Digital Commons Network^™

The Pax Gene Eyegone Facilitates Repression Of Eye Development In Tribolium, Nazanin Zarinkamar, Xiaoyun Yang, Riyue Bao, Frank Friedrich, Rolf Beutel, Markus Friedrich

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The Pax transcription factor gene eyegone (eyg) participates in many developmental processes in Drosophila, including the Notch signaling activated postembryonic growth of the eye primordium, global development of the adult head and the development of the antenna. In contrast to other Pax genes, the functional conservation of eyg in species other than Drosophila has not yet been explored.

Results

We investigated the role of eyg during the postembryonic development of the red flour beetle Tribolium castaneum. Our results indicate conserved roles in antennal but not in eye development. Besides segmentation defects in the antenna, Tribolium eyg knockdown animals …

Combinatorial Effect Of Non-Steroidal Anti-Inflammatory Drugs And Nf-Κb Inhibitors In Ovarian Cancer Therapy, Luiz F. Zerbini, Rodrigo E. Tamura, Ricardo G. Correa, Akos Czibere, Jason Coideiro, Manoj Bhasin, Fernando M. Simabuco, Yihong Wang, Xuesong Gu, Linglin Li, Devanand Sarkar, Jin-Rong Zhou, Paul B. Fisher, Towia A. Libermann

Human and Molecular Genetics Publications

Several epidemiological studies have correlated the use of non-steroidal anti-inflammatory drugs (NSAID) with reduced risk of ovarian cancer, the most lethal gynecological cancer, diagnosed usually in late stages of the disease. We have previously established that the pro-apoptotic cytokine melanoma differentiation associated gene-7/Interleukin-24 (mda-7/IL-24) is a crucial mediator of NSAID-induced apoptosis in prostate, breast, renal and stomach cancer cells. In this report we evaluated various structurally different NSAIDs for their efficacies to induce apoptosis and mda-7/IL-24 expression in ovarian cancer cells. While several NSAIDs induced apoptosis, Sulindac Sulfide and Diclofenac most potently induced apoptosis and reduced tumor …

Pitx2 Is Overexpressed In Follicular Cell-Derived Thyroid Cancer And Promotes Thyroid Cancer Proliferation By Regulating Cell Cycle, Yue Huang

Theses, Dissertations and Capstones

Thyroid cancer is the most prevailing malignancy of the endocrine system. Its incidence is rapidly rising at the second fastest rate of all malignancies in the United States, making it a significant health problem. Although the majority of thyroid cancer is slowly-growing and well-differentiated, available treatment options are very limited, and most of them require complete removal of the thyroid gland and surrounding tissues. Patients who have undergone thyroid removal have to take life-long hormone replacement therapy, which is very inconvenient and costly. Therefore, there is an urgent need to develop new treatments for this disease. As a prerequisite for …

Effect Of Aging On Cellular Mechanotransduction, Miaozong Wu, Jacqueline Fannin, Kevin M. Rice, Bin Wang, Eric R. Blough

MIIR Faculty Research

Aging is becoming a critical heath care issue and a burgeoning economic burden on society. Mechanotransduction is the ability of the cell to sense, process, and respond to mechanical stimuli and is an important regulator of physiologic function that has been found to play a role in regulating gene expression, protein synthesis, cell differentiation, tissue growth, and most recently, the pathophysiology of disease. Here we will review some of the recent findings of this field and attempt, where possible, to present changes in mechanotransduction that are associated with the aging process in several selected physiological systems, including musculoskeletal, cardiovascular, neuronal, …

Fusion, 2011, George Washington University, William H. Beaumont Medical Research Honor Society

Fusion

No abstract provided.

From Good Intentions To Proven Interventions: Effectiveness Of Actions To Reduce The Health Impacts Of Air Pollution, Luisa V. Giles, Prabjit Barn, Nino Kuenzli, Isabelle Romieu, Murray A. Mittleman, Stephan Van Eeden, Ryan Allen, Chris Carlsten, Dave Stieb, Curtis W. Noonan, Audrey Smargiassi, Joel D. Kaufman, Shakoor Hajat, Tom Kosatsky, Michael Brauer

Biomedical and Pharmaceutical Sciences Faculty Publications

BACKGROUND: Associations between air pollution and a multitude of health effects are now well established. Given ubiquitous exposure to some level of air pollution, the attributable health burden can be high, particularly for susceptible populations. OBJECTIVES: An international multidisciplinary workshop was convened to discuss evidence of the effectiveness of actions to reduce health impacts of air pollution at both the community and individual level. The overall aim was to summarize current knowledge regarding air pollution exposure and health impacts leading to public health recommendations. DISCUSSION: During the workshop, experts reviewed the biological mechanisms of action of air pollution in the …

