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Ef24, A Curcumin Analogue Inhibits The Migration And Invasion Of Highly Metastatic Breast Cancer Cells, Noor Abushagur, Debarshi Roy, Atasi De Chatterjee, Siddhartha Das Jul 2012

Ef24, A Curcumin Analogue Inhibits The Migration And Invasion Of Highly Metastatic Breast Cancer Cells, Noor Abushagur, Debarshi Roy, Atasi De Chatterjee, Siddhartha Das

COURI Symposium Abstracts, Summer 2012

In 2011, American Cancer Society reported that about 230,000 women were diagnosed with breast cancer in the US, and among them 40,000 died. This disease targets women of all ages and races, and although survival rates have increased recently, it is still a huge problem that influences the lives of millions of people. In case of non-metastatic breast cancers, patients are usually responsive to various treatments, but in patients with metastatic breast cancer the current medications are not fully effective. The goal of the current study is to evaluate the efficacy of a newly synthesized anti-cancer agent, EF-24, on metastatic …


Surveillance Of Mosquitoes For Arthropod-Borne Viruses In El Paso, Tx., Stephanie Coronado, Douglas Watts Jul 2012

Surveillance Of Mosquitoes For Arthropod-Borne Viruses In El Paso, Tx., Stephanie Coronado, Douglas Watts

COURI Symposium Abstracts, Summer 2012

West Nile encephalitis is the only arthropod-borne virus that causes annual cases of human illness in El Paso, Texas. Cases more commonly affect the young and elderly and the illness may range from a mild febrile disease to fatal encephalitis. The primary vector(s) of West Nile virus are Culex species mosquitoes, including Culex tarsalis and Culex quinquefaciatus. Further, surveillance is needed to determine the relative importance of these and possibly other mosquito species. More recently, cases of dengue fever and fatal hemorrhagic fever have been occurring in communities along the USA-Mexico border. Dengue has been endemic in Mexico since the …


Regulation Of Lipogenesis By Cyclin-Dependent Kinase 8-Mediated Control Of Srebp-1., Xiaoping Zhao, Daorong Feng, Qun Wang, Arian Abdulla, Xiao-Jun Xie, Jie Zhou, Yan Sun, Ellen S Yang, Lu-Ping Liu, Bhavapriya Vaitheesvaran, Lauren Bridges, Irwin J Kurland, Randy Strich, Jian-Quan Ni, Chenguang Wang, Johan Ericsson, Jeffrey E Pessin, Jun-Yuan Ji, Fajun Yang Jul 2012

Regulation Of Lipogenesis By Cyclin-Dependent Kinase 8-Mediated Control Of Srebp-1., Xiaoping Zhao, Daorong Feng, Qun Wang, Arian Abdulla, Xiao-Jun Xie, Jie Zhou, Yan Sun, Ellen S Yang, Lu-Ping Liu, Bhavapriya Vaitheesvaran, Lauren Bridges, Irwin J Kurland, Randy Strich, Jian-Quan Ni, Chenguang Wang, Johan Ericsson, Jeffrey E Pessin, Jun-Yuan Ji, Fajun Yang

Department of Cancer Biology Faculty Papers

Altered lipid metabolism underlies several major human diseases, including obesity and type 2 diabetes. However, lipid metabolism pathophysiology remains poorly understood at the molecular level. Insulin is the primary stimulator of hepatic lipogenesis through activation of the SREBP-1c transcription factor. Here we identified cyclin-dependent kinase 8 (CDK8) and its regulatory partner cyclin C (CycC) as negative regulators of the lipogenic pathway in Drosophila, mammalian hepatocytes, and mouse liver. The inhibitory effect of CDK8 and CycC on de novo lipogenesis was mediated through CDK8 phosphorylation of nuclear SREBP-1c at a conserved threonine residue. Phosphorylation by CDK8 enhanced SREBP-1c ubiquitination and protein …


Gastrointestinal Cell Mediated Immunity And The Microsporidia, Magali M. Moretto, Imtiaz A. Khan, Louis M. Weiss Jul 2012

Gastrointestinal Cell Mediated Immunity And The Microsporidia, Magali M. Moretto, Imtiaz A. Khan, Louis M. Weiss

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.


