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The Development Of Humoral And Cellular Responses To Plasmodium Falciparum Malaria In The Hypoendemic Peruvian Amazon And Potential Clinical Protection, Eva Helen Clark Jan 2010

The Development Of Humoral And Cellular Responses To Plasmodium Falciparum Malaria In The Hypoendemic Peruvian Amazon And Potential Clinical Protection, Eva Helen Clark

All ETDs from UAB

Each year 300-500 million cases of Plasmodium falciparum malaria occur, leading to more than 1 million deaths. In high malaria transmission regions, development of immunity from severe infection requires 2-10 years of persistent parasitemia. This delay has been attributed to difficulties in the development of protective humoral responses. Indeed, anti-malarial antibody responses tend to be short-lived, and immunologic memory seems to be dysfunctional in high-transmission regions. In contrast, in the low-transmission Peruvian Amazon >60% of infections are asymptomatic, suggesting that clinical immunity occurs despite low parasite exposure. To analyze more precisely the naturally-acquired humoral responses to malarial antigens and their …


The Role Of Usp14 In Regulating Synaptic Development And Function Of The Neuromuscular Junctions, Ping-Chung Chen Jan 2010

The Role Of Usp14 In Regulating Synaptic Development And Function Of The Neuromuscular Junctions, Ping-Chung Chen

All ETDs from UAB

The ubiquitin proteasome system (UPS) plays critical roles in regulating multiple cellular functions, including protein abundance, trafficking, and cell signaling. In the nervous system, the UPS has been implicated in controlling a wide diversity of cellular process such as synaptic transmission, axon outgrowth, axon targeting, and synapse development. Although impairment of the UPS is observed in both neurodegenerative and developmental diseases, the mechanisms underlying how UPS dysregulation contributes to disease pathogenesis are not known. The proteasome, an approximate 2.5 megadaltons protein complex composed of 19S and 20S assemblies, is the site of ubiquitin-dependent protein degradation. Recent studies have demonstrated dysfunction …


The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon Jan 2010

The Role Of Gli1 In Eralpha-Negative Breast Cancer: Promoting Survival, Migration, Invasion, And Metastasis, Yeon-Jin Kwon

All ETDs from UAB

Glioma-associated oncogene homolog 1 (Gli1) is a well-known oncogene and a transcription factor that mediates several signaling pathways important for tumor progression, such as hedgehog, TGFß, Ras, and EGFR. Although Gli1 is known to play an important role in cancers of brain, skin, prostate, and the pancreas, the role of Gli1 in breast cancer was not previously well-defined. Therefore, this dissertation focuses on defining the role of Gli1 and the mechanism underlying Gli1-mediated transcription in breast cancer. Interestingly, the major findings of the dissertation clearly indicate that Gli1 promotes cell survival and is predictive of a poor outcome in Estrogen …


Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley Jan 2010

Cgmp Pde As A Novel Molecular Target For The Prevention And Treatment Of Breast Cancer, Heather Nicole Tinsley

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Breast cancer remains a major health concern, despite efforts to develop improved therapeutics. Chemoprevention is a promising strategy for reducing breast cancer-related morbidity and mortality. However, with the exception of the selective estrogen receptor modulators (SERMs), which have limited efficacy and severe toxicities, no drugs have been approved for breast cancer chemoprevention. Studies demonstrate that certain nonsteroidal anti-inflammatory drugs (NSAIDs) display promising chemopreventive efficacy. Unfortunately, the depletion of physiologically important prostaglandins due to inhibition of the cyclooxygenase (COX) enzymes results in potentially fatal toxicities, which exclude the use of NSAIDs and COX-2 selective inhibitors for chemoprevention. Ample data, however, suggest …


Dna Replication And Cytokinesis In Drosophila Melanogaster, Anton Svitin Jan 2010

Dna Replication And Cytokinesis In Drosophila Melanogaster, Anton Svitin

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DNA replication and cytokinesis are two important parts of the cell division process. Our studies address different aspects of both of these processes and potential links between them. One of the best approaches for studying DNA replication in eukaryotes has been an analysis in cell free in vitro systems. The existing cell free replication systems for Drosophila are relatively ineffective. In the first part of this work, we have developed an optimized in vitro system to study DNA replication using early egg extracts of Drosophila. Our studies indicate that this system proves to be an extremely useful tool for a …


