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2010

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Articles 271 - 300 of 351

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Amino Acid Transport In Thermophiles: Characterization Of An Arginine-Binding Protein In Thermotoga Maritima, Matthew S. Luchansky, Bryan S. Der, Sabato D'Auria, Gabriella Pocsfalvi, Luisa Iozzion, Daniela Marasco, Jonathan D. Dattelbaum Jan 2010

Amino Acid Transport In Thermophiles: Characterization Of An Arginine-Binding Protein In Thermotoga Maritima, Matthew S. Luchansky, Bryan S. Der, Sabato D'Auria, Gabriella Pocsfalvi, Luisa Iozzion, Daniela Marasco, Jonathan D. Dattelbaum

Chemistry Faculty Publications

Members of the periplasmic binding protein superfamily are involved in the selective passage of ligands through bacterial cell membranes. The hyperthermophilic eubacterium Thermotoga maritima was found to encode a highly stable and specific periplasmic arginine-binding protein (TM0593). Following signal sequence removal and overexpression in Escherichia coli, TM0593 was purified by thermoprecipitation and affinity chromatography. The ultra-stable protein with a monomeric molecular weight of 27.7 kDa was found to exist as both a homodimer and homotrimer at appreciable concentrations even under strongly denaturing conditions, with an estimated transition temperature of 116 °C. Its multimeric structure may provide further evidence of …

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Amino Acid Transport In Thermophiles: Characterization Of An Arginine-Binding Protein In Thermotoga Maritima. 2. Molecular Organization And Structural Stability, Andrea Scirè, Anna Marabotti, Maria Staiano, Luisa Iozzion, Matthew S. Luchansky, Bryan S. Der, Jonathan D. Dattelbaum, Fabio Tanfani, Sabato D'Auria Jan 2010

Amino Acid Transport In Thermophiles: Characterization Of An Arginine-Binding Protein In Thermotoga Maritima. 2. Molecular Organization And Structural Stability, Andrea Scirè, Anna Marabotti, Maria Staiano, Luisa Iozzion, Matthew S. Luchansky, Bryan S. Der, Jonathan D. Dattelbaum, Fabio Tanfani, Sabato D'Auria

Chemistry Faculty Publications

ABC transport systems provide selective passage of metabolites across cell membranes and typically require the presence of a soluble binding protein with high specificity to a specific ligand. In addition to their primary role in nutrient gathering, the binding proteins associated with bacterial transport systems have been studied for their potential to serve as design scaffolds for the development of fluorescent protein biosensors. In this work, we used Fourier transform infrared spectroscopy and molecular dynamics simulations to investigate the physicochemical properties of a hyperthermophilic binding protein from Thermotoga maritima. We demonstrated preferential binding for the polar amino acid arginine …

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Ligand-Protein Interactions Of Inhibitors With Dengue Virus Type 2 Serine Protease : A Structural Study., Rozana Othman Jan 2010

Ligand-Protein Interactions Of Inhibitors With Dengue Virus Type 2 Serine Protease : A Structural Study., Rozana Othman

Student Works (2010-2019)

Dengue is a serious infectious disease that is endemic in over 100 countries. There has been an estimate of 50 million infection per year globally, with more than 2.5 billion people are at risk for epidemic transmission. Two principal illnesses associated with dengue are Dengue Fever (DF) and Dengue Haemorrhagic Fever (DHF). To date, there is no licensed vaccine or therapeutic drug available for these illnesses, although there have been reports of some vaccine candidates in clinical trials. Treatments have only been supportive thus far. This thesis describes part of our ongoing effort to search for a lead therapeutic agent …

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The Effect Of Heating On The Antioxidants Content In Edible Oil., Premanand Krishnan Jan 2010

The Effect Of Heating On The Antioxidants Content In Edible Oil., Premanand Krishnan

Student Works (2010-2019)

There are many types edible oils with various brand found in the market. The types of oils involved in the analysis for the antioxidants content were palm oil, olive oil, canola oil, sunflower oil, soy bean oil, corn oil, gingerly oil, rice bran oil, mixed oil and ayurvedic oil. The method used to evaluate the amount antioxidants in this study was 2, 2-diphenyl-1-picrylhydrazyl (DPPH). In this test, the scavenging of the DPPH radicals was followed by monitoring the decrease in absorbance at 515 nm. Heating the oil samples to various temperatures shows negative effect on the antioxidants content. The antioxidants …

