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Articles 1 - 30 of 94
Full-Text Articles in Medical Sciences
A Pil1–Sle1–Syj1–Tax4 Functional Pathway Links Eisosomes With Pi(4,5)P2 Regulation, Ruth Kabeche, Assen Roguev, Nevan J. Krogan, James B. Moseley
A Pil1–Sle1–Syj1–Tax4 Functional Pathway Links Eisosomes With Pi(4,5)P2 Regulation, Ruth Kabeche, Assen Roguev, Nevan J. Krogan, James B. Moseley
Dartmouth Scholarship
Stable compartments of the plasma membrane promote a wide range of cellular functions. In yeast cells, cytosolic structures called eisosomes generate prominent cortical invaginations of unknown function. Through a series of genetic screens in fission yeast, we found that the eisosome proteins Pil1 and Sle1 function with the synaptojanin-like lipid phosphatase Syj1 and its ligand Tax4. This genetic pathway connects eisosome function with the hydrolysis of phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] in cells. Defects in PI(4,5)P2 regulation led to eisosome defects, and we found that the core eisosome protein Pil1 can bind to and tubulate liposomes containing PI(4,5)P2. Mutations in components of …
Biochemical Assay Optimization And Computational Screening Efforts To Identify Potential Luxs Inhibitors, Keeshia Q. Wang
Biochemical Assay Optimization And Computational Screening Efforts To Identify Potential Luxs Inhibitors, Keeshia Q. Wang
Master's Theses
Quorum sensing (QS) is a process of coordination of bacterial gene expression in response to cell population. System two QS is regulated by the small signaling molecule autoinducer-2 (AI-2) and is implicated in the infectious behaviors of various bacterial species. AI-2 is biosynthesized from S-ribosylhomocysteine (SRH) by the enzyme LuxS and induces interspecies cell-to-cell communication. Inhibition of LuxS would therefore inhibit interspecies QS. Herein, a search for novel molecular species that will competitively bind with SRH in the LuxS binding site is performed in silico. Computational screening results are then validated in vitro using an optimized LuxS inhibition …
Interactions Of Peptide Triazole Thiols With Env Gp120 Induce Irreversible Breakdown And Inactivation Of Hiv-1 Virions, Arangassery Bastian, Mark Contarino, Lauren D. Bailey, Rachna Aneja, Diogo Rodrigo Magalhaes Moreira, Kevin Freedman, Karyn Mcfadden, Caitlin Duffy, Ali Emileh
Interactions Of Peptide Triazole Thiols With Env Gp120 Induce Irreversible Breakdown And Inactivation Of Hiv-1 Virions, Arangassery Bastian, Mark Contarino, Lauren D. Bailey, Rachna Aneja, Diogo Rodrigo Magalhaes Moreira, Kevin Freedman, Karyn Mcfadden, Caitlin Duffy, Ali Emileh
Dartmouth Scholarship
Background: We examined the underlying mechanism of action of the peptide triazole thiol, KR13 that has been shown previously to specifically bind gp120, block cell receptor site interactions and potently inhibit HIV-1 infectivity.
