Biochemistry, Biophysics, and Structural Biology Commons^™

Prion-Like C-Terminal Domain Of Tdp-43 And Α-Synuclein Interact Synergistically To Generate Neurotoxic Hybrid Fibrils, Shailendra Dhakal, Courtney E. Wyant, Hannah E. George, Sarah E. Morgan, Vijayaraghavan Rangachari

Faculty Publications

Aberrant aggregation and amyloid formation of tar DNA binding protein (TDP-43) and α-synuclein (αS) underlie frontotemporal dementia (FTD) and Parkinson’s disease (PD), respectively. Amyloid inclusions of TDP-43 and αS are also commonly co-observed in amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB) and Alzheimer disease (AD). Emerging evidence from cellular and animal models show colocalization of the TDP-43 and αS aggregates, raising the possibility of direct interactions and co-aggregation between the two proteins. In this report, we set out to answer this question by investigating the interactions between αS and prion-like pathogenic C-terminal domain of TDP-43 (TDP-43 PrLD). PrLD …

A Polyaniline-Based Sensor Of Nucleic Acids, Partha Sengupta, Jared Gloria, Marcus K. Parker, Alex S. Flynt

Faculty Publications

Detection of nucleic acids is at the center of diagnostic technologies used in research and the clinic. Standard approaches used in these technologies rely on enzymatic modification that can introduce bias and artifacts. A critical element of next generation detection platforms will be direct molecular sensing, thereby avoiding a need for amplification or labels. Advanced nanomaterials may provide the suitable chemical modalities to realize label-free sensors. Conjugated polymers are ideal for biological sensing, possessing properties compatible with biomolecules and exhibit high sensitivity to localized environmental changes. In this article, a method is presented for detecting nucleic acids using the electroconductive …

Functional, Sub-100 Nm Polymer Nanoparticles Via Thiol-Ene Miniemulsion Photopolymerization, Douglas Amato, Dahlia Amato, Alex S. Flynt, Derek L. Patton

Faculty Publications

In this work, sub-100 nm crosslinked polythioether nanoparticles were synthesized via thiol–ene photopolymerization in miniemulsion using high-energy homogenization. The effects of the miniemulsion formulation and homogenization parameters – including inhibitor concentration, surfactant concentration, organic weight fraction, ultrasonication time and amplitude – on nanoparticle size and size distribution were investigated. Thiol–ene nanoparticles with a mean particle diameter of 46 nm were obtained under optimized conditions for the current system at 2.5 wt% organic fraction and 20 mM surfactant concentration. In an effort to demonstrate potential utility of thiol–ene nanoparticles, we exploit the step-growth radical mechanism of thiol–ene photopolymerization under non-stoichiometric conditions …

Designing And Evaluating The Multicom Protein Local And Global Model Quality Prediction Methods In The Casp10 Experiment, Renzhi Cao, Zheng Wang, Jianlin Cheng

Faculty Publications

Background: Protein model quality assessment is an essential component of generating and using protein structural models. During the Tenth Critical Assessment of Techniques for Protein Structure Prediction (CASP10), we developed and tested four automated methods (MULTICOM-REFINE, MULTICOM-CLUSTER, MULTICOM-NOVEL, and MULTICOM-CONSTRUCT) that predicted both local and global quality of protein structural models.

Results: MULTICOM-REFINE was a clustering approach that used the average pairwise structural similarity between models to measure the global quality and the average Euclidean distance between a model and several top ranked models to measure the local quality. MULTICOM-CLUSTER and MULTICOM-NOVEL were two new support vector machine-based …

Biocompatibility Of Synthetic Poly(Ester Urethane)/Polyhedral Oligomeric Silsesquioxane Matrices With Embryonic Stem Cell Proliferation And Differentiation, Yan-Lin Guo, Wenshou Wang, Joshua U. Otaigbe

