Biological Phenomena, Cell Phenomena, and Immunity Commons^™

Escherichia Coli Itat Is A Type Ii Toxin That Inhibits Translation By Acetylating Isoleucyl-Trnaile, Brendan Wilcox, Ilya Osterman, Marina Serebryakova, Dmitry Lukyanov, Ekaterina Komarova, Bridget Gollan, Natalia Morozova, Yuri I Wolf, Kira S Makarova, Sophie Helaine, Petr Sergiev, Svetlana Dubiley, Sergei Borukhov, Konstantin Severinov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Prokaryotic toxin-antitoxin (TA) modules are highly abundant and are involved in stress response and drug tolerance. The most common type II TA modules consist of two interacting proteins. The type II toxins are diverse enzymes targeting various essential intracellular targets. The antitoxin binds to cognate toxin and inhibits its function. Recently, TA modules whose toxins are GNAT-family acetyltransferases were described. For two such systems, the target of acetylation was shown to be aminoacyl-tRNA: the TacT toxin targets aminoacylated elongator tRNAs, while AtaT targets the amino acid moiety of initiating tRNAMet. We show that the itaRT gene pair from Escherichia coli …

Inhibition Of Ribosome Biogenesis Through Genetic And Chemical Approaches, Leonid Anikin

Graduate School of Biomedical Sciences Theses and Dissertations

In order to maintain the ability to generate proteins, proliferating cells must continuously generate ribosomes, designating up to 80% of their energy to ribosome biogenesis (RBG). RBG involves transcription of rDNA by RNA polymerases I (Pol I) and III (Pol III), expression of approximately 80 ribosomal proteins, and assembly of these components in a process referred to as ribosome maturation. During maturation, the Pol I transcribed 47S pre-rRNA undergoes a number of processing events, while simultaneously interacting with processing factors and ribosomal proteins that drive pre-ribosome assembly. Inhibition of RBG has become one of the pursued targets for cancer therapy …

Targeting Ribosome Assembly Factors Selectively Protects P53 Positive Cells From Chemotherapeutic Agents, Russell T. Sapio, Anastasiya Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J. Manna, N. Minkovsky, Dimitri G Pestov

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Many chemotherapeutic agents act in a nondiscriminatory fashion, targeting both cancerous and noncancerous cells in Sphase and Mphase. One approach to reduce the toxic side effects in normal tissue is to exploit the differences in p53 functionality between cancerous and noncancerous cells. For example, activating p53 signaling by nongenotoxic means can transiently arrest noncancerous p53 positive cells in G1 phase and protect them from the cytotoxic effects of chemotherapeutic drugs. However, since most cancerous cells have faulty p53 signaling, they will proceed to cycle, and continue to be affected by the drug. In this study we asked if this G1‐phase …

Chat Expression In Chlamydia Muridarum-Infected Female Murine Genital Tract, Hallie Sartain

Undergraduate Honors Theses

Chlamydia trachomatis is the most prevalent agent of bacterial sexually transmitted infections in the world. However, a profuse number of cases are unreported, as the infection is often asymptomatic. Sequelae such as pelvic inflammatory disease, an increased risk of cervical cancer, premature birth, and perinatal infections in pregnant women can occur. Inflammation occurs in the body in response to infection or injury. Although inflammation can lead to some unwanted secondary effects, such as pain, it serves to return the body to homeostasis by restoring injured tissues and eliminating pathogens. One recently identified connection between the central nervous system and the …

A Review Of Ankylosing Spondylitis, Hannah L. Owen

Senior Honors Theses

Ankylosing spondylitis (AS) is a systemic autoimmune disorder that induces ankylosis of the spine (fusion of the vertebrae at their various joints) and inflammatory arthritis of peripheral joints among other symptoms. Overexpression of cytokines, the presence of genetic mutations not exclusive to the human leucocyte antigen (HLA)-B27 region, and environmental factors all have large roles in the progressive development of AS. Although a definitive pathology continues to be sought after, researchers believe the adaptive immune system in AS patients attacks fibrocartilaginous entheses (supportive connective tissue between bone and attached structures like tendon, ligament, and fascia).

