Biochemistry, Biophysics, and Structural Biology Commons^™

Advances In Gene Ontology Utilization Improve Statistical Power Of Annotation Enrichment, Eugene Waverly Hinderer Iii, Robert M. Flight, Rashmi Dubey, James N. Macleod, Hunter N. B. Moseley

Maxwell H. Gluck Equine Research Center Faculty Publications

Gene-annotation enrichment is a common method for utilizing ontology-based annotations in gene and gene-product centric knowledgebases. Effective utilization of these annotations requires inferring semantic linkages by tracing paths through edges in the ontological graph, referred to as relations. However, some relations are semantically problematic with respect to scope, necessitating their omission or modification lest erroneous term mappings occur. To address these issues, we created the Gene Ontology Categorization Suite, or GOcats—a novel tool that organizes the Gene Ontology into subgraphs representing user-defined concepts, while ensuring that all appropriate relations are congruent with respect to scoping semantics. Here, we demonstrate the …

Metabolic Engineering Of Cyanobacteria For Production Of Chemicals, Po-Cheng Lin

McKelvey School of Engineering Graduate Student Theses & Dissertations

Concerns over the impact of climate change caused by CO2 emission have driven the research and development of renewable energies. Microbial production of chemicals is being viewed as a feasible approach to reduce the use of fossil fuels and minimize the impact of climate change. With recent advances in synthetic biology, microorganisms can be engineered to synthesize petroleum-based chemicals and plant-derived compounds. Cyanobacteria are photosynthetic prokaryotes that use only sunlight, CO2, and trace minerals for growth. Compared to other microbial hosts, cyanobacteria are attractive platforms for sustainable bioproduction, because they can directly convert CO2 into products. However, the major challenge …

Metabolic Engineering Of Cyanobacteria For Production Of Chemicals, Po-Cheng Lin

McKelvey School of Engineering Graduate Student Theses & Dissertations

Concerns over the impact of climate change caused by CO2 emission have driven the research and development of renewable energies. Microbial production of chemicals is being viewed as a feasible approach to reduce the use of fossil fuels and minimize the impact of climate change. With recent advances in synthetic biology, microorganisms can be engineered to synthesize petroleum-based chemicals and plant-derived compounds. Cyanobacteria are photosynthetic prokaryotes that use only sunlight, CO2, and trace minerals for growth. Compared to other microbial hosts, cyanobacteria are attractive platforms for sustainable bioproduction, because they can directly convert CO2 into products. However, the major challenge …

Understanding Excitation Energy Quenching In Isia, Hui-Yuan Steven Chen

McKelvey School of Engineering Graduate Student Theses & Dissertations

Cyanobacteria are photoautotrophic organisms that contribute a significant amount of global primary productivity. They are found in freshwater, marine and even some extremely severe environments. Among those environments, iron deficiency is one of the most common stress conditions in cyanobacterial habitats. To survive, cyanobacteria have evolved and developed several strategies to alleviate the damage caused by iron deficiency.

Iron stress-inducible protein (IsiA) is a chlorophyll-binding membrane protein found in cyanobacteria grown in iron-deficient conditions. During the past decades, considerable effort has been put on understanding how IsiA functions to help cyanobacteria survive iron deficiency. It has been reported that IsiA …

Selective Alteration Of The Root Morphology Of Arabidopsis Thaliana By Synthetic Anion Transporters (Sats), Mohit Patel, Evan Garrad, Steven Korb, Saeedeh Negin, Michael Gokel, Sergey Sedinkin, Shanheng Yin, George Gokel

Chemistry & Biochemistry Faculty Works

No abstract provided.

