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- Creators: Arizona State University
- Creators: Bjorklund, Reed
- Resource Type: Text
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 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
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 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
Description
The RAS/MAPK (RAS/Mitogen Activated Protein Kinase) pathway is a highly conserved, canonical signaling cascade that is highly involved in cellular growth and proliferation as well as cell migration. As such, it plays an important role in development, specifically in development of the nervous system. Activation of ERK is indispensable for the differentiation of Embryonic Stem Cells (ESC) into neuronal precursors (Li z et al, 2006). ERK signaling has also shown to mediate Schwann cell myelination of the peripheral nervous system (PNS) as well as oligodendrocyte proliferation (Newbern et al, 2011). The class of developmental disorders that result in the dysregulation of RAS signaling are known as RASopathies. The molecular and cell-specific consequences of these various pathway mutations remain to be elucidated. While there is evidence for altered DNA transcription in RASopathies, there is little work examining the effects of the RASopathy-linked mutations on protein translation and post-translational modifications in vivo. RASopathies have phenotypic and molecular similarities to other disorders such as Fragile X Syndrome (FXS) and Tuberous Sclerosis (TSC) that show evidence of aberrant protein synthesis and affect related pathways. There are also well-defined downstream RAS pathway elements involved in translation. Additionally, aberrant corticospinal axon outgrowth has been observed in disease models of RASopathies (Xing et al, 2016). For these reasons, this present study examines a subset of proteins involved in translation and translational regulation in the context of RASopathy disease states. Results indicate that in both of the tested RASopathy model systems, there is altered mTOR expression. Additionally the loss of function model showed a decrease in rps6 activation. This data supports a role for the selective dysregulation of translational control elements in RASopathy models. This data also indicates that the primary candidate mechanism for control of altered translation in these modes is through the altered expression of mTOR.
ContributorsHilbert, Alexander Robert (Author) / Newbern, Jason (Thesis director) / Olive, M. Foster (Committee member) / Bjorklund, Reed (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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 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.
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
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 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
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