Matching Items (38)
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A potential new class of cancer chemotherapeutic agents has been synthesized by varying the 2 position of a benzimidazole based extended amidine. Compounds 6-amino-2-chloromethyl-4-imino-1-(2-methansulfonoxyethyl)-5-methyl-1H-benzimidazole-7-one (1A) and 6-amino-2-hydroxypropyl-4-imino-1-(2-methansulfonoxyethyl)-5-methyl-1H-benzimidazole-7-one (1B) were assayed at the National Cancer Institute's (NCI) Developmental Therapeutic Program (DTP) and found to be cytotoxic at sub-micromolar concentrations, and have

A potential new class of cancer chemotherapeutic agents has been synthesized by varying the 2 position of a benzimidazole based extended amidine. Compounds 6-amino-2-chloromethyl-4-imino-1-(2-methansulfonoxyethyl)-5-methyl-1H-benzimidazole-7-one (1A) and 6-amino-2-hydroxypropyl-4-imino-1-(2-methansulfonoxyethyl)-5-methyl-1H-benzimidazole-7-one (1B) were assayed at the National Cancer Institute's (NCI) Developmental Therapeutic Program (DTP) and found to be cytotoxic at sub-micromolar concentrations, and have shown between a 100 and a 1000-fold increase in specificity towards lung, colon, CNS, and melanoma cell lines. These ATP mimics have been found to correlate with sequestosome 1 (SQSTM1), a protein implicated in drug resistance and cell survival in various cancer cell lines. Using the DTP COMPARE algorithm, compounds 1A and 1B were shown to correlate to each other at 77%, but failed to correlate with other benzimidazole based extended amidines previously synthesized in this laboratory suggesting they operate through a different biological mechanism.
ContributorsDarzi, Evan (Author) / Skibo, Edward (Thesis advisor) / Gould, Ian (Committee member) / Francisco, Wilson (Committee member) / Arizona State University (Publisher)
Created2011
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Protein crystallization has become an extremely important tool in biochemistry since the first structure of the protein Myoglobin was solved in 1958. Survival of motor neuron protein has proved to be an elusive target in regards to producing crystals of sufficient quality for X-ray diffraction. One form of Survival of

Protein crystallization has become an extremely important tool in biochemistry since the first structure of the protein Myoglobin was solved in 1958. Survival of motor neuron protein has proved to be an elusive target in regards to producing crystals of sufficient quality for X-ray diffraction. One form of Survival of motor neuron protein has been found to be a cause of the disease Spinal Muscular Atrophy that currently affects 1 in 6000 live births. The production, purification and crystallization of Survival of motor neuron protein are detailed. The Fenna-Matthews-Olson (FMO) protein from Pelodictyon phaeum is responsible for the transfer of energy from the chlorosome complex to the reaction center of the bacteria. The three-dimensional structure of the protein has been solved to a resolution of 2.0Å with the Rwork and Rfree values being 16.6% and 19.9% respectively. This new structure is compared to the FMO protein structures of Prosthecocholoris aestuarii 2K and Chlorobium tepidum. The early structures of FMO contained seven bacteriochlorophyll-a (BChl) molecules but the recent discovery that there is an eighth BChl molecule in Ptc. aestuarii 2K and Cbl. tepidum and now in Pld. phaeum requires that the energy transfer mechanism be reexamined. Simulated spectra are fitted to the experimental optical spectra to determine how the BChl molecules transfer energy through the protein. The inclusion of the eighth BChl molecule within these simulations may have an impact on how energy transfer through FMO can be described. In conclusion, a reliable method of purifying and crystallizing the SMNWT protein is detailed, the placement of the 8th BChl-a within the electron density and the implications on energy transfer within the FMO protein when the 8th BChl-a is included from the green sulfur bacteria Pld. phaeum is discussed.
ContributorsLarson, Chadwick R (Author) / Allen, James P. (Thesis advisor) / Francisco, Wilson (Committee member) / Chen, Julian (Committee member) / Arizona State University (Publisher)
Created2010
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Description
An organism's ability to maintain optimal body temperature is extremely important for sustaining physiological and behavioral processes necessary for survival. However, like other physiological systems, thermobiology can be influenced by the availability of resources. Water is a vital resource that has profound implications on many aspects of biological function, including