Germline Transgenesis And Insertional Mutagenesis In Schistosoma Mansoni Mediated By Murine Leukemia Virus, Gabriel Rinaldi, Sabine E. Eckert, Isheng J. Tsai, Suttas Suttiprapa, Kristine J. Kines, Jose F. Tort, Victoria H. Mann, Daniel J. Turner, Matthew Berriman, Paul J. Brindley Jul 2012

Germline Transgenesis And Insertional Mutagenesis In Schistosoma Mansoni Mediated By Murine Leukemia Virus, Gabriel Rinaldi, Sabine E. Eckert, Isheng J. Tsai, Suttas Suttiprapa, Kristine J. Kines, Jose F. Tort, Victoria H. Mann, Daniel J. Turner, Matthew Berriman, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Functional studies will facilitate characterization of role and essentiality of newly available genome sequences of the human schistosomes, Schistosoma mansoni, S. japonicum and S. haematobium. To develop transgenesis as a functional approach for these pathogens, we previously demonstrated that pseudotyped murine leukemia virus (MLV) can transduce schistosomes leading to chromosomal integration of reporter transgenes and short hairpin RNA cassettes. Here we investigated vertical transmission of transgenes through the developmental cycle of S. mansoni after introducing transgenes into eggs. Although MLV infection of schistosome eggs from mouse livers was efficient in terms of snail infectivity, >10-fold higher transgene copy …


Systemic Sclerosis Disease Modification Clinical Trials Design: Quo Vadis?, Fabian A. Mendoza, Md, Lynette L Keyes-Elstein, Sergio A. Jimenez Jul 2012

Systemic Sclerosis Disease Modification Clinical Trials Design: Quo Vadis?, Fabian A. Mendoza, Md, Lynette L Keyes-Elstein, Sergio A. Jimenez

Scleroderma Center Faculty Papers

The purpose of this manuscript is to discuss relevant aspects of clinical trials for Systemic Sclerosis (SSc) and to identify important considerations for the design of SSc disease modification clinical trials. Placebo randomized controlled trials with appropriate identification of SSc patients with diffuse progressive SSc skin involvement of recent onset, along with a rescue strategy for patients with worsening lung and skin involvement are suggested. If change in skin thickening is a major outcome of the study, the selection of patients with recent onset of disease and a predetermined degree of skin involvement are crucial requirements. The trial duration should …


Overexpression Of A Novel Cell Cycle Regulator Ecdysoneless In Breast Cancer: A Marker Of Poor Prognosis In Her2/Neu-Overexpressing Breast Cancer Patients., Xiangshan Zhao, Sameer Mirza, Alaa Alshareeda, Ying Zhang, Channabasavaiah B. Gurumurthy, Aditya Bele, Jun Hyun Kim, Shakur Mohibi, Monica Goswami, Subodh M. Lele, William West, Fang Qiu, Ian O. Ellis, Emad A. Rakha, Andrew R. Green, Hamid Band, Vimla Band Jul 2012

Overexpression Of A Novel Cell Cycle Regulator Ecdysoneless In Breast Cancer: A Marker Of Poor Prognosis In Her2/Neu-Overexpressing Breast Cancer Patients., Xiangshan Zhao, Sameer Mirza, Alaa Alshareeda, Ying Zhang, Channabasavaiah B. Gurumurthy, Aditya Bele, Jun Hyun Kim, Shakur Mohibi, Monica Goswami, Subodh M. Lele, William West, Fang Qiu, Ian O. Ellis, Emad A. Rakha, Andrew R. Green, Hamid Band, Vimla Band

Journal Articles: Genetics, Cell Biology & Anatomy

Uncontrolled proliferation is one of the hallmarks of breast cancer. We have previously identified the human Ecd protein (human ortholog of Drosophila Ecdysoneless, hereafter called Ecd) as a novel promoter of mammalian cell cycle progression, a function related to its ability to remove the repressive effects of Rb-family tumor suppressors on E2F transcription factors. Given the frequent dysregulation of cell cycle regulatory components in human cancer, we used immunohistochemistry of paraffin-embedded tissues to examine Ecd expression in normal breast tissue versus tissues representing increasing breast cancer progression. Initial studies of a smaller cohort without outcomes information showed that Ecd expression …


