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Engineering A Bcr-Abl–Activated Caspase For The Selective Elimination Of Leukemic Cells, Manabu Kurokawa, Takahiro Ito, Chih-Sheng Yang, Chen Zhao

Dartmouth Scholarship

Increased understanding of the precise molecular mechanisms involved in cell survival and cell death signaling pathways offers the promise of harnessing these molecules to eliminate cancer cells without damaging normal cells. Tyrosine kinase oncoproteins promote the genesis of leukemias through both increased cell proliferation and inhibition of apoptotic cell death. Although tyrosine kinase inhibitors, such as the BCR-ABL inhibitor imatinib, have demonstrated remarkable efficacy in the clinic, drug-resistant leukemias emerge in some patients because of either the acquisition of point mutations or amplification of the tyrosine kinase, resulting in a poor long-term prognosis. Here, we exploit the molecular mechanisms of …

Associations Between Cadmium Exposure And Neurocognitive Test Scores In A Cross-Sectional Study Of Us Adults, Timothy Ciesielski, David C. Bellinger, Joel Schwartz, Russ Hauser, Robert O. Wright

Dartmouth Scholarship

Background: Low-level environmental cadmium exposure and neurotoxicity has not been well studied in adults. Our goal was to evaluate associations between neurocognitive exam scores and a biomarker of cumulative cadmium exposure among adults in the Third National Health and Nutrition Examination Survey (NHANES III).

Methods: NHANES III is a nationally representative cross-sectional survey of the U.S. population conducted between 1988 and 1994. We analyzed data from a subset of participants, age 20–59, who participated in a computer-based neurocognitive evaluation. There were four outcome measures: the Simple Reaction Time Test (SRTT: visual motor speed), the Symbol Digit Substitution Test (SDST: attention/perception), …

Maintenance Of Mitochondrial Genomic Integrity In The Absence Of Manganese Superoxide Dismutase In Mouse Liver Hepatocytes., Anthony R. Cyr, Kyle E. Brown, Michael L. Mccormick, Mitchell C. Coleman, Adam J. Case, George S. Watts, Bernard W. Futscher, Douglas R. Spitz, Frederick E. Domann

Journal Articles: Cellular & Integrative Physiology

Manganese superoxide dismutase, encoded by the Sod2 gene, is a ubiquitously expressed mitochondrial antioxidant enzyme that is essential for mammalian life. Mice born with constitutive genetic knockout of Sod2 do not survive the neonatal stage, which renders the longitudinal study of the biochemical and metabolic effects of Sod2 loss difficult. However, multiple studies have demonstrated that tissue-specific knockout of Sod2 in murine liver yields no observable gross pathology or injury to the mouse. We hypothesized that Sod2 loss may have sub-pathologic effects on liver biology, including the acquisition of reactive oxygen species-mediated mitochondrial DNA mutations. To evaluate this, we established …

Cytoplasmic Localization Of Alteration/Deficiency In Activation 3 (Ada3) Predicts Poor Clinical Outcome In Breast Cancer Patients., Sameer Mirza, Emad A. Rakha, Alaa Alshareeda, Shakur Mohibi, Xiangshan Zhao, Bryan J. Katafiasz, Jun Wang, Channabasavaiah B. Gurumurthy, Aditya Bele, Ian O. Ellis, Andrew R. Green, Hamid Band, Vimla Band

Journal Articles: Genetics, Cell Biology & Anatomy

Transcriptional activation by estrogen receptor (ER) is a key step to breast oncogenesis. Given previous findings that ADA3 is a critical component of HAT complexes that regulate ER function and evidence that overexpression of other ER coactivators such as SRC-3 is associated with clinical outcomes in breast cancer, the current study was designed to assess the potential significance of ADA3 expression/localization in human breast cancer patients. In this study, we analyzed ADA3 expression in breast cancer tissue specimens and assessed the correlation of ADA3 staining with cancer progression and patient outcome. Tissue microarrays prepared from large series of breast cancer …

