Other Biochemistry, Biophysics, and Structural Biology Commons^™

Editorial: Rising Stars In Microbial Physiology And Metabolism: 2022, Nicole R. Buan, Ulrike Kappler

Department of Biochemistry: Faculty Publications

This Research Topic was initiated to highlight work by young authors, the rising stars in the field of microbial physiology and metabolism. Microbial physiology and metabolism is an interdisciplinary field of research that seeks to uncover how the metabolic pathways of a cell work together to determine cell fate and function, whether that be growth, replication, pathogenicity, predation, respiration and fermentation, homeostasis or death. Ultimately, researchers like the ones featured here seek to integrate biological information and physicochemical parameters to try to find the underlying rules governing microbial function so that we can understand, predict and design microbes and microbial …

Chloroquine And Cytosolic Galectins Affect Endosomal Escape Of Antisense Oligonucleotides After Stabilin-Mediated Endocytosis, Ekta Pandey, Ed Harris

Department of Biochemistry: Faculty Publications

Non-DNA-binding Stabilin-2/HARE receptors expressed on liver sinusoidal endothelial cells specifically bind to and internalize several classes of phosphorothioate antisense oligonucleotides (PS-ASOs). After Stabilin-mediated uptake, PS-ASOs are trafficked within endosomes (>97%–99%), ultimately resulting in destruction in the lysosome. The ASO entrapment in endosomes lowers therapeutic efficacy, thereby increasing the overall dose for patients. Here, we use confocal microscopy to characterize the intracellular route transverse by PS-ASOs after Stabilin receptor-mediated uptake in stable recombinant Stabilin-1 and -2 cell lines. We found that PS-ASOs as well as the Stabilin-2 receptor transverse the classic path: clathrincoated vesicle-early endosome-late endosome-lysosome. Chloroquine exposure facilitated endosomal …

A Novel Method Of Rapid Detection For Heavy Metal Copper Ion Via A Specific Copper Chelator Bathocuproinedisulfonic Acid Disodium Salt, Yali Wang, Tinglin Ma, Joseph Brake, Zhaoyue Sun, Jiayu Huang, Jing Li, Xiaobin Wu

Department of Biochemistry: Faculty Publications

The extensive usage and production of copper may lead to toxic effects in organisms due to its accumulation in the environment. Traditional methods for copper detection are time consuming and infeasible for field usage. It is necessary to discover a real-time, rapid and economical method for detecting copper to ensure human health and environmental safety. Here we developed a colorimetric paper strip method and optimized spectrum method for rapid detection of copper ion based on the specific copper chelator bathocuproinedisulfonic acid disodium salt (BCS). Both biological assays and chemical methods verified the specificity of BCS for copper. The optimized reaction …

Putrescine Detected In Strains Of Staphylococcus Aureus, Javier Seravalli, Frank Portugal

Department of Biochemistry: Faculty Publications

Most forms of life, including the archaea, bacteria, and eukaryotes synthesize the polyamine putrescine. Although putrescine is widely distributed, several Gram-positive bacteria, including Staphylococcus aureus (S. aureus), appear to be the exceptions. We report here that strains of S. aureus can produce the polyamine putrescine, as well as the derivative N-acetyl-putrescine. Three strains of S. aureus from the American Type Culture Collection (ATCC), one strain listed in the National Center for Biotechnology Information (NCBI) database, whose genomic sequence is well defined, and well as eight strains from S. aureus-induced brain abscesses of individual patients from multiple …

Type Iv Pilus-Mediated Inhibition Of Acinetobacter Baumannii Biofilm Formation By Phenothiazine Compounds, Nam Vo, Benjamin S. Sidner, Yafan Yu, Kurt H. Piepenbrink

Department of Biochemistry: Faculty Publications

Infections by pathogenic Acinetobacter species represent a significant burden on the health care system, despite their relative rarity, due to the difficulty of treating infections through oral antibiotics. Multidrug resistance is commonly observed in clinical Acinetobacter infections and multiple molecular mechanisms have been identified for this resistance, including multidrug efflux pumps, carbapenemase enzymes, and the formation of bacterial biofilm in persistent infections. Phenothiazine compounds have been identified as a potential inhibitor of type IV pilus production in multiple Gram-negative bacterial species. Here, we report the ability of two phenothiazines to inhibit type IV pilus-dependent surface (twitching) motility and biofilm formation …

