Biochemistry, Biophysics, and Structural Biology Commons^™

In Silico Identification Of Potential Inhibitors Of The Sars‑Cov‑2 Nucleocapsid Through Molecular Docking‑Based Drug Repurposing, Rukhsar Afreen, Saleem Iqbal, Ab Rauf Shah, Heena Afreen, Maitreyi College, Mohd. Shkir

Department of Biochemistry: Faculty Publications

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic, and its effects on people worldwide continue to grow. Protein-targeted therapeutics are currently unavailable for this virus. As with other coronaviruses, the nucleocapsid (N) protein is the most conserved RNA-binding structural protein of SARS-CoV-2. The N protein is an appealing target because of its functional role in viral transcription and replication. Therefore, molecular docking method for structure-based drug design was used to investigate the binding energy and binding modes of various anti-N inhibitors in depth. The inhibitors selected were originally developed to target stress granules and other molecules involved in RNA …

Modelling Juxtacrine Mediated Tumor-Fibroblast Interactions In Three-Dimensional Co-Cultures Of Pancreatic Ductal Adenocarcinoma, Eric Struth

Graduate Masters Theses

The tumor-microenvironment is a rich and complex milieu of mutated cancer cells and otherwise healthy cells engaged in dynamic interactions. Fibroblasts, the most abundant cellular component of human connective tissues, are implicated in a tumor promoting process known as stromal crosstalk. This stromal crosstalk is driven by numerous signaling pathways including contact mediated juxtacrine signaling and directed long distance paracrine signaling. Recent research suggests these signaling pathways are particularly important for two distinct types of fibroblasts. Mayofibroblastic cancer associated fibroblasts (MyCAFs) are associated with tumor suppression and shown to rely primarily on juxtacrine signaling, while inflammatory cancer associated fibroblasts (iCAFs) …

The Effects Of Aging On Wound Healing And Limb Regeneration In The Axolotl, Hande Sahin

Graduate Masters Theses

The Mexican axolotl is capable of regenerating various parts of its body and maintains this capacity throughout its entire life. Although this ability is sustained through adulthood, multiple regenerative processes appear to be negatively affected by aging. Here, we focus on evaluating the effect of aging on the rate of wound healing and limb regeneration. We have developed new in vivo, and ex vivo assays to characterize wound healing and identify differences between young and aged animals during this process. We have also characterized morphological features of mature skin from both groups of animals and although there are no obvious …

Targeting Heat Shock 27 Kda Protein Induces Androgen Receptor Degradation, Yaxin Li

ETD Archive

Glioblastoma (GBM) is the most common and aggressive brain tumor, with very poor prognosis. Androgen receptor (AR) plays a significant role in the progression of GBM, and anti-androgen agents have the potential to be used for the treatment of GBM. However, AR mutation commonly happens in GBM, which makes the anti-androgen agents less effective. Heat shock 27 kDa protein (HSP27) is a well-documented chaperone protein to stabilize AR. Inhibition of HSP27 results in AR degradation regardless the mutation status of AR, which makes HSP27 a good target to abolish AR in GBM. Identified compound I ((N-(3-((2,5-dimethoxybenzyl)oxy)-4-(methylsulfonamido) phenyl)-4-methoxybenzamide) inhibits GBM cell …

A Concise Synthetic Method For Constructing 3-Substituted Piperazine-2-Acetic Acid Esters From 1,2-Diamines, Srinivas Chamakuri, Sunny Ann Tang, Kevin A Tran, Shiva Krishna Reddy Guduru, Peter K Bolin, Kevin R Mackenzie, Damian W Young

Faculty, Staff and Students Publications

We report a short synthetic route for synthesizing 2,3-substituted piperazine acetic acid esters. Optically pure amino acids were efficiently converted into 1,2-diamines that could be utilized to deliver the title 2,3-substituted piperazines in five steps with a high enantiomeric purity. The novel route facilitated, for the first time, the synthesis of 3-phenyl substituted-2-piperazine acetic acid esters that were difficult to achieve using other methods; however, in this case, the products underwent racemization.

