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Biology

2014

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Full-Text Articles in Biochemistry

Characterization Of A Putative Phospholipase D ´ Like Gene As A Lipid Signaling Modulator And Its Role In Salicylic Acid Mediated Defense Pathway In Nicotiana Tabacum, Phillip T. Dean Dec 2014

Characterization Of A Putative Phospholipase D ´ Like Gene As A Lipid Signaling Modulator And Its Role In Salicylic Acid Mediated Defense Pathway In Nicotiana Tabacum, Phillip T. Dean

Electronic Theses and Dissertations

Plants are in a perpetual evolutionary arms race with a wide range of pathogens. Their sessile nature has led plants to evolve defense mechanisms that can quickly recognize a unique stressor and deploy a resistance tailored for a specific attack. The salicylic acid (SA) mediated defense pathway has been shown to be one of the major defense tactics plants can initiate to defend themselves against microbial pathogens. Following a pathogen attack high levels of methyl salicylate (MeSA) are produced that can be converted to SA by the enzyme salicylic acid binding protein 2 (SABP2). A yeast two-hybrid screening was performed …


An Active Role For The Ribosome In Determining The Fate Of Oxidized Mrna, Carrie L. Simms, Benjamin H. Hudson, John W. Mosior, Ali S. Rangwala, Hani S. Zaher Nov 2014

An Active Role For The Ribosome In Determining The Fate Of Oxidized Mrna, Carrie L. Simms, Benjamin H. Hudson, John W. Mosior, Ali S. Rangwala, Hani S. Zaher

Biology Faculty Publications & Presentations

Chemical damage to RNA affects its functional properties and thus may pose a significant hurdle to the translational apparatus; however, the effects of damaged mRNA on the speed and accuracy of the decoding process and their interplay with quality-control processes are not known. Here, we systematically explore the effects of oxidative damage on the decoding process using a well-defined bacterial in vitro translation system. We find that the oxidative lesion 8-oxoguanosine (8-oxoG) reduces the rate of peptide-bond formation by more than three orders of magnitude independent of its position within the codon. Interestingly, 8-oxoG had little effect on the fidelity …


Ribosomes Left In The Dust: Diverse Strategies For Peptide-Mediated Translation Stalling, Benjamin H. Hudson, Hani S. Zaher Nov 2014

Ribosomes Left In The Dust: Diverse Strategies For Peptide-Mediated Translation Stalling, Benjamin H. Hudson, Hani S. Zaher

Biology Faculty Publications & Presentations

In two recent papers, Arenz et al. (2014a) and Bischoff et al. (2014) provide structural insights into drug-induced, peptide-mediated stalling of the ribosome.


Cross-Disciplinary Sciences At Gettysburg College: Second Annual Poster Presentation, X-Sig Oct 2014

Cross-Disciplinary Sciences At Gettysburg College: Second Annual Poster Presentation, X-Sig

Student Publications

This booklet includes Biology student presentations by: Taylor Bury, Abigail Dworkin-Brodsky, Mary Pearce, Jasper Leavitt, Morgan Panzer, Ellen Petley, Kalli Qutub, Taylor Randell, Samantha Eck, Lana McDowell, Jenn Soroka, Celina Harris, Natalie Tanke, Alexandra Turano, and Caroline Garliss.

This booklet includes Biochemistry & Molecular Biology student presentations by: Matthew Dunworth, Andrew Sydenstricker, Brianne Tomko, Albert Vill, Warren Campbell, David Van Doren, Kevin Mrugalski, Stacey Heaver, Alecia Achimovich, and Katherine Boas.

This booklet includes Chemistry student presentations by: Kristen Baker, Laura Lee, Kathryn Fodale, Daniel Ruff, Michael Counihan, Ida DiMucci, Joshua Sgroi, Celina Harris, and Natalie Tanke.

