Biochemistry, Biophysics, and Structural Biology Commons^™

Comparative Proteomic Analyses Of The Parietal Lobe From Rhesus Monkeys Fed A High-Fat/Sugar Diet With And Without Resveratrol Supplementation, Relative To A Healthy Diet: Insights Into The Roles Of Unhealthy Diets And Resveratrol On Function, Aaron M. Swomley, Judy C. Triplett, Jeriel T. Keeney, Govind Warrier, Kevin J. Pearson, Julie A. Mattison, Rafael De Cabo, Jian Cai, Jon B. Klein, D. Allan Butterfield

Chemistry Faculty Publications

A diet consisting of a high intake of saturated fat and refined sugars is characteristic of a Western-diet and has been shown to have a substantial negative effect on human health. Expression proteomics were used to investigate changes to the parietal lobe proteome of rhesus monkeys consuming either a high fat and sugar (HFS) diet, a HFS diet supplemented with resveratrol (HFS+RSV), or a healthy control diet for 2 years. Here we discuss the modifications in the levels of 12 specific proteins involved in various cellular systems including metabolism, neurotransmission, structural integrity, and general cellular signaling following a nutritional intervention. …

Do Elevated Levels Of Glutathione Decrease The Toxicity Of Plasticizers In Mouse Liver Cells?, Khatoon Albahrani

All Master's Theses

Phthalates are esters of phthalic acid that play a crucial role in the manufacturing industries for enhancing the properties of plastic materials. Di-(2-ethylhexyl) phthalate (DEHP) is one of the most common phthalates used in a variety of products including food packaging and medical equipment. Their use has caused public health concerns because of their toxic effects on reproductive and developmental processes. This study aims to investigate the response of two mouse hepatoma cell lines to the effects of DEHP and its bioactive metabolite mono (2-ethylhexyl) phthalate (MEHP). Cells were exposed to four concentrations (10, 50, 100, and 300 µM) of …

The T6a Modification Acts As A Positive Determinant For The Anticodon Nuclease Prrc, And Is Distinctively Nonessential In Streptococcus Mutans, Jo Marie Bacusmo, Silvia S. Orsini, Jennifer Hu, Michael Demott, Patrick C. Thiaville, Ameer Elfarash, Mellie June Paulines, Diego Rojas-Benítez, Birthe Meineke, Christopher Deutsch, Dirk Iwata-Reuyl, Patrick A. Limbach, Peter C. Dedon, Kelly C. Rice, Stewart Shuman, Valérie De Crécy-Lagard

Chemistry Faculty Publications and Presentations

Endoribonuclease toxins (ribotoxins) are produced by bacteria and fungi to respond to stress, eliminate non-self competitor species, or interdict virus infection. PrrC is a bacterial ribotoxin that targets and cleaves tRNALys UUU in the anticodon loop. In vitro studies suggested that the post-transcriptional modification threonylcarbamoyl adenosine (t⁶A) is required for PrrC activity but this prediction had never been validated in vivo. Here, by using t⁶A-deficient yeast derivatives, it is shown that t⁶A is a positive determinant for PrrC proteins from various bacterial species. Streptococcus mutans is one of the few bacteria where the t …

Synthesis And Development Of Zwitterionic Pei (Zpei) For Optimized Delivery Of Nucleic Acids, Joseph Raleigh Duke Iii

Theses and Dissertations--Chemistry

Gene therapy holds promise for the treatment a wide range of diseases ranging from cystic fibrosis to cardiovascular disease to cancer. The need for safe and efficient gene delivery methods remains the primary barrier to human gene therapy. Non-viral vector materials, including polymers, can be designed to be biocompatible and non-immunogenic, but lack the efficiency to be clinically relevant. Gene therapy awaits the development of new materials that are both safe and efficient. Here, we have synthesized a series of modified zwitterionic polymers based on the common transfecting agent polyethylenimine (PEI). Using a variety of biochemical and biophysical methods we …

The Maculoprotective Effect Of A Thiol Antioxidant In Retinal Degeneration Models, Hsiu-Jen Wang