AS markedly reduces proper systemic …

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, Peican Zhu, Hamidreza Montazeri Aliabadi, Hasan Uludag, Jie Han

Pharmacy Faculty Articles and Research

The investigation of vulnerable components in a signaling pathway can contribute to development of drug therapy addressing aberrations in that pathway. Here, an original signaling pathway is derived from the published literature on breast cancer models. New stochastic logical models are then developed to analyze the vulnerability of the components in multiple signalling sub-pathways involved in this signaling cascade. The computational results are consistent with the experimental results, where the selected proteins were silenced using specific siRNAs and the viability of the cells were analyzed 72 hours after silencing. The genes elF4E and NFkB are found to have nearly no …

Design, Synthesis, And Evaluation Of Chitosan Conjugated Ggrgdsk Peptides As A Cancer Cell-Targeting Molecular Transporter, Naglaa Salem El-Sayed, Amir Nasrolahi Shirazi, Magda Goda El-Meligy, Ahmed Kamel El-Ziaty, Zenat A. Nagieb, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Targeting cancer cells using integrin receptor is one of the promising targeting strategies in drug delivery. In this study, we conjugated an integrin-binding ligand (GGRGDSK) peptide to chitosan oligosaccharide (COS) using (sulfo-SMCC) bifunctional linker affording COS-SMCC-GGRGDSK. The conjugated polymer was characterized by FT-IR, ¹H NMR, ¹³C NMR, and SEM. COS-SMCC-GGRGDSK did not show cytotoxicity up to a concentration of 1 mg/mL in the human leukemia cell line (CCRF-CEM). The conjugate was evaluated for its ability to enhance the cellular uptake of cell-impermeable cargoes (e.g., FAM and F′-G(pY)EEI phosphopeptide) in CCRF-CEM, and human ovarian carcinoma (SK-OV-3) cancer …

How The Manipulation Of The Ras Homolog Enriched In Striatum Alters The Behavioral And Molecular Progression Of Huntington’S Disease, Franklin A. Lee

University of New Orleans Theses and Dissertations

Huntington’s disease is an incurable, progressive neurological disorder characterized by loss of motor control, psychiatric dysfunction, and eventual dystonia leading to death. Despite the fact that this disorder is caused by a mutation in one single gene, there is no cure. The mutant Huntingtin (mHtt) protein is expressed ubiquitously throughout the brain but frank cell death is limited to the striatum. Recent work has suggested that Rhes, Ras homolog enriched in striatum, which is selectively expressed in the striatum, may play a role in Huntington’s disease neuropathology. In vitro studies have shown Rhes to be an E3 ligase for the …

Facile, Regio-And Diastereoselective Synthesis Of Spiro-Pyrrolidine And Pyrrolizine Derivatives And Evaluation Of Their Antiproliferative Activities, Abdulrahman I. Almansour, Raju Suresh Kumar, Farzana Beevi, Amir Nasrolahi Shirazi, Hasnah Osman, Rusli Ismail, Tan Soo Chen, Brian Sullivan, Kellen Mccaffrey, Alaa Nahhas, Keykavous Parang, Mohamed Ashraf Ali

Pharmacy Faculty Articles and Research

A number of novel spiro-pyrrolidines/pyrrolizines derivatives were synthesized through [3+2]-cycloaddition of azomethine ylides with 3,5-bis[(E)-arylmethylidene] tetrahydro-4(1H)-pyridinones 2a-n. Azomethine ylides were generated in situ from the reaction of 1H-indole-2,3-dione (isatin, 3) with N-methylglycine (sarcosine), phenylglycine, or proline. All compounds (50 M) were evaluated for their antiproliferative activity against human breast carcinoma (MDA-MB-231), leukemia lymphoblastic (CCRF-CEM), and ovarian carcinoma (SK-OV-3) cells. N-alpha-Phenyl substituted spiro-pyrrolidine derivatives (5a-n) showed higher antiproliferative activity in MDA-MB-231 than other cancer cell lines. Among spiro-pyrrolizines 6a-n, a number of derivatives including 6a-c and 6i-m showed a comparable activity with doxorubicin in all three cell lines. Among all compounds …

Cyclic Peptide-Capped Gold Nanoparticles For Enhanced Sirna Delivery, Amir Nasrolahi Shirazi, Karissa L. Paquin, Niall G. Howlett, Dindyal Mandal, Keykavous Parang

Pharmacy Faculty Articles and Research

Previously, we have reported the synthesis of a homochiral L-cyclic peptide [WR]5 and its use for delivery of anti-HIV drugs and biomolecules. A physical mixture of HAuCl4 and the peptide generated peptide-capped gold nanoparticles. Here, [WR]5 and [WR]5-AuNPs were tested for their efficiency to deliver a small interfering RNA molecule (siRNA) in human cervix adenocarcinoma (HeLa) cells. Flow cytometry investigation revealed that the intracellular uptake of a fluorescence-labeled non-targeting siRNA (200 nM) was enhanced in the presence of [WR]5 and [WR]5-AuNPs by 2- and 3.8-fold when compared with that of siRNA alone after 24 h incubation. Comparative toxicity results showed …