An Attenuated Zika Virus Encoding Non-Glycosylated Envelope (E) And Non-Structural Protein 1 (Ns1) Confers Complete Protection Against Lethal Challenge In A Mouse Model, Arun S. Annamalai, Aryamav Pattnaik, Bikash R. Sahoo, Zack P. Guinn, Brianna L. Bullard, Eric A. Weaver, David J. Steffen, Sathish Kumar Natarajan, Thomas M. Petro, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Zika virus (ZIKV), a mosquito-transmitted flavivirus, emerged in the last decade causing serious human diseases, including congenital microcephaly in newborns and Guillain-Barré syndrome in adults. Although many vaccine platforms are at various stages of development, no licensed vaccines are currently available. Previously, we described a mutant MR766 ZIKV (m2MR) bearing an E protein mutation (N154A) that prevented its glycosylation, resulting in attenuation and defective neuroinvasion. To further attenuate m2MR for its potential use as a live viral vaccine, we incorporated additional mutations into m2MR by substituting the asparagine residues in the glycosylation sites (N130 and N207) of NS1 with alanine …

Characterization Of The Role Of Acetylated Ape1 In Dna Damage Repair And Transcriptional Regulation, Shrabasti Roychoudhury

Theses & Dissertations

Apurinic/apyrimidinic (AP) sites are the most frequently formed DNA lesions in the genome. The primary enzyme to repair AP sites in mammalian cells is the AP endonuclease (APE1), which functions through the base excision repair (BER) pathway. Mammalian APE1 has a unique N-terminal unstructured tail and has both DNA repair and transcriptional regulatory activities. Our lab discovered that APE1 can be regulated via post-translational acetylation of lysine residues 6, 7, 27, 31, and 32. The role of mammalian APE1 in repair has been extensively studied and well characterized. However, the regulatory role of APE1 acetylation (AcAPE1) in the context of …

Endothelial Iqgap1 Regulates Leukocyte Transmigration By Directing The Lbrc To The Site Of Diapedesis, David P. Sullivan, Prarthana J. Dalal, Fanny Jaulin, David B. Sacks, Geri Kreitzer, William A. Muller

Publications and Research

Transendothelial migration (TEM) of leukocytes across the endothelium is critical for inflammation. In the endothelium, TEM requires the coordination of membrane movements and cytoskeletal interactions, including, prominently, recruitment of the lateral border recycling compartment (LBRC). The scaffold protein IQGAP1 was recently identified in a screen for LBRC-interacting proteins. Knockdown of endothelial IQGAP1 disrupted the directed movement of the LBRC and substantially reduced leukocyte TEM. Expression of truncated IQGAP1 constructs demonstrated that the calponin homology domain is required for IQGAP1 localization to endothelial borders and that the IQ domain, on the same IQGAP1 polypeptide, is required for its function in TEM. …

Synthesis And Evaluations Of “1,4-Triazolyl Combretacoumarins” And Desmethoxy Analogs, Tashrique A. Khandaker, Jessica D. Hess, Renato Aguilera, Graciela Andrei, Robert Snoeck, Dominique Schols, Padmanava Pradhan, Mahesh K. Lakshman

Publications and Research

1,4-Triazolyl combretacoumarins have been prepared by linking the trimethoxyarene unit of combretastatin A4 with coumarins, via a 1,2,3-triazole. For this, 4-azidocoumarins were accessed by a sequential two-step, one-pot reaction of 4-hydroxycoumarins with (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP), followed by reaction with NaN₃. In the reaction with BOP, a coumarin-derived phosphonium ion intermediate seems to form, leading to an O⁴-(benzotriazolyl)coumarin derivative. For the CuAAC reaction of azidocoumarins with 5-ethynyl-1,2,3-trimethoxybenzene, catalytic [(MeCN)₄Cu]PF₆ in CH₂Cl₂/MeOH with 2,6-lutidine, at 50 ^oC, was suitable. The 4-azidocoumarins were less reactive as compared to PhN₃ and …

Characterization Of Endothelial Nitric Oxide Synthase Serine-600 Phosphorylation, Kevin Patel

Master of Science in Chemical Sciences Theses

Endothelial nitric oxide synthase (eNOS) is part of a family of three nitric oxide synthase (NOS) enzymes that catalyze the production of nitric oxide (NO). NO is a gaseous, free-radical signaling molecule that has a variety of cellular and physiological functions that range from maintaining cardiovascular homeostasis to neurotransmission. The function of NO greatly depends on the concentration and is cell type specific. eNOS is the most regulated of the three NOS isoforms and the mechanisms of regulation can be through protein-protein interactions and posttranslational modifications. A connection with eNOS and the cell cycle has begun to form with recent …

