Biochemistry Commons^™

Clinical Applications Of Infrared And Raman Spectroscopy: State Of Play And Future Challenges, Matthew Baker, Hugh Byrne, John Chalmers, Peter Gardner, Royston Goodacre, Alex Henderson, Sergei Kazarian, Francis Martin, Julian Moger, Nick Stone, Josep Sule-Suso

Articles

Vibrational spectroscopies, based on Infrared absorption and/or Raman scattering provide a detailed fingerprint of a material, based on the chemical content. Diagnostic and prognostic tools based on these technologies have the potential to revolutionise our clinical systems leading to improved patient outcome, more efficient public services and significant economic savings. However, despite these strong drivers, there are many fundamental scientific and technological challenges which have limited the implementation of this technology in the clinical arena, although recent years have seen significant progress in addressing these challenges. This review examines (i) the state of the art of clinical applications of infrared …

Role Of Leptin And Dyslipidemia In Chronic Kidney Disease, Sabeela Noor, Faiza Alam, Syeda Sadia Fatima, Mahnur Khan, Rehana Rehman

Department of Biological & Biomedical Sciences

Chronic kidney disease (CKD) patients are at an increased risk of cardiovascular complications and plasma leptin level is elevated in cardio renal syndrome. We wanted to explore leptin levels in patients with different stages of CKD and find its association with risk of cardiovascular disease. This cross-sectional study was conducted in Nephrology Department of Jinnah Post Graduate Medical Centre (JPMC) from January 2014 to September 2014. Group I comprised of controls (GFR=116±8.3, n = 44) acquired from general population, CKD patients were grouped as II, III and IV respectively with GFR; 85.77±9.9 (n = 42), 53.84±9.9 (n=42) and 20.22±8.4 (n …

Functional And Structural Impact Of The Loss Of The Leucine-Rich Repeat Protein Lrit1 In The Mouse Retina., Catherine Ann Cobb

Electronic Theses and Dissertations

Mutations in genes encoding the leucine-rich repeat (LRR) proteins nyctalopin and LRIT3 lead to complete congenital stationary night blindness because they are critical to depolarizing bipolar cell function in the retina. LRIT3 has two closely related family members, LRIT1 and LRIT2. In silico analyses of publicly available RNA-Seq data showed that Lrit1 was highly expressed in the retina. Here I describe the expression pattern and impact of loss of LRIT1 on retinal function. To enable these studies, we used CRISPR/Cas9 technology to create an Lrit1^-/- mouse line. Retinal morphology and morphometry analyses showed no gross changes in retinal structure …

Nanoscale Organization Of The Small Gtpase Rac1, Kelsey Maxwell

Dissertations and Theses (Open Access)

Rac1 is a small, guanine-nucleotide binding protein that cycles between an inactive GDP-bound and active GTP-bound state to regulate actin-mediated motility, migration, and adhesion. Plasma membrane (PM) localization is essential for its biological activity. Rac1 PM targeting is directed by a C-terminal membrane anchor that encompasses a geranylgeranyl-cysteine-methyl-ester, palmitoyl, and a polybasic domain (PBD) of contiguous lysine and arginine residues. Using high-resolution imaging combined with spatial mapping analysis, I found that Rac1 forms nanoclusters on the PM. Cycling between the GTP- and GDP-bound states, Rac1 forms nanoclusters that are non-overlapping, consequently undergoing guanine nucleotide-dependent spatial segregation. I further found that …

A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo

Undergraduate Theses

Chalcones, a precursor to flavonoids, are chemical compounds found naturally in plants. The chalcones’ structure consists of a ketone bridge attached to two aromatic rings. Varying substituents on the aromatic rings allow for different affects, including anti-cancer properties. As a Michael acceptor, chalcones interact with pathways that cause inhibition of the initiation, promotion, and progression of cancer tumors. We have screened 32 compounds for growth inhibition in lung cells that vary the flexibility and confirmation of the 3 carbon bridge between the two aromatic rings as well as the effects of electronic modifications to the aromatic ring. We have found …

