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Dahp Oxime: A Transition State Mimic Inhibitor Of Dahp Synthase, Naresh Balachandran 2014 McMaster University

Dahp Oxime: A Transition State Mimic Inhibitor Of Dahp Synthase, Naresh Balachandran

Open Access Dissertations and Theses

The rise of bacterial infections and increase of antibiotic resistant bacteria has become a major problem in the treatment of bacterial infections. The use and overuse of antibiotics, and the inherent ability of bacteria to adapt to their environment, have lead to the emergence of strains that are resistant to all antibiotics. Ideally, new targets for antibacterial drug therapy would be essential to the virulence of most or all bacteria. That is, antibiotics exploiting these targets would have broad spectrum activity. 3-Deoxy-D-arabinoheptulosonate-7- phosphate (DAHP) synthase could be such a target. This enzyme catalyzes the condensation of erythrose 4-phosphate (E4P) and ...


A Characterization Of The Dynamic Interaction Between The Pro-Apoptotic Protein Bid And The Mitochondrial Outer Membrane, Aisha Shamas-Din Ms. 2014 McMaster University

A Characterization Of The Dynamic Interaction Between The Pro-Apoptotic Protein Bid And The Mitochondrial Outer Membrane, Aisha Shamas-Din Ms.

Open Access Dissertations and Theses

Bcl-2 family of proteins regulate apoptosis at the level of the mitochondrial outer membrane (MOM) through both protein-protein and protein-membrane interactions. While the role of the membrane as the “locus of action” has been recognized, the detailed molecular mechanisms and the consequences of the interactions of Bcl-2 family members with the membrane are yet to be fully understood. The findings presented here focus on the dynamic interactions of Bcl-2 proteins, most notably tBid with the MOM, and their functional significance on mitochondrial outer membrane permeabilization. We show that the activation of tBid is a multi-step process that is regulated by ...


Permaculture Design: On The Practice Of Radical Imagination, Katja Rothe 2014 University of Massachusetts - Amherst

Permaculture Design: On The Practice Of Radical Imagination, Katja Rothe

communication +1

Permaculture design is a concept that aims at transforming not only agriculture, but also city planning, architecture, development, etc. In short it aims to change human habitats. It is part of a new ecological paradigm that is currently spreading in popularity from the urban gardening movement to various other alternative movements such as the slow movement, sustainable architecture, etc. Permaculture design defines itself as building on systems theory (as formulated in particular by Howard Thomas Odum and Christopher Alexander). However I would like to propose that the afterlife of systems theory as expressed in the concept of permaculture, first developed ...


Targeting Grp78 In Cancer With Nucleic Acid Bioconjugates, Pradeepkumar L. Patel 2014 Seton Hall University

Targeting Grp78 In Cancer With Nucleic Acid Bioconjugates, Pradeepkumar L. Patel

Seton Hall University Dissertations and Theses (ETDs)

Nucleic acid bioconjugates have gained widespread use in medicinal chemistry research programs aimed at fighting human malignancies such as cancer, diabetes, genetic and infectious diseases. Their popularity stems from their ability to accelerate the drug development process by conjugating chemical functionality that may improve the pharmacology of a bioactive nucleoside. Moreover, this strategy has been proven to be effective with small molecule nucleoside analogs and those derived from lengthy oligonucleotide sequences. Considering these fruitful applications, my research and this thesis aims to explore the synthesis, characterization and therapeutic potential of novel classes of nucleic acid bioconjugates.

These are based on ...