An organism's ability to maintain optimal body temperature is extremely important for sustaining physiological and behavioral processes necessary for survival. However, like other physiological systems, thermobiology can be influenced by the availability of resources. Water is a vital resource that has profound implications on many aspects of biological function, including thermoregulatory pathways. However, water availability has a tendency fluctuate within any given ecosystem. While several studies have investigated the influence of water availability on a range of thermoregulatory pathways, very little attention has been given to its influence on Voluntary Maximum Temperature (VMT). We investigated the effects of dehydration on Voluntary Maximum Temperature in a captive population of Gila monsters (Heloderma suspectum). Gila monsters are large-bodied, desert dwelling lizards that experience periods of seasonal dehydration. Additionally, the effects of dehydration on their physiology and behavior have been extensively studied. We hypothesized that dehydration would reduce VMT. As expected, there was a significant decrease in exit temperature as blood osmolality increased. This is presumed to be in an effort to decrease water loss. Adaptations that allow desert dwelling organisms to conserve water are highly advantageous due to seasonal water constraints. Our findings offer insight on how the behavior of these organisms may change in response to changes in climate.
ContributorsHartson, Callie Elizabeth (Author) / DeNardo, Dale (Thesis director) / Angilletta, Michael (Committee member) / Camacho, Agus (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Animals are thought to die at high temperatures because proteins and cell membranes lose their structural integrity. Alternatively, a newer hypothesis (the oxygen and capacity limitation of thermal tolerance, or OCLTT) states that death occurs because oxygen supply becomes limited at high temperatures. Consequently, animals exposed to hypoxia are more

Animals are thought to die at high temperatures because proteins and cell membranes lose their structural integrity. Alternatively, a newer hypothesis (the oxygen and capacity limitation of thermal tolerance, or OCLTT) states that death occurs because oxygen supply becomes limited at high temperatures. Consequently, animals exposed to hypoxia are more sensitive to heating than those exposed to normoxia or hyperoxia. We hypothesized that animals raised in hypoxia would acclimate to the low oxygen supply, thereby making them less sensitive to heating. Such acclimation would be expressed as greater heat tolerance and better flight performance in individuals raised at lower oxygen concentrations. We raised flies (Drosophila melanogaster) from eggs to adults under oxygen concentrations ranging from 10% to 31% and measured two aspects of thermal tolerance: 1) the time required for flies to lose motor function at 39.5°C at normoxia (21%), referred to as knock-down time, and 2) flight performance at 37°, 39°, or 41°C and 12%, 21%, or 31% oxygen. Contrary to our prediction, flies from all treatments had the same knock-down time. However, flight performance at hypoxia was greatest for flies raised in hypoxia, but flight performance at normoxia and hyperoxia was greatest for flies raised at hyperoxia. Thus, flight performance acclimated to oxygen supply during development, but heat tolerance did not. Our data does not support the OCLTT hypothesis, but instead supports the beneficial acclimation hypothesis, which proposes that acclimation improves the function of an organism during environmental change.
ContributorsShiehzadegan, Shayan (Co-author) / VadenBrooks, John (Co-author) / Le, Jackie (Co-author) / Smith, Colton (Co-author) / Shiehzadegan, Shima (Co-author) / Angilletta, Michael (Co-author, Thesis director) / VandenBrooks, John (Committee member) / Klok, C. J. (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Lactate is a commonly known biochemical that is usually produced under anaerobic conditions. This makes it a useful marker for examining the possibility that Drosophila melanogaster undergoes natural hypoxic states during development due to the rate of growth. To analyze this observation and its potential for explaining developmental changes, a

Lactate is a commonly known biochemical that is usually produced under anaerobic conditions. This makes it a useful marker for examining the possibility that Drosophila melanogaster undergoes natural hypoxic states during development due to the rate of growth. To analyze this observation and its potential for explaining developmental changes, a lactate assay was used to quantify lactate produced across time points in the third larval instar and across early adulthood. Lactate assay results showed near-zero lactate levels for both larvae and adults. There were confounding factors present in larval lactate assays which made analysis difficult. However, the results of the adult lactate assays seem to indicate an inability to produce large amounts of lactate regardless of time point in adulthood, suggesting that adults do not naturally experience hypoxia during or after eclosion.

ContributorsWiertek, Marcellina Emilia (Author) / Harrison, Jon (Thesis director) / Angilletta, Michael (Committee member) / Talal, Stav (Committee member) / Historical, Philosophical & Religious Studies (Contributor) / Historical, Philosophical & Religious Studies, Sch (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Studies of animal contests often focus solely on a single static measurement of fighting ability, such as the size or the strength of the individual. However, recent studies have highlighted the importance of individual variation in the dynamic behaviors used during a fight, such as, assessment strategies, decision making, and

