Digital Commons Network^™

Dopamine Receptor Antagonists As Potential Therapeutic Agents For Adpkd., Parama Paul, Sreekumar Ramachandran, Sheng Xia, Jay R. Unruh, Juliana Conkright-Fincham, Rong Li

Manuscripts, Articles, Book Chapters and Other Papers

Autosomal dominant polycystic kidney disease (ADPKD) is caused mostly by mutations in polycystin-1 or polycystin-2. Fluid flow leads to polycystin-dependent calcium influx and nuclear export of histone deacetylase 5 (HDAC5), which facilitates the maintenance of renal epithelial architecture by de-repression of MEF2C target genes. Here, we screened a small-molecule library to find drugs that promotes nuclear export of HDAC5. We found that dopamine receptor antagonists, domperidone and loxapine succinate, stimulate export of HDAC5, even in Pkd1-/-cells. Domperidone targets Drd3 receptor to modulate the phosphorylation of HDAC5. Domperidone treatment increases HDAC5 phosphorylation likely by reducing protein phosphatase 2A (PP2A) activity, thus …

A Consensus Guide To Capturing The Ability To Inhibit Actions And Impulsive Behaviors In The Stop-Signal Task., Frederick Verbruggen, Adam R Aron, Guido Ph Band, Christian Beste, Patrick G Bissett, Adam T Brockett, Joshua W Brown, Samuel R Chamberlain, Christopher D Chambers, Hans Colonius, Lorenza S Colzato, Brian D Corneil, James P Coxon, Annie Dupuis, Dawn M Eagle, Hugh Garavan, Ian Greenhouse, Andrew Heathcote, René J Huster, Sara Jahfari, J Leon Kenemans, Inge Leunissen, Chiang-Shan R Li, Gordon D Logan, Dora Matzke, Sharon Morein-Zamir, Aditya Murthy, Martin Paré, Russell A Poldrack, K Richard Ridderinkhof, Trevor W Robbins, Matthew Roesch, Katya Rubia, Russell J Schachar, Jeffrey D Schall, Ann-Kathrin Stock, Nicole C Swann, Katharine N Thakkar, Maurits W Van Der Molen, Luc Vermeylen, Matthijs Vink, Jan R Wessel, Robert Whelan, Bram B Zandbelt, C Nico Boehler

Brain and Mind Institute Researchers' Publications

Response inhibition is essential for navigating everyday life. Its derailment is considered integral to numerous neurological and psychiatric disorders, and more generally, to a wide range of behavioral and health problems. Response-inhibition efficiency furthermore correlates with treatment outcome in some of these conditions. The stop-signal task is an essential tool to determine how quickly response inhibition is implemented. Despite its apparent simplicity, there are many features (ranging from task design to data analysis) that vary across studies in ways that can easily compromise the validity of the obtained results. Our goal is to facilitate a more accurate use of the …

Development And Evaluation Of A One-Step Multiplex Real-Time Taqman® Rt-Qpcr Assay For The Detection And Genotyping Of Equine G3 And G14 Rotaviruses In Fecal Samples, Mariano Carossino, Maria E. Barrandeguy, Erdal Erol, Yanqiu Li, Udeni B. R. Balasuriya

Veterinary Science Faculty Publications

Background: Equine rotavirus A (ERVA) is the leading cause of diarrhea in neonatal foals and has a negative impact on equine breeding enterprises worldwide. Among ERVA strains infecting foals, the genotypes G3P[12] and G14P[12] are the most prevalent, while infections by strains with other genomic arrangements are infrequent. The identification of circulating strains of ERVA is critical for diagnostic and surveillance purposes, as well as to understand their molecular epidemiology. Current genotyping methods available for ERVA and rotaviruses affecting other animal species rely on Sanger sequencing and are significantly time-consuming, costly and labor intensive. Here, we developed the first one-step …

Down Syndrome Mouse Models Have An Abnormal Enteric Nervous System, Ellen M Schill, Christina M Wright, Alisha Jamil, Jonathan M Lacombe, Randall J Roper, Robert O Heuckeroth

Open Access Publications

Children with trisomy 21 (Down syndrome [DS]) have a 130-fold increased incidence of Hirschsprung Disease (HSCR), a developmental defect where the enteric nervous system (ENS) is missing from distal bowel (i.e., distal bowel is aganglionic). Treatment for HSCR is surgical resection of aganglionic bowel, but many children have bowel problems after surgery. Post-surgical problems like enterocolitis and soiling are especially common in children with DS. To determine how trisomy 21 affects ENS development, we evaluated the ENS in two DS mouse models, Ts65Dn and Tc1. These mice are trisomic for many chromosome 21 homologous genes, including Dscam and Dyrk1a, which …