Doctoral Dissertations

"Age-related macular degeneration (AMD) is a leading cause of irreversible blindness among adults, age 60 and older, in developed countries. While oxidative stress is implicated in the pathogenesis of AMD, clinical studies have shown that dietary antioxidants can delay progression of AMD. Currently, there is no FDA-approved treatment for AMD. Therefore, we hypothesized that N-acetylcysteine amide (NACA), a thiol antioxidant, would protect retinal pigment epithelium and impede the progression of retinal degeneration. The goal of this work was to evaluate the efficacy of NACA in preventing retinal pigment epithelial cell and photoreceptor death in AMD models. To achieve this, we …

An Effective Computational Method Incorporating Multiple Secondary Structure Predictions In Topology Determination For Cryo-Em Images, Abhishek Biswas, Desh Ranjan, Mohammad Zubair, Stephanie Zeil, Kamal Al Nasr, Jing He

Computer Science Faculty Publications

A key idea in de novo modeling of a medium-resolution density image obtained from cryo-electron microscopy is to compute the optimal mapping between the secondary structure traces observed in the density image and those predicted on the protein sequence. When secondary structures are not determined precisely, either from the image or from the amino acid sequence of the protein, the computational problem becomes more complex. We present an efficient method that addresses the secondary structure placement problem in presence of multiple secondary structure predictions and computes the optimal mapping. We tested the method using 12 simulated images from alpha-proteins and …

Comparing An Atomic Model Or Structure To A Corresponding Cryo-Electron Microscopy Image At The Central Axis Of A Helix, Stephanie Zeil, Julio Kovacs, Willy Wriggers, Jing He

Computer Science Faculty Publications

Three-dimensional density maps of biological specimens from cryo-electron microscopy (cryo-EM) can be interpreted in the form of atomic models that are modeled into the density, or they can be compared to known atomic structures. When the central axis of a helix is detectable in a cryo-EM density map, it is possible to quantify the agreement between this central axis and a central axis calculated from the atomic model or structure. We propose a novel arc-length association method to compare the two axes reliably. This method was applied to 79 helices in simulated density maps and six case studies using cryo-EM …

Disrupted Superior Collicular Activity May Reveal Cervical Dystonia Disease Pathomechanisms, Eavan M. Mcgovern, Owen Killian, Shruti Narashimham, Brendan Quinlivan, John Butler, Rebecca Beck, Ines Beiser, Laura W. Williams, Ronan P. Killeen, Michael Farrell, Sean O'Riordan, Richard B. Reilly, Michael Hutchinson

Articles

Cervical dystonia is a common neurological movement disorder characterised by muscle contractions causing abnormal movements and postures affecting the head and neck. The neural networks underpinning this condition are incompletely understood. While animal models suggest a role for the superior colliculus in its pathophysiology, this link has yet to be established in humans. The present experiment was designed to test the hypothesis that disrupted superior collicular processing is evident in affected patients and in relatives harbouring a disease-specific endophenotype (abnormal temporal discrimination). The study participants were 16 cervical dystonia patients, 16 unaffected first-degree relatives with abnormal temporal discrimination, 16 unaffected …

The Chemistry Of The Flint Water Crisis, Ernest M. Oleksy

The Downtown Review: An Interdisciplinary Journal Written and Peer-Reviewed by Mandel Honors College Students at Cleveland State University

Politics and science do not always go hand-in-hand. Nowhere was this more clear than in the Flint Water Crisis. Negligence towards growing levels of lead poisoning in drinking water led to incredibly deleterious effects on Flint's citizens. The chemistry of equilibrium and the shortcomings of local leaders led to Flint's water becoming a crisis.

Phthalate Plasticizers Covalently Linked To Pvc Via Copper-Free Or Copper Catalyzed Axide-Alkyne Cycloadditions, Aruna Earla, Li Longbo, Philip Costanzo, Rebecca Braslau

Chemistry and Biochemistry

Plasticization of PVC was carried out by covalently linking phthalate derivatives via copper-free (thermal) or copper catalyzed azide-alkyne cycloadditions. Di(2-ethylhexyl) phthalate derivatives (DEHP-ether and DEHP-ester) were synthesized and appended to PVC at two different densities. The glass transition temperatures of the modified PVC decreased with increasing content of plasticizer. PVC-DEHP-ether gave lower glass transition temperatures than PVC-DEHP-ester, reflecting the enhanced flexibility of the ether versus ester linker.

