Organisms Commons^™

Targeted Aav5-Smad7 Gene Therapy Inhibits Corneal Scarring In Vivo, Suneel Gupta, Jason T. Rodier, Ajay Sharma, Elizabeth A. Giuliano, Prashant R. Sinha, Nathan P. Hesemann, Arkasubhra Ghosh, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Corneal scarring is due to aberrant activity of the transforming growth factor β (TGFβ) signaling pathway following traumatic, mechanical, infectious, or surgical injury. Altered TGFβ signaling cascade leads to downstream Smad (Suppressor of mothers against decapentaplegic) protein-mediated signaling events that regulate expression of extracellular matrix and myogenic proteins. These events lead to transdifferentiation of keratocytes into myofibroblasts through fibroblasts and often results in permanent corneal scarring. Hence, therapeutic targets that reduce transdifferentiation of fibroblasts into myofibroblasts may provide a clinically relevant approach to treat corneal fibrosis and improve long-term visual outcomes. Smad7 protein regulates the functional effects of TGFβ signaling …

Hendra Virus Fusion Protein Transmembrane Domain Contributes To Pre-Fusion Protein Stability, Stacy Webb, Tamas Nagy, Hunter Moseley, Michael G. Fried, Rebecca Ellis Dutch

Molecular and Cellular Biochemistry Faculty Publications

Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains …

Osteoblast-Derived Fgf9 Regulates Skeletal Homeostasis, Liping Wang, Theresa M. Roth, Marcia J. Abbott, Linh Ho, Lalita Wattanachanya, Robert A. Nissenson

Health Sciences and Kinesiology Faculty Articles

FGF9 has complex and important roles in skeletal development and repair. We have previously observed that Fgf9 expression in osteoblasts (OBs) is regulated by G protein signaling and therefore the present study was done to determine whether OB-derived FGF9 was important in skeletal homeostasis. To directly test this idea, we deleted functional expression of Fgf9 gene in OBs using a 2.3 kb collagen type I promoter-driven Cre transgenic mouse line (Fgf9^{OB −/−}). Both Fgf9 knockout (Fgf9^{OB −/−}) and the Fgf9 floxed littermates (Fgf9^fl/fl) mice were fully backcrossed and maintained in an FBV/N background. Three …

Cyclic Ac253, A Novel Amylin Receptor Antagonist, Improves Cognitive Deficits In A Mouse Model Of Alzheimer’S Disease, Rania Soudy, Aarti Patel, Wen Fu, Kamaljit Kaur, David Mactavish, David Westaway, Rachel Davey, Jeffrey Zajac, Jack Jhamandas

Pharmacy Faculty Articles and Research

Introduction: Amylin receptor serves as a portal for the expression of deleterious effects of amyloid b-protein (Ab), a key pathologic hallmark of Alzheimer’s disease. Previously, we showed that AC253, an amylin receptor antagonist, is neuroprotective against Ab toxicity in vitro and abrogates Ab-induced impairment of hippocampal long-term potentiation.

Methods: Amyloid precursor protein–overexpressing TgCRND8 mice received intracerebroventricularly AC253 for 5 months. New cyclized peptide cAC253 was synthesized and administered intraperitoneally three times a week for 10 weeks in the same mouse model. Cognitive functions were monitored, and pathologic changes were quantified biochemically and immunohistochemically.