Lens Cataract: Biochemical Analysis Of The Alpha Crystallins, David Ray Stella Jan 2010

Lens Cataract: Biochemical Analysis Of The Alpha Crystallins, David Ray Stella

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The cataract is a common ailment affecting the aged population. It appears over time and affects the quality of one’s life by the eventual loss of vision. Currently, there is no effective strategy to prevent or treatment to reverse the development of a cataract. As well, there is no consensus on one particular mechanism or sequence of events that contributes to its formation. In order to better understand the possible etiology of the cataract, it is necessary to define the biochemical changes that occur to lens proteins as one ages, as these are the key players in the prevention of …


Exosomal Curcumin: Its Bioavailability And Potential Anti-Inflammation Activity, Dongmei Sun Jan 2010

Exosomal Curcumin: Its Bioavailability And Potential Anti-Inflammation Activity, Dongmei Sun

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Curcumin, a pleiotropic polyphenol derived from turmeric plants Curcuma Longa with rhizome, exhibits strong evidence as an anti-inflammation, anti-oxidant and anti-cancer reagent both in vitro and in vivo. Due to its low stability and systemic bioavailability, a large amount of curcumin has to be administrated to achieve therapeutic effects both in animal and in human. The major effort to overcome this barrier is making by encapsulation of curcumin into nanoparticles such as polymers and liposomes; some promising data have demonstrated the effectiveness of such method. Exosomes are vesicle-like nanoparticles secreted by living cells. Exosomes contain both cell surface molecules and …


Protective Antibodies To The Proline-Rich And Alpha Helical Regions Of Pneumococcal Surface Protein A And Their Detection In An In Vitro Surrogate Assay, Calvin Clay Daniels Jan 2010

Protective Antibodies To The Proline-Rich And Alpha Helical Regions Of Pneumococcal Surface Protein A And Their Detection In An In Vitro Surrogate Assay, Calvin Clay Daniels

All ETDs from UAB

Current pneumococcal vaccines containing pneumococcal capsular polysaccharide antigens protect against infection by pneumococci. However, this protection is limited to strains expressing the capsule types included in the vaccine. Since the introduction of these vaccines, the increase in incidence of infection by serotypes not targeted by the vaccine, a process called "serotype replacement," and the growing antibiotic resistance of replacement strains both stress the need for vaccines with broader protection. The alpha-helical region of a protein present on all clinical isolates of pneumococci, Pneumococcal Surface Protein A (PspA), elicits protective immunity. Downstream of the alpha-helical region is a highly conserved region …


Preclinical Pharmacology Of Novel Synthetic Iminoquinones As Anticancer Agents, Scharri Ezell Jan 2010

Preclinical Pharmacology Of Novel Synthetic Iminoquinones As Anticancer Agents, Scharri Ezell

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Prostate cancer is the most common male malignancy and the second leading cause of cancer related death in the United States. Despite recent advances in the detection, diagnosis, and treatment of prostate cancer, there is a need for more effective therapies. Unfortunately, most conventional therapeutic modalities, such as androgen ablation therapy, frequently result in androgen-independent cancers. These cancers are typically more aggressive, metastatic, and resistant to chemotherapeutic agents than androgen-dependent prostate cancer. Therefore, agents that are effective against both androgen-sensitive and androgen-independent, as well as genetically diverse cancers are critically needed. The objective of the dissertation research was to address …


Regulation Of Mucosal Innate And Adaptive Immune Responses To Commensal Microbiota, Ting Feng Jan 2010

Regulation Of Mucosal Innate And Adaptive Immune Responses To Commensal Microbiota, Ting Feng

All ETDs from UAB

Host immune responses to the commensal microbiota are tightly controlled. Multiple levels of regulation reinforce intestinal homeostasis, including regulation by mucosal dendritic cells (DCs), regulatory T (Treg) cells, and the microbiota itself. However, the mechanisms involved are still largely unknown. Our current studies indicate that mucosal DCs originate and develop in the bone marrow, the latter of which is driven by retinoic acid (RA). Bone marrow cells express the RA-synthesizing enzyme ALDH, and provide RA to DC precursors in the bone marrow niche. RA induces DCs to express gut-homing CCR9 and ALDH1a2, and endows them with the ability to promote …


Identification And Validation Of Biodosimetry Markers In Multiple Models Of Radiation Exposure, Ashley Nicole Filiano Jan 2010

