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Metabolic Regulation Of Mtor Activation And Endoplasmic Reticulum Stress In The Heart, Shiraj Sen

Dissertations and Theses (Open Access)

When subjected to increased workload, the heart responds metabolically by increasing its reliance on glucose and structurally by increasing the size of myocytes. Whether changes in metabolism regulate the structural remodeling process is unknown. A likely candidate for a link between metabolism and growth in the heart is the mammalian target of rapamycin (mTOR), which couples energy and nutrient metabolism to cell growth. Recently, sustained mTOR activation has also been implicated in the development of endoplasmic reticulum (ER) stress. We explored possible mechanisms by which acute metabolic changes in the hemodynamically stressed heart regulate mTOR activation, ER stress and cardiac …

Regulation Of Protein Degradation In The Heart By Amp-Activated Protein Kinase, Kedryn K. Baskin

Dissertations and Theses (Open Access)

The degradation of proteins by the ubiquitin proteasome system is essential for cellular homeostasis in the heart. An important regulator of metabolic homeostasis is AMP-activated protein kinase (AMPK). During nutrient deprivation, AMPK is activated and intracellular proteolysis is enhanced through the ubiquitin proteasome system (UPS). Whether AMPK plays a role in protein degradation through the UPS in the heart is not known. Here I present data in support of the hypothesis that AMPK transcriptionally regulates key players in the UPS, which, under extreme conditions can be detrimental to the heart. The ubiquitin ligases MAFbx /Atrogin-1 and MuRF1, key regulators of …

Is Less Really More?: Determining The Efficacy And Advantages Of Low Dose Chemotherapy, Natalie Toews

Senior Honors Theses

Chemotherapy is the preferred treatment for patients with breast cancer nationwide; however, the dosage and duration of this treatment have come under recent scrutiny. The efficacy of high dose chemotherapy is many times inadequate, and the adverse physical effects resulting from this regimen have a negative holistic impact on the patients. Studies suggest that low dose chemotherapy, through antiangiogenesis, affects the spread of breast cancer carcinomas and may produce less harmful side effects in relation to the heart, brain, and eyes. Thus, oncological research proposes that a low dose regimen improves the patient’s quality of life and may be an …

Clinical Utility Of Folate-Containing Oral Contraceptives., Zohra S Lassi, Zulfiqar Ahmed Bhutta

Woman and Child Health

Folate is a generic term for a water-soluble B-complex vitamin which plays an important role in protein synthesis and metabolism and other processes related to cell multiplication and tissue growth. Pregnant and lactating women are at increased risk of folic acid deficiency because generally their dietary folate is insufficient to meet their physiological requirements and the metabolic demands of the growing fetus. The evidence pertaining to the reduction of the risk of neural tube defects (NTDs) due to folate is so compelling that supplementation with 400 mug of folic acid to all women trying to conceive until 12 weeks of …

Proceedings - Wright State University Boonshoft School Of Medicine Fourth Annual Medical Student Research Symposium: Celebrating Medical Student Scholarship, Office Of Research Affairs, Boonshoft School Of Medicine

Medical Student Research Symposium Proceedings

The student abstract booklet is a compilation of abstracts from students' oral and poster presentations at Wright State University's Fourth Annual Boonshoft School of Medicine Medical Student Research Symposium held on April 5, 2012.

Genetic Polymorphism In A Vegf-Independent Angiogenesis Gene Angpt1 And Overall Survival Of Colorectal Cancer Patients After Surgical Resection, Jingyao Dai, Shaogui Wan, Feng Zhou, Ronald E. Myers, Xu Guo, Bingshan Li, Xiaoying Fu, Juan P. Palazzo, Kefeng Dou, Hushan Yang, Jinliang Xing

Kimmel Cancer Center Faculty Papers

Background

The VEGF-independent angiogenic signaling plays an important role in the development of colorectal cancer (CRC). However, its implication in the clinical outcome of CRC has not been reported. This study aimed to investigate the association between genetic variations in several major VEGF-independent signaling pathway genes and the overall survival of CRC patients.

Methods

Seven single nucleotide polymorphisms (SNPs) in four important VEGF-independent angiogenic genes (ANGPT1, AMOT, DLL4 and ENG) were genotyped in a Chinese population with 408 CRC patients.