Results: AC253, when administered …

Taurine's Effect On Cocaine Reward And Neurogenesis In The Adolescent Male Rat Brain., Avery E. Villa-Gonzalez

Dissertations and Theses

Adolescence is a developmentally critical transition from childhood to adulthood including both maturation of the body and the brain. Neuroplastic changes result in dynamic organization of the brain during adolescence, leaving them vulnerable to development of mental illness and drug-seeking behavior. According to the United Nations Office on Drugs and Crime, the psychostimulant cocaine is the second most popular illicit drug in the world. Cocaine, amongst having many detrimental effects, has shown to also decrease hippocampal neurogenesis, resulting in decreased neuroplasticity and cognitive dysfunction. Previous students in our laboratory have shown that treatment of adult male rats with the essential …

Structure-Function Investigation Of Proteins Involved In Cellulose Biosynthesis By Escherichia Coli, Thomas Brenner

Theses and Dissertations (Comprehensive)

Bacteria thrive within multicellular communities called biofilms consisting of a self-produced matrix. Biofilm matrices improve bacterial adherence to surfaces while creating a barrier from host immune responses, disinfectants, antibiotics and other environmental factors. Persistent colonization by the widely distributed pathogens, Escherichia coli and Salmonella spp., has been linked to production of biofilms composed of the exopolysaccharide cellulose. Cellulose-containing biofilms are also important to Acetobacter, Sarcina, Rhizobium and Agrobacterium species to form symbiotic and pathogenic interactions. In Enterobacteriaceae, two operons (bcsABZC and bcsEFG) are proposed to encode for proteins that form a cellulose biosynthetic complex that spans the …

Surveillance, Epidemiological, And Virological Detection Of Highly Pathogenic H5n1 Avian Influenza Viruses In Duck And Poultry From Bangladesh, Wahedul Karim Ansari, Md Safiullah Parvej, Mohamed E. El Zowalaty, Sally Jackson, Stephen A. Bustin, Adel K. Ibrahim, Md Tanvir Rahman, Han Zhang, Mohammad Ferdousur Rahman Khan, Md Mostakin Ahamd, Md. Fasiur Rahman, Marzia Rahman, Khm Nazmul H. Nazir, Sultan Ahmed, Md Liakot Hossenn, Md Abdul Kafi, Mat Yamage, Nitish C. Debnath, Graba Ahmed, Hossam Ashour, Md Masoud, Ayman Noreddin, Md B. Rahman

Pharmacy Faculty Articles and Research

Avian influenza viruses (AIVs) continue to pose a global threat. Waterfowl are the main reservoir and are responsible for the spillover of AIVs to other hosts. This study was conducted as part of routine surveillance activities in Bangladesh and it reports on the serological and molecular detection of H5N1 AIV subtype. A total of 2169 cloacal and 2191 oropharyngeal swabs as well as 1725 sera samples were collected from live birds including duck and chicken in different locations in Bangladesh between the years of 2013 and 2014. Samples were tested using virus isolation, serological tests and molecular methods of RT-PCR. …

Antibiotic Drug Discovery With An Eye Towards Overcoming Drug Resistance, Daniel Towner Hoagland

Theses and Dissertations (ETD)

As a species, humans have become ever reliant on the use of antibiotics to facilitate our everyday lives. The widespread emergence of resistance to currently used antibiotics is commonly attributed to an over use in our society. Such resistance, coupled with a lack of innovation and production of novel antibiotic drugs, threatens to return humanity to an era similar to one before the discovery of the first antibiotics. The need to find new agents to be used in this fight is paramount, as well as learning from our recent failures to produce such compounds. This document will highlight my efforts …

Endocidal Regulation Of Secondary Metabolites In The Producing Organisms, Shiyou Li, Ping Wang, Wei Yuan, Zushang Su, Steven H. Bullard

Faculty Publications

Secondary metabolites are defined as organic compounds that are not directly involved in the normal growth, development, and reproduction of an organism. They are widely believed to be responsible for interactions between the producing organism and its environment, with the producer avoiding their toxicities. In our experiments, however, none of the randomly selected 44 species representing different groups of plants and insects can avoid autotoxicity by its endogenous metabolites once made available. We coined the term endocides (endogenous biocides) to describe such metabolites that can poison or inhibit the parent via induced biosynthesis or external applications. Dosage-dependent endocides can selectively …

Inhibition Of Bacterial Growth And Prevention Of Bacterial Adhesion With Localized Nitric Oxide Delivery, Julia Osborne

Dissertations, Master's Theses and Master's Reports

Bacterial infections continue to be a problem at the site of an indwelling medical device, and over the years, various bacterial strains have become more resistant to current antibiotic treatments. Bacterial infection at an indwelling medical device can be dangerous and affect the performance of the medical device which can ultimately lead to the failure of the device due to bacterial resistance to treatment.

