Matching Items (690)
Description
Objective
The objective of this study is to compare amyloid β (Aβ) PET positive and negative patients to their neuropsychological profiles. There is a definitive link between Aβ deposits and cognitive disorders such as MCI or Alzheimer’s disease (AD), but does its presence justify the costly imaging tests based on its clinical context?
Background
Amnestic MCI is largely considered prodromal to AD/dementia in a high majority of cases. [1] Many studies have shown a positive correlation between Aβ PET positive individuals and their likelihood to progress to AD. Aβ deposits in the brain are not always a sign of AD or even MCI, and many elderly people live normal lives with elevated levels. The presence of Aβ in the brain should be carefully considered alongside other tests before making a clinical diagnosis of MCI or AD.
Methods
130 subjects from Barrow Neurological Institute (Phoenix, AZ) were included in this study. Amyloid PET report data was pulled from Dignity Health St. Joseph’s Hospital and Medical Center Outpatient Imaging. Amyloid PET scans obtained by using F-18 florbetapir compound and reviewed by an expert radiologist providing a qualitative status of amyloid-beta positive (+) or negative (-). All data was anonymized and categorized into positive amyloid PET, negative amyloid PET, and clinical diagnosis based on neuropsychological profiles.
Results
The demographic data indicated that 38.5% of the 91 patients diagnosed as amnestic MCI were amyloid PET negative while 61.5% were amyloid PET positive. Of the 39 patients diagnosed as Dementia or AD 15.4% were amyloid PET negative and 84.6% were amyloid PET positive. Correlational analysis between diagnosis and neuropsychological variables suggests that some variables correlate well while others do not. There is a significant correlation between diagnosis and dementia rating scale (DRS) r(24) = -.762, between diagnosis and TrailsB Test r(39) = .397, between diagnosis and phonetic fluency r(30) = -.383, between diagnosis and semantic fluency r(29) = -.369, and between diagnosis and the Boston Naming Test (BNT) r(36) = -.312. Comparing the PET positive and PET negative groups there is a marginal significance in the Boston Naming Test (T=1.945, P=.060) suggesting PET positive individuals test lower than PET negative.
Conclusion
Based on all the results of this study, amyloid PET is still a clinical indicator that an individual might be MCI or dementia/AD, but it has its exceptions. A small number of patients diagnosed as dementia/AD had a negative amyloid PET suggesting that beta amyloid plaques are not the only cause of the disease. There is a strong suggestion that amyloid plaques are a major factor in the progression of dementia or AD, however the results from an amyloid PET cannot be directly related to a diagnosis.
The objective of this study is to compare amyloid β (Aβ) PET positive and negative patients to their neuropsychological profiles. There is a definitive link between Aβ deposits and cognitive disorders such as MCI or Alzheimer’s disease (AD), but does its presence justify the costly imaging tests based on its clinical context?
Background
Amnestic MCI is largely considered prodromal to AD/dementia in a high majority of cases. [1] Many studies have shown a positive correlation between Aβ PET positive individuals and their likelihood to progress to AD. Aβ deposits in the brain are not always a sign of AD or even MCI, and many elderly people live normal lives with elevated levels. The presence of Aβ in the brain should be carefully considered alongside other tests before making a clinical diagnosis of MCI or AD.
Methods
130 subjects from Barrow Neurological Institute (Phoenix, AZ) were included in this study. Amyloid PET report data was pulled from Dignity Health St. Joseph’s Hospital and Medical Center Outpatient Imaging. Amyloid PET scans obtained by using F-18 florbetapir compound and reviewed by an expert radiologist providing a qualitative status of amyloid-beta positive (+) or negative (-). All data was anonymized and categorized into positive amyloid PET, negative amyloid PET, and clinical diagnosis based on neuropsychological profiles.