Two-Compartment Tumor Metabolism: Autophagy In The Tumor Microenvironment And Oxidative Mitochondrial Metabolism (Oxphos) In Cancer Cells., Ahmed F Salem, Diana Whitaker-Menezes, Zhao Lin, Ubaldo E. Martinez-Outshoorn, Herbert B Tanowitz, Mazhar Salim Al-Zoubi, Anthony Howell, Richard Pestell, Federica Sotgia, Michael P. Lisanti Jul 2012

Two-Compartment Tumor Metabolism: Autophagy In The Tumor Microenvironment And Oxidative Mitochondrial Metabolism (Oxphos) In Cancer Cells., Ahmed F Salem, Diana Whitaker-Menezes, Zhao Lin, Ubaldo E. Martinez-Outshoorn, Herbert B Tanowitz, Mazhar Salim Al-Zoubi, Anthony Howell, Richard Pestell, Federica Sotgia, Michael P. Lisanti

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Previously, we proposed a new paradigm to explain the compartment-specific role of autophagy in tumor metabolism. In this model, autophagy and mitochondrial dysfunction in the tumor stroma promotes cellular catabolism, which results in the production of recycled nutrients. These chemical building blocks and high-energy "fuels" would then drive the anabolic growth of tumors, via autophagy resistance and oxidative mitochondrial metabolism in cancer cells. We have termed this new form of stromal-epithelial metabolic coupling: "two-compartment tumor metabolism." Here, we stringently tested this energy-transfer hypothesis, by genetically creating (1) constitutively autophagic fibroblasts, with mitochondrial dysfunction or (2) autophagy-resistant cancer cells, with increased …


Microbial Co-Occurrence Relationships In The Human Microbiome, Karoline Faust, J. Fah Sathirapongsasuti, Jacques Izard, Dirk Gevers, Jeroen Raes, Curtis Huttenhower Jul 2012

Microbial Co-Occurrence Relationships In The Human Microbiome, Karoline Faust, J. Fah Sathirapongsasuti, Jacques Izard, Dirk Gevers, Jeroen Raes, Curtis Huttenhower

Department of Food Science and Technology: Faculty Publications

The healthy microbiota show remarkable variability within and among individuals. In addition to external exposures, ecological relationships (both oppositional and symbiotic) between microbial inhabitants are important contributors to this variation. It is thus of interest to assess what relationships might exist among microbes and determine their underlying reasons. The initial Human Microbiome Project (HMP) cohort, comprising 239 individuals and 18 different microbial habitats, provides an unprecedented resource to detect, catalog, and analyze such relationships. Here, we applied an ensemble method based on multiple similarity measures in combination with generalized boosted linear models (GBLMs) to taxonomic marker (16S rRNA gene) profiles …


Prevalence Of Streptococci And Increased Polymicrobial Diversity Associated With Cystic Fibrosis Patient Stability, L. M. Filkins, T. H. Hampton, A. H. Gifford, M. J. Gross, D. A. Hogan, M. L. Sogin, H. G. Morrison, B. J. Paster, G. A. O'Toole Jun 2012

Prevalence Of Streptococci And Increased Polymicrobial Diversity Associated With Cystic Fibrosis Patient Stability, L. M. Filkins, T. H. Hampton, A. H. Gifford, M. J. Gross, D. A. Hogan, M. L. Sogin, H. G. Morrison, B. J. Paster, G. A. O'Toole

Dartmouth Scholarship

Diverse microbial communities chronically colonize the lungs of cystic fibrosis patients. Pyrosequencing of amplicons for hypervariable regions in the 16S rRNA gene generated taxonomic profiles of bacterial communities for sputum genomic DNA samples from 22 patients during a state of clinical stability (outpatients) and 13 patients during acute exacerbation (inpatients). We employed quantitative PCR (qPCR) to confirm the detection of Pseudomonas aeruginosa and Streptococcus by the pyrosequencing data and human oral microbe identification microarray (HOMIM) analysis to determine the species of the streptococci identified by pyrosequencing. We show that outpatient sputum samples have significantly higher bacterial diversity than inpatients, but …


Associations Between Toenail Arsenic Concentration And Dietary Factors In A New Hampshire Ppopulation, Joann F. Gruber, Margaret R. Karagas, Diane Gilbert-Diamond, Pamela J. Bagley, M Scot Zens, Vicki Sayarath, Tracy Punshon, J Steven Morris, Kathryn L. Cottingham Jun 2012