Results: KR13, the sulfhydryl blocked KR13b and its parent non-sulfhydryl peptide triazole, HNG156, induced gp120 shedding but only KR13 induced p24 capsid protein release. The resulting virion post virolysis had an altered morphology, contained no gp120, but retained gp41 that bound to neutralizing gp41 antibodies. Remarkably, HIV-1 p24 release by KR13 was inhibited by enfuvirtide, which blocks formation of the gp41 6-helix bundle during membrane fusion, while …
Diabetes Alters Vascular Mechanotransduction: Pressure-Induced Regulation Of Mitogen Activated Protein Kinases In The Rat Inferior Vena Cava, Kevin M. Rice, Devashish H. Desai, Sunil K. Kakarla, Anjaiah Katta, Deborah L. Preston, Paulette Wehner, Eric R. Blough
Diabetes Alters Vascular Mechanotransduction: Pressure-Induced Regulation Of Mitogen Activated Protein Kinases In The Rat Inferior Vena Cava, Kevin M. Rice, Devashish H. Desai, Sunil K. Kakarla, Anjaiah Katta, Deborah L. Preston, Paulette Wehner, Eric R. Blough
Deborah L Preston
Background Diabetes mellitus is an important risk factor for increased vein graft failure after bypass surgery. However, the cellular and molecular mechanism(s) underlying vessel attrition in this population remain largely unexplored. Recent reports have suggested that the pathological remodeling of vein grafts may be mediated by mechanically-induced activation of the mitogen activated protein kinase (MAPK) signaling pathways and the MAPK-related induction of caspase-3 activity. On the basis of these findings, we hypothesized that diabetes may be associated with alterations in how veins "sense" and "respond" to altered mechanical loading. Methods Inferior venae cavae (IVC) from the non-diabetic lean (LNZ) and …
Uniaxial Stretch-Induced Regulation Of Mitogen-Activated Protein Kinase, Akt And P70s6 Kinase In The Ageing Fischer 344 × Brown Norway Rat Aorta, Kevin M. Rice, Devashish H. Desai, Deborah L. Preston, Paulette S. Wehner, Eric R. Blough
Uniaxial Stretch-Induced Regulation Of Mitogen-Activated Protein Kinase, Akt And P70s6 Kinase In The Ageing Fischer 344 × Brown Norway Rat Aorta, Kevin M. Rice, Devashish H. Desai, Deborah L. Preston, Paulette S. Wehner, Eric R. Blough
Deborah L Preston
The effects of ageing on the cardiovascular system contribute to substantial alterations in cellular morphology and function. The variables regulating these changes are unknown; however, one set of signalling molecules that may be of particular importance in mediating numerous cellular responses, including control of cell growth, differentiation and adaptation, are the proteins associated with the mitogen-activated protein kinase (MAPK) signalling systems. The MAPKs, in conjunction with the p70 S6k signalling cascade, have emerged as critical components for regulating numerous mechanotransduction-related cellular responses. Here we investigate the ability of uniaxial stretch to activate the MAPK and p70 S6k pathways in adult …
Phosphate Esters, Thiophosphate Esters And Metal Thiophosphates As Lubricant Additives, David W. Johnson, John E. Hils
Phosphate Esters, Thiophosphate Esters And Metal Thiophosphates As Lubricant Additives, David W. Johnson, John E. Hils
Chemistry Faculty Publications
Phosphate esters, thiophosphate esters and metal thiophosphates have been used as lubricant additives for over 50 years. While their use has been extensive, a detailed knowledge of how they work has been a much more recent development. In this paper, the use of phosphate esters and thiophosphate esters as anti-wear or extreme pressure additives is reviewed with an emphasis on their mechanism of action. The review includes the use of alkyl phosphates, triaryl phosphates and metal containing thiophosphate esters. The mechanisms of these materials interacting with a range of iron and steel based bearing material are examined.