Ef-P Post-Translational Modification Has Variable Impact On Polyproline Translation In Bacillus Subtilis, Anne Witzky, Katherine R. Hummels, Rodney Tollerson Ii, Andrei Rajkovic, Lisa A. Jones, Daniel B. Kearns, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P (EF-P) is a ubiquitous translation factor that facilitates translation of polyproline motifs. In order to perform this function, EF-P generally requires posttranslational modification (PTM) on a conserved residue. Although the position of the modification is highly conserved, the structure can vary widely between organisms. In Bacillus subtilis, EF-P is modified at Lys³² with a 5-aminopentanol moiety. Here, we use a forward genetic screen to identify genes involved in 5-aminopentanolylation. Tandem mass spectrometry analysis of the PTM mutant strains indicated that ynbB, gsaB, and ymfI are required for modification and that yaaO, yfkA, and …

Toxicological Assessment Of Nanomaterials: The Role Of In Vitro Raman Microspectroscopic Analysis, Esen Efeoglu, Marcus Maher, Alan Casey, Hugh Byrne

Articles

The acceleration of nanomaterials research has brought about increased demands for rapid analysis of their bioactivity, in a multi-parametric fashion, to minimise the gap between potential applications and knowledge of their toxicological properties. The potential of Raman microspectroscopy for the analysis of biological systems with the aid of multivariate analysis techniques has been demonstrated. In this study, an overview of recent efforts towards establishing a ‘label-free high content nanotoxicological assessment technique’ using Raman microspectroscopy is presented. The current state of the art for cellular toxicity assessment and the potential of Raman microspectroscopy are discussed, and the spectral markers of the …

Inpatient Satisfaction At Different Public Sector Hospitals Of A Metropolitan City In Pakistan: A Comparative Cross-Sectional Study, Mehwish Hussain, Rehana Rehman, Zia Ikramuddin, Nava Asad, Ayesha Farooq

Department of Biological & Biomedical Sciences

Objective: To observe inpatient satisfaction at different public sector hospitals of Karachi, Pakistan.
Methods: A cross sectional study was carried out during 2010-2012 in four major public sector hospitals of Karachi. A total of 710 patients completed the study. Responses were gathered in a self-structured questionnaire that comprised of four dimensions of satisfaction with doctor, staff, administration and treatment. Average Score of each dimension was taken and compared using one way analysis of variance.
Result: Satisfaction with doctors, staff and administration of provincial and federal hospitals were comparatively similar (P > 0.05). However, satisfaction with treatment significantly differed in all four …

Cross Talk Between Serum Kisspeptin-Leptin During Assisted Reproduction Techniques, Rehana Rehman, Zehra Jamil, Aqsa Khalid, Syeda Sadia Fatima

Department of Biological & Biomedical Sciences

Background & Objective: Leptin facilitates onset of puberty by impact on hypothalamic Kisspeptin, gonadotropin releasing hormone, follicle stimulating and luteinizing hormone. The link of peripheral Leptin-Kisspeptin in regulating the ovarian and endometrial tissue in relation to adiposity is unknown. Therefore, we wanted to identify Kisspeptin-Leptin association with body mass index (BMI) and success of assisted reproductive treatments (ART) in infertile females.
Methods: A cross sectional study was carried from August 2014 till May 2016 after receiving ethical approval at Australian Concept Infertility Medical Centre, and Aga Khan University. The study group comprised of females with an age range …

Role Of The Snf2 Homolog, Irc20, In Yeast Genome Maintenance, Deena Mohamed Galal Eldin Ahmed

Theses

In eukaryotes, DNA is wrapped around histone proteins forming a highly compact structure, the chromatin. All DNA-based processes must occur within the complex organization of the chromatin, and this requires modulation of its structure when needed. This is accomplished by covalent histone modifications that alter histone-DNA contacts, as well as through the actions of ATP-dependent chromatin remodelers. These multi-subunit complexes play major roles in transcription regulation, replication and repairing DNA damage. This thesis aims to characterize a poorly studied member of the SWI/SNF family of ATPases/helicases, Irc20, from Saccharomyces cerevisiae. Previously, Irc20 has been shown to be involved in …