Identification And Validation Of Biodosimetry Markers In Multiple Models Of Radiation Exposure, Ashley Nicole Filiano

All ETDs from UAB

Following a radiological or nuclear disaster, radiation dose assessment is imperative to minimize morbidity and mortality through rationally directed medical intervention. Current methods of retrospective dosimetry are not amenable to mass exposure scenarios and remain limited to monitoring of clinical symptoms (nausea/vomiting and lymphocyte depletion) and cytogenetic analysis. The goal of this study was to identify radiation biomarkers capable of qualitative (non-irradiated/irradiated) and quantitative (dose) assessment of radiation exposure. Initial analyses revealed 17 radiation-responsive cytokine/chemokine genes in blood samples from 6 pediatric cancer patients undergoing fractionated total body irradiation (TBI). These 17 genes were combined with 29 additional IR-inducible genes …


Cellular Mechanisms Involved In Host Responses To Porphyromonas Gingivalis And Its Virulence Factor Hemagglutinin B, Dalia Emil Gaddis Jan 2010

Cellular Mechanisms Involved In Host Responses To Porphyromonas Gingivalis And Its Virulence Factor Hemagglutinin B, Dalia Emil Gaddis

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Porphyromonas gingivalis is a main causative agent for adult chronic periodontitis and immunization with its virulence factor Hemagglutinin B (HagB) provides protection against infection. Toll-like receptors (TLRs) recognize various microbial products and are crucial in eliciting and regulating the innate and adaptive immune responses to infections. The objective of this dissertation was to investigate the cellular mechanisms that influence the innate and adaptive immune response to HagB and P. gingivalis, focusing on the role of TLR signaling in the response. We started with investigating the ability of HagB to activate dendritic cells (DC), the most efficient antigen-presenting cell in priming …


Role Of 14-3-3&Tau In Autophagy And Role Of Edd In P53 Regulation, Shiyun Ling Jan 2010

Role Of 14-3-3&Tau In Autophagy And Role Of Edd In P53 Regulation, Shiyun Ling

All ETDs from UAB

Unrestricted cell proliferation and suppression of cell death are two essential events for tumor development. My dissertation research involves two proteins, 14-3-3 &tau and EDD which are involved in diverse pathways related to these two fields in recent studies. Previous study demonstrates that 14-3-3ô regulates p21 degradation. Up-regulation of 14-3-3ô is seen in breast cancer and is correlated with the down-regulation of p21 in breast cancer. Amplification or overexpression of EDD was observed in breast cancer and ovarian cancers. Illustrating the new roles of these two proteins in proliferation and cell death will advance our knowledge in tumorigenesis and help …


Lim Kinase 1 And Twinstar In Synaptic Plasticity Of Drosophila Motoneurons, James Brian Machamer Jan 2010

Lim Kinase 1 And Twinstar In Synaptic Plasticity Of Drosophila Motoneurons, James Brian Machamer

All ETDs from UAB

Modification of the actin cytoskeleton is essential for synaptic plasticity, which is believed to underlie the brain's capacity for learning and memory. Regulation of the actin cytoskeleton by LIM Kinases (LIMK1 and LIMK2) and their downstream targets Actin Depolymerization Factor/Cofilin (ADF/Cofilin) in the mouse forebrain modulates dendritic spine morphology, synaptic function, long-term potentiation (LTP), and learning and memory, but appear dispensable for the regulation of most forms of presynaptic plasticity. However, these analyses were performed in mice mutant for single members of these gene families, and thus the interpretation of these results is confounded by potential compensatory activity of homologous …


Developing A Screen To Identify Small Molecule Inhibitors That Disrupt Protein-Protein Interactions In Mycobacteria, Deborah Mai Jan 2010

Developing A Screen To Identify Small Molecule Inhibitors That Disrupt Protein-Protein Interactions In Mycobacteria, Deborah Mai

All ETDs from UAB

Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB) and infects nearly one-third of the world's population. The same TB chemotherapeutic regimen has been administered for more than 50 years, and can be improved by developing innovative methods to discover new anti-TB drugs. This work describes a newly established high-throughput screen (HTS) platform technology based on Mycobacterial-Protein Fragment Complementation (M-PFC) to identify small molecule inhibitors of protein-protein interactions in mycobacteria. M-PFC HTS employs both whole cell and target-based approaches, and offers flexibility in selecting an appropriate protein interaction target for HTS. Selectable drug targets can include interactions of essential …


