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Environmental Cost Vs. Health Benefit Of Radioisotope Usage In Medicine, Nicholas Whiting 2019 Rowan University

Environmental Cost Vs. Health Benefit Of Radioisotope Usage In Medicine, Nicholas Whiting

Open Educational Resources

This module is developed for implementation in a class that discusses the use of radioisotopes in a biomedical setting. The inspiration is a class I teach (Advanced Biomedical Instrumentation), which covers the use of radioisotopes as tracers in biomedical imaging (scintigraphy, SPECT, PET, etc.). The goal of the module is to go further in depth regarding the environmental impact of the use of radioisotopes (from their generation to their disposal—keeping track of any radioactive byproducts), and compare that to the potential for benefits in the quality and/or quantity of a patient’s life (does using the radioisotopes allow ...


Cold Atmospheric Plasma Induces Accumulation Of Lysosomes And Caspase-Independent Cell Death In U373mg Glioblastoma Multiforme Cells, Gillian Conway, Zhonglei He, Ana L. Hutanu, George P. Cribaro, Eline Manaloto, Alan Casey, Damien Traynor, Vladimir Milosavljevic, Orla Howe, Carlos Barcia, James T. Murray, Patrick J. Cullen, James Curtin 2019 Technological University Dublin

Cold Atmospheric Plasma Induces Accumulation Of Lysosomes And Caspase-Independent Cell Death In U373mg Glioblastoma Multiforme Cells, Gillian Conway, Zhonglei He, Ana L. Hutanu, George P. Cribaro, Eline Manaloto, Alan Casey, Damien Traynor, Vladimir Milosavljevic, Orla Howe, Carlos Barcia, James T. Murray, Patrick J. Cullen, James Curtin

Articles

Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma ...


Synthesis Of Crosslinkable Poly(Ester Amide)S For Cell Encapsulation And Delivery, Yu Ting (Natalie) Liang 2019 The University of Western Ontario

Synthesis Of Crosslinkable Poly(Ester Amide)S For Cell Encapsulation And Delivery, Yu Ting (Natalie) Liang

Electronic Thesis and Dissertation Repository

Tissue engineering using adipose-derived stromal cells (ASCs) shows promise for soft tissue regeneration. Biodegradable polymers are potential biomaterials as they support the growth and delivery of cells. Specifically, poly(ester amide)s (PEAs) are a class of biodegradable polymers with tunable structures that have been shown to exhibit low cytotoxicity and support the growth of various cell types. This thesis involved the development of new water soluble amino acid-based PEAs with crosslinkable moieties to enable formation of hydrogel scaffolds for ASC encapsulation. These hydrophilic phenylalanine-based and alanine-based PEAs were synthesized by solution polycondensation and photo-crosslinked into a series of hydrogels ...


Evaluation Of Epas1 Variants For Association With Bovine Congestive Heart Failure [Version 1; Peer Review: 2 Approved], Michael P. Heaton, Adam S. Bassett, Katherine J. Whitman, Greta M. Krafsur, Sang M. Lee, Jaden M. Carlson, Halden J. Clark, Helen R. Smith, Madeline C. Pelster, Veronica Basnayake, Dale M. Grotelueschen, B. Vander Ley 2019 U.S. Meat Animal Research Center

Evaluation Of Epas1 Variants For Association With Bovine Congestive Heart Failure [Version 1; Peer Review: 2 Approved], Michael P. Heaton, Adam S. Bassett, Katherine J. Whitman, Greta M. Krafsur, Sang M. Lee, Jaden M. Carlson, Halden J. Clark, Helen R. Smith, Madeline C. Pelster, Veronica Basnayake, Dale M. Grotelueschen, B. Vander Ley

Papers in Veterinary and Biomedical Science

Background: Bovine congestive heart failure (BCHF) has become increasingly prevalent in feedlot cattle in the Western Great Plains of North America. BCHF is an untreatable complex condition involving pulmonary hypertension that culminates in right ventricular failure and death. A protein variant of hypoxia-inducible factor 2 alpha (HIF2α, encoded by the endothelial PAS domain-containing protein 1 gene, EPAS1) was previously reported to be associated with pulmonary hypertension at altitudes exceeding 2,000 m. Our aim was to evaluate EPAS1 haplotypes for association with BCHF in feedlot cattle raised at moderate altitudes (1,200 m).

Methods: Paired samples of clinical cases and ...