Hematopoietic Stem Cells And Betaherpesvirus Latency, Lindsey B. Crawford

Department of Biochemistry: Faculty Publications

The human betaherpesviruses including human cytomegalovirus (HCMV), human herpesvirus (HHV)-6a and HHV-6b, and HHV-7 infect and establish latency in CD34+ hematopoietic stem and progenitor cells (HPCs). The diverse repertoire of HPCs in humans and the complex interactions between these viruses and host HPCs regulate the viral lifecycle, including latency. Precise manipulation of host and viral factors contribute to preferential maintenance of the viral genome, increased host cell survival, and specific manipulation of the cellular environment including suppression of neighboring cells and immune control. The dynamic control of these processes by the virus regulate inter- and intra-host signals critical to the …

Solving The Cable Equation, A Second-Order Time Dependent Pde For Non-Ideal Cables With Action Potentials In The Mammalian Brain Using Kss Methods, Nirmohi Charbe

Master's Theses

In this thesis we shall perform the comparisons of a Krylov Subspace Spectral method with Forward Euler, Backward Euler and Crank-Nicolson to solve the Cable Equation. The Cable Equation measures action potentials in axons in a mammalian brain treated as an ideal cable in the first part of the study. We shall subject this problem to the further assumption of a non-ideal cable. Assume a non-uniform cross section area along the longitudinal axis. At the present time, the effects of torsion, curvature and material capacitance are ignored. There is particular interest to generalize the application of the PDEs including and …

Bola3 And Nfu1 Link Mitoribosome Iron-Sulfur Cluster Assembly To Multiple Mitochondrial Dysfunctions Syndrome, Hui Zhong, Alexandre Janer, Oleh Khalimonchuk, Hana Antonicka, Eric Shoubridge, Antoni Barrientos

Department of Biochemistry: Faculty Publications

The human mitochondrial ribosome contains three [2Fe-2S] clusters whose assembly pathway, role, and implications for mitochondrial and metabolic diseases are unknown. Here, structure-function correlation studies show that the clusters play a structural role during mitoribosome assembly. To uncover the assembly pathway, we have examined the effect of silencing the expression of Fe-S cluster biosynthetic and delivery factors on mitoribosome stability. We find that the mitoribosome receives its [2Fe-2S] clusters from the GLRX5-BOLA3 node. Additionally, the assembly of the small subunit depends on the mitoribosome biogenesis factor METTL17, recently reported containing a [4Fe-4S] cluster, which we propose is inserted via the …

Antimicrobial Activity And Mechanism Of Amyloid Proteins And Synthetic Conjugated Polyelectrolytes, Fahimeh Maghsoodi

Nanoscience and Microsystems ETDs

Although the exact cause of Alzheimer’s disease (AD) is still unknown, it is widely considered that the accumulation of amyloid plaques composed of the amyloid-β (Aβ) peptide in the brain is linked to neurodegeneration. Co-localization of viral DNA with Aβ plaques, the association of brain infection and AD, and research indicating the protective effect of Aβ against bacteria and fungi in mice and human cells have led to the hypothesis that Aβ expression and deposition may be central to its function as an antimicrobial peptide (AMP). In my thesis research, we seek to elucidate how Aβ functions as an AMP …

Du Undergraduate Showcase: Research, Scholarship, And Creative Works, Caitlyn Aldersea, Justin Bravo, Sam Allen, Anna Block, Connor Block, Emma Buechler, Maria De Los Angeles Bustillos, Arianna Carlson, William Christensen, Olivia Kachulis, Noah Craver, Kate Dillon, Muskan Fatima, Angel Fernandes, Emma Finch, Colleen Cassidy, Amy Fishman, Andrea Francis, Stacia Fritz, Simran Gill, Emma Gries, Rylie Hansen, Shannon Powers, Jacqueline Martinez, Zachary Harker, Ashley Hasty, Mykaela Tanino-Springsteen, Kathleen Hopps, Adelaide Kerenick, Colin Kleckner, Ci Koehring, Elijah Kruger, Braden Krumholz, Maddie Leake, Lyneé Alves, Seraphina Loukas, Yatzari Lozano Vazquez, Haley Maki, Emily Martinez, Sierra Mckinney, Audrey Mitchell, Kipling Newman, Audrey Ng, Megan Lucyshyn, Andrew Nguyen, Stevie Ostman, Casandra Pearson, Alexandra Penney, Julia Gielczynski, Tyler Ball, Anna Rini, Christina Rorres, Simon Ruland, Helayna Schafer, Emma Sellers, Sarah Schuller, Claire Shaver, Kevin Summers, Isabella Shaw, Madison Sinar, Claudia Pena, Apshara Siwakoti, Carter Sorensen, Madi Sousa, Anna Sparling, Alexandra Revier, Brandon Thierry, Dylan Tyree, Maggie Williams, Lauren Wols