Expression And Function Of Ca2+-Activated K+ Channels In Uterine Arteries, Ronghui Zhu
Expression And Function Of Ca2+-Activated K+ Channels In Uterine Arteries, Ronghui Zhu
Loma Linda University Electronic Theses, Dissertations & Projects
Chronic hypoxia during pregnancy is one of the most common insults to the maternal cardiovascular system and fetal development, and is associated with increased uterine vascular tone and heightened risk of preeclampsia and fetal intrauterine growth restriction (IUGR). The present study tested the hypothesis that calcium-activated potassium (KCa) channels play an essential role in uterine vascular adaptation to pregnancy, which is inhibited by chronic hypoxia during gestation. Uterine arteries (UAs) were isolated from nonpregnant ewes (NPUAs) and near-term pregnant ewes (PUAs) that had been maintained at sea level (~300 m) or exposed to high altitude (3,801 m) for 110 days. …
Characterization Of The Functional Role And Therapeutic Potential Of Microrna Mir-125a In Acute Myeloid Leukemia, Melanie Lorraine Ufkin
Characterization Of The Functional Role And Therapeutic Potential Of Microrna Mir-125a In Acute Myeloid Leukemia, Melanie Lorraine Ufkin
Electronic Theses and Dissertations
Acute myeloid leukemia (AML) is a heterogeneous disease marked by a highly variable clinical course and response to therapy. The average age of individuals diagnosed with AML is approximately 69 years old. Due to age of the patient and how quickly the disease progresses, many are unable to receive therapy, leading to death between 4 and 12 weeks after diagnosis. More effective and less cytotoxic treatments are crucial for those diagnosed with AML. Therefore my work has been focused on understanding genetic pathways altered within AML to develop new-targeted therapies. Specifically, I have been studying microRNAs (miR), which regulate proteins …
A Novel Mechanism Of Enhanced Susceptibility To Bacterial Pneumonia In Influenza-Infected Hosts, Hazem Elsayed Ghoneim
A Novel Mechanism Of Enhanced Susceptibility To Bacterial Pneumonia In Influenza-Infected Hosts, Hazem Elsayed Ghoneim
Theses and Dissertations (ETD)
Viruses such as influenza suppress host immune function by a variety of methods. This may result in a significant morbidity through several pathways, including facilitation of secondary bacterial pneumonia from pathogens such as Streptococcus pneumoniae. Lungresident alveolar macrophages (AMs) act as the first line of innate cellular immunity against respiratory bacterial pathogens, including pneumococcus. Therefore, they represent an attractive target for study Before investigating the impact of influenza infection on resident AMs, we first characterized different subsets of lung-resident macrophages in naïve mice using a novel in vivo labeling approach in conjunction with multicolor flow cytometric analysis and confocal microscopic …
Molecular Level Interaction Of Human Fibroblast Growth Factor-1 (Hfgf-1) With Phloridzin, Rammohan Paripelly
Molecular Level Interaction Of Human Fibroblast Growth Factor-1 (Hfgf-1) With Phloridzin, Rammohan Paripelly
Masters Theses & Specialist Projects
Fibroblast growth factors (FGFs) are a family of growth factors which includes twenty three proteins. FGFs work as modulators for various cellular activities like mitosis, differentiation and survival. Among the FGF family, human fibroblast growth factor-1 (hFGF-1), which is also known as acidic fibroblast growth factor, is a potent angiogenic agent, involved in the formation of new blood vessels in various tissues. hFGF-1 is regarded as a prototype of the FGF family. It serves as one of the potential targets in tumor inhibition and obesity due to its involvement in new blood vessel formation in cancerous regions and adipose tissues. …
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
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 …
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
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 …
Antioxidants Condition Pleiotropic Vascular Responses To Exogenous H2o2: Role Of Modulation Of Vascular Tp Receptors And The Heme Oxygenase System, Nitin Puri, Fan Zhang, Sumit R. Monu, Komal R. Sodhi, Lars Bellner, Brian D. Lamon, Yilun Zhang, Nader G. Abraham, Alberto Nasjletti
Antioxidants Condition Pleiotropic Vascular Responses To Exogenous H2o2: Role Of Modulation Of Vascular Tp Receptors And The Heme Oxygenase System, Nitin Puri, Fan Zhang, Sumit R. Monu, Komal R. Sodhi, Lars Bellner, Brian D. Lamon, Yilun Zhang, Nader G. Abraham, Alberto Nasjletti
Biochemistry and Microbiology
Aims: Hydrogen peroxide (H(2)O(2)), a nonradical oxidant, is employed to ascertain the role of redox mechanisms in regulation of vascular tone. Where both dilation and constriction have been reported, we examined the hypothesis that the ability of H(2)O(2) to effect vasoconstriction or dilation is conditioned by redox mechanisms and may be modulated by antioxidants.
Results: Exogenous H(2)O(2) (0.1-10.0 μM), dose-dependently reduced the internal diameter of rat renal interlobular and 3rd-order mesenteric arteries (p<0.05). This response was obliterated in arteries pretreated with antioxidants, including tempol, pegylated superoxide dismutase (PEG-SOD), butylated hydroxytoluene (BHT), and biliverdin (BV). However, as opposed to tempol or PEG-SOD, BHT & BV, antioxidants targeting radicals downstream of H(2)O(2), also uncovered vasodilation.
