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Biochemistry, Biophysics, and Structural Biology Commons

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2015

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Articles 601 - 630 of 645

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

The Relative Importance Of Methanogenesis In The Decomposition Of Organic Matter In Northern Peatlands, J. Elizabeth Corbett, Malak M. Tfaily, David J. Burdige, Paul H. Glaser, Jeffrey P. Chanton Jan 2015

The Relative Importance Of Methanogenesis In The Decomposition Of Organic Matter In Northern Peatlands, J. Elizabeth Corbett, Malak M. Tfaily, David J. Burdige, Paul H. Glaser, Jeffrey P. Chanton

OES Faculty Publications

Using an isotope-mass balance approach and assuming the equimolar production of CO2 and CH4 from methanogenesis (e.g., anaerobic decomposition of cellulose), we calculate that the proportion of total CO2 production from methanogenesis varies from 37 to 83% across a variety of northern peatlands. In a relative sense, methanogenesis was a more important pathway for decomposition in bogs (80 ± 13% of CO2 production) than in fens (64 ± 5.7% of CO2 production), but because fens contain more labile substrates they may support higher CH4 production overall. The concentration of CO2 produced from methanogenesis (CO …


Alternate Germinants Of C. Difficile, A Leading Hospital Pathogen, Sean Tanzey, Ernesto Abel-Santos Jan 2015

Alternate Germinants Of C. Difficile, A Leading Hospital Pathogen, Sean Tanzey, Ernesto Abel-Santos

McNair Poster Presentations

Clostridium difficile infections (CDI) are the leading nosocomial infections worldwide. Humans are asymptomatic carriers of C. difficile spores in the intestinal tract. The process known as germination occurs when otherwise harmless C. difficile spores are converted to toxin-producing cells upon recognition of bile salts in humans. This distinctive transition ultimately leads to the onset of disease and recurrent CDI. Germination profiles will be characterized in response to peptidoglycan (PG) fragments isolated from various bacterial species. These specific peptidoglycan fragments contain different amino acid residues that may induce different germination responses. Purification and structural determination of the peptidoglycan fragments will be …


Regional-Scale Simulations Of Fungal Spore Aerosols Using An Emission Parameterization Adapted To Local Measurements Of Fluorescent Biological Aerosol Particles, M. Hummell, C. Hoose, M. Gallagher, D. A. Healy, J. A. Huffmann, David O'Connor, U. Poschl, C. Pohlker, N. H. Robinson, M. Schnaiter, J. R. Sodeau, M. Stengel, E. Toprak, H. Vogel Jan 2015

Regional-Scale Simulations Of Fungal Spore Aerosols Using An Emission Parameterization Adapted To Local Measurements Of Fluorescent Biological Aerosol Particles, M. Hummell, C. Hoose, M. Gallagher, D. A. Healy, J. A. Huffmann, David O'Connor, U. Poschl, C. Pohlker, N. H. Robinson, M. Schnaiter, J. R. Sodeau, M. Stengel, E. Toprak, H. Vogel

Articles

Fungal spores as a prominent type of primary biological aerosol particles (PBAP) have been incorporated into the COSMO-ART (Consortium for Small-scale Modelling- Aerosols and Reactive Trace gases) regional atmospheric model. Two literature-based emission rates for fungal spores derived from fungal spore colony counts and chemical tracer measurements were used as a parameterization baseline for this study. A third, new emission parameterization for fluorescent biological aerosol particles (FBAP) was adapted to field measurements from four locations across Europe. FBAP concentrations can be regarded as a lower estimate of total PBAP concentrations. Size distributions of FBAP often show a distinct mode at …


Dysregulation Of Micrornas In Blood As Biomarkers For Diagnosing Prostate Cancer, Rhonda W. Daniel Jan 2015

Dysregulation Of Micrornas In Blood As Biomarkers For Diagnosing Prostate Cancer, Rhonda W. Daniel

Theses and Dissertations

Prostate cancer is the most common noncutaneous cancer among men, yet current diagnostic methods are insufficient and more reliable diagnostic markers need to be developed. The answer that can bridge this gap and enable more efficient diagnoses may lie in microRNAs. These small, single stranded RNA molecules impact protein expression at the translational level and regulate important cellular pathways. Dysregulation of these small RNA molecules can have tumorigenic effects on cells and lead to many types of cancers.