Pathology In Practice, Timothy L. Cushing, David J. Steffen, Gerald E. Duhamel

School of Veterinary and Biomedical Sciences: Faculty Publications

A 1.5-year-old second-parity Large Black X Tamworth cross sow from a well-managed 20-sow, unvaccinated, pasture-raised herd of pigs in upstate New York aborted a litter of 7 variably mummified near-term fetuses and stillborn piglets. This sow had no signs of ill health other than abortion; it was housed in a group with 4 other sows and a 2-year-old Gloucestershire Old Spot boar. One of the stillborn piglets from this litter was submitted to the New York State Animal Health Diagnostic Center for necropsy; no placental tissue was submitted with the piglet. A second sow from this group had aborted a …

The Healthy Incentive For Pre-Schools (Hip) Project: The Development, Validation, Evaluation And Implementation Of An Healthy Incentive Scheme In The Irish Full Day Care Pre-School Setting., Charlotte Johnston Molloy

Doctoral

While many children are now cared for outside the home, inadequate nutrition and physical activity practices in pre-schools have been reported. This study aimed to develop a validated nutrition and health related evaluation tool and an education information resource for pre-schools, and determine whether their use can promote improved food service and nutrition and physical activity practices in this setting. Following a pilot phase undertaken in Co. Wicklow (n 12), pre-schools providing a full day care service in the Midland Area of Ireland were invited to participate in the study (n, 100). Direct observation was used to collect data (food …

Potentials Of Plasma Ngal And Mic-1 As Biomarker(S) In The Diagnosis Of Lethal Pancreatic Cancer., Sukhwinder Kaur, Subhankar Chakraborty, Michael J. Baine, Kavita Mallya, Lynette M. Smith, Aaron Sasson, Randall Brand, Sushovan Guha, Maneesh Jain, Uwe Wittel, Shailender K. Singh, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer (PC) is lethal malignancy with very high mortality rate. Absence of sensitive and specific marker(s) is one of the major factors for poor prognosis of PC patients. In pilot studies using small set of patients, secreted acute phase proteins neutrophil gelatinase associated lipocalin (NGAL) and TGF-β family member macrophage inhibitory cytokine-1 (MIC-1) are proposed as most potential biomarkers specifically elevated in the blood of PC patients. However, their performance as diagnostic markers for PC, particularly in pre-treatment patients, remains unknown. In order to evaluate the diagnostic efficacy of NGAL and MIC-1, their levels were measured in plasma samples …

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

Control Of Candida Albicans Metabolism And Biofilm Formation By Pseudomonas Aeruginosa Phenazines, Diana K. Morales, Nora Grahl, Chinweike Okegbe, Lars E. P. Dietrich, Nicholas J. Jacobs, Deborah A. Hogan

Dartmouth Scholarship

Candidaalbicanshasdevelopmentalprogramsthatgoverntransitionsbetweenyeastandfilamentousmorphologies and between unattached and biofilm lifestyles. Here, we report that filamentation, intercellular adherence, and biofilm develop- ment were inhibited during interactions between Candida albicans and Pseudomonas aeruginosa through the action of P. aeruginosa-produced phenazines. While phenazines are toxic to C. albicans at millimolar concentrations, we found that lower concentrations of any of three different phenazines (pyocyanin, phenazine methosulfate, and phenazine-1-carboxylate) allowed growth but affected the development of C. albicans wrinkled colony biofilms and inhibited the fungal yeast-to-filament transition. Phenazines impaired C. albicans growth on nonfermentable carbon sources and led to increased production of fer- mentation products (ethanol, glycerol, and …

Nanotubes As Mitochondrial Uncouplers, Patrick G. Sullivan

Neuroscience Faculty Patents

A method of uncoupling mitochondria in a subject including administering nanotubes to the subject in a therapeutically effective amount, wherein the nanotubes are self-rectifying is provided. A method of decreasing reactive oxygen species and decreasing detrimental loading of Ca²⁺ into mitochondria is provided, including administering a pharmaceutically effective amount of nanotubes into the subject. A method of reducing weight, treating cancer, reducing the effects of traumatic brain injury, or reducing the effects of ageing, in a subject including administering a pharmaceutically effective amount of nanotubes into the subject is also provided.

What Is The Origin Of Pancreatic Adenocarcinoma?, Parviz M. Pour, K. K. Panday, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

No abstract provided.