Nitric Oxide (NO) has been shown to possess antibacterial properties to prevent and inhibit bacterial growth. NO releasing coatings on indwelling medical devices could provide a reduction in bacterial infections that occur at the device site …

Anti-Tb And Antibacterial Activities Of Natural Products Extracts, Douglas Armstrong, Nathan Krause, Drew Frey

Faculty Scholarship – Chemistry

Samples of numerous plant species were received from the southwestern part of the USA from Richard Spjut, and plant samples were collected here in Illinois. All were extracted with typical solvents, giving crude residues, some of which were subjected to counter-current or flash chromatographic methods. Some of the crude extracts and chromatographic fractions had anti-tuberculosis and/or antibacterial activity.

In a general way, bioactive natural products are dealt with very well by Liang & Fang, 2006. More specifically, the southwestern part of the United States has a large variety of indigenous plants, many of which have not been investigated for their …

Application Of Ichip To Grow “Uncultivable” Microorganisms And Its Impact On Antibiotic Discovery, Rinzhin T. Sherpa, Caretta J. Reese, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Purpose. Antibiotics have revolutionized modern medicine, allowing significant progress in healthcare and improvement in life expectancy. Development of antibiotic resistance by pathogenic bacteria is a natural phenomenon; however, the rate of antibiotic resistance emergence is increasing at an alarming rate, due to indiscriminate use of antibiotics in healthcare, agriculture and even everyday products. Traditionally, antibiotic discovery has been conducted by screening extracts of microorganisms for antimicrobial activity. However, this conventional source has been over-used to such an extent that it poses the risk of “running out” of new antibiotics. Aiming to increase access to a greater diversity of microorganisms, …

Effects Of Pringle Maneuver And Partial Hepatectomy On The Pharmacokinetics And Blood–Brain Barrier Permeability Of Sodium Fluorescein In Rats, Mohammad K. Miah, Imam H. Shaik, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Liver diseases are known to affect the function of remote organs. The aim of the present study was to investigate the effects of Pringle maneuver, which results in hepatic ischemia–reperfusion (IR) injury, and partial hepatectomy (Hx) on the pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a widely used marker of blood–brain barrier (BBB) permeability. Rats were subjected to Pringle maneuver (total hepatic ischemia) for 20 min with (HxIR) or without (IR) 70% hepatectomy. Sham-operated animals underwent laparotomy only. After 15 min or 8 h of reperfusion, a single 25-mg/kg dose of FL was injected intravenously and serial …

Effect Of Novel Dietary Supplement On Metabolism In Vitro And In Vivo, Robert A. Vaughan, Ailish C. White, Jason R. Beam, Nicholas P. Gannon, Randi Garcia-Smith, Roy M. Salgado, Marco Bisoffi, Kristina A. Trujillo, Carole A. Conn, Christine M. Mermier

Health Sciences and Kinesiology Faculty Articles

Obesity is an increasingly prevalent and preventable morbidity with multiple behavioral, surgical and pharmacological interventions currently available. Commercial dietary supplements are often advertised to stimulate metabolism and cause rapid weight and/or fat loss, although few well-controlled studies have demonstrated such effects. We describe a commercially available dietary supplement (purportedly containing caffeine, catechins, and other metabolic stimulators) on resting metabolic rate in humans, and on metabolism, mitochondrial content, and related gene expression in vitro. Human males ingested either a placebo or commercially available supplement (RF) in a randomized double-blind placebo-controlled cross-over fashion. Metabolic rate, respiratory exchange ratio, and blood pressure were …

Exploration Of Putative Mitochondrial Gene Expression In Crithidia Fasciculata As A Model For Pathogenic Trypanosomes Causing Human Disease, Baylye Boxall, Nadjean Sagesse

Georgia State Undergraduate Research Conference

No abstract provided.

