Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 30 of 48

Full-Text Articles in Medicine and Health Sciences

Evasion Of Lps-Tlr4 Signaling As A Virulence Determinate For Yersinia Pestis, Sara Montminy Paquette Dec 2009

Evasion Of Lps-Tlr4 Signaling As A Virulence Determinate For Yersinia Pestis, Sara Montminy Paquette

GSBS Dissertations and Theses

Yersinia pestis, the gram-negative causative agent of plague, is a master of immune evasion. The bacterium possesses a type three secretion system which translocates Yop effector proteins into host immune cells to inhibit a number of immune and cell signaling cascades. Interestingly, this apparatus is not expressed at low temperatures such as those found within the flea vector and is therefore neither in place nor functional when the bacteria are first transmitted into a mammalian host. However, the bacterium is still able to avoid activating the immune system, even very early during infection.

When grown at 37°C (human body ...


Identification Of The Function Of The Vpx Protein Of Primate Lentiviruses: A Dissertation, Xiaonan Zhu Dec 2009

Identification Of The Function Of The Vpx Protein Of Primate Lentiviruses: A Dissertation, Xiaonan Zhu

GSBS Dissertations and Theses

Primate lentiviruses encode four “accessory proteins” including Vif, Vpu, Nef, and Vpr/ Vpx. Vif and Vpu counteract the antiviral effects of cellular restrictions to early and late steps in the viral replication cycle. The functions of Vpx/ Vpr are not well understood. This study presents evidence that the Vpx proteins of HIV-2/ SIVSMpromote HIV-1 infection by antagonizing an antiviral restriction in myeloid cells.

Fusion of macrophages in which Vpx was essential for virus infection, with COS cells in which Vpx was dispensable for virus infection, generated heterokaryons that supported infection by wild-type SIV but not Vpx-deleted SIV. The ...


The Role Of Macropinocytosis In Sonic Hedgehog-Induced Axon Growth And Guidance: A Dissertation, Adrianne L. Kolpak Dec 2009

The Role Of Macropinocytosis In Sonic Hedgehog-Induced Axon Growth And Guidance: A Dissertation, Adrianne L. Kolpak

GSBS Dissertations and Theses

Axon pathfinding is an important process required for the establishment of proper neuronal connections during development. An increasing number of secreted and membrane-anchored molecules have been identified as axon guidance cues, which can act as positive or negative factors to increase or decrease the growth of axons and influence the direction of axonal growth. These axon guidance factors present in the extracellular environment interact with receptors present on the growth cone, a structure located at the tip of the axon which functions as the motor unit for the axon. Upon binding to their receptors on the growth cone, the guidance ...


Pathophysiology Of Respiratory Failure Following Acute Organophosphate Poisoning : A Dissertation, Romolo Joseph Gaspari Dec 2009

Pathophysiology Of Respiratory Failure Following Acute Organophosphate Poisoning : A Dissertation, Romolo Joseph Gaspari

GSBS Dissertations and Theses

Organophosphate (OP) poisoning is a health issue worldwide with over 200,000 deaths per year. Although not a problem in most developed countries, in some third world countries, one third of a hospital’s population could be patients with OP exposure. Even with the most aggressive therapy, 10-40% of patients admitted to an intensive care unit will die. Research into the best practice for treating OP poisoning is lacking, due somewhat to a lack of detailed understanding of the physiology of OP poisoning. Our research uses animal models of acute OP poisoning to explore the mechanism of OP-induced respiratory failure ...