Results
The demographic data indicated that 38.5% of the 91 patients diagnosed as amnestic MCI were amyloid PET negative while 61.5% were amyloid PET positive. Of the 39 patients diagnosed as Dementia or AD 15.4% were amyloid PET negative and 84.6% were amyloid PET positive. Correlational analysis between diagnosis and neuropsychological variables suggests that some variables correlate well while others do not. There is a significant correlation between diagnosis and dementia rating scale (DRS) r(24) = -.762, between diagnosis and TrailsB Test r(39) = .397, between diagnosis and phonetic fluency r(30) = -.383, between diagnosis and semantic fluency r(29) = -.369, and between diagnosis and the Boston Naming Test (BNT) r(36) = -.312. Comparing the PET positive and PET negative groups there is a marginal significance in the Boston Naming Test (T=1.945, P=.060) suggesting PET positive individuals test lower than PET negative.
Conclusion
Based on all the results of this study, amyloid PET is still a clinical indicator that an individual might be MCI or dementia/AD, but it has its exceptions. A small number of patients diagnosed as dementia/AD had a negative amyloid PET suggesting that beta amyloid plaques are not the only cause of the disease. There is a strong suggestion that amyloid plaques are a major factor in the progression of dementia or AD, however the results from an amyloid PET cannot be directly related to a diagnosis.
ContributorsSorenson, Keaton Andrew (Author) / Azuma, Tamiko (Thesis director) / DeCourt, Boris (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
The goal of this study was to investigate the possibility of catch bond formation between nectin and actin during cellular adhesion by modeling the actin-filament binding protein, afadin, out of equilibrium. This was done through the in silico methodology of Molecular Dynamics (MD); more specifically using Steered Molecular Dynamics (SMD) and Replica Exchange Molecular Dynamics (REMD). The methodology of this experiment centered around generating physiologically probable structures through REMD, then using MD and SMD methods to generate structures in the absence and presence of force respectively. These structures were then analyzed through Solvent Accessible Surface Area (SASA) measurements to assess the overall compactness of the structure, which led to implicit observations on the overall resistance of force that this structure has. Overall, it was found that the structure displayed more compact conformations in the presence of force as the SASA values of the binding pocket and individual residues involved in the system tend to decrease as force was applied. This is indicative of more stable conformations and a force resistant quality that is indicative of catch bonding, thus leading to the natural conclusion that this structure displays catch bond character.
ContributorsChapman, Jonathan (Author) / Singharoy, Abhishek (Thesis director) / Beckstein, Oliver (Committee member) / Ros, Robert (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor)
Created2024-05
Description
The primary channel responsible for cold thermo-transduction in mammals is the transient receptor potential melastatin 8 (TRPM8) channel. TRPM8 is a polymodal, nonselective cation channel with an activation that is dependent on a variety of signals, including the membrane potential, calcium concentration, temperature, and ligands such as menthol. Mathematical modeling provides valuable insight into biochemical phenomena, such as the activity of these channels, which are difficult to observe experimentally. Here, we propose a TRPM8 gating model, represented as a system of ordinary differential equations with menthol, calcium, voltage, and temperature dependencies. We use voltage-clamp data from transfected HEK293 cells in the presence of menthol to create a menthol-dependent voltage shift of activation. We fit the parameters of the TRPM8 gating model to replicate experimental TRPM8 transfected HEK293 cell voltage clamp electrophysiology data using a genetic algorithm. Using k-means clustering, we note eight clusters within 110 total parameter sets consisting of parameter solutions that provide a good fit to the experimental data. We then replicate novel fixed-voltage temperature ramp and fixed-temperature voltage ramp experimental data, demonstrating that our model can replicate the dynamic behaviors of TRPM8. With this TRPM8 gating model, we analyze the various parameter sets obtained from the genetic algorithm and find that different parameter combinations of calcium decay, calcium voltage shift of activation, and temperature sensitivity are able to match static voltage clamp data although differ in their effects on hysteresis and maximal current within prolonged temperature ramp simulations.
ContributorsDudebout, Eric (Author) / Crook, Sharon (Thesis director) / Van Horn, Wade (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor)
Created2024-05
DescriptionIn this project we explored the possibility of creating an international student festival here at ASU through interviews and research. We compiled together everything that would be needed to run such an event efficiently and properly.
