Physics Commons^™

Using Dna Flow-Stretching Assay As A Tool To Validate The Tagging Of Dna-Binding Proteins For Single-Molecule Experiments, Miranda Molina, Lindsey E. Way, Zhongqing Ren, Qin Liao, Bianca Guerra, Brandon Shields, Xindan Wang, Hyeongjun Kim

Physics and Astronomy Faculty Publications and Presentations

Highlights

• KCK tag can alter protein properties both quantitatively and qualitatively

• Electrostatic interactions between the KCK tag and DNA contribute to the artifacts

• Adding a short peptide tag to ParB protein does not lead to its in vivo changes

• Single-molecule DNA flow-stretching assay can detect protein property changes

Motivation

Single-molecule fluorescence microscopy has been extensively used in modern biology to define the molecular action of proteins. Appending short peptide tags is a common strategy to enhance fluorescence labeling. Here, we evaluate the impact of a commonly used tag, the lysine-cysteine-lysine (KCK) tag, on protein behavior in single-molecule DNA flow-stretching assay, …

Identification And Characterization Of Bisbenzimide Compounds That Inhibit Human Cytomegalovirus Replication, Nicole Falci Finardi, Hyeongjun Kim, Lee Z. Hernandez, Matthew R. G. Russell, Catherine M-K Ho, Vattipally B. Sreenu, Hannah A. Wenham, Andy Merritt, Blair L. Strang

Physics and Astronomy Faculty Publications and Presentations

The shortcomings of current anti-human cytomegalovirus (HCMV) drugs has stimulated a search for anti-HCMV compounds with novel targets. We screened collections of bioactive compounds and identified a range of compounds with the potential to inhibit HCMV replication. Of these compounds, we selected bisbenzimide compound RO-90-7501 for further study. We generated analogues of RO-90-7501 and found that one compound, MRT00210423, had increased anti-HCMV activity compared to RO-90-7501. Using a combination of compound analogues, microscopy and biochemical assays we found RO-90-7501 and MRT00210423 interacted with DNA. In single molecule microscopy experiments we found RO-90-7501, but not MRT00210423, was able to compact DNA, …

Grappling With Covid-19 By Imposing And Lifting Nonpharmaceutical Interventions In Sri Lanka: A Modeling Perspective, Mahesh Jayaweera, Chamath Dannongoda, Dilum Dilshan, Janith Dissanayake, Hasini Perera, Jagath Manatunge, Buddhika Gunawardana

Physics and Astronomy Faculty Publications and Presentations

The imposition and lifting of non-pharmaceutical interventions (NPIs) to avert the COVID19 pandemic have gained popularity worldwide and will continue to be enforced until herd immunity is achieved. We developed a linear regression model to ascertain the nexus between the time-varying reproduction number averaged over a time window of six days (Rts) and seven NPIs: contact tracing, quarantine efforts, social distancing and health checks, hand hygiene, wearing of facemasks, lockdown and isolation, and health-related supports. Our analysis suggests that the second wave that emerged in Sri Lanka in early October 2020 continued despite numerous NPIs. The model indicates that the …

Identification Of Receptor Ligands In Apo B100 Reveals Potential Functional Domains, Juan Guevara Jr., Jamie Romo Jr., Ernesto Hernandez, Natalia Valentinova Guevara

Physics and Astronomy Faculty Publications and Presentations

LDL, VLDL and other members of the low-density lipoparticles (LLPs) enter cells through a large family of receptors. The actual receptor ligand(s) in apolipoprotein B100, one of the main proteins of LLP, remain(s) unknown. The objective of this study was to identify true receptor ligand(s) in apo B100, a molecule of 4,563 residues. Apo B100 contains 33 analogues of Cardin-Weintraub Arginine/Lysine-based receptor ligand motifs and shares key Lysine motifs and sequence similarity with the LDL receptor-associated protein, RAP, MESD, and heat shock proteins. Eleven FITC-labeled synthetic peptides of 21 – 42 residues, with at least one ligand, were tested for …

Depth-Resolved Multispectral Sub-Surface Imaging Using Multifunctional Upconversion Phosphors With Paramagnetic Properties, Zaven Ovanesyan, L. Christopher Mimun, Gangadharan Ajith Kumar, Brian G. Yust, Chamath Dannongoda, Karen S. Martirosyan, Dhiraj K. Sardar

