Matching Items (9)
Filtering by

Clear all filters

152140-Thumbnail Image.png
Description
Specificity and affinity towards a given ligand/epitope limit target-specific delivery. Companies can spend between $500 million to $2 billion attempting to discover a new drug or therapy; a significant portion of this expense funds high-throughput screening to find the most successful target-specific compound available. A more recent addition to discovering

Specificity and affinity towards a given ligand/epitope limit target-specific delivery. Companies can spend between $500 million to $2 billion attempting to discover a new drug or therapy; a significant portion of this expense funds high-throughput screening to find the most successful target-specific compound available. A more recent addition to discovering highly specific targets is the application of phage display utilizing single chain variable fragment antibodies (scFv). The aim of this research was to employ phage display to identify pathologies related to traumatic brain injury (TBI), particularly astrogliosis. A unique biopanning method against viable astrocyte cultures activated with TGF-β achieved this aim. Four scFv clones of interest showed varying relative affinities toward astrocytes. One of those four showed the ability to identify reactive astroctyes over basal astrocytes through max signal readings, while another showed a statistical significance in max signal reading toward basal astrocytes. Future studies will include further affinity characterization assays. This work contributes to the development of targeting therapeutics and diagnostics for TBI.
ContributorsMarsh, William (Author) / Stabenfeldt, Sarah (Thesis advisor) / Caplan, Michael (Committee member) / Sierks, Michael (Committee member) / Arizona State University (Publisher)
Created2013
149791-Thumbnail Image.png
Description
Emotion recognition through facial expression plays a critical role in communication. Review of studies investigating individuals with traumatic brain injury (TBI) and emotion recognition indicates significantly poorer performance compared to controls. The purpose of the study was to determine the effects of different media presentation on emotion recognition in individuals

Emotion recognition through facial expression plays a critical role in communication. Review of studies investigating individuals with traumatic brain injury (TBI) and emotion recognition indicates significantly poorer performance compared to controls. The purpose of the study was to determine the effects of different media presentation on emotion recognition in individuals with TBI, and if results differ depending on severity of TBI. Adults with and without TBI participated in the study and were assessed using the The Awareness of Social Inferences Test: Emotion Evaluation Test (TASIT:EET) and the Facial Expressions of Emotion-Stimuli and Tests (FEEST) The Ekman 60 Faces Test (E-60-FT). Results indicated that individuals with TBI perform significantly more poorly on emotion recognition tasks compared to age and education matched controls. Additionally, emotion recognition abilities greatly differ between mild and severe TBI groups, and TBI participants performed better with the static presentation compared to dynamic presentation.
ContributorsBrown, Cassie Anne (Author) / Wright, Heather H (Thesis advisor) / Stats-Caldwell, Denise (Committee member) / Ingram, Kelly (Committee member) / Arizona State University (Publisher)
Created2011
172008-Thumbnail Image.png
Description
Nearly four decades after HIV (Human Immunodeficiency Virus) was identified as the causal agent of the AIDS (Acquired Immunodeficiency Syndrome) pandemic, it remains a top global health concern impacting millions of people around the world particularly in Sub-Saharan Africa. Despite significant scientific, governmental and nongovernmental organizational efforts, most HIV-infected patients

Nearly four decades after HIV (Human Immunodeficiency Virus) was identified as the causal agent of the AIDS (Acquired Immunodeficiency Syndrome) pandemic, it remains a top global health concern impacting millions of people around the world particularly in Sub-Saharan Africa. Despite significant scientific, governmental and nongovernmental organizational efforts, most HIV-infected patients do not have access to prevention and treatment. Since cure is not available yet, developing a vaccine to prevent HIV from spreading is a priority. Previous studies have worked on an HIV vaccine platform using attenuated Vaccinia vector and plant-produced HIV virus-like particles (VLPs) to deliver Gag and dgp41 antigens as a heterologous prime-boost strategy. To further study this work, I conducted immunogenicity studies in rabbits which exhibited high IgG responses against Gag (p < 0.002) and less to dgp41. To increase the immunogenicity to dgp41, focusing on MPER, a combination of IgG fusions with VLPs as a vaccine platform was studied in mice. Both IgG fusion constructs showed similar serum results, though Gag-specific serum IgG responses were significantly higher (p < 0.007) for the recombinant immune complex (RIC) group than hexamer forming complexes (Hex). In an effort to expand the use of HIV VLPs, RSV (Respiratory Syncytial Virus) pre-fusion stabilized F (pre-F) protein was presented by self-assembling HIV-1 Gag as a potential vaccine strategy for RSV infections. Multiple constructs were designed to assemble into chimeric VLPs and tested for recombinant plant expression. Mouse immunogenicity study using these chimeric VLPs showed significantly high F-specific IgG (p < 0.001) in serum and superior IgA in mucosal samples for the group that received one of the pre-F stabilized VLP constructs. Moreover, when the same antigen was administered with cholera toxin intranasally, it generated IgA response in nasal flush higher than when it was administered subcutaneously. To summarize, this study showed the efficiency of a plant-produced VLP-based system as an adaptable chimeric vaccine platform for potential use with various viral antigens in pursuit of a vaccine strategy that is immunogenic in animal studies.
ContributorsKamzina, Aigerim (Author) / Mor, Tsafrir TM (Thesis advisor) / Mason, Hugh HM (Committee member) / Jacobs, Bertram BJ (Committee member) / Blattman, Joseph JB (Committee member) / Arizona State University (Publisher)
Created2022
158647-Thumbnail Image.png
Description
Mild TBI (mTBI) has been associated with subtle executive function (EF) and