Studies of animal contests often focus solely on a single static measurement of fighting ability, such as the size or the strength of the individual. However, recent studies have highlighted the importance of individual variation in the dynamic behaviors used during a fight, such as, assessment strategies, decision making, and fine motor control, as being strong predictors of the outcome of aggression. Here, I combined morphological and behavioral data to discover how these features interact during aggressing interactions in male virile crayfish, Faxonius virilis. I predicted that individual variation in behavioral skill for decision making (i.e., number of strikes thrown), would determine the outcome of contest success in addition to morphological measurements (e.g. body size, relative claw size). To evaluate this prediction, I filmed staged territorial interactions between male F. virilis and later analyzed trial behaviors (e.g. strike, pinches, and bout time) and aggressive outcomes. I found very little support for skill to predict win/loss outcome in trials. Instead, I found that larger crayfish engaged in aggression for longer compared to smaller crayfish, but that larger crayfish did not engage in a greater number of claw strikes or pinches when controlling for encounter duration. Future studies should continue to investigate the role of skill, by using finer-scale techniques such as 3D tracking software, which could track advanced measurements (e.g. speed, angle, and movement efficiency). Such studies would provide a more comprehensive understanding of the relative influence of fighting skill technique on territorial contests.

ContributorsNguyen, Phillip Huy (Author) / Angilletta, Michael (Thesis director) / McGraw, Kevin (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

Due to what is known as the “biologically desert fallacy” and the pervasive westernized ideal of wilderness that has influenced widespread American Conservation culture for millennia, urban areas have long been deemed as areas devoid of biodiversity. However, cities can contribute significantly to regional biodiversity and provide vital niches for

Due to what is known as the “biologically desert fallacy” and the pervasive westernized ideal of wilderness that has influenced widespread American Conservation culture for millennia, urban areas have long been deemed as areas devoid of biodiversity. However, cities can contribute significantly to regional biodiversity and provide vital niches for wildlife, illuminating the growing awareness that cities are crucial to the future of conservation and combating the global biodiversity crisis. In terms of the biodiversity crisis, bats are a relevant species of concern. In many studies, different bat species have been broadly classified according to their ability to adapt to urban environments. There is evidence that urban areas can filter bat species based on traits and behavior, with many bats possessing traits that do not allow them to live in cities. The three broad categories are urban avoiders, urban adapters, or urban exploiters based upon where their abundance is highest along a gradient of urban intensity. A common example of an urban exploiter bat is a Mexican Free-tailed bat, which can thrive and rely on urban environments and it is found in the Phoenix Metropolitan area. Bats are important as even in urban environments they play vital ecological roles such as cactus pollination, insect management, and seed dispersal. Bat Crazy is a thesis project focused on urban enhancement and the field of urban biodiversity. The goals of this thesis are to observe how bio-conscious urban cities that work to promote species conservation can serve as a positive tool to promote biodiversity and foster community education and engagement for their urban environment.

ContributorsKaiser, Nicole (Author) / Senko, Jesse (Thesis director) / Angilletta, Michael (Committee member) / Lynch, John (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Life Sciences (Contributor)
Created2023-05
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Description
The migratory grasshopper (Melanoplus sanguinipes) is one of the most economically important grasshoppers in the western rangelands of the United States (US), capable of causing incredible amounts of damage to crops and rangelands. While M. sanguinipes has been the focus of many research studies, areas like field nutritional physiology and

The migratory grasshopper (Melanoplus sanguinipes) is one of the most economically important grasshoppers in the western rangelands of the United States (US), capable of causing incredible amounts of damage to crops and rangelands. While M. sanguinipes has been the focus of many research studies, areas like field nutritional physiology and ecology, and interactions between nutritional physiology and biopesticide resistance have very little research. This dissertation presents a multifaceted approach through three research-driven chapters that examine the nutritional physiology of M. sanguinipes and how it interacts with an entomopathogenic fungus for grasshopper management, as well as the challenges of using biopesticides for grasshopper management. Using the Geometric Framework for Nutrition (GFN), I established baseline macronutrient intake for M. sanguinipes, both in laboratory and field populations. Through this work, I found that field and lab populations can exhibit different protein (p) to carbohydrate (c) ratios, or Intake Targets (ITs), but that the field populations had ITs that matched the nutrients available in their environment. I also used the GFN to show that infections with the fungal entomopathogen Metarhizium robertsii DWR2009 did not alter ITs in M. sanguinipes. Although, when confined to carbohydrate- or protein-biased diets, infected grasshoppers had a slightly extended lifespan relative to grasshoppers fed balanced protein:carbohydrate diets. Interestingly, in a postmortem for the grasshopper, the fungus was only able to effectively sporulate on grasshoppers fed the 1p:1c diets, suggesting that grasshopper diet can have substantial impacts on the spread of fungal biopesticides throughout a population, in the absence of any inhibitory abiotic factors. Lastly, I examined the major barriers to fungal and microsporidian biopesticide usage in the United States, including low efficacy, thermal and environmental sensitivity, non-target effects, unregistered or restricted use, and economic or accessibility barriers. I also explored potential solutions to these challenges. This dissertation's focus on Melanoplus sanguinipes and Metarhizium roberstii Strain DWR2009, generates new information about how nutritional physiology and immunology intersect to impact M. sanguinipes performance. The methodology in each of the experimental chapters provides a framework for examining other problematic grasshopper species, by determining baseline nutritional physiology, and coupling nutrition with immunology to maximize the effectiveness of biological pesticides.
ContributorsZembrzuski, Deanna (Author) / Cease, Arianne (Thesis advisor) / Harrison, Jon (Committee member) / Angilletta, Michael (Committee member) / Jaronski, Stefan (Committee member) / Arizona State University (Publisher)
Created2023
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Despite theoretical models predicting that signals should only evolve if they convey honest information, dishonest signals may persist. Interestingly, crustaceans have been crucial in furthering biologists understanding of how and why dishonest signals persist; because many crustaceans wield claws that function as dishonest signals. For example, male fiddler crabs have