Associations Between Toenail Arsenic Concentration And Dietary Factors In A New Hampshire Ppopulation, Joann F. Gruber, Margaret R. Karagas, Diane Gilbert-Diamond, Pamela J. Bagley, M Scot Zens, Vicki Sayarath, Tracy Punshon, J Steven Morris, Kathryn L. Cottingham

Dartmouth Scholarship

Background: Dietary factors such as folate, vitamin B12, protein, and methionine are important for the excretion of arsenic via one-carbon metabolism in undernourished populations exposed to high levels of arsenic via drinking water. However, the effects of dietary factors on toenail arsenic concentrations in well-nourished populations exposed to relatively low levels of water arsenic are unknown.

Methods: As part of a population-based case-control study of skin and bladder cancer from the USA, we evaluated relationships between consumption of dietary factors and arsenic concentrations in toenail clippings. Consumption of each dietary factor was determined from a validated food frequency questionnaire. We …


Il-4 Engagement Of The Type 1 Il-4 Receptor Complex Enhances Mouse Eosinophil Migration To Eotaxin-1 In Vitro, Nicola M. Heller, William M. Gwinn, Raymond P. Donnelly, Stephanie L. Constant, Achsah D. Keegan Jun 2012

Il-4 Engagement Of The Type 1 Il-4 Receptor Complex Enhances Mouse Eosinophil Migration To Eotaxin-1 In Vitro, Nicola M. Heller, William M. Gwinn, Raymond P. Donnelly, Stephanie L. Constant, Achsah D. Keegan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Previous work from our laboratory demonstrated that IL-4Rα expression on a myeloid cell type was responsible for enhancement of Th2-driven eosinophilic inflammation in a mouse model of allergic lung inflammation. Subsequently, we have shown that IL-4 signaling through type I IL-4 receptors on monocytes/macrophages strongly induced activation of the IRS-2 pathway and a subset of genes characteristic of alternatively activated macrophages. The direct effect(s) of IL-4 and IL-13 on mouse eosinophils are not clear. The goal of this study was determine the effect of IL-4 and IL-13 on mouse eosinophil function.

Methods

Standard Transwell chemotaxis assay was used to …


Visualizing Spatiotemporal Dynamics Of Apoptosis After G1 Arrest By Human T Cell Leukemia Virus Type 1 Tax And Insights Into Gene Expression Changes Using Microarray-Based Gene Expression Analysis., Mariluz Araínga, Hironobu Murakami, Yoko Aida Jun 2012

Visualizing Spatiotemporal Dynamics Of Apoptosis After G1 Arrest By Human T Cell Leukemia Virus Type 1 Tax And Insights Into Gene Expression Changes Using Microarray-Based Gene Expression Analysis., Mariluz Araínga, Hironobu Murakami, Yoko Aida

Journal Articles: Pharmacology & Experimental Neuroscience

BACKGROUND: Human T cell leukemia virus type 1 (HTLV-1) Tax is a potent activator of viral and cellular gene expression that interacts with a number of cellular proteins. Many reports show that Tax is capable of regulating cell cycle progression and apoptosis both positively and negatively. However, it still remains to understand why the Tax oncoprotein induces cell cycle arrest and apoptosis, or whether Tax-induced apoptosis is dependent upon its ability to induce G1 arrest. The present study used time-lapse imaging to explore the spatiotemporal patterns of cell cycle dynamics in Tax-expressing HeLa cells containing the fluorescent ubiquitination-based cell cycle …


Characterizing The Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis And Metastatic Progression Using Mouse Models Of Breast Cancer., Suehyb Alkhatib Jun 2012

Characterizing The Role Of Nucleosome Remodeling Factor (Nurf) In Tumorigenesis And Metastatic Progression Using Mouse Models Of Breast Cancer., Suehyb Alkhatib

Theses and Dissertations

Increasingly the role of epigenetic machinery as a bridge between underlying DNA sequence and cellular phenotype is being discovered. The establishment of a myriad of unique cellular types sharing identical gene sequences in a multicellular organism gives a broad sense for the inherent role of epigenetic influence on cell differentiation. Importantly, the epigenetic mechanisms involved in establishing cell identity unsurprisingly contribute to diseased states, including cancer. Recent research continues to elucidate contributory roles of epigenetic mechanisms, such as DNA methylation, histone modification, and microRNA regulation, in human cancers. Additionally, chromatin remodelers, such as the Nucleosome Remodeling Factor (NURF), have been …