cognitive-communication deficits. In bilinguals, there are unique cognitive demands required to control and process two languages effectively. Surprisingly, little is known about the impact of mTBI on EF, communication, and language control in bilinguals. Therefore, the aim of this

Mild TBI (mTBI) has been associated with subtle executive function (EF) and

cognitive-communication deficits. In bilinguals, there are unique cognitive demands required to control and process two languages effectively. Surprisingly, little is known about the impact of mTBI on EF, communication, and language control in bilinguals. Therefore, the aim of this study was to examine the cognitive-communication abilities in bilinguals with a history of mTBI, identify any language control impairments, and explore the relationship between these language control impairments and domain-general cognitive control abilities. To this end, three-hundred and twenty-seven monolingual and bilingual college students with and without mTBI history participated in two experiments. In these experiments, EF, communication, and language control were examined using experimental and clinical tasks as well as self-rating scales. In Experiment 1, there was an interaction between mTBI history and language group (monolinguals vs. bilinguals) in how participants performed on a clinical measure of EF and a verbal fluency task. That is, only bilinguals with mTBI scored significantly lower on these tasks. In addition, there was a significant correlation between errors on a language switching task and performance on non-verbal EF tasks. In Experiment 2, a subgroup of bilinguals with persistent cognitive and behavioral symptoms reported greater everyday communication challenges in their first and second languages. Also, unbalanced bilinguals reported greater EF difficulties than monolinguals and balanced bilinguals regardless of mTBI history. In conclusion, bilinguals may face unique cognitive-communication challenges after mTBI. Factors related to the bilingual experience (e.g., language balance, daily language use) should be

considered in clinical evaluation and future research.
ContributorsAlateeq, Halah (Author) / Azuma, Tamiko (Thesis advisor) / Ratiu, Ileana (Committee member) / Lavoie, Michael (Committee member) / Arizona State University (Publisher)
Created2020
161991-Thumbnail Image.png
Description
Traumatic Brain Injury (TBI) affects approximately two million people on an annual basis and increases the frequency and onset of Alzheimer’s disease (AD) and other related dementias (ADRDs). Mechanical damage and shearing of neuronal axons are thought to be responsible for producing toxic variants of proteins that contribute to disease

