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Membrane proteins are very important for all living cells, being involved in respiration, photosynthesis, cellular uptake and signal transduction, amongst other vital functions. However, less than 300 unique membrane protein structures have been determined to date, often due to difficulties associated with the growth of sufficiently large and well-ordered crystals.

Membrane proteins are very important for all living cells, being involved in respiration, photosynthesis, cellular uptake and signal transduction, amongst other vital functions. However, less than 300 unique membrane protein structures have been determined to date, often due to difficulties associated with the growth of sufficiently large and well-ordered crystals. This work has been focused on showing the first proof of concept for using membrane protein nanocrystals and microcrystals for high-resolution structure determination. Upon determining that crystals of the membrane protein Photosystem I, which is the largest and most complex membrane protein crystallized to date, exist with only a hundred unit cells with sizes of less than 200 nm on an edge, work was done to develop a technique that could exploit the growth of the Photosystem I nanocrystals and microcrystals. Femtosecond X-ray protein nanocrystallography was developed for use at the first high-energy X-ray free electron laser, the LCLS at SLAC National Accelerator Laboratory, in which a liquid jet would bring fully hydrated Photosystem I nanocrystals into the interaction region of the pulsed X-ray source. Diffraction patterns were recorded from millions of individual PSI nanocrystals and data from thousands of different, randomly oriented crystallites were integrated using Monte Carlo integration of the peak intensities. The short pulses ( 70 fs) provided by the LCLS allowed the possibility to collect the diffraction data before the onset of radiation damage, exploiting the diffract-before-destroy principle. At the initial experiments at the AMO beamline using 6.9- Å wavelength, Bragg peaks were recorded to 8.5- Å resolution, and an electron-density map was determined that did not show any effects of X-ray-induced radiation damage. Recently, femtosecond X-ray protein nanocrystallography experiments were done at the CXI beamline of the LCLS using 1.3- Å wavelength, and Bragg reflections were recorded to 3- Å resolution; the data are currently being processed. Many additional techniques still need to be developed to explore the femtosecond nanocrystallography technique for experimental phasing and time-resolved X-ray crystallography experiments. The first proof-of-principle results for the femtosecond nanocrystallography technique indicate the incredible potential of the technique to offer a new route to the structure determination of membrane proteins.
ContributorsHunter, Mark (Author) / Fromme, Petra (Thesis advisor) / Wolf, George (Committee member) / Levitus, Marcia (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Molybdenum (Mo) is a key trace nutrient for biological assimilation of nitrogen, either as nitrogen gas (N2) or nitrate (NO3-). Although Mo is the most abundant metal in seawater (105 nM), its concentration is low (<5 nM) in most freshwaters today, and it was scarce in the ocean before 600

Molybdenum (Mo) is a key trace nutrient for biological assimilation of nitrogen, either as nitrogen gas (N2) or nitrate (NO3-). Although Mo is the most abundant metal in seawater (105 nM), its concentration is low (<5 nM) in most freshwaters today, and it was scarce in the ocean before 600 million years ago. The use of Mo for nitrogen assimilation can be understood in terms of the changing Mo availability through time; for instance, the higher Mo content of eukaryotic vs. prokaryotic nitrate reductase may have stalled proliferation of eukaryotes in low-Mo Proterozoic oceans. Field and laboratory experiments were performed to study Mo requirements for NO3- assimilation and N2 fixation, respectively. Molybdenum-nitrate addition experiments at Castle Lake, California revealed interannual and depth variability in plankton community response, perhaps resulting from differences in species composition and/or ammonium availability. Furthermore, lake sediments were elevated in Mo compared to soils and bedrock in the watershed. Box modeling suggested that the largest source of Mo to the lake was particulate matter from the watershed. Month-long laboratory experiments with heterocystous cyanobacteria (HC) showed that <1 nM Mo led to low N2 fixation rates, while 10 nM Mo was sufficient for optimal rates. At 1500 nM Mo, freshwater HC hyperaccumulated Mo intercellularly, whereas coastal HC did not. These differences in storage capacity were likely due to the presence in freshwater HC of the small molybdate-binding protein, Mop, and its absence in coastal and marine cyanobacterial species. Expression of the mop gene was regulated by Mo availability in the freshwater HC species Nostoc sp. PCC 7120. Under low Mo (<1 nM) conditions, mop gene expression was up-regulated compared to higher Mo (150 and 3000 nM) treatments, but the subunit composition of the Mop protein changed, suggesting that Mop does not bind Mo in the same manner at <1 nM Mo that it can at higher Mo concentrations. These findings support a role for Mop as a Mo storage protein in HC and suggest that freshwater HC control Mo cellular homeostasis at the post-translational level. Mop's widespread distribution in prokaryotes lends support to the theory that it may be an ancient protein inherited from low-Mo Precambrian oceans.
ContributorsGlass, Jennifer (Author) / Anbar, Ariel D (Thesis advisor) / Shock, Everett L (Committee member) / Jones, Anne K (Committee member) / Hartnett, Hilairy E (Committee member) / Elser, James J (Committee member) / Fromme, Petra (Committee member) / Arizona State University (Publisher)
Created2011
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Description
Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising

Anti-retroviral drugs and AIDS prevention programs have helped to decrease the rate of new HIV-1 infections in some communities, however, a prophylactic vaccine is still needed to control the epidemic world-wide. Despite over two decades of research, a vaccine against HIV-1 remains elusive, although recent clinical trials have shown promising results. Recent successes have focused on highly conserved, mucosally-targeted antigens within HIV-1 such as the membrane proximal external region (MPER) of the envelope protein, gp41. MPER has been shown to play critical roles in the viral mucosal transmission, though this peptide is not immunogenic on its own. Gag is a structural protein configuring the enveloped virus particles, and has been suggested to constitute a target of the cellular immunity potentially controlling the viral load. It was hypothesized that HIV-1 enveloped virus-like particles (VLPs) consisting of Gag and a deconstructed form of gp41 comprising the MPER, transmembrane, and cytoplasmic domains (dgp41) could be expressed in plants. Plant-optimized HIV-1 genes were constructed and expressed in Nicotiana benthamiana by stable transformation, or transiently using a tobacco mosaic virus-based expression system or a combination of both. Results of biophysical, biochemical and electron microscopy characterization demonstrated that plant cells could support not only the formation of HIV-1 Gag VLPs, but also the accumulation of VLPs that incorporated dgp41. These particles were purified and utilized in mice immunization experiments. Prime-boost strategies combining systemic and mucosal priming with systemic boosting using two different vaccine candidates (VLPs and CTB-MPR - a fusion of MPER and the B-subunit of cholera toxin) were administered to BALB/c mice. Serum antibody responses against both the Gag and gp41 antigens could be elicited in mice systemically primed with VLPs and these responses could be recalled following systemic boosting with VLPs. In addition, mucosal priming with VLPs allowed for a robust boosting response against Gag and gp41 when boosted with either candidate. Functional assays of these antibodies are in progress to test the antibodies' effectiveness in neutralizing and preventing mucosal transmission of HIV-1. This immunogenicity of plant-based Gag/dgp41 VLPs represents an important milestone on the road towards a broadly-efficacious and inexpensive subunit vaccine against HIV-1.
ContributorsKessans, Sarah (Author) / Mor, Tsafrir S (Thesis advisor) / Matoba, Nobuyuki (Committee member) / Mason, Hugh (Committee member) / Hogue, Brenda (Committee member) / Fromme, Petra (Committee member) / Arizona State University (Publisher)
Created2011
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Description

This case study describes an adult patient whose brachial plexus injury was treated with various modalities and exercise. The participant of this study was a 76 year old female who sustained a brachial plexus injury during an elective reverse total shoulder arthroplasty. The initial evaluation reported only passive range of

This case study describes an adult patient whose brachial plexus injury was treated with various modalities and exercise. The participant of this study was a 76 year old female who sustained a brachial plexus injury during an elective reverse total shoulder arthroplasty. The initial evaluation reported only passive range of motion with 90 degrees shoulder flexion, 85 degrees abduction, and 30 degrees external rotation. Muscle testing yielded significantly limited wrist and digit extension strength. Testing of sensation found diminished protective sensation along the median nerve distribution, including the thumb, index finger, and middle finger. Occupational therapy was initiated for postoperative treatment of the shoulder as well as treatment of the brachial plexus palsy. Therapy consisted of static splinting for healing structures and sensory reeducation through massage, finding objects with the eyes occluded, and fluidotherapy. Additionally, various exercises and modalities for improving motion and strength were initiated, including proprioceptive neuromuscular reeducation, passive/active assist/active exercises, dynamic splinting, muscle stimulation, kinesio tape, functional activities, and tendon glides. After five months, active range of motion in the shoulder, elbow, and wrist was finally achieved and median nerve sensation had improved. After nine months, elbow motion was within normal limits and wrist motion had significantly improved. Upon muscle testing, the elbow, forearm, wrist, and hand had made significant gains in strength. However, shoulder strength and motion was still limited. Overall, treatment made a significant improvement in the patient’s functionality.

