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The Cell And Molecular Biology Of Neurodegenerative Diseases: An Overview, Heather L. Montie, Thomas M. Durcan Nov 2013

The Cell And Molecular Biology Of Neurodegenerative Diseases: An Overview, Heather L. Montie, Thomas M. Durcan

PCOM Scholarly Works

There is no abstract for this article.


A Cell Permeable Peptide Targeting The Intracellular Loop 2 Of Endothelin B Receptor Reduces Pulmonary Hypertension In A Hypoxic Rat Model, Daniel S. Green, Chamila Rupasinghe, Rod Warburton, Jamie L. Wilson, Christine O. Sallum, Linda Taylor, Achan Yatawara, Dale Mierke, Peter Polgar, Nicholas Hill Nov 2013

A Cell Permeable Peptide Targeting The Intracellular Loop 2 Of Endothelin B Receptor Reduces Pulmonary Hypertension In A Hypoxic Rat Model, Daniel S. Green, Chamila Rupasinghe, Rod Warburton, Jamie L. Wilson, Christine O. Sallum, Linda Taylor, Achan Yatawara, Dale Mierke, Peter Polgar, Nicholas Hill

Dartmouth Scholarship

Cell permeable peptides (CPP) aid cellular uptake of targeted cargo across the hydrophobic plasma membrane. CPP-mediated cargo delivery of receptor signaling motifs provides an opportunity to regulate specific receptor initiated signaling cascades. Both endothelin-1 receptors, ETA and ETB, have been targets of antagonist therapies for individuals with pulmonary arterial hypertension (PAH). These therapies have had success but have been accompanied by adverse reactions. Also, unlike the CPP which target specific signaling cascades, the antagonists target the entire function of the receptor. Using the CPP strategy of biased antagonism of the ETB receptor’s intracellular loop 2 (ICB2), we demonstrate blunting of …


A Process Similar To Autophagy Is Associated With Cytocidal Chloroquine Resistance In Plasmodium Falciparum, David Gaviria, Michelle F. Paguio, Lindsey B. Turnbull, Asako Tan, Amila Siriwardana, Debasish Ghosh, Michael T. Ferdig, Anthony P. Sinai, Paul D. Roepe Nov 2013

A Process Similar To Autophagy Is Associated With Cytocidal Chloroquine Resistance In Plasmodium Falciparum, David Gaviria, Michelle F. Paguio, Lindsey B. Turnbull, Asako Tan, Amila Siriwardana, Debasish Ghosh, Michael T. Ferdig, Anthony P. Sinai, Paul D. Roepe

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Resistance to the cytostatic activity of the antimalarial drug chloroquine (CQ) is becoming well understood, however, resistance to cytocidal effects of CQ is largely unexplored. We find that PfCRT mutations that almost fully recapitulate P. falciparum cytostatic CQ resistance (CQR(CS)) as quantified by CQ IC50 shift, account for only 10-20% of cytocidal CQR (CQR(CC)) as quantified by CQ LD50 shift. Quantitative trait loci (QTL) analysis of the progeny of a chloroquine sensitive (CQS; strain HB3)×chloroquine resistant (CQR; strain Dd2) genetic cross identifies distinct genetic architectures for CQR(CS) vs CQR(CC) phenotypes, including identification of novel interacting chromosomal loci that influence CQ …


Novel Pancreatic Cancer Cell Lines Derived From Genetically Engineered Mouse Models Of Spontaneous Pancreatic Adenocarcinoma: Applications In Diagnosis And Therapy., María P. Torres, Satyanarayana Rachagani, Joshua J. Souchek, Kavita Mallya, Sonny L. Johansson, Surinder K. Batra Nov 2013

Novel Pancreatic Cancer Cell Lines Derived From Genetically Engineered Mouse Models Of Spontaneous Pancreatic Adenocarcinoma: Applications In Diagnosis And Therapy., María P. Torres, Satyanarayana Rachagani, Joshua J. Souchek, Kavita Mallya, Sonny L. Johansson, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer (PC) remains one of the most lethal human malignancies with poor prognosis. Despite all advances in preclinical research, there have not been significant translation of novel therapies into the clinics. The development of genetically engineered mouse (GEM) models that produce spontaneous pancreatic adenocarcinoma (PDAC) have increased our understanding of the pathogenesis of the disease. Although these PDAC mouse models are ideal for studying potential therapies and specific genetic mutations, there is a need for developing syngeneic cell lines from these models. In this study, we describe the successful establishment and characterization of three cell lines derived from two …