Traumatic Brain Injury (TBI) affects approximately two million people on an annual basis and increases the frequency and onset of Alzheimer’s disease (AD) and other related dementias (ADRDs). Mechanical damage and shearing of neuronal axons are thought to be responsible for producing toxic variants of proteins that contribute to disease pathology. Specifically, the tau, beta amyloid, alpha-synuclein, and TAR-binding DNA Protein-43 (TDP-43) variants contribute to the heterogenous pathology mechanisms of neurodegenerative diseases. The Sierks lab at Arizona State University has aimed to study how these protein variants collectively interact to contribute to pathologies characteristic of AD/ADRDs. This study focuses on the accumulation of toxic oligomeric variants of TDP-43 secondary to TBI. The first aim of this study was to identify the protein variant fingerprint as a function time following experimental diffuse TBI. The second aim was to investigate if toxic variants of TDP-43 were associated with cognitive and motor functional deficits. C57BL/6 mice were subjected to a single or repetitive diffuse TBI via midline fluid percussion injury or a control surgery (sham). Post-injury, mice were evaluated for cognitive performance, sensorimotor function, and depressive-like behavior at 7-, 14-, and 28-days post-injury. Tissue was collected for immunohistochemistry and stained for ADTDP-3, a single chain antibody variable fragment (ScFv) which binds to toxic variants of TDP-43 in amyotrophic lateral sclerosis (ALS) and AD tissue. A one-way analysis of variance (ANOVA) was performed to compare staining intensity across various brain regions. Subsequently, a Pearson correlation was performed to compare behavioral task performance to staining intensity by brain region for each injury group. There were significantly elevated levels of ADTDP3 binding in all regions except for the hippocampus, and there was a significant correlation between the cortex staining intensity vs the cognitive behavior test at 7 days post-injury. There was also a significant correlation between the thalamus staining intensity and sensorimotor test at 7 days post-injury. These findings support the hypothesis that the accumulation of toxic variants of TDP-43 can contribute to neurodegenerative pathology and loss of function. These variants also may contribute to behavioral deficits secondary to diffuse TBI.
ContributorsAftab, Umar Syed (Author) / Sierks, Michael R (Thesis advisor) / Rowe, Rachel K (Thesis advisor) / Newbern, Jason M (Committee member) / Arizona State University (Publisher)
Created2021
Description
Recent studies in traumatic brain injury (TBI) have found a temporal window where therapeutics on the nanometer scale can cross the blood-brain barrier and enter the parenchyma. Developing protein-based therapeutics is attractive for a number of reasons, yet, the production pipeline for high yield and consistent bioactive recombinant proteins remains

Recent studies in traumatic brain injury (TBI) have found a temporal window where therapeutics on the nanometer scale can cross the blood-brain barrier and enter the parenchyma. Developing protein-based therapeutics is attractive for a number of reasons, yet, the production pipeline for high yield and consistent bioactive recombinant proteins remains a major obstacle. Previous studies for recombinant protein production has utilized gram-negative hosts such as Escherichia coli (E. coli) due to its well-established genetics and fast growth for recombinant protein production. However, using gram-negative hosts require lysis that calls for additional optimization and also introduces endotoxins and proteases that contribute to protein degradation. This project directly addressed this issue and evaluated the potential to use a gram-positive host such as Brevibacillus choshinensis (Brevi) which does not require lysis as the proteins are expressed directly into the supernatant. This host was utilized to produce variants of Stock 11 (S11) protein as a proof-of-concept towards this methodology. Variants of S11 were synthesized using different restriction enzymes which will alter the location of protein tags that may affect production or purification. Factors such as incubation time, incubation temperature, and media were optimized for each variant of S11 using a robust design of experiments. All variants of S11 were grown using optimized parameters prior to purification via affinity chromatography. Results showed the efficiency of using Brevi as a potential host for domain antibody production in the Stabenfeldt lab. Future aims will focus on troubleshooting the purification process to optimize the protein production pipeline.
ContributorsEmbrador, Glenna Bea Rebano (Author) / Stabenfeldt, Sarah (Thesis director) / Plaisier, Christopher (Committee member) / Harrington Bioengineering Program (Contributor, Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
164830-Thumbnail Image.png
Description

Traumatic brain injury (TBI) is defined as an injury to the head that disrupts normal brain function. TBI has been described as a disease process that can lead to an increased risk for developing chronic neurodegenerative diseases, like frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). A pathological hallmark

Traumatic brain injury (TBI) is defined as an injury to the head that disrupts normal brain function. TBI has been described as a disease process that can lead to an increased risk for developing chronic neurodegenerative diseases, like frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). A pathological hallmark of FTLD and a hallmark of ALS is the nuclear mislocalization of TAR DNA Binding Protein 43 (TDP-43). This project aims to explore neurodegenerative effects of TBI on cortical lesion area using immunohistochemical markers of TDP-43 proteinopathies. We analyzed the total percent of NEUN positive cells displaying TDP-43 nuclear mislocalization. We found that the percent of NEUN positive cells displaying TDP-43 nuclear mislocalization was significantly higher in cortical tissue following TBI when compared to the age-matched control brains. The cortical lesion area was analyzed for each injured brain sample, with respect to days post-injury (DPI), and it was found that there were no statistically significant differences between cortical lesion areas across time points. The percent of NEUN positive cells displaying TDP-43 nuclear mislocalization was analyzed for each cortical tissue sample, with respect to cortical lesion area, and it was found that there were no statistically significant differences between the percent of NEUN positive cells displaying TDP-43 nuclear mislocalization, with respect to cortical lesion area. In conclusion, we found no correlation between the percent of cortical NEUN positive cells displaying TDP-43 nuclear mislocalization with respect to the size of the cortical lesion area.

