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The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’S Disease
life Review The Baseline Structure of the Enteric Nervous System and Its Role in Parkinson’s Disease Gianfranco Natale 1,2,* , Larisa Ryskalin 1 , Gabriele Morucci 1 , Gloria Lazzeri 1, Alessandro Frati 3,4 and Francesco Fornai 1,4 1 Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; [email protected] (L.R.); [email protected] (G.M.); [email protected] (G.L.); [email protected] (F.F.) 2 Museum of Human Anatomy “Filippo Civinini”, University of Pisa, 56126 Pisa, Italy 3 Neurosurgery Division, Human Neurosciences Department, Sapienza University of Rome, 00135 Rome, Italy; [email protected] 4 Istituto di Ricovero e Cura a Carattere Scientifico (I.R.C.C.S.) Neuromed, 86077 Pozzilli, Italy * Correspondence: [email protected] Abstract: The gastrointestinal (GI) tract is provided with a peculiar nervous network, known as the enteric nervous system (ENS), which is dedicated to the fine control of digestive functions. This forms a complex network, which includes several types of neurons, as well as glial cells. Despite extensive studies, a comprehensive classification of these neurons is still lacking. The complexity of ENS is magnified by a multiple control of the central nervous system, and bidirectional communication between various central nervous areas and the gut occurs. This lends substance to the complexity of the microbiota–gut–brain axis, which represents the network governing homeostasis through nervous, endocrine, immune, and metabolic pathways. The present manuscript is dedicated to Citation: Natale, G.; Ryskalin, L.; identifying various neuronal cytotypes belonging to ENS in baseline conditions. -
Genetic Modulation of GABA Levels in the Anterior Cingulate Cortex by GAD1 and COMT
Neuropsychopharmacology (2010) 35, 1708–1717 & 2010 Nature Publishing Group All rights reserved 0893-133X/10 $32.00 www.neuropsychopharmacology.org Genetic Modulation of GABA Levels in the Anterior Cingulate Cortex by GAD1 and COMT 1,2 1,2 3 1,2 Stefano Marenco* , Antonina A Savostyanova , Jan Willem van der Veen , Matthew Geramita , 1,2 1,2 1 1,2 1 Alexa Stern , Alan S Barnett , Bhaskar Kolachana , Eugenia Radulescu , Fengyu Zhang , 1 1 3 1 Joseph H Callicott , Richard E Straub , Jun Shen and Daniel R Weinberger 1 2 Clinical Brain Disorders Branch, GCAP, IRP, NIMH, Bethesda, MD, USA; Unit for Multimodal Imaging Genetics, Clinical Brain Disorders Branch, 3 GCAP, IRP, NIMH, Bethesda, MD, USA; Magnetic Resonance Spectroscopy Unit, MAP, IRP, NIMH, Bethesda, MD, USA g-Aminobutyric acid (GABA)-ergic transmission is critical for normal cortical function and is likely abnormal in a variety of neuropsychiatric disorders. We tested the in vivo effects of variations in two genes implicated in GABA function on GABA concentrations in prefrontal cortex of living subjects: glutamic acid decarboxylase 1 (GAD1), which encodes GAD67, and catechol-o-methyltransferase (COMT), which regulates synaptic dopamine in the cortex. We studied six single nucleotide polymorphisms (SNPs) in GAD1 previously associated with risk for schizophrenia or cognitive dysfunction and the val158met polymorphism in COMT in 116 healthy volunteers using proton magnetic resonance spectroscopy. Two of the GAD1 SNPs (rs1978340 (p ¼ 0.005) and rs769390 (p ¼ 0.004)) showed effects on GABA levels as did COMT val158met (p ¼ 0.04). We then tested three SNPs in GAD1 (rs1978340, rs11542313, and rs769390) for interaction with COMT val158met based on previous clinical results. -
Characterization of the CRM Gene Family and Elucidating the Function of Oscfm2 in Rice