Faculty Publications

Incorporation of polyhedral oligomeric silsesquioxanes (POSS) into poly(ester urethanes) (PEU) as a building block results in a PEU/POSS hybrid polymer with increased mechanical strength and thermostability. An attractive feature of the new polymer is that it forms a porous matrix when cast in the form of a thin film, making it potentially useful in tissue engineering. In this study, we present detailed microscopic analysis of the PEU/POSS matrix and demonstrate its biocompatibility with cell culture. The PEU/POSS polymer forms a continuous porous matrix with open pores and interconnected grooves. From SEM image analysis, it is calculated that there are about …

Mouse Embryonic Stem Cells Lacking P38Α And P38Δ Can Differentiate To Endothelial Cells, Smooth Muscle Cells, And Epithelial Cells, Samujjwal Chakraborty, Baobin Kang, Faqing Huang, Yan-Lin Guo

Faculty Publications

The p38 mitogen-activated protein (MAP) kinases (p38) are important signaling molecules that regulate various cellular processes. Four isoforms of p38 family, p38α, p38β, p38γ, and p38δ, have been identified in mammalian cells. Previous studies have shown that p38α knockout is embryonic lethal in mice. At the cellular level, p38α is abundantly expressed in mouse embryonic stem cells (ESCs), but p38α knockout (p38α-/-) ESCs can differentiate to endothelial cells (ECs), smooth muscle cells (SMCs), and neurons. We speculate that the lost function of p38α in p38α-/- ESCs may be compensated for by the redundant function of other isoforms. To test this …

Reproductive Function For A C-Terminus Extended, Male-Transmitted Cytochrome C Oxidase Subunit Ii Protein Expressed In Both Spermatozoa And Eggs, Rumela Chakrabarti, Jennifer M. Walker, E.G. Chapman, S.P. Shepardson, R.J. Trdan, J.P. Curole, G.T. Watters, D.T. Stewart, S. Vijayaraghavan, W.R. Hoeh

Faculty Publications

Our previous study documented expression of a male-transmitted cytochrome c oxidase subunit II protein (MCOX2), with a C-terminus extension (MCOX2e), in unionoidean bivalve testes and sperm mitochondria. Here, we present evidence demonstrating that MCOX2 is seasonally expressed in testis, with a peak shortly before fertilization that is independent of sperm density. MCOX2 is localized to the inner and outer sperm mitochondrial membranes and the MCOX2 antibody’s epitope is conserved across >65 million years of evolution. We also demonstrate the presence of male-transmitted mtDNA and season-specific MCOX2 spatial variation in ovaries. We hypothesize …

Two Glucose-Sensing Pathways Converge On Rgt1 To Regulate Expression Of Glucose Transporter Genes In Saccharomyces Cerevisiae, Jeong-Ho Kim, Mark Johnston

Faculty Publications

The yeast Saccharomyces cerevisiae deploys two different types of glucose sensors on its cell surface that operate in distinct glucose signaling pathways: the glucose transporter-like Snf3 and Rgt2 proteins and the Gpr1 receptor that is coupled to Gpa2, a G-protein α subunit. The ultimate target of the Snf3/Rgt2 pathway is Rgt1, a transcription factor that regulates expression of HXT genes encoding glucose transporters. We have found that the cAMP-dependent protein kinase A (PKA), which is activated by the Gpr1/Gpa2 glucose-sensing pathway and by a glucose-sensing pathway that works through Ras1 and Ras2, catalyzes phosphorylation of Rgt1 and regulates its function. …

Some Plant Leaves Have Orientation-Dependent Epr And Nmr Spectra, Douglas C. Mccain, Ted C. Selig, Govindjee, John L. Markley

Faculty Publications

Proton nuclear magnetic resonance (¹H NMR) spectra of leaves from 50 plant species were obtained at a spectrometer frequency of 470 MHz. Water present in leaf samples gives rise to characteristic spectral patterns. Most species show only one broad ¹H NMR peak; however, the leaves of some plants display complex, orientation-dependent spectra in which a common three-line pattern is discerned. The pattern varies with the angle between the leaf surface and the external magnetic field. Proton relaxation measurements show the presence of at least two water compartments in the leaves. The compartments are responsible for different components …