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

Engineering Of Escherichia Coli 2-Oxoglutarate Dehydrogenase Complex With Mechanistic And Synthetic Goals, Joydeep Chakraborty Aug 2019

Engineering Of Escherichia Coli 2-Oxoglutarate Dehydrogenase Complex With Mechanistic And Synthetic Goals, Joydeep Chakraborty

Dissertations

The Escherichia coli 2-oxoglutarate dehydrogenase complex (OGDHc) compromises multiple copies of three enzymes - 2-oxoglutarate dehydrogenase (E1o), dihydrolipoyl succinyltransferase (E2o), and dihydrolipoyl dehydrogenase (E3). OGDHc is found in the Krebs cycle and catalyzes the formation of the all-important succinyl-Coenzyme A (succinyl-CoA). OGDHc was engineered to understand the catalytic mechanism and optimized for chemical synthetic goals.

Succinyl-CoA formation takes place within the catalytic domain of E2o via a transesterification reaction. The succinyl group from the thiol ester of S8-succinyldihydrolipoyl-E2o is transferred to the thiol group of CoA. Mechanistic studies were designed to investigate enzymatic transthioesterification. His375 and Asp374 was shown to be ...


Roles Of Phospholipases And Ribosomal S6 Kinase In Lipid Remodeling And Growth In Arabidopsis Response To Phosphate Deprivation, Yuan Su Apr 2018

Roles Of Phospholipases And Ribosomal S6 Kinase In Lipid Remodeling And Growth In Arabidopsis Response To Phosphate Deprivation, Yuan Su

Dissertations

Phosphate (Pi) is one of three macronutrients for plants, which is vital for plant growth and development. Understanding the mechanism by which plants respond and adapt to Pi deficiency not only unveils functions of genes and pathways involved, but also provides potential tools to manipulate crops to better stand Pi stress in low Pi-containing lands. One of the significant metabolic changes in plants under Pi starvation is the membrane lipid remodeling that converts Pi-containing lipids such as phospholipids to Pi-free lipids, such as glycolipids. To elucidate the metabolism and regulation of lipid remodeling, this dissertation characterizes the role of two ...


The Characterization Of The Transcription Factor Msab And Its Role In Staphylococcal Virulence, Justin Batte Apr 2018

The Characterization Of The Transcription Factor Msab And Its Role In Staphylococcal Virulence, Justin Batte

Dissertations

Staphylococcus aureus is a common human pathogen that is responsible for a wide range of infections, ranging from relative minor skin infections to life-threatening disease such as bacteremia, septicemia, and endocarditis. S. aureus possesses many different virulent factors that aid in its ability to cause this wide array of infections. One major virulence factor includes the production of capsular polysaccharide (CP). The production of CP plays a major role in the virulence response during infection specifically by providing S. aureus an antiphagocytic mechanism that allows the pathogen to evade phagocytosis during an infection. S. aureus has developed complex genetic regulatory ...


A Discrete Loop In Serca N-Domain Plays A Role In Serca Headpiece Dynamics And Function, Olga N. Raguimova Jan 2018

A Discrete Loop In Serca N-Domain Plays A Role In Serca Headpiece Dynamics And Function, Olga N. Raguimova

Dissertations

The sarco/endoplasmic reticulum calcium ATPase (SERCA) is the major regulator of Ca2+ levels in the cell. Deficient calcium handling in the heart has been linked to heart failure, a leading cause of death in developed countries. As of today, targeting SERCA to enhance cardiac function has not been successful due to lack of details about SERCA structural dynamics during Ca2+ transport.

In my research, I utilized MD simulations and variety of physical assays to determine the role of Nβ5-β6 loop in regulation of SERCA structural dynamics during Ca2+ transport. Previous MD simulations by our lab predicted that the Nβ5-β6 ...