Intestinal Gucy2c Prevents Tgf-Β Secretion Coordinating Desmoplasia And Hyperproliferation In Colorectal Cancer., Ahmara V Gibbons, Jieru Egeria Lin, Gilbert Won Kim, Glen P Marszalowicz, Peng Li, Brian Arthur Stoecker, Erik S Blomain, Satish Rattan, Adam E. Snook, Stephanie Schulz, Scott A Waldman Nov 2013

Intestinal Gucy2c Prevents Tgf-Β Secretion Coordinating Desmoplasia And Hyperproliferation In Colorectal Cancer., Ahmara V Gibbons, Jieru Egeria Lin, Gilbert Won Kim, Glen P Marszalowicz, Peng Li, Brian Arthur Stoecker, Erik S Blomain, Satish Rattan, Adam E. Snook, Stephanie Schulz, Scott A Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Tumorigenesis is a multistep process that reflects intimate reciprocal interactions between epithelia and underlying stroma. However, tumor-initiating mechanisms coordinating transformation of both epithelial and stromal components are not defined. In humans and mice, initiation of colorectal cancer is universally associated with loss of guanylin and uroguanylin, the endogenous ligands for the tumor suppressor guanylyl cyclase C (GUCY2C), disrupting a network of homeostatic mechanisms along the crypt-surface axis. Here, we reveal that silencing GUCY2C in human colon cancer cells increases Akt-dependent TGF-β secretion, activating fibroblasts through TGF-β type I receptors and Smad3 phosphorylation. In turn, activating TGF-β signaling induces fibroblasts to …


Amlodipine Reduces Angii-Induced Aortic Aneurysms And Atherosclerosis In Hypercholesterolemic Mice, Xiaofeng Chen, Debra L. Rateri, Deborah A. Howatt, Anju Balakrishnan, Jessica J. Moorleghen, Andrew J. Morris, Richard Charnigo, Lisa A. Cassis, Alan Daugherty Nov 2013

Amlodipine Reduces Angii-Induced Aortic Aneurysms And Atherosclerosis In Hypercholesterolemic Mice, Xiaofeng Chen, Debra L. Rateri, Deborah A. Howatt, Anju Balakrishnan, Jessica J. Moorleghen, Andrew J. Morris, Richard Charnigo, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: The purpose of this study was to determine effects of amlodipine, a dihydropyridine calcium channel blocker, on development of angiotensin II (AngII)-induced vascular pathologies.

METHODS AND RESULTS: Male LDL receptor -/- mice were infused with vehicle, amlodipine (5 mg/kg/d), AngII (1,000 ng/kg/min), or AngII + amlodipine for 4 weeks through osmotic pumps (n=10/group). Mice were fed a saturated fat-enriched diet for 1 week prior to pump implantation and during 4 weeks of infusion. Infusion of amlodipine resulted in plasma concentrations of 32 ± 2 ng/ml and 27 ± 2 ng/ml for mice in saline + amlodipine and AngII + …


One, Two And Three-Dimensional Ultrasound Measurements Of Carotid Atherosclerosis Before And After Cardiac Rehabilitation: Preliminary Results Of A Randomized Controlled Trial., Tamas J Lindenmaier, Daniel N Buchanan, Damien Pike, Tim Hartley, Robert D Reid, J David Spence, Richard Chan, Michael Sharma, Peter L Prior, Neville Suskin, Grace Parraga Nov 2013

One, Two And Three-Dimensional Ultrasound Measurements Of Carotid Atherosclerosis Before And After Cardiac Rehabilitation: Preliminary Results Of A Randomized Controlled Trial., Tamas J Lindenmaier, Daniel N Buchanan, Damien Pike, Tim Hartley, Robert D Reid, J David Spence, Richard Chan, Michael Sharma, Peter L Prior, Neville Suskin, Grace Parraga

Medical Biophysics Publications

BACKGROUND: It is still not known how patients who are post-transient ischemic attack (TIA) or post-stroke might benefit from prospectively planned comprehensive cardiac rehabilitation (CCR). In this pilot evaluation of a larger ongoing randomized-controlled-trial, we evaluated ultrasound (US) measurements of carotid atherosclerosis in subjects following TIA or mild non-disabling stroke and their relationship with risk factors before and after 6-months of CCR.