Increased Liver Tumor Formation In Neutral Sphingomyelinase-2-Deficient Mice, Liansheng Zhong, Ji Na Kong, Michael B. Dinkins, Silvia Leanhart, Zhihui Zhu, Stefka D. Spassieva, Haiyan Qin, Hsuan-Pei Lin, Ahmed Elsherbini, Rebecca Wang, Xue Jiang, Mariana N. Nikolova‑Karakashian, Guanghu Wang, Erhard Bieberich

Physiology Faculty Publications

Sphingolipids are key signaling lipids in cancer. Genome-wide studies have identified neutral SMase-2 (nSMase2), an enzyme generating ceramide from SM, as a potential repressor for hepatocellular carcinoma. However, little is known about the sphingolipids regulated by nSMase2 and their roles in liver tumor development. We discovered growth of spontaneous liver tumors in 27.3% (9 of 33) of aged male nSMase2-deficient (fro/fro) mice. Lipidomics analysis showed a marked increase of SM in the tumor. Unexpectedly, tumor tissues presented with more than a 7-fold increase of C₁₆-ceramide, concurrent with upregulation of ceramide synthase 5. The fro/fro liver tumor, …

The Effect Of Ammonia On The Germination And Outgrowth Of Bacillius Globigii, Joseph B. Kunicki

Theses and Dissertations

This research investigated the germination and outgrowth of Bacillus globigii in the presence of ammonia in laboratory scale experiments. Germination was measured by monitoring the release of dipicolinic acid, an organic compound present in bacterial spores, while outgrowth was measured using phase-bright microscopy and semi-automated counting procedures. The ammonia-N concentrations investigated generally did not cause statistically significant differences in the initial 1-hr germination rates or the average 3-hr outgrowth rates of Bacillus globigii spores in batch style experiments. The average 1-hr germination rates observed in the absence of ammonia-N was 0.0258 hr^-1 for the water and buffer controls and …

A Chimeric Nucleobase - Phenylazo Derivative As An Intrinsic Nucleobase Quencher, Gyeongsu Park, Timothy Martin-Chan, Amer El Samm, Robert H.E. Hudson

Western Research Forum

Molecular beacons are important bioanalytical probes which are most often

constructed from a single-stranded oligonucleotide which has been labeled at

opposite termini with a fluorophore and a quencher. When the fluorophore and

quencher are in close proximity, no fluorescence is observed due to FRET

(Fluorescence Resonance Energy Transfer). DABCYL (4-dimethylaminoazobenzene-

4'-carboxylic acid) has been used as a quencher in the molecular beacon to absorbs

excitation energy from a fluorophore and to dissipate the energy as heat. However,

DABCYL is unable to form a base-pair and is conventionally placed as an overhanging

residue. This produces a derivative wherein the chromophore has …

Developing Novel Therapeutics For Bacterial Lung Infections, Brandon J. Baer, Ruud Veldhuizen, Cory Yamashita

Western Research Forum

Background: Bacterial lung infections are leading causes of death worldwide. Unfortunately, increasing resistance to antibiotics and the inflammation often accompanying these infections are leading to poor outcomes despite antibiotic intervention. Complicating treatment further, the tree-like branching structure of the lung makes drug delivery to distal sites of infection difficult. Our research aims to address these challenges by developing new therapeutics and new tools to improve and assess drug delivery, bacterial killing and inflammation. Our therapy combines host defense peptides, which have been shown to kill antibiotic-resistant bacteria and down regulate inflammation, with a pulmonary vehicle, exogenous surfactant, that can improve …

Studies Of Amino Acid Mutations In Drug Resistance Of The Smo Protein, Eunice Wintona

UNO Student Research and Creative Activity Fair

Smoothened receptor (SMO) is a protein that in humans, is encoded by the SMO gene. A systemic mutation in its binding pocket helps predict the sensitivity of mutant proteins to different drugs. Known as a GPCR-like receptor, it is a component of the hedgehog signaling pathway; a pathway involved in body patterning and the regulation of adult stem cells. An uncontrolled or inappropriate activation of the Hedgehog pathway drives tumor progression in cancers and a number of birth defects. To achieve these goals, the molecular modeling software MOE was used to build small molecules and drug molecules like Vismodegib and …