Currently the Prostate-Stimulating Antigen (PSA) is used as a diagnostic marker for prostate cancer. However, many factors can elevate PSA levels such …


Hif-Independent Responses In Hypoxia, Divya Padmanabha Jan 2015

Hif-Independent Responses In Hypoxia, Divya Padmanabha

Theses and Dissertations

The adaptive response to hypoxia is accompanied by widespread transcriptional changes that allow for prolonged survival in low oxygen. Many of these changes are directly regulated by the conserved hypoxia-inducible factor-1 (HIF-1) complex; however, even in its absence, many oxygen-sensitive transcripts in Caenorhabditis elegans are appropriately regulated in hypoxia. To identify mediators of these non-HIF-dependent responses, I established a hif-1 mutant reporter line that expresses GFP in hypoxia or when worms are treated with the hypoxia mimetic cobalt chloride (cobalt chloride). The reporter is selective and HIF-independent, in that it remains insensitive to a number of cellular stresses, but is …


Bacterial Expression Of Plant Pyruvate Kinase, Kristina Fuller Jan 2015

Bacterial Expression Of Plant Pyruvate Kinase, Kristina Fuller

STAR Program Research Presentations

Pyruvate kinases serve an important role in regulating glycolysis pathways. Different pyruvate kinase isozymes can dictate which of several different products will be formed during the final step of glycolysis. Being able to reliably copy active pyruvate kinases (PK) would allow study of the different isozymes, with the goal of eventually creating plants that are more nutritionally beneficial for humans. This study focused on improving the protocol for replicating each of two isolated PK isozymes from the model plant Arabidopsis thaliana. Previous attempts had resulted in the PK denaturing and consequently precipitating out of solution and so we manipulated the …


Editors' Note, Laura B. Regassa, Delena Gatch Jan 2015

Editors' Note, Laura B. Regassa, Delena Gatch

Biology: Faculty Publications

Dear colleagues,

The International Journal for the Scholarship of Teaching & Learning is undergoing some major changes.

  • The layout of the journal has been overhauled, giving it a look that better aligns with the quality of the content. As we continue to struggle with SoTL “counting” as scholarship at some institutions, it is important to package our work in a way that reinforces its value. We hope you enjoy the new look!
  • Articles are being assigned DOI (digital object identifier) numbers. All articles, past and present, will be tagged and linked to metadata as indexing is completed over the next …


Synthesis And Characterization Of Core-Shell Zinc Silica Nanoparticles And Zinc Silica Nanogels For Agricultural Applications., Megan Berroth Jan 2015

Synthesis And Characterization Of Core-Shell Zinc Silica Nanoparticles And Zinc Silica Nanogels For Agricultural Applications., Megan Berroth

Electronic Theses and Dissertations

Plant pathogens are a serious problem facing the agricultural industry today. Current methodologies use copper based biocides as the main form of defense. Unfortunately this can lead to damaging environmental effects and increased rates of antimicrobial resistance. In this study, antimicrobial activity of multiple alternative zinc-based nanoformulations were tested against three important plant pathogens: Xanthomonas alfalfae, Pseudomonas syringae, and Clavobacter michiganensis. Xanthomonas sub species cause Citrus canker, a devastating disease that affects millions of citrus trees worldwide while the latter two affect tomato crops. Materials synthesis was completed and the resulting nanoformulations were characterized by Atomic Absorption Spectroscopy, Scanning Electron …


Fmf Assay For Assessing Vaccine Generated Antibodies In A Biomimetic Manner, Vipra Dhir Jan 2015

Fmf Assay For Assessing Vaccine Generated Antibodies In A Biomimetic Manner, Vipra Dhir