Extracellular Vesicles As Biological Shuttles For Targeted Therapies., Stefania Raimondo, Gianluca Giavaresi, Aurelio Lorico, Riccardo Alessandro

College of Osteopathic Medicine (TUN) Publications and Research

The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)-specialized membrane-bound nanocarriers for intercellular communication-suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, …

Molecular Evolutionary Trends And Feeding Ecology Diversification In The Hemiptera, Anchored By The Milkweed Bug Genome, Kristen A. Panfilio, Iris M. Vargas Jentzsch, Joshua B. Benoit, Deniz Erezyilmaz, Yuichiro Suzuki, Stefano Colella, Hugh M. Robertson, Monica F. Poelchau, Robert M. Waterhouse, Panagiotis Ioannidis, Matthew T. Weirauch, Daniel S. T. Hughes, Shwetha C. Murali, John H. Werren, Chris G. C. Jacobs, Elizabeth J. Duncan, David Armisén, Barbara M. I. Vreede, Patrice Baa-Puyoulet, Chloé S. Berger, Chun-Che Chang, Hsu Chao, Mei-Ju M. Chen, Yen-Ta Chen, Christopher P. Childers, Ariel D. Chipman, Andrew G. Cridge, Antonin J. J. Crumière, Peter K. Dearden, Elise M. Didion, Subba Reddy Palli, Jayendra Nath Shukla

Entomology Faculty Publications

Background: The Hemiptera (aphids, cicadas, and true bugs) are a key insect order, with high diversity for feeding ecology and excellent experimental tractability for molecular genetics. Building upon recent sequencing of hemipteran pests such as phloem-feeding aphids and blood-feeding bed bugs, we present the genome sequence and comparative analyses centered on the milkweed bug Oncopeltus fasciatus, a seed feeder of the family Lygaeidae.

Results: The 926-Mb Oncopeltus genome is well represented by the current assembly and official gene set. We use our genomic and RNA-seq data not only to characterize the protein-coding gene repertoire and perform isoform-specific RNAi, but …

Clc Expanded Learning Opportunity Club: Living World, Celeste Kenworthy, Aurora Kenworthy

Honors Program: Expanded Learning Clubs

An afterschool club that focuses on building understanding and enjoyment of nature and the environment through interactive and collaborative activities.

A Mixture Of U.S. Food And Drug Administration-Approved Monoaminergic Drugs Protects The Retina From Light Damage In Diverse Models Of Night Blindness, Henri Leinonen, Elliot H. Choi, Anthony Gardella, Vladimir J. Kefalov, Krzysztof Palczewski

Open Access Publications

Purpose: The purpose of this study was to test the extent of light damage in different models of night blindness and apply these paradigms in testing the therapeutic efficacy of combination therapy by drugs acting on the Gi, Gs, and Gq protein-coupled receptors.

Methods: Acute bright light exposure was used to test susceptibility to light damage in mice lacking the following crucial phototransduction proteins: rod transducin (GNAT1), cone transducin (GNAT2), visual arrestin 1 (ARR1), and rhodopsin kinase 1 (GRK1). Mice were intraperitoneally injected with either vehicle or drug combination consisting of metoprolol (β1-receptor antagonist), bromocriptine (dopamine family-2 receptor agonist) and …

Proteomic Alterations Of Hdl In Youth With Type 1 Diabetes And Their Associations With Glycemic Control: A Case-Control Study, Evgenia Gourgari, Junfeng Ma, Martin P. Playford, Nehal N. Mehta, Radoslav Goldman, Alan T. Remaley, Scott M. Gordon

Saha Cardiovascular Research Center Faculty Publications

Background: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition.