Investigation Of Dual Stage Acridones As A Potent Malaria Treatment, Stephanie Huezo

Dissertations, Masters Theses, Capstones, and Culminating Projects

The need for potent antimalarials to prevent the emergence of drug resistant Plasmodium falciparum is urgent. Discovery of novel acridone chemotypes have shown promise for a new antimalarial drug treatment. Presently, two acridone chemotypes have intrinsic antimalarial potency against chloroquine sensitive and multidrug resistant parasites. Acridones lacking an N10 side chain are known as chemotype I acridones, whereas, chemotype II acridones are defined as having an alkyl side chain at the same position. The N10 substitution of chemotype II acridones is thought to target heme and inhibit hemozoin formation within the parasite’s digestive vacuole, and is known to provide synergistic …

Effects Of Cannabidiol On Contractions And Calcium Signaling In Rat Ventricular Myocytes, Ramez M. Ali, Lina T. Al Kury, Keun-Hang Susan Yang, Anwar Qureshi, Mohanraj Rajesh, Sehamuddin Galadari, Yaroslav M. Shuba, Frank Christopher Howarth, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca2+ was measured in cells loaded with the Ca2+ sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca2+ currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (1 μM) caused a significant decrease in the amplitudes of …

Effects Of (R)-(-)-5-Methyl-1-Nicotinoyl-2-Pyrazoline On Glutamate Transporter 1 And Cysteine/Glutamate Exchanger As Well As Ethanol Drinking Behavior In Male, Alcohol-Preferring Rats, Munaf Aal-Aaboda, Hasan Alhaddad, Francis Osowik, Surya M. Nauli, Youssef Sari

Pharmacy Faculty Articles and Research

Alcohol consumption is largely associated with alterations in the extracellular glutamate concentrations in several brain reward regions. We recently showed that glutamate transporter 1 (GLT-1) is downregulated following chronic exposure to ethanol for 5 weeks in alcohol-preferring (P) rats and that upregulation of the GLT-1 levels in nucleus accumbens and prefrontal cortex results, in part, in attenuating ethanol consumption. Cystine glutamate antiporter (xCT) is also downregulated after chronic ethanol exposure in P rats, and its upregulation could be valuable in attenuating ethanol drinking. This study examines the effect of a synthetic compound, (R)-(−)-5-methyl-1-nicotinoyl-2-pyrazoline (MS-153), on ethanol drinking and expressions of …

Characterization Of A Novel Protease In Staphylococcus Aureus, Adam L. Johnson

Theses and Dissertations

A newly discovered cysteine protease, Prp, has been shown to perform an essential, site-specific cleavage of ribosomal protein L27 in Staphylococcus aureus. In Firmicutes and related bacteria, ribosomal protein L27 is encoded with a conserved N-terminal extension that must be removed to expose residues critical for ribosome function. Uncleavable and pre-cleaved variants were unable to complement an L27 deletion in S. aureus, indicating that this N-terminal processing event is essential and likely plays an important regulatory role. The gene encoding the responsible protease (prp) has been shown to be essential, and is found in all organisms …

Targeting The Small- And Intermediate Conductance Ca2+- Activated Potassium Channels: The Drug Binding Pocket At The Channel/Calmodulin Interface, Meng Cui, Guangrong Qin, Kunqian Yu, M. Scott Bowers, Miao Zhang

Pharmacy Faculty Articles and Research

The small- and intermediate-conductance Ca 2+ -activated potassium (SK/IK) channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca 2+ sensitivity of the SK/IK channels stems from a constitutively bound Ca 2+ -binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been …

