Open Access. Powered by Scholars. Published by Universities.®

Medical Biochemistry

Institution
Keyword
Publication Year
Publication
Publication Type

Articles 31 - 60 of 79

Full-Text Articles in Biological Phenomena, Cell Phenomena, and Immunity

Saturation Mutagenesis Reveals Manifold Determinants Of Exon Definition., Shengdong Ke, Vincent Anquetil, Jorge Rojas Zamalloa, Alisha Maity, Anthony Yang, Mauricio A. Arias, Sergey Kalachikov, James J Russo, Jingyue Ju, Lawrence A. Chasin Jan 2018

Saturation Mutagenesis Reveals Manifold Determinants Of Exon Definition., Shengdong Ke, Vincent Anquetil, Jorge Rojas Zamalloa, Alisha Maity, Anthony Yang, Mauricio A. Arias, Sergey Kalachikov, James J Russo, Jingyue Ju, Lawrence A. Chasin

Student Papers, Posters & Projects

To illuminate the extent and roles of exonic sequences in the splicing of human RNA transcripts, we conducted saturation mutagenesis of a 51-nt internal exon in a three-exon minigene. All possible single and tandem dinucleotide substitutions were surveyed. Using high-throughput genetics, 5560 minigene molecules were assayed for splicing in human HEK293 cells. Up to 70% of mutations produced substantial (greater than twofold) phenotypes of either increased or decreased splicing. Of all predicted secondary structural elements, only a single 15-nt stem-loop showed a strong correlation with splicing, acting negatively. The in vitro formation of exon-protein complexes between the mutant molecules and …


Inactivation Of Endoplasmic Reticulum Stress And The Prevention Of Neurodegenerative Diseases, Ian James Martins Jan 2018

Inactivation Of Endoplasmic Reticulum Stress And The Prevention Of Neurodegenerative Diseases, Ian James Martins

Research outputs 2014 to 2021

Biotherapeutics and nutritional therapy are essential for the treatment of endoplasmic reticulum (ER) stress in diabetes and neurodegenerative diseases. Oxidative stress and nutrient excess may induce ER stress associated with activation of the unfolded protein response and connected to cell death. The heat shock gene Sirtuin 1 (Sirt 1) is important to the heat shock response with amyloid beta aggregation associated with the induction of mitophagy and ER stress in neuron cells. Genomic medicine that activates nuclear Sirt 1 is essential for the prevention of mitochondrial apoptosis and ER stress. Inhibitors such as drugs, alcohol, excess caffeine and palmitic acid …


Effect Of Extracellular Survivin And Lymphoma Exosomes On Natural Killer Cells, Heather R. Ferguson Bennit Sep 2017

Effect Of Extracellular Survivin And Lymphoma Exosomes On Natural Killer Cells, Heather R. Ferguson Bennit

Loma Linda University Electronic Theses, Dissertations & Projects

Tumors alter their microenvironment to promote survival using methods such as angiogenesis promotion, growth signals, and immune suppression. The immune system becomes unresponsive to transformed neoplastic cells through a variety of methods including T cell suppression, increased myeloid-derived suppressor cells (MDSCs), and reduced natural killer (NK) cell activity. NK cells have inherent killing capabilities and thus are among the first responders in recognizing and destroying abnormal cells. However, many types of cancers inhibit the surveillance and cytotoxic abilities of NK cells by releasing exosomes, vesicles that can modulate the tumor microenvironment (TME) and intercellular communication for the purpose of enhancing …


Diagnostic Effectiveness Of High-Sensitivity Troponins, Sean R. Bodin, Jacqueline Ramirez May 2017

Diagnostic Effectiveness Of High-Sensitivity Troponins, Sean R. Bodin, Jacqueline Ramirez

Physician Assistant Capstones, 2016 to 2019

Background: Acute myocardial infarctions (AMI) are a leading cause of death in the United States. The key to increasing survivability is early recognition to expedite the proper treatment modalities. In conjunction with the clinical presentation and electrocardiograms, the use of cardiac biomarkers is exponentially important in not only recognizing a cardiac event but also determining the extent of injury. Advancement in laboratory technology has led to the development of high-sensitive troponin (hs-troponin) assays which can detect smaller cardiac troponin serum levels compared to conventional troponin assays. This implies that the use of hs-troponin assays is more effective in the …