DU Undergraduate Research Journal Archive

DU Undergraduate Showcase: Research, Scholarship, and Creative Works

Effects Of Group Ii Metal Binding On The Stability Of Dna I-Motif Structures, Charlotte Powers

Honors Theses

B-form DNA can adopt alternative structures while in superhelical duress. Alternative DNA structures are favored when there is an asymmetric distribution on complementary DNA strands. Cytosine rich strands may utilize cytosine-cytosine base pairing to form a four-stranded structure known as the i-motif (iM). The stability of iMs is affected by several factors such as DNA sequence, temperature, pH, ionic strength of the solution, and crowded conditions. While the effects of temperature, pH, and crowding conditions on iM stability have been well documented, the effects of ion presence in a solution has been less studied. Hence, those studies are the basis …

Modeling Accuracy Matters: Aligning Molecular Dynamics With 2d Nmr Derived Noe Restraints, Milan Patel

Honors Scholar Theses

Among structural biology techniques, Nuclear Magnetic Resonance (NMR) provides a holistic view of structure that is close to protein structure in situ. Namely, NMR imaging allows for the solution state of the protein to be observed, derived from Nuclear Overhauser Effect restraints (NOEs). NOEs are a distance range in which hydrogen pairs are observed to stay within range of, and therefore experimental data which computational models can be compared against. To that end, we investigated the effects of adding the NOE restraints as distance restraints in Molecular Dynamics (MD) simulations on the 24 residue HP24stab derived villin headpiece subdomain to …

Serving Justice Case By Case, Michael Becker

WRIT: Journal of First-Year Writing

Forensic Science is an integral part of serving justice in today's society, and majority of the world has little understanding of what forensics is. Read this article on forensic science and how it relates to writing in today's world.

Ins And Outs Of Rocker Switch Mechanism In Major Facilitator Superfamily Of Transporters, Stephanie Sauve, Joseph Williamson, Adithya Polasa, Mahmoud Moradi

Chemistry & Biochemistry Faculty Publications and Presentations

The major facilitator superfamily (MFS) of transporters consists of three classes of membrane transporters: symporters, uniporters, and antiporters. Despite such diverse functions, MFS transporters are believed to undergo similar conformational changes within their distinct transport cycles, known as the rocker-switch mechanism. While the similarities between conformational changes are noteworthy, the differences are also important since they could potentially explain the distinct functions of symporters, uniporters, and antiporters of the MFS superfamily. We reviewed a variety of experimental and computational structural data on a select number of antiporters, symporters, and uniporters from the MFS family to compare the similarities and differences …

A Multiscale Mechanistic Model Of Human Dendritic Cells For In-Silico Investigation Of Immune Responses And Novel Therapeutics Discovery, Sara Sadat Aghamiri, Bhanwar Lal Puniya, Rada Amin, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) with the unique ability to mediate inflammatory responses of the immune system. Given the critical role of DCs in shaping immunity, they present an attractive avenue as a therapeutic target to program the immune system and reverse immune disease disorders. To ensure appropriate immune response, DCs utilize intricate and complex molecular and cellular interactions that converge into a seamless phenotype. Computational models open novel frontiers in research by integrating large-scale interaction to interrogate the influence of complex biological behavior across scales. The ability to model large biological networks will likely pave the …

Editorial: Structure And Function Of Chloroplasts, Volume Iii, Hongbo Gao, Alistair J. Mccormick, Rebecca Roston, Yan Lu