ContributorsMorlock, Callista (Author) / Ramos, Christopher (Thesis director) / Thomas, Karen (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Within the pediatric hospitalization experience, fear and anxiety are two emotions commonly felt by children of all ages. Hospitalized children can greatly benefit from interventions designed to help them cope with these emotions throughout their medical experiences. This study draws on each of our clinical experiences as volunteers at Phoenix

Within the pediatric hospitalization experience, fear and anxiety are two emotions commonly felt by children of all ages. Hospitalized children can greatly benefit from interventions designed to help them cope with these emotions throughout their medical experiences. This study draws on each of our clinical experiences as volunteers at Phoenix Children’s Hospital, and uses a qualitative analysis of three semi-structured interviews with currently employed Child Life Specialists to understand and analyze the use of medical play, a form of play intervention with a medical theme or medical equipment. We explore the goals and benefits of medical play for hospitalized pediatric patients, the process of using medical play as an intervention, including the activity design process, the assessments and adjustments made throughout the child’s hospitalization, and the considerations and limitations to implementing medical play activities. Ultimately, we found that the element of fun that defines play can be channeled into medical play activities implemented by skilled Child Life Specialists, who are experts in their field, in clinical settings to promote several different and beneficial goals, including pediatric patient coping.

ContributorsGarciapena, Danae (Co-author) / Aguiar, Lara (Co-author) / Loebenberg, Abby (Thesis director) / Swanson, Jodi (Committee member) / College of Health Solutions (Contributor) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Background: The purpose of this study was to assess the efficacy of a lifestyle intervention on cardiorespiratory fitness in Latino youth with obesity and prediabetes. <br/>Methods: Participants (n=50) in this study were taken from a larger randomized controlled trial (n=180, BMI ≥ 95th percentile). Youth participated in a 6-month lifestyle

Background: The purpose of this study was to assess the efficacy of a lifestyle intervention on cardiorespiratory fitness in Latino youth with obesity and prediabetes. <br/>Methods: Participants (n=50) in this study were taken from a larger randomized controlled trial (n=180, BMI ≥ 95th percentile). Youth participated in a 6-month lifestyle intervention that included physical activity (60 minutes, 3x/week) and nutrition and wellness classes (60 minutes, 1x/week) delivered to families at the Lincoln Family YMCA in Downtown Phoenix. The primary outcome was cardiorespiratory fitness measured at baseline and post-intervention.<br/>Results: The mean BMI for the sample was 33.17 ± 4.54 kg/m2, which put the participants in the 98.4th percentile. At baseline, the mean VO2max was 2737.02 ± 488.89 mL/min. The mean relative VO2max was 30.65 ± 3.87 mL/kg/min. VO2max values significantly increased from baseline to post-intervention (2737.022 ± 483.977 mL/min vs 2932.654 ± 96.062 mL/min, p<0.001). <br/>Conclusion: Culturally-grounded, family-focused lifestyle interventions are a promising approach for improving cardiorespiratory fitness in high-risk youth at risk for diabetes.

ContributorsEstrada, Lourdes Alexa (Author) / Shaibi, Gabriel (Thesis director) / Peña, Armando (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

The following paper explores the various effects of stress on the endocrine system. Many understand that being stressed can jeopardize maintaining adequate health, but what specifically happens when humans are stressed? Why does stress affect human health? This paper delves into background information, previous research, and the depths to which

The following paper explores the various effects of stress on the endocrine system. Many understand that being stressed can jeopardize maintaining adequate health, but what specifically happens when humans are stressed? Why does stress affect human health? This paper delves into background information, previous research, and the depths to which stress negatively affects the body. The effects stress has on the endocrine system, specifically on the hypothalamic-pituitary-thyroid axis (HPT) and hypothalamic-pituitary-adrenal axis (HPA), is discussed, and additionally, at home de-stressing methods are researched. The study included a set of participants at Arizona State University. The method took place over the course of 2 weeks: one normal week, and the other with the implementation of a de-stressing method. The normal week involved the participants living their daily lives with the addition of a stress-measuring survey, while the second week involved implementing a de-stressing method and stress-measuring survey. The purpose of this study was to discover if there was a correlation between performing these relaxation activities and decreasing stress levels in ASU students. The results found that students reported they felt more relaxed and calm after the activities. Overall, this thesis provides information and first hand research on the effects of stress and stress-reducing activities and discusses the importance of maintaining lower stress levels throughout everyday life.

ContributorsWeissmann, Megan Diane (Co-author) / Gebara, Nayla (Co-author) / Don, Rachael (Thesis director) / Irving, Andrea (Committee member) / Kizer, Elizabeth (Committee member) / College of Health Solutions (Contributor) / Edson College of Nursing and Health Innovation (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

The purpose of this Barrett Thesis Project is to review the existing literature on ACL injuries specifically regarding their risk factors, prevention, and recovery options. The content of the review has been placed into four sections: physiological factors, biomechanical factors, surgery and recovery factors, as well as training factors.

