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- All Subjects: HIV
- Creators: Jacobs, Bertram
- Creators: Lake, Douglas
Description
Infertility has become an increasing problem in developed countries and in many cases can be attributed to compromised sperm quality. Assessment of male fertility typically utilizes semen analysis which mainly examines sperm morphology, however many males whose sperm appear normal are sub- or infertile, suggesting that sperm from these males may be deficient in a protein or suite of proteins. To date, very little is known about the composition of sperm or the complex maturation process that confers motility and fertilization competency to sperm. Chapter 1 discusses the use of whole cell mass spectrometry to identify 1247 proteins comprising the Rhesus macaque (Macaca mulatta) sperm proteome, a commonly used model of human reproduction. This study provides a more robust proxy of human sperm composition than was previously available and facilitates studies of sperm using the rhesus macaque as a model. Chapters 2 & 3 provide a systems level overview of changes in sperm proteome composition that occurs during epididymal transit. Chapter 2 reports the proteomes of sperm collected from the caput, corpus and cauda segments of the mouse epididymis, identifying 1536, 1720 and 1234 proteins respectively. Chapter 3 reports the sperm proteome from four distinct segments of the Rhesus macaque epididymis, including the caput, proximal corpus, distal corpus and cauda, identifying 1951, 2014, 1764 and 1423 proteins respectively. These studies identify a number of proteins that are added and removed from sperm during epididymal transit which likely play an important role in the sperm maturation process. To date no comparative evolutionary studies of sperm proteomes have been undertaken. Chapter 4 compares four mammalian sperm proteomes including the human, macaque, mouse and rat. This study identified 98 proteins common to all four sperm proteomes, 82 primate and 90 rodent lineage-specific proteins and 494, 467, 566, and 193 species specific proteins in the human, macaque, mouse and rat sperm proteomes respectively and discusses how differences in sperm composition may ultimately lead to functional differences across species. Finally, chapter 5 uses sperm proteome data to inform the preliminary design of a rodent contraceptive vaccine delivered orally using recombinant attenuated Salmonella vaccine vectors.
ContributorsSkerget, Sheri Jo (Author) / Karr, Timothy L. (Thesis advisor) / Lake, Douglas (Committee member) / Petritis, Konstantinos (Committee member) / Arizona State University (Publisher)
Created2013
Description
Studies have demonstrated that viruses such as human immunodeficiency virus [HIV], M13 bacteriophage, and murine cytomegalovirus [MCMV] have been effectively inactivated by exposure to ultra short-pulsed lasers (6,7,10,11,14,15,17). Ultra short pulse laser shows promise as a new method for non-invasive antiviral treatments (17). This method can be used to prevent problems such as drug resistance that is currently rising in numbers. According to the Center for Disease Control [CDC], there are more than two million people in the United States of America that are infected with antimicrobial-resistant infections and at least 23,000 deaths per year occur as a result (19). In this study, ultra-short pulses, specifically Ti-Sapphire Laser [USP Ti-Sapphire Laser] will be evaluated for viral inactivation. The virus chosen for this study was MS2 bacteriophage, which is a non- enveloped, icosahedral, single-stranded RNA [ssRNA] bacteriophages that infects F+ pilus Escherichia coli (16). It was hypothesized that ultrashort pulses from a Ti-Sapphire laser will inactivate MS2 bacteriophage. Inactivation was measured using plaque-forming units [PFU/mL] as an indicator. It was expected that there would be an increase in inactivation of MS2 bacteriophage with an increase in irradiation duration. The results indicated that MS2 bacteriophage was highly sensitive to irradiation treatments of the USP Ti-Sapphire Laser. The concentration of MS2 bacteriophage decreased by 107 PFU/mL after being treated for various time periods ranging from 5 minutes to 150 minutes. Longer duration of USP Ti- Sapphire Laser treatment inactivated more MS2 Bacteriophage.
