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Augmented Cocaine Seeking In Response To Stress Or Crf Delivered Into The Ventral Tegmental Area Following Long-Access Self-Administration Is Mediated By Crf Receptor Type 1 But Not Crf Receptor Type 2, Jordan M. Blacktop, Chad Seubert, David A. Baker, Nathan Ferda, Geng Lee, Evan N. Graf, John R. Mantsch Aug 2011

Augmented Cocaine Seeking In Response To Stress Or Crf Delivered Into The Ventral Tegmental Area Following Long-Access Self-Administration Is Mediated By Crf Receptor Type 1 But Not Crf Receptor Type 2, Jordan M. Blacktop, Chad Seubert, David A. Baker, Nathan Ferda, Geng Lee, Evan N. Graf, John R. Mantsch

Biomedical Sciences Faculty Research and Publications

Stressful events are determinants of relapse in recovering cocaine addicts. Excessive cocaine use may increase susceptibility to stressor-induced relapse through alterations in brain corticotropin-releasing factor (CRF) regulation of neurocircuitry involved in drug seeking. We previously reported that the reinstatement of cocaine seeking by a stressor (footshock) is CRF dependent and is augmented in rats that self-administered cocaine under long-access (LgA; 6 h daily) conditions for 14 d when compared with rats provided shorter daily cocaine access [short access (ShA) rats; 2 h daily]. Further, we have demonstrated that reinstatement in response to intracerebroventricular CRF administration is heightened in LgA rats. …


Natural And Synthetic Corticosteroids Inhibit Uptake2-Mediated Transport In Cns Neurons, Jonathan E. Hill, Khadijah Makky, Lalita Shrestha, Cecilia J. Hillard, Paul J. Gasser Aug 2011

Natural And Synthetic Corticosteroids Inhibit Uptake2-Mediated Transport In Cns Neurons, Jonathan E. Hill, Khadijah Makky, Lalita Shrestha, Cecilia J. Hillard, Paul J. Gasser

Biomedical Sciences Faculty Research and Publications

In addition to exerting actions via mineralocorticoid and glucocorticoid receptors, corticosteroids also act by inhibiting uptake2, a high-capacity monoamine transport system originally described in peripheral tissues. Recent studies have demonstrated that uptake2 transporters are expressed in the brain and play roles in monoamine clearance, suggesting that they mediate some corticosteroid effects on physiological and behavioral processes. However, the sensitivity of brain uptake2 to many natural and synthetic corticosteroids has not been characterized. Cultured rat cerebellar granule neurons (CGNs) were previously shown to exhibit corticosterone-sensitive accumulation of the uptake2 substrate1-methyl-4-phenylpyridinium (MPP+). We examined the …


A Role For Mir-296 In The Regulation Of Lipoapoptosis By Targeting Puma., Sophie C. Cazanave, Justin L. Mott, Nafisa A. Elmi, Steven F. Bronk, Howard C. Masuoka, Michael R. Charlton, Gregory J. Gores Aug 2011

A Role For Mir-296 In The Regulation Of Lipoapoptosis By Targeting Puma., Sophie C. Cazanave, Justin L. Mott, Nafisa A. Elmi, Steven F. Bronk, Howard C. Masuoka, Michael R. Charlton, Gregory J. Gores

Journal Articles: Biochemistry & Molecular Biology

Saturated free fatty acids (FFA) induce hepatocyte lipoapoptosis, a key mediator of liver injury in nonalcoholic fatty liver disease (NAFLD). Lipoapoptosis involves the upregulation of the BH3-only protein PUMA, a potent pro-apoptotic protein. Given that dysregulation of hepatic microRNA expression has been observed in NAFLD, we examined the role of miRNA in regulating PUMA expression during lipotoxicity. By in silico analysis, we identified two putative binding sites for miR-296-5p within the 3' untranslated region (UTR) of PUMA mRNA. Enforced miR-296-5p levels efficiently reduced PUMA protein expression in Huh-7 cells, while antagonism of miR-296-5p function increased PUMA cellular levels. Reporter gene …


