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HIM 1990-2015

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Full-Text Articles in Molecular Biology

Regulation Of Vldl Trafficking By Orp 10, Philip A. Wessels Jan 2015

Regulation Of Vldl Trafficking By Orp 10, Philip A. Wessels

HIM 1990-2015

Of the challenges facing the improvement of human health, none has taken the forefront quite like the endeavor to discover novel treatments for heart disease. As heart disease has now become the leading cause of death throughout the world [1], the medical community has made incredible strides in the mission to treat atherosclerosis which is the major contributor to heart disease. Very Low Density Lipoproteins (VLDL) are secreted by the liver and subsequently converted to Low Density Lipoproteins (LDL). Many factors contribute to the narrowing of the arterial walls, however oxidized LDL is the main factor that leads to the …


Detection Of Drug-Resistance Conferring Snps In Mycobacterium Tuberculosis Using Binary Dnazymes, Marina Addario Jan 2015

Detection Of Drug-Resistance Conferring Snps In Mycobacterium Tuberculosis Using Binary Dnazymes, Marina Addario

HIM 1990-2015

Mycobacterium tuberculosis (Mtb) is the pathogen that causes Tuberculosis (TB) and is responsible for an average of 1.5 million deaths annually. Although a treatment regimen does exist, Multi-Drug Resistant (MDR-TB) and eXtremely Drug Resistant (XDR-TB) TB strains are becoming a more prevalent concern partly due to failure of patient compliance with the current six to nine month drug treatment regimen. The current diagnostic methods are not able to identify these MDR and XDR-TB strains efficiently therefore more effective point-of-care (POC) diagnostics and drug susceptibility testing (DST) are urgently needed to detect drug resistance and facilitate prompt, appropriate treatment plans. In …


Development Of Novel Fluorescent Tools For Investigating Virulence Factors And Drug Susceptibility In Mycobacterium Tuberculosis, Kaley Wilburn Jan 2015

Development Of Novel Fluorescent Tools For Investigating Virulence Factors And Drug Susceptibility In Mycobacterium Tuberculosis, Kaley Wilburn

HIM 1990-2015

Mycobacterium tuberculosis (Mtb) is the causative agent of Tuberculosis (TB), a life-threatening disease primarily affecting the lungs that infects about one third of the world's population and causes 1.3 million deaths annually. It is estimated that TB has been infecting humans for around 70,000 years and has killed more people than any other infectious disease. The highly effective, persistent, and multifaceted virulence strategies that have allowed Mtb to continue to spread and thrive for so long are still poorly understood at the molecular level. This lack of knowledge contributes to ongoing challenges to curing TB. Although drugs capable of killing …


Elucidating The Molecular Pathway Of Atypical Plasmodium Falciparum Kinases Through Substrate Characterization, Daniel Segarra Jan 2015

Elucidating The Molecular Pathway Of Atypical Plasmodium Falciparum Kinases Through Substrate Characterization, Daniel Segarra

HIM 1990-2015

Plasmodium falciparum, the organism responsible for the most prevalent and most virulent cases of malaria in humans, poses a major burden to the developing world. The parasite is increasingly developing resistance to traditional therapies, such as chloroquine, so the need to determine novel drug targets is more prevalent than ever. One such method involves targeting proteins unique to the malarial proteome that do not have homologues in humans. An especially promising group of targets are protein kinases, which are involved in many different biochemical pathways within the cell. Eukaryotic cell cycle progression is moderated by a family of protein kinases …


Melatonin And Neurogenesis: A Comparative Study Of The Efficacy Of Melatonin, Its Precursors, And L-Dopa On Neural Stem Cell Metabolism In Human Adult Neurospheres, Omar Heriba Dec 2014

Melatonin And Neurogenesis: A Comparative Study Of The Efficacy Of Melatonin, Its Precursors, And L-Dopa On Neural Stem Cell Metabolism In Human Adult Neurospheres, Omar Heriba

HIM 1990-2015

Human neurosphere stem cells offer promising potential for the treatment of neurodegenerative diseases. Their well characterized multi-potency of differentiating into neurons, astrocytes, and oligodendrocytes when exposed to the optimum exogenous growth factors make them an exciting area of study (38). Finding novel endogenous methods of modulating stem cell metabolism will allow for the safer treatment of various brain disorders (34). In this experiment, melatonin, N-acetylserotonin, L-tryptophan, and L-DOPA are added in three different concentrations to neurospheres suspended in HNSC/GBM media with less than optimal concentrations of exogenous epidermal growth factor (EGF) and fibroblast growth factor (FGF). The alamarBlue assay (resazurin) …


