Biochemistry Commons^™

Detection And Characterization Of Mineralo-Organic Nanoparticles In Human Kidneys, Tsui-Yin Wong, Cheng-Yeu Wu, Jan Martel, Cheng-Wei Lin, Fu-Yung Hsu, David M. Ojcius, Paul Y. Lin, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Ectopic calcification is associated with various human diseases, including atherosclerosis, cancer, chronic kidney disease, and diabetes mellitus. Although mineral nanoparticles have been detected in calcified blood vessels, the nature and role of these particles in the human body remain unclear. Here we show for the first time that human kidney tissues obtained from end-stage chronic kidney disease or renal cancer patients contain round, multilamellar mineral particles of 50 to 1,500 nm, whereas no particles are observed in healthy controls. The mineral particles are found mainly in the extracellular matrix surrounding the convoluted tubules, collecting ducts and loops of Henle as …

Hirsutella Sinensis Mycelium Attenuates Bleomycin-Induced Pulmonary Inflammation And Fibrosis In Vivo, Tsung-Teng Huang, Hsin-Chih Lai, Yun-Fei Ko, David M. Ojcius, Ying-Wei Lan, Jan Martel, John Ding-E. Young, Kowit-Yu Chong

All Dugoni School of Dentistry Faculty Articles

Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1β and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-β1–induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1–treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, …

Two-Ply Channels For Faster Wicking In Paper-Based Microfluidic Devices, Conor K. Camplisson, Kevin M. Schilling, William L. Pedrotti, Howard A. Stone, Andres W. Martinez

Chemistry and Biochemistry

This article describes the development of porous two-ply channels for paper-based microfluidic devices that wick fluids significantly faster than conventional, porous, single-ply channels. The two-ply channels were made by stacking two single-ply channels on top of each other and were fabricated entirely out of paper, wax and toner using two commercially available printers, a convection oven and a thermal laminator. The wicking in paper-based channels was studied and modeled using a modified Lucas–Washburn equation to account for the effect of evaporation, and a paper-based titration device incorporating two-ply channels was demonstrated.

The Generation, Exploitation And Future Of Induced Pluripotent Stem Cells, Jacob Steenwyk

Scholarly Undergraduate Research Journal at Clark (SURJ)

The foundational advancements of John Gurdon and Shinya Yamanaka have improved understanding of dedifferen- tiation of cells to a pluripotent state. The seminal discovery established a novel system to study disease pathogenesis, drug screening, and toxicity, as well as sprouted the new field of regenerative medicine. In this article, the method- ology to obtain dedifferentiated cells, known as induced pluripotent stem (iPS) cells, subsequent validation, and application of which are reviewed. The experiments investigated here aim to demonstrate the capacity of iPS cells to replace the ethically-gray human embryonic cells by developing human livers and viable, healthy animals. It is …

Biochemical Effects Of Meditation: A Literature Review, William C. Daube, Charles E. Jakobsche

Scholarly Undergraduate Research Journal at Clark (SURJ)

Meditation is an activity that can help reduce stress and anxiety from daily life as well as help cultivate overall feel- ings of peacefulness, relaxation, and contentment. This review describes several studies that have been used to assess how meditation can influence the body at the molecular level. The presented results focus on small-molecule metab- olites, which are broadly defined as naturally-produced molecules that weigh less than approximately 1000 Da. The results show that meditation can significantly affect hormones and neurotransmitters such as cortisol, dehydroepi- androstrone, serotonin, melatonin, and epinephrine. Some common and modern experimental techniques that are relevant to …

Structure Based Drug Design Targeting Bacterial Antibiotic Resistance And Alzheimer's Disease, Eric Michael Lewandowski

USF Tampa Graduate Theses and Dissertations

Structure based drug design is a rapidly advancing discipline that examines how protein targets structurally interact with small molecules, or known inhibitors, and then uses this information to lead inhibitor optimization efforts. In the case of novel inhibitors, protein structural information is first obtained via X-ray crystallography, NMR studies, or a combination of both approaches. Then, computational molecular docking is often used to screen, in silico, millions of small molecules and calculate the potential interactions they may have with the target protein’s binding pocket, in hopes of identifying novel low affinity inhibitors. By examining the interactions these small, low affinity, …