biomolecules Article Characterization of the CRM Gene Family and Elucidating the Function of OsCFM2 in Rice Qiang Zhang y , Lan Shen y, Deyong Ren, Jiang Hu, Li Zhu, Zhenyu Gao, Guangheng Zhang , Longbiao Guo, Dali Zeng and Qian Qian * State Key Laboratory of Rice Biology/China National Rice Research Institute, Chinese Academy of Agricultural Sciences, Hangzhou 310006, China; [email protected] (Q.Z.); [email protected] (L.S.); [email protected] (D.R.); [email protected] (J.H.); [email protected] (L.Z.); [email protected] (Z.G.); [email protected] (G.Z.); [email protected] (L.G.); [email protected] (D.Z.) * Correspondence: [email protected]; Tel.: +86-571-6337-0483 These authors contributed equally to this work. y Received: 10 January 2020; Accepted: 17 February 2020; Published: 18 February 2020 Abstract: The chloroplast RNA splicing and ribosome maturation (CRM) domain-containing proteins regulate the expression of chloroplast or mitochondrial genes that influence plant growth and development. Although 14 CRM domain proteins have previously been identified in rice, there are few studies of these gene expression patterns in various tissues and under abiotic stress. In our study, we found that 14 CRM domain-containing proteins have a conservative motif1. Under salt stress, the expression levels of 14 CRM genes were downregulated. However, under drought and cold stress, the expression level of some CRM genes was increased. The analysis of gene expression patterns showed that 14 CRM genes were expressed in all tissues but especially highly expressed in leaves. In addition, we analyzed the functions of OsCFM2 and found that this protein influences chloroplast development by regulating the splicing of a group I and five group II introns. -
Identifying Genes in Monoamine Nuclei That May Determine Stress Vulnerability and Depressive Behavior in Wistar–Kyoto Rats
Neuropsychopharmacology (2006) 31, 2449–2461 & 2006 Nature Publishing Group All rights reserved 0893-133X/06 $30.00 www.neuropsychopharmacology.org Identifying Genes in Monoamine Nuclei that may Determine Stress Vulnerability and Depressive Behavior in Wistar–Kyoto Rats 1 2 2 ,1 Kimberly A Pearson , Alisson Stephen , Sheryl G Beck and Rita J Valentino* 1Department of Pediatrics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA; 2Department of Anesthesiology and Critical Care Medicine, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA The Wistar–Kyoto (WKY) rat is stress sensitive and exhibits depressive-like behavior. The locus coeruleus (LC)–norepinephrine and dorsal raphe (DR)–serotonin systems mediate certain aspects of the stress response and have been implicated in depression. Microarray technology was used to identify gene expression differences in the LC and DR between WKY vs Sprague–Dawley (SD) rats that might account for the WKY phenotype. RNA was isolated from microdissected LC and DR, amplified, and hybridized to microarrays (1 array/ subject, n ¼ 4/group). Significance of microarray (SAM) analysis revealed increased expression of 66 genes in the LC and 19 genes in the DR and decreased expression of 33 genes in the DR of WKY rats. Hierarchical clustering identified differences in gene expression profiles of WKY vs SD rats that generally concurred with SAM. Notably, genes that encoded for enzymes involved in norepinephrine turnover, amino-acid receptors, and certain G-protein-coupled receptors were elevated in the LC of WKY rats. The DR of WKY rats showed decreased expression of genes encoding several potassium channels and neurofilament genes. The chromosomal locations of 15 genes that were differentially expressed in WKY rats were near loci identified as contributing to depressive-like behaviors in the rat. -
( 12 ) Patent Application Publication ( 10 ) Pub . No .: US 2020/0407740 A1 CUI Et Al
US 20200407740A1 IN ( 19 ) United States ( 12 ) Patent Application Publication ( 10 ) Pub . No .: US 2020/0407740 A1 CUI et al. ( 43 ) Pub . Date : Dec. 31 , 2020 ( 54 ) MATERIALS AND METHODS FOR Publication Classification CONTROLLING BUNDLE SHEATH CELL ( 51 ) Int. CI . FATE AND FUNCTION IN PLANTS C12N 15/82 ( 2006.01 ) ( 71 ) Applicant: FLORIDA STATE UNIVERSITY ( 52 ) U.S. CI . RESEARCH FOUNDATION , INC . , CPC C12N 15/8225 ( 2013.01 ) ; C12N 15/8269 Tallahassee, FL ( US ) ( 2013.01 ) ; C12N 15/8261 ( 2013.01 ) ( 57 ) ABSTRACT ( 72 ) Inventors : HONGCHANG CUI , The subject invention concerns materials and methods for TALLAHASSEE , FL (US ); DANYU increasing and / or improving photosynthetic efficiency in KONG , BLACKSBURG , VA (US ); plants, and in particular, C3 plants. In particular, the subject YUELING HAO , TALLAHASSEE , FL invention provides for means to increase the number of ( US ) bundle sheath ( BS ) cells in plants , to improve the efficiency of photosynthesis in BS cells , and to increase channels between BS and mesophyll ( M ) cells . In one embodiment, a ( 21 ) Appl . No .: 17 / 007,043 method of the invention concerns altering the expression level or pattern of one or more of SHR , SCR , and / or SCL23 in a plant. The subject invention also pertains to genetically ( 22 ) Filed : Aug. 31 , 2020 modified plants , and in particular, C3 plants, that exhibit increased expression of one or more of SHR , SCR , and / or SCL23 . Transformed and transgenic plants are contemplated Related U.S. Application Data within the scope of the invention . The subject invention also ( 62 ) Division of application No. 14 / 898,046 , filed on Dec. concerns methods for increasing expression of photosyn 11 , 2015 , filed as application No. -
The CRM Domain: an RNA Binding Module Derived from an Ancient Ribosome-Associated Protein
JOBNAME: RNA 13#1 2007 PAGE: 1 OUTPUT: Thursday December 7 00:09:11 2006 csh/RNA/127813/rna1396 Downloaded from rnajournal.cshlp.org on September 28, 2021 - Published by Cold Spring Harbor Laboratory Press The CRM domain: An RNA binding module derived from an ancient ribosome-associated protein ALICE BARKAN,1 LARIK KLIPCAN,2 OREN OSTERSETZER,2 TETSUYA KAWAMURA,1,3 YUKARI ASAKURA,1 and KENNETH P. WATKINS1 1Institute of Molecular Biology, University of Oregon, Eugene, Oregon 97403-1229, USA 2Agricultural Research Organization, Volcani Center, Bet Dagan 50250, Israel ABSTRACT The CRS1–YhbY domain (also called the CRM domain) is represented as a stand-alone protein in Archaea and Bacteria, and in a family of single- and multidomain proteins in plants. The function of this domain is unknown, but structural data and the presence of the domain in several proteins known to interact with RNA have led to the proposal that it binds RNA. Here we describe a phylogenetic analysis of the domain, its incorporation into diverse proteins in plants, and biochemical properties of a prokaryotic and eukaryotic representative of the domain family. We show that a bacterial member of the family, Escherichia coli YhbY, is associated with pre-50S ribosomal subunits, suggesting that YhbY functions in ribosome assembly. GFP fused to a single-domain CRM protein from maize localizes to the nucleolus, suggesting that an analogous activity may have been retained in plants. We show further that an isolated maize CRM domain has RNA binding activity in vitro, and that a small motif shared with KH RNA binding domains, a conserved ‘‘GxxG’’ loop, contributes to its RNA binding activity. -
Regulation of the Glutamate/Glutamine Cycle by Nitric Oxide in the Central Nervous System
University of Pennsylvania ScholarlyCommons Publicly Accessible Penn Dissertations 2015 Regulation of the Glutamate/glutamine Cycle by Nitric Oxide in the Central Nervous System Karthik Anderson Raju University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/edissertations Part of the Biochemistry Commons, Biology Commons, and the Neuroscience and Neurobiology Commons Recommended Citation Raju, Karthik Anderson, "Regulation of the Glutamate/glutamine Cycle by Nitric Oxide in the Central Nervous System" (2015). Publicly Accessible Penn Dissertations. 1962. https://repository.upenn.edu/edissertations/1962 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/edissertations/1962 For more information, please contact [email protected]. Regulation of the Glutamate/glutamine Cycle by Nitric Oxide in the Central Nervous System Abstract Nitric oxide (˙NO) is a critical contributor to glutamatergic neurotransmission in the central nervous system (CNS). Much of its influence is due ot the ability of this molecule to regulate protein structure and function through its posttranslational modification of cysteine esidues,r a process known as S- nitrosylation. However, little is known about the extent of this modification and its associated functional effects in the brain under physiological conditions. We employed mass spectrometry (MS)-based methodologies to interrogate the S-nitrosocysteine proteome in wild-type (WT), neuronal nitric oxide synthase-deficient (nNOS-/-), -
The Mitochondrial Pentatricopeptide Repeat Protein PPR18 Is Required for the Cis-Splicing of Nad4 Intron 1 and Essential to Seed Development in Maize