Maf1, A Repressor Of Rna Polymerase Iii-Dependent Transcription, Regulates Bone Mass, Ellen Phillips, Naseer Ahmad, Li Sun, James Iben, Christopher J Walkey, Aleksandra Rusin, Tony Yuen, Clifford J Rosen, Ian M Willis, Mone Zaidi, Deborah L Johnson

Faculty, Staff and Students Publications

MAF1, a key repressor of RNA polymerase (pol) III-mediated transcription, has been shown to promote mesoderm formation in vitro. Here, we show that MAF1 plays a critical role in regulating osteoblast differentiation and bone mass. Global deletion of MAF1 (Maf1-/- mice) produced a high bone mass phenotype. However, osteoblasts isolated from Maf1-/- mice showed reduced osteoblastogenesis ex vivo. Therefore, we determined the phenotype of mice overexpressing MAF1 in cells from the mesenchymal lineage (Prx1-Cre;LSL-MAF1 mice). These mice showed increased bone mass. Ex vivo, cells from these mice showed enhanced osteoblastogenesis concordant with their high …

Cysteine Metallochemistry And Metal Binding: Quantification Of The Thermodynamic Foundations Of Cellular Homeostasis, Matthew R. Mehlenbacher

Dartmouth College Ph.D Dissertations

Metals are required for life. Many metalloproteins contain cysteine in their metal-binding site (MBS) and cysteines are unique in that they are reactive, and strongly bind certain metals, which aid in metal selectivity and specificity. Using isothermal titration calorimetry (ITC), the thermodynamic foundation for metal binding, cellular protection, and transcriptional regulation, which all utilize cysteines in their MBS, are quantified.

In bacteria there are metalloprotein pathways that actively uptake mercury, which are regulated by the metalloregulatory protein MerR. MerR de-represses the transcription of these mer proteins in a metal-dependent manner. Using ITC, the thermodynamic foundation of the negative allosteric coupling …

Targeting Aberrant Replication And Dna Repair Events For Treating Breast Cancers, Subapriya Rajamanickam, Jun Hyoung Park, Panneerdoss Subbarayalu, Santosh Timilsina, Kaitlyn Bates, Pooja Yadav, Saif S R Nirzhor, Vijay Eedunuri, Tabrez A Mohammad, Kwang Hwa Jung, Benjamin Onyeagucha, Nourhan Abdelfattah, Raymond Benevides, Grace Lee, Yidong Chen, Ratna Vadlamudi, Andrew Brenner, Virginia Kaklamani, Ismail Jatoi, John Kuhn, Robert Hromas, Yogesh K Gupta, Benny A Kaipparettu, Jack L Arbiser, Manjeet K Rao

Faculty, Staff and Students Publications

The major limitations of DNA-targeting chemotherapy drugs include life-threatening toxicity, acquired resistance and occurrence of secondary cancers. Here, we report a small molecule, Carbazole Blue (CB), that binds to DNA and inhibits cancer growth and metastasis by targeting DNA-related processes that tumor cells use but not the normal cells. We show that CB inhibits the expression of pro-tumorigenic genes that promote unchecked replication and aberrant DNA repair that cancer cells get addicted to survive. In contrast to chemotherapy drugs, systemic delivery of CB suppressed breast cancer growth and metastasis with no toxicity in pre-clinical mouse models. Using PDX and ex …

A New Insight Into Fungal Cell Wall Architecture By Functional Genomics And Solid-State Nmr Along With Recent Advancements In Dynamic Nuclear Polarization For Analyzing Biomolecules, Arnab Chakraborty

LSU Master's Theses

This dissertation summarizes the findings related to the way by which supramolecular architecture of fungal cell wall changes with genetic mutation, dispensing genes responsible for biosynthesis of cell wall polysaccharides. This is necessary because without perfect picture of how supramolecular assembly changes with genetic mutation it is hard to assess new anti-fungal targets. Alongside this we have highlighted how recent advancement into Dynamic Nuclear Polarization (DNP) methods improved characterization of biomolecules both in case of labeled and unlabeled samples.