Uncovering The Identity And Metabolism Of Bacterial Coa-Rna, Joseph R. Spangler May 2017

Uncovering The Identity And Metabolism Of Bacterial Coa-Rna, Joseph R. Spangler

Dissertations

Coenzyme A is an indispensable molecule in all known life with roles in metabolism, gene regulation, and macromolecule synthesis. As CoA is derived from RNA itself, it’s incorporation into RNA by in vitro methods has proven useful in research probing the origin of life based on the RNA World theory. The discovery in contemporary bacteria of RNA modified with CoA, however, provided an unexpected twist to previously well-characterized bacterial systems. The identity of sequences associated with CoA-RNA has been elusive since their discovery in 2009 based on the difficulties in isolation while maintaining RNA quality. The aim of this ...


Investigating The Functional Role Of Tick Antioxidants In Hematophagy And Vector Competence, Deepak Kumar Dec 2016

Investigating The Functional Role Of Tick Antioxidants In Hematophagy And Vector Competence, Deepak Kumar

Dissertations

Ticks are obligate hematophagous arthropods and harbor several pathogens which transmit various diseases to humans and their domesticated animals. Host blood- digestion in a tick midgut (MG) generates several reactive oxygen species (ROS), which are extremely toxic to essential macromolecules (e.g. DNA, proteins, and lipids) within the cell, resulting in high oxidative stress. Thus, this dissertation focuses on the questions of how tick homeostasis responds to high oxidative stress, and how ticks and their harbored pathogens survive the high surge of oxidative stress during blood digestion. We are specifically interested in the tick-pathogen, Rickettsia parkeri (R. parkeri, Rp), harbored ...


Characterization Of Glycine Rich Proteins From The Salivary Glands Of The Lone Star Tick Amblyomma Americanum, Rebekah Lynn Bullard May 2016

Characterization Of Glycine Rich Proteins From The Salivary Glands Of The Lone Star Tick Amblyomma Americanum, Rebekah Lynn Bullard

Dissertations

Ticks are blood sucking arthropods that feed on living hosts for up to three weeks. The ticks secrete a multitude of pharmacologically active proteins into the host during feeding which allow the tick to avoid the host immune response, establish a blood pool, and form a firm attachment. The firm attachment is facilitated by the formation of a cement cone which surrounds the tick mouthparts and intertwine between the host skin layers. In this study, gene expression of 44 A. americanum genes was measured throughout the bloodmeal to reveal the differential expression of these genes. Each of the genes tested ...


The Role Of Foxo Transcription Factors In Alcohol-Induced Deficient Fracture Repair, Philip M. Roper Jan 2016

The Role Of Foxo Transcription Factors In Alcohol-Induced Deficient Fracture Repair, Philip M. Roper

Dissertations

Proper and complete repair of a bone fracture is essential in quality of life maintenance, but poor healing and fracture malunion are still medically and socially relevant problems. Alcohol abuse impairs normal fracture healing, leading to delayed or incomplete union. This dissertation aims to clarify mechanisms behind this alcohol-induced impaired healing, thereby elucidating potential methods of intervention.

Alcohol-induced oxidative stress has been linked to many morbidities associated with alcohol abuse. This dissertation elucidates a potential mechanism through which alcohol inhibits fracture healing by increasing oxidative stress. Using a rodent model, I found that alcohol exposure decreases fracture callus formation and ...


The Role Of Microrna In Cardioprotection: Ischemic Preconditioning And Mesenchymal Stem Cell Paracrine Effects, Kristin Luther Jan 2016

The Role Of Microrna In Cardioprotection: Ischemic Preconditioning And Mesenchymal Stem Cell Paracrine Effects, Kristin Luther

Dissertations

Changes in gene expression and protein levels are an important aspect of cardioprotection in which short non-coding RNA known as miRNA may play a key regulatory role. We investigated the functions of several miRNAs in the context of two cardioprotective stimuli, ischemic preconditioning (IPC) and mesenchymal stem cell (MSC) paracrine effects. We hypothesized that downregulation of a set of miRNAs (miR-148a/b, miR-30b, and let-7a*) augments expression of protective heat shock proteins during IPC, and that MSC exosomes transfer miR-21 to cardiomyocytes, resulting in downregulation of pro-apoptotic genes and reduction of infarct size.