Electronic Theses and Dissertations

Traditional functional assays such as hemagglutination inhibition (HAI) and micro-neutralization (MN) assays have been routinely used for assessing the vaccine response, since influenza vaccine has been administered in people (1940). Such assays are not always predictive regarding the protection conferred by the influenza vaccine and are not able to monitor neutralization related to stem region of influenza hemagglutinin responsible for virus membrane fusion in the endosomes. In order to study Influenza vaccine response in a more biomimetic manner and overcome the deficiencies of the traditional functional assays, we developed a fluorescent membrane fusion assay (fMF). The assay uses viruses labeled …


Functional Identification Of Nucleus Tractus Solitarius (Nts) Barosensitive Neurons: Effect Of Chronic Intermittent Hypoxia (Cih), Jenya Kolpakova Jan 2015

Functional Identification Of Nucleus Tractus Solitarius (Nts) Barosensitive Neurons: Effect Of Chronic Intermittent Hypoxia (Cih), Jenya Kolpakova

Electronic Theses and Dissertations

Chronic Intermittent Hypoxia (CIH) is a model used to study obstructive sleep apnea (OSA). Previously, we showed that baroreflex control of heart rate (HR) (baroreflex sensitivity) is reduced in CIH rats. While afferent function and HR in response to vagal efferent stimulation are enhanced, the effect of CIH on the central components, in particular NTS, is still not completely understood. F344 rats (3-4 mo) were exposed either to CIH or room air (RA) for 35-50 days. Following CIH exposure, rats were anaesthetized with Ket/Ace. Using single-unit extracellular recording technique, we recorded NTS barosensitive neurons in response to arterial pressure (AP) …


Nanoparticle Behavior In Biological Gels And Biofluids: The Impact Of Interactions With Charged Biogels And The Formation Of Protein Coronas On Nanoparticles, Xiaolu Zhang Jan 2015

Nanoparticle Behavior In Biological Gels And Biofluids: The Impact Of Interactions With Charged Biogels And The Formation Of Protein Coronas On Nanoparticles, Xiaolu Zhang

Theses and Dissertations--Chemistry

With the rapid growth of nanotechnology, situations where nanomaterials will interact with biological systems will unquestionably grow. Therefore, it is increasingly understood that interactions between nanomaterials and biological environments will play an essential role in nanomedicine. Biological polymer networks, including mucus and the extracellular matrix, serve as a filter for the exchange of molecules and nanoparticles. Such polymer networks are complex and heterogeneous hydrogel environments that regulate transport processes through finely tuned particle-network interactions. In chapters 3 and 4, we investigate the role of electrostatics on the basic mechanisms governing the diffusion of charged molecules inside model polymer networks by …


Fors 401: Forensic Biochemistry—A Peer Review Of Teaching Project Inquiry Portfolio, Ashley Hall Jan 2015

Fors 401: Forensic Biochemistry—A Peer Review Of Teaching Project Inquiry Portfolio, Ashley Hall

UNL Faculty Course Portfolios

Students who participate in active and experiential learning activities develop a better understanding of basic scientific principles and are also more likely to be retained in a STEM discipline. Developing such activities, however, can be difficult. In the present study, we sought to develop classroom activities to engage university students and increase understanding of the theory and practice of forensic science. One common accessory amongst the target audience was the ever-present media, both social and popular (entertainment). In fact, a majority of students report watching at least one of the many popular forensic science shows on TV. Therefore, we hypothesized …


A Comparison Of Whole Body Mercury Concentrations Of Mummichogs (Fundulus Heteroclitus) And Atlantic Silversides (Menidia Menidia), Daniel P. Ferons Jan 2015

A Comparison Of Whole Body Mercury Concentrations Of Mummichogs (Fundulus Heteroclitus) And Atlantic Silversides (Menidia Menidia), Daniel P. Ferons

