have been developed that bind the virus, no therapeutic has shown the efficacy needed for FDA approval. Here, a library of 50 peptide based

The devastating 2014 Ebola virus outbreak in Western Africa demonstrated the lack of therapeutic approaches available for the virus. Although monoclonal antibodies (mAb) and other molecules have been developed that bind the virus, no therapeutic has shown the efficacy needed for FDA approval. Here, a library of 50 peptide based ligands that bind the glycoprotein of the Zaire Ebola virus (GP) were developed. Using whole virus screening of vesicular stomatitis virus pseudotyped with GP, low affinity peptides were identified for ligand construction. In depth analysis showed that two of the peptide based molecules bound the Zaire GP with <100 nM KD. One of these two ligands was blocked by a known neutralizing mAb, 2G4, and showed cross-reactivity to the Sudan GP. This work presents ligands with promise for therapeutic applications across multiple variants of the Ebola virus.
ContributorsRabinowitz, Joshua Avraam (Author) / Diehnelt, Chris (Thesis director) / Johnston, Stephen (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Both technological and scientific fields continue to revolutionize in a similar fashion; however, a major difference is that high-tech corporations have found models to continue progressions while still keeping product costs low. The main objective was to identify which, if any, components of certain technological models could be used with

Both technological and scientific fields continue to revolutionize in a similar fashion; however, a major difference is that high-tech corporations have found models to continue progressions while still keeping product costs low. The main objective was to identify which, if any, components of certain technological models could be used with the vaccine and pharmaceutical markets to significantly lower their costs. Smartphones and computers were the two main items investigated while the two main items from the scientific standpoint were vaccines and pharmaceuticals. One concept had the ability to conceivably decrease the costs of vaccines and drugs and that was "market competition". If the United States were able to allow competition within the vaccine and drug companies, it would allow for the product prices to be best affected. It would only take a few small companies to generate generic versions of the drugs and decrease the prices. It would force the larger competition to most likely decrease their prices. Furthermore, the PC companies use a cumulative density function (CDF) to effectively divide their price setting in each product cycle. It was predicted that if this CDF model were applied to the vaccine and drug markets, the prices would no longer have to be extreme. The corporations would be able to set the highest price for the wealthiest consumers and then slowly begin to decrease the costs for the middle and lower class. Unfortunately, the problem within the vaccine and pharmaceutical markets was not the lack of innovation or business models. The problem lied with their liberty to choose product costs due to poor U.S. government regulations.
ContributorsCalderon, Gerardo (Author) / Johnston, Stephen (Thesis director) / Diehnelt, Chris (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Historically, studies of condition-dependent signals in animals have been male-centric, but recent work suggests that female ornaments can also communicate individual quality (e.g., disease state, fecundity). There has been a surge of interest in how urbanization alters signaling traits, but we know little about if and how cities affect signal

Historically, studies of condition-dependent signals in animals have been male-centric, but recent work suggests that female ornaments can also communicate individual quality (e.g., disease state, fecundity). There has been a surge of interest in how urbanization alters signaling traits, but we know little about if and how cities affect signal expression in female animals. We measured carotenoid-based plumage coloration and coccidian (Isospora spp) parasite burden in desert and city populations of house finches to examine urban impacts on male and female health and attractiveness. In earlier work, we showed that male house finches are less colorful and more parasitized in the city, and we again detected that pattern in this study for males. However, though city females are also less colorful than their rural counterparts, we found that rural females were more parasitized. Also, regardless of sex and unlike rural birds, more colorful birds in the city were more heavily infected with coccidia. These results show that urban environments can disrupt signal honesty in female animals and highlight the need for more studies on how cities affect disease and condition-dependent traits in both male and female animals.
ContributorsSykes, Brooke Emma (Author) / McGraw, Kevin (Thesis director) / Sweazea, Karen (Committee member) / Hutton, Pierce (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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There are two electrophysiological states of sleep in birds (rapid-eye-movement sleep [REM] and slow-wave sleep [SWS]), which have different functions and costs. REM improves memory consolidation, while SWS is neuro-restorative but also exposes the animal to more risk during this deep-sleep phase. Birds who sleep in more exposed microsites are known