A Gender-Based Comparison In Health Behaviors And State Of Happiness Among University Students, Rehana Rehman, Amara Zafar, Aleena Mohib, Mukhtiar Baig

Department of Biological & Biomedical Sciences

Objective: The presence of good healthy behaviors among university students is imperative for their future life. This study aimed to compare positive health behaviors and state of happiness between the two genders of Bahria University (BU), Karachi, Pakistan.
Subjects and methods: This cross-sectional study was conducted at BU, Karachi, Pakistan. A total 813 students participated in this study. The healthquestionnaire, adapted from Health and Behavior Survey and the Subjective Happiness Scale, was used to assess self-reported happiness. The data were analyzed using IBM SPSS version 22.
Results: Overall self-reported health behaviors were found to be more prevalent in females as …

Lack Of Association Of Statin Use With Vitamin D Levels In A Hospital Based Population Of Type 2 Diabetes Mellitus Patients, Khalida Iqbal, Najmul Islam, Iqbal Azam Syed, Naseema Mehboobali, Mohammad Perwaiz Iqbal

Department of Biological & Biomedical Sciences

Objective: To investigate the relationship of statins (drug given to reduce serum levels of LDL-cholesterol) on vitamin D levels of Pakistani type 2 diabetes mellitus (DM) patients in a hospital in Karachi.
Methods: In a cross-sectional survey, 312 consecutive patients with type 2 DM (219 males and 93 females, age 22-70 years) were recruited with informed consent. A questionnaire was administered to find out whether they were statin users or non-users. Serum was analyzed for concentrations of 25(OH) vitamin D [25(OH)D] and other related biomarkers such as serum cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, phosphate and calcium using kit methods. Multiple Linear …

Curcumin Potentiates The Function Of Human Α7-Nicotinic Acetylcholine Receptors Expressed In Sh-Ep1 Cells, Eslam El Nebrisi, Lina T. Al Kury, Keun-Hang Susan Yang, Petrilla Jayaprakash, Frank Christopher Howarth, Nadine Kabbani, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Effects of curcumin, a biologically active ingredient of turmeric, were tested on the Ca²⁺transients induced by the activation of α₇ subunit of the human nicotinic acetylcholine (α₇nACh) receptor expressed in SH-EP1 cells. Curcumin caused a significant potentiation of choline (1 mM)-induced Ca²⁺ transients with an EC₅₀ value of 133 nM. The potentiating effect of curcumin was not observed in Ca²⁺ transients induced by high K⁺ (60 mM) containing solutions or activation of α₄β₂ nACh receptors and the extent of curcumin potentiation was not altered in the presence of …

The Potential Of Achiral Sponge-Derived And Synthetic Bromoindoles As Selective Cytotoxins Against Panc-1 Tumor Cells., Nicholas Lorig-Roach, Frances Hamkins-Indik, Tyler A. Johnson, Karen Tenney, Frederick A. Valeriote, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

Our quest to isolate and characterize natural products with in vitro solid tumor selectivity is driven by access to repositories of Indo-Pacific sponge extracts. In this project an extract of a species of Haplosclerida sponge obtained from the US NCI Natural Products Repository displayed, by in vitro disk diffusion assay (DDA) and IC

Adp-Ribosylation Factor-Like 2 (Arl2) Regulates Cilia Stability And Development Of Outer Segments In Rod Photoreceptor Neurons, Zachary C. Wright, Yuriy Loskutov, Daniel Murphy, Peter Stoilov, Elena Pugacheva, Andrew F.X. Goldberg, Visvanathan Ramamurthy

Faculty & Staff Scholarship

Photoreceptor cells are specialized neurons with a sensory cilium carrying an elaborate membrane structure, the outer segment (OS). Inherited mutations in genes involved in ciliogenesis frequently result in OS malformation and blindness. ADP-ribosylation factor-like 2 (ARL2) has recently been implicated in OS formation through its association with Binder of ARL2 (BART or ARL2BP), a protein linked to inherited blinding disease. To test the role of ARL2 in vision we created a transgenic mouse model expressing a tagged-dominant active form of human ARL2 (ARL2-Q70L) under a rod-specific promoter. Transgenic ARL2-Q70L animals exhibit reduced photoreceptor cell function as early as post-natal day …