IPC increased the level of Hsp70, Hsp90 ...


The Endosomal Sorting Complex Required For Transport Pathway Mediates Chemokine Receptor Cxcr4 Akt Signaling By Promoting Lysosomal Degradation Of Mtor Antagonist Deptor, Rita Ramkaran Verma Jan 2015

The Endosomal Sorting Complex Required For Transport Pathway Mediates Chemokine Receptor Cxcr4 Akt Signaling By Promoting Lysosomal Degradation Of Mtor Antagonist Deptor, Rita Ramkaran Verma

Dissertations

The chemokine receptor CXCR4 is a member of the G protein-coupled receptor (GPCR) family. The cognate ligand for CXCR4 is the C-X-C chemokine known as CXCL12. The CXCL12/CXCR4 signaling axis is essential for a number of developmental processes including organogenesis, vascularization of the GI tract and hematopoiesis. Dysregulated CXCR4 signaling is also implicated in a variety of pathological conditions such as WHIM (Warts, Hypogammaglobunemia, Infections and myelokathexis) syndrome, cardiovascular disease and cancer. Despite its role in several pathologies, the molecular mechanisms mediating CXCR4 signaling are not completely understood. Upon CXCL12 binding to CXCR4, several signaling pathways are activated including ...


Eliminating Acute Myeloid Leukemia Stem Cells By Targeting The Niche Microenviromnent: Co-Inhibition Of Tnf/Il1- Jnk And Nf-Κb, Andrew Volk Jan 2015

Eliminating Acute Myeloid Leukemia Stem Cells By Targeting The Niche Microenviromnent: Co-Inhibition Of Tnf/Il1- Jnk And Nf-Κb, Andrew Volk

Dissertations

Leukemia Stem Cells (LSCs) from Acute Myeloid Leukemia (AML) require the activity of the transcription factor NF-kB to maintain stemness and drive tumor formation. Blocking NF-kB can preferentially eliminate LSCs in vitro with minimal effects on healthy Hematopoietic Stem and Progenitor Cells (HSPCs), making NF-kB a compelling target for anti-leukemia therapies. However, blocking NF-kB in vivo can only extend survival for a short period of time before transplanted mice succumb to the disease. I propose this is due to components of the in vivo niche supporting LSC survival and compensating for the inhibition of NF-kB.

I observed patients with partially ...


The Mir-17-92 Cluster Contributes To Mll Leukemia Development Through The Repression Of The Meis1 Competitor Pknox1, Yousaf Anwar Mian Jan 2015

The Mir-17-92 Cluster Contributes To Mll Leukemia Development Through The Repression Of The Meis1 Competitor Pknox1, Yousaf Anwar Mian

Dissertations

Mixed lineage leukemias have a relatively poor prognosis and arise as a result of translocations between the MLL gene and one of multiple partner genes. Downstream targets of MLL are aberrantly upregulated and include the developmentally important HOX genes and MEIS1, as well as multiple miRNAs, including the miR-17-92 cluster and miR-196b. Here I utilize custom anti-miRNA oligonucleotides to examine the contribution of specific miRNAs to MLL leukemias both as individual miRNAs and in cooperation with other miRNAs. Combinatorial treatment with antagomirs against miR-17 and miR-19a of the miR-17-92 cluster dramatically reduces colony forming ability of MLL-fusion containing cell lines ...


Characterization And Role Of Msaabcr In Biofilm Development And Virulence In Staphylococcus Aureus, Gyan Sundar Sahukhal Dec 2014

Characterization And Role Of Msaabcr In Biofilm Development And Virulence In Staphylococcus Aureus, Gyan Sundar Sahukhal

Dissertations

Community-acquired, methicillin-resistant Staphylococcus aureus strains often cause localized infections in immune-compromised hosts, but some strains show enhanced virulence leading to severe infections even among healthy individuals with no predisposing risk factors. The genetic basis for this enhanced virulence has yet to be determined. S. aureus possesses a wide variety of virulence factors, the expression of which is carefully coordinated by a variety of regulators. Several virulence regulators have been well characterized, but others have yet to be thoroughly investigated. Previously, the msa gene as a regulator of several virulence genes, biofilm development, and antibiotic ...