Lipid Extraction From Scenedesmus Sp. Microalgae For Biodiesel Production Using Hot Compressed Hexane, Hee-Yong Shin, Jae-Hun Ryu, Seong-Youl Bae, Czarena L. Crofcheck, Mark Crocker

Center for Applied Energy Research Faculty and Staff Publications

Lipid extraction from Scenedesmus sp. microalgae using hot compressed hexane (HCH) was investigated. Extraction performance was evaluated near the critical point of hexane and was compared with that of hexane extraction performed at room temperature and pressure, and the Bligh and Dyer extraction method. Experimental data showed that HCH significantly improves the lipid yield and rate of lipid extraction compared to the use of hexane at ambient conditions. High yields of biodiesel-convertible lipid fractions were rapidly achieved at the critical point of hexane, at a level comparable to that of the Bligh and Dyer method.

Uhplc-Ms/Ms Analysis Of Arachidonic Acid And 10 Of Its Major Cytochrome P450 Metabolites As Free Acids In Rat Livers: Effects Of Hepatic Ischemia, Vindhya Edpuganti, Reza Mehvar

Pharmacy Faculty Articles and Research

The cytochrome P450 metabolites of arachidonic acid (AA) are mostly present in tissues, such as the liver, as bound to phospholipids, with only a small fraction available as free acids. The purpose of this study was to develop and validate a UHPLC-MS/MS method for quantitation of free liver concentrations of AA and four epoxygenated (5,6-, 8,9-, 11,12-, and 14,15-EET), four dihydroxylated (5,6-, 8,9-, 11,12-, and 14,15-DHET), and two ω/(ω-1) hydroxylated (19- and 20- HETEs) metabolites of AA in rat livers using deuterated internal standards. The analytes were rapidly and efficiently (79-92%) recovered from 100 mg of fresh liver into methanol. …

The Effects Of Ocean Acidification And Eutrophication On The Growth, Lipid Composition And Toxicity Of The Marine Raphidophyte Heterosigma Akashiwo., Julia Rose Matheson

Electronic Thesis and Dissertation Repository

Anthropogenic forcing, such as ocean acidification caused by rising carbon dioxide emissions, and eutrophication due to increased nutrient loadings in run-off, are causing major changes to the biogeochemistry of the oceans. As a consequence, coastal phytoplankton are susceptible to altered biogeochemical environments. This study examined the effect of a lower pH and increased levels of nutrients on the common coastal harmful alga, Heterosigma akashiwo. Growth rates, maximal cell yields, neutral lipid accumulation and toxicity of cells grown under various pH and nutrients regimes were measured. H. akashiwo growth was near maximal when grown at lower pH levels. There was …

Mamba Juice: Expression Of Exogenous Mambalgin Peptide Using The Pgapzα Vector System, Lydia Studdard, Kristin Vanmouwerik, Merhawi Yigzaw, Reza Alavi

Georgia State Undergraduate Research Conference

No abstract provided.

Integrating Phage Therapy Into Western Medicine, Jacob B. Jaminet

Undergraduate Research Posters

The World Health Organization has described the rise of antibiotic use as a “global heath security emergency” (who.int). With the growing concern about antibiotic resistant bacteria, there has been an increased interest in bacteriophages. Bacteriophages are high-specific viruses that only infect bacteria. The use of bacteriophages medicinally to treat bacteria is called phage therapy. Research in phage therapy gained momentum until the introduction of antibiotics. While the USA and other Western countries accepted antibiotics, the Soviet Union and their satellite nations still continued to research phages. Since the funding for research was supplied by the Soviet military, the results of …

Effects Of Hepatic Ischemia-Reperfusion Injury On The P-Glycoprotein Activity At The Liver Canalicular Membrane And Blood-Brain Barrier Determined By In Vivo Administration Of Rhodamine 123 In Rats, M. K. Miah, Imam H. Shaik, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Purpose To investigate the effects of normothermic hepatic ischemia-reperfusion (IR) injury on the activity of P-glycoprotein (P-gp) in the liver and at the blood-brain barrier (BBB) of rats using rhodamine 123 (RH-123) as an in vivo marker.