Physics and Astronomy Faculty Publications and Presentations

Molecular imaging is very promising technique used for surgical guidance, which requires advancements related to properties of imaging agents and subsequent data retrieval methods from measured multispectral images. In this article, an upconversion material is introduced for subsurface near-infrared imaging and for the depth recovery of the material embedded below the biological tissue. The results confirm significant correlation between the analytical depth estimate of the material under the tissue and the measured ratio of emitted light from the material at two different wavelengths. Experiments with biological tissue samples demonstrate depth resolved imaging using the rare earth doped multifunctional phosphors. In …

Analogs Of Ldl Receptor Ligand Motifs In Dengue Envelope And Capsid Proteins As Potential Codes For Cell Entry, Juan Guevara Jr., Jamie Romo Jr., Troy Mcwhorter, Natalia Valentinova Guevara

Physics and Astronomy Faculty Publications and Presentations

It is established that cell entry of low density lipoprotein particles (LLPs) containing Apo B100 and Apo E is mediated by receptors and GAGs. Receptor ligand motifs, XBBBXXBX, XBBXBX, and ΨBΨXB, and mono- and bipartite NLS sequences are abundant in Apo E and Apo B100 as well as in envelope and capsid proteins of Dengue viruses 1-4 (DENV1-4). Synthetic, fluorescence-labeled peptides of sequences in DENV2 envelope protein, and DENV3 capsid that include these motifs were used to conduct a qualitative assessment of cell binding and entry capacity using …

Mri Characterization Of Cobalt Dichloride-N-Acetyl Cysteine (C4) Contrast Agent Marker For Prostate Brachytherapy, Tze Yee Lim, R. Jason Stafford, Rajat J. Kudchadker, Madhuri Sankaranarayanapillai, Geoffrey Ibbott, Arvind Rao, Karen S. Martirosyan, Steven J. Frank

Physics and Astronomy Faculty Publications and Presentations

Brachytherapy, a radiotherapy technique for treating prostate cancer, involves the implantation of numerous radioactive seeds into the prostate. While the implanted seeds can be easily identified on a CT image, distinguishing the prostate and surrounding soft tissues is not as straightforward. Magnetic Resonance Imaging (MRI) offers superior anatomical delineation, but the seeds appear as dark voids and are difficult to identify, thus creating a conundrum. Cobalt dichloride-N-acetylcysteine (C4) has previously been shown to be promising as an encapsulated contrast agent marker. We performed spin-lattice relaxation time (T1) and spin-spin relaxation time (T2) measurements of C4 solutions with varying cobalt dichloride …

A Biodistribution And Toxicity Study Of Cobalt Dichloride–Nacetyl Cysteine (C4) As An Implantable Mri Marker For Prostate Cancer Treatment, Steven J. Frank, Mary J. Johansen, Karen S. Martirosyan, Mihai Gagea, Carolyn S. Van Pelt

Physics and Astronomy Faculty Publications and Presentations

Purpose—C4, a cobalt dichloride–N-acetyl cysteine complex, is being developed as a positivesignal magnetic resonance imaging (MRI) marker to localize implanted radioactive seeds in prostate brachytherapy. We evaluated the toxicity and biodistribution of C4 in rats with the goal of simulating systemic effects of potential leakage from C4 MRI markers within the prostate.

Methods—9 μl doses (equivalent to leakage from 120 markers in a human) of control (0.9% sodium chloride), 1% (proposed for clinical use) and 10% C4 solution were injected into the prostates of male Sprague-Dawley rats via laparotomy. Organ toxicity and cobalt disposition in plasma, tissues, feces …

Thermosensitive Magnetic Nanoparticles For Self-Controlled Hyperthermia Cancer Treatment, Karen S. Martirosyan

Physics and Astronomy Faculty Publications and Presentations

Magnetic nanoparticles show remarkable phenomena such as superparamagnetism, high field irreversibility and high saturation magnetization [1]. The study of magnetic nanoparticles has been a very active research field due to many important applications such as drug delivery, imaging and hyperthermia cancer treatment [2]. Hyperthermia has been used for many years to treat a wide variety of tumors in patients and used as well as an adjunct to cancer radiotherapy or chemotherapy [3,4]. Its use is based on the fact that tumor cells are more sensitive to temperature in the range of 42–45°C (which yields necrosis, coagulation, or carbonization) than normal …