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The Thermal Characteristic Of Imipenem Encapsulated In Low And High Molecular Weight Of Polyethylene Glycol., Abdul Aziz Ismail Jan 2010

The Thermal Characteristic Of Imipenem Encapsulated In Low And High Molecular Weight Of Polyethylene Glycol., Abdul Aziz Ismail

Student Works (2010-2019)

Microencapsulation technique is widely used in pharmaceutical industries to control the release of a drug. Biodegradable polymer such as Polyethylene glycol (PEG) is frequently used as encapsulation material. This study has tried to produce microencapsulation product of Imipenem antibiotics in Polyethylene Glycol.Commercially available product called Tienam® was used as a major source of Imipenem. We used freeze-drying method to produce the microencapsulation products. The successful of producing of this product is confirmed by the yellowish appearance of the product whereby it shows the colour properties of Tienam® Thermal analysis using Differential Scanning Calorimeter (DSC) was used to characterize pure materials …

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Characterization Of Microrna172 And Its Potential Target In Oil Palm (Elaeis Guineensis Jaq.), Fatemeh Mehrpooyan Jan 2010

Characterization Of Microrna172 And Its Potential Target In Oil Palm (Elaeis Guineensis Jaq.), Fatemeh Mehrpooyan

Student Works (2010-2019)

Oil palm (Elaeis guineensis) is the world’s major perennial monocot crop and contributes highly to the economies of South East Asia. As the oil palm fruit is the source of the main economic output for this crop, floral development is a critical process related to oil palm productivity. miR172 has been shown to be an important regulator of the AP2 family transcription factors involved in floral timing in a number of plants and belongs to a group of highly conserved miRNA that can be identified based on sequence homology. Six oil palm miR172 paralogs, representing two distinct mature miR172 sequences, …

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Studies Of Antioxidant Activity Of Bioactive Compounds Derived From Ardisia Crispa., Hassan Mahmood Kzar Jindal Jan 2010

Studies Of Antioxidant Activity Of Bioactive Compounds Derived From Ardisia Crispa., Hassan Mahmood Kzar Jindal

Student Works (2010-2019)

In recent times, researches have focused on medicinal plants in order to extract natural and low cost antioxidants that can help protect the human body against oxidative stress, and replace the synthetic additives that might be carcinogenic. In present study, the crude extracts of leaves and fruits from Ardisia crispa were investigated for their chemical constituents and antioxidant activity. Preliminary phytochemical screening of the crude extracts via TLC analysis revealed the presence of several secondary compounds mainly, terpenoids and phenolic compounds in addition to alkaloids and saponins. HPLC analysis showed the possibility of presence of gallic acid in the fruits …

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Diversity And Antioxidant Activity Of Trametes Fr. In Malaysia., Noraswati Mohd Nor Rashid Jan 2010

Diversity And Antioxidant Activity Of Trametes Fr. In Malaysia., Noraswati Mohd Nor Rashid

Student Works (2010-2019)

Research on antioxidant properties as a natural antioxidant, particularly in polypores, have been widely done since the past decade. It is known that antioxidant capacity is essential in protecting organisms and cells from damage brought on by oxidative which is believed to be the cause for ageing and degenerative diseases. In this study, biodiversity and antioxidant activity of Malaysian Trametes spp. which is from the group of polypores were investigated. Polypores were collected in Peninsular Malaysia forests from the year 2006 until 2007. The species were identified by taxonomic keys based on macromorphology and micromorphology analysis. Trametes hirsuta, T. pocas, …

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In Vitro Cultures For Production Of Zerumbone And Mass Propagation In Zingiber Zerumbet Smith., Farah Diana Idris Jan 2010

In Vitro Cultures For Production Of Zerumbone And Mass Propagation In Zingiber Zerumbet Smith., Farah Diana Idris

Student Works (2010-2019)