METHODS: Carotid ultrasound (US) measurements of one-dimensional intima-media-thickness (IMT), two-dimensional total-plaque-area (TPA), three-dimensional total-plaque-volume (TPV) and vessel-wall-volume (VWV) were acquired before and after 6-months CCR for 39 subjects who had previously experienced a TIA and provided written informed …


Heterogeneity Of Functional Properties Of Clone 66 Murine Breast Cancer Cells Expressing Various Stem Cell Phenotypes, Partha Mukhopadhyay, Tracy Farrell, Gayatri Sharma, Timothy R. Mcguire, Barbara O'Kane, J. Graham Sharp Nov 2013

Heterogeneity Of Functional Properties Of Clone 66 Murine Breast Cancer Cells Expressing Various Stem Cell Phenotypes, Partha Mukhopadhyay, Tracy Farrell, Gayatri Sharma, Timothy R. Mcguire, Barbara O'Kane, J. Graham Sharp

Journal Articles: Genetics, Cell Biology & Anatomy

INTRODUCTION:

Breast cancer grows, metastasizes and relapses from rare, therapy resistant cells with a stem cell phenotype (cancer stem cells/CSCs). However, there is a lack of studies comparing the functions of CSCs isolated using different phenotypes in order to determine if CSCs are homogeneous or heterogeneous.

METHODS:

Cells with various stem cell phenotypes were isolated by sorting from Clone 66 murine breast cancer cells that grow orthotopically in immune intact syngeneic mice. These populations were compared by in vitro functional assays for proliferation, growth, sphere and colony formation; and in vivo limiting dilution analysis of tumorigenesis.

RESULTS:

The proportion of …


Suprachiasmatic Astrocytes Modulate The Circadian Clock In Response To Tnf-Α, José M. Duhart, María Juliana Leone, Natalia Paladino, Jennifer A. Evans, Oscar Castanon-Cervantes, Alec J. Davidson, Diego A. Golombek Nov 2013

Suprachiasmatic Astrocytes Modulate The Circadian Clock In Response To Tnf-Α, José M. Duhart, María Juliana Leone, Natalia Paladino, Jennifer A. Evans, Oscar Castanon-Cervantes, Alec J. Davidson, Diego A. Golombek

Biomedical Sciences Faculty Research and Publications

The immune and the circadian systems interact in a bidirectional fashion. The master circadian oscillator, located in the suprachiasmatic nuclei (SCN) of the hypothalamus, responds to peripheral and local immune stimuli, such as proinflammatory cytokines and bacterial endotoxin. Astrocytes exert several immune functions in the CNS, and there is growing evidence that points toward a role of these cells in the regulation of circadian rhythms. The aim of this work was to assess the response of SCN astrocytes to immune stimuli, particularly to the proinflammatory cytokine TNF-α. TNF-α applied to cultures of SCN astrocytes from Per2luc knockin mice altered …


Probiotics: Finding The Right Regulatory Balance, Diane E. Hoffmann, Claire M. Fraser-Liggett, Frank B. Palumbo, Jacques Ravel, Karen H. Rothenberg, Virginia Rowthorn Oct 2013

Probiotics: Finding The Right Regulatory Balance, Diane E. Hoffmann, Claire M. Fraser-Liggett, Frank B. Palumbo, Jacques Ravel, Karen H. Rothenberg, Virginia Rowthorn

Faculty Scholarship

Some products marketed as drugs should be excused from Phase I trials, but safety and efficacy claims for dietary supplements should be more tightly regulated.


Expression Of Mucoid Induction Factor Muce Is Dependent Upon The Alternate Sigma Factor Algu In Pseudomonas Aeruginosa, Yeshi Yin, F. Heath Damron, T. Ryan Withers, Christopher L. Prichett, Xin Wang, Michael J. Schurr, Hongwei Yu Oct 2013

Expression Of Mucoid Induction Factor Muce Is Dependent Upon The Alternate Sigma Factor Algu In Pseudomonas Aeruginosa, Yeshi Yin, F. Heath Damron, T. Ryan Withers, Christopher L. Prichett, Xin Wang, Michael J. Schurr, Hongwei Yu

Biochemistry and Microbiology

Background

Alginate overproduction in P. aeruginosa, also referred to as mucoidy, is a poor prognostic marker for patients with cystic fibrosis (CF). We previously reported the construction of a unique mucoid strain which overexpresses a small envelope protein MucE leading to activation of the protease AlgW. AlgW then degrades the anti-sigma factor MucA thus releasing the alternative sigma factor AlgU/T (σ22) to initiate transcription of the alginate biosynthetic operon.