There are two electrophysiological states of sleep in birds (rapid-eye-movement sleep [REM] and slow-wave sleep [SWS]), which have different functions and costs. REM improves memory consolidation, while SWS is neuro-restorative but also exposes the animal to more risk during this deep-sleep phase. Birds who sleep in more exposed microsites are known to invest proportionally less in SWS (presumably to ensure proper vigilance), but otherwise little else is known about the ecological or behavioral predictors of how much time birds devote to REM v. SWS sleep. In this comparative analysis, we examine how proportional time spent in SWS v. REM is related to brain mass and duration of the incubation period in adults. Brain mass and incubation period were chosen as predictors of sleep state investment because brain mass is positively correlated with body size (and may show a relationship between physical development and sleep) and incubation period can be a link used to show similarities and differences between birds and mammals (using mammalian gestation period). We hypothesized that (1) species with larger brains (relative to body size and also while controlling for phylogeny) would have higher demands for information processing, and possibly proportionally outweigh neuro-repair, and thus devote more time to REM and that (2) species with longer incubation periods would have proportionally more REM due to the extended time required for overnight predator vigilance (and not falling into deep sleep) while on the nest. We found, using neurophysiological data from literature on 27 bird species, that adults from species with longer incubation periods spent proportionally more time in REM sleep, but that relative brain size was not significantly associated with relative time spent in REM or SWS. We therefore provide evidence that mammalian and avian REM in response to incubation/gestation period have convergently evolved. Our results suggest that overnight environmental conditions (e.g. sleep site exposure) might have a greater effect on sleep parameters than gross morphological attributes.
ContributorsRaiffe, Joshua Sapell (Author) / McGraw, Kevin (Thesis director) / Deviche, Pierre (Committee member) / Hutton, Pierce (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Humans have greatly altered the night-time photic environment via the production of artificial light at night (ALAN; e.g. street lights, car traffic, billboards, lit buildings). ALAN is problematic because it may significantly alter the seasonal/daily physiological rhythms or behaviors of animals. There has been considerable interest in the impacts of

Humans have greatly altered the night-time photic environment via the production of artificial light at night (ALAN; e.g. street lights, car traffic, billboards, lit buildings). ALAN is problematic because it may significantly alter the seasonal/daily physiological rhythms or behaviors of animals. There has been considerable interest in the impacts of ALAN on health in humans and lab animals, but most such work has centered on adults and we know comparatively little about effects on young animals. We exposed 3-week-old king quail (Excalfactoria chinensis) to a constant overnight blue-light regime for 6 weeks and assessed weekly bactericidal activity of plasma against Escherichia coli - a commonly employed metric of innate immunity in animals. We found that chronic ALAN exposure significantly increased immune function, and that this elevation in immune performance manifested at different developmental time points in males and females. These results counter the pervasive notion that overnight light exposure is universally physiologically harmful to diurnal organisms and indicate that ALAN can provide sex-specific, short-term immunological boosts to developing animals.
ContributorsSaini, Chandan (Author) / McGraw, Kevin (Thesis director) / Hutton, Pierce (Committee member) / Sweazea, Karen (Committee member) / Department of Psychology (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-12
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ABSTRACT Peptide microarrays may prove to be a powerful tool for proteomics research and clinical diagnosis applications. Fodor et al. and Maurer et al. have shown proof-of-concept methods of light- and electrochemically-directed peptide microarray fabrication on glass and semiconductor microchips respectively. In this work, peptide microarray fabrication based on the

ABSTRACT Peptide microarrays may prove to be a powerful tool for proteomics research and clinical diagnosis applications. Fodor et al. and Maurer et al. have shown proof-of-concept methods of light- and electrochemically-directed peptide microarray fabrication on glass and semiconductor microchips respectively. In this work, peptide microarray fabrication based on the abovementioned techniques were optimized. In addition, MALDI mass spectrometry based peptide synthesis characterization on semiconductor microchips was developed and novel applications of a CombiMatrix (CBMX) platform for electrochemically controlled synthesis were explored. We have investigated performance of 2-(2-nitrophenyl)propoxycarbonyl (NPPOC) derivatives as photo-labile protecting group. Specifically, influence of substituents on 4 and 5 positions of phenyl ring of NPPOC group on the rate of photolysis and the yield of the amine was investigated. The results indicated that substituents capable of forming a π-network with the nitro group enhanced the rate of photolysis and yield. Once such properly substituted NPPOC groups were used, the rate of photolysis/yield depended on the nature of protected amino group indicating that a different chemical step during the photo-cleavage process became the rate limiting step. We also focused on electrochemically-directed parallel synthesis of high-density peptide microarrays using the CBMX technology referred to above which uses electrochemically generated acids to perform patterned chemistry. Several issues related to peptide synthesis on the CBMX platform were studied and optimized, with emphasis placed on the reactions of electro-generated acids during the deprotection step of peptide synthesis. We have developed a MALDI mass spectrometry based method to determine the chemical composition of microarray synthesis, directly on the feature. This method utilizes non-diffusional chemical cleavage from the surface, thereby making the chemical characterization of high-density microarray features simple, accurate, and amenable to high-throughput. CBMX Corp. has developed a microarray reader which is based on electro-chemical detection of redox chemical species. Several parameters of the instrument were studied and optimized and novel redox applications of peptide microarrays on CBMX platform were also investigated using the instrument. These include (i) a search of metal binding catalytic peptides to reduce overpotential associated with water oxidation reaction and (ii) an immobilization of peptide microarrays using electro-polymerized polypyrrole.
ContributorsKumar, Pallav (Author) / Woodbury, Neal (Thesis advisor) / Allen, James (Committee member) / Johnston, Stephen (Committee member) / Arizona State University (Publisher)
Created2013
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Particulate Guanylyl Cyclase Receptor A (pGC-A) is an atrial natriuretic peptide receptor, which plays a vital role in controlling cardiovascular, renal, and endocrine functions. The extracellular domain of pGC-A interacts with natriuretic peptides and triggers the intracellular guanylyl cyclase domain to convert GTP to cGMP. To effectively develop a method