This booklet include Health …


Dietary Carbohydrates Influence The Structure And Function Of The Intestinal Alpha-Glucosidases, Mohammad Chegeni Oct 2014

Dietary Carbohydrates Influence The Structure And Function Of The Intestinal Alpha-Glucosidases, Mohammad Chegeni

Open Access Dissertations

As the primary products of starch digestion by pancreatic α-amylase, maltooligosaccharides (including maltose) are the main substrates for the α-glucosidases at the intestinal brush border. Here, maltose was shown to induce the formation of a higher molecular weight (HMW) sucrase-isomaltase (SI) species in Caco-2 cells that sorts more quickly to the enterocyte surface to act as a digestive enzyme. As this finding suggested a maltose sensing ability of small intestinal enterocytes, molecular mechanisms associated with the maturation and trafficking of HMW SI were further investigated. A pulse-chase experiment using [ 35S]-methionine revealed a higher rate of early trafficking and …


Towards A Paradigm Shift In The Modeling Of Soil Organic Carbon Decomposition For Earth System Models, Yujie He Oct 2014

Towards A Paradigm Shift In The Modeling Of Soil Organic Carbon Decomposition For Earth System Models, Yujie He

Open Access Dissertations

Soils are the largest terrestrial carbon pools and contain approximately 2200 Pg of carbon. Thus, the dynamics of soil carbon plays an important role in the global carbon cycle and climate system. Earth System Models are used to project future interactions between terrestrial ecosystem carbon dynamics and climate. However, these models often predict a wide range of soil carbon responses and their formulations have lagged behind recent soil science advances, omitting key biogeochemical mechanisms. In contrast, recent mechanistically-based biogeochemical models that explicitly account for microbial biomass pools and enzyme kinetics that catalyze soil carbon decomposition produce notably different results and …


Structural And Biochemical Studies Of The Carboxyltransferase Domain From Pyruvate Carboxylase, Adam David Lietzan Oct 2014

Structural And Biochemical Studies Of The Carboxyltransferase Domain From Pyruvate Carboxylase, Adam David Lietzan

Dissertations (1934 -)

Pyruvate carboxylase (PC; E.C. 6.4.1.1), a multifunctional biotin-dependent enzyme, catalyzes the bicarbonate- and MgATP-dependent carboxylation of pyruvate to oxaloacetate. To complete the overall reaction, the tethered biotin prosthetic group must first gain access to the biotin carboxylase domain and become carboxylated, and then translocate to the carboxyltransferase (CT) domain where the carboxyl group is transferred from biotin to pyruvate. Kinetic analyses of PC have suggested that the spatially distinct reactions, which occur in the active sites of the BC and CT domains, are well coordinated. To gain insights into the molecular events necessary for coordinating catalysis in the CT domain, …


The Chevrolet Cruze Luv 1.4 Engine, Gabriel Leiner Aug 2014

The Chevrolet Cruze Luv 1.4 Engine, Gabriel Leiner

Gabriel Leiner

In the future, this research suggests that designing highways and cars with features built into the structures of the roads themselves that implicitly influence typical drivers to achieve better fuel economy without making an active effort. These types of “intuitively” fuel efficient highways and cars are proposed, defined and modeled within the scope of this paper.


Determining The Binding Between Saga Subunits And Spliceosomal Components, Peyton J. Spreacker, Rachel L. Stegeman, Vikki M. Weake Aug 2014

Determining The Binding Between Saga Subunits And Spliceosomal Components, Peyton J. Spreacker, Rachel L. Stegeman, Vikki M. Weake

The Summer Undergraduate Research Fellowship (SURF) Symposium

Proper gene regulation is vital to the health and development of an organism. Determining the relationship between splicing, transcription, and chromatin structure is vital for understanding gene regulation as a whole. There have been previous studies linking these elements pairwise; however, no evidence exists for a direct link between all three. Recent data shows that splicing components of the U2 small nuclear ribonucleic protein (snRNP) co-purify with Spt-Ada-Gcn5-acetyltransferase (SAGA), a highly conserved transcriptional co-activator and chromatin modifier. We hypothesize that SAGA binds with splicing components through a multi-protein binding surface with certain core components based on preliminary yeast two-hybrid data. …


