Matching Items (110)
Description
Methicillin-Resistant Staphylococcus aureus (MRSA) infections are a major challenge to healthcare professionals. Treatment of MRSA is expensive, and otherwise avoidable deaths occur every year in the United States due to MRSA infections. Additionally, such infections lengthen patients’ stays in hospitals, keeping them out of work and adversely affecting the economy. Beta lactam antibiotics used to be highly effective against S. aureus infections, but resistance mechanisms have rendered methicillin, oxacillin, and other beta lactam antibiotics ineffective against these infections. A promising avenue for MRSA treatment lies in the use of synthetic antibodies—molecules that bind with specificity to a given compound. Synbody 14 is an example of such a synbody, and has been designed with MRSA treatment in mind. Mouse model studies have even associated Syn14 treatment with reduced weight loss and morbidity in MRSA-infected mice. In this experiment, in vitro activity of Syn 14 and oxacillin was assessed. Early experiments measured Syn 14 and oxacillin’s effectiveness in inhibiting colony growth in growth media, mouse serum, and mouse blood. Syn14 and oxacillin had limited efficacy against USA300 strain MRSA, though interestingly it was noted that Syn14 outperformed oxacillin in mouse serum and whole mouse blood, indicating the benefits of its binding properties. A second experiment measured the impact that a mix of oxacillin and Syn 14 had on colony growth, as well as the effect of adding them simultaneously or one after the other. While use of either bactericidal alone did not show a major inhibitory effect on USA300 MRSA colony growth, their use in combination showed major decreases in colony growth. Moreover, it was found that unlike other combination therapies, Syn14 and oxacillin did not require simultaneous addition to MRSA cells to achieve inhibition of cell growth. They merely required that Syn14 be added first. This result suggests Syn14’s possible utility in therapeutic settings, as the time insensitivity of synergy removes a major hurdle to clinical use—the difficulty in ensuring that two drugs reach an affected area at the same time. Syn14 remains a promising antimicrobial agent, and further study should focus on its precise mechanism of action and suitability in clinical treatment of MRSA infections.
ContributorsMichael, Alexander (Author) / Diehnelt, Chris (Thesis director) / Stafford, Phillip (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2015-05
Description
We, a team of students and faculty in the life sciences at Arizona State University (ASU), currently teach an Introduction to Biology course in a Level 5, or maximum-security unit with the support of the Arizona Department of Corrections and the Prison Education Program at ASU. This course aims to enhance current programs at the unit by offering inmates an opportunity to practice literacy and math skills, while also providing exposure to a new academic field (science, and specifically biology). Numerous studies, including a 2005 study from the Arizona Department of Corrections (ADC), have found that vocational programs, including prison education programs, reduce recidivism rates (ADC 2005, Esperian 2010, Jancic 1988, Steurer et al. 2001, Ubic 2002) and may provide additional benefits such as engagement with a world outside the justice system (Duguid 1992), the opportunity for inmates to revise personal patterns of rejecting education that they may regret, and the ability of inmate parents to deliberately set a good example for their children (Hall and Killacky 2008). Teaching in a maximum security prison unit poses special challenges, which include a prohibition on most outside materials (except paper), severe restrictions on student-teacher and student-student interactions, and the inability to perform any lab exercises except limited computer simulations. Lack of literature discussing theoretical and practical aspects of teaching science in such environment has prompted us to conduct an ongoing study to generate notes and recommendations from this class through the use of surveys, academic evaluation of students' work and ongoing feedback from both teachers and students to inform teaching practices in future science classes in high-security prison units.
