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CIL 6.22095 – Epitaph for Q. Marcius Publilianus, aged two years, five months, and three days, dedicated by his extended family, 1st-2nd century CE
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Ohl 95, no. 11 – Columbarium plaque for P. Cornelius Synistor, 1st century CE
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Investigating novel roles of UPF3 interactions in Nonsense Mediated mRNA Decay
Get PDFRNA quality control is important in maintaining cellular processes and preventing disease. Nonsense mediated mRNA decay (NMD) is a conserved pathway in eukaryotes that proofreads messenger RNA (mRNA) by recognizing premature termination codons (PTCs), preventing the accumulation of deleterious effects of toxic peptides. The UPF3 protein is a core factor in NMD with two paralogs in vertebrates: UPF3A and UPF3B. The paralogs play partially redundant roles in the NMD pathway, with UPF3A being a weaker activator. Previous work in our lab has shown that the middle or “mid” domain of UPF3 underlies differential NMD activity between the paralogs. The UPF3 paralogs also diverge in their physiological roles. UPF3B knockout mice exhibit defects in neuronal development whereas knockout of UPF3A knockout is embryonic lethal. Furthermore, mutations in human UPF3B are associated with intellectual disability, autism, and schizophrenia. Despite UPF3 being an integral NMD factor, its interactions and how these differ between paralogs are not fully understood. Using proteomics and cell based immunoprecipitation in HCT116 cells, our lab has identified novel binding partners of UPF3A and UPF3B. Using FLAG Immunoprecipitation (FLAG-IP), we verified interactions with transcriptional regulator RBBP5, and nucleocytoplasmic shuttling factors, ALKBH5 and KPNA3. Using FLAG-IP and Western blotting, I found that the mid domain did not appear to underlie differential binding of ALKBH5 between UPFA and UPF3B. Finally, we used siRNA mediated knockdown in HCT116 WT cells and RT-qPCR of known NMD targets to deplete UPF3 binding partners and measure their effect on NMD of endogenous PTC-containing mRNAs. Interestingly, in preliminary experiments depletion of KPNA3 and transcriptional elongation regulator, MLLT1 led to reduced levels of PTC-containing isoforms of endogenous NMD targets, but not their PTC-less counterparts. Future work will continue to determine whether UPF3 binding partners affect NMD efficiency, and whether these interactions are critical for UPF3 function in the NMD pathway.No embargoAcademic Major: Molecular Genetic
Arvcf Prevents Age-Dependent Cataracts by Stabilizing Adherens Junctions and Cytoskeletal Proteins
No full textBiological Sciences: 2nd Place (The Ohio State University Edward F. Hayes Advanced
Research Forum)The eye lens focuses light paths onto the retina to produce a clear, unobstructed image for optimal vision. However, cellular disruptions can lead to cataracts, a lens disease caused by a loss of transparency. Despite age being the highest risk factor for cataract development, the molecular changes that occur between a young, clear lens to an aged, opaque lens remain relatively unknown. We have demonstrated that genetic ablation of a critical component of adherens junctions, Arvcf, leads to premature cataracts in mice. As this suggests that the loss of Arvcf exacerbates a molecular process in aging, we hypothesize that lens transparency is dependent upon stable cell adhesion in the membrane cytoskeleton. To test this, we compared control and Arvcf-deficient mouse lenses using proteomic and histological methods. Co-immunoprecipitation experiments demonstrate that Arvcf is required for adherens junctional protein associated with N-Cadherin. We also identified novel cytoskeletal and intermediate filaments that associate with Arvcf and N-Cadherin. Immunofluorescent spinning disk confocal microscopy of N-Cadherin, Ankyrin-B, and α-II spectrin show that Arvcf is likely required for maintaining protrusive membrane localization of these associated proteins. Together, these data suggest that the loss of adhesion and cytoskeletal protein association is a biomarker in the aging cataract.A three-year embargo was granted for this item
AbioGenesis: An Origin Story – Personal Myth, A Collective Reason; The Anthropological Mechanism of Storytelling
Get PDFThis thesis is a commentary on the anthropological mechanism of theater as a healing modality for acute traumas within individual and collective economies. It is illustrated through leveraging social allegory and personal narrative. Its experimental applications initialized community based workshops focused on 'conscious play' as a primary modality and the project culminated in a fully stage rendering in the semester of its completion.College of The Arts and SciencesNo embargoAcademic Major: EnglishAcademic Major: Theatr
Predicting Flow Characteristics Within a Subspace Located at Various Positions Behind a Cylinder
Get PDFProducing simulations to train naval pilots requires accurate modeling of complex aerodynamic phenomena. The air wake behind a ship is one of the flow
conditions pilots may encounter during a mission. Modeling an aircraft’s trajectory through this region presents a challenge due to the turbulence present in this
area. Difficulty in rapid modeling limits this flow field’s inclusion in flight training software. Neural network (NN) modeling is a possible method to characterize
the aerodynamics of this flow faster than current techniques. Using the flow past a cylinder case simplifies the ship wake case into a more elementary form. This simplistic model was used to evaluate a NN’s ability to predict turbulent flows.