An Examination Of Student Outcomes In Studio Chemistry, Alan L. Kiste, Gregory E. Scott, Jesse Paul Bukenberger, Miles Markmann, Jennifer Moore

Chemistry and Biochemistry

Twenty years ago, a major curriculum revision at a large, comprehensive university in the Western United States led to the implementation of an integrated lecture/laboratory (studio) experience for our engineering students taking general chemistry. Based on these twenty years of experience, construction of four purpose-built studio classrooms to house the majority of the remaining general chemistry courses was completed in 2013. A detailed study of the effects of the entire ecology of the studio experience on student success was initiated at that time. Data from content knowledge pre- and post-tests, learning attitudes surveys, and student course evaluations show positive effects …

Characterization Of Wy 14,643 And Its Complex With Aldose Reductase, Michael Sawaya, Malkhey Verma, Vaishnavi Balendiran, Nigam Rath, Duilio Cascio, Ganesaratnam Balendiran

Chemistry & Biochemistry Faculty Works

The peroxisome proliferator, WY 14,643 exhibits a pure non-competitive inhibition pattern in the aldehyde reduction and in alcohol oxidation activities of human Aldose reductase (hAR). Fluorescence emission measurements of the equilibrium dissociation constants, Kd, of oxidized (hAR•NADP+) and reduced (hAR•NADPH) holoenzyme complexes display a 2-fold difference between them. Kd values for the dissociation of WY 14,643 from the oxidized (hAR•NADP+•WY 14,643) and reduced (hAR•NADPH•WY 14,643) ternary complexes are comparable to each other. The ternary complex structure of hAR•NADP+•WY 14,643 reveals the first structural evidence of a fibrate class drug binding to hAR. These observations demonstrate how fibrate molecules such as …

Electrogenerated Chemiluminescence Study Of Semiconductor Nanoparticles Towards Sensitive Detection Of Biomolecules, Yiliyasi Wusimanjiang

Dissertations

The main focus of this dissertation is to unfold the fundamental aspects of electrogenerated chemiluminescence (ECL) generation from semiconductor nanoparticles (also known as quantum dots or QDs) within different ECL systems. The ECL and photo-physical interactions between the CdTe QDs (λ_emission= ~760 nm) and the CdSe QDs (λ_emission= ~550 nm), as well as the effects of carbon nanotubes on ECL of QDs were separately investigated. Optimum experimental conditions for peptide bond formation on an electrode surface through EDC (1-ethyl-3-(-3-dimethylaminopropyl) carbodiimide hydrochloride)/NHS (N-Hydroxysulfosuccinimide) coupling were also revealed using cyclic voltammetry technique. Based on the information …

Interactions In The Cpsrp Dependent Targeting Of Light Harvesting Chlorophyll Binding Protein To The Thylakoid Membrane, Rory Henderson

Graduate Theses and Dissertations

Targeting of proteins is a critical component of cellular function. A universally conserved targeting system of the cytosol utilizes a signal recognition particle (SRP) to target many proteins contranslationally to the endoplasmic reticulum in eukaryotes or the inner membrane in prokaryotes. A homologous SRP system exists in the chloroplast that delivers light harvesting chlorophyll binding proteins (LHCP) to they thylakoid membrane. The chloroplast SRP (cpSRP) is a heterodimer composed of a novel 43 kDa subunit and a 54 kDa subunit homologous to a component of the SRP system, SRP54. Many details regarding the interactions between the proteins of the cpSRP …

Bioorthogonal Reactions: Synthesis And Evaluation Of Different Ligands In Copper Catalyzed Azide-Alkyne1,3-Dipolar Cycloaddition (Cuaac), Zainab Abdullah Almansaf