Results

In the current study, we mapped the mucE transcriptional start site, and determined that PmucE activity was dependent on AlgU. Additionally, the presence of triclosan and …


Mycological Study For A Management Plan Of A Neotropical Show Cave (Brazil), Erika Linzi Silva Taylor, Maria Aparecida De Resende Stoianoff, Rodrigo Lopes Ferreira Oct 2013

Mycological Study For A Management Plan Of A Neotropical Show Cave (Brazil), Erika Linzi Silva Taylor, Maria Aparecida De Resende Stoianoff, Rodrigo Lopes Ferreira

International Journal of Speleology

Caves are stable environments with characteristics favoring the development of microorganisms. The allocthonous input of organic matter and microbes into the warm Neotropical caves may favor the development of filamentous fungi, including pathogenic species. Histoplasma capsulatum is a pathogenic species commonly found in caves and associated with bat and bird guano. Many Brazilian caves have been historically visited due to scenic and religious tourism. The objective of this study was to perform a microbiology study for a management plan of a show cave in Brazil, focusing on the presence and distribution of pathogenic and opportunistic fungi in the cave. Statistics …


Lactobacillus Acidophilus Alleviates Platelet-Activating Factor-Induced Inflammatory Responses In Human Intestinal Epithelial Cells, Alip Borthakur, Sumit Bhattacharyya, Anoop Kumar, Arivarasu Natarajan Anbazhagan, Joanne K. Tobacman, Pradeep K. Dudeja Oct 2013

Lactobacillus Acidophilus Alleviates Platelet-Activating Factor-Induced Inflammatory Responses In Human Intestinal Epithelial Cells, Alip Borthakur, Sumit Bhattacharyya, Anoop Kumar, Arivarasu Natarajan Anbazhagan, Joanne K. Tobacman, Pradeep K. Dudeja

Clinical & Translational Sciences

Probiotics have been used as alternative prevention and therapy modalities in intestinal inflammatory disorders including inflammatory bowel diseases (IBD) and necrotizing enterocolitis (NEC). Pathophysiology of IBD and NEC includes the production of diverse lipid mediators, including platelet-activating factor (PAF) that mediate inflammatory responses in the disease. PAF is known to activate NF-kB, however, the mechanisms of PAF-induced inflammation are not fully defined. We have recently described a novel PAF-triggered pathway of NF-κB activation and IL-8 production in intestinal epithelial cells (IECs), requiring the pivotal role of the adaptor protein Bcl10 and its interactions with CARMA3 and MALT1. The current studies …


Synthesis And Antiproliferative Activities Of Quebecol And Its Analogs, Kasiviswanadharaju Pericherla, Amir Nasrolahi Shirazi, V. Kameshwara Rao, Rakesh Tiwari, Nicholas Dasilva, Kellen Mccaffrey, Yousef A. Beni, Antonio González- Sarrías, Navindra P. Seeram, Keykavous Parang, Anil Kumar Oct 2013

Synthesis And Antiproliferative Activities Of Quebecol And Its Analogs, Kasiviswanadharaju Pericherla, Amir Nasrolahi Shirazi, V. Kameshwara Rao, Rakesh Tiwari, Nicholas Dasilva, Kellen Mccaffrey, Yousef A. Beni, Antonio González- Sarrías, Navindra P. Seeram, Keykavous Parang, Anil Kumar

Pharmacy Faculty Articles and Research

Simple and efficient synthesis of quebecol and a number of its analogs was accomplished in five steps. The synthesized compounds were evaluated for antiproliferative activities against human cervix adenocarcinoma (HeLa), human ovarian carcinoma (SK-OV-3), human colon carcinoma (HT-29), and human breast adenocarcinoma (MCF-7) cancer cell lines. Among all the compounds, 7c, 7d, 7f, and 8f exhibited antiproliferative activities against four tested cell lines with inhibition over 80% at 75 mu M after 72 h, whereas, compound 7b and 7g were more selective towards MCF-7 cell line. The IC50 values for compounds 7c, 7d, and 7f were 85.1 mu M, 78.7 …