Antiviral Responses In Mouse Embryonic Stem Cells: Differential Development Of Cellular Mechanisms In Type I Interferon Production And Response, Ruoxing Wang Aug 2014

Antiviral Responses In Mouse Embryonic Stem Cells: Differential Development Of Cellular Mechanisms In Type I Interferon Production And Response, Ruoxing Wang

Dissertations

Embryonic stem cells (ESCs) have been recognized as a promising cell source for regenerative medicine. Intensive research over the past decade has led to the possibility that ESC-derived cells will be used for the treatment of human diseases. However, increasing evidence indicates that ESC-derived cells generated by the current differentiation methods are not fully functional. It is recently recognized that ESC-derived cells lack innate immunity to a wide range of infectious agents and inflammatory cytokines. When used in patients, ESC-derived cells would be placed in wounded sites that are exposed to various pathogens and inflammatory cytokines; therefore, their viability and ...


The Role Of Af9 And Af9-Mediated Protein Interactions In Hematopoiesis And Leukemogenesis, Alyson Anne Lokken Jan 2014

The Role Of Af9 And Af9-Mediated Protein Interactions In Hematopoiesis And Leukemogenesis, Alyson Anne Lokken

Dissertations

The AF9 protein is one of the most common chromosomal translocation partners of the MLL gene in MLL leukemia. Wild-type AF9 is a member of the pTEFb transcription elongation complex, and interacts with gene regulatory proteins such as AF4/AF5q31, DOT1L, Pc3/CBX8 and BCoR. These interactions are retained in the oncogenic MLL-AF9 fusion protein, and may be required for leukemic transformation.

Using bone marrow progenitor cells isolated from conditional Af9 knockout mice, we examined in vitro differentiation of hematopoietic progenitor cells to the erythroid, myeloid and megakaryocytic lineages in the presence or absence of Af9. Based on previously published ...


Investigating The Role Of The Pgf2 Alpha/Calcineurin-Signaling Pathway In The Regulation Of Adipogenesis, Damodaran Annamalai Jan 2014

Investigating The Role Of The Pgf2 Alpha/Calcineurin-Signaling Pathway In The Regulation Of Adipogenesis, Damodaran Annamalai

Dissertations

Prostaglandin F2α (PGF2α) is a potent physiological inhibitor of adipocyte differentiation. In previous studies, we demonstrated that PGF2α inhibits adipogenesis via activation of the calcium-regulated protein phosphatase, calcineurin. In this current study, we have now extended these findings to identify the IL-11 cytokine and the Nurr1 orphan nuclear hormone receptor as functionally important downstream transcriptional targets of the PGF2α/calcineurin-pathway involved in the inhibition of adipocyte differentiation. In the case of IL-11, we show that this cytokine acts in an autocrine fashion to inhibit adipogenesis via the essential actions of the gp130 cytokine co-receptor signaling subunit. Further, by using a ...


Targeting The Notch-1/Igf-1r/Akt Axis In At Orthotopic Model Of Advanced Non-Small Cell Lung Cancer, Shuang Liang Jan 2013

Targeting The Notch-1/Igf-1r/Akt Axis In At Orthotopic Model Of Advanced Non-Small Cell Lung Cancer, Shuang Liang

Dissertations

Lung cancer is the leading cause of cancer death in the U.S. and worldwide. The most frequent type of lung cancer is non-small cell lung cancer (NSCLC). NSCLC is mostly diagnosed at advanced stages (stage IIIB 18% of cases, stage IV 40% of cases) due to the lack of effective early detection methods. Thus, the discovery of alternative therapeutic strategies is of extreme importance.