Graduate Theses and Dissertations

The Copper CatalyzedAzide-Alkyne1,3-Dipolar Cycloaddition (CuAAC) reaction has unique features that qualify it to be one of the best click reactions. Its applications have been shown in different aspects and for multiple purposes. The oxidative degradation of biological systems (labile proteins and live cells) is, however, generally recognized as the major problem when using this reaction in living systems. Reactive oxidation species can be easily produced in the presence of copper(II), ascorbate and air, and this is the main cause of toxicity. However, the uses of ligands have shown a major impact on reducing copper toxicity, protecting Cu(I) from the redox …

Conformationally Superarmed S-Ethyl Glycosyl Donors As Effective Building Blocks For Chemoselective Oligosaccharide Synthesis In One Pot, Mithila Bandara, Jagodige Yasomanee, Nigam Rath, Christian Pedersen, Mikael Bols, Alexei Demchenko

Chemistry & Biochemistry Faculty Works

A new series of superarmed glycosyl donors has been investigated. It was demonstrated that the S-ethyl leaving group allows for high reactivity, which is much higher than that of equally equipped S-phenyl glycosyl donors that were previously investigated by our groups. The superarmed S-ethyl glycosyl donors equipped with a 2-O-benzoyl group gave complete β-stereoselectivity. Utility of the new glycosyl donors has been demonstrated in a one-pot one-addition oligosaccharide synthesis with all of the reaction components present from the beginning.

Development Of In Vivo Systems For Detecting And Studying Ribosome Inhibition By Small Molecules, Shijie Huang

Chemistry and Chemical Biology ETDs

The ribosome is the quintessential antibacterial drug target, with many structurally and mechanistically distinct classes of antibacterial agents acting by inhibiting ribosome function. Detecting and quantifying ribosome inhibition by small molecules and investigating their binding modes and mechanisms of action are critical to antibacterial drug discovery and development efforts. To develop a ribosome inhibition assay that is operationally simple, yet provides direct information on the drug target and the mechanism of action, we have developed engineered E. coli strains harboring an orthogonal ribosome controlled green fluorescent protein reporter that produce fluorescent signal when the O-ribosome is inhibited. As a proof …

Engineering Small Molecule Based Dimerization To Induce Translation And Provide Optogenetic Control, Catherine Wright

Chemistry and Chemical Biology ETDs

We wanted to develop a system that combines the spatial control of photoactivation and control of translation to build a tool to spatially control translation in neurons. This kind of tool could be used to investigate the role of spatially controlled translation of any protein in neural behavior. In this way the development and growth of neural processes could be studied to elucidate the mechanisms for spatially sensitive events such as pathfinding, repair, or long-term potentiation.

Chemically induced dimerization was used to install a switch into the activation of translation for specific genes. An abscisic acid (ABA) dependent dimerization of …

Infrared Spectroscopy Of The Nitrogenase Mofe Protein Under Electrochemical Control: Potential-Triggered Co Binding, P. Paengnakorn, Philip A. Ash, Sudipta K. Shaw, Karamatullah Danyal, T. Chen, Dennis R. Dean, Lance C. Seefeldt, Kylie A. Vincent

Chemistry and Biochemistry Faculty Publications

We demonstrate electrochemical control of the nitrogenase MoFe protein, in the absence of Fe protein or ATP, using europium(III/II) polyaminocarboxylate complexes as electron transfer mediators. This allows the potential dependence of proton reduction and inhibitor (CO) binding to the active site FeMo-cofactor to be established. Reduction of protons to H2 is catalyzed by the wild type MoFe protein and Β-98^Tyr→His and Β-^99Phe→His variants of the MoFe protein at potentials more negative than -800 mV (vs. SHE), with greater electrocatalytic proton reduction rates observed for the variants compared to the wild type protein. Electrocatalytic proton reduction is strongly …

Teaching Systems Biology Of The Circadian Clock With Journal Articles And Matlab, Stephanie R. Taylor

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Extracting Biochemical Parameters From Protein Distributions Of Vascular Cells, Partha Srinivasan

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Atomic Tiles: Manipulative Resources For Exploring Bonding And Molecular Structure, Alan L. Kiste, Rebecca G. Hooper, Gregory E. Scott, Seth Bush

Chemistry and Biochemistry

A simple manipulative resource, Atomic Tiles, is described for scaffolding the learning of Lewis structures without using algorithmic, rule-based methods of drawing. Students use Atomic Tiles to (1) create models of bonding that lead to drawing Lewis structures, (2) use the structures they create to infer patterns required for rational structures and common organic functional groups, (3) translate between Lewis structures and molecular models, and (4) use molecular models to identify isomers.