Identification Of Soybean Lipoxygenase Products By Gas Chromatography-Mass Spectrometry (Ge-Ms), Rehan Ahmad Malik 2014 Minnesota State University, Mankato

Identification Of Soybean Lipoxygenase Products By Gas Chromatography-Mass Spectrometry (Ge-Ms), Rehan Ahmad Malik

Journal of Undergraduate Research at Minnesota State University, Mankato

Lipoxygenases (LOXs) are enzymes which catalyze peroxidation of polyunsaturated fatty acids containing at least one cis, cis 1, 4-pentadiene moiety to form conjugated diene-hydroperoxides. Soybean seeds contain three LOX isoenzymes while at least five different isoenzymes are in the vegetative tissue. Lipoxygenases have been related to several functions i.e. plant growth, defense mechanisms against pathogens and pests, and lipid metabolism. Given the proposed roles of LOX isoenzymes and the presence of multiple LOX isoenzymes in soybean vegetative tissue, it is likely that individual isoenzymes play specific functions. Do the isoenzymes show differences in which products they form? The basic ...


Regulation Of Saga By The N-Terminus Of Spt7 In Saccharomyces Cerevisiae, Dominik Dobransky 2014 Western University

Regulation Of Saga By The N-Terminus Of Spt7 In Saccharomyces Cerevisiae, Dominik Dobransky

University of Western Ontario - Electronic Thesis and Dissertation Repository

Spt7 is a 1,332 residue protein critical for maintaining structural integrity of the SAGA complex. I demonstrated that the extreme N-terminus of Spt7 plays an important role in SAGA function. Deletion of the first 73 (Spt773-1332) and 121 (Spt7121-1332) N- terminal residues resulted in slow growth, decreased transcriptional activation at PHO5 and INO1, and a partial decrease in acetylation at lysine 18 of histone H3 at PHO5. The Spt7121-1332 mutant did not affect Spt7’s association with Gcn5 or Tra1, or its localization within the cell. Mutation of the first four positively charged residues to glutamine ...


The Role Of The Pre-Sensor 1 Β Hairpin In Minichromosome Maintenance 2-7 Function, Simon K. W. Lam 2014 Western University

The Role Of The Pre-Sensor 1 Β Hairpin In Minichromosome Maintenance 2-7 Function, Simon K. W. Lam

University of Western Ontario - Electronic Thesis and Dissertation Repository

The pre-sensor 1 (PS1) hairpin is found in helicases of the AAA+ family (ATPases associated with a variety of cellular activities) of proteins and is implicated in DNA translocation during DNA unwinding. To determine whether the PS1 b hairpin is required in the eukaryotic replicative helicase, Mcm2-7 (also comprised of AAA+ proteins), we mutated the conserved lysine residue in the PS1 hairpin in each of the S. cerevisiae Mcm subunits to alanine. Only the PS1 hairpin of Mcm3 was essential for viability, while mutation of the PS1 hairpin in the remaining Mcm subunits resulted in minimal phenotypes, with the exception ...


Submonomer Synthesis And Structure-Activity Relationship Studies Of Azapeptide Inhibitors Of The Insulin Receptor Tyrosine Kinase, Lathamol A. Kurian 2014 Seton Hall University

Submonomer Synthesis And Structure-Activity Relationship Studies Of Azapeptide Inhibitors Of The Insulin Receptor Tyrosine Kinase, Lathamol A. Kurian

Seton Hall University Dissertations and Theses (ETDs)

Azapeptides are a class of peptide mimics (peptidomimetics), which have served as valuable tools for the development of peptide based therapeutic agents. The therapeutic promise of azapeptides has been correlated to its primary sequence modification which translates into bio-active secondary structures that improves the pharmacological properties of the native peptide sequence. More specifically, azapeptides contain a semicarbazide within the peptide backbone which restricts the peptide bond torsion angles (φ, ψ) into pre-organized b-turn secondary structures. Thus, azapeptides have been shown to stabilize bio-active b-turn secondary structures responsible for high affinity and selective binding to a target receptor or ...


