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Examining the Conners 3–Short Form Predictability on Comorbid ADHD Symptomatology in Children that have been Diagnosed with ASD
No full textThesis completed as part of fulfillment for PSY 4999: Honors Thesis and with the support of the principal investigator and mentor, Dr. Blythe Corbett.With the publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) in 2013, newfound interest grew around the comorbidity of ASD and ADHD. However, the restructuring of both diagnosable descriptors has led to concerns surrounding prevalence rates, deliverable treatments, and identification of comorbid symptomatology. This study focuses on the use of the Conners, Third Edition-Parent Short Form [C3-P(S)]. In the current longitudinal study with 239 participants of typically developing youth (n=102) and youth with ASD (n=137), the C3-P(S) is administered alongside other screening and diagnostic tools. Using the data gathered from the measure alongside their diagnosis of ASD, the study aims to analyze if there is a significant difference between the C3-P(S) subscale scores of the TD and ASD groups. From there, this project serves to make predictions around whether participants present with a profile of co-occurring ADHD symptoms. A second goal is to observe which of the six subscales stands out the most in predicting ADHD comorbid symptomatology in participants who meet the criteria based on the C3-P(S). The results of this study found significant differences among all categories of the C3-P(S) between TD and ASD youth. A larger percentage of ASD children met criteria for ADHD as compared to their TD peers. Additionally, among participants who met screener criteria for ADHD, children with ASD scored significantly higher in the hyperactivity/impulsivity, learning problems, and peer relations subscales. These findings suggest potential predictability of differentiating ASD and ADHD symptomatology using the C3-P(S) if paired with more robust diagnostic tools.Thesis completed in partial fulfillment of the requirements of the Honors Program in Psychological Science
STRUCTURAL BASIS OF O-SIALOGLYCAN RECOGNITION AND SELECTIVITY IN α2,3 SELECTIVE STREPTOCOCCAL SERINE RICH REPEAT ADHESINS AND α2,6 LINKAGE SPECIFIC BACTERIAL SIALYLTRANSFERASES
No full textGlycans play an essential role in biological processes, but our knowledge of their structure and function is limited as compared to other biological molecules. Glycan structure is highly variable. In vivo, glycan structure is determined by enzymes that synthesize, transfer, and cleave monosaccharides. Misregulation of any of these glycan processing steps can lead to human disease. For example, mutations in many types of cancer perturb glycoprocessing pathways. This can lead to overrepresentation of glycans on cancer cells, which help to evade the immune system. To better understand the efficacy of targeting sialoglycans for cancer and to provide improved tools for cancer detection, probes specific for these glycans are needed. Instead of relying on nonspecific antibodies or unstable mammalian and viral glycan binding proteins as probe scaffolds, we can use bacterial proteins with native glycan binding properties. Many bacterial GBPs have been well characterized both structurally and biochemically. To understand more about how bacterial adhesins recognize sialic acid, I crystallized the binding region of a serine rich repeat adhesin from Streptococcus sanguinis strain SK1. This adhesin is particularly interesting for its slightly less common sialic acid recognition motif as well as its tandem Siglec domains. Through structural analysis I determined both Siglec domains are capable of binding glycans. Additionally, some noncanonical motifs bind sialic acid similarly to canonical ones. To better encompass the diversity in amino acid sequence of the sialic acid recognition motif, I redefined the motif from YTRY to ФTRX. Additional research engineering these Siglec-like binding regions from streptococcal adhesins to selectively bind α2,3 sialoglycans demonstrates feasibility for developing bacterial GBPs into selective probes. This same principal can be used to develop probes for α2,6 sialoglycans such as sTn. To my knowledge, there do not exist any naturally occurring lectins that bind α2,6 sialoglycans that can be repurposed as probes. Instead, of using a binding protein, an enzyme can be used. Here, I structurally and biochemically characterize a catalytically inactive mutant of the α2,6 sialyltransferase from Pasteurella multocida
Exploring the Genetic Architecture of Uterine Fibroids
No full textUterine fibroids (UF) are common benign tumors of the uterus affecting majority of females over their lifetime and are the number one cause of hysterectomies in the United States. Genetics are known to influence UF risk from previous familial and genome wide association studies (GWAS). UF have a variety associated comorbidities and phenotypes whose directionality relationship with UF is unknown. To identify high genetic risk for UF individuals, I constructed a meta PRS using summary statistics from FinnGen and Biobank Japan and the program PRS-CSx and validated it using 10-fold cross validation (10x CV) in Electronic Medical Records and Genomics (eMERGE) Network and BioVU. A previous phenome wide association study (PheWAS) for fibroids identified hundreds of associated phenotypes in the clinical phenome. Using mendelian randomization (MR), I assigned directionality to the relationships discovered. UF were found to be causal towards several other genitourinary phenotypes such as endometriosis and ovarian cysts, neoplasms, such as benign neoplasms of ovary and skin cancer, and appears to share horizontal pleiotropy with breast cancer and other breast conditions. From RNA-seq, I identified seven differentially expressed gens (DEGs) had previously been implicated by GWAS studies. Many of the genes are oncogenic. From this project, we can conclude that PRS can be built and applied to UF for prediction modeling. We also observed transcriptional differences in UF that reflect cancerous cell conditions and find that UF is causal towards other neoplasms
Characterization of Angiogenesis Assays to Probe Metabolic Profiles of Tip and Stalk Cells