A Study Of Defensive Mechanisms Employed By Two Species Of Nudibranchs Using Toxicity And Unpalatability Analyses, Sean Youn

Independent Study Project (ISP) Collection

Nudibranchs are marine invertebrates that have developed an intriguing defense mechanism, including warning coloration and the use of chemicals accumulated through their sponge diet. The goal of this study was to determine whether the strength of chemical defenses differs between dietary and accumulated secondary metabolites for two species: Glossodoris vespa and Ceratosoma brevicaudatum. First, NMR spectroscopy was used to not only identify specific compounds in the mantle (outer covering) and the viscera (gut) but also to analyze the possibility of nudibranch species transporting more toxic compounds for defensive purposes. Next, toxicity (brine shrimp) and palatability (Palaemon shrimp) assays were used …

Development Of Dihydrochalcone Functionalized Gold Nanoparticles For Augmented Antineoplastic Activity, Jason N. Payne

Masters Theses & Specialist Projects

Phloridzin, an antidiabetic and antineoplastic agent usually found in fruit trees, is a dihydrochalcone constituent that has a clinical/pharmaceutical significance as a sodiumglucose linked transport 2 (SGLT2) inhibitor. Phloridzin never experienced widespread clinical usage in the pharmaceutical market due to its side effects and poor bioavailability when compared to other antidiabetic therapeutics. The poor bioavailability is primarily attributed to the degradation of the glycosidic bond of the phloridzin, resulting in the formation of phloretin, the aglycone of phloridzin and glucose. While phloretin displays a reduced capacity of SGLT2 inhibition, this nutraceutical shows enhanced antineoplastic activity in comparison to phloridzin. Gold …

Visible-Light Generation Of High-Valent Metal-Oxo Intermediates And A Biomimetic Oxidation Catalyzed By Manganese Porphyrins With Iodobenzene Diacetate, Ka Wai Kwong

Masters Theses & Specialist Projects

High-valent iron-oxo intermediates play central roles as active oxidants in enzymatic and synthetic catalytic oxidations. Many transition metal catalysts are designed for biomimetic studies of the predominant oxidation catalysts in Nature, the cytochrome P450 enzymes.

In this work, a new photochemical method to generate high-valent iron-oxo porphyrin models was discovered. As controlled by the electronic nature of porphyrin ligands, iron(IV)-oxo porphyrin radical cations (Compound I model) and iron(IV)-oxo porphyrin derivatives (Compound II model) were produced. These observations indicate that the photochemical reactions involve a heterolytic cleavage of O-Br in precursors to give a putative iron(V)-oxo intermediate, which might relax to …

Bioenergetics: Experimental Demonstration Of Excess Protons And Related Features, Haitham A. Saeed

Chemistry & Biochemistry Theses & Dissertations

Over the last 50 years, ever since the Nobel-prize work of Peter Mitchell’s Chemiosmotic theory, the question whether bioenergetics energy transduction occurs through localized or delocalized protons has been a controversial issue among scientists. Recently, a proton-electrostatics localization hypothesis was formulated which may provide a new and clear understanding of localized and delocalized proton-coupling energy transduction in many biological systems. The aim of this dissertation was to test this new hypothesis.