ContributorsLarson, Anika Jade (Author) / Mor, Tsafrir (Thesis director) / Brownell, Sara (Committee member) / Lockard, Joe (Committee member) / Barrett, The Honors College (Contributor) / School of Politics and Global Studies (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
Peptides offer great promise as targeted affinity ligands, but the space of possible peptide sequences is vast, making experimental identification of lead candidates expensive, difficult, and uncertain. Computational modeling can narrow the search by estimating the affinity and specificity of a given peptide in relation to a predetermined protein target. The predictive performance of computational models of interactions of intermediate-length peptides with proteins can be improved by taking into account the stochastic nature of the encounter and binding dynamics. A theoretical case is made for the hypothesis that, because of the flexibility of the peptide and the structural complexity of the target protein, interactions are best characterized by an ensemble of possible bound configurations rather than a single “lock and key” fit. A model incorporating these factors is proposed and evaluated. A comprehensive dataset of 3,924 peptide-protein interface structures was extracted from the Protein Data Bank (PDB) and descriptors were computed characterizing the geometry and energetics of each interface. The characteristics of these interfaces are shown to be generally consistent with the proposed model, and heuristics for design and selection of peptide ligands are derived. The curated and energy-minimized interface structure dataset and a relational database containing the detailed results of analysis and energy modeling are made publicly available via a web repository. A novel analytical technique based on the proposed theoretical model, Virtual Scanning Probe Mapping (VSPM), is implemented in software to analyze the interaction between a target protein of known structure and a peptide of specified sequence, producing a spatial map indicating the most likely peptide binding regions on the protein target. The resulting predictions are shown to be superior to those of two other published methods, and support the validity of the stochastic binding model.
ContributorsEmery, Jack Scott (Author) / Pizziconi, Vincent B (Thesis advisor) / Woodbury, Neal W (Thesis advisor) / Guilbeau, Eric J (Committee member) / Stafford, Phillip (Committee member) / Taylor, Thomas (Committee member) / Towe, Bruce C (Committee member) / Arizona State University (Publisher)
Created2010
Description
Bacteria with antibiotic resistance are becoming a growing concern as the number of infections they are causing continue to increase. Many potential solutions are being researched in order to combat these pathogens. One such microbe is Pseudomonas aeruginosa, which causes acute and chronic human infections. It frequently colonizes the lungs of cystic fibrosis patients and is deadly. For these reasons, P. aeruginosa has been heavily studied in order to determine a solution to antibiotic resistance. One possible solution is the development of synbodies, which have been developed at the Biodesign Institute at Arizona State University. Synbodies are constructed from peptides that have antibacterial activity and were determined to have specificity for a target bacterium. These synbodies were tested in this study to determine whether or not some of them are able to inhibit P. aeruginosa growth. P. aeruginosa can also form multicellular communities called biofilms and these are known to cause approximately 65% of all human infections. After conducting minimum inhibitory assays, the efficacy of certain peptides and synbodies against biofilm inhibition was assessed. A recent study has shown that low concentrations of a specific peptide can cause biofilm disruption, where the biofilm structure breaks apart and the cells within it disperse into the supernatant. Taking into account this study and peptide data regarding biofilm inhibition from Dr. Aurélie Crabbé’s lab, screened peptides were tested against biofilm to see if dispersion would occur.
ContributorsPatel, Justin Hemant (Author) / Diehnelt, Chris (Thesis director) / Stafford, Phillip (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor) / School of Historical, Philosophical and Religious Studies (Contributor)
Created2015-05
Description
Antibodies are essential for structural determinations and functional studies of membrane proteins, but antibody generation is limited by the availability of properly-folded and purified antigen. We describe the first application of genetic immunization to a structurally diverse set of membrane proteins to show that immunization of mice with DNA alone produced antibodies against 71% (n = 17) of the bacterial and viral targets. Antibody production correlated with prior reports of target immunogenicity in host organisms, underscoring the efficiency of this DNA-gold micronanoplex approach. To generate each antigen for antibody characterization, we also developed a simple in vitro membrane protein expression and capture method. Antibody specificity was demonstrated upon identifying, for the first time, membrane-directed heterologous expression of the native sequences of the FopA and FTT1525 virulence determinants from the select agent Francisella tularensis SCHU S4. These approaches will accelerate future structural and functional investigations of therapeutically-relevant membrane proteins.