Translocation And Function Of Akt In The Mitochondria, Keri A. Mans Jan 2010

Translocation And Function Of Akt In The Mitochondria, Keri A. Mans

All ETDs from UAB

The ubiquitously expressed kinase Akt is a known survival protein, and is involved in multiple cell signaling cascades, notably the phosphatidylinositol 3-kinase (PI3K) pathway. Active Akt translocates from the plasma membrane to different subcellular compartments, including mitochondria, where it phosphorylates compartment-specific substrates. The mechanism of this translocation and the specific function of Akt within the mitochondria remains a mystery. The goals of this study were to elucidate the mechanism by which Akt enters the mitochondria and examine the role of Akt in mitochondrial function. Finally, the possibilities of using post-mortem human brain tissue to study mitochondrial function in normal and …


Translation Initiation Signaling Components Altered By Mechanical Load Dictate Skeletal Muscle Hypertrophy, David Lawrence Mayhew Jan 2010

Translation Initiation Signaling Components Altered By Mechanical Load Dictate Skeletal Muscle Hypertrophy, David Lawrence Mayhew

All ETDs from UAB

The regulation of protein synthesis (i.e., mRNA translation) is an energetically costly and extensively regulated process, which is primarily regulated at the initiation step. Mechanical load is a potent stimulus of translation in skeletal muscle, and thus this tissue provides an excellent model system to study the plasticity of the translational apparatus. We investigated the effects of alterations in translation initiation cell signaling pathways in skeletal muscle using a variety of in vitro and in vivo mouse and human model systems. Collectively, our results suggest that, although many proteins in translational signaling pathways are responsive to mechanical load, the response …


Fiber Modification Of Adenoviral Vectors For Cancer Gene Therapy, Miho Murakami Jan 2010

Fiber Modification Of Adenoviral Vectors For Cancer Gene Therapy, Miho Murakami

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Cancer still remains a major public health concern despite improvements in primary prevention, early detection and advanced treatments. Cancer gene therapy using human adenovirus serotype 5 (HAdV-5) as a vector has been explored as a new therapeutic approach. HAdV-5 infection is initiated by binding to the coxsackie virus and adenovirus receptor (CAR), its primary cellular receptor. However, the levels and patterns of expression of CAR vary greatly in clinical tumor tissue samples, and the expression lev-els tend to decrease as the tumors progress. The low level expression of CAR in target cancer cells diminishes the utility of HAdV-5 as a …


Poxvirus Evolution: The Role Of Horizontal Gene Transfer, Mary Rebecca Odom Jan 2010

Poxvirus Evolution: The Role Of Horizontal Gene Transfer, Mary Rebecca Odom

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We have investigated the set of all poxvirus proteins for information about the origins of protein coding genes of the Poxviridae family of viruses. A global assessment of all poxvirus proteins for levels of similarity to proteins of other organisms, including eukaryotes, viruses, and prokaryotes, has suggested trends and relationships informative about poxvirus evolution and poxvirus interactions with hosts. Our research has focused on the poxvirus proteins subset this assessment identified as likely to have evolutionary histories involving horizontal gene transfer (HGT). We have used phylogenetic reconstructions to individually determine the sources of more than 70 horizontally transferred genes present …


A Nucleolar Specificity Factor For E2f1 Induced Cell Death, Jason Chang Paik Jan 2010

A Nucleolar Specificity Factor For E2f1 Induced Cell Death, Jason Chang Paik

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The E2F family of transcription factors are important regulators of cell proliferation, and are often dysregulated in cancers. One member of the E2F family, E2F1, also has the ability to induce apoptosis; therefore, uncovering how E2F1-induced apoptosis is controlled is of interest in understanding tumorigenesis. To this end, we identified RRP1B as a novel target specifically induced by E2F1. RRP1B expression is specifically upregulated by E2F1 overexpression, but not other E2F family members. RRP1B expression is correlated with E2F1 expression during the cell cycle, and is significantly induced after DNA damage. The minimal RRP1B promoter region responsive to E2F1 was …