International Journal of Molecular Sciences Article The Mitochondrial Pentatricopeptide Repeat Protein PPR18 Is Required for the cis-Splicing of nad4 Intron 1 and Essential to Seed Development in Maize Rui Liu 1, Shi-Kai Cao 1 , Aqib Sayyed 1, Chunhui Xu 1, Feng Sun 1, Xiaomin Wang 2 and Bao-Cai Tan 1,* 1 Key Laboratory of Plant Development and Environment Adaptation Biology, Ministry of Education, School of Life Sciences, Shandong University, Qingdao 266237, China; [email protected] (R.L.); [email protected] (S.-K.C.); [email protected] (A.S.); [email protected] (C.X.); [email protected] (F.S.) 2 Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, School of Life Sciences, Lanzhou University, Lanzhou 730000, China; [email protected] * Correspondence: [email protected] Received: 10 May 2020; Accepted: 2 June 2020; Published: 5 June 2020 Abstract: Pentatricopeptide repeat (PPR) protein comprises a large family, participating in various aspects of organellar RNA metabolism in land plants. There are approximately 600 PPR proteins in maize, but the functions of many PPR proteins remain unknown. In this study, we defined the function of PPR18 in the cis-splicing of nad4 intron 1 in mitochondria and seed development in maize. Loss function of PPR18 seriously impairs embryo and endosperm development, resulting in the empty pericarp (emp) phenotype in maize. PPR18 encodes a mitochondrion-targeted P-type PPR protein with 18 PPR motifs. Transcripts analysis indicated that the splicing of nad4 intron 1 is impaired in the ppr18 mutant, resulting in the absence of nad4 transcript, leading to severely reduced assembly and activity of mitochondrial complex I and dramatically reduced respiration rate. -
Purification and Characterization of Glutamate Decarboxylase
Food Sci. Technol. Res., 9 (3), 283–287, 2003 Purification and Characterization of Glutamate Decarboxylase from Aspergillus oryzae Kimi TSUCHIYA,1 Kenryo NISHIMURA1 and Masayoshi IWAHARA2 1Kumamoto Industrial Research Institute, Higashimachi, Kumamoto, 862-0901, Japan 2Sojo University, 4-22-1, Ikeda, Kumamoto-City, Kumamoto, 860-0082, Japan Received December 25, 2002; Accepted June 14, 2003 We purified glutamate decarboxylase (GAD) [EC4.1.1.15] from Aspergillus oryzae and characterized its biochem- ical and kinetic properties. GAD was purified by ammonium sulfate at 30–70% saturation and chromatographies on Sephacryl S-300, DEAE-FF and CM-FF. The purification of GAD from the crude enzyme solution was 40-fold and the recovery rate was 4.9%. About 230 g of purified enzyme was obtained from 20 g of the mycelia of A. oryzae. The purified preparation of the enzyme showed a single protein band on SDS-PAGE. The molecular weight of purified GAD by SDS-PAGE and gel filtration was estimated to be 48 kDa and 300 kDa, respectively, suggesting that purified GAD had a hexameric structure. The Km value for L-glutamic acid, a substrate of the enzyme, was estimated to be 13 mM. The optimum pH and temperature of GAD were 5.5 and 60˚C, respectively. The GAD activity was stable up to 40˚C. Keywords: glutamate decarboxylase, Aspergillus oryzae, purification, ␥-amino-butyric acid Glutamate decarboxylase (GAD; EC4.1.1.15) produces ␥- production in food processing by effective utilization of the GAD amino-butyric acid (GABA) from glutamate. GABA has several from A. oryzae. In this study, we purified GAD from the myceli- physiological effects on the human body, including neurotrans- um of A. -
Dependent Enzymes. a Hypothesis Philipp Christen*, Patrik Kasper, Heinz Gehring, Michael Sterk Bioehemisches Institut, Universitgit Ziirich, Winterthurerstr
FEBS Letters 389 (1996) 12-14 FEBS 16909 Minireview Stereochemical constraint in the evolution of pyridoxal-5'-phosphate- dependent enzymes. A hypothesis Philipp Christen*, Patrik Kasper, Heinz Gehring, Michael Sterk Bioehemisches Institut, Universitgit Ziirich, Winterthurerstr. 