Cobalt-Centred Boron Molecular Drums With The Highest Coordination Number In The Cob16− Cluster, Ivan A. Popov, Tian Jian, Gary V. Lopez, Alexander I. Boldyrev, Lai-Sheng Wang

Chemistry and Biochemistry Faculty Publications

The electron deficiency and strong bonding capacity of boron have led to a vast variety of molecular structures in chemistry and materials science. Here we report the observation of highly symmetric cobalt-centered boron drum-like structures of CoB16⁻, characterized by photoelectron spectroscopy and ab initio calculations. The photoelectron spectra display a relatively simple spectral pattern, suggesting a high symmetry structure. Two nearly degenerate isomers with D8d(I) and C4v (II) symmetries are found computationally to compete for the global minimum. These drum-like structures consist of two B8 rings sandwiching a cobalt atom, which has the highest …

Temporal Variation In Optical Properties Of Chromophoric Dissolved Organic Matter (Cdom) In Southern California Coastal Waters With Nearshore Kelp And Seagrass, Catherine D. Clark, Warren J. De Bruyn, Paige Aiona

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Optical properties of chromophoric dissolved organic matter (CDOM) were measured in surf zone waters in diurnal field studies at a Southern California beach with nearshore kelp and seagrass beds and intertidal plant wrack. Absorption coefficients (aCDOM(300 nm)) ranged from 0.35 m21 to 3.7 m21 with short-term variability<1 h, increases at ebb and flood tides and higher values (6 m21) during an offshore storm event. Spectral slopes (S) ranged from 0.0028 nm21 to 0.017 nm21, with higher values after the storm; S was generally inversely correlated with aCDOM(300 nm). 3-D excitation–emission matrix spectra (EEMs) for samples with lower S values had humic-type peaks associated with terrestrial material (A, C), marine microbial material (M) and protein peaks, characteristic of freshly produced organic material. Samples with high S values had no or reduced protein peaks, consistent with aged material. Fluorescent indexes (f450/f500 >2.5, BIX>1.1) were consistent with microbial aquatic sources. Leachates of senescent kelp and seagrass had protein and humic-type EEM peaks. After solar simulator irradiation (4 h), protein peaks rapidly photochemically degraded, humic-type peak C increased in intensity and peak M disappeared. Optical characteristics of kelp leachates were most similar to field samples, …

Multi-Dimensional Glycan Microarrays With Glyco-Macroligands, Satya Nandana Narla, Huan Nie, Yu Li, Xue-Long Sun

Chemistry Faculty Publications

Glycan microarray has become a powerful high-throughput tool for examining binding interactions of carbohydrates with the carbohydrate binding biomolecules like proteins, enzymes, antibodies etc. It has shown great potential for biomedical research and applications, such as antibody detection and profiling, vaccine development, biomarker discovery, and drug screening. Most glycan microarrays were made with monovalent glycans immobilized directly onto the array surface via either covalent or non-covalent bond, which afford a multivalent glycans in two dimensional (2D) displaying. A variety of glyco-macroligands have been developed to mimic multivalent carbohydrate-protein interactions for studying carbohydrate-protein interactions and biomedical research and applications. Recently, a …

Ligand Frameworks For Transition-Metal Complexes That Model Metalloenzyme Active, Denan Wang

Dissertations (1934 -)

Advances in the field of biomimetic inorganic chemistry require the design of sophisticated ligand frameworks that reflect the amazing complexity of metalloenzyme active sites. For instance, most active sites feature extensive hydrogen-bonding interactions between ligands bound to the metal center (the “first” coordination sphere) and nearby units in the outer (or “second”) sphere. Since these interactions modify the structural and electronic properties of the active sites, a number of inorganic chemists have sought to design ligands that permit outer-sphere functional groups to interact with first-sphere donors. This dissertation describes our contribution to these broader efforts to model the second coordination …