Autophagy And Senescence In Cancer-Associated Fibroblasts Metabolically Supports Tumor Growth And Metastasis Via Glycolysis And Ketone Production., Claudia Capparelli, Carmela Guido, Diana Whitaker-Menezes, Phd, Gloria Bonuccelli, Renee Balliet, Timothy G Pestell, Allison F Goldberg, Richard Pestell, Anthony Howell, Sharon Sneddon, Ruth Birbe, Aristotelis Tsirigos, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P. Lisanti Jun 2012

Autophagy And Senescence In Cancer-Associated Fibroblasts Metabolically Supports Tumor Growth And Metastasis Via Glycolysis And Ketone Production., Claudia Capparelli, Carmela Guido, Diana Whitaker-Menezes, Phd, Gloria Bonuccelli, Renee Balliet, Timothy G Pestell, Allison F Goldberg, Richard Pestell, Anthony Howell, Sharon Sneddon, Ruth Birbe, Aristotelis Tsirigos, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P. Lisanti

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Senescent fibroblasts are known to promote tumor growth. However, the exact mechanism remains largely unknown. An important clue comes from recent studies linking autophagy with the onset of senescence. Thus, autophagy and senescence may be part of the same physiological process, known as the autophagy-senescence transition (AST). To test this hypothesis, human fibroblasts immortalized with telomerase (hTERT-BJ1) were stably transfected with autophagy genes (BNIP3, CTSB or ATG16L1). Their overexpression was sufficient to induce a constitutive autophagic phenotype, with features of mitophagy, mitochondrial dysfunction and a shift toward aerobic glycolysis, resulting in L-lactate and ketone body production. Autophagic fibroblasts also showed …


Ctgf Drives Autophagy, Glycolysis And Senescence In Cancer-Associated Fibroblasts Via Hif1 Activation, Metabolically Promoting Tumor Growth., Claudia Capparelli, Diana Whitaker-Menezes, Carmela Guido, Renee Balliet, Timothy G Pestell, Anthony Howell, Sharon Sneddon, Richard Pestell, Ubaldo E. Martinez-Outshoorn, Michael P. Lisanti, Federica Sotgia Jun 2012

Ctgf Drives Autophagy, Glycolysis And Senescence In Cancer-Associated Fibroblasts Via Hif1 Activation, Metabolically Promoting Tumor Growth., Claudia Capparelli, Diana Whitaker-Menezes, Carmela Guido, Renee Balliet, Timothy G Pestell, Anthony Howell, Sharon Sneddon, Richard Pestell, Ubaldo E. Martinez-Outshoorn, Michael P. Lisanti, Federica Sotgia

Department of Stem Cell Biology and Regenerative Medicine Faculty Papers & Presentations

Previous studies have demonstrated that loss of caveolin-1 (Cav-1) in stromal cells drives the activation of the TGF-β signaling, with increased transcription of TGF-β target genes, such as connective tissue growth factor (CTGF). In addition, loss of stromal Cav-1 results in the metabolic reprogramming of cancer-associated fibroblasts, with the induction of autophagy and glycolysis. However, it remains unknown if activation of the TGF-β / CTGF pathway regulates the metabolism of cancer-associated fibroblasts. Therefore, we investigated whether CTGF modulates metabolism in the tumor microenvironment. For this purpose, CTGF was overexpressed in normal human fibroblasts or MDA-MB-231 breast cancer cells. Overexpression of …


Lapg, Required For Modulating Biofilm Formation By Pseudomonas Fluorescens Pf0-1, Is A Calcium-Dependent Protease, Chelsea D. Boyd, Debashree Chatterjee, Holger Sondermann, George A. O'Toole Jun 2012

Lapg, Required For Modulating Biofilm Formation By Pseudomonas Fluorescens Pf0-1, Is A Calcium-Dependent Protease, Chelsea D. Boyd, Debashree Chatterjee, Holger Sondermann, George A. O'Toole