Particulate Guanylyl Cyclase Receptor A (pGC-A) is an atrial natriuretic peptide receptor, which plays a vital role in controlling cardiovascular, renal, and endocrine functions. The extracellular domain of pGC-A interacts with natriuretic peptides and triggers the intracellular guanylyl cyclase domain to convert GTP to cGMP. To effectively develop a method that can regulate pGC-A, structural information regarding its intact form is necessary. Currently, only the extracellular domain structure of rat pGC-A has been determined. However, structural data regarding the transmembrane domain, as well as functional intracellular domain regions, need to be elucidated.This dissertation presents detailed information regarding pGC-A expression and optimization in the baculovirus expression vector system, along with the first purification method for purifying functional intact human pGC-A. The first in vitro evidence of a purified intact human pGC-A tetramer was detected in detergent micellar solution. Intact pGC-A is currently proposed to function as a homodimer. Upon analyzing my findings and acknowledging that dimer formation is required for pGC-A functionality, I proposed the first tetramer complex model composed of two functional subunits (homodimer). Forming tetramer complexes on the cell membrane increases pGC-A binding efficiency and ligand sensitivity. Currently, a two-step mechanism has been proposed for ATP-dependent pGC-A signal transduction. Based on cGMP functional assay results, it can be suggested that the binding ligand also moderately activates pGC-A, and that ATP is not crucial for the activation of guanylyl cyclase. Instead, three modulators can regulate different activation levels in intact pGC-A. Crystallization of purified intact pGC-A was performed to determine its structure. During the crystallization condition screening process, I successfully selected seven promising initial crystallization conditions for intact human pGC-A crystallization. One selected condition led to the formation of excellent needle-shaped crystals. During the serial crystallography diffraction experiment, five diffraction patterns were detected. The highest diffraction resolution spot reached 3 Å. This work will allow the determination of the intact human pGC-A structure while also providing structural information on the protein signal transduction mechanism. Further structural knowledge may potentially lead to improved drug design. More precise mutation experiments could help verify the current pGC-A signal transduction and activation mechanism.
ContributorsZhang, Shangji (Author) / Fromme, Petra (Thesis advisor) / Johnston, Stephen (Committee member) / Mazor, Yuval (Committee member) / Arizona State University (Publisher)
Created2021
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Animals use diverse signal types (e.g. visual, auditory) to honestly advertise their genotypic and/or phenotypic quality to prospective mates or rivals. Behavioral displays and other dynamically updateable signals (e.g. songs, vibrations) can reliably reveal an individual’s quality in real-time, but it is unclear whether more fixed traits like feather coloration,

Animals use diverse signal types (e.g. visual, auditory) to honestly advertise their genotypic and/or phenotypic quality to prospective mates or rivals. Behavioral displays and other dynamically updateable signals (e.g. songs, vibrations) can reliably reveal an individual’s quality in real-time, but it is unclear whether more fixed traits like feather coloration, which is often developed months before breeding, still reveal an individual’s quality at the time of signal use. To address this gap, we investigated if various indices of health and condition – including body condition (residual body mass), poxvirus infection, degree of habitat urbanization, and circulating levels of ketones, glucose, vitamins, and carotenoids – were related to the expression of male plumage coloration at the start of the spring breeding season in wild male house finches (Haemorhous mexicanus), a species in which many studies have demonstrated a link between plumage redness and the health and condition of individuals at the time the feathers are grown in late summer and autumn. We found that, at the time of pair formation, plumage hue was correlated with body condition, such that redder males were in better condition (i.e. higher residual mass). Also, as in previous studies, we found that rural males had redder plumage; however, urban males had more saturated plumage. In sum, these results reveal that feather coloration developed long before breeding still can be indicative to choosy mates of a male’s current condition and suggest that females who prefer to mate with redder males may also gain proximate material benefits (e.g. better incubation provisioning) by mating with these individuals in good current condition.