Characterization Of Inhibitors Of Fatty Acid Transport Protein-2 In Cell And Animal Models, Nipun Saini

Department of Biochemistry: Dissertations, Theses, and Student Research

Obesity is correlated with insulin resistance and elevated levels of glucose, triglycerides and free fatty acids in blood. This affects overall metabolism and leads to disease. In the obese state, fat also accumulates in non-adipose tissue including liver, muscle and pancreas, where it can lead to cellular dysfunction and death. Currently, only a limited number of drugs are available to combat obesity and it is clear that new drugs, which more narrowly target the metabolic pathways involved, are required. Fatty Acid Transport Proteins (FATPs) are bifunctional proteins involved in the uptake and activation of fatty acids by esterification with coenzyme …

Image-Charge Detection €“ Novel Instrumentation And Applications, Brandon Lee Barney

Theses and Dissertations

Image-charge detection is an analytical technique in which a highly-charged particle is detected by the magnitude of the image current that it generates in a detecting electrode. This current is represented as a voltage between the charged particle and the sensing electrode. It is a single particle detection method, ideal for the analysis of large, variable mass particles such as biological cells. Some of the physical properties of Bacillus subtilis spores were explored using different applications of image-charge detection. B. subtilis is a gram-negative spore-forming bacteria that has been shown to exhibit extremophile behavior. The particular extremophile behavior that was …

Exploiting Cancer Cell Signaling And Metabolism: Implications For Therapeutic Approach, Suman Mukhopadhyay

Dissertations, Theses, and Capstone Projects

Over the last decade, metabolic dysregulation in cancer cells has stimulated a significant amount of interest in basic research. It has been established that cancer cells increase glucose uptake and alter the fate of glycolytic and tricarboxylic acid (TCA) cycle intermediates for the synthesis of biological molecules to accommodate high rates of cellular growth and proliferation. Moreover, it is more prominent that some metabolic dysregulations are specific to particular oncogenes. Exploiting the dysregulated metabolic dependency of cancer cells with therapeutic means could represent a novel approach for clinical aspect.

To meet the need of increased anabolic metabolism cancer cells engage …

Characterizing Migratory Signaling Pathways Of Transplantable Retinal Progenitor Cells And Photoreceptor Precursor Cells Toward Restoration Of Degenerative Retina ' A Systems Biology Approach, Uchenna John Unachukwu

Dissertations, Theses, and Capstone Projects

A common feature of several heterogeneous diseases that result in retinal degeneration (RD) is photoreceptor loss, leading to an irreversible decline in visual function [15-17]. There are no cell replacement treatments available for RD diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Although many RD cases are of a genetic origin, a promising strategy to treat diseased phenotypes is by replacing lost photoreceptor cells, for synaptic integration and restoration of visual function. To advance photoreceptor-replacement strategies as a practical therapy, in light of highly restricted integration rates reported across studies, this body of research focused on defining …

Knowledge Discovery And Prediction Modeling Of Protein-Drug Binding Kinetic By Integrating Machine Learning, Normal Mode Analysis And Molecular Dynamics Simulation, See Hong Chiu

Dissertations, Theses, and Capstone Projects

One of the unaddressed challenges in drug discovery is that drug potency measured by protein-ligand binding affinity, such as IC₅₀ and K_d in vitro, is not correlated with drug activity in vivo. Computational modeling is playing an increasing role in designing efficient therapeutics. However, existing computational methods for the high-throughput study of protein-ligand interactions (PLI) mainly focus on the prediction of the binding affinity. This is the combined effect of association (k_on) and dissociation (k_off) rate constants. Few works have been produced to predict koff or its reciprocal, residence time, which is a key …

The Role Of Atp And Cleavage Factor Phosphorylation In Pre-Mrna 3' Cleavage Reaction, Asya Khleborodova

Dissertations, Theses, and Capstone Projects

The 3' end cleavage/polyadenylation (3' processing) is important in generating a functional messenger RNA (mRNA) transcript. It is long-known that ATP can significantly stimulate the in vitro cleavage of adenovirus type 2 L3 (Ad2L3) RNA substrate. Here, we used ATP analogs in structure-activity assays to show that the structural features of ATP and its analogs determine in vitro 3' cleavage efficiency. More specifically, we demonstrate that the structure of the nitrogenous base, the nucleotide sugar and the triphosphate group contribute to the efficiency of the nucleotide-stimulated in vitro 3' cleavage reaction.