Despite theoretical models predicting that signals should only evolve if they convey honest information, dishonest signals may persist. Interestingly, crustaceans have been crucial in furthering biologists understanding of how and why dishonest signals persist; because many crustaceans wield claws that function as dishonest signals. For example, male fiddler crabs have claws that grow to large sizes but are incapable of inflicting severe damage to opponents, thus acting as a dishonest signal of their strength. Although initial work suggested that dishonest signaling was common throughout Crustacea, biologists understanding of the generality of dishonest communication is lacking. To resolve these issues, I combined morphological, behavioral, and comparative studies to investigate whether crayfish engage in dishonest communication. First, I found that regenerated claws in virile crayfish (Faxonius virilis) produce 40% weaker pinching forces compared to original claws. These results suggest that claw regeneration in crayfish may be the functional mechanism that produces dishonest signals. Second, I conducted two studies that investigated what traits determine dominance in staged contests; one on intrasexual contests in both male and female F. virilis, and a second between intra- and interspecific contests between male F. virilis and male red swamp crayfish (Procambarus clarkii). In both studies, I did not find support the hypothesis that large but weak claws function as dishonest signals; because claw size did not predict the outcome of signaling interactions and claw strength did not predict the outcome of physical fights. Lastly, I conducted a comparative study between six species of crayfish — three stream-dwelling species that use their claws as weapons and signals, and three burrowing species that use their claws for excavating burrows. Despite all six species possessing claws that unreliably predicted claw strength, I found no support for the hypothesis that their claws function as dishonest signals in any of these species. Thus, my dissertation results suggest that despite having claws that unreliably predict their strength, such unreliable signals do not equate to dishonest signals. Altogether, my work highlights the importance of collecting behavioral data in studies of dishonest communication and stresses the importance of separating unreliable signals from dishonest signals.
ContributorsGraham, Zackary (Author) / Angilletta, Michael (Thesis advisor) / Martins, Emilia (Committee member) / McGraw, Kevin (Committee member) / Pratt, Stephen (Committee member) / Wilson, Robbie (Committee member) / Arizona State University (Publisher)
Created2021
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Description
I am evaluating the genomic basis of a model of heat tolerance in which organisms succumb to warming when their demand for oxygen exceeds their supply. This model predicts that tolerance of hypoxia should correlate genetically with tolerance of heat. To evaluate this prediction, I tested heat and hypoxia tolerance

I am evaluating the genomic basis of a model of heat tolerance in which organisms succumb to warming when their demand for oxygen exceeds their supply. This model predicts that tolerance of hypoxia should correlate genetically with tolerance of heat. To evaluate this prediction, I tested heat and hypoxia tolerance in several genetic lines of Drosophila melanogaster. I hypothesized that genotypes that can fly better at high temperatures are also able to fly well at hypoxia. Genotypes from the Drosophila Genetic Reference Panel (DGRP) were assessed for flight at hypoxia and normal temperature (12% O2 and 25°C) as well as normoxia and high temperature (21% O2 and 39°C). After testing 66 lines from the DGRP, the oxygen- and capacity-limited thermal tolerance theory is supported; hypoxia-resistant lines are more likely to be heat-resistant. This supports previous research, which suggested an interaction between the tolerance of the two environmental variables. I used this data to perform a genome-wide association study to find specific single-nucleotide polymorphisms associated with heat tolerance and hypoxia tolerance but found no specific genomic markers. Understanding factors that limit an organism’s stress tolerance as well as the regions of the genome that dictate this phenotype should enable us to predict how organisms may respond to the growing threat of climate change.
ContributorsFredette-Roman, Jacob Daniel (Author) / Angilletta, Michael (Thesis director) / VandenBrooks, John (Committee member) / Youngblood, Jacob (Committee member) / School of Life Sciences (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2020-05