ContributorsApablasa, Nayeli Aleysa (Author) / Stout, Valerie (Thesis director) / Jacobs, Bertram (Committee member) / Tsen, Kong-Thong (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
Valley Fever, also known as coccidioidomycosis, is a respiratory disease that affects 10,000 people annually, primarily in Arizona and California. Due to a lack of gene annotation, diagnosis and treatment of Valley Fever is severely limited. In turn, gene annotation efforts are also hampered by incomplete genome sequencing. We intend to use proteogenomic analysis to reannotate the Coccidioides posadasii str. Silveira genome from protein-level data. Protein samples extracted from both phases of Silveira were fragmented into peptides, sequenced, and compared against databases of known and predicted proteins sequences, as well as a de novo six-frame translation of the genome. 288 unique peptides were located that did not match a known Silveira annotation, and of those 169 were associated with another Coccidioides strain. Additionally, 17 peptides were found at the boundary of, or outside of, the current gene annotation comprising four distinct clusters. For one of these clusters, we were able to calculate a lower bound and an estimate for the size of the gap between two Silveira contigs using the Coccidioides immitis RS transcript associated with that cluster's peptides \u2014 these predictions were consistent with the current annotation's scaffold structure. Three peptides were associated with an actively translated transposon, and a putative active site was located within an intact LTR retrotransposon. We note that gene annotation is necessarily hindered by the quality and level of detail in prior genome sequencing efforts, and recommend that future studies involving reannotation include additional sequencing as well as gene annotation via proteogenomics or other methods.
ContributorsSherrard, Andrew (Author) / Lake, Douglas (Thesis director) / Grys, Thomas (Committee member) / Mitchell, Natalie (Committee member) / Computing and Informatics Program (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
Description
In the years following the HIV epidemic, much has changed in the way of public health, the social epidemic of stigma has remained. It is the assertion of the authors that stigma can be combatted through the propagation of accurate education and exposure to the lasting negative impacts of social stigma on persons living with HIV in the United States at present. Although individuals who are not apart of this community cannot truly understand the impacts of HIV-related stigma on those directly impacted by it, a sense of understanding and compassion may be elicited through the breakdown of social stigma into comprehensible components and the provision of stigma-inspired artwork. In addition to providing a background on the scientific basis of Human immunodeficiency virus and its spread, the authors have elected to utilize public engagement by means of an anonymous survey as well as personal interactions with HIV advocates to synthesize paintings. Responses were collected from approximately 300 survey participants via social media with no demographic information collected. It was the hope of the authors that the lack of identifying questions may prompt participants to answer freely and honestly to improve overall understanding of social perceptions of HIV and its related stigma. These paintings and resources deemed appropriate based on the results of the aforementioned survey are to be displayed on a webpage for easier access and engagement with a broader audience.Moreover, this webpage is intended to be maintained and utilized beyond the timeframe of this Undergraduate Honors Thesis for the intended purpose of promoting stigma-free HIV advocacy and education.
ContributorsRidgley, Nathan Laurence (Co-author) / Luigs, Stephanie (Co-author) / Jacobs, Bertram (Thesis director) / Salamone, Damien (Committee member) / Spencer, Glen (Committee member) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
While the entire human genome has been sequenced, the understanding of its functional elements remains unclear. The Encyclopedia of DNA Elements (ENCODE) project analyzed 1% of the human genome and found that the majority of the human genome is transcribed, including non-protein coding regions. The hypothesis is that some of the "non-coding" sequences are translated into peptides and small proteins. Using mass spectrometry numerous peptides derived from the ENCODE transcriptome were identified. Peptides and small proteins were also found from non-coding regions of the 1% of the human genome that the ENCODE did not find transcripts for. A large portion of these peptides mapped to the intronic regions of known genes, thus it is suspected that they may be undiscovered exons present in alternative spliceoforms of certain genes. Further studies proved the existence of polyadenylated RNAs coding for these peptides. Although their functional significance has not been determined, I anticipate the findings will lead to the discovery of new splice variants of known genes and possibly new transcriptional and translational mechanisms.
