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Articles 1621 - 1650 of 1904

Full-Text Articles in Life Sciences

Ion Channel Modulation By Photocaged Dioctanoyl Pip2, Junghoon Ha Aug 2009

Ion Channel Modulation By Photocaged Dioctanoyl Pip2, Junghoon Ha

Theses and Dissertations

Phosphatidylinositol bisphosphate (PIP2) directly regulates electrophysiological activity in a diverse family of ion channels whether the effect is stimulatory or inhibitory. Much has been unveiled about the apparent affinity and modulatory function of PIP2 using a chemically modified dioctanoyl PIP2 (diC8), a membrane delimited cytosolic co-factor in inside-out macropatch experiments. Yet, the scarcity of molecular tools that permit fine external control in whole-cell systems has precluded future studies from probing the physiological role of PIP2 in cells in the presence of a fully intact cytoplasm. Here we introduce light as an external control for PIP2 through photocaging of diC8, and …

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Marrying Immunotherapy And Chemotherapy: A Cancer Therapy Based On T Lymphocyte Expansion Augmented By Alternate Gamma Chain Cytokines And Gemcitabine-Mediated Inhibition Of Myeloid Derived Suppressor Cells, Esther Cha Aug 2009

Marrying Immunotherapy And Chemotherapy: A Cancer Therapy Based On T Lymphocyte Expansion Augmented By Alternate Gamma Chain Cytokines And Gemcitabine-Mediated Inhibition Of Myeloid Derived Suppressor Cells, Esther Cha

Theses and Dissertations

Successful adoptive immunotherapy (AIT) for cancer relies on the infusion of in vitro expanded, tumor-reactive lymphocytes with a goal of generating productive tumor immunity. Previously, our lab has developed a protocol to activate selectively tumor-reactive T lymphocytes in vitro using two pharmacologic agents, bryostatin-1 and ionomycin. Following the pharmacological stimulation, conventionally, IL-2 is added to stimulate in vitro proliferation. In this report, alternate cytokines from the common cytokine receptor γ-chain family, namely IL-7 and IL-15, were explored as the alternative cytokine supplements. We found that tumor DLN cells activated in vitro with B/I and cultured in IL-7/15 alternate common γ-chain …

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Schizophrenia Candidate Genes Study, Grace Lee Jul 2009

Schizophrenia Candidate Genes Study, Grace Lee

Theses and Dissertations

Schizophrenia is a debilitating disorder caused by the interaction of genetic and environmental factors. In this study, we identified candidate genes and single nucleotide polymorphisms from two genome-wide association studies, GAIN and CATIE. Nine SNPs representing four candidate genes were selected for replication studies with our Irish samples: Irish Case-Control Study of Schizophrenia (ICCSS), the Irish Study of High-Density Schizophrenia Families (ISHDSF), and the Irish Trio Study of Schizophrenia (ITRIO). In the ITRIO sample, rs4704591 (CMYA5 gene) showed nominal significance (p = 0.0447947). Combining ICCSS, ISHDSF, and ITRIO samples for rs4704591 increased sample size and power and yielded a p-value …

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Evaluation Of Association Of Microrna-122 With Histological Severity Of Recurrent Hcv Infection In Liver Transplant Recipients, Jihee Suh Jul 2009

Evaluation Of Association Of Microrna-122 With Histological Severity Of Recurrent Hcv Infection In Liver Transplant Recipients, Jihee Suh

Theses and Dissertations

Hepatitis C virus recurrence (which is defined by detection of HCV RNA in serum) in post-transplanted liver is universal but the progression of infection remains unpredictable, varying from case to case. It has been estimated that 75%-80% of the HCV recurrence patients will suffer chronic hepatitis C infection and up to a third of them will progress into the development of fibrosis and cirrhosis within 5 years post-transplantation. Therefore, finding ways to predict early on the progression of fibrosis can contribute to better prognoses. Recent literatures have mentioned that the hepatitis C virus relies on the host microRNA-122 (miR-122) for …