Innovations: Redox-dependent vasoconstriction to H(2)O(2) was blocked by inhibitors of cyclooxygenase (COX) (indomethacin-10 μM), thromboxane (TP) synthase (CGS13080-10 μM), and TP receptor antagonist (SQ29548-1 μM). However, H(2)O(2) …
0.05).>Microrna Function In Human Diseases, Sathish Kumar Natarajan, Mary A. Smith, Cody J. Wehrkamp, Ashley M. Mohr, Justin L. Mott
Microrna Function In Human Diseases, Sathish Kumar Natarajan, Mary A. Smith, Cody J. Wehrkamp, Ashley M. Mohr, Justin L. Mott
Journal Articles: Biochemistry & Molecular Biology
MicroRNAs are emerging as a hot topic in research, and rightfully so. They show great promise as targets of treatment and as markers for common human diseases, such as cancer and metabolic diseases. In this review, we address some of the basic questions regarding micro- RNA function in human disease and the clinical significance of microRNAs. Specifically, micro- RNAs in epigenetics, cancer, and metabolic diseases are discussed, with examples taken from cholangiocarcinoma and nonalcoholic fatty liver disease.
Microrna-200c Modulates The Expression Of Muc4 And Muc16 By Directly Targeting Their Coding Sequences In Human Pancreatic Cancer., Prakash Radhakrishnan, Ashley M. Mohr, Paul M. Grandgenett, Maria M. Steele, Surinder K. Batra, Michael A. Hollingsworth
Microrna-200c Modulates The Expression Of Muc4 And Muc16 By Directly Targeting Their Coding Sequences In Human Pancreatic Cancer., Prakash Radhakrishnan, Ashley M. Mohr, Paul M. Grandgenett, Maria M. Steele, Surinder K. Batra, Michael A. Hollingsworth
Journal Articles: Biochemistry & Molecular Biology
Transmembrane mucins, MUC4 and MUC16 are associated with tumor progression and metastatic potential in human pancreatic adenocarcinoma. We discovered that miR-200c interacts with specific sequences within the coding sequence of MUC4 and MUC16 mRNAs, and evaluated the regulatory nature of this association. Pancreatic cancer cell lines S2.028 and T3M-4 transfected with miR-200c showed a 4.18 and 8.50 fold down regulation of MUC4 mRNA, and 4.68 and 4.82 fold down regulation of MUC16 mRNA compared to mock-transfected cells, respectively. A significant reduction of glycoprotein expression was also observed. These results indicate that miR-200c overexpression regulates MUC4 and MUC16 mucins in pancreatic …
Emerging Trends For Radioimmunotherapy In Solid Tumors., Maneesh Jain, Suprit Gupta, Sukhwinder Kaur, Moorthy P. Ponnusamy, Surinder K. Batra
Emerging Trends For Radioimmunotherapy In Solid Tumors., Maneesh Jain, Suprit Gupta, Sukhwinder Kaur, Moorthy P. Ponnusamy, Surinder K. Batra
Journal Articles: Biochemistry & Molecular Biology
Due to its ability to target both known and occult lesions, radioimmunotherapy (RIT) is an attractive therapeutic modality for solid tumors. Poor tumor uptake and undesirable pharmacokinetics, however, have precluded the administration of radioimmunoconjugates at therapeutically relevant doses thereby limiting the clinical utility of RIT. In solid tumors, efficacy of RIT is further compromised by heterogeneities in blood flow, tumor stroma, expression of target antigens and radioresistance. As a result significant efforts have been invested toward developing strategies to overcome these impediments. Further, there is an emerging interest in exploiting short-range, high energy α-particle emitting radionuclides for the eradication of …
Effects Of Acute Or Chronic Ethanol Exposure During Adolescence On Behavioral Inhibition And Efficiency In A Modified Water Maze Task, Shawn K. Acheson, Craig Bearison, Mary-Louise Risher, Sabri H. Abdelwahab, Wilkie A. Wilson, H. Scott Swartzwelder