Dartmouth Scholarship

Biofilm formation by Pseudomonas fluorescens Pf0-1 requires the cell surface adhesin LapA. We previously reported that LapG, a periplasmic cysteine protease of P. fluorescens, cleaves the N terminus of LapA, thus releasing this adhesin from the cell surface and resulting in loss of the ability to make a biofilm. The activity of LapG is regulated by the inner membrane-localized cyclic-di-GMP receptor LapD via direct protein-protein interactions. Here we present chelation and metal add-back studies demonstrating that calcium availability regulates biofilm formation by P. fluorescens Pf0-1. The determination that LapG is a calcium-dependent protease, based on in vivo and in vitro …


Engrailed Cooperates Directly With Extradenticle And Homothorax On A Distinct Class Of Homeodomain Binding Sites To Repress Sloppy Paired., Miki Fujioka, Brian Gebelein, Zenobia C Cofer, Richard S Mann, James B Jaynes Jun 2012

Engrailed Cooperates Directly With Extradenticle And Homothorax On A Distinct Class Of Homeodomain Binding Sites To Repress Sloppy Paired., Miki Fujioka, Brian Gebelein, Zenobia C Cofer, Richard S Mann, James B Jaynes

Department of Biochemistry and Molecular Biology Faculty Papers

Even skipped (Eve) and Engrailed (En) are homeodomain-containing transcriptional repressors with similar DNA binding specificities that are sequentially expressed in Drosophila embryos. The sloppy-paired (slp) locus is a target of repression by both Eve and En. At blastoderm, Eve is expressed in 7 stripes that restrict the posterior border of slp stripes, allowing engrailed (en) gene expression to be initiated in odd-numbered parasegments. En, in turn, prevents expansion of slp stripes after Eve is turned off. Prior studies showed that the two tandem slp transcription units are regulated by cis-regulatory modules (CRMs) with activities that overlap in space and time. …


Structure, Function And Diversity Of The Healthy Human Microbiome, Curtis Huttenhower, Jacques Izard Jun 2012

Structure, Function And Diversity Of The Healthy Human Microbiome, Curtis Huttenhower, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. …


Antioxidant Rescue Of Nf1/Ras-Induced Myelin And Vasculature Dysfunction, Debra A. Mayes, Tilat A. Rizvi, Shyra J. Miller, Rachel Oberst, Anat Stemmer-Rachamimov, Nancy Ratner Jun 2012

Antioxidant Rescue Of Nf1/Ras-Induced Myelin And Vasculature Dysfunction, Debra A. Mayes, Tilat A. Rizvi, Shyra J. Miller, Rachel Oberst, Anat Stemmer-Rachamimov, Nancy Ratner

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.


Elucidating Genetic And Environmental Influences On Alcohol-Related Phenotypes, Jacquelyn Meyers Jun 2012

Elucidating Genetic And Environmental Influences On Alcohol-Related Phenotypes, Jacquelyn Meyers

Theses and Dissertations

Decades of work has led researchers to believe that risk for complex behavioral phenotypes, such as alcohol use disorders, is likely influenced by multiple genes of small effect acting in conjunction with each other and the environment. Currently, the field of psychiatric genetics is developing methodologies for the identification of genetic risk variants that predispose individuals to the development of complex behavioral disorders. Several challenges related to the complex and polygenic nature of these phenotypes, must be considered. This dissertation study attempts to address these important challenges in the context of alcohol use disorders and related phenotypes. A rich twin …


Unique Features And Neuronal Properties In A Multisensory Cortex, W. Alex Foxworthy Jun 2012

Unique Features And Neuronal Properties In A Multisensory Cortex, W. Alex Foxworthy

Theses and Dissertations

UNIQUE FEAUTRES OF ORGANIZATION AND NEURONAL PROPERTIES IN A MULTISENSORY CORTEX Multisensory processing is a ubiquitous sensory effect that underlies a wide variety of behaviors, such as detection and orientation, as well as perceptual phenomena from speech comprehension to binding. Such multisensory perceptual effects are presumed to be based in cortex, especially within areas known to contain multisensory neurons. However, unlike their lower-level/primary sensory cortical counterparts, little is known about the connectional, functional and laminar organization of higher-level multisensory cortex. Therefore, to examine the fundamental features of neuronal processing and organization in the multisensory cortical area of the posterior parietal …