No full textAngiogenesis is the generation of new blood vessels from existing vasculature and is essential for growth and development of the human body. However, it also plays a role in many pathological processes, such as tumor growth. Angiogenesis is characterized by two distinct endothelial cell phenotypes: tip cells that lead the sprout and stalk cells that follow and proliferate to form the new vessel. It has been previously reported that angiogenesis is highly dependent on the physical properties of the ECM, and denser matrices have been shown to result in increased tip cell metabolism due to increased energetic requirements for cell migration. However, the specific impact of the ECM on the metabolism of the stalk endothelial subtype is not well known. Stalk cells have been shown to interact with the ECM to a lesser degree than tip cells and are not thought to play a large role in cell migration, so we hypothesized the difference in tip and stalk metabolism would increase with matrix density. To investigate this, we first characterized and compared the spheroid and microbead models of angiogenesis to ensure that the optimal model was used for the subsequent investigation. The spheroid assay was selected for this analysis because it produced increased angiogenic output and longer strands that were ideal for studying cell-cell interactions. Unexpectedly, we found no significant difference in tip-stalk metabolism in different matrix densities. This could suggest that stalk cells are able to adapt their metabolism in response to matrix density changes and could interact with the ECM to a higher degree than previously thought
Dosage, Fidelity, and Child Outcomes in a Small Randomized Controlled Trial of EMT en Español
No full textThe purpose of the current study was to examine the dosage and fidelity of EMT en Español strategies that are posited to drive change in child outcomes. The study is a re-analysis of data collected during the National Institutes of Health (NIH) R21 grant “Teaching Spanish-speaking Caregivers to Implement EMT en Español: A Small Randomized Trial.” Data from caregiver child interactions (CCX) at pre-test, post-test, and follow-up were coded for target level language within matched turns, the putative active ingredient in the intervention. Additionally, data from a comprehensive caregiver fidelity checklist representing implementation of the package of EMT en Español component was collected. The relation between caregiver’s dosage and fidelity of the intervention and child language and communication outcomes were analyzed using t-tests and linear regression models. Results indicated that caregivers in the intervention group increased their dosage of the active ingredient and overall fidelity scores significantly more than those caregivers in the control group at both post-test and follow-up. Dosage and fidelity at post-test were predictors of child conceptual vocabulary at follow-up. The findings from this study have potential importance for early intervention and clinical practice
A Priori Estimates for the Linearized Relativistic Euler Equations with a Physical Vacuum Boundary and an Ideal Gas Equation of State
No full textIn this work, we will provide a key result on the relativistic Euler equations with an ideal gas equation of state and a physical vacuum boundary. More specifically, we will prove a priori estimates for the linearized system in weighted Sobolev spaces. As seen in works such as (Disconzi et al., 2022), analysis of the linearized equations often plays a crucial role in developing a local well-posedness theory for the non-linear problem, and our main result is an important step in this direction for the ideal gas equation of state. Our focus will be on choosing the correct thermodynamic variables, developing a weighted book-keeping scheme, and then providing energy estimates for the linearized system
Self-regulated Learning: Selecting Between Worked Example and Problem Solving for Contents with Different Assigned Values
No full textEffective use of learning strategies is crucial for self-regulated learning. Previous research has shown that novice learners benefit more from using worked examples before problem solving. This study incorporated a manipulation from the study time allocation literature to examine how undergraduate students regulate their use of worked examples and problem solving when learning problem-solving procedures with different assigned posttest values, some worth five points in the posttest and others worth one point. Vanderbilt students learned to solve four types of probability problems and selected between the two learning strategies for each of the 24 problems. Results revealed that although students’ overall selection of worked examples did not differ between problem types with different assigned point values, they made more switches between the two learning strategies when they were studying probability problem types with higher assigned point values than problem types with lower assigned point values. After making a mistake while problem-solving, students more often opted to study worked examples than if they solved the problem correctly. Also, students spent more time overall studying problem types that are worth more points and had higher categorization accuracy at posttest than problem types that are worth fewer points. These findings raise a number of questions about students’ reasoning behind each choice of worked example or problem solving and each switch between them. They also suggest some future directions to consider, such as exploring how students combine and leverage different learning strategies to enhance learning outcomes effectively
Matrix Rigidity Influences Breast Cancer Cell Behavior at Bone Marrow-Like Microenvironments
No full textMetastases of breast cancer is a prevalent problem with common sites including the brain, lymph nodes, liver, lung and bone. In the bone microenvironment, metastatic breast cancer cells can form osteolytic lesions and affect the integrity of the bone, causing pathological fractures and impairing patient quality of life. Although signaling mechanisms of osteolysis have been evaluated, little is known about how the mechanical cues of the bone marrow promotes tumor cell growth and invasion. Several models show that the physical forces of the primary microenvironment influence breast cancer cell invasion, but the mechanical cues of the bone microenvironment remain a gap in knowledge. In this project, we utilized model systems to evaluate how matrix rigidities mimicking the bone marrow may contribute to tumor cell invasion and proliferation.
