Physiology Commons^™

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly …

Minimal Information For Studies Of Extracellular Vesicles 2018 (Misev2018): A Position Statement Of The International Society For Extracellular Vesicles And Update Of The Misev2014 Guidelines, Clotilde Théry, Kenneth W. Witwer, Elena Aikawa, Maria Jose Alcaraz, Johnathon D. Anderson, Ramaroson Andriantsitohaina, Anna Antoniou, Tanina Arab, Fabienne Archer, Georgia K. Atkin-Smith, D. Craig Ayre, Jean-Marie Bach, Daniel Bachurski, Hossein Baharvand, Leonora Balaj, Shawn Baldacchino, Natalie N. Bauer, Amy A. Baxter, Mary Bebawy, Carla Beckham, Apolonija Bedina Zavec, Adberrahim Benmoussa, Anna C. Berardi, Paolo Bergese, Ewa Bielska, Cherie Blenkiron, Sylwia Bobis-Wozowicz, Eric Boilard, Wilfred Boireau, Antonella Bongiovanni, Ivan Vechetti

Physiology Faculty Publications

The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines …

Emerging Roles Of The Membrane Potential: Action Beyond The Action Potential, Lina Abdul Kadir, Michael Stacey, Richard Barrett-Jolley

Bioelectrics Publications

Whilst the phenomenon of an electrical resting membrane potential (RMP) is a central tenet of biology, it is nearly always discussed as a phenomenon that facilitates the propagation of action potentials in excitable tissue, muscle, and nerve. However, as ion channel research shifts beyond these tissues, it became clear that the RMP is a feature of virtually all cells studied. The RMP is maintained by the cell's compliment of ion channels. Transcriptome sequencing is increasingly revealing that equally rich compliments of ion channels exist in both excitable and non-excitable tissue. In this review, we discuss a range of critical roles …

Modified Cantilever Arrays Improve Sensitivity And Reproducibility Of Nanomechanical Sensing In Living Cells, Samadhan B. Patil, Rajai M. Al-Jehani, Hashem Etayash, Valerian Turbe, Keren Jiang, Joe Bailey, Walid Al-Akkad, Rania Soudy, Kamaljit Kaur, Rachel A. Mckendry, Thomas Thundat, Joseph W. Ndieyira

Pharmacy Faculty Articles and Research

Mechanical signaling involved in molecular interactions lies at the heart of materials science and biological systems, but the mechanisms involved are poorly understood. Here we use nanomechanical sensors and intact human cells to provide unique insights into the signaling pathways of connectivity networks, which deliver the ability to probe cells to produce biologically relevant, quantifiable and reproducible signals. We quantify the mechanical signals from malignant cancer cells, with 10 cells per ml in 1000-fold excess of non-neoplastic human epithelial cells. Moreover, we demonstrate that a direct link between cells and molecules creates a continuous connectivity which acts like a percolating …

Effects Of Maternal Protein Restriction On The Pulmonary Surfactant System During The Early Life And Adulthood, Reza Khazaee

Electronic Thesis and Dissertation Repository

Fetal growth restriction (FGR) is defined by low birth weight and contributes to a variety of adult-onset diseases with different severities between males and females. However, the effects of FGR on the pulmonary surfactant are not fully elucidated. In this thesis, first, we investigated the FGR effects on the lung function and the surfactant system at the early postnatal life. It was hypothesized that FGR contributes to alterations of lung mechanics and the surfactant system during the neonatal period. Second, we assessed the FGR effects on the surfactant system in response to sepsis in adulthood. It was hypothesized that FGR …

Effect Of Larval Starvation On Lipid Content Of Drosophila Melanogaster Over 15 Days, Fabian Leija, Allen Gibbs

LSAMP Poster Presentations

Starvation-resistant Drosophila melanogaster, common fruit flies, deriving from 121 generations of starvation selection, have resulted in genetically, behaviorally, and physiologically different individuals compared to non-resistant counterparts. Starvation-resistant Drosophila are more obese, containing twice as much lipids as control flies.This is a result of starvation-resistant fly larva feeding for 5 days and then entering the pupa stage while non-resistant flies only feed for 4 days.