ContributorsLacno, James (Author) / Coleman, Audrey (Co-author) / Seagrave, Adam (Thesis director) / Bhatti-Klug, Renee (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor)
Created2024-05
Description
Fumonisins are fungal metabolites found in corn and cereals. Fumonisins pose health risks, including suspected carcinogenicity, yet their mechanism of toxicity remains unclear. While modifications in the human gut microbiome can impact host health, the effects of fumonisins on the microbiome are not well understood. Thus, our study aimed to assess a possible dose-response relationship between fumonisin B1 (FB1) and the gut microbiome. We utilized in vitro anaerobic bioreactors with media simulating most of the nutrients in the human large intestine, inoculated them with fecal samples from 19 healthy adults and treated them with FB1 at concentrations of 0, 10, 100, and 1000 ppb. Analyses of bioreactor headspace revealed declining methane production over time, possibly influenced by the addition of dimethyl sulfoxide (DMSO). Significant differences in acetic acid production were observed in 10 ppb reactor (Day 2) and 100 ppb reactor (Day 8) when compared to 0 ppb control. Microbiome analysis showed minimal shifts in microbial relative abundances during FB1 treatment, except for Desulfovibrio desulfuricans C at Day 8 when compared between 0 ppb and 10 ppb as well as 10 ppb and 1000 ppb at Day 16. Alpha diversity analyses indicated significant differences in observed features within bioreactors of different treatments, with some variation in Faith’s Phylogenetic Diversity between the 0 ppb and 10 ppb bioreactors. Beta diversity analyses, however, revealed no significant differences between bioreactors. Overall, our findings suggest no clear dose-response relationship between FB1 treatment and gut microbiome composition/functions. The presence of DMSO may have obscured potential effects. This research will help contribute to our understanding of mycotoxicity influence on the human gut microbiome.
ContributorsSanchez Carreon, Aurely (Author) / Krajmalnik-Brown, Rosa (Thesis director) / Cheng, Qiwen (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor)
Created2024-05
Description
Curanderismo can be defined as a blend between ancient Aztec natural healing methods and modern day Catholicism. Today, it is practiced through various techniques, which can be observed in yerberias. Upon visiting these yerberias, the attendants were interviewed to understand which products are commonly sold, what they are used to treat, and the cultural significance behind the practice. After purchasing a number of products from each yerberia, a literature analysis of potential biochemical pathways was conducted to determine if these products have efficacy in what they treat. While potential pathways were found for a number of the products, it has been determined that further clinical research must be conducted to state whether these products are effective in treatment.
ContributorsDickey, Erin (Author) / Mullenmeister, William (Co-author) / Breitweiser, Mya (Co-author) / Holechek, Susan (Thesis director) / Redding, Kevin (Committee member) / Barrett, The Honors College (Contributor) / School of International Letters and Cultures (Contributor) / School of Molecular Sciences (Contributor)
Created2024-05
Description
Misincorporation of uracil bases into DNA can lead to mutations after transcription. Uracil-DNA glycosylase (UDG) is an enzyme that removes uracil bases from DNA, leaving an apurinic/apyrimidinic site. Different efficiencies of uracil base removal by UDG have been observed at different sites in DNA. A previous study found that UDG has a higher specificity constant for DNA sequences that are more flexible, specifically that those with uracil in a context of thymine adjacent on the 5’ side and adenine adjacent on the 3’ side (TUA sequence) bound UDG better than those with an adenine adjacent on the 5’ side and thymine adjacent on the 3’ side (AUT sequence) context. The purpose of this study is to expand the previous one by determining whether the ratios observed between TUA and AUT specificity constants within DNA sequences that are otherwise the same are also observed across a third sequence context that was not included in the first study. The hypothesis that same ratio would be observed is somewhat supported as the new sequence has a specificity constant of 1.24±0.043 ✕ 107 M-1s-1. However, conclusions to be drawn from this are limited by the wide margin of error seen among trials of the same concentrations.