Lempoyang (Zingiber zerumbet Smith.) is an important plant which has been propagated because of its medicinal values. Lempoyang is widely used as a folk medicine in Asian countries such as Malaysia, Indonesia, India and Taiwan. Zerumbone, a cyclic sesqueterpene found to be the major and main bioactive compound that gives great potential in medicinal purposes especially in the treatment of chronic diseases based on recent reports. Recently, it was found that zerumbone inhibited the growth of human leukemia cell line, HL-60 cell. Even though there are so many great values contain in the lempoyang but it is hard to obtain …

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Identification And Characterization Of Oxalate Oxidoreductase, A Novel Thiamine Pyrophosphate-Dependent 2-Oxoacid Oxidoreductase That Enables Anaerobic Growth On Oxalate, Elizabeth Pierce, Donald F. Becker, Stephen W. Ragsdale Jan 2010

Identification And Characterization Of Oxalate Oxidoreductase, A Novel Thiamine Pyrophosphate-Dependent 2-Oxoacid Oxidoreductase That Enables Anaerobic Growth On Oxalate, Elizabeth Pierce, Donald F. Becker, Stephen W. Ragsdale

Department of Biochemistry: Faculty Publications

Moorella thermoacetica is an anaerobic acetogen, a class of bacteria that is found in the soil, the animal gastrointestinal tract, and the rumen. This organism engages the Wood-Ljungdahl pathway of anaerobic CO2 fixation for heterotrophic or autotrophic growth. This paper describes a novel enzyme, oxalate oxidoreductase (OOR), that enables M. thermoacetica to grow on oxalate, which is produced in soil and is a common component of kidney stones. Exposure to oxalate leads to the induction of three proteins that are subunits of OOR, which oxidizes oxalate coupled to the production of two electrons and CO2 or bicarbonate. Like …

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Functional Hybrid Rubisco Enzymes With Plant Small Subunits And Algal Large Subunits Engineered Rbcs Cdna For Expression In Chlamydomonas, Todor Genkov, Moritz Meyer, Howard Griffiths, Robert J. Spreitzer Jan 2010

Functional Hybrid Rubisco Enzymes With Plant Small Subunits And Algal Large Subunits Engineered Rbcs Cdna For Expression In Chlamydomonas, Todor Genkov, Moritz Meyer, Howard Griffiths, Robert J. Spreitzer

Department of Biochemistry: Faculty Publications

There has been much interest in the chloroplast-encoded large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) as a target for engineering an increase in net CO2 fixation in photosynthesis. Improvements in the enzyme would lead to an increase in the production of food, fiber, and renewable energy. Although the large subunit contains the active site, a family of rbcS nuclear genes encodes the Rubisco small subunits, which can also influence the carboxylation catalytic efficiency and CO2/O2 specificity of the enzyme. To further define the role of the small subunit in Rubisco function, small subunits from spinach, Arabidopsis, …

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Increased Perfusion And Angiogenesis In A Hindlimb Ischemia Model With Plasmid Fgf-2 Delivered By Noninvasive Electroporation, B. Ferraro, Y. L. Cruz, M. Baldwin, D. Coppola, R. Heller Jan 2010

Increased Perfusion And Angiogenesis In A Hindlimb Ischemia Model With Plasmid Fgf-2 Delivered By Noninvasive Electroporation, B. Ferraro, Y. L. Cruz, M. Baldwin, D. Coppola, R. Heller

Bioelectrics Publications

Gene therapy approaches delivering fibroblast growth factor-2 (FGF-2) have shown promise as a potential treatment for increasing blood flow to ischemic limbs. Currently, effective noninvasive techniques to deliver plasmids encoding genes of therapeutic interest, such as FGF-2, are limited. We sought to determine if intradermal injection of plasmid DNA encoding FGF-2 (pFGF) followed by noninvasive cutaneous electroporation (pFGFE+) could increase blood flow and angiogenesis in a rat model of hindlimb ischemia. pFGFE+ or control treatments were administered on postoperative day 0. Compared to injection of pFGF alone (pFGFE-), delivery of pFGFE+ significantly increased FGF-2 expression for 10 days. Further, the …

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Dielectrophoretic Choking Phenomenon In A Converging-Diverging Microchannel, Ye Ai, Shizhi Qian, Sheng Liu, Sang W. Joo Jan 2010

Dielectrophoretic Choking Phenomenon In A Converging-Diverging Microchannel, Ye Ai, Shizhi Qian, Sheng Liu, Sang W. Joo