Regulation Of The Cdc14-Like Phosphatase Clp1 In Schizosaccharomyces Pombe And Identification Of Sid2 Kinase Substrates: A Dissertation, Chun-Ti Chen Nov 2009

Regulation Of The Cdc14-Like Phosphatase Clp1 In Schizosaccharomyces Pombe And Identification Of Sid2 Kinase Substrates: A Dissertation, Chun-Ti Chen

GSBS Dissertations and Theses

Coordination of mitosis and cytokinesis is crucial to generate healthy daughter cells with equal amounts of genetic and cytoplasmic materials. In the fission yeast Schizosaccharomyces pombe, an evolutionarily conserved Cdc14-like phosphatase (Clp1) functions to couple mitosis and cytokinesis by antagonizing CDK activity. The activity of Clp1 is thought to be regulated in part by its subcellular localization. It is sequestered in the nucleolus and the spindle pole body (SPB) during interphase. Upon mitotic entry, it is released into the cytoplasm and localized to the kinetochores, the actomyosin ring, and the mitotic spindle to carry out distinct functions. It is not ...


Elucidation Of The Role Of The Exocyst Subunit Sec6p In Exocytosis: A Dissertation, Daniel Niron Brewer Nov 2009

Elucidation Of The Role Of The Exocyst Subunit Sec6p In Exocytosis: A Dissertation, Daniel Niron Brewer

GSBS Dissertations and Theses

Trafficking of protein and lipid cargo through the secretory pathway in eukaryotic cells is mediated by membrane-bound vesicles. Secretory vesicles are targeted to sites of exocytosis on the plasma membrane in part by a conserved multi-subunit protein complex termed the exocyst. In addition to tethering vesicles to the plasma membrane, the exocyst complex and components therein may also add a layer of regulation by directly controlling assembly of the SNARE complex, which is required for membrane fusion, as well as other regulatory factors such as Sec1p. In the past, we have shown that Sec6p interacts with Sec9p in vivo and ...


Endoderm Patterning In Zebrafish: Pancreas Development: A Dissertation, Kristen M. Alexa Nov 2009

Endoderm Patterning In Zebrafish: Pancreas Development: A Dissertation, Kristen M. Alexa

GSBS Dissertations and Theses

The pancreas is located below the liver and adjacent to the small intestine where it connects to the duodenum. It consists of exocrine and endocrine components. The exocrine portion makes enzymes which are deposited in the duodenum to digest fats, proteins, and carbohydrates. Exocrine tissue also makes bicarbonates that neutralize stomach acids. The endocrine portion produces hormones such as insulin and glucagon which are released into the blood stream. These hormones regulate glucose transport into the body's cells and are crucial for energy production. The pancreas is associated with diseases such as cancer, diabetes, Annular pancreas and Nesidioblastosis. Annular ...


Co-Evolution Of Hiv-1 Protease And Its Substrates: A Dissertation, Madhavi Kolli Nov 2009

Co-Evolution Of Hiv-1 Protease And Its Substrates: A Dissertation, Madhavi Kolli

GSBS Dissertations and Theses

Drug resistance is the most important factor that influences the successful treatment of individuals infected with the human immunodeficiency virus type 1 (HIV-1), the causative organism of the acquired immunodeficiency syndrome (AIDS). Tremendous advances in our understanding of HIV and AIDS have led to the development of Highly Active Antiretroviral Therapy (HAART), a combination of drugs that includes HIV-1 reverse transcriptase, protease, and more recently, integrase and entry inhibitors, to combat the virus. Though HAART has been successful in reducing AIDS-related morbidity and mortality, HIV rapidly evolves resistance leading to therapy failure. Thus, a better understanding of the mechanisms of ...


Caspase Mediated Cleavage, Iap Binding, Ubiquitination And Kinase Activation : Defining The Molecular Mechanisms Required For Drosophila Nf-Кb Signaling: A Dissertation, Nicholas Paul Paquette Nov 2009

Caspase Mediated Cleavage, Iap Binding, Ubiquitination And Kinase Activation : Defining The Molecular Mechanisms Required For Drosophila Nf-Кb Signaling: A Dissertation, Nicholas Paul Paquette

GSBS Dissertations and Theses

Innate immunity is the first line of defense against invading pathogens. Vertebrate innate immunity provides both initial protection, and activates adaptive immune responses, including memory. As a result, the study of innate immune signaling is crucial for understanding the interactions between host and pathogen. Unlike mammals, the insect Drosophila melanogasterlack classical adaptive immunity, relying on innate immune signaling via the Toll and IMD pathways to detect and respond to invading pathogens. Once activated these pathways lead to the rapid and robust production of a variety of antimicrobial peptides. These peptides are secreted directly into the hemolymph and assist in ...