ContributorsDepinto, Kathryn (Author) / McGraw, Kevin (Thesis director) / Sweazea, Karen (Committee member) / Webb, Emily (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / Department of Psychology (Contributor)
Created2021-12
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Bioindicators of wildlife health are useful tools for studying the viability of various organisms and populations, and can include a range of phenotypic variables, such as behavior, body size, and physiological parameters, such as circulating hormones and nutrients. Few studies have investigated the utility of total plasma protein as a

Bioindicators of wildlife health are useful tools for studying the viability of various organisms and populations, and can include a range of phenotypic variables, such as behavior, body size, and physiological parameters, such as circulating hormones and nutrients. Few studies have investigated the utility of total plasma protein as a predictor of environmental or nutritional variation among birds, as well as variation across different seasons and life-history stages. Here I examined relationships between plasma protein and season, urbanization, sex, body condition, molt status, and disease state in house finches (Haemorhous mexicanus). I sampled blood from house finches across three seasons (winter, summer and fall 2021) and measured plasma protein levels using a Bradford assay. I also collected data including condition, sex, and poxvirus infection state at capture, as well as fecal samples to assess gut parasitism (coccidiosis). During the fall season I also estimated molt status, as number of actively growing feathers. I found circulating plasma protein concentration to be lower in the fall during molt than during winter or summer. I also found a significant relationship between circulating protein levels and capture site, as well as novel links to molt state and pox presence, with urban birds, those infected with pox, and those in more intense molt having higher protein levels. My results support the hypotheses that plasma protein concentration can be indicative of a bird’s body molt (which demands considerable protein for feather synthesis) and degree of habitat urbanization, although future work is needed to determine why protein levels were higher in virus-infected birds.

ContributorsDrake, Dean (Author) / McGraw, Kevin (Thesis director) / Sweazea, Karen (Committee member) / Jackson, Daniel (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2022-05
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Reproduction is energetically costly and seasonal breeding has evolved to capitalize on predictable increases in food availability. The synchronization of breeding with periods of peak food availability is especially important for small birds, most of which do not store an extensive amount of energy. The annual change in photoperiod is

Reproduction is energetically costly and seasonal breeding has evolved to capitalize on predictable increases in food availability. The synchronization of breeding with periods of peak food availability is especially important for small birds, most of which do not store an extensive amount of energy. The annual change in photoperiod is the primary environmental cue regulating reproductive development, but must be integrated with supplementary cues relating to local energetic conditions. Photoperiodic regulation of the reproductive neuroendocrine system is well described in seasonally breeding birds, but the mechanisms that these animals use to integrate supplementary cues remain unclear. I hypothesized that (a) environmental cues that negatively affect energy balance inhibit reproductive development by acting at multiple levels along the reproductive endocrine axis including the hypothalamus (b) that the availability of metabolic fuels conveys alterations in energy balance to the reproductive system. I investigated these hypotheses in male house finches, Haemorhous mexicanus, caught in the wild and brought into captivity. I first experimentally reduced body condition through food restriction and found that gonadal development and function are inhibited and these changes are associated with changes in hypothalamic gonadotropin-releasing hormone (GnRH). I then investigated this neuroendocrine integration and found that finches maintain reproductive flexibility through modifying the release of accumulated GnRH stores in response to energetic conditions. Lastly, I investigated the role of metabolic fuels in coordinating reproductive responses under two different models of negative energy balance, decreased energy intake (food restriction) and increased energy expenditure (high temperatures). Exposure to high temperatures lowered body condition and reduced food intake. Reproductive development was inhibited under both energy challenges, and occurred with decreased gonadal gene expression of enzymes involved in steroid synthesis. Minor changes in fuel utilization occurred under food restriction but not high temperatures. My results support the hypothesis that negative energy balance inhibits reproductive development through multilevel effects on the hypothalamus and gonads. These studies are among the first to demonstrate a negative effect of high temperatures on reproductive development in a wild bird. Overall, the above findings provide important foundations for investigations into adaptive responses of breeding in energetically variable environments.
ContributorsValle, Shelley (Author) / Deviche, Pierre (Thesis advisor) / McGraw, Kevin (Committee member) / Orchinik, Miles (Committee member) / Propper, Catherine (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2018