Small Molecule Antagonists Of Melanopsin-Mediated Phototransduction, Kenneth A. Jones, Megumi Hatori, Ludovic S. Mure, Jayne R. Bramley, Roman Artymyshyn, Sang-Phyo Hong, Mohammad Marzabadi, Huailing Zhong, Jeffrey Sprouse, Quansheng Zhu, Andrew T. E. Hartwick, Patricia J. Sollars, Gary E. Pickard, Satchidananda Panda Oct 2013

Small Molecule Antagonists Of Melanopsin-Mediated Phototransduction, Kenneth A. Jones, Megumi Hatori, Ludovic S. Mure, Jayne R. Bramley, Roman Artymyshyn, Sang-Phyo Hong, Mohammad Marzabadi, Huailing Zhong, Jeffrey Sprouse, Quansheng Zhu, Andrew T. E. Hartwick, Patricia J. Sollars, Gary E. Pickard, Satchidananda Panda

School of Veterinary and Biomedical Sciences: Faculty Publications

Melanopsin, expressed in a subset of retinal ganglion cells, mediates behavioral adaptation to ambient light and other non-image forming photic responses. This has raised the possibility that pharmacological manipulation of melanopsin can modulate several CNS responses including photophobia, sleep, circadian rhythms and neuroendocrine function. Here we describe the identification of a potent synthetic melanopsin antagonist with in vivo activity. Novel sulfonamide compounds inhibiting melanopsin (opsinamides) compete with retinal binding to melanopsin and inhibit its function without affecting rod/cone mediated responses. In vivo administration of opsinamides to mice specifically and reversibly modified melanopsin-dependent light responses including the pupillary light reflex and …


Primary Blast Traumatic Brain Injury In The Rat: Relating Diffusion Tensor Imaging And Behavior, Matthew D. Budde, Alok Shah, Michael Mccrea, William E. Cullinan, Frank A. Pintar, Brian D. Stemper Oct 2013

Primary Blast Traumatic Brain Injury In The Rat: Relating Diffusion Tensor Imaging And Behavior, Matthew D. Budde, Alok Shah, Michael Mccrea, William E. Cullinan, Frank A. Pintar, Brian D. Stemper

Biomedical Sciences Faculty Research and Publications

The incidence of traumatic brain injury (TBI) among military personnel is at its highest point in U.S. history. Experimental animal models of blast have provided a wealth of insight into blast injury. The mechanisms of neurotrauma caused by blast, however, are still under debate. Specifically, it is unclear whether the blast shockwave in the absence of head motion is sufficient to induce brain trauma. In this study, the consequences of blast injury were investigated in a rat model of primary blast TBI. Animals were exposed to blast shockwaves with peak reflected overpressures of either 100 or 450 kPa (39 and …


Generating Hypotheses About Care Needs Of High Utilizers: Lessons From Patient Interviews., Dawn B Mautner, Hauchie Pang, Jeffrey C Brenner, Judy A Shea, Kennen S Gross, Rosemary Frasso, Carolyn C Cannuscio Oct 2013

Generating Hypotheses About Care Needs Of High Utilizers: Lessons From Patient Interviews., Dawn B Mautner, Hauchie Pang, Jeffrey C Brenner, Judy A Shea, Kennen S Gross, Rosemary Frasso, Carolyn C Cannuscio

Department of Family & Community Medicine Faculty Papers

Informed by a largely secondary and quantitative literature, efforts to improve care and outcomes for complex patients with high levels of emergency and hospital-based health care utilization have offered mixed results. This qualitative study identifies psychosocial factors and life experiences described by these patients that may be important to their care needs. Semi-structured interviews were conducted with 19 patients of the Camden Coalition of Healthcare Providers' Care Management Team. Investigators coded transcripts using a priori and inductively-derived codes, then identified 3 key themes: (1) Early-life instability and traumas, including parental loss, unstable or violent relationships, and transiency, informed many participants' …


Scavenger Receptor Class B Type I Regulates Cellular Cholesterol Metabolism And Cell Signaling Associated With Breast Cancer Development., Christiane Danilo, Jorge L Gutierrez-Pajares, Maria Antonietta Mainieri, Isabelle Mercier, Michael P. Lisanti, Philippe G. Frank Sep 2013

