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Theses/Dissertations

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Life Sciences

2007

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Full-Text Articles in Medicine and Health Sciences

Feline Lentivirus: Molecular Analysis And Epidemiology In Southern African Lions, Hayley Rebecca Adams Dec 2007

Feline Lentivirus: Molecular Analysis And Epidemiology In Southern African Lions, Hayley Rebecca Adams

Doctoral Dissertations

Feline immunodeficiency virus is a retrovirus of domestic cats causing significant lifelong infection. Infection has also been detected in nondomestic species, including African lions. It is endemic in certain populations in east and southern Africa. Infection leads to immunologic dysfunction and immunosuppressive disease in domestic cats; however, little research exists about the pathogenic effects of infection in lions and its epidemiological impact on free-ranging and captive populations. Little is known about the lentivirus in these populations at the molecular and host level. Analysis of the virus from these populations is necessary for development of detection assays that are both sensitive …


Conferred Immunity Against The H1n1 Type A Influenza Virus In Madin-Darby Canine Kidney Cells Via Cecropin B Transfection Therapy., Tomasz P. Stryjewski Nov 2007

Conferred Immunity Against The H1n1 Type A Influenza Virus In Madin-Darby Canine Kidney Cells Via Cecropin B Transfection Therapy., Tomasz P. Stryjewski

Honors Theses

No abstract provided.


Antimicrobial Activity Screening Of Recombinant And Synthetic Varasin A Defensin From The Hard Tick Dermacentor Variabilis Against Various Bacteria, Julia A. Sharp Oct 2007

Antimicrobial Activity Screening Of Recombinant And Synthetic Varasin A Defensin From The Hard Tick Dermacentor Variabilis Against Various Bacteria, Julia A. Sharp

Biological Sciences Theses & Dissertations

Hematophagous arthropods, such as ticks and mosquitoes, rely on their innate immune system for defense against pathogens ingested in a blood meal as well as those acquired through injury. In response to pathogen recognition, the production of antimicrobial peptides, such as defensin, is typically upregulated. Varisin, a defensin, is thought to be a key component in the immunocompetence of the hard tick D. variabilis against Borrelia burgdorferi, the causative agent of Lyme disease. To study the antimicrobial effects of varisin, recombinant varisin was expressed by both insect cells and E coli. Purification of the protein followed by enterokinase treatment yielded …


The Role Of Nogo-A During Development Of The Chick Central Nervous System, Shelly A. Caltharp Aug 2007

The Role Of Nogo-A During Development Of The Chick Central Nervous System, Shelly A. Caltharp

Loma Linda University Electronic Theses, Dissertations & Projects

Nogo-A is a potent inhibitor of axon regeneration that is expressed by myelin forming oligodendrocytes of the adult central nervous system (CNS). However, neuronal expression of Nogo-A during development suggests an additional role. Little is known about the putative functions of Nogo-A during embryonic development. To examine its potential role we isolated and analyzed the Nogo-A sequence in the chick, we localized its mRNA expression pattern and cell-specific distribution during key phases of cortical development, and studied regulation of its expression during phases that showed promise of function based on expression patterns.

Our results revealed five previously undescribed Nogo-A specific …


The Effect Of Mtad On Eight Strains Of E. Faecalis In Contaminated Root Canals, Bradley M. Newberry Aug 2007

The Effect Of Mtad On Eight Strains Of E. Faecalis In Contaminated Root Canals, Bradley M. Newberry

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this investigation was to determine the antimicrobial effect of Biopure MTAD (a mixture of a tetracycline isomer, an acid, and a detergent) as a final irrigant on eight strains of Enterococcus faecalis (E. faecalis) in contaminated root canals of extracted human teeth. In addition, the Minimum Inhibitory Concentration (MIC) and Minimum Lethal Concentration (MLC) of MTAD were also measured on the same strains of bacteria. Two-hundred and forty extracted human teeth were instrumented using 1.3% NaOCl followed by 17% EDTA to remove the smear layer. The teeth were randomly contaminated with one of eight strains of E. …


Evidence For Disease Mediated Extinction: Correlation Between An Introduced Pathogen And Extinction Of Rattus Macleari On Christmas Island, Kelly B. Wyatt Jul 2007

Evidence For Disease Mediated Extinction: Correlation Between An Introduced Pathogen And Extinction Of Rattus Macleari On Christmas Island, Kelly B. Wyatt