Klf2 Is Required For Normal Mouse Cardiovascular Development, Aditi Raghunath Chiplunkar

Theses and Dissertations

Krüppel-like factor 2 (KLF2) is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV) canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5) in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2-/- embryos die earlier, by E11.5. E9.5 FVB/N KLF2-/- hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By …

Hd-Cnv: Hotspot Detector For Copy Number Variants., Jenna L Butler, Marjorie Elizabeth Osborne Locke, Kathleen A Hill, Mark Daley

Brain and Mind Institute Researchers' Publications

SUMMARY: Copy number variants (CNVs) are a major source of genetic variation. Comparing CNVs between samples is important in elucidating their potential effects in a wide variety of biological contexts. HD-CNV (hotspot detector for copy number variants) is a tool for downstream analysis of previously identified CNV regions from multiple samples, and it detects recurrent regions by finding cliques in an interval graph generated from the input. It creates a unique graphical representation of the data, as well as summary spreadsheets and UCSC (University of California, Santa Cruz) Genome Browser track files. The interval graph, when viewed with other software …

The Role Of Dax-1 In Regulating Pluripotency In Mouse Embryonic Stem Cells, Anthony Torres

Master's Theses

The orphan receptor Dax-1 is highly expressed in pluripotent embryonic stem (ES) cells and shows a correlative reduction in expression as these cells differentiate. While it is known that Dax-1 is expressed in pluripotent mouse ES cells, the precise function of Dax-1 in these cells is not as well understood. Recent studies employing RNA interference (RNAi) to specifically reduce the expression of the Dax-1 gene in mouse ES cells found that upon the knock down of Dax-1, ES cells differentiated. These findings indicate that Dax-1 functions in a novel role in the maintenance of a relatively undifferentiated state in ES …

Long-Term Upregulation Of Inflammation And Suppression Of Cell Proliferation In The Brain Of Adult Rats Exposed To Traumatic Brain Injury Using The Controlled Cortical Impact Model, Sandra A. Acosta, Naoki Tajiri, Kazutaka Shinozuka, Hiroto Ishikawa, Bethany Grimmig, David M. Diamond, Paul R. Sanberg, Paula C. Bickford, Yuji Kaneko, Cesario V. Borlongan

Psychology Faculty Publications

The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal …

Cyclooxygenase-2 Dependent Metabolism Of 20-Hete Increases Adiposity And Adipocyte Enlargement In Mesenchymal Stem Cell-Derived Adipocytes, Dong Hyun Kim, Nitin Puri, Komal Sodhi, John R. Falck, Nader G. Abraham, Joseph I. Shapiro M.D., Michal L. Schwartzman

Biochemistry and Microbiology

Abstract 20-Hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a product of the cytochrome P450 (CYP)-catalyzed [1] -hydroxylation of arachidonic acid, induces oxidative stress and, in clinical studies, is associated with increased body mass index (BMI) and the metabolic syndrome. This study was designed to examine the effects of exogenous 20- HETE on mesenchymal stem cell (MSC)-derived adipocytes.

The expression levels of CYP4A11 and CYP4F2 (major 20-HETE synthases in humans) in MSCs decreased during adipocyte differentiation; however, exogenous administration of 20-HETE (0.1–1 M) increased adipogenesis in a dose dependent manner in these cells ( P < 0.05). The inability of a 20-HETE analog to reproduce these effects suggested the involvement of a metabolic product of 20-HETE in mediating its pro-adipogenic effects. A cyclooxygenase (COX)-1 selective inhibitor enhanced, whereas a COX-2 selective or a dual COX-1/2 inhibitor attenuated adipogenesis induced by 20-HETE. The COX-derived metabolite of 20-HETE, 20-OH-PGE 2 , enhanced adipogenesis and lipid accumulation in MSCs. The pro-adipogenic effects of 20-HETE and 20-OH-PGE 2 resulted in the increased expression of the adipogenic regulators PPAR and -catenin in MSC-derived adipocytes. Taken together we show for the fi rst time that 20-HETE-derived COX-2-dependent 20-OH-PGE 2 enhances mature infl amed adipocyte hypertrophy in MSC undergoing adipogenic differentiation. — Kim, D. H., N. Puri, K. Sodhi, J. R. Falck, N. G. Abraham, J. Shapiro, and M. L. Schwartzman. Cyclooxygenase-2 dependent metabolism of 20-HETE increasesadiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes.