Results

One SNP, rs1954727 in ANGPT1, was significantly associated with CRC overall survival. Compared to …

Regulation Of Iron-Related Molecules In The Rat Hippocampus: Sex- And Age-Associated Differences, Srinivasarao Thulluri, Miaozong Wu, Eric R. Blough, Nandini D.P.K. Manne, Ashley B. Litchfield, Bin Wang

MIIR Faculty Research

Iron accumulation, especially that of free oxidized ferrous iron, has been shown to induce tissue oxidative damage and contribute to brain aging and the development of neurodegenerative disease. Here we examine whether sex and advanced age affect the expression of iron-related molecules that participate in regulating free iron levels (heme oxygenase I (HOI), iron-regulatory protein I (IRPI), and ferritin heavy chain (FTH)) and whether changes in the expression of these molecules are associated with differences in the expression of alpha-synuclein (ASN) which is thought to be a critical regulator in the pathogenesis of neurodegeneration. Using a well-established aging animal model, …

Single-Chain Vαvβ T Cell Receptors Function Without Mispairing With Endogenous Tcr Chains1, David H. Aggen, Adam S. Chervin, Thomas M. Schmitt, Boris Engels, Jennifer D. Stone, Sarah A. Richman, Kurt H. Piepenbrink, Brian M. Baker, Philip D. Greenberg, Hans Schreiber, David M. Kranz

Food for Health: Publications

Transduction of exogenous T cell receptor (TCR) genes into patients’ activated peripheral blood T cells is a potent strategy to generate large numbers of specific T cells for adoptive therapy of cancer and viral diseases. However, the remarkable clinical promise of this powerful approach is still being overshadowed by a serious potential consequence: mispairing of the exogenous TCR chains with endogenous TCR chains. These “mixed” heterodimers can generate new specificities that result in graft-versus-host reactions. Engineering TCR constant regions of the exogenous chains with a cysteine promotes proper pairing and reduces the mispairing, but, as we show here, does not …

Cosmetic Neurology: Enhancement Of The Mind And Attention Deficit Hyperactive Disorder Medication Abuse Among College Students, Mary M. Huff

Senior Honors Theses

Cosmetic neurology is becoming increasingly popular, and it is not just sleep deprived, over worked college students who are interested. People are beginning to seek off-label prescriptions for medications that are typically used to treat disorders such as attention deficit hyperactive disorder (ADHD) or narcolepsy, while researchers are trying to create drugs used solely for mind enhancement purposes. Along with these drugs come many legal and ethical quandaries relating to the regulation of current use as well as the what ifs of future possibilities. A survey was conducted among college students regarding the diagnosis of ADHD, the abuse of ADHD …

Antioxidant, Antimicrobial Properties And Phenolics Of Different Solvent Extracts From Bark, Leaves And Seeds Of Pongamia Pinnata (L.) Pierre, Zahid Iqbal Sajid, Farooq Anwar, Ghulam Shabir, Ghulam Rasul, Khalid M. Alkharfy, Anwarul Hassan Gilani

Department of Biological & Biomedical Sciences

This study appraises the antioxidant and antimicrobial attributes of various solvent extracts (absolute methanol, aqueous methanol, absolute ethanol, aqueous ethanol, absolute acetone, aqueous acetone, and deionized water) from bark, leaves and seeds of Pongamia pinnata (L.) Pierre. Maximum extraction yield of antioxidant components from bark (16.31%), leaves (11.42%) and seeds (21.51%) of P. pinnata was obtained using aqueous methanol (20:80). Of the extracts tested, the bark extract, obtained with aqueous methanol, exhibited greater levels of total phenolics [6.94 g GAE/100 g dry weight (DW)], total flavonoids (3.44 g CE/100 g DW), inhibition of linoleic acid peroxidation (69.23%) and DPPH radical …

Effects Of Restricted Fructose Access On Body Weight And Blood Pressure Circadian Rhythms, Danielle Senador, Swapnil Vijay Shewale, Maria Claudia Irigoyen, Khalid M. Elased, Mariana Morris

Pharmacology and Toxicology Faculty Publications

High-fructose diet is known to produce cardiovascular and metabolic pathologies. The objective was to determine whether the timing of high fructose (10% liquid solution) intake affect the metabolic and cardiovascular outcomes. Male C57BL mice with radiotelemetric probes were divided into four groups: (1) 24 h water (control); (2) 24 h fructose (F24); (3) 12 h fructose during the light phase (F12L); (4) 12 h fructose during the dark phase (F12D). All fructose groups had higher fluid intake. Body weight was increased in mice on restricted access with no difference in total caloric intake. Fasting glycemia was higher in groups with …