Investigation Of The Electrode Polarization Effect For Biosensor Applications, Anil Koklu

Mechanical Engineering Research Theses and Dissertations

My research focuses on electrokinetic transport. Particularly, in this dissertation, we focus on fabrication and testing of micro electrodes with nanostructured surfaces to minimize the electrode polarization (EP) effects for biosensor applications. In the first study, electrochemical deposition of gold nanoparticles on to planar gold electrodes was used to generate rough surfaces. Dendritic nanostructures that reduced EP up to two orders of magnitude was obtained by optimizing the deposition conditions. These structures also enhanced dielectrophoresis (DEP) response of our bio-chips, making them usable in physiological buffers. In further studies we discovered a universal scaling of EP in the frequency domain, …

Parallel Multipole Expansion Algorithms And Their Biology Applications, Jiahui Chen

Mathematics Theses and Dissertations

N-body pairwise interactions are ubiquitous in scientific areas such as astrophysics, fluids mechanics, electrical engineering, molecular biology, etc. Computing these interactions using direct sum of an O(N) cost is expensive, whereas multipole expansion methods, such as the fast multipole method (FMM) or treecode, can reduce the cost to O(N) or O(N log N). This thesis focuses on developing numerical algorithms of Cartesian FMM and treecode, as well as using these algorithms to directly or implicitly solve biological problems involving pairwise interactions. This thesis consists of the following topics. 1) A cyclic parallel scheme is developed to handle the load balancing …

How To Untie A Protein Knot., Sitao Yin, Brittiny Dhital, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

The origin of protein backbone threading through a topological knot remains elusive. To understand the evolutionary origin of protein knots, in this issue of StructureKo et al. (2019) used circular permutation to untie a knotted protein. They showed that a domain-swapped dimer releases the knot and the associated high-energy state for substrate binding.

Effective Statistical Energy Function Based Protein Un/Structure Prediction, Avdesh Mishra

LSU New Orleans Theses and Dissertations

Proteins are an important component of living organisms, composed of one or more polypeptide chains, each containing hundreds or even thousands of amino acids of 20 standard types. The structure of a protein from the sequence determines crucial functions of proteins such as initiating metabolic reactions, DNA replication, cell signaling, and transporting molecules. In the past, proteins were considered to always have a well-defined stable shape (structured proteins), however, it has recently been shown that there exist intrinsically disordered proteins (IDPs), which lack a fixed or ordered 3D structure, have dynamic characteristics and therefore, exist in multiple states. Based on …

Iron-Sulfur Cluster Assembly; In Vivo Analysis Of The Methanogenic Suf System, Evan Dunkle

LSU Master's Theses

Iron-sulfur (Fe-S) clusters are among the most ancient and prevalent of all biological cofactors. Their assembly into associated proteins is a tightly regulated process with many organisms employing multiple cluster assembly pathways. Much is known about Fe-S cluster assembly in aerobic organisms such as Escherichia coli (E. coli) but little is known in regards to cluster assembly in more ancient organisms such as methanogens. Methanogens are members of the domain of Archaea and are defined by their ability to generate methane as a byproduct of their main energy generating pathway. Methanogens also have significantly higher Fe-S cluster content …

Incidence And Prevalence Of Francisella Noatunensis Subsp. Orientalis (Fno) Pathogenic Infections In Feral Hawaiian Tilapia, Daquille Peppers

Biology Theses

Aquaculture has become a major food source for many countries and continues to grow each year. However, many of the fishes that are farmed are susceptible to pathogenic infections such as Francisellosis, a bacterial infection that contributes to disease and high mortality rate in many populations of farmed and wild fish around the world. In 1994, feral and farmed populations of tilapia (e.g. Oreochromis mossambicus) on Oahu, Hawaii were found to be infected with a novel Francisellosis strain, Francisella noatunensis subsp. orientalis (Fno). To prevent the spread of this pathogen, the Hawaii Department of Aquaculture (HDOA) initiated …

Podophyllum Peltatum: Relationship Of Colony Size And Age, Emily Holst, Heidi Keswick, David P. Warners

Student Papers and Reports

No abstract provided.