Mechanical & Aerospace Engineering Faculty Publications

Experiments show that particles smaller than the throat size of converging-diverging microchannels can sometimes be trapped near the throat. This critical phenomenon is associated with the negative dc dielectrophoresis arising from nonuniform electric fields in the microchannels. A finite-element model, accounting for the particle-fluid-electric field interactions, is employed to investigate the conditions for this dielectrophoretic (DEP) choking in a converging-diverging microchannel for the first time. It is shown quantitatively that the DEP choking occurs for high nonuniformity of electric fields, high ratio of particle size to throat size, and high ratio of particle's zeta potential to that of microchannel. © …

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Synthesis And Evaluation Of Azetidinone Analogues Of Combretastatin A-4 As Tubulin Targeting Agents, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Orla Bergin, Seema M. Nathwani, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan Jan 2010

Synthesis And Evaluation Of Azetidinone Analogues Of Combretastatin A-4 As Tubulin Targeting Agents, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Orla Bergin, Seema M. Nathwani, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

Articles

The synthesis and antiproliferative activity of a new series of rigid analogues of combretastatin A-4 are described which contain the 1,4-diaryl-2-azetidinone (β-lactam) ring system in place of the usual ethylene bridge present in the natural combretastatin stilbene products. These novel compounds are also substituted at position 3 of the β-lactam ring with an aryl ring. A number of analogues showed potent nanomolar activity in human MCF-7 and MDA-MB-231 breast cancer cell lines, displayed in vitro inhibition of tubulin polymerization and did not cause significant cytotoxicity in normal murine breast epithelial cells. 4-(4-Methoxyaryl)-substituted compound 32, 4-(3-hydroxy-4-methoxyaryl)-substituted compounds 35 and 41 and …

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Electric Pulses To Prepare Feeder Cells For Sustaining And Culturing Of Undifferentiated Embryonic Stem Cells, Lauren M. Browning, Tao Huang, Xiao-Hong Nancy Xu Jan 2010

Electric Pulses To Prepare Feeder Cells For Sustaining And Culturing Of Undifferentiated Embryonic Stem Cells, Lauren M. Browning, Tao Huang, Xiao-Hong Nancy Xu

Chemistry & Biochemistry Faculty Publications

Current challenges in embryonic-stem-cell (ESC) research include inability of sustaining and culturing of undifferentiated ESCs over time. Growth-arrested feeder cells are essential to the culture and sustaining of undifferentiated ESCs, and they are currently prepared using gammaradiation and chemical inactivation. Both techniques have severe limitations. In this study, we developed a new, simple and effective technique (pulsed-electric-fields, PEFs) to produce viable growth-arrested cells (RTS34st) and used them as high-quality feeder cells to culture and sustain undifferentiated zebrafish ESCs over time. The cells were exposed to 25 sequential 10- nanosecond-electric-pulses (10nsEPs) of 25, 40 and 150 kV/cm with 1s pulse interval, …

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Chloroquine Susceptibility And Reversibility In A Plasmodium Falciparum Genetic Cross, Jigar J. Patel, Drew Thacker, John C. Tan, Perri Pleeter, Lisa Checkley, Joseph M. Gonzales, Bingbing Deng, Paul D. Roepe, Roland A. Cooper, Michael T. Ferdig Jan 2010

Chloroquine Susceptibility And Reversibility In A Plasmodium Falciparum Genetic Cross, Jigar J. Patel, Drew Thacker, John C. Tan, Perri Pleeter, Lisa Checkley, Joseph M. Gonzales, Bingbing Deng, Paul D. Roepe, Roland A. Cooper, Michael T. Ferdig

Biological Sciences Faculty Publications

Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT) are major determinants of verapamil (VP)-reversible CQ resistance (CQR). In the presence of mutant PfCRT, additional genes contribute to the wide range of CQ susceptibilities observed. It is not known if these genes influence mechanisms of chemosensitization by CQR reversal agents. Using quantitative trait locus (QTL) mapping of progeny clones from the HB3 x Dd2 cross, we show that the P. falciparum multidrug resistance gene 1 (pfmdr1) interacts with the South-East Asia-derived mutant pfcrt haplotype to modulate CQR levels. A novel chromosome 7 locus is predicted to contribute …