Chemical Epitope Targeting: Review Of A Novel Screening Technology, Qurrat Ul-Ain, Rene Kandler, Dylan Gillespie, Arundhati Nag 2019 Clark University

Chemical Epitope Targeting: Review Of A Novel Screening Technology, Qurrat Ul-Ain, Rene Kandler, Dylan Gillespie, Arundhati Nag

Scholarly Undergraduate Research Journal at Clark

Chemical Epitope Targeting is a novel technology developed for designing peptide ligands with high affinity and specificity against specific regions of a protein that may be inaccessible to small molecules or antibodies. In this review, we summarize the key steps and significant applications of this technology. Operating on the same principles as antibody-antigen interactions, this technique involves chemically synthesizing the region of interest on the protein, called the epitope, as a polypeptide with a biotin detection tag and a strategically placed alkyne or azide presenting amino acid. The constructed epitope is screened against a comprehensive linear or cyclic One Bead ...


The Central Role Of The Tail In Switching Off 10s Myosin Ii Activity, Shixin Yang, Kyounghwan Lee, John L. Woodhead, Osamu Sato, Mitsuo Ikebe, Roger Craig 2019 University of Massachusetts Medical School

The Central Role Of The Tail In Switching Off 10s Myosin Ii Activity, Shixin Yang, Kyounghwan Lee, John L. Woodhead, Osamu Sato, Mitsuo Ikebe, Roger Craig

Radiology Publications and Presentations

Myosin II is a motor protein with two heads and an extended tail that plays an essential role in cell motility. Its active form is a polymer (myosin filament) that pulls on actin to generate motion. Its inactive form is a monomer with a compact structure (10S sedimentation coefficient), in which the tail is folded and the two heads interact with each other, inhibiting activity. This conformation is thought to function in cells as an energy-conserving form of the molecule suitable for storage as well as transport to sites of filament assembly. The mechanism of inhibition of the compact molecule ...


Hyaluronan At The Brain-Environment Interface, Donald M. Thevalingam 2019 The Graduate Center, City University of New York

Hyaluronan At The Brain-Environment Interface, Donald M. Thevalingam

All Dissertations, Theses, and Capstone Projects

Hyaluronan (HA; Hyaluronic Acid), a primary scaffolding component of the brain extracellular matrix, serves as an integral structural component to the brain extracellular space (ECS). The fossorial African naked mole-rat (Heterocephalus glaber; NM-R), a mammal which lives in a low-oxygen environment and is capable of tolerating hypoxia and hypercapnia, has been shown to synthesize and sustain a unique high-molecular-mass variant of hyaluronan macromolecule (HMM-HA). This body of work highlights HA’s role in mediating the interplay between brain ECM composition, ECS structure, and cell viability.

Here we employ the NM-R as a unique animal model to observe the role of ...


Minimalistic Peptide-Based Supramolecular Systems Relevant To The Chemical Origin Of Life, Daniela Kroiss 2019 The Graduate Center, City University of New York

Minimalistic Peptide-Based Supramolecular Systems Relevant To The Chemical Origin Of Life, Daniela Kroiss

All Dissertations, Theses, and Capstone Projects

All forms of life are based on biopolymers, which are made up of a selection of simple building blocks, such as amino acids, nucleotides, fatty acids and sugars. Their individual properties govern their interactions, giving rise to complex supramolecular structures with highly specialized functionality, including ligand recognition, catalysis and compartmentalization. In this thesis, we aim to answer the question whether short peptides could have acted as precursors of modern proteins during prebiotic evolution. Using a combination of experimental and computational techniques, we screened a large molecular search space for peptide sequences that are capable of forming supramolecular complexes with adenosine ...


Renal Specific Rnai Delivery By Fibrillar Nanoparticle Excipients, Sam Wong 2019 The Graduate Center, City University of New York

Renal Specific Rnai Delivery By Fibrillar Nanoparticle Excipients, Sam Wong

All Dissertations, Theses, and Capstone Projects

RNA interference (RNAi) is a powerful tool to manipulate the phenotype of an organism by silencing the expression of specific genes and is viewed as a highly promising platform for treating undruggable targets and disorders where small molecule drugs and antibodies would fail. However, development of RNAi based therapies has faced major barriers including cellular and tissue-specific uptake of the Small Interfering RNA (siRNA). Utilizing different nanoparticles as RNAi excipients, cellular uptake and gene silencing potency can be greatly improved. The research in Dr. McDevitt groups has fibrillar carbon nanotubes (CNT) as carriers for siRNA for gene silencing in vitro ...