Effects Of Acute Or Chronic Ethanol Exposure During Adolescence On Behavioral Inhibition And Efficiency In A Modified Water Maze Task, Shawn K. Acheson, Craig Bearison, Mary-Louise Risher, Sabri H. Abdelwahab, Wilkie A. Wilson, H. Scott Swartzwelder
Biomedical Sciences
Ethanol is well known to adversely affect frontal executive functioning, which continues to develop throughout adolescence and into young adulthood. This is also a developmental window in which ethanol is misused by a significant number of adolescents. We examined the effects of acute and chronic ethanol exposure during adolescence on behavioral inhibition and efficiency using a modified water maze task. During acquisition, rats were trained to find a stable visible platform onto which they could escape. During the test phase, the stable platform was converted to a visible floating platform (providing no escape) and a new hidden platform was added …
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
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 …
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
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 …
Structure, Theoretical Studies And Coupling Reactions Of Some New Cyclic Boronic Esters, Andrew Kuttler, Sravanthi Durganala, Albert Fratini, Alexander Morgan, Vladimir Benin
Structure, Theoretical Studies And Coupling Reactions Of Some New Cyclic Boronic Esters, Andrew Kuttler, Sravanthi Durganala, Albert Fratini, Alexander Morgan, Vladimir Benin
Chemistry Faculty Publications
The present report describes the X-ray structural and theoretical studies of some new pinacolboronate esters, and it also outlines the use of the target structures in Suzuki coupling reactions to produce new aromatic or heteroaromatic esters and amides. X-ray structural analysis of the studied compounds revealed that the pinacolborane ring's position with respect to the benzene ring varies, depending on the particular environment. An ortho-positioned carboxylic ester (methyl ester) causes a nearly perpendicular orientation of the pinacolborane unit with respect to the benzene ring, whereas an ortho-positioned amide (N,N-dimethylamide) causes the pinacolborane unit to orient itself nearly coplanar. A plausible …
Bioengineering The Expression Of Active Recombinant Human Cathepsin G, Enteropeptidase, Neutrophil Elastase, And C-Reactive Protein In Yeast, Eliot T. Smith
Bioengineering The Expression Of Active Recombinant Human Cathepsin G, Enteropeptidase, Neutrophil Elastase, And C-Reactive Protein In Yeast, Eliot T. Smith
Electronic Theses and Dissertations
The yeasts Pichia pastoris and Kluyveromyces lactis were used to express several recombinant human proteins for further biochemical characterization. Two substitution variants of recombinant human enteropeptidase light chain (rhEPL) were engineered to modify the extended substrate specificity of this serine protease. Both were secreted as active enzymes in excess of 1.7 mg/L in P. pastoris fermentation broth. The substitution variant rhEPL R96Q showed significantly reduced specificities for the preferred substrate sequences DDDDK and DDDDR; however, the rhEPL Y174R variant displayed improved specificities for these substrate sequences relative to all other reported variants of this enzyme. The neutrophil serine proteases human …
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
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 …
Macromolecular Complexes Of Cystic Fibrosis Transmembrane Conductance Regulator Alter Fluid Transport In Inflammatory Bowel Disorders, Kavisha Arora
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 …