Poly(Arginine) Derived Cancer-Targeting Peptides For The Development Of A Cancer-Targeted Gene Therapy Approach In Hepg2 Liver Cancer Cells, Stesha C. Joseph 2014 Seton Hall University

Poly(Arginine) Derived Cancer-Targeting Peptides For The Development Of A Cancer-Targeted Gene Therapy Approach In Hepg2 Liver Cancer Cells, Stesha C. Joseph

Seton Hall University Dissertations and Theses (ETDs)

Cancer is a disease that has eluded medicinal approaches for many years and as a result new and improved therapeutic approaches are in constant demand. Although chemotherapy and radiation treatments have assisted in suppressing the growth of tumors, their poor selectivity and efficacy are major limitations for effective therapy en route towards the development of a cure for the cancer epidemic. With the mission of conquering cancer at heart, researchers have pursued a new form of cancer therapy, aptly named, a cancer targeting approach. This method revolves around the selection of a suitable biomarker, typically a cell surface receptor overexpressed ...


The Effect Of Maternal Aldosterone Levels On The Expression Of 11b-Hsd Isoenzymes In Normal And Hypertensive Rat Placentae, Nicole Jorissen 2014 Minnesota State University, Mankato

The Effect Of Maternal Aldosterone Levels On The Expression Of 11b-Hsd Isoenzymes In Normal And Hypertensive Rat Placentae, Nicole Jorissen

Journal of Undergraduate Research at Minnesota State University, Mankato

In this project, we developed a Western blotting procedure to semi-quantitate levels of 11β-HSD1 and 11β-HSD2 in whole cell extracts. Then, we applied this technique to analyze the effect of reduced maternal aldosterone levels on the expression of 11β-HSD1 and 11β-HSD2 isoenzymes in the placental tissue in both normal and hypertensive rats. These enzymes control levels of glucocorticoids which compete for aldosterone’s mineralocorticoid receptor. Overstimulation of this receptor results in hypertension. If aldosterone levels decrease, levels of the enzymes controlling active glucocorticoid concentrations might change to compensate for the lowered aldosterone levels. Decreased placental 11β-HSD2 expression could affect hypertension ...


The Roles Of Matrix-Associated Periostin In An In Vitro Model Of Hypertrophic Scarring, Justin D. Crawford 2014 Western University

The Roles Of Matrix-Associated Periostin In An In Vitro Model Of Hypertrophic Scarring, Justin D. Crawford

University of Western Ontario - Electronic Thesis and Dissertation Repository

Abnormal scarring is a type of benign fibrosis of the skin that can restrict mobility, dexterity and quality of life. There are few, if any, truly effective treatment options for these conditions. Hypertrophic scarring is a common form of abnormal scarring characterized by increased fibroblast proliferation and differentiation of apoptosis-resistant and hyper-contractile myofibroblasts that promote excessive deposition and contracture of the extracellular matrix (ECM). Periostin, a secreted ECM protein, is transiently expressed during normal cutaneous wound repair, but is abnormally abundant and persistent in abnormal scars and other benign fibroses that display enhanced fibroblast proliferation and myofibroblast differentiation. The objectives ...


Evaluation Of Pretreatment Methods In The Production Of Ethanol From Cattail Leaves, Kristen Krahmer, Elijah Wreh 2014 Minnesota State University, Mankato

Evaluation Of Pretreatment Methods In The Production Of Ethanol From Cattail Leaves, Kristen Krahmer, Elijah Wreh

Journal of Undergraduate Research at Minnesota State University, Mankato

Previous research in this lab indicated that cattails are a potential source of biomass for the production of cellulosic ethanol since their carbohydrate composition is comparable to that of other plants being considered for biofuel production. To further test their viability, we tested various pretreatment methods on dried cattail leaves. Before polysaccharides in plants can be enzymatically hydrolyzed to fermentable sugars, the plant material must be pretreated to render the polysaccharides accessible to the enzymes. The purpose of this project has been to compare the efficiency of sulfuric acid and ammonia pretreatment methods in preparing cattail biomass for ethanol production ...