The purpose of this Barrett Thesis Project is to review the existing literature on ACL injuries specifically regarding their risk factors, prevention, and recovery options. The content of the review has been placed into four sections: physiological factors, biomechanical factors, surgery and recovery factors, as well as training factors. Physiological factors look at static structures and their impact on ACL injuries, more specifically, the role that variations on physical structure values can have on injury incidence. Biomechanical factors focus on the ways that movement can contribute to injury and the ways that incorrect movement or unanticipated movement can have on the structures of the knee. Surgery and recovery factors look at surgical techniques that have been used to correct ACL injuries and the details of their function as well as certain surgical techniques that have differing rates of success and how they can impact re-injury and rehabilitation rates. Finally, training factors analyze techniques that can be used in both pre-injury or post-injury situations therefore, this section looks at the ways that training can minimize re-injury as well as work towards preventing the initial injury. Overall, this research review looks at how these factors come together to contribute to an ACL injury and the ways that injury incidence can be minimized. Risk factors come together in order to create an undesirable situation in which the ACL ligament ruptures. These risk factors are either physiological or biomechanical in nature. As a result of injury, certain surgical techniques can be used that impact the success of a patient. Evidence for the benefit of training factors can then be applied in order to reduce injury risk or prevent future injuries.

ContributorsIsrael, Kyle (Co-author) / Fang, Charles (Co-author) / Ramos, Christopher (Thesis director) / Larson, David (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
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Description

Background: The US population faces a continual increase in obesity prevalence, raising health concerns due to associated comorbidities ranked as leading causes of preventable, premature death world-wide. Scientists have found a link between obesity-associated conditions and oxidative stress (OS). To date, renewed interest in the effectiveness of dietary regimens in

Background: The US population faces a continual increase in obesity prevalence, raising health concerns due to associated comorbidities ranked as leading causes of preventable, premature death world-wide. Scientists have found a link between obesity-associated conditions and oxidative stress (OS). To date, renewed interest in the effectiveness of dietary regimens in decreasing body weight is a popular research topic. Intermittent fasting (IF) is a popular and promising weight management strategy. To date, there have been no systematic reviews examining whether IF can reduce oxidative stress in overweight/obese adults. <br/><br/>Objective: Conduct a systematic review to evaluate the effects of intermittent fasting (IF) regimens on circulating markers of oxidative stress in overweight/obese adults compared to continuous calorie restriction (CR). <br/><br/>Methods: Databases PubMed, SCOPUS, ProQuest, and Cochrane were searched on February 21, 2021 for eligible articles limiting selection to those in the English language. Predefined search terms and restrictions were applied by two of the authors conducting the search. References from articles generated were also considered. Selected articles were limited to randomized controlled trials (RCTs) and human trials evaluating the effects of intermittent fasting (IF) dietary regimens in comparison to continuous calorie restriction (CR). Study populations considered were limited to those within the range of 18-65 years having a body mass index (BMI) of ≥25 kg/m2 and in otherwise generally good health with the absence of pre-existing acute or chronic conditions. The Academy of Nutrition and Dietetics Evidence Analysis Library Quality Rating Worksheet was used to assess the methodological quality of each of the studies and the Academy of Nutrition and Dietetics Grade Definitions and Conclusion Grading Table were used to appraise the quality of evidence.<br/><br/>Results: Six articles met eligibility criteria and were included in this review. Cumulatively 355 overweight/obese participants were assessed. Quality ratings performed by two of the authors revealed a high-quality rating for all six of the articles. One of the articles reported a significant IF associated difference in circulating 8-isoprostane concentrations and another article reported a significant decrease in circulating oxidative lipoproteins concentrations. The remaining articles showed no significant difference on OS markers following IF. <br/><br/>Conclusions: Based on the six articles included in this systematic review, IF was concluded to have limited impact on reducing circulating markers of OS in overweight/obese adults. Overall, the evidence was heterogeneous in relation to IF interventions and outcomes precluding a meta-analysis. Consequently, evidence to make dietary recommendations for reducing oxidative stress with IF interventions is insufficient at this point.

ContributorsMcevoy, Carissa Nicole (Author) / Sweazea, Karen (Thesis director) / Sears, Dorothy (Committee member) / Mohr, Alex (Committee member) / College of Health Solutions (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description

In my undergraduate honors thesis, I strive to convey my idea that dance is more than just movement, it’s one of the many artistic tools used to express emotions; which therefore has the power to storytell without words. It is my hope to create a captivating form of art that

In my undergraduate honors thesis, I strive to convey my idea that dance is more than just movement, it’s one of the many artistic tools used to express emotions; which therefore has the power to storytell without words. It is my hope to create a captivating form of art that you not only view, but can interact and interpret.

ContributorsSawant, Sarika (Author) / Roses-Thema, Cynthia (Thesis director) / Sulikowski, James (Committee member) / College of Health Solutions (Contributor) / School of Music, Dance and Theatre (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05