Pneumococcal Vaccine Response And Aging In Human, Saeyoung Park Jan 2010

Pneumococcal Vaccine Response And Aging In Human, Saeyoung Park

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Streptococcus pneumoniae is a major human pathogen, especially for young children and older adults. To protect from pneumococcal diseases, 23-valent pneumococcal polysaccharide vaccine (PPV23) has been used clinically since 1983. However, PPV23 is not so effective among old adults with its protective efficacy diminishing with age. We confirmed that young and old adults, who were immunized with PPV23, have comparable pneumococcal polysaccharide (PS) specific IgG levels. Interestingly, we found that old adults had lower IgA and IgM antibody levels than young adults for three serotypes (serotype 14, 18C and 23F). Consistent with the previous results, opsonic capacities of immune sera …


Regulation Of Vascular Smooth Muscle Cell Signaling And Metabolism By Platelet-Derived Growth Factor, Jessica Perez Jan 2010

Regulation Of Vascular Smooth Muscle Cell Signaling And Metabolism By Platelet-Derived Growth Factor, Jessica Perez

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Growth factors are important inducers of vascular cell growth whose regulation is altered during the pathogenesis of atherosclerosis. An increase in growth factor and cytokine production, as well as lipid oxidation is observed in cardiovascular disease (CVD) and contributes to altered vascular cell signaling, exacerbated atherosclerotic lesions and heart failure. A change in cellular bioenergetic status due to mitochondrial dysfunction or damage has also been noted in CVD. In this thesis, we first examine cell signaling pathways in vascular smooth muscle cells (VSMC) which are activated in response to platelet-derived growth factor (PDGF) and regulate the cell cycle protein changes …


Molecular Mechanisms Of Breast Cancer Metastasis: Gap Junction Intercellular Communication And The Bone Microenvironment, Thomas Morgan Bodenstine Jan 2010

Molecular Mechanisms Of Breast Cancer Metastasis: Gap Junction Intercellular Communication And The Bone Microenvironment, Thomas Morgan Bodenstine

All ETDs from UAB

Metastatic disease accounts for the overwhelming majority of cancer related deaths. More specifically, breast cancer remains one of the leading causes of death in women and breast cancer cells metastasize to bone more than any other secondary site. Upon arriving within the bone microenvironment, breast cancer cells interact with bone marrow cells, leading to changes in bone biology that favor growth of the cancer cells. Additionally, some cancer cells are capable of direct cellular communication with cells at metastatic sites via dysregulation of a family of proteins known as connexins. This direct, physical communication is known as gap junctional intercellular …


Role Of Heme Oxygenase-1 In Acute Kidney Injury, Subhashini Bolisetty Jan 2010

Role Of Heme Oxygenase-1 In Acute Kidney Injury, Subhashini Bolisetty

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Acute kidney injury (AKI), defined as the rapid loss of kidney function, is often seen in the setting of multiple organ failure in critically ill patients. Lack of established therapeutic approaches to overcome AKI has lead to unacceptably high incidence of morbidity and mortality in these patients. The molecular mechanisms that lead to AKI often have oxidative stress as a common pathogenic event. The kidney responds by prompt induction of its own anti-oxidant machinery including the highly inducible, anti-inflammatory and anti-apoptotic gene-heme oxygenase-1 (HO-1). This microsomal enzyme degrades pro-oxidant heme, which is released from heme proteins. The cytoprotective properties of …


Role Of Transient Receptor Potential Canonical Channels In Glioma Cell Biology, Valerie Christine Bomben Jan 2010

Role Of Transient Receptor Potential Canonical Channels In Glioma Cell Biology, Valerie Christine Bomben

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ROLE OF TRANSIENT RECEPTOR POTENTIAL CANONICAL CHANNELS IN GLIOMA CELL BIOLOGY VALERIE C. BOMBEN DEPARTMENT OF NEUROBIOLOGY ABSTRACT Gliomas, primary brain tumors derived from glial cells, constitute the majority of malignant tumors within the central nervous system. The most malignant of these tumors, grade IV Glioblastoma multiforme, are characterized by extensive proliferation, cellular and nuclear atypia, angiogenesis, areas of necrosis, and widespread invasion into the brain parenchyma. Data from our lab and others have implicated ion channels in the invasion and proliferation of glioma cells. Moreover, calcium signaling in gliomas and other cells has been implicated in both migration and …


Analyzing Dna Topology And Transcription In Salmonella Enterica Serovar Typhimurium During Dichotomous Growth, Betty M. Booker Jan 2010