Single Tube, Multiple Enzyme Reaction For Detection Of Uv And Oxidative Damage In Forensic Physiological Stains, Nicholas J. Eurek 2014 University of Nebraska - Lincoln

Single Tube, Multiple Enzyme Reaction For Detection Of Uv And Oxidative Damage In Forensic Physiological Stains, Nicholas J. Eurek

Theses and Dissertations in Biochemistry

For decades, the use of DNA as a biological tool has revolutionized forensic investigations. The primary use of this genetic evidence is for identification of a victim or suspect through short tandem repeat (STR) profiling. However, the usefulness of this evidence can be compromised through inhibition of PCR, damage to the DNA, or low copy number. Here, we investigate damage induced to DNA by environmental factors. UV light is known to damage DNA by the formation of cyclobutane pyrimidine dimers, 6-4 photoproducts, and strand breaks. These lesions can stall polymerase action or misincorporate bases during extension. Oxidative damage is also ...


Xrf Analyses Of Prehanford Orchards, Komal Rana 2014 California Polytechnic State University

Xrf Analyses Of Prehanford Orchards, Komal Rana

STEM Teacher and Researcher (STAR) Program Posters

Subsequent to 1943, the use of Lead Arsenic was banned from the Orchards standing on the Hanford site. This use of Lead Arsenate pesticide was popular among the orchard owners and was dispersed over the site in a myriad of ways. The presence of the traces of lead and arsenic are found today, more than half a century later. Using a portable X-ray florescence analyzer (XRF), the values of lead and arsenic are evaluated while determining the efficiency of the equipment itself. Samples from different decision sites were collected, with lead arsenic values in the low, high and medium range ...


Roles For B-Raf Kinase In The Specific Regulation Of Α4Β1 Integrin In T Cells, Wells S. Brown 2014 Texas Medical Center Library

Roles For B-Raf Kinase In The Specific Regulation Of Α4Β1 Integrin In T Cells, Wells S. Brown

UT GSBS Dissertations and Theses (Open Access)

The regulation of integrin-mediated adhesion is of vital importance to adaptive and innate immunity. Integrins are versatile proteins and mediate T cell migration and trafficking by binding to ECM or other cells, as well as initiating intracellular signaling cascades promoting survival or activation. The mitogen activated-protein kinase (MAPK) pathway is known to be downstream from integrins and regulate survival, differentiation, and motility. However, secondary roles for canonical MAPK pathway members are being discovered. We show chemical inhibition of RAF by Sorafenib or shRNA-mediated knockdown of B-Raf reduces T cell resistance to shear stress to α4β1 integrin ligands vascular cell adhesion ...


Egfr Modulates Microrna Maturation In Response To Hypoxia Through Phosphorylation Of Argonaute2, Jia Shen 2014 Texas Medical Center Library

Egfr Modulates Microrna Maturation In Response To Hypoxia Through Phosphorylation Of Argonaute2, Jia Shen

UT GSBS Dissertations and Theses (Open Access)

MicroRNAs (miRNAs) are generated by two-step processing to yield small RNAs that negatively regulate target gene expression at posttranscriptional level. Deregulation of miRNAs has been linked to diverse pathological processes, including cancer. Recent studies have also implicated miRNAs in regulatory roles to cope with a spectrum of stresses, such as hypoxia, which is frequently encountered in the poorly angiogenic core of a solid tumor. However, the upstream regulators of miRNA biogenesis machineries remain obscure, raising the question of how tumor cells efficiently coordinate and impose specificity on miRNA expression and function in response to stresses. Here, we show that EGFR ...