First study utilized Solid-state NMR (SSNMR) which is a non-destructive technique hence enabled us for the first time to deduce how …

Flippase Inhibitors As Antimicrobial Agents, Robert Tancer

Seton Hall University Dissertations and Theses (ETDs)

Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the …

Alterations Of The Gut Microbial Community Structure And Function With Aging In The Spontaneously Hypertensive Stroke Prone Rat, Huanan Shi, James W Nelson, Sharon Phillips, Joseph F Petrosino, Robert M Bryan, David J Durgan

Faculty, Staff and Students Publications

Gut dysbiosis, a pathological imbalance of bacteria, has been shown to contribute to the development of hypertension (HT), systemic- and neuro-inflammation, and blood-brain barrier (BBB) disruption in spontaneously hypertensive stroke prone rats (SHRSP). However, to date individual species that contribute to HT in the SHRSP model have not been identified. One potential reason, is that nearly all studies of the SHRSP gut microbiota have analyzed samples from rats with established HT. The goal of this study was to examine the SHRSP gut microbiota before, during, and after the onset of hypertension, and in normotensive WKY control rats over the same …

Inferring Dynamics Of Biological Systems, Tracey G. Oellerich

Biology and Medicine Through Mathematics Conference

No abstract provided.

Guard-Cell-Targeted Overexpression Of Arabidopsis Hexokinase 1 Can Improve Water Use Efficiency In Field-Grown Tobacco Plants, Liana G. Acevedo-Siaca, Katarzyna Glowacka, Steven M. Driever, Coralie E. Salesse-Smith, Nitsan Lugassi, David Granot, Stephen P. Long, Johannes Kromdijk

Department of Biochemistry: Faculty Publications

Water deficit currently acts as one of the largest limiting factors for agricultural productivity worldwide. Additionally, limitation by water scarcity is projected to continue in the future with the further onset of effects of global climate change. As a result, it is critical to develop or breed for crops that have increased water use efficiency and that are more capable of coping with water scarce conditions. However, increased intrinsic water use efficiency (iWUE) typically brings a trade-off with CO₂ assimilation as all gas exchange is mediated by stomata, through which CO₂ enters the leaf while water vapor exits. …

Cell‑Controlled Dynamic Surfaces For Skeletal Stem Cell Growth And Differentiation, Hilary J. Anderson, Jugal Kishore Sahoo, Julia Wells, Sebastiaan Van Nuffel, Hala S. Dhowre, Richard O. C. Oreffo, Mischa Zelzer, Rein V. Ulijn, Matthew J. Dalby

Advanced Science Research Center

Skeletal stem cells (SSCs, or mesenchymal stromal cells typically referred to as mesenchymal stem cells from the bone marrow) are a dynamic progenitor population that can enter quiescence, self-renew or differentiate depending on regenerative demand and cues from their niche environment. However, ex vivo, in culture, they are grown typically on hard polystyrene surfaces, and this leads to rapid loss of the SSC phenotype. While materials are being developed that can control SSC growth and differentiation, very few examples of dynamic interfaces that reflect the plastic nature of the stem cells have, to date, been developed. Achieving such interfaces is …

Du Undergraduate Showcase: Research, Scholarship, And Creative Works: Abstracts, Emma Aggeler, Elena Arroway, Daisy T. Booker, Justin Bravo, Kyle Bucholtz, Megan Burnham, Nicole Choi, Spencer Cockerell, Rosie Contino, Jackson Garske, Kaitlyn Glover, Caroline Hamilton, Haley Hartmann, Madalyne Heiken, Colin Holter, Leah Huzjak, Alyssa Jeng, Cole Jernigan, Chad Kashiwa, Adelaide Kerenick, Emily King, Abigail Langeberg, Maddie Leake, Meredith Lemons, Alec Mackay, Greer Mckinley, Ori Miller, Guy Milliman, Katherine Miromonti, Audrey Mitchell, Lauren Moak, Megan Morrell, Gelella Nebiyu, Zdenek Otruba, Toni V. Panzera, Kassidy Patarino, Sneha Patil, Alexandra Penney, Kevin Persky, Caitlin Pham, Gabriela Recinos, Mary Ringgenberg, Chase Routt, Olivia Schneider, Roman Shrestha, Arlo Simmerman, Alec Smith, Tessa Smith, Nhi-Lac Thai, Kyle Thurmann, Casey Tindall, Amelia Trembath, Maria Trubetskaya, Zachary Vangelisti, Peter Vo, Abby Walker, David Winter, Grayden Wolfe, Leah York

DU Undergraduate Research Journal Archive

Abstracts from the DU Undergraduate Showcase.