Role Of Dendritic Cells In Pathology Of Respiratory Syncytial Virus Infection In Neonates, Bishwas Shrestha May 2017

Role Of Dendritic Cells In Pathology Of Respiratory Syncytial Virus Infection In Neonates, Bishwas Shrestha

Theses and Dissertations (ETD)

Respiratory syncytial virus (RSV) is one of the leading causes of bronchiolitis in children. We have shown that neonatal mice respond to primary RSV infection with T helper type 2 (Th2) biased immune responses, which are enhanced following reinfection. Dendritic cells (DCs) including myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) play important roles in driving host responses to RSV infection. mDCs present antigens to help Th cells differentiate, and pDCs protect against viral infection through type I interferons (IFNs). Despite data demonstrating importance of mDCs and pDCs in protection against RSV, it has not been studied in an age appropriate …


Peroxiredoxin Catalysis At Atomic Resolution, Arden Perkins, Derek Parsonage, Kimberly J. Nelson, O. Maduka Ogba, Paul Ha-Yeon Cheong, Leslie B. Poole, P. Andrew Karplus Sep 2016

Peroxiredoxin Catalysis At Atomic Resolution, Arden Perkins, Derek Parsonage, Kimberly J. Nelson, O. Maduka Ogba, Paul Ha-Yeon Cheong, Leslie B. Poole, P. Andrew Karplus

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Peroxiredoxins (Prxs) are ubiquitous cysteine-based peroxidases that guard cells against oxidative damage, are virulence factors for pathogens, and are involved in eukaryotic redox regulatory pathways. We have analyzed catalytically active crystals to capture atomic resolution snapshots of a PrxQ-subfamily enzyme (from Xanthomonas campestris) proceeding through thiolate, sulfenate, and sulfinate species. These analyses provide structures of unprecedented accuracy for seeding theoretical studies, and show novel conformational intermediates giving insight into the reaction pathway. Based on a highly non-standard geometry seen for the sulfenate intermediate, we infer that the sulfenate formation itself can strongly promote local unfolding of the active site to …


Loss Of Exogenous Androgen Dependence By Prostate Tumor Cells Is Associated With Elevated Glucuronidation Potential, Brenna M. Zimmer, Michelle E. Howell, Qin Wei, Linlin Ma, Trevor Romsdahl, Eileen G. Loughman, Jennifer E. Markham, Javier Seravalli, Joseph J. Barycki, Melanie A. Simpson Aug 2016

Loss Of Exogenous Androgen Dependence By Prostate Tumor Cells Is Associated With Elevated Glucuronidation Potential, Brenna M. Zimmer, Michelle E. Howell, Qin Wei, Linlin Ma, Trevor Romsdahl, Eileen G. Loughman, Jennifer E. Markham, Javier Seravalli, Joseph J. Barycki, Melanie A. Simpson

Department of Biochemistry: Faculty Publications

Prostate epithelial cells control the potency and availability of androgen hormones in part by inactivation and elimination. UDP-glucose dehydrogenase (UGDH) catalyzes the NAD+-dependent oxidation of UDP-glucose to UDP-glucuronate, an essential precursor for androgen inactivation by the prostate glucuronidation enzymes UGT2B15 and UGT2B17. UGDH expression is androgen stimulated, which increases the production of UDP-glucuronate, and fuels UGT-catalyzed glucuronidation. In this study, we compared the glucuronidation potential and its impact on androgen-mediated gene expression in an isogenic LNCaP model for androgen dependent versus castration resistant prostate cancer. Despite significantly lower androgen-glucuronide output, LNCaP 81 castration resistant tumor cells expressed higher …


Pten Signaling In Regulatory T Cells And Inflammatory Disease, Sharad Krishna Shrestha May 2016

Pten Signaling In Regulatory T Cells And Inflammatory Disease, Sharad Krishna Shrestha

Theses and Dissertations (ETD)