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Lysophosphatidic Acid Is A Mediator Of Interleukin-6 Production In Ovarian Cancer Cells, David Dang Jul 2009

Lysophosphatidic Acid Is A Mediator Of Interleukin-6 Production In Ovarian Cancer Cells, David Dang

Theses and Dissertations

Lysophosphatidic acid (LPA) is a naturally occurring bioactive lysophospholipid that mediates a broad range of cellular processes such as cell proliferation, survival, migration and invasion. LPA also plays a potential role in human oncogenesis as suggested by elevated expression of its receptors and its producing enzymes in malignant tissues. In the current study, we demonstrated that LPA is a potent mediator of interleukin-6 (IL-6) production in ovarian cancer. IL-6 is a pleiotropic cytokine which is thought to be an important mediator of ovarian cancer development and progression. Here, we demonstrated that IL-6 levels are indeed increased in the plasma of …

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Effects Of Biofilm Age And Composition On Oyster Larval Setting, Alaina Hart Jul 2009

Effects Of Biofilm Age And Composition On Oyster Larval Setting, Alaina Hart

Theses and Dissertations

The lack of success in restoring oyster, Crassostrea virginica, populations to Chesapeake Bay and its tributaries has raised many questions about why many restoration efforts have failed. A number of studies have focused on the larval stage of oysters and considered the variables that impact oyster setting behavior in an effort to understand why oyster populations have not recovered. Studies that have examined setting surfaces suggest that biofilms promote oyster larval settlement; however, similar studies with barnacle larvae have found an inhibitory relationship. The present study utilized field-produced biofilms of different ages to determine if natural biofilms inhibit or promote …

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A Cellular Mechanism For Dendritic Spine Loss Following Traumautic Brain Injury In Rat, Brian Low Jul 2009

A Cellular Mechanism For Dendritic Spine Loss Following Traumautic Brain Injury In Rat, Brian Low

Theses and Dissertations

Traumatic brain injury is a leading cause of death and disability in the United States. The injury is often composed of two processes: the primary injury, which can involve irreversible loss of tissue, and the secondary injury, which involves a cascade of reactive processes such as excitotoxicity that occur in the hours and days after the initial insult. Excitotoxic stimulation of neuronal circuits can lead to cellular dysfunction and modulation of neuronal sensitivity. One mechanism of dysfunction involves the calcium-regulated phosphatase, calcineurin. Calcineurin has been shown to be involved in the modulation of the neuronal post-synaptic structures known as dendritic …

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Role Of Endothelin-1 In The Regulation Of The Swelling-Activated Cl- Current In Atrial Myocytes, Wu Deng Jul 2009

Role Of Endothelin-1 In The Regulation Of The Swelling-Activated Cl- Current In Atrial Myocytes, Wu Deng

Theses and Dissertations

Swelling-activated Cl- current (ICl,swell) is an outwardly rectifying Cl- current that influences cardiac electric activities and acts as a potential effector of mechanoelectrical feedback that antagonizes the effects of stretch-activated cation channels. Persistent activation of ICl,swell has been observed in multiple models of cardiovascular diseases. Previously we showed that angiotensin II (AngII) signaling and reactive oxygen species (ROS) produced by NADPH oxidase (NOX) are involved in the activation of ICl, swell by both beta1-integrin stretch and osmotic swelling. Because endothelin-1 (ET-1) is a potential downstream mediator of AngII and ETA receptor blockade abrogates AngII-induced ROS generation, we studied how ET-1 …

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Genetic Differentiation Of The Parasitoid, Cotesia Congregata (Say), Based On Host-Plant Complex, Georgia Karns Jul 2009

Genetic Differentiation Of The Parasitoid, Cotesia Congregata (Say), Based On Host-Plant Complex, Georgia Karns