Age-Associated Alterations In The F344xbn Rat Heart And The Efficacy Of Chronic Acetaminophen Ingestion As A Therapeutic Approach, Sunil K. Kakarla

Theses, Dissertations and Capstones

Despite advances in therapeutic and diagnostic strategies cardiovascular disease still remains the leading cause of death in older people. Recent studies suggest that age- related elevations in oxidative stress are associated with increases in cardiac apoptosis and compensatory hypertrophy of the remaining cardiomyocytes. Acetaminophen has been shown to exhibit cardioprotective effects following ischemia-reperfusion injury by acting as an antioxidant. Here, we investigate the molecular mechanisms underlying aging associated cardiac remodeling in male F344XBN rats and examine the efficacy of chronic acetaminophen ingestion as a therapeutic approach.

Aging in male F344XBN rats is characterized by a significant increase in heart size, …

Identification Of Genes Involved In Hematopoietic Stem Cell Differentiation And Leukemia Differentiation And Leukemia, Jasjeet Bhullar

Theses, Dissertations and Capstones

Hematopoiesis is maintained by a proper balance between self renewal and multipotent differentiation of the hematopoietic stem cells (HSC). Acute myelogenous leukemia (AML) is characterized by the blockage in the differentiation of HSC, while self renewal and proliferation is preserved. It is important to understand the mechanisms involved in the inhibition of hematopoietic differentiation and maintenance of the HSC state in order to develop better therapies for AML. In these studies I have explored the role of Hsp90, omega-3 fatty acids and YB-1 in hematopoietic differentiation. EML, a hematopoietic precursor cell line, was used as a model for the hematopoietic …

A Kenyan Perspective On The Use Of Animals In Science Education And Scientific Research In Africa And Prospects For Improvement, Charles Kimwele, Duncan Matheka, Hope Ferdowsian

Experimentation Collection

Introduction: Animal experimentation is common in Africa, a region that accords little priority on animal protection in comparison to economic and social development. The current study aimed at investigating the prevalence of animal experimentation in Kenya, and to review shortfalls in policy, legislation, implementation and enforcement that result in inadequate animal care in Kenya and other African nations. Methods: Data was collected using questionnaires, administered at 39 highly ranked academic and research institutions aiming to identify those that used animals, their sources of animals, and application of the three Rs. Perceived challenges to the use of non-animal alternatives and common …

Muscle Plasticity And Intramuscular Signaling In The Insulin-Resistant Obese Zucker Rat, Anjaiah Katta

Theses, Dissertations and Capstones

The ability to increase skeletal muscle mass may have important implications for the treatment of insulin resistance (IR) and diabetes [1-3]. Recent data suggest that IR muscle may adapt differently than normal muscle; however, molecular mechanism(s) responsible for this finding are not well understood [4]. Herein, we investigate the molecular mechanisms underlying the skeletal muscle remodeling in the IR Obese Zucker (OZ) rat.

The OZ rat is characterized by skeletal muscle insulin resistance, hyperglycemia, and hyperlipidemia. Compared to LZ rats, our data demonstrate that soleus muscle hypertrophy was significantly attenuated in the OZ rats after 3-weeks of muscle overload and …

Dysglycemia Induces Abnormal Circadian Blood Pressure Variability, Sivarajan Kumarasamy, Kathirvel Gopalakrishnan, Dong Hyun Kim, Nader G. Abraham, William D. Johnson, Bina Joe, Alok K. Gupta

Biochemistry and Microbiology

Background: Prediabetes (PreDM) in asymptomatic adults is associated with abnormal circadian blood pressure variability (abnormal CBPV).

Hypothesis: Systemic inflammation and glycemia influence circadian blood pressure variability.