Analyzing Dna Topology And Transcription In Salmonella Enterica Serovar Typhimurium During Dichotomous Growth, Betty M. Booker

All ETDs from UAB

The bacterial chromosome is dynamic. The principle goal of my research is to understand how DNA topology is altered by transcription in Salmonella enterica serovar Typhimurium LT2. Gamma delta-resolution requires two direct repeat Res sites to pair a plectonemic synapse. Previous work from our lab showed that the zones of high transcription inhibited gamma delta-resolution. Using phage λ recombineering methods, we have developed Salmonella strains to study ribosomal RNA operons, which are the most highly transcribed genes in bacteria. We propose a molecular model for how supercoiling generated by high levels of transcription modifies chromosome structure.


Evolution Of Pneumococcal Serogroup 6, Preston Eugene Bratcher Jan 2010

Evolution Of Pneumococcal Serogroup 6, Preston Eugene Bratcher

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Serogroup 6 of Streptococcus pneumoniae has been known to contain three serotypes, named 6A, 6B and 6C, with highly homologous capsule gene loci. The 6A and 6B capsule gene loci consistently differ from each other by only one nucleotide in the wciP gene. The 6A capsule gene locus has a galactosyltransferase (wciNα), which has been replaced with a glucosyltransferase (wciNß) in the 6C capsule gene locus. We considered that a new serotype, 6D, would be possible if the glucosyltransferase found in 6C strains was combined with the wciP gene from a 6B strain. We demonstrate that this gene combination yields …


Regulation Of Apoptosis By Smac, Iaps , And The Ubiquitin Proteasome System, Stephen Peter Burke Jan 2010

Regulation Of Apoptosis By Smac, Iaps , And The Ubiquitin Proteasome System, Stephen Peter Burke

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Apoptosis, or programmed cell death, is essential for the development and maintenance of mammalian tissues. Activation of cysteinyl aspartate specific proteases, called caspases, is crucial to the implementation apoptosis. During apoptosis, the second mito-chondrial derived activator of caspase (Smac), augments caspase activity by antagonizing the inhibitor of apoptosis proteins (IAPs) down-regulation of caspase function. Smac protein synthesis occurs in the cytosol from a nuclear gene. Mitochondrial import of Smac leads to proteolytic removal of the first 55 amino acids, exposing a novel amino-terminus composed Ala56-Val-Pro-Ile59, which is an inhibitor of apoptosis binding motif (IBM). The IBM facilitates the interactions with …


Hpv Dna Partitioning During Mitosis As Followed By Fluorescence Microscopy, Robert J. Carter Jan 2010

Hpv Dna Partitioning During Mitosis As Followed By Fluorescence Microscopy, Robert J. Carter

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Human papillomaviruses (HPVs) are small, double-stranded deoxyribonucleic acid (DNA) tumor viruses capable of establishing persistent infections in the epithelia. After infecting actively-dividing basal cells, the papillomavirus (PV) genome is main-tained as extrachromosomal nuclear plasmids. It is largely unknown how the viral ge-nome is maintained in actively-dividing cells. Our lab demonstrated that several HPV genotypes appear to employ a distinct strategy to facilitate partitioning of HPV DNA into daughter cells during mitosis. Association of the HPV-11 origin of replication (ori)-binding protein E2 with the mitotic apparatus via cellular adapter proteins is thought to mediate equal partitioning of HPV genomes into daughter …


A Dual Protease Inhibitor/Receptor Antagonist With Therapeutic Implications For Chronic Inflammatory Lung Diseases, Matthew Thomas Hardison Jan 2010

A Dual Protease Inhibitor/Receptor Antagonist With Therapeutic Implications For Chronic Inflammatory Lung Diseases, Matthew Thomas Hardison

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Chronic neutrophilic inflammation is a hallmark of numerous pulmonary diseases. It is commonly associated with declining lung function, collagen turnover, and increased protease activity. Our laboratory has recently published several articles describing a biologically active collagen breakdown product, proline-glycine-proline (PGP) and its more active amino-terminus acetylated form, N-α-PGP. PGP acts via classical chemokine receptors CXCR1 and 2 to draw neutrophils (PMNs) into sites of inflammation in what is potentially a feed-forward mechanism of disease. The tri-peptide appears to be a bio-marker in certain clinical diseases like cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). The present work first details …