Inhibition Of Cholinergic Signaling Causes Apoptosis In Human Bronchioalveolar Carcinoma, Jamie K. Lau, Kathleen C. Brown, Brent A. Thornhill, Clayton M. Crabtree, Aaron M. Dom, Theodore R. Witte, W. Elaine Hardman, Christopher A. Mcnees, Cody A. Stover, A. Betts Carpenter, Haitao Luo, Yi C. Chen, Brandon S. Shiflett, Piyali Dasgupta

Biochemistry and Microbiology

Recent case-controlled clinical studies show that bronchioalveolar carcinomas (BAC) are correlated with smoking. Nicotine, the addictive component of cigarettes, accelerates cell proliferation through nicotinic acetylcholine receptors (nAChR). In this study, we show that human BACs produce acetylcholine (ACh) and contain several cholinergic factors including acetylcholinesterase (AChE), choline acetyltransferase (ChAT), choline transporter 1 (CHT1, SLC5A7), vesicular acetylcholine transporter (VAChT, SLC18A3), and nACh receptors (AChRs, CHRNAs). Nicotine increased the production of ACh in human BACs, and ACh acts as a growth factor for these cells. Nicotine-induced ACh production was mediated by α7-, α3β2-, and β3-nAChRs, ChAT and VAChT pathways. We observed that …

Ricin B Chain-Insulin Fusion Protein Immunomodulation Of Type 1 Diabetes, James Edward Carter Iii

Loma Linda University Electronic Theses, Dissertations & Projects

Type 1 diabetes mellitus (T1D) is a debilitating chronic inflammatory disease of the insulin-producing pancreatic islet β-cells that results from a combination of genetic and environmental factors. Attempts to suppress Th1-mediated autoimmune diseases such as T1D by mucosal delivery of autoantigens for immunotolerization have yielded only partial success. Attainment of satisfactory levels of sustained immunological tolerance remains to be accomplished. To restore self-tolerance requires delivery of sufficient amounts of autoantigen to stimulate regulatory T helper cells that function to survey the gut and induce tolerance to consumed antigens such as food. Oral delivery of autoantigens has previously been shown to …

Efficacy Of Deferasirox In Preventing Complications Of Iron Overload In The Iron Overloaded Gerbil, Rabaa M. Al-Rousan

Theses, Dissertations and Capstones

Iron overload is a significant, world-wide problem that results in several chronic diseases including cardiovascular, hepatic and pancreatic complications.The newly developed, orally effective, iron chelating agent deferasirox is thought to offer tremendous promise as an alternative to deferoxamine. However, the efficacy and safety profile of deferasirox is not yet clear. In the present study, the efficacy of deferasirox in removing iron from target tissues has been examined using the gerbil model of iron overload. Deferasirox administration resulted in a significant reduction of iron from cardiac and hepatic tissue. In addition deferasirox reduced iron induced increase in cardiac and hepatic oxidative …

Stat5 Regulation Of Bcl10 Parallels Constitutive Nfkappab Activation In Lymphoid Tumor Cells., Zsuzsanna S Nagy, Matthew J Lebaron, Jeremy A Ross, Abhisek Mitra, Hallgeir Rui, Robert A Kirken

Department of Cancer Biology Faculty Papers

BACKGROUND: Signal Transducer and Activator of Transcription 5 A and B (STAT5) are key survival factors in cells of the lymphoid lineage. Identification of novel, tissue-specific STAT5 regulated genes would advance the ability to combat diseases due to aberrant STAT5 signaling. In the present work a library of human STAT5 bound genomic elements was created and validated. RESULTS: Of several STAT5 responsive genomic regulatory elements identified, one was located within the first intron of the human BCL10 gene. Chromatin immuno-precipitation reactions confirmed constitutive in vivo STAT5 binding to this intronic fragment in various human lymphoid tumor cell lines. Interestingly, non-phosphorylated …

Immune Evasion By Rabies Viruses Through The Maintenance Of Blood-Brain Barrier Integrity., Anirban Roy, Douglas C. Hooper