Electronic Theses and Dissertations

Few studies have focused on mercury cycling within salt marsh estuaries. Mummichogs (Fundulus heteroclitus) and Atlantic silversides (Menidia menidia) are two species of forage fish that live year round in South Carolina salt marshes. During high tide, mummichogs feed from the water column, sediment, and off of smooth cordgrass while Atlantic silversides prey upon zooplankton. In this study, total and methyl mercury within mummichogs and Atlantic silversides from Dunn Sound, SC were quantified and compared over four seasons throughout 2014. Gut contents were also quantified and compared to determine if there was a dietary impact on the concentrations of total …


Constitutive Activity In Orphan G Protein Coupled Receptors, Adam Lee Martin Jan 2015

Constitutive Activity In Orphan G Protein Coupled Receptors, Adam Lee Martin

Doctoral Dissertations

"The goal of this research was to use a distal signaling pathway analysis to evaluate the extent of agonist independent constitutive signaling among orphan class-A G protein coupled receptors (GPCRs). These receptors translate extracellular signals via conformational change into intracellular activation of different G proteins and subsequent second messenger synthesis. These small molecules regulate cellular biochemistry, eventually leading to nuclear signaling that results in changes in gene expression. Some GPCRs are capable of signaling in the absence of an activating ligand, a phenomenon called constitutive activity that is inhibited via an "inverse-agonist". The use of cAMP dependent Luciferase expression is …


Effects Of N-Acetylcysteine Amide In Preventing/Treating Cataracts, Sri Krishna Yasaswi Maddirala Jan 2015

Effects Of N-Acetylcysteine Amide In Preventing/Treating Cataracts, Sri Krishna Yasaswi Maddirala

Doctoral Dissertations

"Cataract, the opacification of an eye lens, is a common pathological abnormality of the lens accounting for approximately 50% of all blindness. The only effective treatment currently available for a cataract is the surgical removal of the affected lens and replacement with an artificial lens for the restoration of vision. Although, cataract surgery is considered to be a very successful procedure in terms of visual outcome, the cost of surgery, need for trained personnel and surgeons, and postsurgical complications, limit the worldwide availability and accessibility of this procedure. Hence, alternative preventive and treatment procedures are worthy of investigation. The lens …


Evolutionary Dynamics Of Speciation And Extinction, Dawn Michelle King Jan 2015

Evolutionary Dynamics Of Speciation And Extinction, Dawn Michelle King

Doctoral Dissertations

Presented here is an interdisciplinary study that draws connections between the fields of physics, mathematics, and evolutionary biology. Importantly, as we move through the Anthropocene Epoch, where human-driven climate change threatens biodiversity, understanding how an evolving population responds to extinction stress could be key to saving endangered ecosystems. With a neutral, agent-based model that incorporates the main principles of Darwinian evolution, such as heritability, variability, and competition, the dynamics of speciation and extinction is investigated. The simulated organisms evolve according to the reaction-diffusion rules of the 2D directed percolation universality class. Offspring are generated according to one of three reproduction …


The Effect Of O Antigen Loss On The Protein Composition And Inflammatory Response Elicited By Klebsiella Pneumoniae, Bethaney Cahill Jan 2015

The Effect Of O Antigen Loss On The Protein Composition And Inflammatory Response Elicited By Klebsiella Pneumoniae, Bethaney Cahill

UNF Graduate Theses and Dissertations

Klebsiella pneumoniae is a Gram-negative pathogen associated with numerous infections. Like all Gram-negative bacteria, K. pneumoniae naturally release outer membrane vesicles (OMVs) during all stages of cellular growth. OMVs are composed of the outer membrane components such as lipopolysaccharide (LPS) and outer membrane proteins and contain cytosolic and periplasmic proteins in the lumen. K. pneumoniae is often found to lack an O antigen. The absence of the O antigen has been reported to alter the protein content of the membrane which may further alter the immune response elicited by K. pneumoniae. Therefore the purpose of this study was to …


The Effects Of Hibernation On The Hemostatic Properties Of The American Bullfrog, Rana Catesbeiana, Kiana Cullinan Jan 2015

The Effects Of Hibernation On The Hemostatic Properties Of The American Bullfrog, Rana Catesbeiana, Kiana Cullinan