In this experiment, we hope to answer the question of whether the starvation-resistant flies are genetically predisposed to be substantially more obese than wild populations or if it is a result of this alternate behavior …

The Role Of Developmental Timing Regulators In Progenitor Proliferation And Cell Fate Specification During Mammalian Neurogenesis, Jennifer S. Romer-Seibert

Graduate School of Biomedical Sciences Theses and Dissertations

Developmental timing is a key aspect of tissue and organ formation in which distinct cell types are generated through a series of steps from common progenitors. These progenitors undergo specific changes in gene expression that signifies both a distinct progenitor type and developmental time point that thereby specifies a particular cell fate at that stage of development. The nervous system is an important setting for understanding developmental timing because different cell types are produced in a certain order and the switch from stem cells to progenitors requires precise timing and regulation. Notable examples of such regulatory molecules include the RNA-binding …

Insight Into Translational Activation In Yeast Mitochondria, Julia Lynn Jones

Graduate School of Biomedical Sciences Theses and Dissertations

Mitochondrial function depends on over a thousand proteins, of which the majority are nuclear DNA-encoded and approximately one percent are mitochondrial DNA-encoded. The mitochondrial DNA of Saccharomyces cerevisiae contains eight protein-encoding genes, seven of which are required for proper function of the respiratory complexes and one encodes a ribosomal protein. The bigenomic nature of the oxidative phosphorylation complexes requires coordinated expression and regulation from both the nuclear and the mitochondrial genomes. It is currently unclear how this regulatory network operates. However, it is thought that nuclear genome-encoded messengers localized to the mitochondria aid in this coordination.

A family of proteins …

Effect Of Morinda Citrifolia (Noni)-Enriched Diet On Hepatic Heat Shock Protein And Lipid Metabolism-Related Genes In Heat Stressed Broiler Chickens, Joshua Flees

Graduate Theses and Dissertations

Heat stress (HS) has been reported to alter fat deposition in broilers, however the underlying molecular mechanisms are not well-defined; therefore, the objectives of the current study were to: (1) determine the effects of acute (2 h) and chronic (3 wk) HS on the expression of key molecular signatures involved in hepatic lipogenic and lipolytic programs; and (2) assess if diet supplementation with dried Noni medicinal plant (0.2% of the diet) modulates these effects. Broilers (n=480 males, 1 d) were randomly assigned to 12 environmental chambers, subjected to two environmental conditions (HS at 35°C vs. thermoneutral condition [TN] at 24°C) …

Overexpression Of Cyb5r3 And Nqo1, Two Nad+-Producing Enzymes, Mimics Aspects Of Caloric Restriction, Alberto Diaz-Ruiz, Michael Lanasa, Joseph Garcia, Hector Mora, Frances Fan, Alejandro Martin-Montalvo, Andrea Di Francesco, Miguel Calvo-Rubio, Andrea Salvador-Pascual, Miguel A. Aon, Kenneth W. Fishbein, Kevin J. Pearson, Jose Manuel Villalba, Placido Navas, Michel Bernier, Rafael De Cabo

Pharmacology and Nutritional Sciences Faculty Publications

Calorie restriction (CR) is one of the most robust means to improve health and survival in model organisms. CR imposes a metabolic program that leads to increased stress resistance and delayed onset of chronic diseases, including cancer. In rodents, CR induces the upregulation of two NADH‐dehydrogenases, namely NAD(P)H:quinone oxidoreductase 1 (Nqo1) and cytochrome b₅ reductase 3 (Cyb5r3), which provide electrons for energy metabolism. It has been proposed that this upregulation may be responsible for some of the beneficial effects of CR, and defects in their activity are linked to aging and several age‐associated diseases. However, …

Developmental Exposure To Xenoestrogens: Effects On The Mouse Mammary Gland Development And Response To Estrogen, Durga Kolla

Masters Theses

Humans experience ubiquitous exposures to estrogenic environmental chemicals from food, personal care products, and other industrial and consumer goods. Bisphenol A (BPA), a well-studied xenoestrogen, is known to alter development of estrogen-sensitive organs including the brain, reproductive tract, and mammary gland. Bisphenol S (BPS), which has a similar chemical structure to BPA, is also used in many consumer products, but its effects on estrogen-sensitive organs in mammals has not been thoroughly examined. In our study, pregnant CD-1 mice were orally exposed to BPS or ethinyl estradiol (EE2, a positive control for estrogenicity) from gestational day 9 through postnatal day (PND) …

