Detailed Review Paper on Retinoid Pathway Signalling
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De Novo MEIS2 Mutation Causes Syndromic Developmental Delay with Persistent Gastro-Esophageal Reflux
Journal of Human Genetics (2016) 61, 835–838 & 2016 The Japan Society of Human Genetics All rights reserved 1434-5161/16 www.nature.com/jhg SHORT COMMUNICATION De novo MEIS2 mutation causes syndromic developmental delay with persistent gastro-esophageal reflux Atsushi Fujita1, Bertrand Isidor2,3, Hugues Piloquet4, Pierre Corre5, Nobuhiko Okamoto6, Mitsuko Nakashima1, Yoshinori Tsurusaki1, Hirotomo Saitsu1, Noriko Miyake1 and Naomichi Matsumoto1 MEIS2 aberrations are considered to be the cause of intellectual disability, cleft palate and cardiac septal defect, as MEIS2 copy number variation is often observed with these phenotypes. To our knowledge, only one nucleotide-level change— specifically, an in-frame MEIS2 deletion—has so far been reported. Here, we report a female patient with a de novo nonsense mutation (c.611C4G, p.Ser204*) in MEIS2. She showed severe intellectual disability, moderate motor/verbal developmental delay, cleft palate, cardiac septal defect, hypermetropia, severe feeding difficulties with gastro-esophageal reflux and constipation. By reviewing this patient and previous patients with MEIS2 point mutations, we found that feeding difficulty with gastro-esophageal reflux appears to be one of the core clinical features of MEIS2 haploinsufficiency, in addition to intellectual disability, cleft palate and cardiac septal defect. Journal of Human Genetics (2016) 61, 835–838; doi:10.1038/jhg.2016.54; published online 26 May 2016 INTRODUCTION at the homeodomain may interfere with DNA binding. Moreover, Meis homeobox 2 (MEIS2;alsoknownasMRG1, NM_170677.4) this female patient also presented with various anomalous features encodes a homeobox (HOX) protein belonging to the three amino and developmental abnormalities. Here, we report on another acid loop extension (TALE) superfamily. -
Expression of HOXB2, a Retinoic Acid Signalingtarget in Pancreatic Cancer and Pancreatic Intraepithelial Neoplasia Davendra Segara,1Andrew V
Cancer Prevention Expression of HOXB2, a Retinoic Acid SignalingTarget in Pancreatic Cancer and Pancreatic Intraepithelial Neoplasia Davendra Segara,1Andrew V. Biankin,1, 2 James G. Kench,1, 3 Catherine C. Langusch,1Amanda C. Dawson,1 David A. Skalicky,1David C. Gotley,4 Maxwell J. Coleman,2 Robert L. Sutherland,1and Susan M. Henshall1 Abstract Purpose: Despite significant progress in understanding the molecular pathology of pancreatic cancer and its precursor lesion: pancreatic intraepithelial neoplasia (PanIN), there remain no molecules with proven clinical utility as prognostic or therapeutic markers. Here, we used oligo- nucleotide microarrays to interrogate mRNA expression of pancreatic cancer tissue and normal pancreas to identify novel molecular pathways dysregulated in the development and progression of pancreatic cancer. Experimental Design: RNA was hybridized toAffymetrix Genechip HG-U133 oligonucleotide microarrays. A relational database integrating data from publicly available resources was created toidentify candidate genes potentially relevant topancreatic cancer. The protein expression of one candidate, homeobox B2 (HOXB2), in PanIN and pancreatic cancer was assessed using immunohistochemistry. Results: We identified aberrant expression of several components of the retinoic acid (RA) signaling pathway (RARa,MUC4,Id-1,MMP9,uPAR,HB-EGF,HOXB6,andHOXB2),manyof which are known to be aberrantly expressed in pancreatic cancer and PanIN. HOXB2, a down- stream target of RA, was up-regulated 6.7-fold in pancreatic cancer compared with normal pan- creas. Immunohistochemistry revealed ectopic expression of HOXB2 in15% of early PanINlesions and 48 of 128 (38%) pancreatic cancer specimens. Expression of HOXB2 was associated with nonresectable tumors and was an independent predictor of poor survival in resected tumors. -