Engineering Of Escherichia Coli 2-Oxoglutarate Dehydrogenase Complex With Mechanistic And Synthetic Goals, Joydeep Chakraborty 2019 New Jersey Institute of Technology

Engineering Of Escherichia Coli 2-Oxoglutarate Dehydrogenase Complex With Mechanistic And Synthetic Goals, Joydeep Chakraborty

Dissertations

The Escherichia coli 2-oxoglutarate dehydrogenase complex (OGDHc) compromises multiple copies of three enzymes - 2-oxoglutarate dehydrogenase (E1o), dihydrolipoyl succinyltransferase (E2o), and dihydrolipoyl dehydrogenase (E3). OGDHc is found in the Krebs cycle and catalyzes the formation of the all-important succinyl-Coenzyme A (succinyl-CoA). OGDHc was engineered to understand the catalytic mechanism and optimized for chemical synthetic goals.

Succinyl-CoA formation takes place within the catalytic domain of E2o via a transesterification reaction. The succinyl group from the thiol ester of S8-succinyldihydrolipoyl-E2o is transferred to the thiol group of CoA. Mechanistic studies were designed to investigate enzymatic transthioesterification. His375 and Asp374 was shown to be ...


A Unified Encyclopedia Of Human Functional Dna Elements Through Fully Automated Annotation Of 164 Human Cell Types, Maxwell W. Libbrecht, Oscar L. Rodriguez, Zhiping Weng, Jeffrey A. Bilmes, Michael M. Hoffman, William Stafford Noble 2019 Simon Fraser University

A Unified Encyclopedia Of Human Functional Dna Elements Through Fully Automated Annotation Of 164 Human Cell Types, Maxwell W. Libbrecht, Oscar L. Rodriguez, Zhiping Weng, Jeffrey A. Bilmes, Michael M. Hoffman, William Stafford Noble

Open Access Articles

Semi-automated genome annotation methods such as Segway take as input a set of genome-wide measurements such as of histone modification or DNA accessibility and output an annotation of genomic activity in the target cell type. Here we present annotations of 164 human cell types using 1615 data sets. To produce these annotations, we automated the label interpretation step to produce a fully automated annotation strategy. Using these annotations, we developed a measure of the importance of each genomic position called the "conservation-associated activity score." We further combined all annotations into a single, cell type-agnostic encyclopedia that catalogs all human regulatory ...


Metnet: Systems Biology Tools For Arabidopsis, Eve Syrkin Wurtele, Ling Li, Dan Berleant, Dianne Cook, Julie A. Dickerson, Jing Ding, Heike Hofmann, Michael Lawrence, Eun-kyung Lee, Jie Li, Wieslawa Mentzen, Leslie Miller, Basil J. Nikolau, NIck Ransom, Yingjun Wang 2019 Iowa State University

Metnet: Systems Biology Tools For Arabidopsis, Eve Syrkin Wurtele, Ling Li, Dan Berleant, Dianne Cook, Julie A. Dickerson, Jing Ding, Heike Hofmann, Michael Lawrence, Eun-Kyung Lee, Jie Li, Wieslawa Mentzen, Leslie Miller, Basil J. Nikolau, Nick Ransom, Yingjun Wang

Ling Li

MetNet (http://metnetdb.org) is an emerging open-source software platform for exploration of disparate experimental data types and regulatory and metabolic networks in the context of Arabidopsis systems biology. The MetNet platform features graph visualization, interactive displays, graph theoretic computations for determining biological distances, a unique multivariate display and statistical analysis tool, graph modeling using the open source statistical analysis language, R, and versatile text mining. The use of these tools is illustrated with data from the bio1 mutant of Arabidopsis.


Early Warning Of Global Change Effects On Catchment Nutrient Exports, Haibin Dong 2019 The University of Western Ontario

Early Warning Of Global Change Effects On Catchment Nutrient Exports, Haibin Dong

Electronic Thesis and Dissertation Repository

Global change scientists seek sentinels of change. On forested landscapes, first-order catchments serve as sentinels of global stressors and their effects on downstream surface waters. Here, I explored global stressors – including climate warming, hydrological intensification, and recovery from atmospheric acidic deposition – and their effects on nutrient exports in 22-year stream chemistry records from 41 forested first-order catchments in a network of North American long-term monitoring sites. First, I used multivariate autoregressive models to establish relationships between changes in global stressors and changes in catchment nutrient exports. Second, I analyzed the residuals of these relationships to determine if there was evidence ...