Xrf Analyses Of Prehanford Orchards, Komal Rana Aug 2014

Xrf Analyses Of Prehanford Orchards, Komal Rana

STAR Program Research Presentations

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 …


Abcb11 Functions With B1 And B19 To Regulate Rootward Auxin Transport, Jesica Elyse Reemmer Jul 2014

Abcb11 Functions With B1 And B19 To Regulate Rootward Auxin Transport, Jesica Elyse Reemmer

Open Access Theses

Auxin transport is essential for the architecture and development of erect plants. In a network of transporters directing auxin flows, ATP-Binding Cassette (ABC) transporters are a ubiquitous family of proteins that actively transport important substrates, including auxins, across the plasma membrane. ABCB1 and ABCB19 have been shown to account for the majority of rootward auxin transport, but residual fluxes to the root tip in Arabidopsis b1b19 double mutants implies the involvement of at least one additional auxin transporter in this process. Of specific interest, the severe dwarfism seen in abcb1abcb19 is strikingly reminiscent of that seen in mutants defective in …


Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park Jul 2014

Key Residues Of Human Cytoplasmic Protein Tyrosine Phosphatase-A And -B For Substrate Binding And Specificity, Byunghyun Park

Open Access Theses

Reversible tyrosine phosphorylation plays an important role in signaling pathways that are essential for regulating cellular growth, differentiation and metabolism. Moreover, several human diseases such as diabetes, obesity and cancers are associated with the deregulation of protein tyrosine phosphatases (PTPs). Several studies provide evidence that PTPs not only contribute to cellular differentiation, but over-expression of these molecules also leads to transformation of non-transfomed cells as well. Based on these results, designing specific PTP inhibitors may ultimately function as potential therapeutic agents to treat various diseases including cancer, diabetes, and autoimmune diseases. EphA2 is a receptor tyrosine kinase which is hypo-phosphorylated …


[Accepted Article Manuscript Version (Postprint)] Auxin Input Pathway Disruptions Are Mitigated By Changes In Auxin Biosynthetic Gene Expression In Arabidopsis, Gretchen Spiess, Amanda Hausman, Peng Yu, Jerry Cohen, Rebekah Rampey, Bethany Zolman Jul 2014

[Accepted Article Manuscript Version (Postprint)] Auxin Input Pathway Disruptions Are Mitigated By Changes In Auxin Biosynthetic Gene Expression In Arabidopsis, Gretchen Spiess, Amanda Hausman, Peng Yu, Jerry Cohen, Rebekah Rampey, Bethany Zolman

Biology Department Faculty Works

Auxin is a phytohormone involved in cell elongation and division. Levels of indole-3-acetic acid (IAA), the primary auxin, are tightly regulated through biosynthesis, degradation, sequestration, and transport. IAA is sequestered in reversible processes by adding amino acids, polyol or simple alcohols, or sugars, forming IAA conjugates, or through a two-carbon elongation forming indole-3-butyric acid. These sequestered forms of IAA alter hormone activity. To gain a better understanding of how auxin homeostasis is maintained, we have generated Arabidopsis (Arabidopsis thaliana) mutants that combine disruptions in the pathways, converting IAA conjugates and indole-3-butyric acid to free IAA. These mutants show phenotypes indicative …


Role Of The Polyadenylation Factor Cstf-50 In Regulating The Brca1/Bard1 E3 Ubiquitin (Ub) Ligase Activity, Danae Fonseca Jun 2014

Role Of The Polyadenylation Factor Cstf-50 In Regulating The Brca1/Bard1 E3 Ubiquitin (Ub) Ligase Activity, Danae Fonseca

Dissertations, Theses, and Capstone Projects

The cellular response to DNA damage is an intricate mechanism that involves the interplay among several pathways. The studies presented in this dissertation focus on the determination and characterization of the role of mRNA processing factor CstF-50 and escort protein p97 in the regulation of the BRCA1/BARD1 E3 ubiquitin (Ub) ligase activity during the DNA damage response (DDR).