Others and we have previously found that Notch signaling plays a crucial role in NSCLC. Our preliminary results indicate that Notch-1 provides necessary survival signals to NSCLC cells by positively regulating IGF-1R to activate the ...


Novel Role Of Erbb-2 In Inhibition Of Jagged-1-Mediated Trans-Activation Of Notch In Breast Cancer, Kinnari Pandya Jan 2013

Novel Role Of Erbb-2 In Inhibition Of Jagged-1-Mediated Trans-Activation Of Notch In Breast Cancer, Kinnari Pandya

Dissertations

The ErbB-2 gene is amplified and the resulting protein product overexpressed in 15-30% of breast tumors, and associated with aggressive behavior and poor overall survival. Currently, there are two FDA approved therapies targeting ErbB-2 for the treatment of ErbB-2 positive breast cancer: trastuzumab, a humanized monoclonal antibody is directed against the extracellular domain of ErbB-2 and lapatinib, a dual EGFR/ErbB-2 tyrosine kinase inhibitor. Unfortunately, anti-ErbB-2 therapy resistance remains a major problem in metastatic breast cancer. Our data suggested that gene amplification or overexpression of ErbB-2 inhibits Notch-1 transcriptional activity and trastuzumab or lapatinib increased

Notch-1 transcriptional activity. Furthermore, Notch-1 ...


Significance Of Protein Interactions In Mediating Af9 Function, Bhavna Malik Jan 2013

Significance Of Protein Interactions In Mediating Af9 Function, Bhavna Malik

Dissertations

Rearrangements of the MLL gene at chromosome band 11q23 have been associated with a heterogeneous group of lymphoid, myeloid and mixed lineage leukemias. MLL rearrangements occur approximately in 70% of infant leukemias and are also common in therapy-related leukemias where patients were previously treated with topoisomerase II inhibitors. Unfortunately, these patients have a poor prognosis. MLL gene rearrangements give rise to chimeric proteins that contain the N-terminal portion of MLL fused to the C-terminal portion of over 50 different fusion partners. The chimeric proteins cause constitutive expression of some MLL target genes such as HOXA9 and MEIS1, and enhanced proliferation ...


Molecular Functions Of Mll Phd3 Binding To Its Ligands Cyp33 And H3k4me3, Gayathree Raman Jan 2013

Molecular Functions Of Mll Phd3 Binding To Its Ligands Cyp33 And H3k4me3, Gayathree Raman

Dissertations

Mixed Lineage Leukemia protein (MLL) is required for proper embryonic development, and hematopoiesis. It is a SET domain containing histone methyl transferase that trimethylates histone H3 on lysine 4 (H3K4Me3), a histone modification that correlates with active transcription. The 3rd PHD finger of MLL binds to H3K4me3. Thus MLL is a "writer" with an embedded "reader" for H3K4Me3. Cyp33 is another known ligand of MLL PHD3. Over expression of Cyp33 results in transcriptional repression of MLL target genes.

The aim of this study is to determine the biological function of MLL PHD3 binding to H3K4Me3 or Cyp33. Cyp33 binding to ...


A Study Of The Therapeutic Potential Of Af4 Mimetic Peptides, Nisha N. Barretto Jan 2013

A Study Of The Therapeutic Potential Of Af4 Mimetic Peptides, Nisha N. Barretto

Dissertations

Mixed lineage leukemias (MLL) are a group of acute and aggressive leukemias. They account for over 70% of infant leukemias, and 10% of acute adult leukemias. Pediatric ALL and therapy related MLL leukemias carry poor prognosis in spite of several advancement in the field of leukemia research. Therefore, new therapies for MLL leukemias are needed.

Majority of MLL leukemias arise due to the balanced translocations of the MLL gene. As a result of these translocations, chimeric MLL fusion proteins are expressed. The most frequently occurring MLL fusion proteins are known to aberrantly recruit the super elongation complex (SEC) resulting in ...