Energetic And Dynamic Analysis Of Inhibitor Binding To Drug-Resistant Hiv-1 Proteases: A Dissertation, Yufeng Cai Nov 2009

Energetic And Dynamic Analysis Of Inhibitor Binding To Drug-Resistant Hiv-1 Proteases: A Dissertation, Yufeng Cai

GSBS Dissertations and Theses

HIV-1 protease is a very important drug target for AIDS therapy. Nine protease inhibitors have been proved by FDA and used in AIDS treatment. Due to the high replication rate and the lack of fidelity of the HIV-1 reverse transcriptase, HIV-1 virus developed various drug-resistant variants. Although experimental methods such as crystallography and isothermal titration calorimetry provide structural and thermodynamic data on drug-resistant variants, they are unable to discern the mechanism by which the mutations confer resistance to inhibitors. Understanding the drug-resistance mechanism is crucial for developing new inhibitors more tolerant to the drug-resistant mutations. Computational methods such as free ...


Sensitization Of Cd8 T Cells During Acute Viral Infections Impacts Bystander And Latecomer Cd8 T Cell Responses : A Dissertation, Heather D. Marshall Oct 2009

Sensitization Of Cd8 T Cells During Acute Viral Infections Impacts Bystander And Latecomer Cd8 T Cell Responses : A Dissertation, Heather D. Marshall

GSBS Dissertations and Theses

Many virus infections induce a transient state of immune suppression in the infected host. Virus-induced T cell suppression can be caused by T cell activation-induced cell death (AICD), dendritic cell (DC) apoptosis, DC dysfunction, and/or the enhanced expression of immune-suppressive cytokines. It has been previously demonstrated that naïve bystander CD8 T cells derived from hosts experiencing an acute virus-specific T cell response underwent AICD when polyclonally activated by anti-CD3 in vitro (Zarozinski et al., 2000). Susceptibility of naïve bystander T cells to AICD could prevent the development of a new T cell response during an ongoing immune response, and ...


Neural Circuit Analyses Of The Olfactory System In Drosophila: Input To Output: A Dissertation, Shamik Dasgupta Sep 2009

Neural Circuit Analyses Of The Olfactory System In Drosophila: Input To Output: A Dissertation, Shamik Dasgupta

GSBS Dissertations and Theses

This thesis focuses on several aspects of olfactory processing in Drosophila. In chapter I and II, I will discuss how odorants are encoded in the brain. In both insects and mammals, olfactory receptor neurons (ORNs) expressing the same odorant receptor gene converge onto the same glomerulus. This topographical organization segregates incoming odor information into combinatorial maps. One prominent theory suggests that insects and mammals discriminate odors based on these distinct combinatorial spatial codes. I tested the combinatorial coding hypothesis by engineering flies that have only one class of functional ORNs and therefore cannot support combinatorial maps. These files can be ...


A Multiparameter Network Reveals Extensive Divergence Between C. Elegans Bhlh Transcription Factors: A Dissertation, Christian A. Grove Sep 2009

A Multiparameter Network Reveals Extensive Divergence Between C. Elegans Bhlh Transcription Factors: A Dissertation, Christian A. Grove

GSBS Dissertations and Theses

It has become increasingly clear that transcription factors (TFs) play crucial roles in the development and day-to-day homeostasis that all biological systems experience. TFs target particular genes in a genome, at the appropriate place and time, to regulate their expression so as to elicit the most appropriate biological response from a cell or multicellular organism. TFs can often be grouped into families based on the presence of similar DNA binding domains, and these families are believed to have expanded and diverged throughout evolution by several rounds of gene duplication and mutation. The extent to which TFs within a family have ...