ContributorsHansen, Debra (Author) / Robida, Mark (Author) / Craciunescu, Felicia (Author) / Loskutov, Andrey (Author) / Dorner, Katerina (Author) / Rodenberry, John-Charles (Author) / Wang, Xiao (Author) / Olson, Tien (Author) / Patel, Hetal (Author) / Fromme, Petra (Author) / Sykes, Kathryn (Author) / Biodesign Institute (Contributor) / Innovations in Medicine (Contributor) / Applied Structural Discovery (Contributor) / College of Liberal Arts and Sciences (Contributor) / School of Molecular Sciences (Contributor)
Created2016-02-24
Description
This thesis contains three chapters, all of which involve using culturally inclusive education to explore the experiences of religious undergraduate biology students. The first chapter is an essay entitled "Toward Culturally Inclusive Undergraduate Biology Education," which describes a literature review performed with the aim of characterizing the landscape of cultural competence and related terms for biology educators and biology education researchers. This chapter highlights the use of 16 different terms related to cultural competence and presents these terms, their definitions, and highlights their similarities and differences. This chapter also identifies gaps in the cultural competence literature, and presents a set of recommendations to support better culturally inclusive interventions in undergraduate science education. The second chapter, entitled "Different Evolution Acceptance Instruments Lead to Different Research Findings," describes a study in which the source of 30 years of conflicting research on the relationship between evolution acceptance and evolution understanding was determined. The results of this study showed that different instruments used to measure evolution acceptance sometimes lead to different research results and conclusions. The final chapter, entitled "Believing That Evolution is Atheistic is Associated with Poor Evolution Education Outcomes Among Religious College Students," describes a study characterizing definitions of evolution that religious undergraduate biology students may hold, and examines the impact that those definitions of evolution have on multiple outcome variables. In this study, we found that among the most religious students, those who thought evolution is atheistic were less accepting of evolution, less comfortable learning evolution, and perceived greater conflict between their personal religious beliefs and evolution than those who thought evolution is agnostic.
ContributorsDunlop, Hayley Marie (Author) / Brownell, Sara (Thesis director) / Collins, James (Committee member) / Barnes, M. Elizabeth (Committee member) / School of Human Evolution & Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Dielectrophoresis has been shown in the recent past to successfully separate bioparticles of very subtle differences at high resolutions using biophysical forces. In this study, we test the biophysical differences of methicillin resistant and susceptible Staph. aureus that are known to have very similar genomes by using a modified gradient insulator-based dielectrophoresis device (g-iDEP). MRSA is commonly seen in hospitals and is the leading killer of infectious bacteria, claiming the lives of around 10,000 people annually. G-iDEP improves many capabilities within the DEP field including sample size, cost, ease of use and analysis time. This is a promising foundation to creating a more clinically optimized diagnostic tool for both separation and detection of bacteria in the healthcare field. The capture on-set potential for fluorescently tagged MRSA (801 ± 34V) is higher than fluorescently tagged MSSA (610 ± 32V), resulting in a higher electrokinetic to dielectrophoretic mobility ratio for MRSA. Since the strains have proven to be genomically similar through sequencing, it is reasonable to attribute this significant biophysical difference to the added PBP2a enzyme in MRSA. These results are consistent with other bacterial studied within in this device and have proven to be reproducible.