ContributorsEngelken, Rylee (Author) / Levitus, Marcia (Thesis director) / Klein-Seetharaman, Judith (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor) / School of Human Evolution & Social Change (Contributor)
Created2024-05
Description
The boarding school system heavily impacted the structure and mental wellness of the
Diné (Navajo) Nation, and these effects can still be felt today across Indian country in the
Southwest. To this day, the general public is not fully aware of how much the Diné community
has suffered from this system. Generally, in American history books, you will not find a chapter
on the Trail of Tears or the Long Walk, which are devastating moments in history of the tribal
communities affected. Nor will you find a chapter on boarding schools and the founding of the
Carlisle Indian School which shaped the standard for American educational systems. The stories of the boarding school system and the forced assimilation of indigenous communities are not common knowledge in mainstream society. Many of these stories do not exist outside of Indigenous communities. The purpose of this thesis is to identify who were the perpetrators of the boarding school system and who were the victims, while proving that Indigenous people
today are still closely connected to their culture and were not completely assimilated. This thesis will identify how boarding school trauma impacted the Diné people of the Navajo tribe and Indigenous peoples across the southwest region between the Four Sacred Mountains: Mount Blanca in south-central Colorado, Mount Taylor in Grants, New Mexico, the San Francisco peaks in Flagstaff, Arizona, and Mount Hesperus near Durango, Colorado. The Diné concepts of K’é and Hózhó are discussed as methods of survivance employed by Diné boarding school survivors and their descendants.
ContributorsTsosie, Autumn (Author) / Lynch, John (Thesis director) / Fixico, Donald (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor)
Created2024-05
Description
Cryptotephra (microscopic volcanic ash) has had significant contributions towards constructing and refining age models and correlating archaeological sites for decades. This thesis will report on cryptotephra from the archaeological site of Kathu Pan, specifically from sinkhole 6, located on the southern edge of the Kalahari basin in the Northern Cape of South Africa. I will investigate the potential of cryptotephra from the Holocene layers of Kathu Pan (KP6) to test the current age model and source it to a specific region and a specific eruption. Both of the samples in this study, kp6-55-70 and kp6-75-90, are high silica rhyolites that date to the Holocene. Based on the geochemical findings, both samples have potential to be sourced from the Main Ethiopian Rift (MER), Guatemala, Indonesia, and New Zealand. The primary sourcing was focused on the Main Ethiopian Rift (MER) and the Turkana Basin in Kenya. Evidence suggests that kp6-75-90 is likely to have originated from the Turkana basin, meanwhile kp6-55-70 requires further sourcing in order to confidently correlate it to a region and an eruption. Further research needs to be completed in order to refine the age model at Kathu Pan 6.
ContributorsCurtiss, Julia (Author) / Campisano, Christopher (Thesis director) / Hirniak, Jayde (Committee member) / Barrett, The Honors College (Contributor) / School of Molecular Sciences (Contributor) / School of International Letters and Cultures (Contributor) / School of Human Evolution & Social Change (Contributor)
Created2024-05
Description
Anelloviruses are small, negative-sense, single-stranded DNA viruses that have are found to be present in over 90% of adult humans. Despite being highly prevalent, little is known about the biology or pathogenic potentials of the anelloviruses. Initially, the family Anelloviridae, contained 14 genera. However, in the last few years, there have been an abundant number of diverse anelloviruses that were identified in various organisms. Thus, a new criterion for anelloviruses classification was necessary to establish new genera and species to accommodate unclassified anelloviruses. As part of an ongoing effort to characterize the human virome of female genital tract (FGT), we performed virome metagenomic sequencing of Peruvian women living with HIV, and we have identified 7 novel anellovirus genome sequences found in cervicovaginal clinical specimens. Through phylogenetic and sequence analyses of the new characterization criteria, we classified the genome sequences as three novel anellovirus genera, provisionally named, Petorquevirus, Sadetorquevirus, and Quoptorquevirus.
ContributorsDo, Eric (Author) / Lim, Efrem (Thesis director) / Kaelin, Emily (Committee member) / Barrett, The Honors College (Contributor) / Economics Program in CLAS (Contributor) / School of Molecular Sciences (Contributor) / School of Life Sciences (Contributor)
Created2024-05