Loss Of Marv1 Promotes Chop Signaling In Mouse Liver, Shad Anthony Mitchell

Graduate School of Biomedical Sciences Theses and Dissertations

Metabolic syndrome (MetS) is a term used to define a set of metabolic diseases: obesity, type 2 diabetes (T2D), hyperlipidemia, hypertension, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic hepatosteatosis (NASH). Those with MetS have a higher incidence of cardiovascular disease and stroke. Current drug treatments for MetS treat the individual pathologies associated with the diseases, rather than directly targeting MetS as a whole. We hypothesize that the inhibition of a ubiquitous lipid transporter known as ARV1 can improve pathologies associated with MetS. To test this hypothesis, we utilized liver tissue from mARV1 knockout mice fed a high-fat diet and examined …

Transcriptional Profiling Reveals Extraordinary Diversity Among Skeletal Muscle Tissues, Erin E. Terry, Xiping Zhang, Christy Hoffmann, Laura D. Hughes, Scott A. Lewis, Jiajia Li, Matthew J. Wallace, Lance A. Riley, Collin M. Douglas, Miguel A. Gutierrez-Monreal, Nicholas F. Lahens, Ming C. Gong, Francisco H. Andrade, Karyn A. Esser, Michael E. Hughes

Physiology Faculty Publications

Skeletal muscle comprises a family of diverse tissues with highly specialized functions. Many acquired diseases, including HIV and COPD, affect specific muscles while sparing others. Even monogenic muscular dystrophies selectively affect certain muscle groups. These observations suggest that factors intrinsic to muscle tissues influence their resistance to disease. Nevertheless, most studies have not addressed transcriptional diversity among skeletal muscles. Here we use RNAseq to profile mRNA expression in skeletal, smooth, and cardiac muscle tissues from mice and rats. Our data set, MuscleDB, reveals extensive transcriptional diversity, with greater than 50% of transcripts differentially expressed among skeletal muscle tissues. We detect …

Visualizing Mutation-Specific Differences In The Trafficking-Deficient Phenotype Of Kv11.1 Proteins Linked To Long Qt Syndrome Type 2, Allison R. Hall, Corey L. Anderson, Jennifer L. Smith, Tooraj Mirshahi, Samy-Claude Elayi, Craig T. January, Brian P. Delisle

Physiology Faculty Publications

KCNH2 encodes the Kv11.1 α-subunit that underlies the rapidly activating delayed-rectifier K⁺ current in the heart. Loss-of-function KCNH2 mutations cause long QT syndrome type 2 (LQT2), and most LQT2-linked missense mutations inhibit the trafficking of Kv11.1 channel protein to the cell surface membrane. Several trafficking-deficient LQT2 mutations (e.g., G601S) generate Kv11.1 proteins that are sequestered in a microtubule-dependent quality control (QC) compartment in the transitional endoplasmic reticulum (ER). We tested the hypothesis that the QC mechanisms that regulate LQT2-linked Kv11.1 protein trafficking are mutation-specific. Confocal imaging analyses of HEK293 cells stably expressing the trafficking-deficient LQT2 mutation F805C showed that, …

Till Death Do Us Part: The Marriage Of Autophagy And Apoptosis., Katrina F Cooper

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Autophagy is a widely conserved catabolic process that is necessary for maintaining cellular homeostasis under normal physiological conditions and driving the cell to switch back to this status quo under times of starvation, hypoxia, and oxidative stress. The potential similarities and differences between basal autophagy and stimulus-induced autophagy are still largely unknown. Both act by clearing aberrant or unnecessary cytoplasmic material, such as misfolded proteins, supernumerary and defective organelles. The relationship between reactive oxygen species (ROS) and autophagy is complex. Cellular ROS is predominantly derived from mitochondria. Autophagy is triggered by this event, and by clearing the defective organelles effectively, …

An Examination Of Preimplantation Embryos And Endometrium Developed During Induced Aluteal Cycles In The Mare, Chelsey Audra Leisinger

LSU Doctoral Dissertations

Changes to the embryonic environment that occur within the first few days of development can have significant effects on subsequent fetal development. The following studies investigate the effects of progesterone-deprivation during the early preimplantation period in the mare. The first study described embryo morphology (diameter, stage, and quality grade) collected from mares with induced aluteal cycles. The second study evaluated the effect of induced aluteal cycles on the future fertility of embryo collections as a potential method for cycle manipulation of embryo donor mares. The third study characterized embryonic and endometrial transcript expression of progesterone-mediated transcripts as well as those …

Pyruvate Kinase Isoform M2 Influences Autophagy And Related Processes In Hepatocellular Carcinoma Cells, Matthew Lin