Med5(Nut1) And Med17(Srb4) Are Direct Targets Of Mediator Histone H4 Tail Interactions, Zhongle Liu, Lawrence C. Myers Jun 2012

Med5(Nut1) And Med17(Srb4) Are Direct Targets Of Mediator Histone H4 Tail Interactions, Zhongle Liu, Lawrence C. Myers

Dartmouth Scholarship

The Mediator complex transmits activation signals from DNA bound transcription factors to the core transcription machinery. In addition to its canonical role in transcriptional activation, recent studies have demonstrated that S. cerevisiae Mediator can interact directly with nucleosomes, and their histone tails. Mutations in Mediator subunits have shown that Mediator and certain chromatin structures mutually impact each other structurally and functionally in vivo. We have taken a UV photo cross-linking approach to further delineate the molecular basis of Mediator chromatin interactions and help determine whether the impact of certain Mediator mutants on chromatin is direct. Specifically, by using histone …


Toward A Working Theory Of Neurorhetorics, Jeffrey L. Honnold Jun 2012

Toward A Working Theory Of Neurorhetorics, Jeffrey L. Honnold

USF Tampa Graduate Theses and Dissertations

This piece makes the claim that rhetoric is first philosophy--before philosophy, epistemology, ontology, or any other field--or that rhetoric is, at the least, on equal footing as these fields because:

empathy--and thusly the impulse for communication--is physiologically hardwired into humans; special distinctions between human and animal are largely artificial constructions, as is evidenced by neurosciences; "hard" science, in the form of neurosciences, is providing entrance points & opportunities for rhetoric to raise its status within the academy; and said neurosciences, in addition to empathy studies, have shown strong evidence supporting linguistic and evolutionary links between humans and other species, thereby …


Selective Impact Of Hiv Disease Progression On The Innate Immune System In The Human Female Reproductive Tract, Timothy Lahey, Mimi Ghosh, John V. Fahey, Zheng Shen, Lucy R. Mukura, Yan Song, Susan Cu-Uvin, Kenneth H. Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira Jun 2012

Selective Impact Of Hiv Disease Progression On The Innate Immune System In The Human Female Reproductive Tract, Timothy Lahey, Mimi Ghosh, John V. Fahey, Zheng Shen, Lucy R. Mukura, Yan Song, Susan Cu-Uvin, Kenneth H. Mayer, Peter F. Wright, John C. Kappes, Christina Ochsenbauer, Charles R. Wira

Dartmouth Scholarship

Background: We have previously demonstrated intrinsic anti-HIV activity in cervicovaginal lavage (CVL) from HIV-infected women with high CD4 counts and not on antiretroviral therapy. However, the impact of HIV disease progression on CVL innate immune responses has not been delineated.

Methods: CVL from 57 HIV-infected women not on antiretroviral therapy were collected by washing the cervicovaginal area with 10 ml of sterile normal saline. We characterized subject HIV disease progression by CD4 count strata: >500 cells/µl, 200-500 cells/µl, or <200 cells/µl of blood. To assess CVL anti-HIV activity, we incubated TZM-bl cells with HIV plus or minus CVL. Antimicrobials, cytokines, chemokines and anti-gp160 HIV IgG antibodies were measured by ELISA and Luminex.


Vasa-Like Dead-Box Rna Helicases Of Schistosoma Mansoni, Danielle E. Skinner, Gabriel Rinaldi, Sutas Suttiprapa, Victoria H. Mann, Pablo Smircich, Alexis A. Cogswell, David L. Williams, Paul J. Brindley Jun 2012

Vasa-Like Dead-Box Rna Helicases Of Schistosoma Mansoni, Danielle E. Skinner, Gabriel Rinaldi, Sutas Suttiprapa, Victoria H. Mann, Pablo Smircich, Alexis A. Cogswell, David L. Williams, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Genome sequences are available for the human blood flukes, Schistosoma japonicum, S. mansoni and S. haematobium. Functional genomic approaches could aid in identifying the role and importance of these newly described schistosome genes. Transgenesis is established for functional genomics in model species, which can lead to gain- or loss-of-functions, facilitate vector-based RNA interference, and represents an effective forward genetics tool for insertional mutagenesis screens. Progress toward routine transgenesis in schistosomes might be expedited if germ cells could be reliably localized in cultured schistosomes. Vasa, a member of the ATP-dependent DEAD-box RNA helicase family, is a prototypic marker of …