Regulatory T (Treg) cells suppress CD4+ T cell responses during homeostasis and inflammation to prevent autoimmunity and other immune disorders. Although the transcriptional and epigenetic programs impacting Treg cell function have been extensively studied, the signaling and metabolic pathways underlying Treg stability and function are not fully understood. In this study, we determined the role of the phosphatase PTEN in Treg cells. We found that specific depletion of PTEN in Treg cells results in excessive TH1 and T follicular helper cells (TFH) responses, associated with elevated germinal center (GC) B cells and spontaneous development of autoimmune and lymphoproliferative disease in …


How The Manipulation Of The Ras Homolog Enriched In Striatum Alters The Behavioral And Molecular Progression Of Huntington’S Disease, Franklin A. Lee Dec 2015

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

LSU 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 …


Qualitatively Assessing The Expression Of Kynurenine Pathway Metabolic Enzymes In Human Glioma Tissue, Kaushik Varadarajan May 2015

Qualitatively Assessing The Expression Of Kynurenine Pathway Metabolic Enzymes In Human Glioma Tissue, Kaushik Varadarajan

Honors College Theses

Gliomas are the most common brain tumor and glioblastoma multiforme (GBM) is the most common type of glioma observed in patients. Prognosis with late stage glioma and GBM is very poor even with recent advances in treatment. Along with treating the tumor, manners of bypassing the blood brain barrier and ensuring the tumor uptakes the treatment is necessary. Because the treatments can harm regular brain cells there is concern about the viability and toxic side effects of many treatments. With all of these challenges posed it is important to understand how glial tumors can be so recurring and difficult to …


The Use Of Shape Memory Polymers As A Tool To Study Human Fibrosarcoma And Murine Mesenchymal Stem Cell Migration, Justin N. Elkhechen May 2015

The Use Of Shape Memory Polymers As A Tool To Study Human Fibrosarcoma And Murine Mesenchymal Stem Cell Migration, Justin N. Elkhechen

Renée Crown University Honors Thesis Projects - All

Shape memory polymers (SMPs) are a class of “smart” materials that can transform between two distinct conformations through external stimuli, such as heat or electricity. Their usage in bioengineering has led to a promising field of research that lies at the interface of cell and mechanobiology, potentially providing insight into cancer therapies and tissue development—two processes that exist in dynamic environments in vivo. The present work involves creating new, shape changing, scaffolds for studies to analyze cell migration upon changes to the environmental topography. Specifically, this Capstone has been primarily focused on the development of a “half and half” fibrous …


Er-Associated Degradation And Cadmium Dependent Rescue Of Pca1, Nathan Smith Nov 2014

Er-Associated Degradation And Cadmium Dependent Rescue Of Pca1, Nathan Smith

Department of Biochemistry: Dissertations, Theses, and Student Research

Protein synthesis and proper folding is an essential process for all organisms. In eukaryotes proteins of the secretory pathway are synthesized and inserted into the lumen or membrane of the endoplasmic reticulum. Eukaryotic cells maintain a mechanism for removal of proteins unable to fold properly. This process is known as ER-associated degradation (ERAD). A poorly functioning ERAD can lead to a build-up of misfolded proteins which has been implicated in several degenerative diseases such as Alzheimer’s, Amyotrophic lateral sclerosis, and Parkinson’s. Thus, the study of how proteins are recognized, extracted from the ER, and degraded is essential for determining methods …


Antioxidant Gene Therapy Against Neuronal Cell Death, Juliana Navarro-Yepes, Laura Zavala-Flores, Anandhan Annadurai, Fang Wang, Maciej Skotak, Namas Chandra, Ming Li, Aglaia Pappa, Daniel Martinez-Fong, Luz Maria Del Razo, Betzabet Quintanilla-Vega, Rodrigo Franco May 2014

Antioxidant Gene Therapy Against Neuronal Cell Death, Juliana Navarro-Yepes, Laura Zavala-Flores, Anandhan Annadurai, Fang Wang, Maciej Skotak, Namas Chandra, Ming Li, Aglaia Pappa, Daniel Martinez-Fong, Luz Maria Del Razo, Betzabet Quintanilla-Vega, Rodrigo Franco

Department of Psychology: Faculty Publications

Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated inmitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. …


Benzyl Isothiocyanate As An Adjuvant Chemotherapy Option For Head And Neck Squamous Cell Carcinoma, Mary Allison Wolf Jan 2014