Extracellular Atp Acts On P2y2 Purinergic Receptors To Facilitate Hiv-1 Infection, Claire Séror, Marie-Therese Melki, Frederic Subra, Syed Qasim Raza, Marlene Bras, Hela Saïdi, Roberta Nardacci, Laurent Voisin, Audrey Paoletti, Frederic Law, Isabelle Martins, Alessandra Amendola, Ali A. Abdul-Sater, Fabiola Ciccosanti, Olivier Delelis, Florence Niedergang, Sylvain Thierry, Najwane Said-Sadier, Christophe Lamaze, Didier Métivier, Jerome Estaquier, Gian Maria Fimia, Laura Falasca, Rita Casetti, Nazanine Modjtahedi, Jean M. Kanellopoulos, Jean-Francois Mouscadet, David M. Ojcius, Mauro Piacentini, Marie-Lise Gougeon, Guido Kroemer, Jean-Luc Perfetini Aug 2011

Extracellular Atp Acts On P2y2 Purinergic Receptors To Facilitate Hiv-1 Infection, Claire Séror, Marie-Therese Melki, Frederic Subra, Syed Qasim Raza, Marlene Bras, Hela Saïdi, Roberta Nardacci, Laurent Voisin, Audrey Paoletti, Frederic Law, Isabelle Martins, Alessandra Amendola, Ali A. Abdul-Sater, Fabiola Ciccosanti, Olivier Delelis, Florence Niedergang, Sylvain Thierry, Najwane Said-Sadier, Christophe Lamaze, Didier Métivier, Jerome Estaquier, Gian Maria Fimia, Laura Falasca, Rita Casetti, Nazanine Modjtahedi, Jean M. Kanellopoulos, Jean-Francois Mouscadet, David M. Ojcius, Mauro Piacentini, Marie-Lise Gougeon, Guido Kroemer, Jean-Luc Perfetini

All Dugoni School of Dentistry Faculty Articles

Extracellular adenosine triphosphate (ATP) can activate purinergic receptors of the plasma membrane and modulate multiple cellular functions. We report that ATP is released from HIV-1 target cells through pannexin-1 channels upon interaction between the HIV-1 envelope protein and specific target cell receptors. Extracellular ATP then acts on purinergic receptors, including P2Y2, to activate proline-rich tyrosine kinase 2 (Pyk2) kinase and transient plasma membrane depolarization, which in turn stimulate fusion between Env-expressing membranes and membranes containing CD4 plus appropriate chemokine co-receptors. Inhibition of any of the constituents of this cascade (pannexin-1, ATP, P2Y2, and Pyk2) impairs the replication of HIV-1 mutant …


Rip1-Dependent And Independent Effects Of Necrostatin-1 In Necrosis And T Cell Activation., Youngsik Cho, Thomas Mcquade, Haibing Zhang, Jianke Zhang, Francis Ka-Ming Chan Aug 2011

Rip1-Dependent And Independent Effects Of Necrostatin-1 In Necrosis And T Cell Activation., Youngsik Cho, Thomas Mcquade, Haibing Zhang, Jianke Zhang, Francis Ka-Ming Chan

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: Programmed necrosis/necroptosis is an emerging form of cell death that plays important roles in mammalian development and the immune system. The pro-necrotic kinases in the receptor interacting protein (RIP) family are crucial mediators of programmed necrosis. Recent advances in necrosis research have been greatly aided by the identification of chemical inhibitors that block programmed necrosis. Necrostatin-1 (Nec-1) and its derivatives were previously shown to target the pro-necrotic kinase RIP1/RIPK1. The protective effect conferred by Nec-1 and its derivatives in many experimental model systems was often attributed to the inhibition of RIP1 function.