Sonic Hedgehog-Gli1 Signaling and Cellular Retinoic Acid Binding Protein 1 Gene Regulation in Motor Neuron Differentiation and Diseases
International Journal of Molecular Sciences Article Sonic Hedgehog-Gli1 Signaling and Cellular Retinoic Acid Binding Protein 1 Gene Regulation in Motor Neuron Differentiation and Diseases Yu-Lung Lin y, Yi-Wei Lin y, Jennifer Nhieu y, Xiaoyin Zhang and Li-Na Wei * Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA; [email protected] (Y.-L.L.); [email protected] (Y.-W.L.); [email protected] (J.N.); [email protected] (X.Z.) * Correspondence: [email protected]; Tel.: +1-612-6259402 Contributed equally. y Received: 29 April 2020; Accepted: 7 June 2020; Published: 9 June 2020 Abstract: Cellular retinoic acid-binding protein 1 (CRABP1) is highly expressed in motor neurons. Degenerated motor neuron-like MN1 cells are engineered by introducing SODG93A or AR-65Q to model degenerated amyotrophic lateral sclerosis (ALS) or spinal bulbar muscular atrophy neurons. Retinoic acid (RA)/sonic hedgehog (Shh)-induced embryonic stem cells differentiation into motor neurons are employed to study up-regulation of Crabp1 by Shh. In SODG93A or AR-65Q MN1 neurons, CRABP1 level is reduced, revealing a correlation of motor neuron degeneration with Crabp1 down-regulation. Up-regulation of Crabp1 by Shh is mediated by glioma-associated oncogene homolog 1 (Gli1) that binds the Gli target sequence in Crabp10s neuron-specific regulatory region upstream of minimal promoter. Gli1 binding triggers chromatin juxtaposition with minimal promoter, activating transcription. Motor neuron differentiation and Crabp1 up-regulation are both inhibited by blunting Shh with Gli inhibitor GANT61. Expression data mining of ALS and spinal muscular atrophy (SMA) motor neurons shows reduced CRABP1, coincided with reduction in Shh-Gli1 signaling components. -
Cell Line-Dependent Variability of Coordinate Expression of P75ntr and CRABP1 and Modulation of Effects of Fenretinide on Neuroblastoma Cells
Hindawi Publishing Corporation Oxidative Medicine and Cellular Longevity Volume 2016, Article ID 7568287, 8 pages http://dx.doi.org/10.1155/2016/7568287 Research Article Cell Line-Dependent Variability of Coordinate Expression of p75NTR and CRABP1 and Modulation of Effects of Fenretinide on Neuroblastoma Cells Yaoli Pu Yang, Simeng Wang, Xingguo Li, and Nina F. Schor Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA Correspondence should be addressed to Nina F. Schor; nina [email protected] Received 10 September 2015; Revised 18 October 2015; Accepted 22 October 2015 Academic Editor: Giuseppe Filomeni Copyright © 2016 Yaoli Pu Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Neuroblastoma is a childhood neural crest tumor. Fenretinide, a retinoic acid analogue, induces accumulation of mitochondrial reactive oxygen species and consequent apoptosis in neuroblastoma cells. The p75 neurotrophin receptor (p75NTR) enhances the antineuroblastoma cell efficacy of fenretinide in vitro. We examined the role of the retinoid binding protein, CRABP1, in p75NTR- mediated potentiation of the efficacy of fenretinide. Knockdown and overexpression, respectively, of either p75NTR or CRABP1 were effected in neuroblastoma cell lines using standard techniques. Expression was determined by qRT-PCR and confirmed atthe protein level by Western blot. Metabolic viability was determined by Alamar blue assay. While protein content of CRABP1 correlated roughly with that of p75NTR in the three neuroblastoid or epithelioid human neuroblastoma cell lines studied, manipulation of p75NTR expression resulted in cell line-dependent, variable change in CRABP1 expression. -