Methods: Dahl salt-sensitive (S) rats (n = 19) after weaning were fed either an American (AD) or a standard (SD) diet. The AD (high-glycemic-index, high-fat) simulated customary human diet, provided daily overabundant calories which over time lead to body weight gain. The SD (low-glycemic-index, low-fat) mirrored desirable balanced human diet for maintaining body weight. Body weight and serum concentrations for fasting glucose (FG), adipokines (leptin and adiponectin), and proinflammatory cytokines [monocyte chemoattractant protein-1 (MCP-1) …

Role Of Leptin And Its Receptors In The Pathogenesis Of Thyroid Cancer, Shahabuddin, Azhar Hussain, Abdul K Siraj, Omar S Khan, Prashant P Bavi, Khawla S Al-Kuraya

Centre for Regenerative Medicine & Stem Cell Research

Leptin is a multifunctional adipose-derived cytokines that play a critical role in bodyweight homeostasis and energy balance. Recently, leptin and leptin receptor dysreulation have been reported in variety of malignant cells including thyroid. Leptin modulates growth and proliferation of cancer cells via activation of various growth and survival signaling pathways including JAK/STAT, PI3-kinase/AKT and/or Map kinases. In this review, current understanding of leptin's role in the pathogenesis of thyroid cancer has been described.

Resveratrol Suppresses Constitutive Activation Of Akt Via Generation Of Ros And Induces Apoptosis In Diffuse Large B Cell Lymphoma Cell Lines, Azhar Hussain, Shahabuddin, Rong Bu, Omar S. Khan, Saeeda O. Ahmed, Maqbool Ahmed, Khawla S. Al-Kuraya

Centre for Regenerative Medicine & Stem Cell Research

Background: We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL). In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4′, 5-trihydroxystilbene), a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL) cells in causing inhibition of cell viability and inducing apoptosis.
Methodology/Principal Findings: We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species …

The Pulmonologist's Role In Caring For Pregnant Women With Regard To The Reproductive Risks Of Diagnostic Radiological Studies Or Radiation Therapy, Robert L. Brent Dr.

The Selected Works of Robert Brent

None

Does Treatment Of Premature Labor With Terbutaline Increase The Risk Of Autism Spectrum Disorders?, Robert L. Brent Dr.

The Selected Works of Robert Brent

none

The Pulmonologist's Role In Caring For Pregnant Women With Regard To The Reproductive Risks Of Diagnostic Radiological Studies Or Radiation Therapy, Robert L. Brent Dr.

The Selected Works of Robert Brent

No abstract

The Role Of The Pediatrican In The Effort To Prevent Congenital Malformations, Robert L. Brent Dr.

The Selected Works of Robert Brent

No

Evaluation Of Reproductive And Developmental Risks Of Caffeine, Robert L. Brent Dr.

The Selected Works of Robert Brent

No abstract provided.

Targeted Decorin Gene Therapy Delivered With Adeno-Associated Virus Effectively Retards Corneal Neovascularization In Vivo, Rajiv R. Mohan, Jonathan C. K. Tovey, Ajay Sharma, Gregory S. Schultz, John W. Cowden, Ashish Tandon

Pharmacy Faculty Articles and Research

Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5) impedes corneal neovascularization (CNV) in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 μl; 5x10^12 vg/ml) application onto the stroma for two minutes after removing corneal epithelium. The levels of CNV were examined with stereomicroscopy, H&E staining, lectin, collagen type IV, CD31 immunocytochemistry and …

Characterization Of Species C Human Adenovirus Serotype 6 (Ad6), Eric A. Weaver, Reeti Khare, Mathew L. Hillestad, Donna Palmer, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Adenovirus serotype (Ad5) is the most studied Ad. Ad1, 2, and 6 are also members of species C Ad and are presumed to have biologies similar to Ad5. In this work, we have compared the ability of Ad1, 2, 5, and 6 to infect liver and muscle after intravenous and intramuscular injection. We found that Ad6 was surprisingly the most potent at liver gene delivery and that Ad1 and Ad2 were markedly weaker than Ad5 and 6. To understand these differences, we sequenced the Ad6 genome. This revealed that the Ad6 fiber protein is surprisingly three shaft repeats shorter than …

Generation Of A Kupffer Cell-Evading Adenovirus For Systemic And Liver-Directed Gene Transfer, Reeti Khare, Shannon M. May, Francesco Vetrini, Eric A. Weaver, Donna Palmer, Amanda Rosewell, Nathan Grove, Philip Ng, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

As much as 90% of an intravenously (i.v.) injected dose of adenovirus serotype 5 (Ad5) is absorbed and destroyed by liver Kupffer cells. Viruses that escape these cells can then transduce hepatocytes after binding factor X (FX). Given that interactions with FX and Kupffer cells are thought to occur on the Ad5 hexon protein, we replaced its exposed hypervariable regions (HVR) with those from Ad6. When tested in vivo in BALB/c mice and in hamsters, the Ad5/6 chimera mediated >10 times higher transduction in the liver. This effect was not due to changes in FX binding. Rather, Ad5/6 appeared to …