Hypoxia Inducible Factors In Alcoholic Liver Disease: A Dissertation, Bharath D. Nath Sep 2009

Hypoxia Inducible Factors In Alcoholic Liver Disease: A Dissertation, Bharath D. Nath

GSBS Dissertations and Theses

Chronic intake of alcohol can result in a range of pathology in the liver. Whilst the earliest changes observed with chronic ethanol, including the accumulation of lipid, or steatosis, are readily reversible upon cessation of alcohol consumption, longer exposure to ethanol may achieve more complex disease states including steatohepatitis, fibrosis, and cirrhosis that can cause irreversible damage and progress to fulminant hepatic failure. A key concept in the pathogenesis of alcoholic liver disease is that chronic ethanol primes the liver to increased injury through an interplay between hepatocytes and non-parenchymal cells, chiefly immune cells, of the liver. These relationships between ...


Mechanisms Of Notch1 Mediated Leukemogenesis: A Dissertation, Kathleen J. Cullion Sep 2009

Mechanisms Of Notch1 Mediated Leukemogenesis: A Dissertation, Kathleen J. Cullion

GSBS Dissertations and Theses

Gain of function NOTCH1 mutations are common in both patients with T-ALL and in mouse models of the disease. Inhibiting the Notch pathway in T-ALL cell lines results in growth arrest and/or apoptosis in vitro, suggesting a requirement for Notch signaling in T-ALL. Therefore, we sought to examine the role of Notch1 signaling in both premalignancy and in the maintenance of leukemic growth. Using a murine model of T-ALL, in which expression of the Tal1 and Lmo2 oncogenes arrests thymocyte development, our preleukemic studies reveal that Notch1 mutations are early events that contribute to the clonal expansion of DN3 ...


Injection Treatment For Lower Back Pain In Older Adults With Lumbar Spinal Stenosis: A Dissertation, Virginia G. Briggs Aug 2009

Injection Treatment For Lower Back Pain In Older Adults With Lumbar Spinal Stenosis: A Dissertation, Virginia G. Briggs

GSBS Dissertations and Theses

Background:Lower back pain is one of the most common health-related complaints in the adult population. Thirty percent of Americans 65 years and older reported symptoms of lower back pain in 2004. With an aging population, the proportion of people over the age of 65 is expected to reach 20% by the year 2030. Because of this increase in older adults, lumbar spinal stenosis (LSS) associated with arthritic changes will also likely increase. In older adults, lower back pain is most often caused by degenerative lumbar spinal stenosis. Stenosis is the narrowing ofthe spinal canal, causing pressure on the nerve ...


Regulation Of Bach1/Fancj Function In Dna Damage Repair: A Dissertation, Jenny X. Xie Aug 2009

Regulation Of Bach1/Fancj Function In Dna Damage Repair: A Dissertation, Jenny X. Xie

GSBS Dissertations and Theses

The DNA damage response (DDR) pathway is a complicated network of interacting proteins that function to sense and remove DNA damage. Upon exposure to DNA damage, a signaling cascade is generated. The damage is either removed, restoring the original genetic sequence, or apoptosis is activated. In the absence of DDR, cells are unable to effectively process DNA damage. Unprocessed DNA damage can lead to chromosomal changes, gene mutations, and malignant transformation. Thus, the proteins involved in DDR are critical for maintaining genomic stability.

One essential DDR protein is the BRCA1 Associated C-terminal Helicase, BACH1. BACH1 was initially identified through its ...


Cytoskeletal Regulation And Morphogen Signaling During Synaptic Outgrowth At The Drosophila Larval Neuromuscular Junction : A Dissertation, Preethi Ramachandran Aug 2009

Cytoskeletal Regulation And Morphogen Signaling During Synaptic Outgrowth At The Drosophila Larval Neuromuscular Junction : A Dissertation, Preethi Ramachandran

GSBS Dissertations and Theses

Synaptic plasticity, in its broadest sense, can be defined as the ability of synapses to be modified structurally and functionally in response to various internal and external factors. Growing evidence has established that at the very core of these modifications are alterations in the cytoskeletal architecture. This discovery has led to the unearthing of a number of signaling pathways that might be involved in cytoskeletal regulation and also in the regulation of other aspects of synapse development and plasticity. In this regard, polarity proteins and secreted morphogens such as the Wnt proteins, typically involved in embryonic development, are emerging as ...