Roles Of Neuregulin1 In Neuromuscular Junction Development, Jiajing Wang

Wayne State University Dissertations

Neuromuscular junction (NMJ) development is a multistep process mediated by coordinated interactions between nerve terminals, target muscles, and peri-synaptic glial cells, and thus requires reciprocal signals derived from every cell type. Neuregulin1s (NRG1s) are a family of predominantly neuronal growth and differentiation factors that are important for many aspects of nervous system development. In this thesis, both the effects of NRG1 on NMJ development and reciprocal effects of neurotrophic factors on NRG1 expression were studied as a means to define the complex regulatory communication at the NMJ. Using the chicken embryo as a model, methods were developed to study the …

Rescuing Acetylcholinesterase From Nerve Agent Inhibition: Protein Dynamics Driven Drug Discovery, Aiyana M. Emigh, Brian Bennion

STAR Program Research Presentations

Severe morbidity and mortality consequences result from irreversible inhibition of human acetylcholinesterase by organophosphates (OPs). Oxime-based reactivators are currently the only available treatments but lack efficacy in the central nervous system (CNS) where the most damage occurs. Computational docking and molecular dynamics (MD) simulations reveal complex structural barriers that may reduce oxime efficacy. These results may guide future drug designs of more effective countermeasures.

Attachments And Neurobiology: Helping Children With Anxiety Disorders And Severe Mood Dysregulation, Gary A. Sibcy, John Kuhnley

Faculty Publications and Presentations

No abstract provided.

Ethanol Regulation Of Serum Glucocorticoid Kinase 1 Expression In Dba2/J Mouse Prefrontal Cortex, Blair N. Costin, Seth M. Dever, Michael F. Miles

Pharmacology and Toxicology Publications

Background

We previously identified a group of glucocorticoid-responsive genes, including Serum Glucocorticoid kinase 1 (Sgk1), regulated by acute ethanol in prefrontal cortex of DBA2/J mice. Acute ethanol activates the hypothalamic pituitary adrenal axis (HPA) causing release of glucocorticoids. Chronic ethanol dysregulates the HPA response in both humans and rodents, possibly contributing to important interactions between stress and alcoholism. Because Sgk1regulates ion channels and learning and memory, we hypothesized that Sgk1 contributes to HPA-dependent acute and adaptive neuronal responses to ethanol. These studies characterized acute and chronic ethanol regulation of Sgk1 mRNA and protein and their relationship with ethanol actions …

Cannabinoid Cb2 Receptors Regulate Central Sensitization And Pain Responses Associated With Osteoarthritis Of The Knee Joint, James J. Burston, David R. Sagar, Pin Shao, Mingfeng Bai, Emma King, Louis Brailsford, Jenna M. Turner, Gareth J. Hathway, Andrew J. Bennett, David A. Walsh, David A. Kendall, Aron H. Lichtman, Victoria Chapman

Pharmacology and Toxicology Publications

Osteoarthritis (OA) of the joint is a prevalent disease accompanied by chronic, debilitating pain. Recent clinical evidence has demonstrated that central sensitization contributes to OA pain. An improved understanding of how OA joint pathology impacts upon the central processing of pain is crucial for the identification of novel analgesic targets/new therapeutic strategies.

Inhibitory cannabinoid 2 (CB2) receptors attenuate peripheral immune cell function and modulate central neuro-immune responses in models of neurodegeneration. Systemic administration of the CB2 receptor agonist JWH133 attenuated OA-induced pain behaviour, and the changes in circulating pro- and anti-inflammatory cytokines exhibited in this model. Electrophysiological studies revealed that …

An Entropy-Based Automated Cell Nuclei Segmentation And Quantification: Application In Analysis Of Wound Healing Process, Varun Oswal, Ashwin Belle, Robert Diegelmann, Kayvan Najarian