To demonstrate the fundamental behavior of localized protons in a pure water-membrane-water system in relation to the newly derived pmf equation, excess protons and excess hydroxyl anions were generated …

Specific Binding Affinity Of The Non-Catalytic Domain Of Eukaryotic Like Type Ib Topoisomerase Of Vaccinia Virus, Benjamin R. Reed

Dissertations, Theses, and Capstone Projects

Topoisomerases are ubiquitous proteins that alter supercoiling in double stranded DNA (dsDNA) during transcription and replication and. vaccinia and the closely related poxvirus variola virus, at 314 amino acids in length, encode the smallest of the type I topoisomerases(TopIB). TopIB is a two domain protein that recognizes the sequence 5’-T/CCCTT, cleaves at the 3’-end and relaxes supercoiling through rotation. The C-terminal domain (CTD) alone contains the catalytic activity and specificity. Deletion of the N-terminal domain results in a greatly reduced rate of relaxation and rapid dissociation. Biochemical data suggests that the N-terminal domain (NTD) is important for pre-cleavage binding and …

Emissions Of Nitrogen-Containing Organic Compounds From The Burning Of Herbaceous And Arboraceous Biomass: Fuel Composition Dependence And The Variability Of Commonly Used Nitrile Tracers, Matthew M. Coggon, Patrick R. Veres, Bin Yuan, Abigail Koss, Carsten Warneke, Jessica B. Gilman, Brian M. Lerner, Jeff Peischl, Kenneth C. Aikin, Chelsea E. Stockwell, Lindsay E. Hatch, Thomas B. Ryerson, James M. Roberts, Robert J. Yokelson, Joost A. De Gouw

Chemistry and Biochemistry Faculty Publications

Volatile organic compounds (VOCs) emitted from residential wood and crop residue burning were measured in Colorado, U.S. When compared to the emissions from crop burning, residential wood burning exhibited markedly lower concentrations of acetonitrile, a commonly used biomass burning tracer. For both herbaceous and arboraceous fuels, the emissions of nitrogen-containing VOCs (NVOCs) strongly depend on the fuel nitrogen content; therefore, low NVOC emissions from residential wood burning result from the combustion of low-nitrogen fuel. Consequently, the emissions of compounds hazardous to human health, such as HNCO and HCN, and the formation of secondary pollutants, such as ozone generated by NOx, …

Field Measurements Of Trace Gases And Aerosols Emitted By Peat Fires In Central Kalimantan, Indonesia, During The 2015 El Niño, Chelsea E. Stockwell, Thilina Jayarathne, Mark A. Cochrane, Kevin C. Ryan, Erianto I. Putra, Bambang H. Saharjo, Ati D. Nurhayati, Israr Albar, Donald R. Blake, Isobel J. Simpson, Elizabeth A. Stone, Robert J. Yokelson

Chemistry and Biochemistry Faculty Publications

Peat fires in Southeast Asia have become a major annual source of trace gases and particles to the regional-global atmosphere. The assessment of their influence on atmospheric chemistry, climate, air quality, and health has been uncertain partly due to a lack of field measurements of the smoke characteristics. During the strong 2015 El Niño event we deployed a mobile smoke sampling team in the Indonesian province of Central Kalimantan on the island of Borneo and made the first, or rare, field measurements of trace gases, aerosol optical properties, and aerosol mass emissions for authentic peat fires burning at various depths …

Nepal Ambient Monitoring And Source Testing Experiment (Namaste): Emissions Of Trace Gases And Light-Absorbing Carbon From Wood And Dung Cooking Fires, Garbage And Crop Residue Burning, Brick Kilns, And Other Sources, Chelsea E. Stockwell, Ted J. Christian, J. Douglas Goetz, Thilina Jayarathne, Prakash V. Bhave, Puppala S. Praveen, Sagar Adhikari, Rashmi Maharjan, Peter F. Decarlo, Elizabeth A. Stone, Eri Saikawa, Donald R. Blake, Isobel J. Simpson, Robert J. Yokelson, Arnico K. Panday

Chemistry and Biochemistry Faculty Publications

The Nepal Ambient Monitoring and Source Testing Experiment (NAMaSTE) campaign took place in and around the Kathmandu Valley and in the Indo-Gangetic Plain (IGP) of southern Nepal during April 2015. The source characterization phase targeted numerous important but undersampled (and often inefficient) combustion sources that are widespread in the developing world such as cooking with a variety of stoves and solid fuels, brick kilns, open burning of municipal solid waste (a.k.a. trash or garbage burning), crop residue burning, generators, irrigation pumps, and motorcycles. NAMaSTE produced the first, or rare, measurements of aerosol optical properties, aerosol mass, and detailed trace gas …