University Scholar Projects

Hepatocellular carcinoma (HCC) is the most common form of liver cancer that affects ~14 million people in the world. Like all cancers, HCC is a disease that arises from unstinted cellular growth initiated by genetic alterations, metabolic changes, and dysregulation in key cellular pathways. Of interest is the relationship between metabolism and cell proliferation/degradation for therapeutic targeting. Pyruvate kinase M2 is a dimeric, glycolytically inactive isoform of the final enzyme involved in glycolysis, that is often upregulated in cancerous tissue. It is thought that the enzymatic function of PKM2 outside of glycolysis contributes to the biosynthesis of anabolic intermediates used …

Regulation Of The Tubulin Homolog Ftsz In Escherichia Coli, Monika S. Buczek

Dissertations, Theses, and Capstone Projects

Escherichia coli is a well-known pathogen, and importantly, a widely used model organism in all fields of biological sciences for cloning, protein purification, and as a model for Gram-negative bacterial species. And yet, researchers do not fully understand how this bacterium replicates and divides. Every year additional division proteins are discovered, which adds complexity to how we understand E. coli undergoes cell division. Due to their specific roles in cytokinesis, some of these proteins may be potential targets for development of antibacterials or bacteriostatics, which are much needed for fighting the current global antibacterial deficit. My thesis work focuses on …

Reconstitution Of Gabaergic Postsynapses In Host Cells, Karthik Kanamalla

Honors Scholar Theses

Type A GABA receptors (GABAARs) can be found embedded in postsynaptic membranes or in a variety of extrasynaptic locations. Receptors with synaptic function are recruited to the postsynapse by submembranous scaffolds composed of gephyrin and collybistin (CB). This study was aimed at assessing whether the ability to interact with the scaffold differentiates synaptic from non-synaptic receptors. Using HEK293 cells as an expression system, and indirect immunofluorescence (IF), co-localization of extrasynaptic receptors α1β3δ and α4β3δ with the CB-gephyrin scaffold was assessed and compared with that of the synaptic receptor α1β3γ2. Results indicated that both extrasynaptic receptors were able to colocalize with …

Maternal Protein Restriction (Mpr): A Risk Factor For Acute Respiratory Distress Syndrome (Ards), Reza Khazaee

Western Research Forum

Background: Acute respiratory distress syndrome (ARDS) is defined as severe lung dysfunction. The lung impairments in ARDS result from alterations to pulmonary surfactant; a lipid-protein mixture coating the inside of the lung and maintains the lungs’ ability to expand easily. Due to a lack of effective pharmacological therapies mortality associated with ARDS is over 30%. Our research focuses on risk factors that indicate a susceptibility to the disease, which could provide new and early therapeutic options. One such potential risk factor is Maternal Protein Restriction (MPR). MPR is defined by low birth weight and contributes to a variety of adult-onset …

Killi-Data News (Winter), Tyrone Genade

Killifish Research Review

Valued readers, it is with a heavy heart that I inform you that this is the last issue of Killi-Data News. The good news is that we will be back as Killifish Research Review. The dissolution of Killi-Data International created a prob- lem: how can the newsletter of a defunct organization live on without that organization? But other additional problems were building in the background. The first issue numbered 15 pages. The previous issue was 28 pages. The number of killifish related papers is increasing while time on our end (the editorial team) is running out. It takes a lot …

Killi-Data News (Fall), Tyrone Genade

Killifish Research Review

Many interesting papers have been published over the last three months. The large volume of papers coupled with the start of the new college semester (and the workload it brings) delayed this issue of Killi-Data News. But better late than never—or so I hope! In this issue Richard van der Laan provides an insightful review of the recent Aphanius papers as to their taxonomic implications and questions. The systematic issues he raises show the importance of the Molecular project: we need to get more samples of the various cyprinodontiforme families to resolve unsettled systematic and taxonomic issues. In the Next …

Killi-Data News (Summer), Tyrone Genade

Killifish Research Review

Over the last three months several interesting and exciting pa- pers have been published. By now most of you have heard the Nothobranchius fish poo news emanating from the Valenzano lab. That paper is reviewed and certainly has repercussions for the health of our captive fish. Polaçik et al have published interesting data with ramifications as to how we breed and incubate annual killifish. The big news in this issue is the paper from the Reznick lab which Jean Huber reviews. The contents of that paper goes to the heart of the question of just what a killifish is. The …