Computer Science Publications

The segmentation and quantification of cell nuclei are two very significant tasks in the analysis of histological images. Accurate results of cell nuclei segmentation are often adapted to a variety of applications such as the detection of cancerous cell nuclei and the observation of overlapping cellular events occurring during wound healing process in the human body. In this paper, an automated entropy-based thresholding system for segmentation and quantification of cell nuclei from histologically stained images has been presented. The proposed translational computation system aims to integrate clinical insight and computational analysis by identifying and segmenting objects of interest within histological …

Genetic, Maternal And Placental Factors In The Association Between Birth Weight And Physical Fitness: A Longitudinal Twin Study, Robert N. H. Touwaslagar, Marji Gielen, Grans E. S. Tan, Antonius L. M. Mulder, Williem J. M. Gerver, Luc J. Zimmermann, Alfons J. H. M. Houben, Maurice P. Zeegers, Catherine Derom, Robert Vlietinck, Hermine Maes, Coen D. A. Stehouwer, Martine Thomis

Human and Molecular Genetics Publications

Background

Adult cardiorespiratory fitness and muscle strength are related to all-cause and cardiovascular mortality. Both are possibly related to birth weight, but it is unclear what the importance is of genetic, maternal and placental factors in these associations.

Design

Peak oxygen uptake and measures of strength, flexibility and balance were obtained yearly during adolescence (10–18 years) in 114 twin pairs in the Leuven Longitudinal Twin Study. Their birth weights had been collected prospectively within the East Flanders Prospective Twin Survey.

Results

We identified linear associations between birth weight and adolescent vertical jump (b = 1.96 cm per kg birth weight, …

Increased Frequency Of Micronuclei In Adults With A History Of Childhood Sexual Abuse: A Discordant Monozygotic Twin Study, Timothy P. York, Jenni Brumelle, Jane Juusola, Kenneth S. Kendler, Lindon J. Eaves, Ananda B. Amstadler, Steven H. Aggen, Kimberly H. Jones, Andrea Ferreira-Gonzalez, Colleen Jackson-Cook

Human and Molecular Genetics Publications

Background

Childhood sexual abuse (CSA) is a traumatic life event associated with an increased lifetime risk for psychopathology/morbidity. The long-term biological consequences of CSA-elicited stress on chromosomal stability in adults are unknown. The primary aim of this study was to determine if the rate of acquired chromosomal changes, measured using the cytokinesis-block micronucleus assay on stimulated peripheral blood lymphocytes, differs in adult female monozygotic twins discordant for CSA.

Methods

Monozygotic twin pairs discordant for CSA were identified from a larger population-based sample of female adult twins for whom the experience of CSA was assessed by self-report (51 individuals including a …

Identification Of Genes Potentially Regulated By Human Polynucleotide Phosphorylase (Hpnpaseold-35) Using Melanoma As A Model, Upneet K. Sokhi, Manny D. Bacolod, Santanu Dasgupta, Luni Emdad, Swadesh K. Das

Human and Molecular Genetics Publications

Human Polynucleotide Phosphorylase (hPNPaseold-35 or PNPT1) is an evolutionarily conserved 3′→5′ exoribonuclease implicated in the regulation of numerous physiological processes including maintenance of mitochondrial homeostasis, mtRNA import and aging-associated inflammation. From an RNase perspective, little is known about the RNA or miRNA species it targets for degradation or whose expression it regulates; except for c-myc and miR-221. To further elucidate the functional implications of hPNPaseold-35 in cellular physiology, we knocked-down and overexpressed hPNPaseold-35 in human melanoma cells and performed gene expression analyses to identify differentially expressed transcripts. Ingenuity Pathway Analysis indicated that knockdown of hPNPaseold-35 resulted in significant …

The Krüppel-Like Factor 2 And Krüppel-Like Factor 4 Genes Interact To Maintain Endothelial Integrity In Mouse Embryonic Vasculogenesis, Aditi R. Chiplunkar, Benjamin C. Curtis, Gabriel L. Eades, Megan S. Kane, Sean J. Fox, Jack L. Haar, Joyce A. Lloyd

Human and Molecular Genetics Publications

Background Krüppel-like Factor 2 (KLF2) plays an important role in vessel maturation during embryonic development. In adult mice, KLF2 regulates expression of the tight junction protein occludin, which may allow KLF2 to maintain vascular integrity. Adult tamoxifen-inducible Krüppel-like Factor 4 (KLF4) knockout mice have thickened arterial intima following vascular injury. The role of KLF4, and the possible overlapping functions of KLF2 and KLF4, in the developing vasculature are not well-studied.