ContributorsWang, Lulu (Author) / Lake, Douglas (Thesis advisor) / Chang, Yung (Committee member) / Touchman, Jeffery (Committee member) / Arizona State University (Publisher)
Created2010
Description
Protein folding is essential in all cells, and misfolded proteins cause many diseases. In the Gram-negative bacterium Escherichia coli, protein folding must be carefully controlled during envelope biogenesis to maintain an effective permeability barrier between the cell and its environment. This study explores the relationship between envelope biogenesis and cell stress, and the return to homeostasis during envelope stress. A major player in envelope biogenesis and stress response is the periplasmic protease DegP. Work presented here explores the growth phenotypes of cells lacking degP, including temperature sensitivity and lowered cell viability. Intriguingly, these cells also accumulate novel cytosolic proteins in their envelope not present in wild-type. Association of novel proteins was found to be growth time- and temperature-dependent, and was reversible, suggesting a dynamic nature of the envelope stress response. Two-dimensional gel electrophoresis of envelopes followed by mass spectrometry identified numerous cytoplasmic proteins, including the elongation factor/chaperone TufA, illuminating a novel cytoplasmic response to envelope stress. A suppressor of temperature sensitivity was characterized which corrects the defect caused by the lack of degP. Through random Tn10 insertion analysis, aribitrarily-primed polymerase chain reaction and three-factor cross, the suppressor was identified as a novel duplication-truncation of rpoE, here called rpoE'. rpoE' serves to subtly increase RpoE levels in the cell, resulting in a slight elevation of the SigmaE stress response. It does so without significantly affecting steady-state levels of outer membrane proteins, but rather by increasing proteolysis in the envelope independently of DegP. A multicopy suppressor of temperature sensitivity in strains lacking degP and expressing mutant OmpC proteins, yfgC, was characterized. Bioinformatics suggests that YfgC is a metalloprotease, and mutation of conserved domains resulted in mislocalization of the protein. yfgC-null mutants displayed additive antibiotic sensitivity and growth defects when combined with null mutation in another periplasmic chaperone, surA, suggesting that the two act in separate pathways during envelope biogenesis. Overexpression of YfgC6his altered steady-state levels of mutant OmpC in the envelope, showing a direct relationship between it and a major constituent of the envelope. Curiously, purified YfgC6his showed an increased propensity for crosslinking in mutant, but not in a wild-type, OmpC background.
ContributorsLeiser, Owen Paul (Author) / Misra, Rajeev (Thesis advisor) / Jacobs, Bertram (Committee member) / Chang, Yung (Committee member) / Stout, Valerie (Committee member) / Arizona State University (Publisher)
Created2010
Description
Anoxia tolerance is strongly correlated with tolerance to heat, desiccation, hyperosmotic shock, freezing, and other general stressors, suggesting that anoxia tolerance is broadly related to stress tolerance. Age affects the capacity of many animals to survive anoxia, but the basis to this ontogenic variation is poorly understood. We exposed adult Drosophila, 1, 3, 5, 7, 9, and 12 days past eclosion, to six hours of anoxia and assessed survival 24-hours post-treatment. Survival of anoxia declined strongly with age (from 80% survival for one-day-old flies to 10% survival for 12 day-old-flies), a surprising result since adult fly senescence in Drosophila is usually observed much later. In anoxia, adenosine triphosphate (ATP) levels declined rapidly (< 30 min) to near-zero levels in both 1 and 12-day old adults; thus the higher anoxia-tolerance of young adults is not due to a better capacity to keep ATP elevated. Relatively few physiological parameters are reported to change over this age range in D. melanogaster, but gut bacterial content increases strongly. As a partial test for a causal link between bacterial load and anoxia tolerance, we replaced food daily, every third day, or every sixth day, and assayed survival of six hours of anoxia and bacterial load at 12 days of age. Anoxia tolerance for 12-day old flies was improved by more food changes and was strongly and negatively affected by bacterial load. These data suggest that increasing bacterial load may play an important role in the age-related decline of anoxia tolerance in Drosophila.