Characterization Of The Nef-Tcr Zeta Interaction And Its Role In Modulation Of Src Family Kinase Activity: A Dissertation, Walter Minsub Kim Aug 2009

Characterization Of The Nef-Tcr Zeta Interaction And Its Role In Modulation Of Src Family Kinase Activity: A Dissertation, Walter Minsub Kim

GSBS Dissertations and Theses

One of the hallmarks of an infection with pathogenic HIV-1 is the elevated level of immune activation that leads to rapid progression to AIDS. Surprisingly, nonhuman primates naturally infected with SIV do not exhibit an augmented activation phenotype nor severe immunodeficiency. One of the viral components implicated in determining the state of immune activation is the accessory protein Nef which has been demonstrated to affect T cell signaling pathways from within the intracellular compartment and for Nef from SIV, to downregulate TCR surface expression. Recently, Nef from HIV-1 and SIV have been demonstrated to bind the ζ chain of the ...


Regulation Of Dna Replication Origins In Fission Yeast: A Dissertation, Naveen Kommajosyula Aug 2009

Regulation Of Dna Replication Origins In Fission Yeast: A Dissertation, Naveen Kommajosyula

GSBS Dissertations and Theses

Cells need to complete DNA replication in a timely and error-free manner. To ensure that replication is completed efficiently and in a finite amount of time, cells regulate origin firing. To prevent any errors from being transmitted to the next generation, cells have the checkpoint mechanism.

The S-phase DNA damage slows replication to allow the cell to repair the damage. The mechanism of replication slowing by the checkpoint was not clear in fission yeast, Schizosaccharomyces pombe, at the start of my thesis. The downstream targets of the DNA damage checkpoint in fission yeast were also unclear. I worked on identifying ...


Respiratory Syncytial Virus (Rsv) Induces Innate Immunity Through Toll-Like Receptors And Acquired Immunity Via The Rsv G Protein: A Dissertation, Matthew R. Murawski Jul 2009

Respiratory Syncytial Virus (Rsv) Induces Innate Immunity Through Toll-Like Receptors And Acquired Immunity Via The Rsv G Protein: A Dissertation, Matthew R. Murawski

GSBS Dissertations and Theses

Respiratory syncytial virus (RSV) causes a common infection that is associated with a range of respiratory illnesses from common cold-like symptoms to serious lower respiratory tract illnesses such as pneumonia and bronchiolitis. RSV is the single most important cause of serious lower respiratory tract illness in children < 1 year of age. Host innate and acquired immune responses activated following RSV infection have been suspected as contributing to RSV disease. Toll-like receptors (TLRs) activate innate and acquired immunity and are candidates for playing key roles in the host immune response to RSV. Leukocytes express TLRs including TLR2, TLR6, TLR3, TLR4, and TLR7 that can potentially interact with RSV and promote immune responses following infection. Using knockout mice, we have demonstrated that TLR2 and TLR6 signaling in leukocytes can activate innate immunity against RSV by promoting TNF-α, IL-6, CCL2 (MCP-1), and CCL5 (RANTES) production. As previously noted, TLR4 also contributed to cytokine activation (71, 90). Furthermore, we demonstrated that signals generated following TLR2 and TLR6 activation were important for controlling viral replication in vivo. Additionally, TLR2 interactions with RSV promoted neutrophil migration and dendritic cell activation within the lung. Collectively, these studies indicate that TLR2 is involved in RSV recognition and subsequent innate immune activation and may play a role in modulating acquired immune responses through DCs.

Despite the fact that RSV is the single ...