Label-Free Enrichment Of Functional Cardiomyocytes Using Microfluidic Deterministic Lateral Flow Displacemen, Boyang Zhang, James V. Green, Shashi K. Murthy, Milica Radisic
Label-Free Enrichment Of Functional Cardiomyocytes Using Microfluidic Deterministic Lateral Flow Displacemen, Boyang Zhang, James V. Green, Shashi K. Murthy, Milica Radisic
Shashi K. Murthy
Progress in cardiac cell replacement therapies and tissue engineering critically depends on our ability to isolate functional cardiomyocytes (CMs) from heterogeneous cell mixtures. Label-free enrichment of cardiomyocytes is desirable for future clinical application of cell based products. Taking advantage of the physical properties of CMs, a microfluidic system was designed to separate CMs from neonatal rat heart tissue digest based on size using the principles of deterministic lateral displacement (DLD). For the first time, we demonstrate enrichment of functional CMs up to 91±2.4% directly from the digested heart tissue without any pre-treatment or labeling. Enriched cardiomyocytes remained viable after sorting …
Profile Of Vismodegib And Its Potential In The Treatment Of Advanced Basal Cell Carcinoma., Muzafar A. Macha, Surinder K. Batra, Apar Kishor Ganti
Profile Of Vismodegib And Its Potential In The Treatment Of Advanced Basal Cell Carcinoma., Muzafar A. Macha, Surinder K. Batra, Apar Kishor Ganti
Journal Articles: Biochemistry & Molecular Biology
Basal cell carcinoma (BCC) is the most common human malignancy. Recent advances in our understanding of the critical biologic pathways implicated in the development and progression of BCC have led to the development of the first molecular targeted therapy for this disease. The hedgehog pathway is mutated in virtually all patients with BCC and recent trials with vismodegib, an inhibitor of this pathway, have shown significant responses. This review will discuss the importance of the hedgehog pathway in the pathogenesis of BCC and describe in detail the pharmacology of vismodegib in relation to its activity in advanced BCC.
Identification Of The Salivary Proteome In Children Throughout The Course Of Dental Eruption, Nada Tabbara
Identification Of The Salivary Proteome In Children Throughout The Course Of Dental Eruption, Nada Tabbara
Electronic Thesis and Dissertation Repository
The salivary proteome is recognized as a valuable source of potential oral and systemic disease biomarkers. Major efforts in salivary research have been dedicated to identify and characterize salivary proteins present in saliva using both classical biochemical methods and proteomics approaches in adults. Despite considerable research on the salivary proteome, little attention has been given to the changes in the salivary proteome occurring in children, specifically from 0-3 years of age. Through the use of anionic PAGE, SDS PAGE, HPLC and MS/MS, salivary protein profiles in children before, during and after dental eruption were compared with edentulous adult controls. We …
Studies On Tracheorelaxant And Anti-Inflammatory Activities Of Rhizomes Of Polygonatum Verticillatum, Haroon Khan, Muhammad Saeed, Hassan Mehmood, Najeeb-Ur Rehman, Naveed Muhammad, Ikram-Ul Haq, Nadeem Ashraf, Kamal Eldin H El-Tahir, Anwar Gilani
Studies On Tracheorelaxant And Anti-Inflammatory Activities Of Rhizomes Of Polygonatum Verticillatum, Haroon Khan, Muhammad Saeed, Hassan Mehmood, Najeeb-Ur Rehman, Naveed Muhammad, Ikram-Ul Haq, Nadeem Ashraf, Kamal Eldin H El-Tahir, Anwar Gilani
Department of Biological & Biomedical Sciences
Background: The present study describes the tracheorelaxant and anti-inflammatory effects of Polygonatum verticillatum which may support its medicinal use in hyperactive airway complaints and inflammatory disorders.