The Evolution Of Host Specialization In The Vertebrate Gut Symbiont Lactobacillus Reuteri, Steven A. Frese, Andrew K. Benson, Gerald W. Tannock, Diane M. Loach, Jaehyoung Kim, Min Zhang, Phaik Lyn Oh, Nicholas C. K. Heng, Prabhu B. Patil, Nathalie Juge, Donald A. Mackenzie, Bruce M. Pearson, Alla Lapidus, Eileen Dalin, Hope Tice, Eugene Goltsman, Miriam Land, Loren Hauser, Natalia Ivanova, Nikos C. Kyrpides, Jens Walter

Jens Walter Publications

Recent research has provided mechanistic insight into the important contributions of the gut microbiota to vertebrate biology, but questions remain about the evolutionary processes that have shaped this symbiosis. In the present study, we showed in experiments with gnotobiotic mice that the evolution of Lactobacillus reuteri with rodents resulted in the emergence of host specialization. To identify genomic events marking adaptations to the murine host, we compared the genome of the rodent isolate L. reuteri 100-23 with that of the human isolate L. reuteri F275, and we identified hundreds of genes that were specific to each strain. In …

The Mechanosensory Role Of Primary Cilia In Vascular Hypertension, Surya M. Nauli, Xingjian Jin, Beerend P. Hierck

Pharmacy Faculty Articles and Research

Local regulation of vascular tone plays an important role in cardiovascular control of blood pressure. Aside from chemical or hormonal regulations, this local homeostasis is highly regulated by fluid-shear stress. It was previously unclear how vascular endothelial cells were able to sense fluid-shear stress. The cellular functions of mechanosensory cilia within vascular system have emerged recently. In particular, hypertension is insidious and remains a continuous problem that evolves during the course of polycystic kidney disease (PKD). The basic and clinical perspectives on primary cilia are discussed with regard to the pathogenesis of hypertension in PKD.

Thiazolyl N-Benzyl-Substituted Acetamide Derivatives: Synthesis, Src Kinase Inhibitory And Anticancer Activities, Asal Fallah-Tafti, Alireza Foroumadi, Rakesh Tiwari, Amir Nasrolahi Shirazi, David G. Hangauer, Yahao Bu, Tahmineh Akbarzadeh, Keykavous Parang, Abbas Shafiee

Pharmacy Faculty Articles and Research

KX2-391 (KX-01/Kinex Pharmaceuticals), N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetamide, is a highly selective Src substrate binding site inhibitor. To understand better the role of pyridine ring and N-benzylsubstitution in KX2-391 and establish the structure-activity relationship, a number of N-benzyl substituted (2-morpholinoethoxy)phenyl)thiazol-4-yl)acetamide derivatives containing thiazole instead of pyridine were synthesized and evaluated for Src kinase inhibitory activities. The unsubstituted N-benzyl derivative (8a) showed the inhibition of c-Src kinase with GI50 values of 1.34 μM and 2.30 M in NIH3T3/c-Src527F and SYF/c-Src527F cells, respectively. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), breast carcinoma (BT-20), and leukemia (CCRF-CEM) cells. …

Polyethylenimine-Conjugated Gold Nanoparticles: Gene Transfer Potential And Low Toxicity In The Cornea, Ajay Sharma, Ashish Tandon, Jonathan C. K. Tovey, Rangan Gupta, J. David Robertson, Jennifer A. Fortune, Alexander M. Klibanov, John W. Cowden, Frank G. Rieger, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

This study examined the gene transfer efficiency and toxicity of 2-kDa polyethylenimine conjugated to gold nanoparticles (PEI2-GNP) in the human cornea in vitro and rabbit cornea in vivo. PEI2-GNP with nitrogen-to-phosphorus (N/P) ratios of up to 180 exhibited significant transgene delivery in the human cornea without altering the viability or phenotype of these cells. Similarly, PEI2-GNP applied to corneal tissues collected after 12 h, 72 h, or 7 days exhibited appreciable gold uptake throughout the rabbit stroma with gradual clearance of GNP over time. Transmission electron microscopy detected GNP in the keratocytes and the extracellular matrix of the rabbit corneas. …