METHODOLOGY/PRINCIPAL FINDINGS: We compared the effect of …


The Effects Of Hypothermia On Status Epilepticus-Induced Acquired Epilepsy, Kristin Phillips Aug 2011

The Effects Of Hypothermia On Status Epilepticus-Induced Acquired Epilepsy, Kristin Phillips

Theses and Dissertations

Status epilepticus (SE) is a type of neurological injury characterized by continuous seizure activity and can lead to molecular and pathophysiological alterations leading to plasticity changes. SE can lead to the development of AE by the process of epileptogenesis, which is a phenomenon that describes the transformation of normal brain tissue into a hyperexcitable neuronal population. It has been demonstrated both in vivo and in vitro that calcium (Ca2+) dynamics are severely altered during and after SE, and these changes play a major role in the progression of epileptogenesis. It has also been reported that preventing the rise in intracellular …


The Role Of The Androgen Receptor Cofactor P44/Wdr77 In Astrocyte Activation, Bryce H. Vincent Aug 2011

The Role Of The Androgen Receptor Cofactor P44/Wdr77 In Astrocyte Activation, Bryce H. Vincent

Dissertations and Theses (Open Access)

Astrogliosis is induced by neuronal damage and is also a pathological feature of the major aging-related neurodegenerative disorders. The mechanisms that control the cascade of astrogliosis have not been well established. In a previous study, we identified a novel androgen receptor (AR)-interacting protein (p44/WDR77) and found that it plays a critical role in the control of proliferation and differentiation of prostate epithelial cells. In the present study, we found that deletion of the p44 gene in the mouse brain caused accelerated aging with dramatic astrogliosis. The p44/WDR77 is expressed in astrocytes and loss of p44/WDR77 expression in astrocytes leads to …


Role Of Prostaglandin E2 In The Regulation Of Pancreatic Stellate Cells Hyper Activity Associated With Pancreatic Cancer, Chantale Charo Aug 2011

Role Of Prostaglandin E2 In The Regulation Of Pancreatic Stellate Cells Hyper Activity Associated With Pancreatic Cancer, Chantale Charo

Dissertations and Theses (Open Access)

Pancreatic cancer is one of the most lethal type of cancer due to its high metastasis rate and resistance to chemotherapy. Pancreatic fibrosis is a constant pathological feature of chronic pancreatitis and the hyperactive stroma associated with pancreatic cancer. Strong evidence supports an important role of cyclooxygenase-2 (COX-2) and COX-2 generated prostaglandin E2 (PGE2) during pancreatic fibrosis. Pancreatic stellate cells (PSC) are the predominant source of extracellular matrix production (ECM), thus being the key players in both diseases. Given this background, the primary objective is to delineate the role of PGE2 on human pancreatic stellate cells (PSC) hyper activation associated …


Echogenic Liposomes For Nitric Oxide Delivery And Breast Cancer Treatment, Soo Yeon Lee Female Aug 2011

Echogenic Liposomes For Nitric Oxide Delivery And Breast Cancer Treatment, Soo Yeon Lee Female

Dissertations and Theses (Open Access)

Liposomes, also known as nontoxic, biodegradable, and non-immunogenic therapeutic delivery vehicles, have been proposed as a carrier for drugs and antitumor agents in cancer chemotherapy. Echogenic liposomes (ELIP) have the potential to entrap air or bioactive gas to enhance acoustic reflectivity in ultrasound and are used as a contrast agent. The innovative part of this study is based on a novel concept to encapsulate nitric oxide (NO) gas into ELIP, deliver it to breast cancer cells, and control its release via direct ultrasound exposure. Studies on the effect of NO in tumor biology have shown that a high levels of …


Clinical Impact Of Couch To P And Rails On Imrt And Arc Therapy, Kiley B. Pulliam Aug 2011

Clinical Impact Of Couch To P And Rails On Imrt And Arc Therapy, Kiley B. Pulliam

Dissertations and Theses (Open Access)

Purpose: To evaluate the clinical impact of the Varian Exact Couch on dose and volume coverage to targets and critical structures and tumor control probability (TCP) for 6-MV IMRT and Arc Therapy.