Could A Common Mechanism Of Protein Degradation Impairment Underlie Many Neurodegenerative Diseases?, David M. Smith

Faculty & Staff Scholarship

At the cellular level, many neurodegenerative diseases (NDs), often considered proteinopathies, are characterized by the accumulation of misfolded and damaged proteins into large insoluble aggregates. Prominent species that accumulate early and play fundamental roles in disease pathogenesis are amyloid β (Aβ) and tau in Alzheimer disease, α-synuclein (α-syn) in Parkinson disease, and polyQ-expanded huntingtin (Htt) in Huntington disease. Although significant efforts have focused on how the cell deals with these protein aggregates, why is it that these misfolded proteins are not degraded normally in the first place? A vast body of literature supports the notion that the cell’s protein degradation …

A Functional Signature Ontology (Fusion) Screen Detects An Ampk Inhibitor With Selective Toxicity Toward Human Colon Tumor Cells, Binita Das, Beth K. Neilsen, Kurt W. Fisher, Drew Gehring, Youcai Hu, Deanna J. Volle, Hyun Seok Kim, Jamie L. Mccall, David L. Kelly, John B. Macmillian, Michael A. White, Robert E. Lewis

Faculty & Staff Scholarship

AMPK is a serine threonine kinase composed of a heterotrimer of a catalytic, kinase-containing α and regulatory β and γ subunits. Here we show that individual AMPK subunit expression and requirement for survival varies across colon cancer cell lines. While AMPKα1 expression is relatively consistent across colon cancer cell lines, AMPKα1 depletion does not induce cell death. Conversely, AMPKα2 is expressed at variable levels in colon cancer cells. In high expressing SW480 and moderate expressing HCT116 colon cancer cells, siRNA-mediated depletion induces cell death. These data suggest that AMPK kinase inhibition may be a useful component of future therapeutic strategies. …

Farnesylation Of The Transducin G Protein Gamma Subunit Is A Prerequisite For Its Ciliary Targeting In Rod Photoreceptors, Celine Brooks, Joseph Murphy, Marycharmain Belcastro, Daniel Heller, Saravanan Kolandaivelu, Oleg Kisselev, Maxim Sokolov

Faculty & Staff Scholarship

Primary cilia are microtubule-based organelles, which protrude from the plasma membrane and receive a wide range of extracellular signals. Various cilia use G protein-coupled receptors (GPCRs) for the detection of these signals. For instance, vertebrate rod photoreceptors use their cilia (also called outer segments) as antennae detecting photons by GPCR rhodopsin. Rhodopsin recognizes incoming light and activates its G protein, transducin, which is composed of three subunits α, β, and γ. Similar to all G protein γ subunits, the transducin Gγ1 subunit undergoes C-terminal prenylation resulting in the addition of an isoprenoid farnesyl; however, the significance of this posttranslational modification …

Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer

Faculty & Staff Scholarship

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/Δ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/Δ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/Δ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/Δ mice never exceeded that …

Functional Characterization Of Scaffold Protein Shoc2, Hyein Jang

Theses and Dissertations--Molecular and Cellular Biochemistry

Signaling scaffolds are critical for the correct spatial organization of enzymes within the ERK1/2 signaling pathway and proper transmission of intracellular information. However, mechanisms that control molecular dynamics within scaffolding complexes, as well as biological activities regulated by the specific assemblies, remain unclear.

The scaffold protein Shoc2 is critical for transmission of the ERK1/2 pathway signals. Shoc2 accelerates ERK1/2 signaling by integrating Ras and RAF-1 enzymes into a multi-protein complex. Germ-line mutations in shoc2 cause Noonan-like RASopathy, a disorder with a wide spectrum of developmental deficiencies. However, the physiological role of Shoc2, the nature of ERK1/2 signals transduced through this …

Interleukin-6 And Exercise; Early Evidence Of A Novel Myokine, Brendan Hogg Mr.