As part of the studies presented in Chapter II, I determined that the polyadenylation factor CstF plays a direct role in DDR, specifically in transcription-coupled repair (TCR), and that it localizes with RNA polymerase II (RNAP II) and BARD1 to sites of …


Biological Surveys Of Selected Lower Grand River Streams: Ionia, Kent, Muskegon, And Ottawa Counties, Michigan, August-September 2014, Michigan Department Of Environmental Quality Water Resources Division Jun 2014

Biological Surveys Of Selected Lower Grand River Streams: Ionia, Kent, Muskegon, And Ottawa Counties, Michigan, August-September 2014, Michigan Department Of Environmental Quality Water Resources Division

Faculty and Professional Research

The biologic integrity and physical habitat conditions of the lower Grand River (Hydrologic Unit Code (HUC) 04050006) and selected tributaries were surveyed during August and September 2014 by staff of the Surface Water Assessment Section (SWAS), Water Resources Division (WRD). The objectives of this study were to: 1. Evaluate the attainment status of the other indigenous aquatic life and wildlife (OIALW) designated use. 2. Identify and investigate effects of nonpoint sources (NPS) of pollution. 3. Satisfy monitoring requests submitted by internal and external customers.


Branching Into Rnai: Synthesis, Characterization And Biology Of Branch And Hyperbranch Sirnas, Anthony Muriithi Maina May 2014

Branching Into Rnai: Synthesis, Characterization And Biology Of Branch And Hyperbranch Sirnas, Anthony Muriithi Maina

Seton Hall University Dissertations and Theses (ETDs)

The cancer epidemic continues to afflict millions of humans world-wide each year and despite a renewed hope with the development of new and improved forms of therapy, a cure for cancer remains an elusive goal. This is partly related to the rise of resilient forms of tumors that have evolved with resistance towards conventional chemotherapy and radiation treatments. Moreover, these non-specific therapeutic regimens are highly toxic, leading to severe immunosuppressive effects which poisons the body and compromises the road towards remission. In an effort to mitigate these limitations, cancer-targeting approaches are currently experiencing a renaissance in the translation of new …


The Effects Of Jasmonic Acid And Chemicals In The Ja Pathway On The Defense Systems And Gene Expression In Moss, Physcomitrella Patens And Amblystegium Serpens, Allison Shanks May 2014

The Effects Of Jasmonic Acid And Chemicals In The Ja Pathway On The Defense Systems And Gene Expression In Moss, Physcomitrella Patens And Amblystegium Serpens, Allison Shanks

Undergraduate Honors Thesis Collection

Systemic acquired resistance (SAR) is a defense system used by plants that results in increased resistance to future pathogen infection following an initial pathogen exposure. SAR in vascular plants has been well documented; however, a similar defense system has only recently been documented in non-vascular plants. It is believed that chemicals in the jasmonic acid (JA) pathway are able to activate the SAR response in vascular plants. The non-vascular plant, Amb/ystegium serpens, will be used as a model to test if SAR is triggered by JA and two other molecules in the JA pathway, 12-oxo-phytodieonic acid, and methyl jasmonate. To …


2-Acylamido Analogues Of N-Acetylglucosamine Prime Formation Of Chitin Oligosaccharides By Yeast Chitin Synthase 2, Jacob Gyore, Archana Parameswar, Carleigh Hebbard, Younghoon Oh, Erfei Bi, Alexei Demchenko, Neil Price, Peter Orlean May 2014

2-Acylamido Analogues Of N-Acetylglucosamine Prime Formation Of Chitin Oligosaccharides By Yeast Chitin Synthase 2, Jacob Gyore, Archana Parameswar, Carleigh Hebbard, Younghoon Oh, Erfei Bi, Alexei Demchenko, Neil Price, Peter Orlean

Chemistry & Biochemistry Faculty Works

Chitin, a homopolymer of β1,4-linked N-acetylglucosamine (GlcNAc) residues, is a key component of the cell walls of fungi and the exoskeletons of arthropods. Chitin synthases transfer GlcNAc from UDP-GlcNAc to preexisting chitin chains in reactions that are typically stimulated by free GlcNAc. The effect of GlcNAc was probed by using a yeast strain expressing a single chitin synthase, Chs2, by examining formation of chitin oligosaccharides (COs) and insoluble chitin, and by replacing GlcNAc with 2-acylamido analogues of GlcNAc. Synthesis of COs was strongly dependent on inclusion of GlcNAc in chitin synthase incubations, and N,N′-diacetylchitobiose (GlcNAc2) was the major reaction product. …