Methods: Five clinical prostate patients were planned with both, 6-MV 8-field IMRT and 6-MV 2-field RapidArc using the Eclipse treatment planning system (TPS). These plans neglected treatment couch attenuation, as is standard clinical practice. Dose distributions were then recalculated in Eclipse with the inclusion of the Varian Exact Couch (imaging couch top) and the rails in varying configurations. The changes in dose and coverage were evaluated using the …


Enforced Expression Of Tbx1 In Fetal Thymic Epithelial Cells Antagonizes Thymus Organogenesis, Kim T. Cardenas Aug 2011

Enforced Expression Of Tbx1 In Fetal Thymic Epithelial Cells Antagonizes Thymus Organogenesis, Kim T. Cardenas

Dissertations and Theses (Open Access)

Enforced expression of Tbx1 in fetal thymic epithelial cells antagonizes

thymus organogenesis

Kim T. Cardenas

The thymus and parathyroid glands originate from organ-specific domains of 3rd pharyngeal pouch (PP) endoderm. At embryonic day 11.5 (E11.5), the ventral thymus and dorsal parathyroid domains can be identified by Foxn1 and Gcm2 expression respectively. Neural crest cells, (NCCs) play a role in regulating patterning of 3rd PP endoderm. In addition, pharyngeal endoderm influences fate determination via secretion of Sonic hedgehog (Shh), a morphogen required for Gcm2 expression and generation of the parathyroid domain. Gcm2 is a downstream target of the transcription factor Tbx1, …


The Mechanism Of Tumorigenesis In The Immortalized Human Pancreatic Cell Lines: Cell Culture Models Of Human Pancreatic Cancer, Zhe Chang Aug 2011

The Mechanism Of Tumorigenesis In The Immortalized Human Pancreatic Cell Lines: Cell Culture Models Of Human Pancreatic Cancer, Zhe Chang

Dissertations and Theses (Open Access)

The mechanism of tumorigenesis in the immortalized human pancreatic cell lines: cell culture models of human pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer in the world. The most common genetic lesions identified in PDAC include activation of K-ras (90%) and Her2 (70%), loss of p16 (95%) and p14 (40%), inactivation p53 (50-75%) and Smad4 (55%). However, the role of these signature gene alterations in PDAC is still not well understood, especially, how these genetic lesions individually or in combination contribute mechanistically to human pancreatic oncogenesis is still elusive. Moreover, a cell culture transformation model with sequential …


Gene By Bmi Interactions Influencing C-Reactive Protein Levels In European-Americans, Sarah Tudor Aug 2011

Gene By Bmi Interactions Influencing C-Reactive Protein Levels In European-Americans, Sarah Tudor

Dissertations and Theses (Open Access)

C-Reactive Protein (CRP) is a biomarker indicating tissue damage, inflammation, and infection. High-sensitivity CRP (hsCRP) is an emerging biomarker often used to estimate an individual’s risk for future coronary heart disease (CHD). hsCRP levels falling below 1.00 mg/l indicate a low risk for developing CHD, levels ranging between 1.00 mg/l and 3.00 mg/l indicate an elevated risk, and levels exceeding 3.00 mg/l indicate high risk. Multiple Genome-Wide Association Studies (GWAS) have identified a number of genetic polymorphisms which influence CRP levels. SNPs implicated in such studies have been found in or near genes of interest including: CRP, APOE, APOC, IL-6, …


Aberrations Of A Putative Tumor Suppressor Gene Sel1l In Pancreatic Ductal Adenocarcinoma, Qian Liu Aug 2011

Aberrations Of A Putative Tumor Suppressor Gene Sel1l In Pancreatic Ductal Adenocarcinoma, Qian Liu

Dissertations and Theses (Open Access)

Introduction: Pancreatic cancer is the fourth leading cause of cancer-related death among males and females in the United States. Sel-1-like (SEL1L) is a putative tumor suppressor gene that is downregulated in a significant proportion of human pancreatic ductal adenocarcinoma (PDAC). It was hypothesized that SEL1L expression could be down-modulated by somatic mutation, loss of heterozygosity (LOH), CpG island hypermethylation and/or aberrantly expressed microRNAs (miRNAs).