Biological Sciences Theses & Dissertations

The Durham Collection and the Cambridge and Oxford University Museums provided the materials to investigate the possibility that the extinction of indigenous rats of Christmas Island was a result of disease introduced by infected ship rats (R. rattus) in 1899. The collections of H.E. Durham in 1901-1902 reveal that R. macleari was present on Christmas Island up to then and includes specimens of R. rattus together with specimens that exhibit characteristics of both R. rattus and R. macleari. Durham's notes indicate both R. rattus and R. macleari specimens were heavily infected with trypanosomes at the time of collection. In …


The Effect Of Intensity Of Aerobic Vo2max Resting Heart Rate And Blood Pressure, Shannan Elizabeth Gormley Jul 2007

The Effect Of Intensity Of Aerobic Vo2max Resting Heart Rate And Blood Pressure, Shannan Elizabeth Gormley

Human Movement Sciences & Special Education Theses & Dissertations

The AGSM recommends 20 to 60 minutes of continuous or intermittent activity 3 to 5 times per week to maintain cardio respiratory fitness (Pollock et al., 1998). The 1996 Surgeon General's Report on Physical Activity and Health indicates that Americans are not meeting these physical activity recommendations (DHHS). Several clear consequences of physical inactivity are the appearance of cardiovascular disease risk factors, such as hypertension, hyperlipidemia and obesity. Two recent review articles suggested that higher intensity exercise will elicit a greater reduction in cardiovascular disease risk factors (Swain and Franklin, 2002; Swain and Franklin, 2006). In order to determine whether …


Electromagnetic Differences In The Brain During Memory Retrieval, Warren Scott Merrifield Jun 2007

Electromagnetic Differences In The Brain During Memory Retrieval, Warren Scott Merrifield

Loma Linda University Electronic Theses, Dissertations & Projects

The primary objectives for this experiment were to analyze the neuroanatomical correlates of autobiographical, episodic and semantic memory, use a different paradigm to promote episodic memory retrieval, and employ a different analysis technique to understand retrieval processes. Autobiographical and episodic memories are personal memories from the past. Autobiographical is more general (e.g. a street name of a house growing up) and episodic is more specific to time (e.g. 13th birthday party that took place on a street). For autobiographical and episodic memory retrieval operations, there is no general consensus as to the localization of function, but bilateral activation of the …


Biochemical Characteristics Of Inconsistent Free T₄ Assays, Kristofer S. Fritz May 2007

Biochemical Characteristics Of Inconsistent Free T₄ Assays, Kristofer S. Fritz

Loma Linda University Electronic Theses, Dissertations & Projects

Serum levels of free thyroxine (T4) are helpful in the clinical evaluation of patients who are suspected of having thyroid disease, since free T4 (unbound) is known to closely relate to hyper, eu and hypothyroidism. There are documented inconsistencies among commercially available direct free thyroxine immunoassays. The biochemical basis for these inconsistencies is not understood and has not been characterized. Direct free T4 measurements have been linked to both T4-binding serum protein concentrations and protein-bound T4 concentrations. A free T4 reference method using direct equilibrium dialysis radioimmunoassay has been well characterized. New …


The Effect Of Radiation And Repeated Sub-Culturing On Tgf-Β1 Signaling In Frtl-5 Cells, Cheryl G. Burrell May 2007

The Effect Of Radiation And Repeated Sub-Culturing On Tgf-Β1 Signaling In Frtl-5 Cells, Cheryl G. Burrell

Loma Linda University Electronic Theses, Dissertations & Projects

From our ongoing in vitro studies using the Fisher Rat Thyroid cell line-5 (FRTL-5) we recorded accelerated growth, reduced follicularization and reduction in thyroxin release that occurred as the cells were repeatedly sub-cultured. We also recorded that these changes occurred earlier and more rapidly following radiation exposure. We determined that TGF-β1 production increased under both conditions. We hypothesized that alteration in the TGF-β1 signaling pathway contributed to the changes observed in the cellular properties of FRTL-5 cells. Our objective was to examine some of the players in the TGF-β1 signaling pathway to determine whether radiation and/or repeated subculturing promoted changes …


Maturational Changes In Cerebrovascular Thick- And Thin-Filament Regulation, Renan Joel Sandoval May 2007

Maturational Changes In Cerebrovascular Thick- And Thin-Filament Regulation, Renan Joel Sandoval