Spectroscopic Description Of The E1 State Of Mo Nitrogenase Based On Mo And Fe X‑Ray Absorption And MöSsbauer Studies, Casey Van Stappen, Roman Davydov, Zhi-Yong Yang, Ruixi Fan, Yisong Guo, Eckhard Bill, Lance C. Seefeldt, Brian M. Hoffman, Serena DeBeer 2019 Max Planck Institute for Chemical Energy Conversion

Spectroscopic Description Of The E1 State Of Mo Nitrogenase Based On Mo And Fe X‑Ray Absorption And MöSsbauer Studies, Casey Van Stappen, Roman Davydov, Zhi-Yong Yang, Ruixi Fan, Yisong Guo, Eckhard Bill, Lance C. Seefeldt, Brian M. Hoffman, Serena Debeer

Chemistry and Biochemistry Faculty Publications

Mo nitrogenase (N2ase) utilizes a two-component protein system, the catalytic MoFe and its electron-transfer partner FeP, to reduce atmospheric dinitrogen (N2) to ammonia (NH3). The FeMo cofactor contained in the MoFe protein serves as the catalytic center for this reaction and has long inspired model chemistry oriented toward activating N2. This field of chemistry has relied heavily on the detailed characterization of how Mo N2ase accomplishes this feat. Understanding the reaction mechanism of Mo N2ase itself has presented one of the most challenging problems in bioinorganic chemistry because of the ephemeral nature of its catalytic intermediates, which ...


Mechanism For Apobec3g Catalytic Exclusion Of Rna And Non-Substrate Dna, William C. Solomon, Wazo Myint, Shurong Hou, Tapan Kanai, Rashmi Tripathi, Nese Kurt Yilmaz, Celia A. Schiffer, Hiroshi Matsuo 2019 University of Minnesota

Mechanism For Apobec3g Catalytic Exclusion Of Rna And Non-Substrate Dna, William C. Solomon, Wazo Myint, Shurong Hou, Tapan Kanai, Rashmi Tripathi, Nese Kurt Yilmaz, Celia A. Schiffer, Hiroshi Matsuo

Schiffer Lab Publications

The potent antiretroviral protein APOBEC3G (A3G) specifically targets and deaminates deoxycytidine nucleotides, generating deoxyuridine, in single stranded DNA (ssDNA) intermediates produced during HIV replication. A non-catalytic domain in A3G binds strongly to RNA, an interaction crucial for recruitment of A3G to the virion; yet, A3G displays no deamination activity for cytidines in viral RNA. Here, we report NMR and molecular dynamics (MD) simulation analysis for interactions between A3Gctd and multiple substrate or non-substrate DNA and RNA, in combination with deamination assays. NMR ssDNA-binding experiments revealed that the interaction with residues in helix1 and loop1 (T201-L220) distinguishes the binding mode of ...


Egfp Insertional Mutagenesis Reveals Multiple Fxr2p Fibrillar States With Differing Ribosome Association In Neurons, Emily E. Stackpole, Michael R. Akins, Mariya Ivshina, Anastasia C. Murthy, Nicolas L. Fawzi, Justin R. Fallon 2019 Brown University

Egfp Insertional Mutagenesis Reveals Multiple Fxr2p Fibrillar States With Differing Ribosome Association In Neurons, Emily E. Stackpole, Michael R. Akins, Mariya Ivshina, Anastasia C. Murthy, Nicolas L. Fawzi, Justin R. Fallon

Open Access Articles

RNA-binding proteins (RBPs) function in higher-order assemblages such as RNA granules to regulate RNA localization and translation. The Fragile X homolog FXR2P is an RBP essential for formation of neuronal Fragile X granules that associate with axonal mRNA and ribosomes in the intact brain. However, the FXR2P domains important for assemblage formation in a cellular system are unknown. Here we used an EGFP insertional mutagenesis approach to probe for FXR2P intrinsic features that influence its structural states. We tested 18 different in-frame FXR2P(EGFP) fusions in neurons and found that the majority did not impact assemblage formation. However, EGFP insertion ...