Material and methods: In 42 PDAC tumors, the SEL1L coding region was amplified using reverse transcription polymerase chain reaction (RT-PCR), and analyzed by agarose gel electrophoresis and sequenced to search for mutations. Using fluorescent …


Tp53 As A Biomarker In Head And Neck Squamous Cell Carcinoma, Thomas J. Ow Md Aug 2011

Tp53 As A Biomarker In Head And Neck Squamous Cell Carcinoma, Thomas J. Ow Md

Dissertations and Theses (Open Access)

Currently, there are no molecular biomarkers that guide treatment decisions for patients with head and neck squamous cell carcinoma (HNSCC). Several retrospective studies have evaluated TP53 in HNSCC, and results have suggested that specific mutations are associated with poor outcome. However, there exists heterogeneity among these studies in the site and stage of disease of the patients reviewed, the treatments rendered, and methods of evaluating TP53 mutation. Thus, it remains unclear as to which patients and in which clinical settings TP53 mutation is most useful in predicting treatment failure.

In the current study, we reviewed the records of a cohort …


Lentiviral-Mediated Rnai Knockdown Yields A Novel Mouse Model For Studying Cyp2b Function, Basma Damiri Aug 2011

Lentiviral-Mediated Rnai Knockdown Yields A Novel Mouse Model For Studying Cyp2b Function, Basma Damiri

All Dissertations

The Cyp2b subfamily contains five members (Cyp2b9, Cyp2b10, Cyp2b13, Cyp2b19, and Cyp2b23) of which three (Cyp2b9, Cyp2b10, Cyp2b13) are hepatic enzymes involved in xenobiotic detoxification. In this study, we made a Cyp2b-knockdown mouse using lentiviral-promoted shRNA homologous to all five Cyp2b subfamily members in FVB/NJ mouse to characterize Cyp2b's role in xenobiotic detoxification. We assessed the in vivo function of Cyp2bs in the toxicity from pesticides (i.e. parathion) and drugs (i.e. zoxazolamine). We demonstrated that Cyp2b isoforms play a key role in parathion and Zoxazolamine metabolism and toxicity. In addition, we in partially phenotyped and characterized Cyp2b-KD model and assessed …


Anticancer Effects Of Red Raspberries On Immune Cells And Blood Parameters, Jannet Romero Aug 2011

Anticancer Effects Of Red Raspberries On Immune Cells And Blood Parameters, Jannet Romero

All Dissertations

There is an abundance of research correlating diets rich in fruits and vegetables to the reduction or prevention of chronic diseases such as cancer and cardiovascular disease. Plants extracts have also been claimed to possess antiviral, antibacterial, and immunological properties. This study focused on the in vitro and in vivo effects of a water extract from lyophilized Meeker red raspberries on tumor cell viability and immune parameters. A large number of studies have demonstrated the cytotoxic effect of different fruit juices and extracts against tumor cell lines in vitro. However, studies also show that the blood plasma levels of berry …


Glutaredoxin 2 Prevents H2o2-Induced Cell Apoptosis By Protecting Complex I Activity In The Mitochondria, Hongli Wu, Kuiyi Xing, Marjorie F. Lou Aug 2011

Glutaredoxin 2 Prevents H2o2-Induced Cell Apoptosis By Protecting Complex I Activity In The Mitochondria, Hongli Wu, Kuiyi Xing, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