(2017) Emerging Significance of Bile Acids
Texas Medical Center Digestive Diseases Center 8th Annual Frontiers in Digestive Diseases Symposium: Emerging Significance of Bile Acids in Digestive & Liver Diseases Saturday, February 11, 2017 Onstead Auditorium, Houston, Texas 77030 Table of Contents ....................................................................................................................................................................... 1 Agenda .......................................................................................................................................................................................... 2 CME Activity............................................................................................................................................................................... 3 List of Abstracts .................................................................................................................................................................... 4 - 6 Abstracts............................................................................................................................................................................... 7 - 41 TMC DDC Leadership ............................................................................................................................................................ 42 List of Participants ............................................................................................................................................................ 43 - 46 Acknowledgements -
Mice Exposed to N-Ethyl-N-Nitrosourea T
Proc. Nati. Acad. Sci. USA Vol. 89, pp. 7866-7870, September 1992 Genetics Mutational spectrum at the Hprt locus in splenic T cells of B6C3F1 mice exposed to N-ethyl-N-nitrosourea T. R. SKOPEK*tt, V. E. WALKER*, J. E. COCHRANEt, T. R. CRAFTt, AND N. F. CARIELLO* *Department of Pathology and tDepartment of Environmental Sciences and Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 Communicated by Kenneth M. Brinkhous, May 26, 1992 ABSTRACT We have determined the mutational spectrum quences for analysis. DGGE is based on the fact that the of N-ethyl-N-nitrosourea (ENU) in exon 3 of the hypoxanthine electrophoretic mobility of a DNA molecule in a polyacryl- guanine) phosphoribosyltransferase gene (Hprt) in splenic T amide gel is considerably reduced as the molecule becomes cells following in vivo exposure ofmale B6C3F1 mice (5-7 weeks partially melted (denatured). Mismatched heteroduplexes old) to ENU. Hpir mutants were isolated by culturing splenic formed by annealing wild-type and mutant DNA sequences T cells in microtiter dishes containing medium supplemented are always less stable than the corresponding perfectly base- with interleukin 2, concanavalin A, and 6-thiouanine. DNA paired homoduplexes and consequently melt at a lower was extracted from 6-thoa ne-sistant colonies and ampli- concentration of denaturant. Therefore, any mutant/wild- fied by the polymerase chain reaction (PCR) using primers type heteroduplex will always travel a shorter distance rel- flanking Hprt exon 3. Identification of mutant sequences and ative to wild-type homoduplexes in a gel containing a dient purification of mutant DNA from contaminating wild-type Hprt ofdenaturant. -