Using The Yeast Two-Hybrid System To Determine The Function Of Parkin E3 Ubiquitin Ligase, Vanessa Nguyen Dec 2014

Using The Yeast Two-Hybrid System To Determine The Function Of Parkin E3 Ubiquitin Ligase, Vanessa Nguyen

HIM 1990-2015

Parkin is a cytosolic E3 ubiquitin ligase that is recruited to the mitochondria during cellular stress and has been suggested to be involved in a variety of biological processes such as mitophagy. The recruitment of Parkin (PARK2) to the mitochondria is dependent upon the kinase activity and the accumulation of PINK1 on damaged mitochondria. Mutations in either PINK1 or Parkin genes disrupt this protective pathway and lead to the accumulation of damaged mitochondria. From a clinical standpoint, mutations in the PARK2 gene have been associated with the progression and onset of autosomal recessive juvenile parkinsonism. Without the presence of a …


The Role Of Intestinal Sweet Taste Receptors (Strs) In The Regulation Of Glucose Absorption: Effects Of Short Term High Sucrose Diet (Hsd), Tania Hussain Jan 2014

The Role Of Intestinal Sweet Taste Receptors (Strs) In The Regulation Of Glucose Absorption: Effects Of Short Term High Sucrose Diet (Hsd), Tania Hussain

HIM 1990-2015

Sweet taste receptors are primarily found in the oral cavity of the mammalian species. However, recent studies have shown that sweet taste receptors can be found in extraoral tissues such as the pancreas, intestines, and adipose tissue. Our lab has previously found that sweet taste receptors are down-regulated on the pancreas in the presence of high plasma glucose levels. In order to assess the possibility that sweet taste receptors respond to high levels of glucose by suppressing its expression, we wanted to see if they reacted similarly on the intestines. We found that intestinal sweet taste receptors are down regulated …


The Glycine And Proline Reductase Systems: An Evolutionary Perspective And Presence In Enterobacteriaceae, Joshua Witt Dec 2013

The Glycine And Proline Reductase Systems: An Evolutionary Perspective And Presence In Enterobacteriaceae, Joshua Witt

HIM 1990-2015

The Glycine and Proline Reduction systems are two of the best characterized selenoenzymes in bacteria and have been found to occur in a wide variety of clostridia [1-5]. These enzymes are utilized to reduce glycine or D-proline to obtain energy via substrate level phosporylation or membrane gradients, respectively [6, 7]. This includes the pathogens C. difficile and C. botulinum [5, 8]. Strains of C. difficile are activate toxigenic pathways whenever either of these pathways is active within the cell [5, 8]. Though evolutionary studies have been conducted on ammonia producing bacteria [9] none has been done to directly characterize these …


The Effects Of Growth Hormone And Thyroxine Treatment On The Insulin Signaling Of Female Ames Dwarf Mouse Skeletal Muscle Tissue, Andrew Do Aug 2013

The Effects Of Growth Hormone And Thyroxine Treatment On The Insulin Signaling Of Female Ames Dwarf Mouse Skeletal Muscle Tissue, Andrew Do

HIM 1990-2015

Ames dwarf (df/df) mice are deficient in anterior pituitary hormones: growth hormone (GH), thyroid stimulating hormone (TSH), and prolactin (PRL) due to a spontaneous, homozygous mutation of prop1[superscript df] gene. These dwarf mice exhibit characteristics such as delayed growth and development coupled with delayed aging, increased lifespan, overall increased insulin sensitivity, as well as resistance to certain diseases and cancers. The mutant mice possess low blood glucose, low serum insulin, and lower body temperature. Their enhanced longevity (about 40-60% longer lifespan than normal mice) is associated with their GH deficiency and disruption in the somatotropic axis (GH/IGF-1 hormonal pathway) as …