Stormwater Capture Via Green Infrastructure In The Plaster Creek Watershed, Kyle Dankert, Ana Singh, Deanna Geelhoed, David P. Warners

Student Papers and Reports

No abstract provided.

Effects Of Halogen, Chalcogen, Pnicogen, And Tetrel Bonds On Ir And Nmr Spectra, Jia Lu, Steve Scheiner

Chemistry and Biochemistry Faculty Publications

Complexes were formed pairing FX, FHY, FH₂Z, and FH₃T (X = Cl, Br, I; Y = S, Se, Te; Z = P, As, Sb; T = Si, Ge, Sn) with NH₃ in order to form an A⋯N noncovalent bond, where A refers to the central atom. Geometries, energetics, atomic charges, and spectroscopic characteristics of these complexes were evaluated via DFT calculations. In all cases, the A–F bond, which is located opposite the base and is responsible for the σ-hole on the A atom, elongates and its stretching frequency undergoes a shift to the red. This …

Elements Of An Effectiveresearch Presentation, Rachel Willand Charnley

Chemistry and Biochemistry Faculty Presentations and Other Materials

No abstract provided.

Temporal Gene Expression Of Mesenchymal Cells In The Pediatric Lung, Quinlen F. Marshall, Soumyaroop Bhattacharya, Gautam Bandyopadhyay, Ravi Misra, Thomas Mariani, Gloria Pryhuber

Chemistry Student Work

INTRODUCTION: The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types (Whitsett, JA. et al. Physiol. Rev, 2019). Murine models demonstrate that pulmonary mesenchymal cells exhibit remarkable heterogeneity in function and morphology during development, however, confirmation of their role is lacking in human neonates and early childhood (Guo, M. et al. Nat. Comm, 2019). In addition, many current human genomic studies of lung maturation suffer from limited sample size, limiting …

Green Team: Ecological Restoration Of Plaster Creek, Yeri Kim, Benjamin Steenwyk, Rachel Warners, David P. Warners, Gail Heffner

Student Papers and Reports

No abstract provided.

Natural Autoantibodies: Origin, Function And Utility For Diagnosis Of Disease, Abhirup Sarkar

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies (aAbs) by the simplest definitions have been described as antibodies against self-antigens and were exclusively associated with autoimmune diseases. Eventually, studies demonstrated that they are abundant in the blood of all human sera, regardless of age, gender, or the presence or absence of disease, and were thus named as ‘natural autoantibodies’. The underlying reason for their ubiquity has remained elusive, but we have hypothesized that they are responsible for clearing blood-borne cell and tissue debris generated under conditions of health and disease. To test this, we chose to use two widely different disease model systems, namely neurodegenerative diseases and …

Sensory Primary Cilium Is A Distinct Signaling Compartment, Rinzhin Tshering Sherpa

Pharmaceutical Sciences (PhD) Dissertations

The primary cilium is a solitary cellular organelle that protrudes from the apical cell membrane. Findings on cilia-dependent mechanosenstation have shown that the primary cilium acts as a transducer of fluid-shear stress into intracellular signaling. Over recent years, studies in primary cilia have intensified after determining a causal relationship between dysfunctional primary cilia and cystic diseases. Along with its mechanosensory function, the primary cilium houses a variety of receptors, ion channels and transporter proteins. Studies in cilia biology have shown that primary cilia are coordinators of signaling pathways such as Hedgehog (Hh), Wnt, and platelet-derived growth factor (PDGF) pathways during …

The Distal Cytoplasmic Tail Of The Influenza A M2 Protein Dynamically Extends From The Membrane, Grace Kim , '17, Hayley E. Raymond , '18, Alice L. Herneisen , '17, Abigail Wong-Rolle , '19, Kathleen P. Howard