It was found that AppNp, an analog of ATP …

Fatty Acid Transport Protein-2 Inhibitor Grassofermata/Cb5 Protects Cells Against Lipid Accumulation And Toxicity, Nipun Saini, Paul N. Black, David Montefusco, Concetta Dirusso

Department of Biochemistry: Faculty Publications

The inhibition of the fatty acid uptake into non-adipose tissues provides an attractive target for prevention of lipotoxicity leading to obesity-associated non-alcoholic fatty liver disease and type 2 diabetes. Fatty acid transport proteins (FATPs) are bifunctional proteins involved in the uptake and activation of fatty acids by esterification with coenzyme A. Here we characterize Grassofermata/CB5, previously identified as a fatty acid uptake inhibitor directed against HsFATP2. The compound was effective in inhibiting the uptake of fatty acids in the low micro-molar range (IC₅₀ 8–11μM) and prevented palmitate-mediated lipid accumulation and cell death in cell lines that are models for …

Heterogeneous Oxidation Of Catechol, Elizabeth A. Pillar, Ruixin Zhou, Marcelo I. Guzman

Chemistry Faculty Publications

Natural and anthropogenic emissions of aromatic hydrocarbons from biomass burning, agro-industrial settings, and fossil fuel combustion contribute precursors to secondary aerosol formation (SOA). How these compounds are processed under humid tropospheric conditions is the focus of current attention to understand their environmental fate. This work shows how catechol thin films, a model for oxygenated aromatic hydrocarbons present in biomass burning and combustion aerosols, undergo heterogeneous oxidation at the air–solid interface under variable relative humidity (RH = 0–90%). The maximum reactive uptake coefficient of O₃(g) by catechol γ_O3 = (7.49 ± 0.35) × 10^–6 occurs for …

Elongation Factor-P At The Crossroads Of The Host-Endosymbiont Interface, Andrei Rajkovic, Anne Witzky, William Navarre, Andrew J. Darwin, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Elongation factor P (EF-P) is an ancient bacterial translational factor that aids the ribosome in polymerizing oligo-prolines. EF-P structurally resembles tRNA and binds in-between the exit and peptidyl sites of the ribosome to accelerate the intrinsically slow reaction of peptidyl-prolyl bond formation. Recent studies have identified in separate organisms, two evolutionarily convergent EF-P post-translational modification systems (EPMS), split predominantly between gammaproteobacteria, and betaproteobacteria. In both cases EF-P receives a post-translational modification, critical for its function, on a highly conserved residue that protrudes into the peptidyl-transfer center of the ribosome. EPMSs are comprised of a gene(s) that synthesizes the precursor molecule …

Characterizing The Rogfp2-Orp1 Fluorescent Biosensor For Detecting Oxidative Stress In Mammalian Cells, Sara A. Doan, Stevie Norcross, Mathew Tantama

The Summer Undergraduate Research Fellowship (SURF) Symposium

Parkinson’s disease is a neurodegenerative disease involving the death of neurons in the substantia nigra and loss of the neurotransmitter, dopamine. The disease leads to progressive loss of motor control. Exact causes and mechanisms by which Parkinson’s disease proceeds are unknown, however, previous experiments determine oxidative stress in mitochondria as a factor that results in cell death. Strategies have been implemented to generate fluorescent biosensors to monitor reactive oxygen species (ROS) concentrations while simultaneously measuring the spatiotemporal distribution and correlation between the ROS, cellular function and organelle. Orp1, an enzyme found in yeast, is a sensitive oxidizing species and when …