Conformational Melding Permits A Conserved Binding Geometry In Tcr Recognition Of Foreign And Self Molecular Mimics, Oleg Y. Borbulevych, Kurt H. Piepenbrink, Brian M. Baker

Food for Health: Publications

Molecular mimicry between foreign and self antigens is a mechanism of T cell receptor cross reactivity and is thought to contribute to the development of autoimmunity. The αβ TCR A6 recognizes the foreign antigen Tax from the virus HTLV-1 when presented by the class I MHC HLA-A2. In a possible link with the autoimmune disease HAM/TSP, A6 also recognizes a self peptide from the neuronal protein HuD in the context of HLA-A2. We found here that the complexes of the HuD and Tax epitopes with HLA-A2 are close but imperfect structural mimics, and that in contrast with other recent structures …

Effect Of Maternal Hypoxia On The Cerebral And Cardiac Tissue Remodeling, Wenni Tong

Loma Linda University Electronic Theses, Dissertations & Projects

Large epidemiological studies and animal studies have indicated a clear association of adverse intrauterine environment with an increased incidence of low birth weight, perinatal mortality, and cardiovascular disease in later adult life. In humans, one of the most common stresses in utero is hypoxia. The goal of this project is to test the hypothesis that fetal hypoxia causes reprogramming of MMPs and TIMPs expression patterns and activities leading to aberrant brain and heart development in the fetuses and neonates. In the first part of project, we tested the hypothesis that maternal hypoxia increases the activity of MMPs and decreases the …

Identifying And Reducing Potential Risks Of Contamination In Food Packaging, Jeffrey Daniel Stollenwerk

Graphic Communication

The purpose of this study was to identify the possible health hazards in food packaging and evaluate each component of food packaging for risks and potential improvements. There have been recent cases in which contaminants have been identified in various food packaging products that pose potential harm to consumers. National authorities, like the Food and Drug Administration and the European Food Standards Agency, regulate these contaminants and create regulations for industry standards.

Contaminants travel from food packaging to the food-surface through a process called migration. Migration varies depending on the usage of different substrates, inks, varnishes, and printing technologies. Each …

An Inside Job: Hacking Into Janus Kinase/Signal Transducer And Activator Of Transcription Signaling Cascades By The Intracellular Protozoan Toxoplasma Gondii, Eric Y. Denkers, David J. Bzik, Barbara A. Fox, Barbara A. Butcher

Dartmouth Scholarship

The intracellular protozoan Toxoplasma gondii is well known for its skill at invading and living within host cells. New discoveries are now also revealing the astounding ability of the parasite to inject effector proteins into the cytoplasm to seize control of the host cell. This review summarizes recent advances in our understanding of one such secretory protein called ROP16. This molecule is released from rhoptries into the host cell during invasion. The ROP16 molecule acts as a kinase, directly activating both signal transducer and activator of transcription 3 (STAT3) and STAT6 signaling pathways. In macrophages, an important and preferential target …

Phase I Evaluation Of Intravenous Ascorbic Acid In Combination With Gemcitabine And Erlotinib In Patients With Metastatic Pancreatic Cancer., Daniel A. Monti, Md, Edith Mitchell, Anthony J Bazzan, Susan Littman, George Zabrecky, Charles J Yeo, Madhaven V Pillai, Andrew B Newberg, Sandeep Deshmukh, Mark Levine

Department of Medical Oncology Faculty Papers

BACKGROUND: Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.

METHODS AND FINDINGS: 14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier). There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of …

Enteric Alpha Defensins In Norm And Pathology., Nikolai A Lisitsyn, Yulia A Bukurova, Inna G Nikitina, George S Krasnov, Yuri Sykulev, Sergey F Beresten

Kimmel Cancer Center Faculty Papers

ABSTRACT: Microbes living in the mammalian gut exist in constant contact with immunity system that prevents infection and maintains homeostasis. Enteric alpha defensins play an important role in regulation of bacterial colonization of the gut, as well as in activation of pro- and anti-inflammatory responses of the adaptive immune system cells in lamina propria. This review summarizes currently available data on functions of mammalian enteric alpha defensins in the immune defense and changes in their secretion in intestinal inflammatory diseases and cancer.