Theses and Dissertations

Endoparasitoids of herbivorous lepidopterans have intimate relationships with their host species as well as the plant on which their host develops. Characteristics of both hosts and plants can affect parasitoid success in tri-trophic systems and thus, drive diversification. Genetic differentiation was estimated for Cotesia congregata (Say) collected from two distinct host-plant complexes, Manduca sexta L. on tobacco (Nicotiana tabacum L.) and Ceratomia catalpae, (Haworth) on catalpa (Catalpa bignonioides Walker), in the mid-Atlantic region of North America using seven microsatellite loci and the mitochondrial COI locus. Microsatellite allele frequencies were differentiated based on host-plant complex, and COI haplotypes from individuals on …

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The Regulation Of Platelet Activating Factor Acetylhydrolase By Oxidized Phospholipids, Rachael Griffiths Jul 2009

The Regulation Of Platelet Activating Factor Acetylhydrolase By Oxidized Phospholipids, Rachael Griffiths

Theses and Dissertations

Platelet-activating factor acetylhydrolase (PAFAH) is elevated in atherosclerosis and may play a role in pathogenesis of this disease. Molecular mechanisms regulating the expression of this lipoprotein-associated PLA2 are indistinct. Mildy oxidized low density lipoprotein (oxLDL) and monocytes (the primary source of PAFAH) are co-localized in early atheromas. Monocytes are activated by oxidized phospholipids (oxPL) in the oxLDL particle. We hypothesized that oxPL-activated monocytes are the source of increased levels of PAFAH in atherosclerosis. We found that PAFAH expression is significantly induced by OxPAPC and in particular long-chain fractions of oxPAPC in monocytes and cytokine-differentiated DC, but not cytokine-differentiated MO. Furthermore, …

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Assessment Of Pre-Pcr Whole Genome Amplification Of Single Pollen Grains Using Flowering Dogwood (Cornus Florida), Candace Dillon Jul 2009

Assessment Of Pre-Pcr Whole Genome Amplification Of Single Pollen Grains Using Flowering Dogwood (Cornus Florida), Candace Dillon

Theses and Dissertations

Studies of gene flow in natural plant populations often focus on either historical or abiotic dispersal methods (e.g. wind, water, gravity), but there is little information available on contemporary, animal-mediated pollen dispersal patterns. Emerging molecular laboratory techniques allow unprecedented insights into spatial patterns of pollen-mediated gene flow. However, to date, technical challenges have limited their widespread application. The genome of a pollen grain can be amplified via whole genome amplification (WGA) prior to traditional amplification via polymerase chain reaction (PCR) to prevent the stochastic effects associated with low copy number amplification. Even still, WGA can suffer from low success rates …

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Understanding The Genetic Consequences Of Rapid Range Expansion: A Case Study Using The Invasive Microstegium Vimineum Trin. (Poaceae), Stephen Baker Jul 2009

Understanding The Genetic Consequences Of Rapid Range Expansion: A Case Study Using The Invasive Microstegium Vimineum Trin. (Poaceae), Stephen Baker

Theses and Dissertations

Global temperature changes are predicted to influence the distributions of plants and can have significant consequences for population genetic structure. Both the nature of these consequences and the processes that shape them are of interest for both conservation genetics and the development of realistic management programs. Rapid range expansion occurs on short temporal scales not conducive to conventional phylogeographical analyses. This paper presents the findings from a population genetic study of the invasive grass Microstegium vimineum Trin. A. Camus throughout the James River Basin of Virginia. Genotypic analysis using Amplified Fragment Length Polymorphism (AFLP) molecular markers were used to test …

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The Genome Scale Metabolic Model Of Cryptosporidium Hominis: Inv209, Niti Vanee Jul 2009

The Genome Scale Metabolic Model Of Cryptosporidium Hominis: Inv209, Niti Vanee

Theses and Dissertations

The apicomplexan Cryptosporidium is a protozoan parasite of humans and other mammals. Cryptosporidium species cause acute gastro-enteritis and diarrheal disease in healthy humans and animals, and cause life-threatening infection in immuno-compromised individuals such as people with AIDS. It has a one-host life cycle and invades intestinal epithelial cells causing diarrhea, or more rarely the pulmonary epithelium. Cryptosporidium carries out all the asexual reproductive stages like several other apicomplexans. Current annotation of this organism predicts it to contain 3884 genes of which only 1581 genes have predicted functions. By using a combination of bioinformatics analysis, biochemical evidence, and high-throughput data, a …