Results Endothelial breaks are observed in a major vessel, the primary head vein (PHV), in KLF2-/-KLF4-/- embryos at E9.5. KLF2-/-KLF4-/- embryos die by E10.5, which is earlier than either single …

Krüppel-Like Factor 2 Is Required For Normal Mouse Cardiac Development, Aditi R. Chiplunkar, Tina K. Lung, Yousef Alhashem, Benjamin A. Koppenhaver, Fadi N. Salloum, Rakesh C. Kukreja, Jack L. Haar, Joyce A. Lloyd

Human and Molecular Genetics Publications

Krüppel-like factor 2 (KLF2) is expressed in endothelial cells in the developing heart, particularly in areas of high shear stress, such as the atrioventricular (AV) canal. KLF2 ablation leads to myocardial thinning, high output cardiac failure and death by mouse embryonic day 14.5 (E14.5) in a mixed genetic background. This work identifies an earlier and more fundamental role for KLF2 in mouse cardiac development in FVB/N mice. FVB/N KLF2−/− embryos die earlier, by E11.5. E9.5 FVB/N KLF2−/− hearts have multiple, disorganized cell layers lining the AV cushions, the primordia of the AV valves, rather than the normal single layer. By …

Targeted Apoptotic Effects Of Thymoquinone And Tamoxifen On Xiap Mediated Akt Regulation In Breast Cancer, Shashi Rajput, B. N. P. Kumar, Siddik Sarkar, Subhasis Das, Belal Azab, Prasanna K. Santhekadur, Swadesh K. Das, Luni Emdad, Devanand Sarkar, Paul B. Fisher, Mahitosh Mandal

Human and Molecular Genetics Publications

X-linked inhibitor of apoptosis protein (XIAP) is constitutively expressed endogenous inhibitor of apoptosis, exhibit its antiapoptotic effect by inactivating key caspases such as caspase-3, caspase-7 and caspase-9 and also play pivotal role in rendering cancer chemoresistance. Our studies showed the coadministration of TQ and TAM resulting in a substantial increase in breast cancer cell apoptosis and marked inhibition of cell growth both in vitro and in vivo. Anti-angiogenic and anti-invasive potential of TQ and TAM was assessed through in vitro studies. This novel combinatorial regimen leads to regulation of multiple cell signaling targets including inactivation of Akt and XIAP degradation. …

Role Of Iron In Ethanol Derived Hepatic Stress, Jesse A. Thornton

Theses, Dissertations and Capstones

Chronic alcohol abuse is the third leading cause of preventable death in the United States. Ethanol metabolism causes liver injury through alterations in hepatic metabolic state, redox status, and acetaldehyde adduct formations. Increased iron absorption is associated with chronic ethanol consumption and may play a role in ethanol induced oxidative stress. We tested the hypothesis that normal labile iron in the liver plays a role in ethanol related pathological stress, using C57/Bl6 mice pair-fed Lieber-DeCarli liquid ethanol diets for 11 and 22 weeks. Normal iron group mice received 55mg/kg iron as ferric citrate, whereas the low iron groups received 5mg/kg. …

Htlv Tax: A Fascinating Multifunctional Co-Regulator Of Viral And Cellular Pathways, Robert Currer, Rachel Van Duyne, Elizabeth Jaworski, Irene Guendel, Gavin Sampey, Ravi Das, Aarthi Narayanan, Fatah Kashanchi

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Human T-cell lymphotropic virus type 1 (HTLV-1) has been identified as the causative agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus infects between 15 and 20 million people worldwide of which approximately 2–5% develop ATL. The past 35 years of research have yielded significant insight into the pathogenesis of HTLV-1, including the molecular characterization of Tax, the viral transactivator, and oncoprotein. In spite of these efforts, the mechanisms of oncogenesis of this pleiotropic protein remain to be fully elucidated. In this review, we illustrate the multiple oncogenic roles of Tax by summarizing a recent …