Loma Linda University Electronic Theses, Dissertations & Projects

The present study focused on the main hypothesis that age-related changes in myofilament Ca2+ sensitivity involve simultaneous changes in the relations between cytosolic Ca2+ transients, myosin phosphorylation, and force development. To define the effects of late fetal and early postnatal maturation, parallel experiments were carried out using cerebral arteries from both term lamb fetuses (140-141 days of gestation) and nonpregnant adult sheep. Fetal and adult cerebral arteries were stimulated by either mechanically, electromechanically, and/or pharmacomechanically-induced contractions, and the relations of cytosolic Ca2+, MLC phosphorylation, and contractile tensions were measured. These measurements allowed for stimulus and age-dependent …


Iron Dysregulation And Inflammation In Alzheimer’S Disease, Shino D. Magaki May 2007

Iron Dysregulation And Inflammation In Alzheimer’S Disease, Shino D. Magaki

Loma Linda University Electronic Theses, Dissertations & Projects

Alzheimer’s disease (AD) is the most common form of senile dementia in the US and worldwide but the causes of its pathogenesis are currently unknown. In this study, we examined two processes that have been implicated in the early stages of AD and other forms of neurodegeneration, iron dysregulation and inflammation, both of which can promote the increased production of amyloid precursor protein (APP). We have measured different pools of brain iron in transgenic iron regulatory protein 2 knockout (IRP2-/-) mice in the early stages of neurodegeneration and in affected brain regions from AD patients at different stages of the …


Regulation Of Alpha-1-Adrenoceptor-Mediated Contractions Of The Uterine Artery By Pkc, Hongying Zhang May 2007

Regulation Of Alpha-1-Adrenoceptor-Mediated Contractions Of The Uterine Artery By Pkc, Hongying Zhang

Loma Linda University Electronic Theses, Dissertations & Projects

Pregnancy is associated with a significant decrease in uterine vascular tone and a striking increase in uterine blood flow, which ensures normal fetal development. Multiple mechanisms are involved in the adaptation of uterine artery contractility during pregnancy. Both protein kinase C (PKC) and activation of ai-adrenoceptors play important roles in the regulation of uterine artery contractility. In addition, PKC mediates the pregnancyassociated decrease in myogenic tone of the uterine artery, and interacts with ajadrenoceptors leading to modulation of ai-adrenoceptor-mediated contractions of vascular smooth muscle. Yet, whether or to what extent PKC regulates ai-adrenoceptormediated contractions of the uterine artery and their …


Radiation-Induced Increases In Pkc Modulate Integrin Expression And Contribute To Fibrotic Changes, Pinal Rushikesh Pandya May 2007

Radiation-Induced Increases In Pkc Modulate Integrin Expression And Contribute To Fibrotic Changes, Pinal Rushikesh Pandya

Loma Linda University Electronic Theses, Dissertations & Projects

The sequences of events in fibrosis are similar to those in wound healing; however, the normal termination and resolution stages do not take place. The initial cellular response following ionizing radiation involves accumulation of the ECM (extracellular matrix) including collagen, fibronectin and the interaction of many growth factors (cytokines) with their receptors. There are a number of unanswered questions regarding many aspects of radiation-induced fibrosis, including the initial triggers and physical changes that initiate the process. We have confirmed that elevated pKC and other cellular changes following radiation are similar to those found at sites of inflammation. This information leads …


The Development Of A Gc/Ms Protocol For The Analysis Of Polysaccharides In Echinacea Purpurea, Michaela Knapp Apr 2007

The Development Of A Gc/Ms Protocol For The Analysis Of Polysaccharides In Echinacea Purpurea, Michaela Knapp

Undergraduate Theses and Capstone Projects

Echinacea purpurea is an herbal supplement used to reduce symptoms of common colds and flu-like illnesses. As of right now, it is not well understood what chemical components in the plant are immunologically active. The four main potentially immunologically active chemical components in E. purpurea are caffeic acid derivatives, alkamides, polyacetylenes, and polysaccharides. In this investigation, a protocol was developed in an attempt to identify polysaccharides present in Puritan’s Pride E. purpurea (aerial) “non-irradiated” herbal supplement First, an estimate of the crude total polysaccharide content in Puritan’s Pride and in a ChromaDex certified botanical standard (E. purpurea -powdered root) was …


Stability Of Eukaryotic Elongation Factor One Alpha Protein In The Cell, Jennifer Watry Apr 2007