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Methionine-R-Sulfoxide Reductases And Biological Importance Of Free Methionine Sulfoxide Reduction, Byung Cheon Lee Jan 2010

Methionine-R-Sulfoxide Reductases And Biological Importance Of Free Methionine Sulfoxide Reduction, Byung Cheon Lee

Department of Biochemistry: Dissertations, Theses, and Student Research

We identified and functionally characterized yeast fRMsr homolog which showed specificity for reduction of free Met-R-SO and contributed to oxidative stress resistance of yeast cells. We further identified three conserved Cys which participate in catalysis through disulfide exchange. Evolutionary analyses revealed that the occurrence of fRMSr is restricted to unicellular organisms. We further found that mammalian MsrA can reduce free Met-S-SO, whereas MsrBs do not reduce free Met-R-SO. Consistent with these findings and the lack of fRMsr, mammalian cells could not grow in media that replaced Met with Met-R-SO. However, they grew in the presence of free Met-S-SO, which was …

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Evaluating The Role Of Evolutionarily Conserved Regions Of Ledgf/P75 In Hiv-1 Infection, Jose Adrian Garcia Jan 2010

Evaluating The Role Of Evolutionarily Conserved Regions Of Ledgf/P75 In Hiv-1 Infection, Jose Adrian Garcia

Open Access Theses & Dissertations

LEDGF/p75 is an important cellular co-factor for lentiviral integration. LEDGF/p75-deficient cells are markedly resistant to HIV-1 infection and re-expression of the wild type protein rescues infectivity. Although the molecular mechanism of LEDGF/p75 in HIV-1 integration is not yet known, this co-factor activity requires the interaction of LEDGF/p75 with both the host chromatin and viral integrase. In order to evaluate the involvement of other LEDGF/p75 regions in HIV-1 infection we constructed a panel of deletion mutants targeting clusters of charged residues that are evolutionarily conserved and predicted to be post-translationally modified. These mutants were evaluated for their ability to rescue HIV-1 …

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Ganglioside-Cytokine Interaction In The Induction Of Primary Brain Cell Death, John Charles Gorbet Jan 2010

Ganglioside-Cytokine Interaction In The Induction Of Primary Brain Cell Death, John Charles Gorbet

Open Access Theses & Dissertations

Gangliosides have been implicated in multiple pathologies affecting the central nervous system (CNS) and recent research has implicated them in playing an active role in the pathogenesis of multiple sclerosis. Empirical studies and theoretical considerations have suggested the possibility of interactions between gangliosides, like GD3, and pro-inflammatory cytokines present in the nervous system. This study sought to investigate the possibility that either individual gangliosides acting alone or complexed with other species interact with the known immune response factor TNF&alpha to initiate or facilitate cell death in the CNS. I examined the cellular viability and gene expression in primary brain cell …

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Computer Aided Drug Design Methods & Quantitative Structure-Activity/Property Relationships, Suman Sirimulla Jan 2010

Computer Aided Drug Design Methods & Quantitative Structure-Activity/Property Relationships, Suman Sirimulla

Open Access Theses & Dissertations

The first part of dissertation consists of development of a QSAR model for 229 mutagenic aromatic amines and a QSPR model of partial molar volumes of amino acids. A common procedure for QSAR analysis consist of data selection (generally sets of homologous series of compounds and their corresponding biological activities), tabulation of trial physicochemical or molecular structural descriptors, followed by a multilinear statistical analysis to derive a statistically valid QSAR correlation of the activity data making use of a subset of the trial descriptors. A final important step is cross-validation to assess the putative predictive (rather than just correlative) capabilities …

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Effects Of The Loss Of Multidrug Resistance Associated Protein 1 On Steroid Homeostasis, Dendritic Cell Function And Compensatory Mechanisms, Jeffrey Charles Sivils Jan 2010

Effects Of The Loss Of Multidrug Resistance Associated Protein 1 On Steroid Homeostasis, Dendritic Cell Function And Compensatory Mechanisms, Jeffrey Charles Sivils