Molecular Mechanisms Regulating Chemokine Receptor Cxcr4 Signaling And Trafficking, Rohit Malik Jan 2012

Molecular Mechanisms Regulating Chemokine Receptor Cxcr4 Signaling And Trafficking, Rohit Malik

Dissertations

CXCR4 is a G protein-coupled receptor (GPCR) that binds to the chemokine, stromal cell-derived factor-1 (SDF-1alpha; a.k.a. CXCL12). The SDF-1alpha/CXCR4 signaling axis plays an essential role during embryogenesis in the development of the heart, brain and vasculature and in the adult mediating immune cell trafficking and stem cell homing to the bone marrow. Dysregulation of SDF-1alpha/CXCR4 signaling is linked to several pathological conditions, including cardiovascular disease, immunological disorders as well as cancer growth and metastasis. However, the mechanisms that govern CXCR4 signaling remain poorly understood. In this dissertation project, we attempt to further our understanding of ...


The Role Of Cyp33 In Mll Mediated Gene Repression, Steven D. Poppen Jan 2012

The Role Of Cyp33 In Mll Mediated Gene Repression, Steven D. Poppen

Dissertations

Mixed Lineage Leukemia (MLL) is a multidomain protein whose gene is translocated in a subset of AML leukemias. Translocation of the MLL gene is present in approximately five percent of adult acute leukemias and ten percent of pediatric leukemias (Daser, A 2004, Look, A 1997, Huret, J 2001) Patients presenting in the clinic at the time of diagnosis with an MLL fusion have been shown to respond poorly to treatment and have a worse prognosis than matched wild type MLL patients (Rubnitz, J 1994, Rubnitz, J 1999). Novel therapies therefore are needed in order to more effectively treat patients with ...


The Specific Role Of The Mll Cxxc Domain In Mll Fusion Protein Function, Laurie Ellen Risner Jan 2011

The Specific Role Of The Mll Cxxc Domain In Mll Fusion Protein Function, Laurie Ellen Risner

Dissertations

The MLL gene was first identified because it is involved in chromosome translocations which produce novel fusion proteins that cause leukemia. The CXXC domain of MLL is a cysteine rich DNA binding domain with specificity for binding unmethylated CpG-containing DNA. The CXXC domain is retained in oncogenic MLL fusions, and is absolutely required for the fusions to cause leukemia. This project explored the role of the CXXC domain by introducing structure-informed point mutations within the MLL CXXC domain that disrupt DNA binding, and by performing domain swap experiments in which different CXXC domains from other proteins, including DNMT1, CGBP and ...


Repression Of Protein Kinase C Delta In Human Squamous Cell Carcinomas By Ras, Fyn And Nf-Kappa B Signaling, Vipin Yadav Jan 2011

Repression Of Protein Kinase C Delta In Human Squamous Cell Carcinomas By Ras, Fyn And Nf-Kappa B Signaling, Vipin Yadav

Dissertations

The delta isoform of Protein Kinase C (PKC-delta) is widely expressed in many normal tissues, including epidermal keratinocytes, and has a critical role in UV-induced apoptosis. However, PKC-delta is frequently lost in chemically or UV-induced mouse skin tumors, as well as in human cutaneous squamous cell carcinomas (SCC). Furthermore, re-expression of PKC-delta in human SCC lines is sufficient to induce apoptosis and suppress tumorigenicity, making PKC-delta a potential tumor suppressor gene for SCCs. The objective of this dissertation is to investigate the mechanism of PKC-delta loss in human SCCs.

To determine the mechanism of PKC-delta loss in human SCCs, we ...


Role Of Notch Signaling In T Cell Polarization, Shilpa Keerthivasan Jan 2011

Role Of Notch Signaling In T Cell Polarization, Shilpa Keerthivasan

Dissertations

The differentiation of CD4+ T cells to different effector lineages in response to pathogenic stimuli is the core of the adaptive immune system. One of the effector subsets recently discovered is Thelper 17 (Th17) and it plays a predominant role in autoimmune diseases and inflammatory disorders.