Pi3k- And Mtor-Dependent Mechanisms Of Lapatinib Resistance And Resulting Therapeutic Opportunities, Samuel Brady 2014 Texas Medical Center Library

Pi3k- And Mtor-Dependent Mechanisms Of Lapatinib Resistance And Resulting Therapeutic Opportunities, Samuel Brady

UT GSBS Dissertations and Theses (Open Access)

Breast cancers with HER2 amplification represent 20-25% of breast cancer cases and are frequently responsive to the HER2 kinase inhibitor lapatinib, but generally for only short duration. We aimed to understand how breast cancers with HER2 amplification become resistant to lapatinib, in order to identify potential therapies that can overcome lapatinib resistance. To establish lapatinib resistance models we treated three HER2+ breast cancer cell lines with lapatinib for several months until they became lapatinib-resistant. We then compared lapatinib-sensitive (parental) cells with their lapatinib-resistant (LapR) counterparts to identify changes conferring lapatinib resistance. We found that activation of PI3K, specifically the p110α ...


Some Effects Of The Human Genome Project On The Erdős Collaboration Graph, Chris Fields 2014 Claremont Colleges

Some Effects Of The Human Genome Project On The Erdős Collaboration Graph, Chris Fields

Journal of Humanistic Mathematics

The Human Genome Project introduced large-scale collaborations involving dozens to hundreds of scientists into biology. It also created a pressing need to solve discrete mathematics problems involving tens of thousands of elements. In this paper, we use minimal path lengths in the Erdős Collaboration Graph between prominent individual researchers as a measure of the distance between disciplines, and we show that the Human Genome Project brought laboratory biology as a whole closer to mathematics. We also define a novel graph reduction method and a metric that emphasizes the robustness of collaborative connections between researchers; these can facilitate the analysis of ...


Experimental Demonstration Of Bindingless Signal Delivery In Human Cells Via Microfluidics, Fang-Tzu Chuang 2014 SelectedWorks

Experimental Demonstration Of Bindingless Signal Delivery In Human Cells Via Microfluidics, Fang-Tzu Chuang

Fang-Tzu Chuang

The cellular signal transduction is commonly believed to rely on the direct “contact” or “binding” of the participating molecule reaction that depends positively on the corresponding molecule concentrations. In living systems, however, it is somewhat difficult to precisely match the corresponding rapid “binding,” depending on the probability of molecular collision, existing in the cellular receptor-ligand interactions. Thus, a question arises that if there is another mechanism (i.e., bindingless) that could promote this signal communication. According to this hypothesis, we report a cellular model based on the examination of intracellular calcium concentration to explore whether the unidentified signal delivery in ...


Drosophila Sirt2/Mammalian Sirt3 Deacetylates Atp Synthase Beta And Regulates Complex V Activity, Motiur Rahman, Niraj K. Nirala, Alka Singh, Lihua Julie Zhu, Kaori Taguchi, Takeshi Bamba, Eiichiro Fukusaki, Leslie M. Shaw, David G. Lambright, Jairaj K. Acharya, Usha R. Acharya 2014 University of Massachusetts Medical School

Drosophila Sirt2/Mammalian Sirt3 Deacetylates Atp Synthase Beta And Regulates Complex V Activity, Motiur Rahman, Niraj K. Nirala, Alka Singh, Lihua Julie Zhu, Kaori Taguchi, Takeshi Bamba, Eiichiro Fukusaki, Leslie M. Shaw, David G. Lambright, Jairaj K. Acharya, Usha R. Acharya

Program in Gene Function and Expression Publications and Presentations

Adenosine triphosphate (ATP) synthase beta, the catalytic subunit of mitochondrial complex V, synthesizes ATP. We show that ATP synthase beta is deacetylated by a human nicotinamide adenine dinucleotide (NAD(+))-dependent protein deacetylase, sirtuin 3, and its Drosophila melanogaster homologue, dSirt2. dsirt2 mutant flies displayed increased acetylation of specific Lys residues in ATP synthase beta and decreased complex V activity. Overexpression of dSirt2 increased complex V activity. Substitution of Lys 259 and Lys 480 with Arg in human ATP synthase beta, mimicking deacetylation, increased complex V activity, whereas substitution with Gln, mimicking acetylation, decreased activity. Mass spectrometry and proteomic experiments from ...


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