190, CH-8057 Ziirieh, Switzerland Received 11 January 1996 cular evolution of B6 enzymes. Alanine aminotransferase, as- Abstract In the transamination reactions undergone by pyri- doxal-5'-phosphate-dependent enzymes that act on L-amino partate aminotransferase, 2,2-dialkylglycine decarboxylase, acids, the C4' atom of the cofactor is without exception glutamate decarboxylase, and serine hydroxymethyltransfer- protonated from the si side. This invariant absolute stereo- ase indeed belong to the large c~ family of homologous B6 chemistry of enzymes not all of which are evolutionarily related enzymes [1-3]. However, the pyridoxal-5'-phosphate-depen- to each other and the inverse stereochemistry in the case of D- dent 13 subunit of tryptophan synthase which shows the alanine aminotransferase might reflect a stereochemical con- same stereochemistry is a member of the [3 family of B6 en- straint in the evolution of these enzymes rather than an zymes which is not homologous with the e~ family [1,4]. accidental historical trait passed on from a common ancestor (About the seventh enzyme, pyridoxamine pyruvate amino- enzyme. Conceivably, the coenzyme and substrate binding sites transferase, no information on primary or tertiary structure of primordial pyridoxal-5'-phosphate-dependent -
(12) Patent Application Publication (10) Pub. No.: US 2016/0115499 A1 CUI Et Al
US 2016O115499A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0115499 A1 CUI et al. (43) Pub. Date: Apr. 28, 2016 (54) MATERALS AND METHODS FOR Publication Classification CONTROLLING BUNDLE SHEATH CELL FATE AND FUNCTION IN PLANTS (51) Int. Cl. CI2N 5/82 (2006.01) (71) Applicant: FLORIDA STATE UNIVERSITY (52) U.S. Cl. RESEARCH FOUNDATION, INC., CPC ........ CI2N 15/8269 (2013.01); C12N 15/8225 Tallahassee, FL (US) (2013.01) (57) ABSTRACT (72) Inventors: HONGCHANG CUI, TALLAHASSEE, The Subject invention concerns materials and methods for FL (US); DANYUKONG, increasing and/or improving photosynthetic efficiency in BLACKSBURG, VA (US); YUELING plants, and in particular, C3 plants. In particular, the Subject HAO, TALLAHASSEE, FL (US) invention provides for means to increase the number of bundle sheath (BS) cells in plants, to improve the efficiency of (21) Appl. No.: 14/898,046 photosynthesis in BS cells, and to increase channels between BS and mesophyll (M) cells. In one embodiment, a method of (22) PCT Fled: Jun. 11, 2014 the invention concerns altering the expression level or pattern of one or more of SHR, SCR, and/or SCL23 in a plant. The (86) PCT NO.: PCT/US2014/041975 Subject invention also pertains to genetically modified plants, S371 (c)(1), and in particular, C3 plants, that exhibit increased expression (2) Date: Dec. 11, 2015 of one or more of SHR, SCR, and/or SCL23. Transformed and transgenic plants are contemplated within the scope of the invention. The Subject invention also concerns methods for increasing expression of photosynthetically important Related U.S. -
The 58-Kilodalton Calmodulin-Binding Glutamate Decarboxylase Is a Ubiquitous Protein in Petunia Organs and Its Expression Is Developmentally Regulated'
Plant Physiol. (1994) 106: 1381-1387 The 58-Kilodalton Calmodulin-Binding Glutamate Decarboxylase Is a Ubiquitous Protein in Petunia Organs and Its Expression Is Developmentally Regulated' Yali Chen, Gideon Baum, and Hillel Fro"* Department of Plant Genetics, Weizmann Institute of Science, 761O0 Rehovot, Israel et al., 1984); heat shock (Mayer et al., 1990); and water stress A cDNA coding for a 58-kD calcium-dependent calmodulin (Rhodes et al., 1986), which is consistent with this role. (CaM)-binding glutamate decarboxylase (GAD) previously isolated Moreover, GAD activity is enhanced at relatively acidic pH in our laboratory from petunia (Petunia hybrida) (G. Baum, Y. (Snedden et al., 1992; Crawford et al., 1994). It was also Chen, T. Arazi, H. Takatsuji, H. Fromm [1993] J Biol Chem 268: suggested that transamination of a-ketoglutarate by GABA 19610-19617) was used to conduct molecular studies of GAD (producing succinic semialdehyde and glutamate) could reg- expression. GAD expression was studied during petunia organ ulate carbon flow through the tricarboxylic acid cycle by development using the GAD cDNA as a probe to detect the GAD mRNA and by the anti-recombinant GAD serum to monitor the bypassing the direct conversion of a-ketoglutarate to succi- levels of GAD. GAD activity was studied in extracts of organs in nate, a step that may be inhibited under certain physiological the course of development. lhe 58-kD CaM-binding GAD is ex- situations (Dixon and Fowden, 1961). In addition, GABA can pressed in all petunia organs tested (flowers and all floral parts, be transaminated even more effectively with pyruvate to leaves, stems, roots, and seeds).