2-Acylamido Analogues Of N-Acetylglucosamine Prime Formation Of Chitin Oligosaccharides By Yeast Chitin Synthase 2, Jacob Gyore, Archana R. Parameswar, Carleigh F. F. Hebbard, Younghoon Oh, Erfei Bi, Alexei V. Demchenko, Neil P. Price, Peter Orlean May 2014

2-Acylamido Analogues Of N-Acetylglucosamine Prime Formation Of Chitin Oligosaccharides By Yeast Chitin Synthase 2, Jacob Gyore, Archana R. Parameswar, Carleigh F. F. Hebbard, Younghoon Oh, Erfei Bi, Alexei V. Demchenko, Neil P. Price, Peter Orlean

Alexei Demchenko

Chitin, a homopolymer of β1,4-linked N-acetylglucosamine (GlcNAc) residues, is a key component of the cell walls of fungi and the exoskeletons of arthropods. Chitin synthases transfer GlcNAc from UDP-GlcNAc to preexisting chitin chains in reactions that are typically stimulated by free GlcNAc. The effect of GlcNAc was probed by using a yeast strain expressing a single chitin synthase, Chs2, by examining formation of chitin oligosaccharides (COs) and insoluble chitin, and by replacing GlcNAc with 2-acylamido analogues of GlcNAc. Synthesis of COs was strongly dependent on inclusion of GlcNAc in chitin synthase incubations, and N,N′-diacetylchitobiose (GlcNAc2) was the major reaction product. …


Defining The Sites Of Interaction Of The Fancd2, Fance, And Fancl Proteins, Joseph Mcclanaghan May 2014

Defining The Sites Of Interaction Of The Fancd2, Fance, And Fancl Proteins, Joseph Mcclanaghan

Senior Honors Projects

Fanconi anemia (FA) is a rare genetic disease characterized by congenital defects, bone marrow failure and increased cancer susceptibility. FA is caused by mutations in any one of 16 genes. These genes encode for proteins that function in the FA-BRCA pathway to repair damaged DNA. Because of its important r­­­ole in DNA repair, this pathway is considered a major cellular tumor suppressor pathway, i.e. is critical for the prevention of cancer. Underscoring this fact, several of the FA genes - including BRCA2, BRIP1, PALB2, and RAD51C - are bona fide breast and ovarian cancer susceptibility genes.

My …


Characterization Of Ftsa-Ftsn Interaction During Escherichia Coli Cell Division, Kimberly.Busiek@Gmail.Com K. Busiek May 2014

Characterization Of Ftsa-Ftsn Interaction During Escherichia Coli Cell Division, Kimberly.Busiek@Gmail.Com K. Busiek

Dissertations & Theses (Open Access)

Division of a bacterial cell into two equal daughter cells requires precise assembly and constriction of the division machinery, or divisome. The Escherichia coli divisome includes nearly a dozen essential cell division proteins that assemble at midcell between segregating sister chromosomes. FtsZ, a homolog of eukaryotic tubulin, is the first essential cell division protein to localize at midcell where it polymerizes into a ring-shaped scaffold (Z ring). Establishment of the Z ring is required for recruitment of downstream cell division proteins including FtsA, a cytoplasmic protein that tethers the Z ring to the inner membrane. Following localization of FtsA and …


Antimicrobial And Antiinsectan Phenolic Metabolites Of Dalea Searlsiae, Gil Belofsky, Mario Aronica, Eric Foss, Jane Diamond, Felipe Santana, Jacob Darley, Patrick F. Dowd, Christina M. Coleman, Daneel Ferreira Apr 2014

Antimicrobial And Antiinsectan Phenolic Metabolites Of Dalea Searlsiae, Gil Belofsky, Mario Aronica, Eric Foss, Jane Diamond, Felipe Santana, Jacob Darley, Patrick F. Dowd, Christina M. Coleman, Daneel Ferreira