Methods: The tracheorelaxant activity of crude extract of the rhizomes of P. verticillatum (PR) was assessed in isolated guinea-pig tracheal tissues immersed in tissue organ bath filled with Tyrode's solution and a continuous supply of carbogen gas (95% O2 and 5% CO2). The contractile and relaxant responses of the tissue were measured using isometric transducers coupled with Power-Lab data acquisition system. The anti-inflammatory effect was evaluated in carrageenan-induced rat paw edema model, while the …
The Tumor Suppressor Tere1 (Ubiad1) Prenyltransferase Regulates The Elevated Cholesterol Phenotype In Castration Resistant Prostate Cancer By Controlling A Program Of Ligand Dependent Sxr Target Genes., William J. Fredericks, Jorge Sepulveda, Priti Lai, John E. Tomaszewski, Ming-Fong Lin, Terry Mcgarvey, Frank J. Rauscher, S. Bruce Malkowicz
The Tumor Suppressor Tere1 (Ubiad1) Prenyltransferase Regulates The Elevated Cholesterol Phenotype In Castration Resistant Prostate Cancer By Controlling A Program Of Ligand Dependent Sxr Target Genes., William J. Fredericks, Jorge Sepulveda, Priti Lai, John E. Tomaszewski, Ming-Fong Lin, Terry Mcgarvey, Frank J. Rauscher, S. Bruce Malkowicz
Journal Articles: Biochemistry & Molecular Biology
Castrate-Resistant Prostate Cancer (CRPC) is characterized by persistent androgen receptor-driven tumor growth in the apparent absence of systemic androgens. Current evidence suggests that CRPC cells can produce their own androgens from endogenous sterol precursors that act in an intracrine manner to stimulate tumor growth. The mechanisms by which CRPC cells become steroidogenic during tumor progression are not well defined. Herein we describe a novel link between the elevated cholesterol phenotype of CRPC and the TERE1 tumor suppressor protein, a prenyltransferase that synthesizes vitamin K-2, which is a potent endogenous ligand for the SXR nuclear hormone receptor. We show that 50% …
Characterization By Nmr Of Reactants And Products Of Hydrofluoroether Isomers, Cf3(Cf2)3och3 And (Cf3)2c(F)Cf2och3, Reacting With Isopropyl Alcohol, Howard Knachel, Vladimir Benin, William E. Moddeman, Janine C. Birkbeck, Thomas A. Kestner, Tayna L. Young
Characterization By Nmr Of Reactants And Products Of Hydrofluoroether Isomers, Cf3(Cf2)3och3 And (Cf3)2c(F)Cf2och3, Reacting With Isopropyl Alcohol, Howard Knachel, Vladimir Benin, William E. Moddeman, Janine C. Birkbeck, Thomas A. Kestner, Tayna L. Young
Chemistry Faculty Publications
The 3M Company product Novec™ 71IPA DL, a mixture of methoxyperfluorobutane, methoxyperfluoroisobutane and 4.5 wt.% isopropyl alcohol, has been found to be very stable at ambient temperature, producing fluoride at the rate of ~1 ppm/year. Our earlier kinetic and theoretical studies have identified the reaction mechanism. This paper identifies the 1H and 19F NMR chemical shifts, multiplicities, and coupling constants of reactants and the major products that result from aging the mixture in sealed Pyrex NMR tubes for periods up to 1.8 years at temperatures from 26 °C to 102 °C. Chemical shifts and coupling constants of fluorine …
Impaired Expression Of Protein Phosphatase 2a Subunits Enhances Metastatic Potential Of Human Prostate Cancer Cells Through Activation Of Akt Pathway., P Pandey, Parthasarathy Seshacharyulu, Srustidhar Das, Satyanarayana Rachagani, Moorthy P. Ponnusamy, Y Yan, Sonny L. Johansson, K Datta, Ming-Fong Lin, Surinder K. Batra
Impaired Expression Of Protein Phosphatase 2a Subunits Enhances Metastatic Potential Of Human Prostate Cancer Cells Through Activation Of Akt Pathway., P Pandey, Parthasarathy Seshacharyulu, Srustidhar Das, Satyanarayana Rachagani, Moorthy P. Ponnusamy, Y Yan, Sonny L. Johansson, K Datta, Ming-Fong Lin, Surinder K. Batra
Journal Articles: Biochemistry & Molecular Biology
BACKGROUND: Protein phosphatase 2A (PP2A) is a dephosphorylating enzyme, loss of which can contribute to prostate cancer (PCa) pathogenesis. The aim of this study was to analyse the transcriptional and translational expression patterns of individual subunits of the PP2A holoenzyme during PCa progression.
METHODS: Immunohistochemistry (IHC), western blot, and real-time PCR was performed on androgen-dependent (AD) and androgen-independent (AI) PCa cells, and benign and malignant prostate tissues for all the three PP2A (scaffold, regulatory, and catalytic) subunits. Mechanistic and functional studies were performed using various biochemical and cellular techniques.
RESULTS: Through immunohistochemical analysis we observed significantly reduced levels of PP2A-A …