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Adaptation At A Shortened Length In Rabbit Femoral Artery, Melissa Bednarek Jul 2009

Adaptation At A Shortened Length In Rabbit Femoral Artery, Melissa Bednarek

Theses and Dissertations

It is well known that the overlap between the thick and thin filaments in striated muscle is responsible for the single active length-tension (L-T) curve. With the lack of visible striations, a sarcomeric unit has not been identified in smooth muscle. Though once thought to function like striated muscle via a sliding filament mechanism of contraction, recent studies on length-adaptation (L-adaptation) in airway smooth muscle (ASM), in which increased tension is generated with repeated contraction, have led to the hypothesis of a dynamic L-T curve in smooth muscle. Although more established in ASM, two studies have shown L-adaptation in vascular …

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Analysis Of Secreted Phosphoprotein-24 And Its Effects During Osteoblast Differentiation In A Mesenchymal Stem Cell Model, Vasquez Jochen Granja Jul 2009

Analysis Of Secreted Phosphoprotein-24 And Its Effects During Osteoblast Differentiation In A Mesenchymal Stem Cell Model, Vasquez Jochen Granja

Theses and Dissertations

Musculoskeletal diseases, in particular osteoporosis, are increasingly becoming more prevalent in the U.S. due to the ageing population (Figure1). It is estimated that one-sixth of 300 million people in U.S. suffer from bone disorders or loss. About 10 million of those people above age 50 suffer from osteoporosis. Patients that suffer from osteoporosis have high morbidity and mortality rates. For instance, patients have decreased bone mineral density (BMD), a measurement of bone density that reflects the strength of bone as represented by calcium content. A decrease in BMD typically leads to an increased risk of bone fractures. In particular, hip …

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An Evaluation Of Bacterial And Fungal Contributions To Organic Matter Decomposition Along A Soil Moisture Gradient, Morgan Rawls Jul 2009

An Evaluation Of Bacterial And Fungal Contributions To Organic Matter Decomposition Along A Soil Moisture Gradient, Morgan Rawls

Theses and Dissertations

The decomposition of plant litter is a critical biological function that aids in nutrient cycling and energy transfers within and between ecosystems. The primary decomposers of dead leaf material are bacteria and fungi, though there is no consensus as to which of these groups is dominant, nor is it known how the abundance and composition of these communities changes over time. The objectives of this study were to examine the relative contributions of bacterial and fungal populations to leaf organic matter (OM) decomposition and to consider the effect of moisture availability on the microbial community. The study was conducted across …

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Intracellular Targets Of Sphingosine-1-Phosphate, Graham Michael Strub Jul 2009

Intracellular Targets Of Sphingosine-1-Phosphate, Graham Michael Strub

Theses and Dissertations

The bioactive lipid mediator sphingosine-1-phosphate (S1P) has emerged as a key regulator of a variety of important physiological functions, including cell growth, cell survival, cell motility, angiogenesis, lymphocyte trafficking, and mast cell function. S1P is formed by two different sphingosine kinases (SphKs) and binds to a family of 5 differentially expressed G-protein coupled receptors (S1PRs). The majority of research to date has focused on the activation of these receptors, but there is compelling evidence to suggest that S1P exerts intracellular functions independent of S1PRs. However no bona fide intracellular targets of S1P have been identified. In my dissertation, I have …

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Synergistic Growth Inhibition And Enhancement Of Cell Death By Combination Of Melanoma Differentiation Associated Gene-7 (Mda-7/Il-24) And Cisplatin In Ovarian Cancer Cell Lines, Renyan Liu Jul 2009

Synergistic Growth Inhibition And Enhancement Of Cell Death By Combination Of Melanoma Differentiation Associated Gene-7 (Mda-7/Il-24) And Cisplatin In Ovarian Cancer Cell Lines, Renyan Liu