Chemistry & Biochemistry Faculty Works

The influenza A M2 protein is a multifunctional membrane-associated homotetramer that orchestrates several essential events in the viral infection cycle. The monomeric subunits of the M2 homotetramer consist of an N-terminal ectodomain, a transmembrane domain, and a C-terminal cytoplasmic domain. The transmembrane domain forms a four-helix proton channel that promotes uncoating of virions upon host cell entry. The membrane-proximal region of the C-terminal domain forms a surface-associated amphipathic helix necessary for viral budding. The structure of the remaining ~34 residues of the distal cytoplasmic tail has yet to be fully characterized despite the functional significance of this region for influenza …

Experimental Nitrogen Addition Alters Structure And Function Of A Boreal Bog: Critical Load And Thresholds Revealed, R. Kelman Wieder, Dale H. Vitt, Melanie A. Vile, Jeremy A. Graham, Jeremy A. Hartsock, Hope Fillingim, Et Al.

Michigan Tech Publications, Part 1

Bogs and fens cover 6% and 21%, respectively, of the 140,329 km² Oil Sands Administrative Area in northern Alberta. Development of the oil sands has led to increasing atmospheric N deposition, with values as high as 17 kg N^.ha^-1yr^-1; regional background deposition is N^.ha^-1yr^-1. Bogs, being ombrotrophic, may be especially susceptible to increasing N deposition. To examine responses to N deposition, over five years, we experimentally applied N (as NH₄NO₃) to a bog near Mariana Lake, Alberta, unaffected by oil sands activities, at …

The Influence Of Mir-322 On Skeletal Muscle Differentiation, Miles Alexander Soyer

Legacy Theses & Dissertations (2009 - 2024)

Skeletal muscle plays a crucial role in coordinating voluntary movement and accounts for nearly 50% of total body mass. Dysregulation in skeletal muscle development is known to cause muscle degenerative diseases including the devastating Duchenne Muscular Dystrophy (DMD). The majority of the biological studies investigating muscle development were based on myogenic transcription factors and signaling molecules including: Pax7, Myf5, MyoD, WNT, TGF-β and BMP. After the discovery of non-coding RNAs including microRNAs, it was postulated that these molecules could regulate gene expression and thus affect differentiation and development. MicroRNAs are small non-coding RNAs (~17-25 nucleotides) that regulate gene expression negatively …

Protein Structure Analysis, Agnieszka Szarecka, Chris Dobson

Peer Reviewed Articles

We describe a series of engaging exercises in which students emulate the process that researchers use to efficiently develop new pharmaceutical drugs, that of rational drug design. The activities are taken from a three- to four-hour workshop regularly conducted with first-year college students and presented here to take place over three to four class periods. Although targeted at college students, these activities may be appropriate at the high school level as well, particularly in an AP Biology course. The exercises introduce students to the topics of bioinformatics and computer modeling, in the context of rational drug design, using free online …

The Dynamin-Like Protein Vps1 Stimulates Endosome-To-Golgi Fusion In Vitro, Jared Christopher Smothers

Graduate Theses/Dissertations

Intracellular membrane fusion events can be reconstituted by exploiting isolated organelles from cellular hosts or artificial membranes made of purified phospholipid components. Artificial construction of membranes provides two significant advantages. First, cellular isolation of the endosome-derived vesicles and TGN (trans-Golgi Network) compartments needed for the fusion assay would be extremely challenging. Second, reconstituting the membranes provides the added benefit of controlling size and lipid compositions to functionally mimic the individual membrane architectures and introduce only the purified proteins that are under investigation. For these reasons, I have developed the first simultaneous lipid and content mixing fusion assays that measures the …

Microrna Identification And Target Prediction In The Whitefly (Bemisia Tabaci), Alexis Aleman

Honors Theses

RNA interference, referred to as RNAi, is a biological phenomenon whereby knock-down of gene expression can be achieved through the use of RNA molecules, including small interfering RNAs (siRNAs) and microRNAs (miRNAs). The use of miRNAs is an endogenous pathway that results in the degradation of the miRNA strand’s complementary messenger RNA (mRNA), preventing the translation of the mRNA and therefore the production of the proteins necessary for gene expression. While RNAi is a biological phenomenon that occurs naturally, it is also a method that can be used and manipulated in the laboratory to try to control the expression of …