Honors Program Theses

It is known that hibernating animals display a drastic reduction in metabolic rate, accompanied by reduced heart rate and rate of blood flow through vessels. Sluggish blood flow increases the risk for developing clots, yet it has been observed that hibernators conclusively display elongated clotting times. This observed impairment may be caused by the decrease in body temperature, due to a negative impact on the functioning of the enzymes involved in coagulation. Some hibernating endotherms, or “warm-blooded” animals, employ biological mechanisms as preventative means to prevent clotting during hibernation, such as the down-regulation of certain clotting factors or the production …


Primer Efficacy In The Dna Barcoding Of Spiders, Rhennetta Jo Bork Jan 2015

Primer Efficacy In The Dna Barcoding Of Spiders, Rhennetta Jo Bork

Honors Program Theses

DNA barcoding is the process of amplifying a 650 base pair segment of the sequence of the mitochondrial gene cytochrome c oxidase (COI), and amplifying this gene with a polymerase chain reaction (PCR). It is used to help identify and distinguish animal species and also to help determine genetic differences in species. DNA barcoding can be especially useful when working with spiders since they tend to be very small and hard to distinguish. However, achieving a DNA barcode can be difficult and thus techniques to improve the method of DNA barcoding can be helpful. This research looked into the different …


Characterization Of The Sufc Atpase During Fe-S Cluster Assembly By The Suf Pathway In Escherichia Coli, Khaleh Mykel Thomas Jan 2015

Characterization Of The Sufc Atpase During Fe-S Cluster Assembly By The Suf Pathway In Escherichia Coli, Khaleh Mykel Thomas

Theses and Dissertations

The gram-negative bacterium E. coli encodes the Suf pathway to assemble iron-sulfur (Fe-S) clusters under iron starvation and oxidative stress conditions. The ATPase activity of SufC is critical for in vivo Fe-S cluster assembly by the Suf pathway. SufC shares homology with the nucleotide binding domain (NBD) of ATP-binding cassette (ABC) transporters and belongs to the AAA+ (ATPases Associated with diverse cellular Activities) ATPase superfamily, a family of proteins that utilizes energy from ATP hydrolysis to perform a variety of cellular functions. SufC forms a stable SufBC2D complex with partner proteins SufB and SufD. The SufBC2D complex serves as a …


Study Of Escherichia Coli Adp-Glucose Pyrophosphorylase Catalysis: Investigating Critical Roles Of Conserved Arg32 And Lys42 Residues, Angela Lynn Mahaffey Jan 2015

Study Of Escherichia Coli Adp-Glucose Pyrophosphorylase Catalysis: Investigating Critical Roles Of Conserved Arg32 And Lys42 Residues, Angela Lynn Mahaffey

Dissertations

Carbohydrates have been most notable as energy sources for mammals, bacteria (glycogen) and plants (starch) – and in many other species. As such the biosynthesis of carbohydrates is essential to the sustainability of many forms of life, on earth. Adenosine-‘5-diphosphate glucose pyrophosphate (ADP-Glc pyrophosphorylase; ADP-Glc PPase) is the allosterically controlled “first committed step” in both the biosynthetic pathways of starch (~25% amylose and ~75% amylopectin, in plants and algae) and glycogen (in bacteria), preceding the starch/glycogen synthase reaction. By catalyzing the following reaction, ATP + α –D-Glc-1P ADP-Glc + PPi , ADP-Glc PPase functions as the primary enzyme in the …


Structure And Molecular Mechanism Of A Plp/Gaba Dependent Transcription Regulator Gabr, Rui Wu Jan 2015

Structure And Molecular Mechanism Of A Plp/Gaba Dependent Transcription Regulator Gabr, Rui Wu

Dissertations

GabR is a member of the MocR/GabR subfamily of the GntR family of bacterial transcription regulators. It regulates the metabolism of γ-aminobutyric acid (GABA), an important nitrogen and carbon source in many bacteria. The crystal structures reported here show that this protein has evolved from the fusion of a type I aminotransferase and a winged helix-turn-helix (wHTH) DNA binding protein to form a chimeric protein that adopts a dimeric head-to-tail configuration. The pyridoxal 5′-phosphate (PLP)-binding regulatory domain of GabR is therefore an example of a coenzyme playing a role in transcription regulation rather than in enzymatic catalysis. Our structural and …