Regulation Of Cancer Cell Survival Mediated By Endogenous Tumor Suppression: A Dissertation, Minakshi Guha Jul 2009

Regulation Of Cancer Cell Survival Mediated By Endogenous Tumor Suppression: A Dissertation, Minakshi Guha

GSBS Dissertations and Theses

Cancer is the second leading cause of death among men and women after heart disease. Though our knowledge associated with the complexities of the cancer network has significantly improved over the past several decades, we have only recently started to get a more complete molecular understanding of the disease. To better comprehend signaling pathways that prevent disease development, we focused our efforts on investigating endogenous tumor suppression networks in controlling effectors of cancer cell survival and proliferation. Survivin is one such effector molecule that controls both cell proliferation and survival. In order to identify how this protein is overexpressed in ...


Long-Range Side Chain-Main Chain Hydrogen Bonds: A Molecular Signature Of The Tim Barrel Architecture: A Dissertation, Xiaoyan Yang Jul 2009

Long-Range Side Chain-Main Chain Hydrogen Bonds: A Molecular Signature Of The Tim Barrel Architecture: A Dissertation, Xiaoyan Yang

GSBS Dissertations and Theses

The hydrophobic effect and hydrogen bonding interactions have long been considered to be the dominant forces in protein folding. However, the contribution of hydrogen bonds to stabilizing proteins has been difficult to clarify. As the intramolecular hydrogen bonds are formed in place of hydrogen bonds with solvent during folding, measures of stability fail to give a significant change in free energy. Previous studies on hydrogen bonding interactions have shown that they are only marginally important.

Three long-range side chain-main chain hydrogen bonds have been found in the alpha subunit of tryptophan synthase (αTS), a (βα)8TIM barrel protein. These ...


Iap Regulation Of Tumor Metastasis: A Dissertation, Swarna Mehrotra Jun 2009

Iap Regulation Of Tumor Metastasis: A Dissertation, Swarna Mehrotra

GSBS Dissertations and Theses

The dissemination of tumor cells to distant organs i.e. metastasis is an exceedingly complex process leading to 90% of all cancer deaths. Despite being so clinically important, little is known about this process that requires tumor cells to leave the primary tumor site, intravasate and transport through the blood stream, extravasate and colonize at secondary sites leading to distant metastases. Survivin, a member of the IAP (Inhibitor of Apoptosis) family with known functions in apoptosis and mitosis, is highly expressed in aggressive tumors and is associated with poor prognosis and adverse clinical outcome. But the mechanistic role of survivin ...


Functional Elements Of EspfU, An Enterohemorrhagic E. Coli Effector That Stimulates Actin Assembly: A Dissertation, Brian M. Skehan Jun 2009

Functional Elements Of EspfU, An Enterohemorrhagic E. Coli Effector That Stimulates Actin Assembly: A Dissertation, Brian M. Skehan

GSBS Dissertations and Theses

Enterohemorrhagic Escherichia coli O157:H7 (EHEC) is an attaching and effacing pathogen that upon attachment to host cells, induce characteristic attaching and effacing lesions and formation of F-actin rich pedestals beneath sites of bacterial attachment. EHEC harbors a Type III secretion system through which it delivers dozens of effectors into the host cell. The two secreted effectors critical for EHEC-mediated actin pedestal formation are the translocated intimin receptor (Tir) and EspFU. EspFU consists of an N-terminal secretion signal and a C-terminus containing six tandem 47-residue proline-rich repeats, each of which can bind and activate the actin nucleation promoting ...


Defining The Role Of Ctbp2 In P53-Independent Tumor Suppressor Function Of Arf: A Dissertation, Ramesh C. Kovi Jun 2009

Defining The Role Of Ctbp2 In P53-Independent Tumor Suppressor Function Of Arf: A Dissertation, Ramesh C. Kovi

GSBS Dissertations and Theses

ARF, a potent tumor suppressor, positively regulates p53 by antagonizing MDM2, a negative regulator of p53, which in turn, results in either apoptosis or cell cycle arrest. ARF also suppresses the proliferation of cells lacking p53, and loss of ARF in p53-null mice, compared with ARF-null or p53-null mice, results in a broadened tumor spectrum and decreased tumor latency. This evidence suggests that ARF exerts both p53-dependent and p53-independent tumor suppressor activity. However, the molecular pathway and mechanism of ARF’s p53-independent tumor suppressor activity is not understood.