Manipulating Aktivated Metabolism Via Mtorc1, Ivan Von Hack Prestinary May 2013

Manipulating Aktivated Metabolism Via Mtorc1, Ivan Von Hack Prestinary

HIM 1990-2015

Although poorly understood, normal cells and cancerous cells of the same type exhibit different patterns of nutrient consumption, processing and utility of metabolic substrates. Differences in substrate uptake, preference, and alternately emphasized metabolic pathways offer opportunities for selective targeting of cancer versus stroma. This may be accomplished by using a sequential approach of nutrient deprivation and pharmaceutical perturbation of metabolic pathways to inhibit cellular proliferation. The purpose of this study was to investigate the effects of restricting glucose and glutamine concentrations, in vitro, to levels that resemble a potential human fasting state. The mammalian target of rapamycin (mTOR), a mediator …


Identification Of Potential Lead Antimalarial Compounds From Marine Microbial Extracts, Abigail Carbonell Jan 2013

Identification Of Potential Lead Antimalarial Compounds From Marine Microbial Extracts, Abigail Carbonell

HIM 1990-2015

Malaria, caused by the parasite Plasmodium falciparum, has a long history as a global health threat. The vector-borne disease causes millions of deaths yearly, especially in developing countries with tropical climates that facilitate transmission. Compounding the problem is the emergence of drug-resistant strains due to overuse of outdated treatments. New compounds with antiplasmodial activity are needed to be developed as effective drugs against malaria. The hypothesis for this project is that marine microorganisms have a high likelihood of yielding novel antiplasmodial chemotypes because of their high diversity, which has not yet been explored for antimalarial development. In this project, microbes …


Development Of An Alkaline Phosphatase Reporter System For Use In The Lyme Disease Spirochete Borrelia Burgdorferi, Selina Sutchu Jan 2013

Development Of An Alkaline Phosphatase Reporter System For Use In The Lyme Disease Spirochete Borrelia Burgdorferi, Selina Sutchu

HIM 1990-2015

The use of the periplasmic alkaline phosphatase (PhoA) reporter protein from E. coli has been critical for definition of the topology of transmembrane proteins of multiple bacterial species. This report demonstrates development of a PhoA reporter system in B. burgdorferi. Codon usage of the E. coli phoA in B. burgdorferi was analyzed and an optimized version of the gene was obtained. In order to assess the differential activity of the reporter system, two optimized PhoA-fusion construct using B. burgdorferi proteins were engineered: one using the periplasmic protein OppAIV and one using the cytoplasmic protein PncA. The activity of PhoA requires …


Expression Of An Epitope Tagged Tarp Effector In Chlamydia Trachomatis, Brenda Nguyen Jan 2013

Expression Of An Epitope Tagged Tarp Effector In Chlamydia Trachomatis, Brenda Nguyen

HIM 1990-2015

Previous studies performed on Chlamydia trachomatis have demonstrated how these obligate intracellular microbes invade host cells through the utilization of secreted effector proteins. One secreted effector called Tarp (translocated actin recruiting protein) is implicated in cytoskeleton rearrangements that promote bacterial entry into the host cell. The focus of our study is to create a plasmid that carries the tarP gene that when transcribed and translated from within Chlamydia trachomatis will generate a c-Myc epitope tagged Tarp. The tag will be used in future studies to track the progression of the protein through the infectious process and will allow us to …


Understanding The Role Of Plasmodium Falciparum Vamp8 Snare Homologue, Katherine Ferreira Jan 2013

Understanding The Role Of Plasmodium Falciparum Vamp8 Snare Homologue, Katherine Ferreira

HIM 1990-2015

Malaria is one of the worlds most deadly infectious diseases and results in almost a million deaths each year, largely in children under the age of five in Sub-Saharan Africa. Outside Africa, malaria is responsible for a large number of cases in the Amazon rainforest of Brazil, Middle East, and in some areas of Asia [37]. According to the World Health Organization, there was an estimated 655, 000 deaths from malaria in 2012. Malaria is caused by a eukaryotic Apicomplexan parasite, Plasmodium, which has three distinct life cycles occurring in the midgut of the female Anopheles mosquito, the liver of …


The Role Of Hsc-70 In Very Low Density Lipoprotein Tranport Vesicle Golgi Fusion Complex Formation, Erika Nafi Valencia Dec 2012

The Role Of Hsc-70 In Very Low Density Lipoprotein Tranport Vesicle Golgi Fusion Complex Formation, Erika Nafi Valencia