Emetine As An Anti-Cancer Therapeutic In Bladder Cancer, Valerie Davidson Jan 2015

Emetine As An Anti-Cancer Therapeutic In Bladder Cancer, Valerie Davidson

Master's Theses

Bladder cancer is a serious health concern among the older population, as it is responsible for thousands of deaths annually in the United States. Patients that are diagnosed with muscle-invasive disease have a 5-year survival rate of only 20 percent. Additionally, muscle-invasive disease has a high metastatic potential; half of all patients develop metastatic disease within 3 years. Patients with muscle-invasive disease are presented with few treatment options aside from surgery. The current standard of care is a chemotherapeutic combination therapy of cisplatin and gemcitabine. This therapy is highly toxic, and due to the high instance of co-morbidities in these …


Genetic Indicators Of Iron Limitation In Wild Populations Of Thalassiosira Oceanica From The Northeast Pacific Ocean, P. Dreux Chappell, Leann P. Whitney, Joselynn R. Wallace, Adam I. Darer, Samua Jean-Charles, Bethany D. Jenkins Jan 2015

Genetic Indicators Of Iron Limitation In Wild Populations Of Thalassiosira Oceanica From The Northeast Pacific Ocean, P. Dreux Chappell, Leann P. Whitney, Joselynn R. Wallace, Adam I. Darer, Samua Jean-Charles, Bethany D. Jenkins

OES Faculty Publications

Assessing the iron (Fe) nutritional status of natural diatom populations has proven challenging as physiological and molecular responses can differ in diatoms of the same genus. We evaluated expression of genes encoding flavodoxin (FLDA1) and an Fe-starvation induced protein (ISIP3) as indicators of Fe limitation in the marine diatom Thalassiosira oceanica. The specificity of the response to Fe limitation was tested in cultures grown under Fe-and macronutrient-deficient conditions, as well as throughout the diurnal light cycle. Both genes showed a robust and specific response to Fe limitation in laboratory cultures and were detected in small volume samples collected from …


The Geotraces Intermediate Data Product 2014, Edward Mawji, Reiner Schlitzer, Elena M. Dodas, Cyril Abadie, Wafa Abouchami, Robert F. Anderson, Gregory A. Cutter Jan 2015

The Geotraces Intermediate Data Product 2014, Edward Mawji, Reiner Schlitzer, Elena M. Dodas, Cyril Abadie, Wafa Abouchami, Robert F. Anderson, Gregory A. Cutter

OES Faculty Publications

The GEOTRACES Intermediate Data Product 2014 (IDP2014) is the first publicly available data product of the international GEOTRACES programme, and contains data measured and quality controlled before the end of 2013. It consists of two parts: (1) a compilation of digital data for more than 200 trace elements and isotopes (TEls) as well as classical hydrographic parameters, and (2) the eGEOTRACES Electronic Atlas providing a strongly inter-linked on-line atlas including more than 300 section plots and 90 animated 3D scenes. The IDP2014 covers the Atlantic, Arctic, and Indian oceans, exhibiting highest data density in the Atlantic. The TEI data in …


The Role Of Srsf3 In Control Of Alternative Splicing Of Cpeb2 In Triple Negative Breast Cancer, Brian P. Griffin Jan 2015

The Role Of Srsf3 In Control Of Alternative Splicing Of Cpeb2 In Triple Negative Breast Cancer, Brian P. Griffin

Theses and Dissertations

In the presented study, we identified that SRSF3 controls the alternative splicing of CPEB2 and consequently promotes a metastatic phenotype in triple negative breast cancer (TNBC). TNBC causes thousands of deaths annually, frequently due to a lack of effective treatments and a high rate of metastasis in patients. Alternative splicing has been found to be dysregulated in numerous cancers, while splicing factors such as SRSF3 are variably expressed. In this study we performed a siRNA panel to screen potential splicing factors, then used specific siRNA to study the effect of its knockdown on cellular function. These results showed that SRSF3 …