Stability Of Eukaryotic Elongation Factor One Alpha Protein In The Cell, Jennifer Watry

Honors Theses

Eukaryotic Elongation Factor One Alpha (eEF1A) is an abundant protein found in every cell of every organism and is involved in functions concerning protein synthesis and degradation, the cytoskeleton, and signaling. How these functions are regulated is not yet understood for this protein. Regulation of the protein may be controlled by transcription of the genes encoding the protein or the stability and modification of the protein. The goal of this project was to determine the stability of eEf1A proteins in Arabidopsis thaliana. Protein stability was determined by treating tissues with cycloheximide, an inhibitor of protein synthesis. Gel electrophoresis and …


The Effect Of Three Foot Orthoses On Plantar Pressure Under The First Metatarsophalangeal Joint Of Pes Planus Foot Type During Standing And Slow Running, Lacey Ann Nordsiden Apr 2007

The Effect Of Three Foot Orthoses On Plantar Pressure Under The First Metatarsophalangeal Joint Of Pes Planus Foot Type During Standing And Slow Running, Lacey Ann Nordsiden

Human Movement Sciences & Special Education Theses & Dissertations

The purpose of this study was to examine the effect of three different foot orthoses on plantar pressure under the first metatarsophalangeal joint during standing and slow running. Twenty physically active participants, 12 males (19.7±1.3 years, 181.5±6.3cm, 83.6±12.3kg) and 8 females (20.8±1.5 years, 172.7±11.2cm, 69.9±14.2kg) with navicular drop greater than 10mm, no history of surgery to the lower extremity, and no history of pain or injury to the 1st metatarsophalangeal joint in the past six months volunteered for the study. Each subject performed standing and slow running tasks with four different orthosis conditions: no orthosis, metatarsal dome, U-shaped orthosis, and …


Down-Regulation Of Natural Killer Cell Activation In Response To Influenza Virus In Older Adults, Yu Jing Apr 2007

Down-Regulation Of Natural Killer Cell Activation In Response To Influenza Virus In Older Adults, Yu Jing

Theses and Dissertations in Biomedical Sciences

Immune senescence contributes to influenza-associated high mortality and morbidity and reduced vaccine efficacy in elderly people. Type I T cell (Thl)-mediated immunity plays a significant role in Immune responses to influenza infection and vaccination. Natural killer (NK) cells secrete significant amount of IFN-7 , a hallmark Thl cytokine, in response to influenza infection. How aging influences human NK cell IFN-7 production in response to influenza virus has not been well documented. In this study we employed human peripheral blood mononuclear cells (PBMC) and performed intracellular cytokine staining and flow cytometry primarily to investigate how aging influences NK cell activation with …


Bactericidal Effects Of Cold Plasma Technology On Geobacillus Stearothermophilus And Bacillus Cereus Microorganisms, Angela Dawn Morris Apr 2007

Bactericidal Effects Of Cold Plasma Technology On Geobacillus Stearothermophilus And Bacillus Cereus Microorganisms, Angela Dawn Morris

Dental Hygiene Theses & Dissertations

Non-equilibrium atmospheric pressure plasma, also known as cold plasma, is a state of matter that consists of a mix of neutral and charged particles. Plasma generates chemically reactive species and ultraviolet radiation making them useful in decontamination applications (Kong & Laroussi, 2003). Research regarding the inactivation of gram-positive bacteria, such as Bacillus atrophaeus, by cold plasma has been studied by Laroussi et al. (2003); however, there is limited research regarding the germicidal effectiveness of cold plasma on the microorganisms Geobacillus stearothermophilus and Bacillus cereus. The purpose of this study was to determine if cold plasma technology inactivates heat …


Physical Characteristics Of An Individual: The Identification Of Biomarkers For Biological Age Determination, Michelle Alvarez Jan 2007

Physical Characteristics Of An Individual: The Identification Of Biomarkers For Biological Age Determination, Michelle Alvarez

Electronic Theses and Dissertations

It is now a matter of routine for the forensic scientist to obtain the genetic profile of an individual from DNA recovered from a biological stain deposited at a crime scene. Potential contributors of the stain must either be known to investigators (i.e. a developed suspect) or the questioned profile must be searched against a database of DNA profiles such as those maintained in the CODIS National DNA database. However, in those instances where there is no developed suspect and no match is obtained after interrogation of appropriate DNA databases, the DNA profile per se presently provides no meaningful information …