Benzyl Isothiocyanate As An Adjuvant Chemotherapy Option For Head And Neck Squamous Cell Carcinoma, Mary Allison Wolf

Theses, Dissertations and Capstones

Isothiocyanates (ITCs) are natural phytochemicals produced by cruciferous vegetables. Recent evidence supports that, in addition to cancer prevention, ITCs can use various mechanisms to target malignant cells. Current therapies for cancer often provoke detrimental side effects, however clinical evidence supports that ITCs have little to no side effects in patients. Consequently, ITCs may be a promising treatment option for cancer patients, especially patients suffering from head and neck squamous cell carcinoma (HNSCC).

Despite recent improvements in cancer treatment, overall survival of advanced HNSCC has not improved in the past three decades. Metastasis and chemoresistance represent two detrimental events that greatly …


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 Jan 2014

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 Jan 2014

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 …


Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu Jun 2013

Truncation Of Type Iv Pilin Induces Mucoidy In Pseudomonas Aeruginosa Strain Pao579, T. Ryan Withers, F. Heath Damron, Yeshi Yin, Hongwei D. Yu

Biochemistry and Microbiology

Pseudomonas aeruginosa is a Gram negative, opportunistic pathogen that uses the overproduction of alginate, a surface polysaccharide, to form biofilms in vivo. Overproduction of alginate, also known as mucoidy, affords the bacterium protection from the host's defenses and facilitates the establishment of chronic lung infections in individuals with cystic fibrosis. Expression of the alginate biosynthetic operon is primarily controlled by the alternative sigma factor AlgU (AlgT/σ22). In a nonmucoid strain, AlgU is sequestered by the transmembrane antisigma factor MucA to the cytoplasmic membrane. AlgU can be released from MucA via regulated intramembrane proteolysis by proteases AlgW and MucP …


Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera Oct 2012

Stem Cell Transplantation Increases Antioxidant Effects In Diabetic Mice, Ming Li, Luca Vanella, Yuming Zhang, Ming Shi, Takashi Takaki, Joseph I. Shapiro M.D., Susuma Ikehera

Biochemistry and Microbiology

Intra bone marrow-bone marrow transplantation (IBM- BMT) + thymus transplantation (TT) has been shown to reduce the incidence of graft versus host disease (GVHD) and restore donor-derived T cell function. In addition, an increase in insulin sensitivity occurred in db/db mice after IBM-BMT+TT treatment. Heme oxygenase (HO)-1 is a stress inducible enzyme which exert antioxidant, antiapoptotic, and immune-modulating properties. We examined whether IBM-BMT+TT could modulate the expression of HO-1 in the kidneys of db/db mice. Six-week-old db/db mice with blood glucose levels higher than 250 mg/dl were treated with IBM-BMT+TT. Six weeks later, the db/db mice showed decreased body weight, …


Mussel Inspired Protein-Mediated Surface Modification To Electrospun Fibers And Their Potential Biomedical Applications, Jingwei Xie, Praveesuda Lorwattanapongsa Michael, Shaoping Zhong, Bing Ma, Matthew R. Macewan, Chwee Teck Lim Apr 2012

Mussel Inspired Protein-Mediated Surface Modification To Electrospun Fibers And Their Potential Biomedical Applications, Jingwei Xie, Praveesuda Lorwattanapongsa Michael, Shaoping Zhong, Bing Ma, Matthew R. Macewan, Chwee Teck Lim

MIIR Faculty Research

Mussel inspired proteins have been demonstrated to serve as a versatile biologic adhesive with numerous applications. The present study illustrates the use of such Mussel inspired proteins (polydopamine) in the fabrication of functionalized bio-inspired nanomaterials capable of both improving cell response and sustained delivery of model probes. X-ray photoelectron spectroscopy analysis confirmed the ability of dopamine to polymerize on the surface of plasma-treated, electrospun poly(ε-caprolactone) (PCL) fiber mats to form polydopamine coating. Transmission electron microscopy images demonstrated that self-polymerization of dopamine was induced by pH shift and that the thickness of polydopamine coating was readily modulated by adjusting the concentration …


Nuclear Receptor Expression And Characterization Of The Major Retinoic Acid Target Gene In Melanoma, Linda L. Eastham Jan 2012