Glutaredoxin 2 (Grx2) belongs to the oxidoreductase family and is an isozyme of glutaredoxin 1 (Grx1) present in the mitochondria, however its function is not well understood. The purpose of this study is to evaluate the potential anti-apoptotic function of Grx2 by examining its ability to protect complex I in the mitochondrial electron transport system using human lens epithelial cells as a model. We found that cells treated with 200 μM hydrogen peroxide (H2O2) for 24 h exhibited decreased viability and became apoptotic with corresponding Bax up-regulation, Bcl-2 down-regulation, caspase 3 activation and mitochondrial cytochrome c leakage. Grx2 over-expression (OE) …


Creation Of Multilinage Adult Stem-Like Cells From Terminally Differentiatied Fibroblasts, John Moore Jul 2011

Creation Of Multilinage Adult Stem-Like Cells From Terminally Differentiatied Fibroblasts, John Moore

Theses and Dissertations

Induced Pluripotent Stem cells (iPScs) are artificially generated cells that demonstrate multilineage differentiation potential. These cells demonstrate similar morphology and high differentiation potential to Embryonic Stem Cells (ESCs). Generation of these cells from a terminally differentiated cell line requires activation of the core pluripotency genes Nanog, Oct4, and Sox2 as well as an oncogenic stimulus such as c-Myc. Here we examine the effect of the Human Pappiloma Virus derived proteins E6 and E7 on the ability of a terminally differentiated fibroblast cell line to a more primitive state and examine its multilineage differentiation capacity. In this paper, we attempt to …


Protection And Attachment Of Vibrio Cholerae Mediated By The Toxin-Coregulated Pilus In The Infant Mouse Model, Shelly J. Krebs, Ronald K. Taylor Jul 2011

Protection And Attachment Of Vibrio Cholerae Mediated By The Toxin-Coregulated Pilus In The Infant Mouse Model, Shelly J. Krebs, Ronald K. Taylor

Dartmouth Scholarship

Colonization of the human small intestine by Vibrio cholerae is an essential step in pathogenesis that requires the type IV toxin-coregulated pilus (TCP). To date, three functions of TCP have been characterized: it serves as the CTXΦ receptor, secretes the colonization factor TcpF, and functions in microcolony formation by mediating bacterium-bacterium interactions. Although type IV pili in other pathogenic bacteria have been characterized as playing a major role in attachment to epithelial cells, there are very few studies to suggest that TCP acts as an attachment factor. Taking this into consideration, we investigated the function of TCP in attachment to …


The Levels Of Analysis Revisited., Scott A Macdougall-Shackleton Jul 2011

The Levels Of Analysis Revisited., Scott A Macdougall-Shackleton

Brain and Mind Institute Researchers' Publications

The term levels of analysis has been used in several ways: to distinguish between ultimate and proximate levels, to categorize different kinds of research questions and to differentiate levels of reductionism. Because questions regarding ultimate function and proximate mechanisms are logically distinct, I suggest that distinguishing between these two levels is the best use of the term. Integrating across levels in research has potential risks, but many benefits. Consideration at one level can help generate novel hypotheses at the other, define categories of behaviour and set criteria that must be addressed. Taking an adaptationist stance thus strengthens research on proximate …


Network Modulation During Complex Syntactic Processing, Dirk B. Den Ouden, Dorothee Saur, Wolfgang Mader, Björn Schelter, Sladjana Lukic, Eisha Wali, Jens Timmer, Cynthia K. Thompson Jul 2011

Network Modulation During Complex Syntactic Processing, Dirk B. Den Ouden, Dorothee Saur, Wolfgang Mader, Björn Schelter, Sladjana Lukic, Eisha Wali, Jens Timmer, Cynthia K. Thompson