Theses and Dissertations

Ovarian cancer is the most lethal gynecological malignancy among women. The current first-line treatments for ovarian cancer are cisplatin, carboplatin and paclitaxel. However, resistance to these platinum-based drugs occurs in the large majority of initially responsive tumors, resulting in fully chemoresistant, fatal disease. Therefore, the resistance to cisplatin therapy has been a critical hurdle in the management of recurrent ovarian cancer. The mechanisms responsible for cisplatin resistance are not completely understood. In the search for new therapies to overcome/bypass cisplatin resistance, melanoma differentiation gene-7 (MDA-7) IL-24, which is a new cytokine, has anti-cancer efficacy by suppressing cell growth and inducing …

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Sphingosine Kinase 1 Inhibitor, A Novel Inducer Of Autophagy, Daniel Meza Jul 2009

Sphingosine Kinase 1 Inhibitor, A Novel Inducer Of Autophagy, Daniel Meza

Theses and Dissertations

Autophagy is the process of “cell self-eating” which has been implicated both in cell survival and cell death. Sphingosine kinase 1 (SphK1) regulates the intracellular balance between ceramide and sphingosine, bioactive lipids associated with cell death, and sphingosine-1-phosphate (S1P), whose actions are associated with survival and proliferation. Previous studies have implicated upregulation of SphK1 in the induction of autophagy. In this study, SK1-I, a SphK1 specific competitive inhibitor, induced autophagy in a concentration and time dependent manner in HCT116 colorectal carcinoma cells. This autophagic response was observed to be more intense in wild type p53 expressing HCT116 cells than in …

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Presence Of Haemosporidia And Flaviviruses In Breeding Prothonotary Warblers (Protonotaria Citrea): An Analysis Of Spatial And Temporal Trends In Infection Prevalence And Associations With Reproductive Success, Elena Grillo Jul 2009

Presence Of Haemosporidia And Flaviviruses In Breeding Prothonotary Warblers (Protonotaria Citrea): An Analysis Of Spatial And Temporal Trends In Infection Prevalence And Associations With Reproductive Success, Elena Grillo

Theses and Dissertations

As Neotropical migratory birds, Prothonotary Warblers are exposed to parasites in both tropical and temperate regions and may act as dispersal agents between geographic areas. This study identifies the prevalence of Haemosporidia, West Nile Virus (WNV), and St. Louis Encephalitis virus (SLEV) in this species. A total of 71.6% of captured Prothonotary Warblers were infected with Haemosporidia during the 2008 breeding season, and infection prevalence increased throughout the season. This temporal change in prevalence is likely due to infection relapse and transmission of new infections. No correlations between reproductive effort and infection status were observed, nor were any associations between …

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Investigating The Role Of Electric Fields In Directing Schwann Cell Behavior, Nishant Magar Jun 2009

Investigating The Role Of Electric Fields In Directing Schwann Cell Behavior, Nishant Magar

Theses and Dissertations

This study examines the potential of Schwann cells (SCs) to be manipulated by electric fields (EFs) in order to improve recovery from spinal cord injury (SCI). It had long been believed that the central nervous system (CNS) is incapable of regeneration, but recent studies have proven otherwise. SC transplants are known to be useful in promoting axon regeneration after SCI, but is not sufficient for functional recovery. EFs are known to exist in vivo, and have been known to drastically affect the morphology and behavior of cells in various tissues. It was the hypothesis of this study that the conditioning …

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Expression Of Chemokines And Vegfs In Hnscc, Crystal Cunningham May 2009

Expression Of Chemokines And Vegfs In Hnscc, Crystal Cunningham

Theses and Dissertations

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. The 5-year survival rate when the cancer remains as a primary tumor is 81% but when it metastasizes to distant sites, defined as a metastatic cancer, it decreases dramatically to 26%. Approaches to prevent these cancers from undergoing these metastatic changes can greatly improve the survival and outcome of these cancer victims. This current study is examining the expression profiles of chemokines and VEGFs in HNSCC. By investigation the underlying pathways involved in the expressions of chemokines and VEGFS we hope to sort out the transcriptional …