Killi-Data News (Spring), Tyrone Genade

Killifish Research Review

This is the start of Killi-Data News’ second year. In this first issue of the year we have the usual review of research pub- lications as well as input from Martin Reichard on his lab’s Nothobranchius research. Martin is responding to my reviews of his lab’s work in the previous edition. I am serious about making sure the content in this newsletter is reliable but I erred in the previous edition and Martin has written extensively to correct my mistake in the section “Erratum”. This reply is welcomed and owed to readers. I must confess that I don’t know everything …

Killi-Data News (Winter), Tyrone Genade

Killifish Research Review

This is the fourth edition, and concluding issue of the first volume, of Killi-Data News and I am happy that it has been well received by readers. At 25 pages this issue is a bit thin- ner than the last but this is because we agreed to make the cut-off for submissions the 1 st of December so we could get this edition out by the New Year. This is an exciting edition full of new species descrip- tions and analyses that will keep taxonomists busy for years to come. Costa has given us two molecular phylogenies on Melanorivulus as …

Killi-Data News (Spring), Tyrone Genade

Killifish Research Review

This is the start of Killi-Data News’ second year. In this first issue of the year we have the usual review of research pub- lications as well as input from Martin Reichard on his lab’s Nothobranchius research. Martin is responding to my reviews of his lab’s work in the previous edition. I am serious about making sure the content in this newsletter is reliable but I erred in the previous edition and Martin has written extensively to correct my mistake in the section “Erratum”. This reply is welcomed and owed to readers. I must confess that I don’t know everything …

Functional Changes Associated With Shroom3 Deficiency And Mutation: Implications In Renal Pathophysiology And Disease, Doyun Ko

Electronic Thesis and Dissertation Repository

Chronic kidney disease (CKD) is a substantial global health burden that has recently been linked to the genetic locus SHROOM3 by several genome-wide association studies. Shroom3 is an actin-binding protein that is necessary for inducing apical constriction in epithelial cells. Our lab has previously shown that Shroom3 is critical for proper kidney development and loss of Shroom3 produces symptoms associated with CKD. As hypertension is both a leading cause and comorbidity of CKD, I hypothesized that loss of Shroom3 confers increased susceptibility to hypertension. Using a high-salt induced model of hypertension, I show that Shroom3 deficient mice do not become …

Appropriate Preconditioning Of The Uterine Endoplasmic Reticulum Stress Response Inhibits Preterm Labor, Judith Ann Ingles

Wayne State University Dissertations

Introduction: In this study, we are testing the overarching hypothesis that preconditioning the myometrial UPR allows for the maintenance of non-apoptotic CASP3 activity and thus sustains uterine quiescence. We have previously demonstrated that the pregnant uterus facilitates uterine quiescence through UPR mediated activation of non-apoptotic CASP3, yet the mechanism in which CASP3 utilizes to avoid its apoptotic cell fate is unresolved. There is a growing body of evidence including our own that demonstrates remote and direct preconditioning with minor stresses propagates cytoprotective mechanisms that allow for the avoidance of apoptotic cell death upon exposure to a subsequent more damaging stress, …

Dysregulation Of Daf-16/Foxo3a-Mediated Stress Responses Accelerates T Oxidative Dna Damage Induced Aging, Aditi U. Gurkar, Andria R. Robinson, Yuxiang Cui, Xuesen Li, Shailaja K. Allani, Amanda Webster, Mariya Muravia, Mohammad Fallahi, Herbert Weissbach, Paul D. Robbins, Yinsheng Wang, Eric E. Kelley, Claudette M. St. Croix, Laura J. Niedernhofer, Matthew S. Gill

Faculty & Staff Scholarship

DNA damage is presumed to be one type of stochastic macromolecular damage that contributes to aging, yet little is known about the precise mechanism by which DNA damage drives aging. Here, we attempt to address this gap in knowledge using DNA repair-deficient C. elegans and mice. ERCC1-XPF is a nuclear endonuclease required for genomic stability and loss of ERCC1 in humans and mice accelerates the incidence of age-related pathologies. Like mice, ercc-1 worms are UV sensitive, shorter lived, display premature functional decline and they accumulate spontaneous oxidative DNA lesions (cyclopurines) more rapidly than wild-type worms. We found that ercc-1 worms …

Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer

Faculty & Staff Scholarship

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/Δ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/Δ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/Δ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/Δ mice never exceeded that …