Graduate Student Theses, Dissertations, & Professional Papers

Interleukin-6 (IL-6) was first identified as a pleiotropic cytokine, with a host of body-wide functions. Cytokine functions are characterized by chronically elevated levels within various inflammatory states. In this regard, IL-6 is largely associated with the acute phase response to many stimuli and performs specific actions when produced from certain cell types. Accrued evidence indicates IL-6 release from skeletal muscle often includes myokine functions. Novel myokine functions are adaptive in nature, and as compared to inflammatory/cytokine roles, exhibit a transient time course. Following exercise plasma IL-6 peaks and returns to resting levels within 1-2 hours. In contrast, IL-6 is observed …

Discovery Of Novel Muraymycin Antibiotics And Insight Into The Biosynthetic Pathway, Zheng Cui

Theses and Dissertations--Pharmacy

New antibiotics with novel targets or mechanisms of action are needed to counter the steady emergence of bacterial pathogens that are resistant to antibiotics used in the clinic. MraY, a promising novel target for antibiotic development, initiates the lipid cycle for the biosynthesis of peptidoglycan cell wall, which is essential for the survival of most, if-not-all, bacteria. MraY is an enzyme that catalyzes the transfer and attachment of phospho-MurNAc-pentapeptide to a lipid carrier, undecaprenylphosphate. Muraymycins are recently discovered lipopeptidyl nucleoside antibiotics that exhibit remarkable antibiotic activity against Gram-positive as well as Gram-negative bacteria by inhibiting MraY. We conducted a thorough …

Esope-Equivalent Pulsing Protocols For Calcium Electroporation: An In Vitro Optimization Study On 2 Cancer Cell Models, Stefania Romeo, Anna Sannino, Maria Rosaria Scarfi, P. Thomas Vernier, Ruggero Cadossi, Julie Gehl, Olga Zeni

Bioelectrics Publications

Reversible electroporation is used to increase the uptake of chemotherapeutic drugs in local tumor treatment (electrochemotherapy) by applying the pulsing protocol (8 rectangular pulses, 1000 V/cm, 100 µs) standardized in the framework of the European Standard Operating Procedure on Electrochemotherapy multicenter trial. Currently, new electrochemotherapy strategies are under development to extend its applicability to tumors with different histology. Electrical parameters and drug type are critical factors. A possible approach is to test pulse parameters different from European Standard Operating Procedure on Electrochemotherapy but with comparable electroporation yield (European Standard Operating Procedure on Electrochemotherapy-equivalent protocols). Moreover, the use of non-toxic drugs …

Size-Dependent Inhibitory Effects Of Antibiotic Drug Nanocarriers Against Pseudomonas Aeruginosa, Feng Ding, Preeyaporn Songkiatisak, Pavan Kumar Cherukuri, Tao Huang, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Multidrug membrane transporters (efflux pumps) are responsible for multidrug resistance (MDR) and the low efficacy of therapeutic drugs. Noble metal nanoparticles (NPs) possess a high surface-area-to-volume ratio and size-dependent plasmonic optical properties, enabling them to serve both as imaging probes to study sized-dependent MDR and as potential drug carriers to circumvent MDR and enhance therapeutic efficacy. To this end, in this study, we synthesized three different sizes of silver nanoparticles (Ag NPs), 2.4 ± 0.7, 13.0 ± 3.1, and 92.6 ± 4.4 nm, functionalized their surface with a monolayer of 11-amino-1-undecanethiol (AUT), and covalently conjugated them with antibiotics (ofloxacin, Oflx) …

Structure Of The Picornavirus Replication Platform: A Potential Drug Target For Inhibiting Virus Replication, Meghan Suzanne Warden

Chemistry & Biochemistry Theses & Dissertations

Picornaviruses are small, positive-stranded RNA viruses, divided into twelve different genera. Members of the Picornaviridae family cause a wide range of human and animal diseases including the common cold, poliomyelitis, foot and mouth disease, and dilated cardiomyopathy. The picornavirus genome is replicated via a highly conserved mechanism involving a presumed cloverleaf structure located at the 5’ noncoding region of the virus genome. The 5’ cloverleaf consists of three stem loops (B, C, and D) and one stem (A), which interact with a variety of virus and host cell proteins during replication. In this dissertation, human rhinovirus serotype 14 (HRV-14) SLB …