Otx But Not Mitf Transcription Factors Are Required For Zebrafish Retinal Pigment Epithelium Development, Brandon M. Lane, James A. Lister

Human and Molecular Genetics Publications

Otx and Mitf transcription factors have been implicated in the development of the retinal pigmented epithelium (RPE), but the relationship between these factors and their specific roles in the development of the RPE have not been fully defined. The role of the three Otx transcription factors (Otx1a, Otx1b, and Otx2) and two Mitf transcription factors (Mitfa and Mitfb) in the development of the zebrafish RPE was explored in these experiments. The loss of Otx activity through morpholino knockdown produced variable eye defects, ranging from delayed RPE pigmentation to severe coloboma, depending on the combination of Otx factors that were targeted. …

The Role Of Ptip In Breast Cancer, Lina Niu

Theses, Dissertations and Capstones

In the U.S., breast cancer comprises about 30% of all cancer cases (excluding skin cancer) in women. Such a high incidence makes breast cancer a significant health concern, but our understanding of the molecular and cellular mechanisms of this disease is still limited. Growing evidence suggests that the development of human breast cancer may involve epigenetics, which attributes changes in phenotype to mechanisms other than changes in the DNA sequence itself. Histones as the chief proteins of chromatin work on gene expression, and methylation of histone 3 lysine 4 (H3K4) results in transcriptional activation. Lately, Paired box (Pax) trans-activation domain-interacting …

Neglected Tropical Diseases As Hidden Causes Of Cardiovascular Disease, Yasmin Moolani, Gene Bukhman, Peter J. Hotez

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Do Photoperiodic Changes In Melatonin Secretion Detrimentally Affect The Female Reproductive Cycle?, Riki Szlafrok

The Science Journal of the Lander College of Arts and Sciences

Melatonin, better known as "the hormone of darkness," is secreted by the pineal gland during the night and helps us fall asleep. Because its internal regulation depends on light, melatonin is part of chronobiology, the study of biological mechanisms and their adaptations to lunar and solar related rhythms (Klein et al. 1991). Therefore, photoperiod changes greatly impact melatonin concentration, influencing changes in neuronal and hormonal mechanisms of the photo neuro-endocrine systems, namely reproduction. Research has shown that a disruption in the circadian rhythm of melatonin due to photoperiod changes detrimentally affects the rhythmic function of the female reproductive cycle. Research …

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 …

The Role Of Vascular Endothelial Growth Factor At The Blood-Brain Barrier In Diabetes, Aileen J. Marcelo

Theses, Dissertations and Capstones

Diabetes is a risk factor for stroke and vascular dementia. Clinical studies using gadolinium-magnetic resonance imaging techniques have shown diabetic patients exhibit a permeability increase at the blood-brain barrier (BBB) (Starr et al, 2003). The BBB, a vascular interface at the level of brain microvascular vessels, functions to provide nutrients and oxygen from the peripheral circulation, mediates waste efflux from the brain, and protects the brain from toxins. These functions are due to the presence of tight junction proteins. Animal studies have shown increased BBB permeability is due to a decrease in these proteins (Hawkins et al, 2007). Based on …

Consumption Of High Ω-3 Fatty Acid Diet Suppressed Prostate Tumorigenesis In C3(1) Tag Mice, Juliana A. Akinsete, Gabriela Ion, Theodore R. Witte, W. Elaine Hardman

Biochemistry and Microbiology

Prostate cancer incidence and mortality are high in the Western world and high ω-6/ω-3 PUFA in the Western diet may be a contributing factor. We investigated whether changing from a diet that approximates ω-6 fat content of the Western diet to a high ω-3 fat diet at adulthood might reduce prostate cancer risk. Female SV 129 mice that had consumed a high ω-6 diet containing corn oil for 2 weeks were bred with homozygous C3(1)Tag transgenic male mice. All male offspring were weaned to the corn oil diet (CO) until postpuberty when half of the male offspring were transferred to …

New Portable Tool To Screen Vestibular And Visual Function—National Institutes Of Health Toolbox Initiative, Rose Marie Rine, Dale Roberts, Bree A. Corbin, Roberta Mckean-Cowdin, Rohit Varma, Jennifer Beaumont, Jerry Slotkin, Michael C. Schubert