Computational fluid dynamics (CFD) simulations provided data on the mass flux of air flowing around a cylinder. The CFD solutions then were decomposed
using the generalized finite element method (GFEM). This process coarsens the CFD grid and introduces enrichment functions. The enrichment functions counteract the information lost when the CFD grid is truncated. Each node of the GFEM grid has a set of coefficients that pairs with the enrichment functions and sets each function’s amplitude. Each NN created predicted these nodal coefficients within a specified subspace behind a cylinder. The NNs used the nodal coefficients from the boundary of the subspace to predict the values of the nodes within the subspace.
Four NN model frameworks were created. The first framework predicted the coefficients only within one stationary subspace behind the cylinder. This framework also predicted each velocity component with an independent NN. The second framework used the same stationary subspace but predicted all the velocity components at once using one NN architecture. The third framework randomly sampled subspaces from behind the cylinder and used three NNs to predict each velocity component. The final model also randomly sampled subspaces but only used one model to predict all the mass flux components.
All the models created performed poorly when predicting the nodal coefficients within the specified subspaces. This conclusion points to a more complex prediction method being needed to solve this problem. NNs that account for transient patterns in the predictions should be analyzed moving forward.Office of Naval ResearchNo embargoAcademic Major: Aerospace Engineerin
Refusals and Reinventions: Engendering New Indigenous and Black Life across the Americas
No full textIntroduction: Por/para la vida (for life) -- A full-dignified-just life : insurgent grief -- The wake work of m/otherhood -- Into the trans break -- Shoal ecopoetics and otroas -- Coda: Tuning into the wood wide web.Item embargoed for three year
Differences in the Relationship Between Structural Connectivity and Functional Activation Following Pediatric TBI
Get PDFTraumatic brain injury (TBI) can cause shearing of white matter (WM) pathways and put children at risk of WM degradation. TBI has also been linked with spatial working memory (SWM) deficits, a crucial aspect of executive function that mainly activates the fronto-parietal network (FPN). WM connections within these cortical areas may be integral to support this ability. This project examines the associations among structural connectivity and functional activation in the FPN during a SWM task along major pathways in children with moderate-to-severe TBI (msTBI), complicated-mild TBI (cmTBI), and orthopedic injury (OI) as a control. Forty-one children with msTBI (n=9, Mage=12.04), cmTBI (n=10, Mage=12.93), and OI (n=22, Mage=11.53) underwent MRI in a 3T Siemens scanner, where a T1-weighted structural, 64-direction DTI, and task-based fMRI scans were collected. The SWM task consisted of four characters that lived in a linear space. Children were presented with characters and an event at a certain location, then ranked how quickly one character would arrive. We utilized Freesurfer’s (v7.3.2) TRACULA to perform automated probabilistic tractography on the corpus callosum (CC), cingulum bundles (CB), bilateral anterior thalamic radiations (ATRs), bilateral longitudinal (i.e., ILF, MLF, and SLF I-III), and bilateral uncinate fasciculi (UF). An FPN region of interest was generated based on a meta-analysis map from Neurosynth, corrected using an FDR of 0.01, and binarized. We extracted individual averages of brain activation for three and four characters contrasted to one character. We fitted a general linear model to WM measures along the tracts of interest and added brain activation as a covariate. We found no significant differences in task accuracy (ps>.05) but could confirm WM differences among and between groups (ps<.05). The groups differed in WM microstructure in the rostrum of the CC, and these were related to brain activation in the FPN (ps<.05). Our findings highlight a possible deficit in SWM due to WM disruption after TBI.Clinical and Translational Research Intramural Award and the Eunice Kennedy Shriver National Institute for Child Health and Human Development (K01 HD083459; Dr. Kristen R. Hoskinson)OSU Center for Cognitive and Behavioral Brain Imaging ADNiR Fellowship (Florencia Ontiveros)No embargoAcademic Major: Neuroscienc