Methods Rats were subjected to 90 min of partial ischemia or sham surgery, followed by 12 or 24 h of reperfusion. Following intravenous injection, the concentrations of RH-123 in blood, bile, brain, and liver were used for pharmacokinetic calculations. The protein levels of P-gp and some other transporters in the liver and brain were also determined by Western blot analysis.

Results P-gp protein …

Effects Of Endogenous Cannabinoid Anandamide On Voltage-Dependent Sodium And Calcium Channels In Rat Ventricular Myocytes, Lina T. Al Kury, Oleg I. Voitychuk, Keun-Hang Susan Yang, Faisal T. Thayyullathil, Petro Doroshenkp, Ali M. Ramez, Yaroslav M. Shuba, Sehamuddin Galadari, Frank Christopher Howarth, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

BACKGROUND AND PURPOSE: The endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes.

EXPERIMENTAL APPROACH: Whole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes.

KEY RESULTS: In the presence of 1-10 μM AEA, suppression of both Na(+) and L-type Ca(2+) channels was observed. Inhibition of Na(+) channels was voltage and Pertussis toxin (PTX) - independent. Radioligand-binding studies indicated that specific binding of [(3) H] batrachotoxin (BTX) to ventricular muscle membranes was also inhibited significantly by 10 μM metAEA, a non-metabolized AEA analogue, with …

Erg11-Mediated Azole Resistance In Candida Albicans, Stephanie Ann Flowers

Theses and Dissertations (ETD)

Although many medically important Candida species are commensal to the gut or colonizers of the skin, these organisms have the propensity to cause disease in the event of a waning immune system. Clinical manifestations of infections with Candida species can range from superficial mucosal infections to deep organ involvement usually resulting from haematogenous spread of infection. Despite significant progress made in the management of patients with fungal infections, the emergence of antifungal resistant clinical isolates creates significant problem in regards to antifungal prophylaxis and empirical treatment strategies. Antifungal resistance is associated with high mortality rates and hefty medical costs. The …

Tigecycline Induction Of Phenol-Soluble Modulins By Invasive Methicillin-Resistant Staphylococcus Aureus Strains, Jason Yamaki, Timothy Synold, Annie Wong-Beringer

Pharmacy Faculty Articles and Research

We examined the effects of tigecycline on three types of exoproteins, α-type phenol-soluble modulins (PSMα1 to PSMα4), α-hemolysin, and protein A, in 13 methicillin-resistant Staphylococcus aureus isolates compared to those of clindamycin and linezolid. Paradoxical increases in PSMαs occurred in 77% of the isolates with tigecycline at 1/4 and 1/8 MICs and clindamycin at 1/8 MIC compared to only 23% of the isolates with linezolid at 1/8 MIC. Induction was specific to PSMα₁ to PSMα₄, as protein A and α-hemolysin production was decreased under the same conditions by all of the antibiotics used.

Human Milk Cortisol Is Associated With Infant Temperament, Katherine R. Grey, Elyssia Poggi Davis, Curt A. Sandman, Laura M. Glynn

Psychology Faculty Articles and Research

The implications of the biologically active elements in milk for the mammalian infant are largely unknown. Animal models demonstrate that transmission of glucocorticoids through milk influences behavior and modifies brain development in offspring. The aim of this study was to determine the relation between human milk cortisol levels and temperament of the breastfed infant. Fifty-two mother and infant pairs participated when the infants were three-months old. Milk cortisol levels were assessed and each mother completed the Infant Behavior Questionnaire (IBQ), a widely used parent-report measure of infant temperament. Analyses revealed a positive association between milk cortisol and the negative affectivity …