All Faculty Scholarship for the College of the Sciences

Continued interest in the chemistry of Dalea spp. led to investigation of Dalea searlsiae, a plant native to areas of the western United States. Methanol extractions of D. searlsiae roots and subsequent chromatographic fractionation afforded the new prenylated and geranylated flavanones malheurans A–D (14) and known flavanones (5 and 6). Known rotenoids (7 and 8) and isoflavones (9 and 10) were isolated from aerial portions. Structure determination of pure compounds was accomplished primarily by extensive 1D- and 2D-NMR spectroscopy. The absolute configurations of compounds 15, 7 …


Novel Insights Into The Mechanisms Of Regulation Of Tyrosine Kinase Receptors By Ras Interference 1, Adriana Galvis Mar 2014

Novel Insights Into The Mechanisms Of Regulation Of Tyrosine Kinase Receptors By Ras Interference 1, Adriana Galvis

FIU Electronic Theses and Dissertations

Receptor-tyrosine kinases (RTKs) are membrane bound receptors characterized by their intrinsic kinase activity. RTK activities play an essential role in several human diseases, including cancer, diabetes and neurodegenerative diseases. RTK activities have been regulated by the expression or silencing of several genes as well as by the utilization of small molecules.

Ras Interference 1 (Rin1) is a multifunctional protein that becomes associated with activated RTKs upon ligand stimulation. Rin1 plays a key role in receptor internalization and in signal transduction via activation of Rab5 and association with active form of Ras. This study has two main objectives: (1) It determines …


Structural Insights Into The Interaction Between A Potent Anti-Inflammatory Protein, Viral Cc Chemokine Inhibitor (Vcci), And The Human Cc Chemokine, Eotaxin-1, Nai-Wei Kuo, Yong-Guang Gao, Megan Schill, Nancy Isern, Cynthia Dupureur, Patricia Liwang Mar 2014

Structural Insights Into The Interaction Between A Potent Anti-Inflammatory Protein, Viral Cc Chemokine Inhibitor (Vcci), And The Human Cc Chemokine, Eotaxin-1, Nai-Wei Kuo, Yong-Guang Gao, Megan Schill, Nancy Isern, Cynthia Dupureur, Patricia Liwang

Chemistry & Biochemistry Faculty Works

Chemokines play important roles in the immune system, not only recruiting leukocytes to the site of infection and inflammation but also guiding cell homing and cell development. The soluble poxvirus-encoded protein viral CC chemokine inhibitor (vCCI), a CC chemokine inhibitor, can bind to human CC chemokines tightly to impair the host immune defense. This protein has no known homologs in eukaryotes and may represent a potent method to stop inflammation. Previously, our structure of the vCCI·MIP-1β (macrophage inflammatory protein-1β) complex indicated that vCCI uses negatively charged residues in β-sheet II to interact with positively charged residues in the MIP-1β N …


Structural Insights Into The Interaction Between A Potent Anti-Inflammatory Protein, Viral Cc Chemokine Inhibitor (Vcci), And The Human Cc Chemokine, Eotaxin-1, Nai-Wei Kuo, Yong-Guang Gao, Megan S. Schill, Nancy Isern, Cynthia M. Dupureur, Patricia J. Liwang Mar 2014

Structural Insights Into The Interaction Between A Potent Anti-Inflammatory Protein, Viral Cc Chemokine Inhibitor (Vcci), And The Human Cc Chemokine, Eotaxin-1, Nai-Wei Kuo, Yong-Guang Gao, Megan S. Schill, Nancy Isern, Cynthia M. Dupureur, Patricia J. Liwang

Cynthia Dupureur

Chemokines play important roles in the immune system, not only recruiting leukocytes to the site of infection and inflammation but also guiding cell homing and cell development. The soluble poxvirus-encoded protein viral CC chemokine inhibitor (vCCI), a CC chemokine inhibitor, can bind to human CC chemokines tightly to impair the host immune defense. This protein has no known homologs in eukaryotes and may represent a potent method to stop inflammation. Previously, our structure of the vCCI·MIP-1β (macrophage inflammatory protein-1β) complex indicated that vCCI uses negatively charged residues in β-sheet II to interact with positively charged residues in the MIP-1β N …