Open Access Theses & Dissertations

The ATP-binding cassette (ABC) superfamily of membrane transporters use energy derived from ATP to eliminate a variety of exogenous and endogenous compounds from cells including anti cancer and anti viral drugs, metals steroids, bilirubin, cAMP, cGMP, leukotrienes , prostaglandins. The multi drug resistance associated protein family (MRP/ABBC) has been acknowledged as a major player involved in multi drug resistance (MDR), in which cancers stop responding a wide array of structurally and functionally unrelated chemotherapy drugs. Cancer is the second leading cause of death in adults in the United States. Although there have been great strides made the treatment of cancers …

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Phosphorylation Of The Glycine Transporter 1, Javier Vargas Medrano Jan 2010

Phosphorylation Of The Glycine Transporter 1, Javier Vargas Medrano

Open Access Theses & Dissertations

The extracellular levels of the neurotransmitter glycine in the brain are tightly regulated by the high-affinity glycine transporter 1 (GlyT1) and the clearance of glycine depends on its rate of transport and the levels of cell surface GlyT1. Over the past years, it has been shown that PKC activation diminishes the activity and promoted phosphorylation of several neurotransmitter transporters including the dopamine, serotonin and norepinephrine transporters however, its role is unknown for the glycine transporter. To get insights into the role of PKC activation on GlyT1 regulation, we used three N-terminus GlyT1 isoforms stably expressed in porcine aortic endothelial (PAE) …

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Isolation, Characterization And Molecular Cloning Of Dnase Iiib From Drosophila Melanogaster, Brenda Cristina Anchondo Jan 2010

Isolation, Characterization And Molecular Cloning Of Dnase Iiib From Drosophila Melanogaster, Brenda Cristina Anchondo

Open Access Theses & Dissertations

Nucleases are enzymes that breakdown nucleic acids; they are classified by their biochemical properties into different groups (Evans et al., 2003). The ββα-Me finger family of nucleases are enzymes that combine structurally different groups but they are defined by a highly evolutionary conserved active site, a stretch of 22 amino acids composed by a β-hairpin (ββ) and α-helix (α) that anchor a catalytic metal ion (Sokolowska et al, 2009). Within this family is found the DNA/RNA non-specific nucleases. Nucleases that belong to the DNA/RNA non-specific group hydrolyze both ds and ss DNA, as well as RNA at equal or similar …

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The Role Of Sumoylation Of Ledgf/P75 In Hiv-1 Infection, Murilo Tadeu Domingues Bueno Jan 2010

The Role Of Sumoylation Of Ledgf/P75 In Hiv-1 Infection, Murilo Tadeu Domingues Bueno

Open Access Theses & Dissertations

The lens epithelium-derived growth factor (LEDGF) proteins p75 and p52 are transcriptional co-activators that protect cells from stresses through modulation of stress and heat shock-related genes. Besides regulating such genes, LEDGF/p75 is also important in the process of HOX gene expression and leukemia transformation driven by the MLL histone methyl transferase complex. By exploiting a similar mechanism of interaction between LEDGF/p75 and MLL, the HIV-1 viral protein Integrase (IN) associates with LEDGF/p75 in order to execute efficient viral DNA integration. This present work has identified that LEDGF proteins are posttranslationally modified by SUMO-1 and -3. SUMOylation was found to target …

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Antibactertial Property And Toxcity Study Of Medicinal Plant Tinospora Crispa L., Altammar Khadijah Ahmed Y. Jan 2010

Antibactertial Property And Toxcity Study Of Medicinal Plant Tinospora Crispa L., Altammar Khadijah Ahmed Y.

Student Works (2010-2019)

Tinospora crispa is a medically important herb used for centuries in traditional medicine for the treatment of various ailments. The aim of this study was to investigate the safety of the aqueous and alcoholic extract of Tinospora crispa by determining its toxicological effects after acute administration in rats, and to investigate the antibacterial activity of both extracts. Disc diffusion and broth dilution methods were carried out in determining the antibacterial effects of the plant extract on the pure cultures of clinical isolates of 8 MRSA and S. aureus ATCC strain. The disc-diffusion method of the ethanolic extracts showed inhibition zone …

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Post-Transcriptional Regulation Of Vibrio Cholerae Virulence Activator Toxt, Basel Hanna Abuaita Jan 2010

Post-Transcriptional Regulation Of Vibrio Cholerae Virulence Activator Toxt, Basel Hanna Abuaita