Physical Therapy Faculty Research

As part of the National Institutes of Health Toolbox initiative, we developed a low-cost, easy-to-administer, and time-efficient test of vestibular and visual function. A computerized test of dynamic visual acuity (cDVA) was used to measure the difference in visual acuity between head still and moving in yaw. Participants included 318 individuals, aged 3 to 85 years (301 without and 17 with vestibular pathology). Adults used Early Treatment of Diabetic Retinopathy Study (ETDRS) optotypes; children used ETDRS, Lea, and HOTV optotypes. Bithermal calorics, rotational chair, and light box testing were used to validate the cDVA. Analysis revealed that the cDVA test …

Erlin2 Promotes Breast Cancer Cell Survival By Modulating Endoplasmic Reticulum Stress Pathways, Guohui Wang, Gang Liu, Xiaogang Wang, Seema Sethi, Rouba Ali-Fehmi, Judith Abrams, Ze Zheng, Kezhong Zhang, Stephen Ethier, Zeng-Quan Yang

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Amplification of the 8p11-12 region has been found in approximately 15% of human breast cancer and is associated with poor prognosis. Previous genomic analysis has led us to identify the endoplasmic reticulum (ER) lipid raft-associated 2 (ERLIN2) gene as one of the candidate oncogenes within the 8p11-12 amplicon in human breast cancer, particularly in the luminal subtype. ERLIN2, an ER membrane protein, has recently been identified as a novel mediator of ER-associated degradation. Yet, the biological roles of ERLIN2 and molecular mechanisms by which ERLIN2 coordinates ER pathways in breast carcinogenesis remain unclear.

Methods

We established the MCF10A-ERLIN2 …

Evaluation Of Gut Modulatory And Bronchodilator Activities Of Amaranthus Spinosus Linn, Mueen Ahmad Chaudhary, Imran Imran, Samra Bashir, Hassan Mehmood, Najeeb-Ur Rehman, Anwarul-Hassan Gilani

Department of Biological & Biomedical Sciences

Background: The aqueous-methanolic extract of Amaranthus spinosus (A. spinosus Linn.,) whole plant, was studied for its laxative, spasmolytic and bronchodilator activities to validate some of its medicinal uses.
Methods: The crude extract of A. spinosus was studied in-vivo for bronchodilator and laxative activities and in-vitro using isolated tissue preparations which were mounted in tissue baths assembly containing physiological salt solutions, maintained at 37°C and aerated with carbogen, to assess the spasmolytic effect and to find out the possible underlying mechanisms.
Results: In the in-vivo experiments in mice, the administration of A. spinosus increased fecal output at doses of 100 …

The Effects Of Smooth Muscle Cells On Engineered Microvasculatures In Fibrin Hydrogels, Areck A. Ucuzian

Dissertations

Capillaries are comprised of two cell types: the endothelial cells (ECs) which line the lumen of the capillary, and the supporting pericytes which are closely apposed to the abluminal surface of the capillary wall (sometimes called mural cells). These pericytes are phenotypic derivations of mesenchymal organ stromal cells (from smooth muscle cells and fibroblasts in blood vessels, for example), are recruited and incorporate into the neocapillaries, and are known to mediate reciprocal interactions with ECs during angiogenesis. The overall purpose of this project is to determine how smooth muscle cells (SMCs) affect angiogenesis during microvascular development in fibrin hydrogels using …

Correlation Of Air Displacement Plethysmography With Alternative Body Fat Measurement Techniques In Men And Women, Brittany L. Reinert, Roberta L. Pohlman, Lynn K. Hartzler

Biological Sciences Faculty Publications

Obesity has reached epidemic proportions with serious health consequences. Techniques used to measure body fat (BF) yield variable BF estimates, and this variability may lead to underestimation or overestimation of BF and subsequent treatment options. The measurements that are most accurate (Dual-Energy X-ray Absorptiometry (DEXA) and Air Displacement Plethysmography (ADP)) are expensive and often unavailable. The purpose of this study is to find the commonly available BF measurement that is the most accurate and practical for individual body types in the general population and compare these measurements to ADP (BOD POD^®) as the standard. Field measurements include skinfolds …

Post Gastric Bypass Hypoglycemia: Four Cases Treated Successfully With Alphaglucosidase Inhibitor Therapy, Shavon S. Frankhouser Do, Aakif N. Ahmad Do, Gretchen A. Perilli Md, Benjamin J. Quintana Md, Marc A. Vengrove Do, Facp

Department of Medicine

No abstract provided.