Communication Sciences and Disorders Faculty Articles and Research

Complex sentence processing is supported by a left-lateralized neural network including inferior frontal cortex and posterior superior temporal cortex. This study investigates the pattern of connectivity and information flow within this network. We used fMRI BOLD data derived from 12 healthy participants reported in an earlier study (Thompson, C. K., Den Ouden, D. B., Bonakdarpour, B., Garibaldi, K., & Parrish, T. B. (2010b). Neural plasticity and treatment-induced recovery of sentence processing in agrammatism. Neuropsychologia, 48(11), 3211–3227) to identify activation peaks associated with object-cleft over syntactically less complex subject-cleft processing. Directed Partial Correlation Analysis was conducted on time series …


A Review Of Common And Rare Genetic Variants In Schizophrenia, Jonathan Luedders Jul 2011

A Review Of Common And Rare Genetic Variants In Schizophrenia, Jonathan Luedders

Theses and Dissertations

Genetic epidemiology has shown a large role for genetic influences on schizophrenia. However, the nature of the variants involved is debated. The common disease-common variant (CDCV) hypothesis suggests that schizophrenia is caused by common alleles with small effect sizes. According to the common disease-rare variant (CDRV) hypothesis, schizophrenia is caused by rare variants with large effect sizes. In recent years, evidence has been found for both common and rare variants in schizophrenia. Several SNPs have been associated with schizophrenia through genome-wide association studies (GWAS), supporting the CDCV hypothesis. In support of the CDRV hypothesis, individuals with schizophrenia have been found …


Expression Profiling And Functional Validation Of Micrornas Involved In Schizophrenia And Bipolar Disorder, Albert H. Kim Jul 2011

Expression Profiling And Functional Validation Of Micrornas Involved In Schizophrenia And Bipolar Disorder, Albert H. Kim

Theses and Dissertations

MicroRNAs (miRNAs) are a family of small non-coding RNAs that regulate gene expression at both the mRNA and protein levels. MiRNAs have been shown to affect neuronal differentiation, synaptosomal complex localization and synapse plasticity, all functions thought to be disrupted in schizophrenia. We investigated the expression of 667 miRNAs (miRBase v.13) in the prefrontal cortex of individuals with schizophrenia (SZ, N = 35) and bipolar disorder (BP, N =35) using a real-time PCR-based Taqman Low Density Array (TLDA). After extensive QC steps, 441 miRNAs were included in the final analyses. At a FDR of 10%, 22 miRNAs were identified as …


Na/K-Atpase Mimetic Pnaktide Peptide Inhibits The Growth Of Human Cancer Cells, Zhichuan Li, Zhongbing Zhang, Joe X. Xie, Xin Li, Jiang Tian, Ting Cai, Hongaun Cui, Hanfei Ding, Joseph I. Shapiro Md, Zijian Xie Jul 2011

Na/K-Atpase Mimetic Pnaktide Peptide Inhibits The Growth Of Human Cancer Cells, Zhichuan Li, Zhongbing Zhang, Joe X. Xie, Xin Li, Jiang Tian, Ting Cai, Hongaun Cui, Hanfei Ding, Joseph I. Shapiro Md, Zijian Xie

Biochemistry and Microbiology

Cells contain a large pool of non-pumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. Supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness …


Upregulation Of Cathepsin D In The Caudate Nucleus Of Primates With Experimental Parkinsonism., Sowmya V. Yelamanchili, Amrita Datta Chaudhuri, Claudia T. Flynn, Howard S. Fox Jul 2011

Upregulation Of Cathepsin D In The Caudate Nucleus Of Primates With Experimental Parkinsonism., Sowmya V. Yelamanchili, Amrita Datta Chaudhuri, Claudia T. Flynn, Howard S. Fox

Journal Articles: Pharmacology & Experimental Neuroscience

BACKGROUND: In Parkinson's disease there is progressive loss of dopamine containing neurons in the substantia nigra pars compacta. The neuronal damage is not limited to the substantia nigra but progresses to other regions of brain, leading to loss of motor control as well as cognitive abnormalities. The purpose of this study was to examine causes of progressive damage in the caudate nucleus, which plays a major role in motor coordination and cognition, in experimental Parkinson's disease.