ContributorsSmithers, Jared (Author) / Hayes, Mark (Thesis director) / Woodbury, Neal (Committee member) / School of Criminology and Criminal Justice (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05
Description
Diabesity is a global epidemic affecting millions worldwide. Diabesity is the term given to the link between obesity and Type II diabetes. It is estimated that ~90% of patients diagnosed with Type II diabetes are overweight or have struggled with excess body fat in the past. Type II diabetes is characterized by insulin resistance which is an impaired response of the body to insulin that leads to high blood glucose levels. Adipose tissue, previously thought of as an inert tissue, is now recognized as a major endocrine organ with an important role in the body's immune response and the development of chronic inflammation. It is speculated that adipose tissue inflammation is a major contributor to insulin resistance particular to Type II diabetes. This literature review explores the popular therapeutic targets and marketed drugs for the treatment of Type II diabetes and their role in decreasing adipose tissue inflammation. rAGE is currently in pre-clinical studies as a possible target to combat adipose tissue inflammation due to its relation to insulin resistance. Metformin and Pioglitazone are two drugs already being marketed that use unique chemical pathways to increase the production of insulin and/or decrease blood glucose levels. Sulfonylureas is one of the first FDA approved drugs used in the treatment of Type II diabetes, however, it has been discredited due to its life-threatening side effects. Bariatric surgery is a form of invasive surgery to rid the body of excess fat and has shown to normalize blood glucose levels. These treatments are all secondary to lifestyle changes, such as diet and exercise which can help halt the progression of Type II diabetes patients.
ContributorsRobles, Alondra Maria (Author) / Woodbury, Neal (Thesis director) / Redding, Kevin (Committee member) / Allen, James (Committee member) / Hendrickson, Kirstin (Committee member) / Sanford School of Social and Family Dynamics (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
In this study, we demonstrate the effectiveness of a cancer type specific FrAmeShifT (FAST) vaccine. A murine breast cancer (mBC) FAST vaccine and a murine pancreatic cancer (mPC) FAST vaccine were tested in the 4T1 breast cancer syngeneic mouse model. The mBC FAST vaccine, both with and without check point inhibitors (CPI), significantly slowed tumor growth, reduced pulmonary metastasis and increased the cell-mediated immune response. In terms of tumor volumes, the mPC FAST vaccine was comparable to the untreated controls. However, a significant difference in tumor volume did emerge when the mPC vaccine was used with CPI. The collective data indicated that the immune checkpoint blockade therapy was only beneficial with suboptimal neoantigens. More importantly, the FAST vaccine, though requiring notably less resources, performed similarly to the personalized version of the frameshift breast cancer vaccine in the same mouse model. Furthermore, because the frameshift peptide (FSP) array provided a strong rationale for a focused vaccine, the FAST vaccine can theoretically be expanded and translated to any human cancer type. Overall, the FAST vaccine is a promising treatment that would provide the most benefit to patients while eliminating most of the challenges associated with current personal cancer vaccines.
ContributorsMurphy, Sierra Nicole (Author) / Johnston, Stephen (Thesis director) / Peterson, Milene (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
The goal of this paper is to discuss the most efficient method to achieve early detection in lung cancers by reducing the occurrences of false-positive readings. Imaging techniques (computed tomography screenings) have greater impact than non-imaging techniques in early detection for lung cancer. On the other hand, positron emission tomography and non-imaging techniques, such as liquid biopsy, are better at distinguishing cancer stages. Therefore, these techniques are not suitable early detection methods for lung cancer. Based on literature reviews, the combination that is most capable of early lung cancer detection incorporate low-dose computed tomography screenings, thin-section computed tomography screenings, and computer-aided diagnosis. Low-dose computed tomography screenings has lower radiation-associated risks compared to the standard-dose computed tomography. This technique can be used as both at the first examination and the follow-up examinations. Thin-section computed tomography screenings can be used as a supplement to check if there is any nodules that have not yet been discovered. Computer-aided diagnosis is an add-on method to make sure the computed tomography screenings images are being correctly labeled. Identifying other contributing factors to the effectiveness of the early lung cancer detection, such as the amount of forced expiratory volume, forced vital capacity, and the presence of emphysema, could also decrease the percentage of false positive outcomes.
ContributorsChuang, Hao-Yun (Author) / Johnston, Stephen (Thesis director) / Peterson, Milene (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05