ContributorsSargent, James (Author) / Harrison, Jon F. (Thesis advisor) / Haydel, Shelly (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2020
Description
Brought on by extended survival due to Highly Active Anti-Retroviral Therapy and increased incidence among older adults, the demographic profile of the HIV epidemic has begun to shift towards the aging population. As people living with HIV (PLWH) begin to age and develop multiple comorbidities, their needs are no longer limited to HIV treatment and disease management; they may require aging services similar to those with a negative HIV status. Increased attention has been placed on HIV and aging to assess the unique needs of older PLWH, however, limited research exists on the preparedness of aging services to provide adequate care to this population. This study aims to assess HIV and aging within Maricopa County, where individuals aged 50 years and older account for nearly half the reported HIV/AIDS cases in the county, and 30% of cases in Arizona. Two focus groups – one with older PLWH and another with aging service professionals – were conducted to gather information about existing aging services and the perspectives of older PLWH regarding their growing needs. Older PLWH were found to experience challenges similar to those that have been well-documented in previous studies: most notably, PTSD and other mental health conditions; fear of the future and isolation; HIV status disclosure and stigma; and economics and financial security. An anonymous survey was developed in conjunction with Aunt Rita’s Foundation to evaluate Maricopa County aging services; it was discovered that providers lack experience with HIV and admit deficiencies in their preparation to address the age-related concerns of older PLWH. The results show that the majority of providers were supportive of offering care to older PLWH and expressed interest in improving their preparedness. Future research is necessary to obtain perspectives from additional aging services in Maricopa County and word towards the development of an aging services directory to connect older PLWH to care.
ContributorsLayon, Sarah (Author) / Jacobs, Bertram (Thesis director) / Coon, David (Committee member) / Spencer, Glen (Committee member) / School of Life Sciences (Contributor) / School of Human Evolution & Social Change (Contributor) / School of Art (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Human Immunodeficiency Virus, or HIV, is a global epidemic, costing over 9.51 million individuals their lives since 2000. There are different modes of transmission of HIV, one such mode being from an HIV positive woman to her child before, during, or after delivery (SIC Curriculum, 2006). Though a global epidemic, not all countries have the same prevalence of mother to child, or MTC, transmission of HIV. In 2016, over 160,000 children under the age of five were newly infected with HIV in sub-Saharan Africa. That is compared to the United States of America, where it is estimated that fewer than 150 new infant HIV infections occur yearly (Glaser Foundation, 2020). Those differences exist despite both countries having access to preventative medication as of 1998.
Additionally, the World Health Organization, or WHO, developed three treatment plans for prevention of MTC transmission of HIV, globally available as of 2010 (WHO, 2010). The goal of the WHO was to globally standardize care of HIV-positive pregnant women and their infants in order to decrease the global prevalence of HIV. The first plan was called Option A, then came Option B, and lastly Option B+. While preventative medication has been available for over twenty years and at least one of these theoretically effective treatment plans has been implemented and is readily available in each country of sub-Saharan Africa, the overall prevalence of MTC transmission of HIV in sub-Saharan Africa has continued to be notably high compared to other countries. Thus, the aim of this thesis is to explore some of the significant obstacles to implementation of the WHO’s treatment plans in sub-Saharan Africa that contribute to that high prevalence. I also suggest possible solutions to those barriers in order to effectively decrease the prevalence of MTC transmission of HIV.
Additionally, the World Health Organization, or WHO, developed three treatment plans for prevention of MTC transmission of HIV, globally available as of 2010 (WHO, 2010). The goal of the WHO was to globally standardize care of HIV-positive pregnant women and their infants in order to decrease the global prevalence of HIV. The first plan was called Option A, then came Option B, and lastly Option B+. While preventative medication has been available for over twenty years and at least one of these theoretically effective treatment plans has been implemented and is readily available in each country of sub-Saharan Africa, the overall prevalence of MTC transmission of HIV in sub-Saharan Africa has continued to be notably high compared to other countries. Thus, the aim of this thesis is to explore some of the significant obstacles to implementation of the WHO’s treatment plans in sub-Saharan Africa that contribute to that high prevalence. I also suggest possible solutions to those barriers in order to effectively decrease the prevalence of MTC transmission of HIV.
ContributorsJones, Sierra Hope (Author) / Jacobs, Bertram (Thesis director) / Maienschein, Jane (Committee member) / School of Molecular Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2020-05