RESULTS: Using chronic 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine treatment of rhesus monkeys to model Parkinson's disease, we found a upregulation of Cathepsin D, a lysosomal aspartic protease, in …


Intracellular Signaling Contributions To Behaviors Relevant To Nicotine Addiction, Lauren Thompson Jul 2011

Intracellular Signaling Contributions To Behaviors Relevant To Nicotine Addiction, Lauren Thompson

Theses and Dissertations

Nicotine is the primary addictive substance in tobacco, and most smokers who quit will relapse within a year. Evidence shows that cigarette craving increases over time, termed “incubation.” The purpose of these studies was to see if protracted abstinence from chronic nicotine increases rat self-administration, an animal model with good face validity for human tobacco use, and if nicotine self-administration during daily exposure/after 8+ days of abstinence is regulated by extracellular signal-regulated kinase (ERK) signaling in the nucleus accumbens (NAc) shell or anterior cingulate cortex (PFC). ERK kinase inhibitor U0126 was infused in the NAc shell or PFC of Long …


Comparison Of Adenoviruses As Oncolytics And Cancer Vaccines In An Immunocompetent B Cell Lymphoma Model, Eric A. Weaver, Christopher Y. Chen, Shannon M. May, Mary E. Barry, Michael A. Barry Jul 2011

Comparison Of Adenoviruses As Oncolytics And Cancer Vaccines In An Immunocompetent B Cell Lymphoma Model, Eric A. Weaver, Christopher Y. Chen, Shannon M. May, Mary E. Barry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

We have screened human adenoviruses (Ads) for oncolytic activity against a variety of mouse and hamster cell lines and have found a number that are susceptible to a variety of Ad serotypes. A20 lymphoma is derived from BALB/c mice and is susceptible to infection and killing by a variety of human Ads. A20 is also a suitable cancer vaccine model, because these cells express a unique immunoglobulin variable region that can be targeted by vaccination. To compare Ads as cancer vaccines versus Ads as oncolytics, A20 tumors were initiated in immunocompetent BALB/c mice. Mice immunized with first-generation Ad5 expressing the …


Racial Differences In The Genetics Of Preeclampsia, Lori Hill Jul 2011

Racial Differences In The Genetics Of Preeclampsia, Lori Hill

Theses and Dissertations

Preeclampsia (PE), characterized by hypertension and proteinuria after 20 weeks of gestation, affects 5-8% of pregnancies worldwide. Although preeclampsia is a significant cause of maternal and perinatal mortality and morbidity, its etiology remains to be elucidated. Racial differences have been observed for preeclampsia, with U.S. Blacks having higher rates and more severe disease, compared to U.S. Whites and Hispanics. One potential source of racial differences in preeclampsia is genetic variation between populations. Genetic susceptibility to preeclampsia is well established, but the specific contributions of maternal vs. fetal genes, and how these vary among racial groups is poorly understood. This dissertation …


Emotional Reactivity And Regulation In Current And Remitted Depression: An Event Related Potential Study, Lauren M. Bylsma Jul 2011

Emotional Reactivity And Regulation In Current And Remitted Depression: An Event Related Potential Study, Lauren M. Bylsma

USF Tampa Graduate Theses and Dissertations

Major Depressive Disorder (MDD) is thought to be characterized by emotion regulation deficits, including decreased use of adaptive strategies such as reappraisal, but little is known about the exact nature of these deficits and whether or not they are specific to the depressed mood state. The late positive potential (LPP) is a sustained positive deflection of the event-related potential (ERP) associated with responding to emotionally-valenced stimuli, and reappraisal strategies have been found to reduce LPP magnitude in response to emotional stimuli in healthy individuals, but this effect has not been examined in MDD. This study utilized ERPs to examine emotional …