We first sought to create a system to mimic the rigidity of the bone marrow (0.5 kPa – 40 kPa) by using an alginate-Matrigel based hydrogel. We fabricated alginate-Matrigel hydrogels with varying calcium sulfate concentrations to tune the rigidity, and we demonstrated that these hydrogels recapitulated the mechanical properties observed in the bone marrow microenvironment (0.7 kPa to 16 kPa). We encapsulated multiple breast cancer cell lines into these hydrogels to assess growth and invasion. Tumor cells in stiffer hydrogels exhibited modest changes in proliferation and enhanced elongation compared to lower stiffness hydrogels, which suggests that stiffer environments mimicking bone marrow promote invasion.
We then investigated the effects of bone-marrow like stiffnesses on estrogen receptor positive breast cancer. We explored the transcriptional changes that occur at different matrix rigidities associated with the bone microenvironment (bone marrow: 0.5 kPa to 32 kPa; cortical and trabecular bone – 2 x 107 kPa). We observed that lower stiffnesses of the bone marrow contributed to increased gene signatures associated with interleukin signaling. Additionally, downstream estrogen signaling outputs were modified but the estrogen receptor expression remained the same across rigidities. These findings give us insights on what may be changing when ER+ tumor cells encounter rigidities associated with the bone microenvironment
Multilingual? Multidisciplinary! Teachers' Collaboration to Support English Language Learners with Visual Impairments
No full textThe purpose of this paper was to determine the following research questions:
(1A) What is the frequency and perception of collaboration between English as a second language (ESL) teachers and teachers of the visually impaired (TVIs)?
(1B) Does the frequency and perception of collaboration differ for professionals based on their students’ visual impairments (i.e., having low vision compared to blindness)?
(2) Does the frequency and perception of collaboration vary for teachers based on individual demographics, such as their perceived preparedness from their teacher education programs or in- service training? Survey results from 81 ESL teachers and 72 TVIs were analyzed. Participants reported about their collaboration regarding 105 students, 61 of which had low vision and 44 of which were blind. The average total collaboration score was 71.95 out of a possible total score of 110. ESL teachers collaboration with a TVI was more frequent when the student was blind compared to when a student had low vision. TVI collaboration with ESL teachers collaborated at the same frequency regardless of if the student was low vision or blind. No statistically significant relationship was found between a participant’s perception and frequency of collaboration and the student’s visual impairment. These results have implications for both professional practice and teacher preparation programs
Structural Optimization of Antioxidant Copolymers for Drug Delivery Applications
No full textOxidative stress, the pathological elevation of reactive oxygen species (ROS), participates in the propagation of many diseases, including osteoarthritis and optic neuropathies. Polymers incorporating ROS-scavenging groups can recapitulate the body’s innate antioxidant defenses to restore oxidative homeostasis and prevent biomolecule oxidation, inflammation, and cell death. Alone or in combination with targeted therapeutics, antioxidant polymers or biomaterials represent a promising avenue for disease treatment. In this work, we first demonstrate the advantages of optimizing a hydrophilic copolymer incorporating the potent ROS-scavenging drug TEMPO for anti-inflammatory activity. The ratio of TEMPO and an inert hydrophilic spacer was varied, and an optimal formulation was determined in vitro. The lead candidate demonstrated ROS scavenging and suppression of cytokine TNFa in a mouse air pouch model of inflammation. In a related project, we formulated antioxidant microparticles for protein and nucleic acid delivery. Candidate polymers were screened for crystallinity and formulation stability, and the optimized structure was first tested for delivery of the protein erythropoietin (EPO) in mouse models of traumatic optic neuropathy and glaucoma. The combined chemical and biological antioxidant activity of the EPO microparticles outperformed the clinical standard poly(lactic-co-glycolic acid) (PLGA) and reduced tissue damage, leading to improved visual function. MP formulations were then adjusted to load small interfering RNA (siRNA) for gene knockdown of pathological targets in a mouse model of osteoarthritis. Sustained release of siRNA in the joint from microparticles resulted in target gene knockdown superior to free siRNA, and knockdown of catabolic protease MMP13 resulted in improved morphology of joint tissues. Overall, this work demonstrates that ROS-scavenging polymers can be used for a variety of applications to improve drug pharmacokinetics and activity, resulting in overall disease mitigation