A Member Of The Novel Fikk Family Of Plasmodium Falciparum Putative Protein Kinases Exhibits Diacylglycerol Kinase Activity And Is Exported To The Host Erythrocyte, David Floyd Curtis Jan 2007

A Member Of The Novel Fikk Family Of Plasmodium Falciparum Putative Protein Kinases Exhibits Diacylglycerol Kinase Activity And Is Exported To The Host Erythrocyte, David Floyd Curtis

Electronic Theses and Dissertations

Plasmodium falciparum is one of four species known to cause malaria in humans and is the species that is associated with the most virulent form of the disease. Malaria causes nearly two million deaths each year, many of these occurring among children in under-developed countries of the world. One reason for this is the prevalence of drug resistant strains of malaria that mitigate the efficacy of existing drugs. Hence, the identification of a new generation of pharmacological agents for malaria is extremely urgent. The recent identification of a group of novel protein kinases within the Plasmodium falciparum genome has provided …


Shear Stress Induced Mtor Signaling In Cultured A7r5 Aortic Smooth Muscle Cell Line, Sriram Prasad Mupparaju Jan 2007

Shear Stress Induced Mtor Signaling In Cultured A7r5 Aortic Smooth Muscle Cell Line, Sriram Prasad Mupparaju

Theses, Dissertations and Capstones

Vascular intervention procedures such as balloon angioplasty and stent implantation lead to denudation of endothelium exposing the underlying smooth muscle layer to effects of blood shear stress. The effect of shear stress on smooth muscle cell signaling has not been studied in depth. In this study, we examined time dependent changes in activation of Akt, mTOR and p70S6k related signaling in response to orbital shear stress on cultured A7r5 cells. A7r5 cells cultured to subconfluence on 150mm culture dishes were subjected to orbital shear of 9.8dynes/cm 2 for zero, 5 min, 15 min, 30 min, 1h, 4h and 24h. The …


Chronic Acetaminophen Treatment Influences Indices Of Reactive Oxygen Species Accumulation In The Aging Fisher 344 X Brown Norway Rat Aorta, Sarath Meduru Jan 2007

Chronic Acetaminophen Treatment Influences Indices Of Reactive Oxygen Species Accumulation In The Aging Fisher 344 X Brown Norway Rat Aorta, Sarath Meduru

Theses, Dissertations and Capstones

We have previously reported that aging in the Fisher 344 X Brown Norway (FBN) rat aorta is characterized by increased levels of ROS and alterations in cell signaling. Acetaminophen was found to scavenge free radicals in recent ischemia-reperfusion studies. Here we examined if chronic treatment with a therapeutic dose of acetaminophen attenuates age-associated increase in aortic ROS accumulation and signaling. FBN rats (27 month old; n=8) were subjected to 6 months of treatment with a therapeutic dose of acetaminophen (30mg/kg/day), with age-matched untreated FBN rats as controls. Protein oxidation levels were altered in control and treated aortae compared to aortae …


The Expression And Function Of Ppar And Hif-1 In Human Melanoma, Caroline Mills Jan 2007

The Expression And Function Of Ppar And Hif-1 In Human Melanoma, Caroline Mills

Theses, Dissertations and Capstones

The first part of my dissertation focuses on the expression and function of PPARs in human melanoma. I found that the A375 cells were significantly growth inhibited in response to PGJ2 and troglitazone treatment. HEMn-LP showed significant growth inhibition in response to troglitazone. I found that PPARγ and PPARδ mRNA is present in both the SK-Mel 28 and A375 cells. The relative level of PPARα mRNA expression is highest in SK-Mel 28 cells, ~3 fold higher relative to both the normal human melanocytes and A375 cells. PPARγ protein was ~50% higher in both SK-Mel 28 and A375 cells relative to …


The Effect Of Walnuts Compared To Fatty Fish On Plasma And Erythrocyte Fatty Acid Composition, Lymphocyte Subsets And Inflammatory Mediators, Yu-Lan Ching Jan 2007

The Effect Of Walnuts Compared To Fatty Fish On Plasma And Erythrocyte Fatty Acid Composition, Lymphocyte Subsets And Inflammatory Mediators, Yu-Lan Ching