Methods: This was a cross-sectional case–control study. Blood samples were obtained from patients with T1DM and …

Prefrontal Corticotropin-Releasing Factor (Crf) Neurons Act Locally To Modulate Frontostriatal Cognition And Circuit Function., Sofiya Hupalo, Andrea J Martin, Rebecca K Green, David M Devilbiss, Craig W Berridge

Rowan-Virtua School of Osteopathic Medicine Departmental Research

The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRF-dependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated …

Homozygous Frameshift Mutations In Fat1 Cause A Syndrome Characterized By Colobomatous-Microphthalmia, Ptosis, Nephropathy And Syndactyly., Najim Lahrouchi, Aman George, Ilham Ratbi, Ronen Schneider, Siham C Elalaoui, Shahida Moosa, Sanita Bharti, Ruchi Sharma, Mones Abu-Asab, Felix Onojafe, Najlae Adadi, Elisabeth M Lodder, Fatima-Zahra Laarabi, Yassine Lamsyah, Hamza Elorch, Imane Chebbar, Alex V Postma, Vassilios Lougaris, Alessandro Plebani, Janine Altmueller, Henriette Kyrieleis, Vardiella Meiner, Helen Mcneill, Kapil Bharti, Stanislas Lyonnet, Bernd Wollnik, Alexandra Henrion-Caude, Amina Berraho, Friedhelm Hildebrandt, Connie R Bezzina, Brian P Brooks, Abdelaziz Sefiani

Open Access Publications

A failure in optic fissure fusion during development can lead to blinding malformations of the eye. Here, we report a syndrome characterized by facial dysmorphism, colobomatous microphthalmia, ptosis and syndactyly with or without nephropathy, associated with homozygous frameshift mutations in FAT1. We show that Fat1 knockout mice and zebrafish embryos homozygous for truncating fat1a mutations exhibit completely penetrant coloboma, recapitulating the most consistent developmental defect observed in affected individuals. In human retinal pigment epithelium (RPE) cells, the primary site for the fusion of optic fissure margins, FAT1 is localized at earliest cell-cell junctions, consistent with a role in facilitating optic …

Comprehensive Gene Expression Meta-Analysis Identifies Signature Genes That Distinguish Microglia From Peripheral Monocytes/Macrophages In Health And Glioma, Verena Haage, Marcus Semtner, Ramon Oliveira Vidal, Daniel Perez Hernandez, Winnie W Pong, Zhihong Chen, Dolores Hambardzumyan, Vincent Magrini, Amy Ly, Jason Walker, Elaine Mardis, Philipp Mertins, Sascha Sauer, Helmut Kettenmann, David H Gutmann

Open Access Publications

Monocytes/macrophages have begun to emerge as key cellular modulators of brain homeostasis and central nervous system (CNS) disease. In the healthy brain, resident microglia are the predominant macrophage cell population; however, under conditions of blood-brain barrier leakage, peripheral monocytes/macrophages can infiltrate the brain and participate in CNS disease pathogenesis. Distinguishing these two populations is often challenging, owing to a paucity of universally accepted and reliable markers. To identify discriminatory marker sets for microglia and peripheral monocytes/macrophages, we employed a large meta-analytic approach using five published murine transcriptional datasets. Following hierarchical clustering, we filtered the top differentially expressed genes (DEGs) through …

Identification Of Novel Regulatory Genes In Apap Induced Hepatocyte Toxicity By A Genome-Wide Crispr-Cas9 Screen., Katherine Shortt, Daniel P. Heruth, Nini Zhang, Weibin Wu, Shipra Singh, Ding-You Li, Li Qin Zhang, Gerald J. Wyckoff, Lei S Qi, Craig A. Friesen, Shui Qing Ye

Manuscripts, Articles, Book Chapters and Other Papers

Acetaminophen (APAP) is a commonly used analgesic responsible for more than half of acute liver failure cases. Identification of previously unknown genetic risk factors would provide mechanistic insights and novel therapeutic targets for APAP-induced liver injury. This study used a genome-wide CRISPR-Cas9 screen to evaluate genes that are protective against, or cause susceptibility to, APAP-induced liver injury. HuH7 human hepatocellular carcinoma cells containing CRISPR-Cas9 gene knockouts were treated with 15 mM APAP for 30 minutes to 4 days. A gene expression profile was developed based on the 1) top screening hits, 2) overlap of expression data from APAP overdose studies, …

Multi-Tissue Transcriptomes Of Caecilian Amphibians Highlight Incomplete Knowledge Of Vertebrate Gene Families, María Torres-Sánchez, Christopher J. Creevey, Etienne Kornobis, David J. Gower, Mark Wilkinson, Diego San Mauro

Neuroscience Faculty Publications

RNA sequencing (RNA-seq) has become one of the most powerful tools to unravel the genomic basis of biological adaptation and diversity. Although challenging, RNA-seq is particularly promising for research on non-model, secretive species that cannot be observed in nature easily and therefore remain comparatively understudied. Among such animals, the caecilians (order Gymnophiona) likely constitute the least known group of vertebrates, despite being an old and remarkably distinct lineage of amphibians. Here, we characterize multi-tissue transcriptomes for five species of caecilians that represent a broad level of diversity across the order. We identified vertebrate homologous elements of caecilian functional genes of …