Department of Biochemistry: Faculty Publications

Chloroplasts are endosymbiotic organelles derived from cyanobacteria. They have a double envelope membrane, including the outer envelope and the inner envelope. A complex membrane system, thylakoids, exists inside the chloroplast. It is the site of the light-dependent reactions of photosynthesis. The stroma is the main site of the carbon fixation reactions. Although photosynthesis is a very complicated process with many proteins involved, there are many other important processes that occur in chloroplasts, including the regulation of photosynthesis, the biogenesis and maintenance of the structures, carbohydrate, lipid, tetrapyrrole, amino acid, and isoprenoid metabolism, production of some phytohormones, production of specialized metabolites, …

Endogenous L- To D-Amino Acid Residue Isomerization Modulates Selectivity Between Distinct Neuropeptide Receptor Family Members, Baba M. Yussif, Cole V. Blasing, James W. Checco

Department of Biochemistry: Faculty Publications

The L- to D-amino acid residue isomerization of neuropeptides is an understudied post-translational modification found in animals across several phyla. Despite its physiological importance, little information is available regarding the impact of endogenous peptide isomerization on receptor recognition and activation. As a result, the full roles peptide isomerization play in biology are not well understood. Here, we identify that the Aplysia allatotropin-related peptide (ATRP) signaling system utilizes L- to D-residue isomerization of one amino acid residue in the neuropeptide ligand to modulate selectivity between two distinct G protein-coupled receptors (GPCRs). We first identified a novel receptor for ATRP that is …

Supplementation Of Sulfide Or Acetate And 2-Mercaptoethane Sulfonate Restores Growth Of The Methanosarcina Acetivorans Δhdrabc Deletion Mutant During Methylotrophic Methanogenesis, Alicia M. Salvi, Niaz Bahar Chowdhury, Rajib Saha, Nicole R. Buan

Department of Biochemistry: Faculty Publications

Methanogenic archaea are important organisms in the global carbon cycle that grow by producing methane gas. Methanosarcina acetivorans is a methanogenic archaeum that can grow using methylated compounds, carbon monoxide, or acetate and produces renewable methane as a byproduct. However, there is limited knowledge of how combinations of substrates may affect metabolic fluxes in methanogens. Previous studies have shown that heterodisulfide reductase, the terminal oxidase in the electron transport system, is an essential enzyme in all methanogens. Deletion of genes encoding the nonessential methylotrophic heterodisulfide reductase enzyme (HdrABC) results in slower growth rate but increased metabolic efficiency. We hypothesized that …

Genome‑Wide Investigation Of Snrk2 Gene Family In Two Jute Species: Corchorus Olitorius And Corchorus Capsularis, Borhan Ahmed, Fakhrul Hasan, Anika Tabassum, Rasel Ahmed, Rajnee Hassan, Ruhul Amin, Mobashwer Alam

Department of Biochemistry: Faculty Publications

Background Sucrose non-fermenting-1 (SNF1)-related protein kinase 2 (SnRK2), a plant-specific serine/threonine kinase family, is associated with metabolic responses, including abscisic acid signaling under biotic and abiotic stresses. So far, no information on a genome-wide investigation and stress-mediated expression profiling of jute SnRK2 is available. Recent whole-genome sequencing of two Corchorus species prompted to identify and characterize this SnRK2 gene family.

Result We identified seven SnRK2 genes of each of Corchorus olitorius (Co) and C. capsularis (Cc) genomes, with similar physico-molecular properties and sub-group patterns of other models and related crops. In both species, the SnRK2 …

Functional Impact Of A Cancer-Related Variant In Human Δ1‑Pyrroline-5-Carboxylate Reductase 1, Oseeyi I. Daudu, Kaylen R. Meeks, Lu Zhang, Javier Seravalli, John J. Tanner, Donald F. Becker

Department of Biochemistry: Faculty Publications

Pyrroline-5-carboxylate reductase (PYCR) is a proline biosynthetic enzyme that catalyzes the NAD(P)H-dependent reduction of Δ¹-pyrroline-5-carboxylate (P5C) to proline. Humans have three PYCR isoforms, with PYCR1 often upregulated in different types of cancers. Here, we studied the biochemical and structural properties of the Thr171Met variant of PYCR1, which is found in patients with malignant melanoma and lung adenocarcinoma. Although PYCR1 is strongly associated with cancer progression, characterization of a PYCR1 variant in cancer patients has not yet been reported. Thr171 is conserved in all three PYCR isozymes and is located near the P5C substrate binding site. We found that …