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Predator And Abiotic Effects On Hatching Phenotype And Survival Of Arboreal Frog Eggs With Implications For Phytoplankton, Jessica Hite May 2009

Predator And Abiotic Effects On Hatching Phenotype And Survival Of Arboreal Frog Eggs With Implications For Phytoplankton, Jessica Hite

Theses and Dissertations

Historically studies have focused on either the terrestrial or aquatic environments independently. However, these systems are inherently linked through numerous pathways including organisms with complex life cycles. Both abiotic factors and predators of these organisms can influence connections by changing the number of prey moving across habitat boundaries and by changing the phenotype of prey. When the focal organisms are primary consumers, these effects may have important implications for ecosystem processes. My study investigated how terrestrial predators and abiotic factors affect the number and phenotype of herbivorous tadpole inputs into a tropical forest pond. I found that predators and abiotic …

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The Small Molecule Bcl-2 Inhibitor Ha14-1 Potentiates The Lethality Of A Regimen Combining Mek1/2 And Chk1 Inhibitors In Multiple Myeloma Cells, Leena Youssefian May 2009

The Small Molecule Bcl-2 Inhibitor Ha14-1 Potentiates The Lethality Of A Regimen Combining Mek1/2 And Chk1 Inhibitors In Multiple Myeloma Cells, Leena Youssefian

Theses and Dissertations

Previously, we have found that the co-administration of MEK1/2 inhibitors and Chk1 inhibitors synergistically induce multiple myeloma cell apoptosis through upregulation of the BH3-only pro-apoptotic protein Bim. However, these apoptotic events were largely blocked by the characteristic over-expression of Bcl-2 of Bcl-xL in multiple myeloma cells. HA14-1, a small molecule Bcl-2 inhibitor, may therefore circumvent this resistance to apoptosis by blocking Bcl-2 and Bcl-xL anti-apoptotic protein actions. In our project, we hypothesize that the co-administration of HA14-1 with MEK/Chk1 inhibitors will enhance apoptosis in multiple myeloma (MM) cells. To test this hypothesis, we exposed MM cells U266 and RPMI8226, or …

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Tacrolimus Is Not Neuroprotective Against Bilirubin Induced Auditory Impairment, Lori Walker Apr 2009

Tacrolimus Is Not Neuroprotective Against Bilirubin Induced Auditory Impairment, Lori Walker

Theses and Dissertations

In newborns, unconjugated bilirubin (UCB) is not readily excreted, and when bilirubin levels exceed the serum albumin binding capacity, pathological levels of UCB exist. Hyperbilirubinemia may lead to auditory damage and ultimately cause a hearing disorder called auditory neuropathy/dys-synchrony, characterized by absent or abnormal brainstem auditory evoked potentials (BAEPs) with evidence of normal inner ear function assessed by either otoacoustic emissions or cochlear microphonic responses. Phototherapy and double volume exchange transfusion are used as treatment methods for neonatal hyperbilirubinemia. Spontaneously jaundiced Gunn rat pups given sulfadimethoxine to displace bilirubin from serum albumin develop bilirubin encephalopathy and have abnormal BAEPs comparable …

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The Second Generation Proteasome Inhibitor Carfilzomib Interacts Synergistically With Hdac Inhibitors In Diffuse Large B-Cell Lymphoma Cells Through Multiple Mechanisms And Circumvents Bortezomib Resistance, Dmitry Lembersky Apr 2009

The Second Generation Proteasome Inhibitor Carfilzomib Interacts Synergistically With Hdac Inhibitors In Diffuse Large B-Cell Lymphoma Cells Through Multiple Mechanisms And Circumvents Bortezomib Resistance, Dmitry Lembersky