Scavenger Receptor Class B Type I Regulates Cellular Cholesterol Metabolism And Cell Signaling Associated With Breast Cancer Development., Christiane Danilo, Jorge L Gutierrez-Pajares, Maria Antonietta Mainieri, Isabelle Mercier, Michael P. Lisanti, Philippe G. Frank

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

INTRODUCTION: Previous studies have identified cholesterol as an important regulator of breast cancer development. High-density lipoprotein (HDL) and its cellular receptor, scavenger receptor class B type I (SR-BI) have both been implicated in the regulation of cellular cholesterol homeostasis, but their functions in cancer remain to be established.

METHODS: In the present study, we have examined the role of HDL and SR-BI in the regulation of cellular signaling pathways in breast cancer cell lines and in the development of tumor in a mouse xenograft model.

RESULTS: Our data show that HDL is capable of stimulating migration and can activate signal …


Role Of Vimf In Gingipain Maturation In Porphyromonas Gingivalis, Arun S. Muthiah Sep 2013

Role Of Vimf In Gingipain Maturation In Porphyromonas Gingivalis, Arun S. Muthiah

Loma Linda University Electronic Theses, Dissertations & Projects

Gingipain activity in Porphyromonas gingivalis, the major etiological agent in adult periodontitis, is post-translationally regulated by unique Vim proteins including VimF, a putative glycosyltransferase. To ascertain the VimF mediated phenotype we first inactivated the vimF gene in P. gingivalis ATCC 33277 (FLL476), a less virulent fimbriated strain. We observed that the vimF-defective mutant (FLL476) showed a phenotype similar to that of the vimF-defective mutant (FLL95) in the P. gingivalis W83 background. While hemagglutination was not detected and autoaggregationn was reduced, biofilm formation was increased in FLL476. Also, invasive capacity decreased for this mutant. Furthermore, fimbrial structures were missing in FLL476, …


The Hiv-1 Protein Vpr Targets The Endoribonuclease Dicer For Proteasomal Degradation To Boost Macrophage Infection, Laurieann Klockow, Hamayun J. Sharifi, Xiaoyun Wen, Meg Flagg, Andrea K.M. Furuya, Michael Nekorchuk, Carlos M.C. De Noronha Sep 2013

The Hiv-1 Protein Vpr Targets The Endoribonuclease Dicer For Proteasomal Degradation To Boost Macrophage Infection, Laurieann Klockow, Hamayun J. Sharifi, Xiaoyun Wen, Meg Flagg, Andrea K.M. Furuya, Michael Nekorchuk, Carlos M.C. De Noronha

Biomedical Sciences Faculty Research and Publications

The HIV-1 protein Vpr enhances macrophage infection, triggers G2 cell cycle arrest, and targets cells for NK-cell killing. Vpr acts through the CRL4DCAF1 ubiquitin ligase complex to cause G2 arrest and trigger expression of NK ligands. Corresponding ubiquitination targets have not been identified. UNG2 and SMUG1 are the only known substrates for Vpr-directed depletion through CRL4DCAF1. Here we identify the endoribonuclease Dicer as a target of HIV-1 Vpr-directed proteasomal degradation through CRL4DCAF1. We show that HIV-1 Vpr inhibits short hairpin RNA function as expected upon reduction of Dicer levels. Dicer inhibits HIV-1 replication in T …


Calpain-2 Compensation Promotes Angiotensin Ii-Induced Ascending And Abdominal Aortic Aneurysms In Calpain-1 Deficient Mice, Venkateswaran Subramanian, Jessica J. Moorleghen, Anju Balakrishnan, Deborah A. Howatt, Athar H. Chishti, Haruhito A. Uchida Aug 2013

Calpain-2 Compensation Promotes Angiotensin Ii-Induced Ascending And Abdominal Aortic Aneurysms In Calpain-1 Deficient Mice, Venkateswaran Subramanian, Jessica J. Moorleghen, Anju Balakrishnan, Deborah A. Howatt, Athar H. Chishti, Haruhito A. Uchida