HIM 1990-2015

Excess production and secretion of very low-density lipoprotein (VLDL) by the liver into the circulatory system is directly related to atherosclerosis, a chronic cardiovascular disease that threatens the lives of many worldwide and continues to be a leading cause of death in the United States. The rate-limiting step in VLDL secretion is its transport from the site of biogenesis, the hepatic endoplasmic reticulum to the cis-Golgi. This step is mediated by a specialized ER- derived vesicle, the VLDL transport vesicle (VTV). Upon exit of the ER the VTV targets, fuses and delivers VLDL into the lumen of the Golgi. The …


Amyloid-Beta42 Toxicity Reduction In Human Neuroblastoma Cells Using Cholera Toxin B Subunit-Myelin Basic Protein Expressed In Chloroplasts, Alexandra Ayache Aug 2012

Amyloid-Beta42 Toxicity Reduction In Human Neuroblastoma Cells Using Cholera Toxin B Subunit-Myelin Basic Protein Expressed In Chloroplasts, Alexandra Ayache

HIM 1990-2015

Alzheimer's disease (AD) is an age progressive neurodegenerative brain disorder, affecting 37 million people worldwide. Cleavage of amyloid precursor protein by ?- and ?-secretase produces the amyloid-beta (A?) protein, which significantly contributes to AD pathogenesis. The A? aggregates, formed at the surface of neurons and intracellularly, cause neurotoxicity and decrease synaptic function. Inhibiting or degrading A? accumulation is a key goal for development of new AD treatments. Evidence shows that human Myelin Basic Protein (MBP) binds to and degrades A? thereby, preventing cytotoxicity. A potential method for oral drug delivery that will allow plant-derived bioencapsulated MBP to pass through intestinal …


Multiple Aspects Of Natural Killer Cell Expansion In Relevance To Immunotherapy For Hematologic Malignancies, Dominic Colosimo Aug 2012

Multiple Aspects Of Natural Killer Cell Expansion In Relevance To Immunotherapy For Hematologic Malignancies, Dominic Colosimo

HIM 1990-2015

Natural Killer (NK) cells are a subset of lymphocytes that regulate adaptive immune responses and utilize "missing self" recognition to activate anti-tumor and anti-viral cytotoxicity. Clinical research, as well as murine and ex vivo models, have shown that a variety of NK cell applications have proven useful as immunotherapeutic treatments for patients with hematologic malignancies. However, the selective expansion of NK cells to yield relevant amounts of these lymphocytes has been a major hurdle in the development of methods for clinical therapeutic use. Here, we demonstrate a novel ex vivo expansion method utilizing k562 leukemic cell lines and soluble cytokines …


Determination Of Selectivity And Potential For Drug Resistance Of Novel Antimalarial Compounds From Nature-Inspired Synthetic Libraries, Eric Keasler May 2012

Determination Of Selectivity And Potential For Drug Resistance Of Novel Antimalarial Compounds From Nature-Inspired Synthetic Libraries, Eric Keasler

HIM 1990-2015

As malaria, caused by Plasmodium spp., continues to afflict millions of people worldwide, there is a dire need for the discovery of novel, inexpensive antimalarial drugs. Although there are effective drugs on the market, the consistent development of drug resistant species has decreased their efficacy, further emphasizing that novel therapeutic measures are urgently needed. Natural products provide the most diverse reservoir for the discovery of unique chemical scaffolds with the potential to effectively combat malarial infections, but, due to their complex structures, they often pose extreme challenges to medicinal chemists during pharmacokinetic optimization. In our laboratory we have performed unbiased, …


Identification Of Plasmodium Falciparum Protein Kinase Substrates And Interacting Proteins, Jessica Yap May 2012

Identification Of Plasmodium Falciparum Protein Kinase Substrates And Interacting Proteins, Jessica Yap

HIM 1990-2015

Characterization of PfPKA and PfPK5 substrates, as well as the proteins they interact with, will help us to develop innovative therapies targeting binding sites.; Malaria is a devastating disease that results in almost one million deaths annually. Most of the victims are children under the age of five in Sub-Saharan Africa. Malaria parasite strains throughout developing countries are continually building resistance to available drugs. Current therapies such as mefloquine, chloroquine, as well as artemisinin are becoming less effective, and this underscores the urgency for therapeutics directed against novel drug targets. In order to identify new drug targets, the molecular biology …


Gold (Iii) Macrocycles Are Dna Intercalators That Inhibit Topoisomerase I And Ii, Alexander Fagenson May 2012