Theses and Dissertations

Mechanisms underlying the interactions between the proteasome inhibitor carfilzomib and HDAC inhibitors were examined in both germinal center (GC) and activated B-cell (ABC) subtypes of human diffuse large B-cell lymphoma (DLBCL). Simultaneous exposure to minimally toxic concentrations of carfilzomib and HDAC inhibitor vorinostat resulted in the release of mitochondrial pro-apoptotic proteins SMAC and cytochrome c, pro-apoptotic caspase activation, and synergistic induction in apoptosis in both ABC and GC DLBCL subtypes. These events were associated with a marked increase in the stress kinase JNK, ROS generation, G2-M cell cycle arrest, as well as induction of DNA damage. Genetic knockdown of JNK …

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Role Of The Porphyromonas Gingivalis Ecf Sigma Factor, Sigh, In Oxidative Stress Response, Sara Sarrafee Apr 2009

Role Of The Porphyromonas Gingivalis Ecf Sigma Factor, Sigh, In Oxidative Stress Response, Sara Sarrafee

Theses and Dissertations

Periodontal disease affects a majority of the US population. Porphyromonas gingivalis is the major etiological agent for development and progression of the disease. P. gingivalis is a hemin-dependent, obligate anaerobe that is found predominantly in periodontal pockets in infected patients. So for, little is known regarding the mechanisms which allow P. gingivalis to survive and sustain itself in the oral cavity. To better understand the adaptive mechanisms of the bacterium to the varying conditions in the oral cavity, regulatory mechanisms must be characterized. Sigma factors (σ) are responsible for initiating transcription by guiding RNA polymerase binding to specific DNA promoter …

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Understanding Evolutionary Relationships In The Angiosperm Order Apiales Based On Analyses Of Organellar Dna Sequences And Nuclear Gene Duplications, Antoine Nicolas Apr 2009

Understanding Evolutionary Relationships In The Angiosperm Order Apiales Based On Analyses Of Organellar Dna Sequences And Nuclear Gene Duplications, Antoine Nicolas

Theses and Dissertations

I studied evolutionary history in the angiosperm order Apiales, with a special emphasis on interactions between form, time, and space. Four broad categories of problems were addressed: interfamilial relationships in Apiales, the assignment of genera traditionally assigned to the Apiaceae subfamily Hydrocotyloideae, the estimation of divergence times of the major clades, and the reconstruction of the biogeographic history of Apiales. We used molecular markers with different evolutionary properties and rates derived from the plastid (trnD-trnT and rpl16), nuclear (RPB2), and mitochondrial (nad1 intron 2) genomes, from more than 250 species representing all major clades in the order. The nuclear RPB2 …

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The Role Of Brca1 In Dna Double-Strand Break Repair, Seth Dever Apr 2009

The Role Of Brca1 In Dna Double-Strand Break Repair, Seth Dever

Theses and Dissertations

Mutations in the breast cancer susceptibility 1 (BRCA1) gene are linked to breast as well as ovarian cancers. However, most cancer-causing mutations within the BRCA1 gene have been found in the N’ and C’ terminal regions of the BRCA1 protein, both believed to be important for DNA double-strand break (DSB) repair. The BRCA1 C’ terminal (BRCT) repeats have been implicated in phospho-serine protein binding whereas the N’ terminal RING domain interacts with the BARD1 protein to form a hetero-dimeric complex with E3 ubiquitin ligase activity. The BRCA1 BRCT domain binds CtIP, BACH1, and RAP80, all of which have been directly …

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Scribble As A Possible Binding Partner For The Map Kinases Erk2 And Erk6, William Allen Apr 2009

Scribble As A Possible Binding Partner For The Map Kinases Erk2 And Erk6, William Allen

Theses and Dissertations

We worked on finding a new kinase regulator to develop basic data to be used for cancer prevention. Our work found a link between three previously unrelated proteins involved in cancer, ERK2 and ERK6 and Scribble. The MAP kinase cascade is involved in cell proliferation, which is highly deregulated in cancer. Through the screening of ERK6 associating molecules, we found the cell polarity, and cell cycle related molecule Scribble. Furthermore, we found that Scribble was a dual-specific kinase regulator. We clearly demonstrated that these ERKs interact with Scribble through the LRR and the PDZ domains of Scribble. We hypothesize that …

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