Hsp90/Axl/Eif4e-Regulated Unfolded Protein Response As An Acquired Vulnerability In Drug-Resistant Kras-Mutant Lung Cancer, Haitang Yang, Shun-Qing Liang, Duo Xu, Zhang Yang, Thomas M. Marti, Yanyun Gao, Gregor J. Kocher, Heng Zhao, Ralph A. Schmid, Ren-Wang Peng 2019 University of Bern

Hsp90/Axl/Eif4e-Regulated Unfolded Protein Response As An Acquired Vulnerability In Drug-Resistant Kras-Mutant Lung Cancer, Haitang Yang, Shun-Qing Liang, Duo Xu, Zhang Yang, Thomas M. Marti, Yanyun Gao, Gregor J. Kocher, Heng Zhao, Ralph A. Schmid, Ren-Wang Peng

Open Access Articles

Drug resistance and tumor heterogeneity are formidable challenges in cancer medicine, which is particularly relevant for KRAS-mutant cancers, the epitome of malignant tumors recalcitrant to targeted therapy efforts and first-line chemotherapy. In this study, we delineate that KRAS-mutant lung cancer cells resistant to pemetrexed (MTA) and anti-MEK drug trametinib acquire an exquisite dependency on endoplasmic reticulum (ER) stress signaling, rendering resistant cancer cells selectively susceptible to blockage of HSP90, the receptor tyrosine kinase AXL, the eukaryotic translation initiation factor 4E (eIF4E), and the unfolded protein response (UPR). Mechanistically, acquisition of drug resistance enables KRAS-mutant lung cancer cells to bypass canonical ...


Promotion Of Adipogenesis By Jmjd6 Requires The At Hook-Like Domain And Is Independent Of Its Catalytic Function, Pablo Reyes-Gutierrez, Jake W. Carrasquillo-Rodriguez, Anthony N. Imbalzano 2019 University of Massachusetts Medical School

Promotion Of Adipogenesis By Jmjd6 Requires The At Hook-Like Domain And Is Independent Of Its Catalytic Function, Pablo Reyes-Gutierrez, Jake W. Carrasquillo-Rodriguez, Anthony N. Imbalzano

Open Access Articles

JMJD6 is a member of the Jumonji C domain containing enzymes that demethylate and/or hydroxylate substrate proteins. It is a multi-functional protein that has been implicated in disparate aspects of transcriptional and post-transcriptional control of gene expression, including but not limited to enhancer and promoter binding, release of paused RNA polymerase II, control of splicing, and interaction with the translation machinery. JMJD6 contributes to multiple aspects of animal development, including adipogenesis modeled in culture. We mutated proposed or characterized domains in the JMJD6 protein to better understand the requirement for JMJD6 in adipogenic differentiation. Mutation of JMJD6 amino acids ...


Trophic Upgrading And Mobilization Of Wax Esters In Microzooplankton, Keyana Roohani, Brad A. Haubrich, Kai-Lou Yue, Nigel D'souza, Amanda Mantalbano, Tatiana Rynearson, Susanne Menden-Deuer, Christopher Reid 2019 University of Nevada, Reno

Trophic Upgrading And Mobilization Of Wax Esters In Microzooplankton, Keyana Roohani, Brad A. Haubrich, Kai-Lou Yue, Nigel D'Souza, Amanda Mantalbano, Tatiana Rynearson, Susanne Menden-Deuer, Christopher Reid

Science and Technology Faculty Journal Articles

Heterotrophic protists play pivotal roles in aquatic ecosystems by transferring matter and energy, including lipids, from primary producers to higher trophic predators. Using Oxyrrhis marina as a model organism, changes to the non-saponifiable protist lipids were investigated under satiation and starvation conditions. During active feeding on the alga Cryptomonas sp., the O. marina hexane soluble non-saponifiable fraction lipid profile reflected its food source with the observed presence of long chain mono-unsaturated fatty alcohols up to C25:1. Evidence of trophic upgrading in O. marina was observed with long chain mono-unsaturated fatty alcohol accumulation of up to C35:1. To the ...


Assessing The Structure-Function Relationships Of The Apolipoprotein(A) Kringle Iv Sub-Type 10 Domain, Matthew J. Borrelli 2019 The University of Western Ontario

Assessing The Structure-Function Relationships Of The Apolipoprotein(A) Kringle Iv Sub-Type 10 Domain, Matthew J. Borrelli

Electronic Thesis and Dissertation Repository

Elevated plasma lipoprotein(a) (Lp(a)) is the most prevalent heritable risk factor in the development of cardiovascular disease. The apolipoprotein(a) (apo(a)) component of Lp(a) is strongly implicated in the pathogenicity of Lp(a). It is hypothesized that the inflammatory potential of Lp(a)/apo(a) is mediated by the lysine binding ability of the apo(a) kringle IV10 (KIV10) domain, along with its covalently bound oxidized phospholipid (oxPL). Using targeted mutagenesis, two novel null alleles for the LPA gene that generate non-secretable apo(a) species have been identified, resulting from amino acid substitutions in the KIV10 ...


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