Roles Of The 15-Kda Selenoprotein (Sep15) In Redox Homeostasis And Cataract Development Revealed By The Analysis Of Sep 15 Knockout Mice, Marina V. Kasaikina, Dmitri E. Fomenko, Vyacheslav M. Labunskyy, Salil A. Lachke, Wenya Qiu, Juliet A. Moncaster, Jie Zhang, Mark W. Wojnarowicz, Sathish Kumar Natarajan, Mikalai I. Malinouski, Ulrich Schweizer, Petra A. Tsuji, Bradley A. Carlson, Richard L. Maas, Marjorie F. Lou, Lee E. Goldstein, Dolph L. Hatfield, Vadim N. Gladyshev

School of Veterinary and Biomedical Sciences: Faculty Publications

The 15-kDa selenoprotein (Sep15) is a thioredoxin-like, endoplasmic reticulum-resident protein involved in the quality control of glycoprotein folding through its interaction with UDP-glucose:glycoprotein glucosyltransferase. Expression of Sep15 is regulated by dietary selenium and the unfolded protein response, but its specific function is not known. In this study, we developed and characterized Sep15 KO mice by targeted removal of exon 2 of the Sep15 gene coding for the cysteinerich UDP-glucose:glycoprotein glucosyltransferase-binding domain. These KO mice synthesized a mutant mRNA, but the shortened protein product could be detected neither in tissues nor in Sep15 KO embryonic fibroblasts. Sep15 KO mice were viable …

Analysis Of Gaba And Glutamate In The Mouse Dorsal Striatum, Stella Wisidagamage

Wayne State University Theses

ABSTRACT

ANALYSIS OF GABA AND GLUTAMATE IN MICE BRAIN

by

STELLA WISIDAGAMA

May 2011

Advisor: Dr. Tiffany Mathews

Major: Chemistry (Analytical)

Degree: Master of Science

GABA and glutamate are the predominant inhibitory and excitatory amino acid neurotransmitters in the central nervous system (CNS), respectively. However, their altered levels cause several neurological diseases including Parkinson's and Huntington's disease, schizophrenia, and epilepsy. It is important to measure their levels in the extra- and intracellular environments to better understand and develop improved therapeutics that will treat these neurological disorders. The principle aim of this study is to study the impacts of different endogenous …

Significant Inhibition Of Corneal Scarring In Vivo With Tissue-Selective, Targeted Aav5 Decorin Gene Therapy, Rajiv R. Mohan, Ashish Tandon, Ajay Sharma, John W. Cowden, Jonathan C. K. Tovey

Pharmacy Faculty Articles and Research

PURPOSE. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the stroma with adeno-associated virus serotype 5 (AAV5) inhibits corneal fibrosis in vivo without significant side effects.

METHODS. An in vivo rabbit model of corneal fibrosis was used. Targeted decorin gene therapy was delivered to the rabbit cornea by a single topical application of AAV5 (100 L; 6.5 1012 g/mL) onto the bare stroma for 2 minutes. The levels of corneal fibrosis were determined with stereomicroscopy, slit lamp biomicroscopy, -smooth muscle actin ( SMA), fibronectin, and F-actin immunocytochemistry, and/or immunoblotting. CD11b, F4/80 immunocytochemistry, and TUNEL assay …

Evaluation Of The Relationship Between Clinical Parameters Of Mineral And Bone Disease, Fibroblast Growth Factor 23, And Related Medication Use Among Hemodialysis Patients, Magdalene Marie Assimon

Legacy Theses & Dissertations (2009 - 2024)

Background

Hypolipidemic And Antioxidant Activity Of Aqueous Extract Of Monascus Purpureus Fermented Indian Rice In High Cholesterol Diet Fed Rats, Aiyalu Rajasekaran, Muthusamy Kalaivani

Turkish Journal of Medical Sciences

To evaluate hypolipidemic and anti-oxidant activities of Monascus purpureus fermented Indian variety of rice. Materials and methods: Indian rice variety IR-532-E-576 was fermented with Monascus purpureus MTCC 1090 (Monascaceae) and extracted with water by boiling. Experimentally induced hyperlipidemia was produced by feeding rats with 2% cholesterol enriched diet for 15 days. Afterwards hypercholesterolemic rats were orally administered with Monascus fermented Indian rice extract at the dose of 1.2 and 2.4 mg/kg bw along with high cholesterol diet for 30 successive days in order to evaluate their expected hypolipidemic activity. Plasma lipid parameters such as total cholesterol, triglycerides, LDL (low density …