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Item Analysis of Pseudo-Symmetry in Protein Homo-Oligomers(2018-12) Rajendran, Catherine Jenifer Rajam; Fang, Shiaofen; Liu, Jing-Yuan; Liang, YaoSymmetry plays a significant role in protein structural assembly and function. This is especially true for large homo-oligomeric protein complexes due to stability and finite control of function. But, symmetry in proteins are not perfect due to unknown reasons and leads to pseudosymmetry. This study focuses on symmetry analysis of homo-oligomers, specifically homo-dimers, homo-trimers and homo-tetramers. We defined Off Symmetry (OS) to measure the overall symmetry of the protein and Structural Index (SI) to quantify the structural difference and Assembly Index (AI) to quantify the assembly difference between the subunits. In most of the symmetrical homo-trimer and homo-tetramer proteins, Assembly Index contributes more to Off Symmetry and in the case of homo-dimer, Structural index contributes more than the Assembly Index. The main chain atom Carbon-Alpha (CA) is more symmetrical than the first side chain atom Carbon-Beta (CB), suggesting protein mobility may contribute to the pseudosymmetry. In addition, Pearson coefficient correlation between their Off-Symmetry and their respective atoms B-Factor (temperature factor) are calculated. We found that the individual residues of a protein in all the subunits are correlated to their average B-Factor of these residues. The correlation with BFactor is stronger in Structure Index than Assembly Index. All these results suggest that protein dynamics play an important role and therefore a larger off-symmetry may indicate a more mobile and flexible protein complex.Item Comparative Analysis of Alzheimer's Disease Cerebrospinal Fluid Biomarkers Measurement by Multiplex SOMAscan Platform and Immunoassay-Based Approach(IOS Press, 2022) Timsina, Jigyasha; Gomez-Fonseca, Duber; Wang, Lihua; Do, Anh; Western, Dan; Alvarez, Ignacio; Aguilar, Miquel; Pastor, Pau; Henson, Rachel L.; Herries, Elizabeth; Xiong, Chengjie; Schindler, Suzanne E.; Fagan, Anne M.; Bateman, Randall J.; Farlow, Martin; Morris, John C.; Perrin, Richard J.; Moulder, Krista; Hassenstab, Jason; Vöglein, Jonathan; Chhatwal, Jasmeer; Mori, Hiroshi; Alzheimer’s Disease Neuroimaging Initiative; Dominantly Inherited Alzheimer Network Consortia; Sung, Yun Ju; Cruchaga, Carlos; Neurology, School of MedicineBackground: The SOMAscan assay has an advantage over immunoassay-based methods because it measures a large number of proteins in a cost-effective manner. However, the performance of this technology compared to the routinely used immunoassay techniques needs to be evaluated. Objective: We performed comparative analyses of SOMAscan and immunoassay-based protein measurements for five cerebrospinal fluid (CSF) proteins associated with Alzheimer's disease (AD) and neurodegeneration: NfL, Neurogranin, sTREM2, VILIP-1, and SNAP-25. Methods: We compared biomarkers measured in ADNI (N = 689), Knight-ADRC (N = 870), DIAN (N = 115), and Barcelona-1 (N = 92) cohorts. Raw protein values were transformed using z-score in order to combine measures from the different studies. sTREM2 and VILIP-1 had more than one analyte in SOMAscan; all available analytes were evaluated. Pearson's correlation coefficients between SOMAscan and immunoassays were calculated. Receiver operating characteristic curve and area under the curve were used to compare prediction accuracy of these biomarkers between the two platforms. Results: Neurogranin, VILIP-1, and NfL showed high correlation between SOMAscan and immunoassay measures (r > 0.9). sTREM2 had a fair correlation (r > 0.6), whereas SNAP-25 showed weak correlation (r = 0.06). Measures in both platforms provided similar predicted performance for all biomarkers except SNAP-25 and one of the sTREM2 analytes. sTREM2 showed higher AUC for SOMAscan based measures. Conclusion: Our data indicate that SOMAscan performs as well as immunoassay approaches for NfL, Neurogranin, VILIP-1, and sTREM2. Our study shows promise for using SOMAscan as an alternative to traditional immunoassay-based measures. Follow-up investigation will be required for SNAP-25 and additional established biomarkers.Item Positive correlation between measures of habitual responding and motivated responding in mice(Wiley, 2024) Bryant, Kathleen G.; Barker, Jacqueline M.; Anatomy, Cell Biology and Physiology, School of MedicineHabit and motivation are thought to be separate processes, with motivated behavior often considered to be goal directed, whereas habits are defined by the absence of goal-directed control over behavior. However, there has been increasing interrogation of the binary nature of habitual versus goal-directed behavior. Furthermore, although drug and alcohol exposure can promote the formation of habits, drug seeking itself can also be highly flexible, pointing toward the need for complex consideration of the parallel processes that drive behavior. The goal of the current study was to determine whether there was a relation between motivation-as measured by progressive ratio-and habit-as measured by contingency degradation-and whether this relation was affected by ethanol exposure history and sex. The results showed that these measures were positively correlated such that greater contingency insensitivity was associated with achieving higher break points on the progressive-ratio task. However, this relation depended on reinforcement schedule history, ethanol exposure history, and sex. These point to potential relations between measures of habit and motivation and stress the importance of carefully parsing behavioral findings and assays. These findings are also expected to inform future substance use research, as drug history may affect these relations.