Gold (Iii) Macrocycles Are Dna Intercalators That Inhibit Topoisomerase I And Ii, Alexander Fagenson

HIM 1990-2015

Human Topoisomerase IB (TOP1) and Topoisomerase II? (TOP2?) are essential nuclear enzymes that control DNA topology during DNA replication, gene transcription and cell division. These enzymes carry out their catalytic function by making transient single-strand (type I) or double-strand (type II) breaks in the DNA. In vivo, these complexes are short-lived but can be exploited by anti-cancer drugs to mechanistically kill cancer cells. Two general classes of compounds can kill cancer cells through a topo-targeted mechanism. Interfacial Poisons (IFPs) act at the enzyme-DNA interface to inhibit the religation reaction, resulting in the accumulation of DNA double-stand breaks (DSBs) in the …


Design, Construction, And Characterization Of The Ysgr Minimal Codon Fab Library For Chaperone-Assisted Rna Crystallography, Sean Holmes May 2012

Design, Construction, And Characterization Of The Ysgr Minimal Codon Fab Library For Chaperone-Assisted Rna Crystallography, Sean Holmes

HIM 1990-2015

Of the entire human genome, 90% of all genetic information is transcribed but only a fraction of that subsequent RNA is translated into proteins. RNAs which are not translated into proteins are deemed non-coding RNAs. Little is known about this large category of noncoding RNAs, although they perform a variety of functions within the cell. RNA crystallography is used to study RNA tertiary structure, which gives insight to the function of these non-coding RNAs. However, complications associated with RNA crystallography arise due to RNA's lack of surface functional group diversity, flexible tertiary structure, and conformational heterogeneity. A novel technique, Chaperone-assisted …


Determination Of The Hydrogen Peroxide Concentration In Rotenone Induced Dopaminergic Cells Using Cyclic Voltammetry And Amplex Red, Kishan Patel May 2012

Determination Of The Hydrogen Peroxide Concentration In Rotenone Induced Dopaminergic Cells Using Cyclic Voltammetry And Amplex Red, Kishan Patel

HIM 1990-2015

Parkinson's disease (PD) is a neurodegenerative condition that affects millions of people worldwide. The exact etiology of PD is unknown. However, it is well established that environmental factors contribute to the onset of PD. In particular, chemicals such as the insecticide Rotenone have been shown to increase the death of dopaminergic (DA) neurons by increasing levels of reactive oxygen species (ROS). ROS such as hydrogen peroxide (H2O2) have been shown to be elevated above basal levels in PD patients. Currently, to measure H2O2 concentrations, a commercially available (Amplex® Red) fluorescent assay is used. However, the assay has limitations: it is …


Protection Of The Female Reproductive Tract In The Prevention Of Hiv, Camila Diaz Jan 2012

Protection Of The Female Reproductive Tract In The Prevention Of Hiv, Camila Diaz

HIM 1990-2015

Worldwide, more than half of all HIV-infected individuals are women. Since mucosal surfaces are the primary gateway for HIV entry, maintaining the integrity of the female reproductive tract (FRT) is essential for preventing infection. The FRT employs many immune mechanisms that serve as the first line of defense against HIV transmission. Among these are vaginal fluid secretions rich in antimicrobial peptides, and commensal bacteria that colonize the vagina and prevent infections. We sought to study vaginal fluid as an innate immune component of the FRT in the prevention of HIV infection. Additionally, we investigated the anti-HIV microbicide candidate RC-101 as …


Physiological Relevance Of A Trna-Dependent Mechanism For Membrane Modification In Enterococcus Faecium, Jesse Harrison Jan 2012

Physiological Relevance Of A Trna-Dependent Mechanism For Membrane Modification In Enterococcus Faecium, Jesse Harrison

HIM 1990-2015

Enterococci were once thought to be harmless, commensal organisms that colonize the gastrointestinal tract of humans and other mammals. In the last 30 years, however, concern has grown in the clinical setting over two particular species, Enterococcus faecalis and Enterococcus faecium, which are frequently found to be the etiologic agents of nosocomial infections. Aminoacyl-phosphatidylglycerol synthases (aaPGSs) are integral membrane proteins that add amino acids to phosphatidylglycerol (PG) in the cellular envelope of bacteria. Addition of amino acids to PG confers resistance to various therapeutic antimicrobial agents, and contributes to evasion of the host immune response in a number of clinically …