Nuclear Receptor Expression And Characterization Of The Major Retinoic Acid Target Gene In Melanoma, Linda L. Eastham

Theses, Dissertations and Capstones

Malignant melanoma is the primary cause of death from all diseases arising from the skin and it is one of the most resistant tumors to standard treatment options. The increasing incidence of melanoma and its poor prognosis makes the understanding of melanoma cell biology very important. Melanoma progression is a complex, multi-step process, and the molecular events leading to melanoma tumor cell proliferation and invasion still need further examination. This study is focused on measuring the expression and activity of two specific genes and their protein counterparts that are altered during melanoma progression. It also examines the mechanism through which …


Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent E. Sollars, Andrea Del Pilar Belalcazar Sep 2011

Domain Requirements For The Diverse Immune Regulatory Functions Of Foxp3, Wei-Ping Zeng, Vincent E. Sollars, Andrea Del Pilar Belalcazar

Biochemistry and Microbiology

Foxp3 is responsible for the major immunological features of Treg cells, including hypoproliferation in vitro, immune suppression of conventional T cells and resistance to Th2 cell differentiation. In addition to the Forkhead domain, the Foxp3 protein contains the N-terminal, zinc finger and leucine zipper domains. To understand how these domains contribute to Foxp3 functions, we systematically compared the roles of these domains in determining the 3 major immunological features of Treg cells. We designed a bridge-mediated mutagenesis method to generate Foxp3 mutants with complete deletion of each of the domains. CD4 T cells expressing the Foxp3 mutant with deletion of …


Autoimmune Responses To Atherosclerotic Lipids: A Study In Murine Models Of Atherosclerosis And Obesity, Hanjing Wu Sep 2011

Autoimmune Responses To Atherosclerotic Lipids: A Study In Murine Models Of Atherosclerosis And Obesity, Hanjing Wu

Dissertations and Theses (Open Access)

Atherosclerosis is a chronic, complex arterial disease characterized by intimal lipid accumulation and inflammation. A unique lipid-binding molecule, namely cluster of differentiation 1d (CD1d), may impact atherosclerosis. Structurally, CD1d acts as a nonpolymorphic cell-surface receptor, resembling the major histocompatibility complex-I (MHC-I). While MHC-I restricts peptide antigen presentation to T cells, CD1d presents lipid antigens to T cells named CD1d-restrictedd T cells. Although increased expression of CD1d has been found in human plaques, the exact nature of CD1d-recognized lipids in atherosclerosis remains to be determined. Three groups of lipids may undergo oxidation in atherosclerosis producing atherogenic lipids: phospholipids, fatty acids, and …


Tca Cycle Inactivation In Staphylococcus Aureus Alters Nitric Oxide Production In Raw 264.7 Cells, Chandirasegaran Massilamany, Arunakumar Gangaplara, Donald J. Gardner, James M. Musser, David J. Steffen, Greg A. Somerville, Jay Reddy Jan 2011

Tca Cycle Inactivation In Staphylococcus Aureus Alters Nitric Oxide Production In Raw 264.7 Cells, Chandirasegaran Massilamany, Arunakumar Gangaplara, Donald J. Gardner, James M. Musser, David J. Steffen, Greg A. Somerville, Jay Reddy

Jay Reddy Publications

Inactivation of the Staphylococcus aureus tricarboxylic acid (TCA) cycle delays the resolution of cutaneous ulcers in a mouse soft tissue infection model. In this study, it was observed that cutaneous lesions in mice infected with wild-type or isogenic aconitase mutant S. aureus strains contained comparable inflammatory infiltrates, suggesting the delayed resolution was independent of the recruitment of immune cells. These observations led us to hypothesize that staphylococcal metabolism can modulate the host immune response. Using an in vitro model system involving RAW 264.7 cells, the authors observed that cells cultured with S. aureus aconitase mutant strains produced significantly lower amounts …


Mir-27b*, An Oxidative Stress-Responsive Microrna Modulates Nuclear Factor-Kb Pathway In Raw 264.7 Cells, Sivasubramani Thulasingam, Chandirasegaran Massilamany, Arunakumar Gangaplara, Hongjiu Dai, Shahlo Yarbaeva, Sakthivel Subramaniam, Jean-Jack Riethoven, James Eudy, Marjorie F. Lou, Jay Reddy Jan 2011