ContributorsWong, Jennifer (Author) / Stabenfeldt, Sarah (Thesis director) / Bjorklund, Reed (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2022-05
163463-Thumbnail Image.png
Description

Annually approximately 1.5 million Americans suffer from a traumatic brain injury (TBI) increasing the risk of developing a further neurological complication later in life [1-3]. The molecular drivers of the subsequent ensuing pathologies after the initial injury event are vast and include signaling processes that may contribute to neurodegenerative diseases

Annually approximately 1.5 million Americans suffer from a traumatic brain injury (TBI) increasing the risk of developing a further neurological complication later in life [1-3]. The molecular drivers of the subsequent ensuing pathologies after the initial injury event are vast and include signaling processes that may contribute to neurodegenerative diseases such as Alzheimer’s Disease (AD). One such molecular signaling pathway that may link TBI to AD is necroptosis. Necroptosis is an atypical mode of cell death compared with traditional apoptosis, both of which have been demonstrated to be present post-TBI [4-6]. Necroptosis is initiated by tissue necrosis factor (TNF) signaling through the RIPK1/RIPK3/MLKL pathway, leading to cell failure and subsequent death. Prior studies in rodent TBI models report necroptotic activity acutely after injury, within 48 hours. Here, the study objective was to recapitulate prior data and characterize MLKL and RIPK1 cortical expression post-TBI with our lab’s controlled cortical impact mouse model. Using standard immunohistochemistry approaches, it was determined that the tissue sections acquired by prior lab members were of poor quality to conduct robust MLKL and RIPK1 immunostaining assessment. Therefore, the thesis focused on presenting the staining method completed. The discussion also expanded on expected results from these studies regarding the spatial distribution necroptotic signaling in this TBI model.

ContributorsHuber, Kristin (Author) / Stabenfeldt, Sarah (Thesis director) / Brafman, David (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor) / School of Molecular Sciences (Contributor)
Created2022-05
Description
Traumatic brain injury (TBI) poses a significant global health concern with substantial health and economic consequences. Patients often face significant consequences after injury, notably persistent cognitive changes and an increased risk of developing neurodegenerative disease later in life. Apart from the immediate insult, the resulting inflammatory response can lead to

Traumatic brain injury (TBI) poses a significant global health concern with substantial health and economic consequences. Patients often face significant consequences after injury, notably persistent cognitive changes and an increased risk of developing neurodegenerative disease later in life. Apart from the immediate insult, the resulting inflammatory response can lead to neuroinflammation, oxidative stress, tissue death, and long-term neurodegeneration. Microglia and astrocytes play critical roles in these inflammatory processes, emphasizing the unmet need for targeted therapies. Vaccine formulations consisting of poly (a-ketoglutarate) (paKG) microparticles (MPs) encapsulating PFK15 (1-(4-pyridinyl)-3-(2-quinolinyl)-2-propen-1-one) and myelin proteolipid protein (PLP) were developed for prior studies and have demonstrated the production of antigen-specific adaptive T-cell responses in the brain, spleen, and lymph nodes of mice, suggesting that these formulations may be able to prevent neuronal inflammation in mice after TBI. The vaccine efficacy was further evaluated through the image analysis of immunohistochemically stained brain tissue sections from naive, saline, and paKG(PFK15+PLP) MPs or paKG(PFK15) MPs treated mice. Though microglia (Iba1), astrocytes (GFAP) and CD86 were visualized in this method, only Iba1 was found to be significantly reduced in the contralateral hemisphere for paKG(PFK15+PLP) MPs and paKG(PFK15) MPs groups when compared to naive (p=0.0373 and p=0.0186, respectively). However, the naive group also showed an unexpectedly high level of CD86 after thresholding (compared to the TBI groups), indicating flaws were present in the analysis pipeline. Challenges of the image analysis process included thresholding setting optimization, folded tissues, bubbles, and saturated punctate signal. These issues may have impacted data accuracy, underscoring the need for rigorous optimization of experimental techniques and imaging methodologies when evaluating the therapeutic potential of the vaccines in mitigating TBI-induced neuroinflammation. Thus, future analyses should consider microglial morphology and employ more accurate thresholding in FIJI/ImageJ to better measure cellular activation and the overall positive signal.
ContributorsSundem, Andrea (Author) / Stabenfeldt, Sarah (Thesis director) / Willingham, Crystal (Committee member) / Barrett, The Honors College (Contributor) / Harrington Bioengineering Program (Contributor)
Created2024-05