In my thesis, I aimed to study the role of Notch cell surface receptors in Th17 differentiation. Using in vitro Th17 differentiation assays of human naïve CD4+ T cells, I have shown that Notch signaling, particularly Notch1, plays a crucial role in Th17 polarization. By using pharmacological inhibitors and specific knockdown of Notch1, I ...


Molecular, Cellular And Systemic Effects Of Atrazine On The Xenopus Laevis Tadpole, Renee Maryanne Zaya Jan 2011

Molecular, Cellular And Systemic Effects Of Atrazine On The Xenopus Laevis Tadpole, Renee Maryanne Zaya

Dissertations

Atrazine is one of the two most commonly used herbicides in the US and it is the most studies are among the first to link physiological effects of atrazine to changes in tissue and gene expression in Xenopus laevis tadpoles. These studies provide the groundwork for future studies into the mechanisms behind responses to chemical stressors generating data resulting in a better understanding of how these chemicals affect us all. commonly found herbicide in ground water. As a result, a great deal of attention has been placed on its use and safety. It has also been implicated to play a ...


Lysine Specific Demethylase-1 And The Brahma Chromatin Remodeling Complex Regulate Conserved Signaling Pathways During Drosophila Wing Development, Brenda Jean Curtis Jan 2010

Lysine Specific Demethylase-1 And The Brahma Chromatin Remodeling Complex Regulate Conserved Signaling Pathways During Drosophila Wing Development, Brenda Jean Curtis

Dissertations

The conserved SWI/SNF chromatin remodeling complex uses the energy from ATP hydrolysis to alter local chromatin environments by disrupting DNA-histone contacts. The Drosophila SWI/SNF counterpart, the Brahma complex, has been shown to have an essential role in regulating the proper expression of many developmentally important genes, including those required for eye and wing tissue morphogenesis. A temperature sensitive mutation in one of the core subunits, SNR1 (SNF5/Ini1/SMARC B1), results in reproducible wing patterning phenotypes that can be enhanced and suppressed by extragenic mutations. SNR1 functions as a regulatory subunit to modulate chromatin remodeling activities of the ...


Developmental Characterization Of Cara Mitad: A Drosophila Nuclear Receptor Co-Regulator, Chhavi Chauhan Jan 2010

Developmental Characterization Of Cara Mitad: A Drosophila Nuclear Receptor Co-Regulator, Chhavi Chauhan

Dissertations

In insects and vertebrates, hormone titers drive cellular proliferation and differentiation events that guide proper development. Nuclear receptors (NR) respond to these hormone signals by activating cascades of gene expression, along with coregulator protein complexes. In Drosophila melanogaster, fluctuating titers of the steroid hormone ecdysone are responsible for coordinating the timing of organismal development. Despite major advances in our understanding of Drosophila NR activities, we lack essential knowledge of the coregulators that are required for their proper function.

We have recently identified the Drosophila cara mitad (cmi) (`dear half') gene. The deduced CMI protein is closely related to the N-terminal ...


The Role Of Igf-1 And Notch Signaling In Thoracic Malignancies., Sandra Eliasz Jan 2010

The Role Of Igf-1 And Notch Signaling In Thoracic Malignancies., Sandra Eliasz

Dissertations

Thoracic malignancies are one of the deadliest of all cancers, being the leading cause of cancer death in the Western world. Thoracic malignancies arise from different tissues; however the most common are of epithelial (commonly referred to as non-small cell lung cancer, or NSCLC), neuroendocrine (small cell lung cancer, or SCLC) and mesothelial origin (malignant mesothelioma, or MM). The DNA oncogenic virus Simian Virus 40 (SV40) has been shown to cooperate with environmental oncogenic fibers in the onset of MM. Insulin like growth factor-1 (IGF-1) signaling plays a central role in all thoracic malignancies and in the process of SV40-mediated ...