Short Communication: Lack Of Association Between Mthfr Gene Polymorphisms And Response To Methotrexate Treatment In Pakistani Patients With Rheumatoid Arthritis, Mohammad Perwaiz Iqbal, Azra Arif Ali, Naseema Mehboobali, Khalida Iqbal

Department of Biological & Biomedical Sciences

Methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms have been reported to be associated with response to methotrexate (MTX) in certain populations of patients with rheumatoid arthritis (RA). This study aims at investigating any relationship of two single nucleotide polymorphisms (SNPs) in MTHFR gene, C677T and A1298C with response to therapy with MTX in Pakistani RA patients. Allelic frequencies of the two polymorphisms (C677T and A1298C) were determined in 67 RA patients (9 males and 58 females; mean age 42.87 ± 13.5 years) who had previously participated in a prospective clinical trial. Fifty-one patients had received MTX and were followed up for response …

Coastal Sediment Elevation Change Following Anthropogenic Mangrove Clearing, Heather Lyn Hayden, Elise F. Granek

Environmental Science and Management Faculty Publications and Presentations

Coastal mangrove forests along tropical shorelines serve as an important interface between land and sea. They provide a physical buffer protecting the coastline from erosion and act as sediment “traps” catching terrestrial sediment, thus preventing smothering of subtidal coral reefs. Coastal development that removes mangrove habitat may impact adjacent nearshore coral reefs through sedimentation and nutrient loading. We examined differences in sediment elevation change between patches of open-coast intact and anthropogenically cleared red mangroves (Rhizophora mangle) on the east side of Turneffe Atoll, Belize, to quantify changes following mangrove clearing. Samples were collected over a 24 month period at five …

An Analytical Method For Detecting Toxic Metal Cations Using Cyclotriveratrylene Derivative Capped Gold Nanoparticles, Zachary R. Osner, Richard C. Holz, Daniel P. Becker Ph.D.

Chemistry: Faculty Publications and Other Works

Cyclotriveratrylene-oxime (CTV-oxime) derivatives that terminate with a dithiolate linker were synthesized enabling the supramolecular scaffold to adhere to gold nanoparticles (AuNPs) with the bowl-shaped cavity of the CTV scaffold exposed for utilization in host–guest chemistry. Exposure of these CTV functionalized AuNPs to varying concentrations of di- and trivalent metal cations resulted in the formation of large CTV-AuNP polymeric clusters and an accompanying a shift in the plasmon resonance. These interactions between the CTV-AuNPs and the metal cations in solution provides proof-of-concept that supramolecular functionalized AuNPs can be used as a simple and straightforward, on-site detection system for toxic metal cations …

O6-Methylguanosine Leads To Position-Dependent Effects On Ribosome Speed And Fidelity, Benjamin H. Hudson, Hani S. Zaher

Biology Faculty Research

Nucleic acids are under constant assault from endogenous and environmental agents that alter their physical and chemical properties. O6-methylation of guanosine (m(6)G) is particularly notable for its high mutagenicity, pairing with T, during DNA replication. Yet, while m(6)G accumulates in both DNA and RNA, little is known about its effects on RNA. Here, we investigate the effects of m(6)G on the decoding process, using a reconstituted bacterial translation system. m(6)G at the first and third position of the codon decreases the accuracy of tRNA selection. The ribosome readily incorporates near-cognate aminoacyl-tRNAs (aa-tRNAs) by forming m(6)G-uridine codon-anticodon pairs. Surprisingly, the introduction …

Intracranial Glioblastomas: New Hope For An Effective Treatment, Arthur J L Cooper

NYMC Faculty Publications

Comment on Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug. [EBioMedicine. 2015]

Investigation Of Behavioral And Cellular Changes In The Maternal Immune Activation Model Of Autism Spectrum Disorders, Shreya Roy