Chemistry-Dependent Adsorption Of Serum Proteins Onto Polyanhydride Microparticles Differentially Influences Dendritic Cell Uptake And Activation, Brenda R. Carrillo-Conde, Amanda E. Ramer-Tait, Michael J. Wannemeuhler, Balaji Narasimhan Jun 2012

Chemistry-Dependent Adsorption Of Serum Proteins Onto Polyanhydride Microparticles Differentially Influences Dendritic Cell Uptake And Activation, Brenda R. Carrillo-Conde, Amanda E. Ramer-Tait, Michael J. Wannemeuhler, Balaji Narasimhan

Amanda Ramer-Tait Publications

The delivery of antigen-loaded microparticles to dendritic cells (DCs) may benefit from surface optimization of the microparticles themselves, thereby exploiting the material properties and introducing signals that mimic pathogens. Following in vivo administration microparticle surface characteristics are likely to be significantly modified as proteins are quickly adsorbed onto their surface. In this work we describe the chemistry-dependent serum protein adsorption patterns on polyanhydride particles and the implications for their molecular interactions with DCs. The enhanced expression of MHC II and CD40 on DCs after incubation with amphiphilic polyanhydride particles, and the increased secretion of IL-6, TNF-α, and IL-12p40 by hydrophobic …


Healthy Volunteer Registries And Ethical Research Principles, Erine A. Kupetsky-Rincon, Walter K. Kraft Jun 2012

Healthy Volunteer Registries And Ethical Research Principles, Erine A. Kupetsky-Rincon, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The dual enrolling of phase I volunteers is a potential risk to subjects. It can also distort study results, threaten study validity, and possibly cause harm to future patients. Existing subject registries differ in structure, funding, and governance. Although the choice of the ideal system is driven by the scope of the risk and the funding mechanism, and is ultimately a value judgment of freedom versus paternalism, none of the registries significantly impinges on the tenets of ethically based research.


Harvesting Murine Alveolar Macrophages And Evaluating Cellular Activation Induced By Polyanhydride Nanoparticles, Ana V. Chavez-Santoscoy, Lucas M. Huntlimer, Amanda E. Ramer-Tait, Michael J. Wannemeuhler, Balaji Narasimhan Jun 2012

Harvesting Murine Alveolar Macrophages And Evaluating Cellular Activation Induced By Polyanhydride Nanoparticles, Ana V. Chavez-Santoscoy, Lucas M. Huntlimer, Amanda E. Ramer-Tait, Michael J. Wannemeuhler, Balaji Narasimhan

Amanda Ramer-Tait Publications

Biodegradable nanoparticles have emerged as a versatile platform for the design and implementation of new intranasal vaccines against respiratory infectious diseases. Specifically, polyanhydride nanoparticles composed of the aliphatic sebacic acid (SA), the aromatic 1,6-bis(p-carboxyphenoxy)hexane (CPH), or the amphiphilic 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) display unique bulk and surface erosion kinetics and can be exploited to slowly release functional biomolecules (e.g. protein antigens, immunoglobulins, etc.) in vivo. These nanoparticles also possess intrinsic adjuvant activity, making them an excellent choice for a vaccine delivery platform.

In order to elucidate the mechanisms governing the activation of innate immunity following intranasal mucosal …


Development Of A Protocol To Measure Gene Expression In The Mouse Tibia, Daniel Hoover Jun 2012

Development Of A Protocol To Measure Gene Expression In The Mouse Tibia, Daniel Hoover

Biomedical Engineering

Numerous molecular factors active in bone tissue direct fracture repair and remodeling which can be altered by disease conditions such as Peripheral Arterial Disease (PAD) and Osteoporosis. Methods of molecular biology are commonly applied to investigate the expression and role of these molecular factors. This project presents a robust three-step protocol for examining gene expression in the mouse tibia. The protocol begins with isolating RNA from a flash frozen tibia sample. The isolated RNA is reverse transcribed into cDNA. Finally, PCR is performed to indentify expressed genes. Establishing this protocol will allow further research into the mechanisms of bone remodeling …