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND AND OBJECTIVE: Recently, we demonstrated that angiotensin II (AngII)-infusion profoundly increased both aortic protein and activity of calpains, calcium-activated cysteine proteases, in mice. In addition, pharmacological inhibition of calpain attenuated AngII-induced abdominal aortic aneurysm (AA) in mice. Recent studies have shown that AngII infusion into mice leads to aneurysmal formation localized to the ascending aorta. However, the precise functional contribution of calpain isoforms (-1 or -2) in AngII-induced abdominal AA formation is not known. Similarly, a functional role of calpain in AngII-induced ascending AA remains to be defined. Using BDA-410, an inhibitor of calpains, and calpain-1 genetic deficient mice, …


Prophylactic Vs. Therapeutic: Dna Vaccine To Metastatic Colorectal Cancer Using Molecular Marker Guanylyl Cyclase-C, Anmol Khurana, Msii Aug 2013

Prophylactic Vs. Therapeutic: Dna Vaccine To Metastatic Colorectal Cancer Using Molecular Marker Guanylyl Cyclase-C, Anmol Khurana, Msii

Summer Training Program in Cancer Immunotherapy

The role of heat-stable enterotoxin receptor guanylyl cyclase C (GCC) is well known for its aberrant chloride conductance in the intestinal epithelium in response to bacterial infection. Recently, its use as a molecular marker to detect metastatic colon cancer has grown, as has its use as oral hormone therapy for tumor suppression. This study investigates the preliminary stages of a DNA dendritic cell-based vaccine development specific to targeting guanylyl cyclase in systemic tissues. Construction of the plasmid as well as its transduction to Class I MHC molecules in antigen-presenting dendritic cells is examined. Future exploration includes a comparative assessment of …


Unraveling The Mechanism Of 2,4-Dinitrofluorobenzene-Associated Cell Death, Franklin Thelmo Aug 2013

Unraveling The Mechanism Of 2,4-Dinitrofluorobenzene-Associated Cell Death, Franklin Thelmo

Summer Training Program in Cancer Immunotherapy

The mechanism by which the hapten 2,4-dinitrophenyl (DNP) mediates cell death is unclear according to current literature. To determine how DNP mediates death in the B16F10 murine melanoma cell line in vitro, cells were modified with 2,4-dinitro-1-fluorobenzene (DNFB). Following modification, cell lysates were collected and analyzed via Western blottings with known apoptotic or necrotic markers. Our results indicated that DNFB treated cells do not express the apoptotic marker Cleaved Caspase-3 and have no change in levels of the necrotic marker Cyclophilin A. We conclude that DNFB is not inducing apoptosis in B16F10 cells. Future research will further examine the …


The Conception Of Gcc- Specific Chimeric Antigen Receptors, Raven Smith-Parris Aug 2013

The Conception Of Gcc- Specific Chimeric Antigen Receptors, Raven Smith-Parris

Summer Training Program in Cancer Immunotherapy

Colorectal Cancer is an aggressive disease that claims the lives of both men and women every year. It is the second leading cause of cancer-related death in the U.S. The overwhelming mortality rate it amasses begs for the discovery of alternative forms of treatment. The nature of cancer requires immunotherapeutic approach that is tumor specific in nature. Adoptive T-cell therapy is an alternative that satisfies these conditions. Guanylyl Cyclase C is a receptor found on the luminal side of the gut that is tissue-specific for the intestinal epithelium. Further, its expression is maintained throughout colorectal tumorigenesis making in an excellent …


2013 Annual Meeting Program Aug 2013

2013 Annual Meeting Program

Journal of the South Carolina Academy of Science

No abstract provided.


The Involvement Of Beta-Catenin In The Inflammatory Response Leading To Autoimmune Diabetes Development., Arin Lee Zirnheld Aug 2013

The Involvement Of Beta-Catenin In The Inflammatory Response Leading To Autoimmune Diabetes Development., Arin Lee Zirnheld

Electronic Theses and Dissertations

We identified and characterized a novel defect in β-catenin expression in bone marrow derived dendritic cells (BMDC) from NOD mice, a model for human Type I diabetes. This protein is expressed at high levels throughout the lifespan of the mouse and correlates with increased pro-inflammatory cytokine production by the BMDC and IFNγ induction by T cells cocultured with the BMDC. These defects, including a similar pattern of pro-inflammatory cytokine production, are also observed in human monocytederived DC from diabetic patients. After exploring several potential mechanisms involved in the accumulation of β-catenin in NOD BMDC, we found that β-catenin is phosphorylated …