Voltage-Independent Sk-Channel Dysfunction Causes Neuronal Hyperexcitability In The Hippocampus Of Fmr1 Knock-Out Mice, Pan-Yue Deng, Dan Carlin, Young Mi Oh, Leila K. Myrick, Stephen T. Warren, Valeria Cavalli, Vitaly A. Klyachko

Open Access Publications

Neuronal hyperexcitability is one of the major characteristics of fragile X syndrome (FXS), yet the molecular mechanisms of this critical dysfunction remain poorly understood. Here we report a major role of voltage-independent potassium (K

Methods To Quantify Nanomaterial Association With, And Distribution Across, The Blood-Brain Barrier In Vivo, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

The role and functional anatomy of the blood-brain barrier (BBB) is summarized to enable the investigator to appropriately address evaluation of nanomaterial interaction with, and distribution across, it into brain tissue (parenchyma). Transport mechanisms across the BBB are presented, in relation to nanomaterial physicochemical properties. Measures and test substances to assess BBB integrity/disruption/permeation are introduced, along with how they are used to interpret the results obtained with the presented methods. Experimental pitfalls and misinterpretation of results of studies of brain nanomaterial uptake are briefly summarized, that can be avoided with the methods presented in this chapter. Two methods are presented. …

Diagnosis Of Schistosoma Mansoni Infections: What Are The Choices In Brazilian Low-Endemic Areas?, Vanessa Silva-Moraes, Lisa M. Shollenberger, Liliane Maria Vidal Siqueira, William Castro-Borges, Donald A. Harn, Rafaella Fortini Queiroz E. Grenfell, Ana Lucia Teles Rabello, Paulo Marcos Zech Coelho

Biological Sciences Faculty Publications

The population of Brazil is currently characterised by many individuals harbouring low-intensity Schistosoma mansoni infections. The Kato-Katz technique is the diagnostic method recommended by the World Health Organization (WHO) to assess these infections, but this method is not sensitive enough in the context of low egg excretion. In this regard, potential alternatives are being employed to overcome the limits of the Kato-Katz technique. In the present review, we evaluated the performance of parasitological and immunological approaches adopted in Brazilian areas. Currently, the diagnostic choices involve a combination of strategies, including the utilisation of antibody methods to screen individuals and then …

Do Teachers Participating In A Therapy Dog Program Perceive An Impact On Students’ Attitudes And Behaviors Toward Reading?, Jenna M. Dragani-Reagan

PCOM Psychology Dissertations

No abstract provided.

Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein

Journal Articles: Eppley Institute

Rab proteins play an essential role in regulating intracellular membrane trafficking processes. Rab activity is dependent upon geranylgeranylation, a post-translational modification that involves the addition of 20-carbon isoprenoid chains via the enzyme geranylgeranyl transferase (GGTase) II. We have focused on the development of inhibitors against geranylgeranyl diphosphate synthase (GGDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abnormal mucin production and these mucins play important roles in tumor development, metastasis and chemo-resistance. We hypothesized that GGDPS inhibitor (GGDPSi) treatment would induce PDAC cell death by disrupting mucin trafficking, thereby inducing the unfolded …

Melatonin Enhances Sorafenib-Induced Cytotoxicity In Flt3-Itd Acute Myeloid Leukemia Cells By Redox Modification, Tian Tian, Jiajun Li, Yizhuo Li, Yun-Xin Lu, Yan-Lai Tang, Hua Wang, Fufu Zheng, Dingbo Shi, Qian Long, Miao Chen, Guillermo Garcia-Manero, Yumin Hu, Lijun Qin, Wuguo Deng

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with an internal tandem duplication in Fms-related tyrosine kinase 3 (FLT3-ITD) is identified as a subgroup with poor outcome and intrinsic resistance to chemotherapy and therefore urgent need for development of novel therapeutic strategies.

Methods: The antitumor effects of melatonin alone or combined with sorafenib were evaluated via flow cytometry and immunoblotting assays in FLT-ITD AML cells. Also, the ex vivo and in vivo models were used to test the synergistic effects of melatonin and sorafenib against leukemia with FLT3/ITD mutation.