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to compare the effects of walnuts vs. fatty fish on circulating inflammatory markers, on lymphocyte subsets, on plasma concentrations of eicosanoids precursor polyunsaturated fatty acid and on erythrocyte membrane fatty acid composition. Under controlled metabolic feeding conditions and randomized crossover (3x3 Latin-square) design, 27 subjects alternately consumed a control diet, a walnut diet (1.5 oz (42.5g) /day of walnuts, 6 times/week) or a fish diet (8 oz (226g) /week of salmon) for 4 weeks each. Consumption of the walnut diet (ALA 5.43 g/day) compared to the fish diet (EPA 170 mg/day and DHA 590 …


Increasing Serum 25-Hydroxyvitamin D As A Possible Deterrent To The Onset Of Multiple Sclerosis, Nicholas J. Perretti Jan 2007

Increasing Serum 25-Hydroxyvitamin D As A Possible Deterrent To The Onset Of Multiple Sclerosis, Nicholas J. Perretti

Seton Hall University Dissertations and Theses (ETDs)

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Xenobiotic Transporters In Lactating Mammary Epithelial Cells: Predictions For Drug Accumulation In Breast Milk, Philip Earle Empey Jan 2007

Xenobiotic Transporters In Lactating Mammary Epithelial Cells: Predictions For Drug Accumulation In Breast Milk, Philip Earle Empey

Theses and Dissertations--Pharmacy

Recent literature has established that breast cancer resistance protein (ABCG2) is upregulated during lactation and is responsible for the greater than predicted accumulation of many drugs in breast milk. The objectives of this project were (1) to investigate the role of this transporter in the reported apically-directed nitrofurantoin flux in the CIT3 cell culture model of lactation, (2) to develop a mathematical model for drug transfer into breast milk to relate initial flux rates, steady-state concentrations, efflux ratios, and in vivo milk to serum ratios (M/S) and (3) to identify xenobiotic transporters that are highly expressed, and therefore potentially important …


Optimization Of Porcine Buccal Mucosa For In Vitro Evaluation, Upendra D. Kulkarni Jan 2007

Optimization Of Porcine Buccal Mucosa For In Vitro Evaluation, Upendra D. Kulkarni

University of the Pacific Theses and Dissertations

Porcine buccal mucosa has been extensively used as in vitro model to study the permeability of drugs and assess their potential to deliver through buccal route. Porcine buccal mucosa is found to be very similar to human oral mucosa in structure and function. However, the in vitro permeation studies across porcine buccal mucosa show high variability which is mostly due to the various experimental and biological variables that are often overlooked while conducting such studies.

The precise nature of the permeability barrier offered by the various tissue layers of buccal mucosa was investigated in this study. It was observed that …


Functional Properties Of L-Glutamate Regulation In Anesthetized And Freely Moving Mice, Kevin N. Hascup Jan 2007

Functional Properties Of L-Glutamate Regulation In Anesthetized And Freely Moving Mice, Kevin N. Hascup

Theses and Dissertations--Neuroscience

L-glutamate (Glu) is the predominant excitatory neurotransmitter in the mammalian central nervous system with involvement encompassing learning and memory, cognition, plasticity, and motor movement. Dysregulation of the glutamatergic system is implicated in several neurological disorders including Parkinson’s disease, Alzheimer’s disease, Huntington’s disease and amyotrophic lateral sclerosis. The mechanisms underlying these neurological disorders are not clear, but evidence suggests that abnormal Glu neurotransmission plays a role. Elevated levels of Glu in the synaptic cleft overstimulate the N-methyl-Daspartate receptor leading to excitotoxicity, which causes neuronal loss in chronic neurological diseases. What is less understood is the source for the elevated Glu levels. …


Retrocyclin Rc-101 Overcomes Cationic Mutations On The Heptad Repeat 2 Of Hiv-1 Gp41, Christopher Fuhrman Jan 2007

Retrocyclin Rc-101 Overcomes Cationic Mutations On The Heptad Repeat 2 Of Hiv-1 Gp41, Christopher Fuhrman

Electronic Theses and Dissertations

Retrocyclin RC-101, a θ-defensin with lectin-like properties, potently inhibits infection by many HIV-1 subtypes by binding to the heptad repeat (HR)-2 region of gp41 and preventing six-helix bundle formation. In the present study, we used in silico computational exploration to identify residues of HR2 that interacted with RC-101 and then analyzed the HIV-1 Sequence Database at LANL for residue variations in the HR1 and HR2 segments that could plausibly impart in vivo resistance. Docking RC-101 to gp41 peptides in silico confirmed its strong preference for HR2 over HR1, and implicated residues crucial for its ability to bind HR2. We mutagenized …