Wayne State University Dissertations

Vibrio cholera, the causative agent of the severe diarreal illness cholera, uses a complex array of gene regulation to induce its virulence determinants. During the early stage of infection, and upon response to unknown signals, virulence genes are turned on. ToxT protein is the primary virulence gene transcription activator. Once ToxT is produced, it amplifies its own expression through an auto-regulatory loop and directly binds and activates expression of various virulence factors including the toxin-coregulated pilus (TCP) and cholera toxin (CT). During the late stage of infection, virulence genes are turned off and the bacteria escape the host to resume …

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Tracking Profiles Of Genomic Instability In Spontaneous Transformation And Tumorigenesis, Lesley Lawrenson Jan 2010

Tracking Profiles Of Genomic Instability In Spontaneous Transformation And Tumorigenesis, Lesley Lawrenson

Wayne State University Dissertations

The dominant paradigm for cancer research focuses on the identification of specific genes for cancer causation and for the discovery of therapeutic targets. Alternatively, the current data emphasize the significance of karyotype heterogeneity in cancer progression over specific gene-based causes of cancer. Variability of a magnitude significant to shift cell populations from homogeneous diploid cells to a mosaic of structural and numerical chromosome alterations reflects the characteristic low-fidelity genome transfer of cancer cell populations. This transition marks the departure from micro-evolutionary gene-level change to macro-evolutionary change that facilitates the generation of many unique karyotypes within a cell population. Considering cancer …

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The Interictal State In Epilepsy And Behavior, Daniel Tice Barkmeier Jan 2010

The Interictal State In Epilepsy And Behavior, Daniel Tice Barkmeier

Wayne State University Dissertations

Epilepsy is one of the most common neurological diseases, affecting up to 1% of the world population. Epilepsy remains poorly understood and there are currently no medications to cure it. Patients with epilepsy have both seizures as well as another type of abnormal activity between seizures, known as interictal spikes. Interictal spikes have thus far been poorly researched, yet growing evidence supports an important role for them in epilepsy. In this project, we first show the high variability between reviewers in marking interictal spikes on intracranial EEG, and then develop and test an automated detection method to solve this problem. …

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Evolution Of Lactate Dehydrogenase Genes In Primates, With Special Consideration Of Nucleotide Organization In Mammalian Promoters, Zack Papper Jan 2010

Evolution Of Lactate Dehydrogenase Genes In Primates, With Special Consideration Of Nucleotide Organization In Mammalian Promoters, Zack Papper

Wayne State University Dissertations

Concomitant with an increase in brain volume and mass, the allocation of energetic resources to the brain increased during stem anthropoid evolution, leading to humans. One mechanism by which this allocation may have occurred is through greater use of lactate as a neuronal fuel. Both the production of lactate, and conversion to pyruvate for use in aerobic metabolism, are catalyzed, in part, by the tetrameric enzyme lactate dehydrogenase (LDH). The two primary LDH genes, LDHA and LDHB, confer different rates of substrate turnover to the LDH enzyme, and these rates lend to the argument that LDHA supports anaerobic while LDHB …

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Enzymology And Medicinal Chemistry Of N5-Carboxyaminoimidazole Ribonucleotide Synthetase : A Novel Antibacterial Target, Hanumantharao Paritala Jan 2010

Enzymology And Medicinal Chemistry Of N5-Carboxyaminoimidazole Ribonucleotide Synthetase : A Novel Antibacterial Target, Hanumantharao Paritala

Wayne State University Dissertations

N5-Carboxyaminoimidazole ribonucleotide synthetase (N5-CAIR synthetase), a key enzyme in microbial de novo purine biosynthesis, catalyzes the conversion of aminoimidazole ribonucleotide (AIR) to N5-CAIR. To date, this enzyme has been observed only in microorganisms, and thus, it represents an ideal target for antimicrobial drug development. Here we report structural and functional studies on the Aspergillus clavatus N5-CAIR synthetase and identification of inhibitors for the enzyme. In collaboration with Dr. Hazel Holden of the University of Wisconsin, the three-dimensional structure of Aspergillus clavatus N5-CAIR synthetase was solved in the presence of either Mg2ATP or MgADP and AIR. These structures, determined to 2.1 …

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