Xlf-Dependent Nonhomologous End Joining Of Complex Dna Double-Strand Breaks With Proximal Thymine Glycol And Screening For Xrcc4-Xlf Interaction Inhibitors, Mohammed Al Mohaini Jan 2015

Xlf-Dependent Nonhomologous End Joining Of Complex Dna Double-Strand Breaks With Proximal Thymine Glycol And Screening For Xrcc4-Xlf Interaction Inhibitors, Mohammed Al Mohaini

Theses and Dissertations

DNA double-strand breaks induced by ionizing radiation are often accompanied by ancillary oxidative base damage that may prevent or delay their repair. In order to better define the features that make some DSBs repair-resistant, XLF-dependent nonhomologous end joining of blunt-ended DSB substrates having the oxidatively modified nonplanar base thymine glycol (Tg) at the first (Tg1) , second (Tg2), third (Tg3) or fifth (Tg5) positions from one 3’ terminus was examined in human whole-cell extracts. Tg at the third position had little effect on end-joining even when present on both ends of the break. However, Tg as the terminal or penultimate …


Pemetrexed, A Modulator Of Amp-Activated Kinase Signaling And An Inhibitor Of Wild Type And Mutant P53, Stuti Agarwal Jan 2015

Pemetrexed, A Modulator Of Amp-Activated Kinase Signaling And An Inhibitor Of Wild Type And Mutant P53, Stuti Agarwal

Theses and Dissertations

New drug discoveries and new approaches towards diagnosis and treatment have improved cancer therapeutics remarkably. One of the most influential and effective discoveries in the field of cancer therapeutics was antimetabolites, such as the antifolates. The interest in antifolates increased as some of the antifolates showed responses in cancers, such as mesothelioma, leukemia, and breast cancers. When pemetrexed (PTX) was discovered, our laboratory had established that the primary mechanism of action of pemetrexed is to inhibit thymidylate 22 synthase (TS) (E. Taylor et al., 1992). Preclinical studies have shown that PTX has a broad range of antitumor activity in human …


Interaction Between Atm Kinase And P53 In Determining Glioma Radiosensitivity, Syed F. Ahmad Jan 2015

Interaction Between Atm Kinase And P53 In Determining Glioma Radiosensitivity, Syed F. Ahmad

Theses and Dissertations

Glioblastoma multiforme (GBM) is the most common primary brain tumor. Studies have shown that targeting the DNA damage response can sensitize cancer cells to DNA damaging agents. Ataxia telangiectasia mutated (ATM) is involved in signaling DNA double strand breaks. Our group has previously shown that ATM inhibitors (ATMi) sensitize GBM cells and tumors to ionizing radiation. This effect is greater when the tumor suppressor p53 is mutated.

The goals of this work include validation of a new ATM inhibitor, AZ32, and elucidation of how ATMi and p53 status interact to promote cell death after radiation. We propose that ATMi and …


Nitric Oxide Synthase Activity And Its Modulation In The Treatment Of Colorectal Cancer, Asim Alam Jan 2015

Nitric Oxide Synthase Activity And Its Modulation In The Treatment Of Colorectal Cancer, Asim Alam

Theses and Dissertations

The American Cancer Society estimates more than 141,000 new cases of and about 50,000 deaths from colorectal cancer every year. Treatment options include surgery, radiation therapy and targeted therapies such as anti-angiogenics. However, no therapies address the key driving factor of colorectal cancer: inflammation. It is well known that chronic inflammatory conditions such as Crohn’s Disease, ulcerative colitis, diabetes, obesity and cigarette smoking all elevate the risk of developing colorectal cancer. One of the hallmarks of chronic inflammation is the elevated levels of reactive oxygen/nitrogen species (ROS/RNS). A primary source of these ROS/RNS is uncoupled Nitric Oxide Synthase (NOS). Under …