The antiapoptotic, metabolically regulated, transcriptional corepressor C-terminal binding protein 2 (CtBP2) has ...


Modeling Co-Occurring Depression And Anxiety In Patients With An Acute Coronary Syndrome: A Dissertation, Mayra Tisminetzky Jun 2009

Modeling Co-Occurring Depression And Anxiety In Patients With An Acute Coronary Syndrome: A Dissertation, Mayra Tisminetzky

GSBS Dissertations and Theses

The purpose of the current project is to illustrate the application of advanced statistical techniques to address research questions about depression and anxiety in patients with an acute coronary syndrome (ACS). The first study, using data from 100 patients who were randomized into a clinical trial of cognitive behavioral therapy, used bivariate mixed models to determine trajectories of depression and anxiety after an ACS, to examine the effects of cognitive behavioral therapy (CBT) on depression and anxiety, and to determine if anxiety and depression symptoms change at the same rate with CBT treatment as indicated by joint modeling of these ...


Study Of The Function And Dynamics Of Myosin Ii And Actin In Cytokinesis: A Dissertation, Mian Zhou May 2009

Study Of The Function And Dynamics Of Myosin Ii And Actin In Cytokinesis: A Dissertation, Mian Zhou

GSBS Dissertations and Theses

Myosin II and actin are two major components of the ingressing cortex during cytokinesis. However, their structural dynamics and functions during cytokinesis are still poorly understood. To study the role of myosin II in cortical actin turnover, dividing normal rat kidney (NRK) cells were treated with blebbistatin, a potent inhibitor of the non-muscle myosin II ATPase. Blebbistatin caused a strong inhibition of actin filament turnover and cytokinesis. Local release of blebbistatin at the equator caused inhibition of cytokinesis, while treatment in the polar region also caused a high frequency of abnormal cytokinesis, suggesting that myosin II may play a global ...


Checkpoint Regulation Of Replication Forks In Response To Dna Damage: A Dissertation, Nicholas Adrian Willis May 2009

Checkpoint Regulation Of Replication Forks In Response To Dna Damage: A Dissertation, Nicholas Adrian Willis

GSBS Dissertations and Theses

Faithful duplication and segregation of undamaged DNA is critical to the survival of all organisms and prevention of oncogenesis in multicellular organisms. To ensure inheritance of intact DNA, cells rely on checkpoints. Checkpoints alter cellular processes in the presence of DNA damage preventing cell cycle transitions until replication is completed or DNA damage is repaired.

Several checkpoints are specific to S-phase. The S-M replication checkpoint prevents mitosis in the presence of unreplicated DNA. Rather than outright halting replication, the S-phase DNA damage checkpoint slows replication in response to DNA damage. This checkpoint utilizes two general mechanisms to slow replication. First ...


Systems Level Processing Of Memory In The Fly Brain: A Dissertation, Michael Jonathan Krashes May 2009

Systems Level Processing Of Memory In The Fly Brain: A Dissertation, Michael Jonathan Krashes

GSBS Dissertations and Theses

Understanding the mechanisms of memory is vital in making sense of the continuity of the self, our experience of time and of the relation between mind and body. The invertebrate Drosophila melanogaster offers us an opportunity to study and comprehend the overwhelming complexity of memory on a smaller scale. The work presented here investigates the neural circuitry in the fly brain required for olfactory memory processing. Our observation that Dorsal Paired Medial (DPM) neurons, which project only to mushroom body (MB) neurons, are required during memory storage but not for acquisition or retrieval, led us to revisit the role of ...