Mir-27b*, An Oxidative Stress-Responsive Microrna Modulates Nuclear Factor-Kb Pathway In Raw 264.7 Cells, Sivasubramani Thulasingam, Chandirasegaran Massilamany, Arunakumar Gangaplara, Hongjiu Dai, Shahlo Yarbaeva, Sakthivel Subramaniam, Jean-Jack Riethoven, James Eudy, Marjorie F. Lou, Jay Reddy

Jay Reddy Publications

Reactive oxygen species (ROS) produced in macrophages is critical for microbial killing, but they also take part in inflammation and antigen presentation functions. MicroRNAs (miRNAs) are endogenous regulators of gene expression, and they can control immune responses. To dissect the complex nature of ROS-mediated effects in macrophages, we sought to characterize miRNAs that are responsive to oxidative stress-induced with hydrogen peroxide (H2O2) in the mouse macrophage cell line, RAW 264.7. We have identified a set of unique miRNAs that are differentially expressed in response to H2O2. These include miR-27a*, miR-27b*, miR-29b*, miR-24-2*, …


Identification Of A Second Mimicry Epitope From Acanthamoeba Castellanii That Induces Cns Autoimmunity By Generating Cross-Reactive T Cells For Mbp 89–101 In Sjl Mice, Chandirasegaran Massilamany, Oluwatoyin A. Asojo, Arunakumar Gangaplara, David J. Steffen, Jay Reddy Jan 2011

Identification Of A Second Mimicry Epitope From Acanthamoeba Castellanii That Induces Cns Autoimmunity By Generating Cross-Reactive T Cells For Mbp 89–101 In Sjl Mice, Chandirasegaran Massilamany, Oluwatoyin A. Asojo, Arunakumar Gangaplara, David J. Steffen, Jay Reddy

Jay Reddy Publications

We had previously reported that Acanthamoeba castellanii (ACA) contains a mimicry epitope for proteolipid protein 139–151 capable of inducing central nervous system (CNS) autoimmunity in SJL/J mice. We now present evidence that ACA also contains a mimicry epitope for myelin basic protein (MBP) 89–101, a derivative from amoebic nicotinamide adenine dinucleotide dehydrogenase subunit 2 (NAD). The epitope, NAD 108–120, contains a discontinuous stretch of six amino acids in the core region (VVFFKNIILIGFL) sharing 46% identity with MBP 89–101 (VHFFKNIVTPRTP; identical residues are underlined). SJL mice immunized with NAD 108–120 develop encephalomyelitis similar to the disease induced by the cognate peptide. …


Identification Of A Second Mimicry Epitope From Acanthamoeba Castellanii That Induces Cns Autoimmunity By Generating Cross-Reactive T Cells For Mbp 89–101 In Sjl Mice, Chandirasegaran Massilamany, Oluwatoyin A. Asojo, Arunakumar Gangaplara, David J. Steffen, Jay Reddy Jan 2011

Identification Of A Second Mimicry Epitope From Acanthamoeba Castellanii That Induces Cns Autoimmunity By Generating Cross-Reactive T Cells For Mbp 89–101 In Sjl Mice, Chandirasegaran Massilamany, Oluwatoyin A. Asojo, Arunakumar Gangaplara, David J. Steffen, Jay Reddy

Jay Reddy Publications

We had previously reported that Acanthamoeba castellanii (ACA) contains a mimicry epitope for proteolipid protein 139–151 capable of inducing central nervous system (CNS) autoimmunity in SJL/J mice. We now present evidence that ACA also contains a mimicry epitope for myelin basic protein (MBP) 89–101, a derivative from amoebic nicotinamide adenine dinucleotide dehydrogenase subunit 2 (NAD). The epitope, NAD 108–120, contains a discontinuous stretch of six amino acids in the core region (VVFFKNIILIGFL) sharing 46% identity with MBP 89–101 (VHFFKNIVTPRTP; identical residues are underlined). SJL mice immunized with NAD 108–120 develop encephalomyelitis similar to the disease induced by the cognate peptide. …