Results: Our study shows for the first time that melatonin inhibits proliferation and induces apoptosis …

Don't Touch Me Like That: Masculinity, Touch, And The Role Of Affect In Media Representations Of Animal Attacks, Carolyn Grace Block

Electronic Theses and Dissertations Archive

This dissertation analyzes masculinity and touch in three highly publicized cases where men intentionally interacted with wild animals and were harmed in the process. I focus predominately on the first week of media coverage following Steve The Crocodile Hunter Irwin who was killed by a massive stingray while filming for a television series off the Great Barrier Reef, Roy Horn of the famed Las Vegas magician duo Siegfried and Roy who was mauled by one of his performing tigers in front of a live audience, and Antoine Yates, an African American man bitten by the pet tiger he kept in …

Resveratrol Attenuates Allergic Asthma And Associated Inflammation In The Lungs Through Regulation Of Mirna-34a That Targets Foxp3 In Mice, Esraah Alharris, Hasan Alghetaa, Ratanesh K. Seth, Saurabh Chatterjee, Narendra P. Singh, Mitzi Nagarkatti, Prakash Nagarkatti

Faculty Publications

Asthma is a chronic inflammatory disease of airways mediated by T-helper 2 (Th2) cells involving complex signaling pathways. Although resveratrol has previously been shown to attenuate allergic asthma, the role of miRNA in this process has not been studied. We investigated the effect of resveratrol on ovalbumin-induced experimental allergic asthma in mice. To that end, BALB/c mice were immunized with ovalbumin (OVA) intraperitoneally followed by oral gavage of vehicle (OVA-veh) or resveratrol (100 mg/kg body) (OVA-res). On day 7, the experimental groups received intranasal challenge of OVA followed by 7 days of additional oral gavage of vehicle or resveratrol. At …

Expanding The Use Of Spectral Libraries In Proteomics., Eric W Deutsch, Yasset Perez-Riverol, Robert J Chalkley, Mathias Wilhelm, Stephen Tate, Timo Sachsenberg, Mathias Walzer, Lukas Käll, Bernard Delanghe, Sebastian Böcker, Emma L Schymanski, Paul Wilmes, Viktoria Dorfer, Bernhard Kuster, Pieter-Jan Volders, Nico Jehmlich, Johannes P C Vissers, Dennis W Wolan, Ana Y Wang, Luis Mendoza, Jim Shofstahl, Andrew W Dowsey, Johannes Griss, Reza M Salek, Steffen Neumann, Pierre-Alain Binz, Henry Lam, Juan Antonio Vizcaíno, Nuno Bandeira, Hannes Röst

Articles, Abstracts, and Reports

The 2017 Dagstuhl Seminar on Computational Proteomics provided an opportunity for a broad discussion on the current state and future directions of the generation and use of peptide tandem mass spectrometry spectral libraries. Their use in proteomics is growing slowly, but there are multiple challenges in the field that must be addressed to further increase the adoption of spectral libraries and related techniques. The primary bottlenecks are the paucity of high quality and comprehensive libraries and the general difficulty of adopting spectral library searching into existing workflows. There are several existing spectral library formats, but none captures a satisfactory level …

Flexible And Fast Mapping Of Peptides To A Proteome With Proteomapper., Luis Mendoza, Eric W Deutsch, Zhi Sun, David S Campbell, David Shteynberg, Robert L Moritz

Articles, Abstracts, and Reports

Bottom-up proteomics relies on the proteolytic or chemical cleavage of proteins into peptides, the identification of those peptides via mass spectrometry, and the mapping of the identified peptides back to the reference proteome to infer which possible proteins are identified. Reliable mapping of peptides to proteins still poses substantial challenges when considering similar proteins, protein families, splice isoforms, sequence variation, and possible residue mass modifications, combined with an imperfect and incomplete understanding of the proteome. The ProteoMapper tool enables a comprehensive and rapid mapping of peptides to a reference proteome. The indexer component creates a segmented index for an input …

Making Covenants With Brute Beasts: Making Room For Non-Human Animals In A Contractualist Framework, Jennifer Lynn Burgis

Open Access Dissertations

In this dissertation I explore the question of whether T.M. Scanlon's contractualist ethical theory can be revised such that the resulting theory makes room for moral obligations to non-human animals. A number of attempts have been made to justify our intuitions regarding the treatment of animals, but none of these has succeeded. I argue that Scanlon's reliance on the rationality criterion is flawed and that a focus on moral capacities creates both a more inclusive and a more satisfying moral framework. By building on Julia Driver's objective consequentialist account of virtue, I am able to support the claim that, at …