The Use Of Silica Nanoparticles For Controlled Drug Delivery Of Nicotine, Jennifer C. Iwenofu

Honors College Theses

Drug molecules can be administered in different ways to the human body. Nanotechnology stands out over other alternatives by delivering drugs to specific locations and reducing reactivity time. In this research, the hydrogen bond between silica nanoparticles and the drug molecule, nicotine, were studied to controllably deliver nicotine by varying pH values.

Isolation And Characterization Of Α-Hcd7 Scfv Expressing Exosomes And Synthesis Of Hybrid Exosome-Liposome For Analyses, Sahil Patel

Biotechnology Theses

The goal of this thesis project is to isolate and characterize exosomes that express anti-human CD7 (α-hCD7) single chain variable fragment (scFv), which will be further utilized for T celltargeted gene editing. To reach this goal, exosomes from HEK 293 cells and Jurkat cells were isolated and characterized with different methodologies. To obtain α-hCD7 scFv-expressing exosomes, the HEK 293 cells were subjected to transfection of custom-plasmid pDisplay-αhCD7 scFv, and the expression of α-hCD7 scFv on the HEK 293-derived exosomes were then confirmed by immunogold staining, western blotting, and flow cytometry. To transfect 293 cells, calcium phosphate transfection was utilized, and …

Contributions Of Vibrational Spectroscopy To Virology: A Review, Iqra Chaudhary, Naomi Jackson, Denise Denning, Luke O'Neill, Hugh Byrne

Articles

Vibrational spectroscopic techniques, both infrared absorption and Raman scattering, are high precision, label free analytical techniques which have found applications in fields as diverse as analytical chemistry, pharmacology, forensics and archeometrics and, in recent times, have attracted increasing attention for biomedical applications. As analytical techniques, they have been applied to the characterisation of viruses as early as the 1970s, and, in the context of the coronavirus disease 2019 (COVID-19) pandemic, have been explored in response to the World Health Organisation as novel methodologies to aid in the global efforts to implement and improve rapid screening of viral infection. This review …

Investigation Of The Direct Effect Of A Precision Ascophyllum Nodosum Biostimulant On Nitrogen Use Efficiency In Wheat Seedlings, Łukasz Łangowski, Oscar Goñi, Elomofe Ikuyinminu, Ewan Feeney, Shane O'Connell

Publications

Reduction in the greenhouse gas (GHG) emissions and nitrogen (N) pollution of ground water by improving nitrogen use efficiency (NUE) in crops has become an intensively investigated research topic in pursuit of a more sustainable future. Although, distinct solutions have been proposed there are only a few reports documenting the detailed interplay between observed plant growth dynamics and changes in plant N related transcriptional and biochemical changes. It was previously demonstrated that the application of a formulated biostimulant (PSI-362) derived from Ascophyllum nodosum (ANE) improves N uptake in Arabidopsis thaliana and in barley. In this study, the effect of PSI-362 …

Mechanisms Of Voltage-Gated Sodium Channel (Nav1.5) Regulation By Intracellular Fgfs, Paweorn Angsutararux

McKelvey School of Engineering Graduate Student Theses & Dissertations

Voltage-gated sodium channels (NaV) conduct the inward current responsible for the initiation and propagation of the electrical signals in myocytes and neurons, known as action potentials (AP). Precise regulation of cardiac NaV1.5 opening and closing is essential for maintaining a normal heart beat. A disruption of NaV1.5 function, especially of its inactivation after opening, results in inherited cardiac arrhythmias such as Long QT Type 3 (LQT3) syndrome. This pathology is caused by an increase in the late INa that enters myocytes later in the AP and prolongs its duration. Late INa is also enhanced in acquired diseases such as heart …