Radially Aligned, Electrospun Nanofibers As Dural Substitutes For Wound Closure And Tissue Regeneration Applications, Jingwei Xie, Matthew R. Macewan, Wilson Z. Ray, Wenying Liu, Daku Y. Siewe, Younan Xia Aug 2010

Radially Aligned, Electrospun Nanofibers As Dural Substitutes For Wound Closure And Tissue Regeneration Applications, Jingwei Xie, Matthew R. Macewan, Wilson Z. Ray, Wenying Liu, Daku Y. Siewe, Younan Xia

MIIR Faculty Research

This paper reports the fabrication of scaffolds consisting of radially aligned poly(ε-caprolactone) nanofibers by utilizing a collector composed of a central point electrode and a peripheral ring electrode. This novel class of scaffolds was able to present nanoscale topographic cues to cultured cells, directing and enhancing their migration from the periphery to the center. We also established that such scaffolds could induce faster cellular migration and population than nonwoven mats consisting of random nanofibers. Dural fibroblast cells cultured on these two types of scaffolds were found to express type I collagen, the main extracellular matrix component in dural mater. The …


Capsaicin Displays Anti-Proliferative Activity Against Human Small Cell Lung Cancer In Cell Culture And Nude Mice Models Via The E2f Pathway, Kathleen C. Brown, Theodore R. Witte, W. Elaine Hardman, Haitao Luo, Yi C. Chen, A. Betts Carpenter, Jamie K. Lau, Piyali Dasgupta Apr 2010

Capsaicin Displays Anti-Proliferative Activity Against Human Small Cell Lung Cancer In Cell Culture And Nude Mice Models Via The E2f Pathway, Kathleen C. Brown, Theodore R. Witte, W. Elaine Hardman, Haitao Luo, Yi C. Chen, A. Betts Carpenter, Jamie K. Lau, Piyali Dasgupta

Biochemistry and Microbiology

Background: Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays antiproliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo.

Methodology/Principal Findings: BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin potently …


Rbc And Wbc Fatty Acid Composition Following Consumption Of An Omega 3 Supplement: Lessons For Future Clinical Trials, Theodore R. Witte, Alexander J. Salazar, Oscar F. Ballester, W. Elaine Hardman Mar 2010

Rbc And Wbc Fatty Acid Composition Following Consumption Of An Omega 3 Supplement: Lessons For Future Clinical Trials, Theodore R. Witte, Alexander J. Salazar, Oscar F. Ballester, W. Elaine Hardman

Biochemistry and Microbiology

Background: Results from increasing numbers of in vitro and in vivo studies have demonstrated that omega 3 fatty acids incorporated in cell culture media or in the diet of the animals can suppress the growth of cancers. When human clinical trials are initiated to determine the ability of omega 3 fatty acids to alter growth or response to chemotherapeutic interventions of cancers, it will be essential to determine the omega 3 intake of individuals in the trial to determine compliance with consumption of the supplement and to correlate with endpoints of efficacy. We wondered if the fatty acid composition of …


An Epitope From Acanthamoeba Castellanii That Cross-React With Proteolipid Protein 139-151-Reactive T Cells Induces Autoimmune Encephalomyelitis In Sjl Mice, Chandirasegaran Massilamany, David Steffan, Jay Reddy Jan 2010

An Epitope From Acanthamoeba Castellanii That Cross-React With Proteolipid Protein 139-151-Reactive T Cells Induces Autoimmune Encephalomyelitis In Sjl Mice, Chandirasegaran Massilamany, David Steffan, Jay Reddy

Jay Reddy Publications

We report here that an epitope (aa, 83-95) derived from Acanthamoeba castellanii (ACA) induces clinical signs of experimental autoimmune encephalomyelitis (EAE) in SJL/J mice reminiscent of the disease induced with myelin proteolipid protein (PLP) 139-151. By using IAs/tetramers, we demonstrate that both ACA 83-95 and PLP 139-151 generate antigen-specific cross-reactive CD4 T cells and the T cells secrete identical patterns of cytokines and induce EAE with a similar severity. These results may provide insights into the pathogenesis of multiple sclerosis and ACA-induced granulomatous encephalitis.