Macromolecular Complexes Of Cystic Fibrosis Transmembrane Conductance Regulator Alter Fluid Transport In Inflammatory Bowel Disorders, Kavisha Arora Aug 2013

Macromolecular Complexes Of Cystic Fibrosis Transmembrane Conductance Regulator Alter Fluid Transport In Inflammatory Bowel Disorders, Kavisha Arora

Theses and Dissertations (ETD)

Macromolecular complexes of cystic fibrosis transmembrane conductance regulator (CFTR) comprise of network of proteins that can regulate cAMP-/cGMP-activated CFTR chloride channel function. We report the physical and functional coupling of CFTR with nitric oxide (NO) producing enzyme-inducible nitric oxide synthase (iNOS) at the apical plasma membrane in inflammatory bowel disease (IBD). The complex formation requires the scaffolding protein Na+ /H+ exchanger regulatory factor 2 (NHERF2). We demonstrate that iNOS is overexpressed at or near the apical plasma membrane of gut epithelial cells in IBD and, through the stimulation of the NO-cGMP pathway, generates compartmentalized cGMP underneath the plasma membrane. This …


Regulating Rsma Expression In Pseudomonas Aeruginosa, Sean D. Stacey Aug 2013

Regulating Rsma Expression In Pseudomonas Aeruginosa, Sean D. Stacey

Electronic Theses and Dissertations

Pseudomonas aeruginosa, a Gram-negative bacillus, commonly infects immunocompromised individuals and uses a variety of virulence factors to persist in these hosts. The posttranscriptional regulator, RsmA, plays a role in the expression of many virulence factors in P. aeruginosa. RsmA up regulates virulence factors used in colonizing hosts. However, regulation of rsmA is not well elucidated. Transposon mutagenesis was performed on P. aeruginosa containing a transcriptional rsmA-lacZ fusion to answer this question. Mutants were screened via β-galactosidase assay and transposon insertions identified via arbitrary PCR. A probable MFS transporter, we named mtpX, was one significant transposon mutant identified. …


Osmotic Stress, Not Aldose Reductase Activity, Directly Induces Growth Factors And Mapk Signaling Changes During Sugar Cataract Formation, Peng Zhang, Kuiyi Xing, James Randazzo, Karen Blessing, Marjorie F. Lou, Peter Kador Aug 2013

Osmotic Stress, Not Aldose Reductase Activity, Directly Induces Growth Factors And Mapk Signaling Changes During Sugar Cataract Formation, Peng Zhang, Kuiyi Xing, James Randazzo, Karen Blessing, Marjorie F. Lou, Peter Kador

School of Veterinary and Biomedical Sciences: Faculty Publications

In sugar cataract formation in rats, aldose reductase (AR) actitvity is not only linked to lenticular sorbitol (diabetic) or galactitol (galactosemic) formation but also to signal transduction changes, cytotoxic signals and activation of apoptosis. Using both in vitro and in vivo techniques, the interrelationship between AR activity, polyol (sorbitol and galactitol) formation, osmotic stress, growth factor induction, and cell signaling changes have been investigated. For in vitro studies, lenses from Sprague Dawley rats were cultured for up to 48 hrs in TC-199-bicarbonate media containing either 30 mM fructose (control), or 30 mM glucose or galctose with/without the aldose reductase inhibitors …


Sparstolonin B Inhibits Pro-Angiogenic Functions And Blocks Cell Cycle Progression In Endothelial Cells, H. R. Bateman, Q. Liang, D. Fan, V. Rodriguez, Susan M. Lessner Aug 2013

Sparstolonin B Inhibits Pro-Angiogenic Functions And Blocks Cell Cycle Progression In Endothelial Cells, H. R. Bateman, Q. Liang, D. Fan, V. Rodriguez, Susan M. Lessner

Faculty Publications

Sparstolonin B (SsnB) is a novel bioactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent. Angiogenesis, the process of new capillary formation from existing blood vessels, is dysregulated in many pathological disorders, including diabetic retinopathy, tumor growth, and atherosclerosis. In functional assays, SsnB inhibited endothelial cell tube formation (Matrigel method) and cell migration (Transwell method) in a dose-dependent manner. Microarray experiments with human umbilical vein endothelial cells (HUVECs) and human coronary artery endothelial cells (HCAECs) demonstrated differential expression of several hundred genes in response to SsnB exposure (916 and 356 …