Identification And Characterization Of Protein Phopshatases Regulating The Sma/Mab Pathway In C. Elegans, Sheng Xiong Feb 2014

Identification And Characterization Of Protein Phopshatases Regulating The Sma/Mab Pathway In C. Elegans, Sheng Xiong

Dissertations, Theses, and Capstone Projects

TGF-beta signaling is a conserved signaling pathway among eukaryotes, which controls various normal cellular responses from cell proliferation to cell death. The mutations in its components are found in developmental disorders and cancer. Therefore, this signaling pathway is extensively investigated so that new therapeutic targets could be discovered and novel drugs could be developed. Previous studies suggested the involvement of phosphatases in regulation of TGF-beta signaling, but these studies were performed in cell culture rather than intact organisms. C. elegans is a tractable organism in which to study signaling in vivo. In C. elegans, growth is controled by a conserved …


Metabolic Checkpoints In Cancer Cell Cycle, Mahesh Saqcena Feb 2014

Metabolic Checkpoints In Cancer Cell Cycle, Mahesh Saqcena

Dissertations, Theses, and Capstone Projects

Growth factors (GFs) as well as nutrient sufficiency regulate cell division in metazoans. The vast majority of mutations that contribute to cancer are in genes that regulate progression through the G1 phase of the cell cycle. A key regulatory site in G1 is the growth factor-dependent Restriction Point (R), where cells get permissive signals to divide. In the absence of GF instructions, cells enter the quiescent G0 state. Despite fundamental differences between GF signaling and nutrient sensing, they both have been confusingly referred to as R and therefore by definition considered to be a singular event in G1. Autonomy from …


Lipid Dependence In Ras-Driven Tumors, Darin Salloum Feb 2014

Lipid Dependence In Ras-Driven Tumors, Darin Salloum

Dissertations, Theses, and Capstone Projects

Over past decade, metabolic alterations in cancer cells have received a substantial amount of interest. It had been established that cancer cells undergo a significant amount of metabolic alterations, and some of these alterations are similar to those in normal highly proliferative cells. However, it is becoming more apparent that many of the metabolic alterations are specific to particular oncogenic signaling pathways. Although altered metabolic machinery makes cancer cells more efficient at promoting growth when nutrients are supplied at the sufficient amounts, the dependency of cancer cells on particular metabolic reprogramming deems cancer cells susceptible to disruptions within metabolic network. …


General Transcription Factors Play Dual Roles In Initiation And Termination, Scott Alan Medler Jan 2014

General Transcription Factors Play Dual Roles In Initiation And Termination, Scott Alan Medler

Wayne State University Dissertations

Gene looping, defined as the interaction of the promoter and the terminator regions of a gene during transcription, is emerging as an important gene regulatory mechanism in eukaryotes. The role of promoter bound general transcription factors during initiation is well established. However, recent studies have revealed that some initiation factors also interact with the 3' end of a gene. The biological role of initiation factors at the 3' end of a gene is unknown. The general transcription factors TFIIB and TFIIH have been found to interact genetically with Ssu72, a component of CPF 3' end processing complex. Accordingly, we found …


The Role Of Angiotensinogen In Atherosclerosis And Obesity, Congqing Wu Jan 2014

The Role Of Angiotensinogen In Atherosclerosis And Obesity, Congqing Wu

Theses and Dissertations--Nutritional Sciences

Angiotensinogen is the only known precursor in the renin-angiotensin system, a hormonal system best known as an essential regulator of blood pressure and fluid homeostasis. Angiotensinogen is sequentially cleaved by renin and angiotensin- converting enzyme to generate angiotensin II. As the major effector peptide, angiotensin II mainly function through angiotensin type 1 receptor.

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and more recently renin inhibitors are widely known as the 3 classic renin-angiotensin system inhibitory drugs against hypertension and atherosclerosis. Here, we developed an array of regents to explore the effects of angiotensinogen inhibition. First, we demonstrated that genetic deficiency of …