Department of Cancer Biology Faculty Papers

The attenuated rabies virus (RV) strain Challenge Virus Standard (CVS)-F3 and a highly pathogenic strain associated with the silver-haired bats (SHBRV) can both be cleared from the central nervous system (CNS) tissues by appropriate antiviral immune mechanisms if the effectors are provided access across the blood-brain barrier (BBB). In the case of SHBRV infection, antiviral immunity develops normally in the periphery but fails to open the BBB, generally resulting in a lethal outcome. To determine whether or not an absence in the CNS targeted immune response is associated with the infection with other pathogenic RV strains, we have assessed the …

Right-Handed 14-Helix In Β3-Peptides From L-Aspartic Acid Monomers, Kamaljit Kaur, Tara Sprules, Wael Soliman, Reem Beleid, Sahar Ahmed

Pharmacy Faculty Articles and Research

β-Peptides made from L-aspartic acid monomers form a new class of β³-peptides. Here we report the first three-dimensional NMR solution structure of a β³-hexapeptide (1) from L-aspartic acid monomers in 2,2,2-trifluoroethanol (TFE). We show that 1 forms a right-handed 14-helical structure in TFE. α-peptides from naturally occurring L-amino acids adopt a right-handed α-helix whereas β³-peptides formed from β³-amino acids derived from naturally occurring L-amino acids form left-handed 14-helices. The right-handed 14-helical conformation of 1 is a better mimic of α-peptide conformations. Using the NMR structure of 1 in TFE, we …

Enterotoxin B Subunit Lectins As Adjuvants For Improvement Of Mucosal Vaccine, Nak-Won Choi

Loma Linda University Electronic Theses, Dissertations & Projects

In comparison with whole organism vaccines, subunit vaccines may be safer for immunization but may lack sufficient immunogenicity to provide complete immunity to the pathogen. To resolve this problem, bacterial and plant enterotoxin B subunit adjuvants containing a variety of receptor-binding properties were used to enhance the immunogenicity of rotavirus subunit vaccines. Enterotoxin B subunit adjuvants were employed to enhance protection against virus infection. Pentameric cholera toxin B subunit (CTB), shiga toxin-1 B subunit (STB) and monomeric ricin toxin B subunit (RTB) molecules were genetically linked to a 90 amino acid peptide from the simian rotavirus (SA11) nonstructural protein NSP4 …

Cellular Responses In Escherichia Coli To Lethal And Sublethal Doses Of Ozone, Indira Ruth Komanapalli

Loma Linda University Electronic Theses, Dissertations & Projects

Ozone is a major component of photochemical smog. High levels of this pollutant, sufficient to affect human health are found in many urban areas worldwide. Though limited studies in humans are supported by extensive findings from animal experiments, a difficulty in interpreting the results of these experiments has lead to an ambiguity on the biochemical mechanism of ozone toxicity. To elucidate the mechanism by which ozone causes cell damage and eventual cell death we conducted a comprehensive study using Escherichia coli K-12 as a model.

Studies on the comparative inactivation of bacteriophage lambda (λ), Escherichia coli, and Candida albicans …

Phosphorylation Of The Rex Protein Of Human T-Cell Leukemia Virus Type 1, Yoshifumi Adachi, Terry D. Copeland, Chiaki Takahashi, Tetsuya Nosaka, Aftab Ahmed, Stephen Oroszlan, Masakazu Hatanaka

Pharmacy Faculty Articles and Research

Rex protein, the posttranscriptional regulator of human T-cell leukemia virus type I (HTLV-I), is required for the control of viral structural protein expression and virus replication. Rex is a phosphoprotein found predominantly in the cell nucleolus, whose function is thought to be regulated by its nucleolar localization and phosphorylation. Therefore, we investigated the in vivo phosphorylation of Rex protein in more detail. Phosphorylation of Rex occurred in all HTLV-I-infected cell lines examined in vivo, primarily at serine residues and to a very small extent at threonine residues. Treatment of cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) led to significant but transient enhancement of …

Interaction Of Putative Estrogens And The Estrogen Receptor System In Leydig Cells In The Balb/C Mouse Testis Resulting In The Initiation Of Dna Synthesis, R. Lloyd Juriansz

Loma Linda University Electronic Theses, Dissertations & Projects

Continuous administration of estrogens for 7-9 months, both steroidal and nonsteroidal, to male BALB/c mice, leads to the formation of testicular Leydig cell tumors. Three days following the subcutaneous implantation of a pellet of estrogen in cholesterol, there is a peak in the incorporation of ³H-tymidine into the DNA of the interstitial cells. These effects are hypothesized to be mediated by the estrogen receptor system in the Leydig cell. Common experimental techniques for the measurement of hormone binding, such as dextran coated charcoal treatment, proved to be impossible to employ in this system, therefore a procedure was developed using …