Targeting The Brd4/Foxo3a/Cdk6 Axis Sensitizes Akt Inhibition In Luminal Breast Cancer, Jingyi Liu, Weijie Guo, Zhibing Duan, Lei Zeng, Yadi Wu, Yule Chen, Fang Tai, Yifan Wang, Yiwei Lin, Qiang Zhang, Yanling He, Jiong Deng, Rachel L. Stewart, Chi Wang, Pengnian Charles Lin, Saghi Ghaffari, B. Mark Evers, Suling Liu, Ming-Ming Zhou, Binhua P. Zhou, Jian Shi

Molecular and Cellular Biochemistry Faculty Publications

BRD4 assembles transcriptional machinery at gene super-enhancer regions and governs the expression of genes that are critical for cancer progression. However, it remains unclear whether BRD4-mediated gene transcription is required for tumor cells to develop drug resistance. Our data show that prolonged treatment of luminal breast cancer cells with AKT inhibitors induces FOXO3a dephosphorylation, nuclear translocation, and disrupts its association with SirT6, eventually leading to FOXO3a acetylation as well as BRD4 recognition. Acetylated FOXO3a recognizes the BD2 domain of BRD4, recruits the BRD4/RNAPII complex to the CDK6 gene promoter, and induces its transcription. Pharmacological inhibition of either BRD4/FOXO3a association or …

Associative And Non-Associative Learning In The Monodelphis Domestica, Ana C. Ramirez

Theses and Dissertations

Learning encompasses multiple important processes that vary within organisms and that are affected by different factors. Two of the most important types of learning are associative and non-associative learning. Even though past research has studied animal learning in multiple species, there is limited research on learning in the Monodelphis domestica. It is imperative to further the knowledge on this species since multiple fields use it as an animal model for research. The current study examined both non-associative and associative learning in the Monodelphis. Non-associative learning was explored by using a habituation-dishabituation paradigm, while associative learning was examined using the …

Rapid And Robust Restoration Of Breathing Long After Spinal Cord Injury, Philippa M. Warren, Stephanie C. Steiger, Thomas E. Dick, Peter M. Macfarlane, Warren J. Alilain, Jerry Silver

Spinal Cord and Brain Injury Research Center Faculty Publications

There exists an abundance of barriers that hinder functional recovery following spinal cord injury, especially at chronic stages. Here, we examine the rescue of breathing up to 1.5 years following cervical hemisection in the rat. In spite of complete hemidiaphragm paralysis, a single injection of chondroitinase ABC in the phrenic motor pool restored robust and persistent diaphragm function while improving neuromuscular junction anatomy. This treatment strategy was more effective when applied chronically than when assessed acutely after injury. The addition of intermittent hypoxia conditioning further strengthened the ventilatory response. However, in a sub-population of animals, this combination treatment caused excess …

Micu1 Interacts With The D-Ring Of The Mcu Pore To Control Its Ca2+ Flux And Sensitivity To Ru360, Melanie Paillard, György Csordás, Kai-Ting Huang, Peter Várnai, Suresh K. Joseph, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Proper control of the mitochondrial Ca²⁺ uniporter’s pore (MCU) is required to allow Ca²⁺ dependent activation of oxidative metabolism and to avoid mitochondrial Ca²⁺ overload and cell death. The MCU’s gatekeeping and cooperative activation is mediated by the Ca²⁺ sensing MICU1 protein, which has been proposed to form dimeric complexes anchored to the EMRE scaffold of MCU. We unexpectedly find that MICU1 suppresses inhibition of MCU by ruthenium red/Ru360, which bind to MCU’s DIME motif, the selectivity filter. This led us to recognize in MICU1’s sequence, a putative DIME Interacting Domain (DID) which is required for …

Proteomics Of Human Liver Membrane Transporters: A Focus On Fetuses And Newborn Infants., Bianca D. Van Groen, Evita Van De Steeg, Miriam G. Mooij, Marola M H Van Lipzig, Barbara A E De Koning, Robert M. Verdijk, Heleen M. Wortelboer, R Gaedigk, Chengpeng Bi, J Steven Leeder, Ron H N Van Schaik, Joost Van Rosmalen, Dick Tibboel, Wouter H. Vaes, Saskia N. De Wildt

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples.

METHODS: Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3, NTCP, OCT1, OATP1B1, OATP1B3, OATP2B1 and ATP1A1 were quantified with LC-MS/MS in isolated crude membrane fractions of snap-frozen post-mortem fetal and pediatric, and surgical adult liver samples. mRNA expression was quantified using RNA sequencing, and genetic variants with TaqMan assays. We explored relationships between protein expression and age …