Theses & Dissertations

Maternal infection during pregnancy, which leads to maternal immune activation (MIA), is an environmental risk factor for autism spectrum disorders (ASD). MIA can be induced in mice and their offspring exhibit behaviors that model the core symptoms of ASD. One of the core behavioral symptoms in ASD patients is presence of increased repetitive behavior, which is modeled by an increase in marble burying in MIA mice. It has been shown that the deficits seen in MIA mice are associated with the dysregulation of cytokine levels in the developing brain, specifically an increase in pro-inflammatory cytokines. In this thesis, I tested …

Characterization And Target Identification Of Non-Toxic Ikkβ Inhibitors For Anticancer Therapy, Elizabeth Blowers

Theses & Dissertations

IKKβ is a key kinase in the canonical NF-κB pathway. Transient activation of IKKβ is required for normal immune response while sustained activation has been implicated in cancer. To date, no IKKβ inhibitor has been approved for clinical use as a chemotherapeutic, likely due to unexpected toxicities associated with blocking the transient activation of IKKβ. We hypothesized that an IKKβ inhibitor that allows transient activation of IKKβ, but not sustained activation of IKKβ, could inhibit cancer growth without inducing toxicity.

As such, we identified a small molecule inhibitor, 13-197, that allows the transient activation of IKKβ but not the sustained …

Biomass Burning Emissions And Potential Air Quality Impacts Of Volatile Organic Compounds And Other Trace Gases From Temperate Fuels Common In The United States, J. B. Gilman, B. M. Lerner, W. C. Kuster, P. D. Goldan, C. Warneke, P. R. Veres, J. M. Roberts, J. A. De Gouw, I. R. Burling, Robert Yokelson

Chemistry and Biochemistry Faculty Publications

A comprehensive suite of instruments was used to quantify the emissions of over 200 organic gases, including methane and volatile organic compounds (VOCs), and 9 inorganic gases from 56 laboratory burns of 18 different biomass fuel types common in the southeastern, southwestern, or northern United States. A gas chromatograph-mass spectrometer (GC-MS) provided extensive chemical detail of discrete air samples collected during a laboratory burn and was complemented by real-time measurements of organic and inorganic species via an open-path Fourier transform infrared spectrometer (OP-FTIR) and 3 different chemical ionization-mass spectrometers. These measurements were conducted in February 2009 at the U.S. Department …

Role Of Ime4 Protein In Pho Regulon Of S.Cerevisiae., Jenisha Ghimire

LSU New Orleans Theses and Dissertations

In the yeast Saccharomyces cerevisiae, the IME4 methyltransferase, interacts genetically with methyl binding protein, Pho92, to affect the expression of PHO regulon target genes. Cells mutant in IME4 or PHO92 show increases in the RNA abundance of PHO regulon target genes. The increase in the RNA abundance of the PHO regulon target genes is not additive in the cells double mutant in IME4 and PHO92. Hence, Ime4 and Pho92 interact in a single pathway in PHO regulon. Surprisingly, cells overexpressing IME4 and MUM2 shows increase in some PHO regulon target genes, indicating that IME4 affects the PHO regulon target …

A Screen To Identify Saga-Activated Genes That Are Required For Proper Photoreceptor Axon Targeting In Drosophila Melanogaster, Kaelan J. Brennan, Vikki M. Weake, Jingqun Q. Ma

The Summer Undergraduate Research Fellowship (SURF) Symposium

The inherited human genetic disease spinocerebellar ataxia type 7 (SCA7) is characterized by progressive neurodegeneration and visual impairment that ultimately leads to blindness. SCA7 results from a mutation in the human ATXN7 gene that causes an expansion of polyglutamine tracts in this gene’s corresponding protein. Human ATXN7 protein serves as a component of the deubiquitylase (DUB) module of the large, multi-subunit complex Spt-Ada-Gcn acetyltransferase, or SAGA. SAGA is a transcriptional coactivator and histone modifier that functions to deubiquitylate histone H2B and allow for transcription of SAGA-mediated genes to occur. In Drosophila, mutations in SAGA DUB’s Nonstop and sgf11 components …