Table S1 the Four Gene Sets Derived from Gene Expression Profiles of Escs and Differentiated Cells
Table S1 The four gene sets derived from gene expression profiles of ESCs and differentiated cells Uniform High Uniform Low ES Up ES Down EntrezID GeneSymbol EntrezID GeneSymbol EntrezID GeneSymbol EntrezID GeneSymbol 269261 Rpl12 11354 Abpa 68239 Krt42 15132 Hbb-bh1 67891 Rpl4 11537 Cfd 26380 Esrrb 15126 Hba-x 55949 Eef1b2 11698 Ambn 73703 Dppa2 15111 Hand2 18148 Npm1 11730 Ang3 67374 Jam2 65255 Asb4 67427 Rps20 11731 Ang2 22702 Zfp42 17292 Mesp1 15481 Hspa8 11807 Apoa2 58865 Tdh 19737 Rgs5 100041686 LOC100041686 11814 Apoc3 26388 Ifi202b 225518 Prdm6 11983 Atpif1 11945 Atp4b 11614 Nr0b1 20378 Frzb 19241 Tmsb4x 12007 Azgp1 76815 Calcoco2 12767 Cxcr4 20116 Rps8 12044 Bcl2a1a 219132 D14Ertd668e 103889 Hoxb2 20103 Rps5 12047 Bcl2a1d 381411 Gm1967 17701 Msx1 14694 Gnb2l1 12049 Bcl2l10 20899 Stra8 23796 Aplnr 19941 Rpl26 12096 Bglap1 78625 1700061G19Rik 12627 Cfc1 12070 Ngfrap1 12097 Bglap2 21816 Tgm1 12622 Cer1 19989 Rpl7 12267 C3ar1 67405 Nts 21385 Tbx2 19896 Rpl10a 12279 C9 435337 EG435337 56720 Tdo2 20044 Rps14 12391 Cav3 545913 Zscan4d 16869 Lhx1 19175 Psmb6 12409 Cbr2 244448 Triml1 22253 Unc5c 22627 Ywhae 12477 Ctla4 69134 2200001I15Rik 14174 Fgf3 19951 Rpl32 12523 Cd84 66065 Hsd17b14 16542 Kdr 66152 1110020P15Rik 12524 Cd86 81879 Tcfcp2l1 15122 Hba-a1 66489 Rpl35 12640 Cga 17907 Mylpf 15414 Hoxb6 15519 Hsp90aa1 12642 Ch25h 26424 Nr5a2 210530 Leprel1 66483 Rpl36al 12655 Chi3l3 83560 Tex14 12338 Capn6 27370 Rps26 12796 Camp 17450 Morc1 20671 Sox17 66576 Uqcrh 12869 Cox8b 79455 Pdcl2 20613 Snai1 22154 Tubb5 12959 Cryba4 231821 Centa1 17897 -
Genetic Variability in the Italian Heavy Draught Horse from Pedigree Data and Genomic Information
Supplementary material for manuscript: Genetic variability in the Italian Heavy Draught Horse from pedigree data and genomic information. Enrico Mancin†, Michela Ablondi†, Roberto Mantovani*, Giuseppe Pigozzi, Alberto Sabbioni and Cristina Sartori ** Correspondence: [email protected] † These two Authors equally contributed to the work Supplementary Figure S1. Mares and foal of Italian Heavy Draught Horse (IHDH; courtesy of Cinzia Stoppa) Supplementary Figure S2. Number of Equivalent Generations (EqGen; above) and pedigree completeness (PC; below) over years in Italian Heavy Draught Horse population. Supplementary Table S1. Descriptive statistics of homozygosity (observed: Ho_obs; expected: Ho_exp; total: Ho_tot) in 267 genotyped individuals of Italian Heavy Draught Horse based on the number of homozygous genotypes. Parameter Mean SD Min Max Ho_obs 35,630.3 500.7 34,291 38,013 Ho_exp 35,707.8 64.0 35,010 35,740 Ho_tot 50,674.5 93.8 49,638 50,714 1 Definitions of the methods for inbreeding are in the text. Supplementary Figure S3. Values of BIC obtained by analyzing values of K from 1 to 10, corresponding on the same amount of clusters defining the proportion of ancestry in the 267 genotyped individuals. Supplementary Table S2. Estimation of genomic effective population size (Ne) traced back to 18 generations ago (Gen. ago). The linkage disequilibrium estimation, adjusted for sampling bias was also included (LD_r2), as well as the relative standard deviation (SD(LD_r2)). Gen. ago Ne LD_r2 SD(LD_r2) 1 100 0.009 0.014 2 108 0.011 0.018 3 118 0.015 0.024 4 126 0.017 0.028 5 134 0.019 0.031 6 143 0.021 0.034 7 156 0.023 0.038 9 173 0.026 0.041 11 189 0.029 0.046 14 213 0.032 0.052 18 241 0.036 0.058 Supplementary Table S3. -
Topoisomerase Ii Inhibitors Induce an Illegitimate Genome Rearrangement Common in Infant Leukemia
TOPOISOMERASE II INHIBITORS INDUCE AN ILLEGITIMATE GENOME REARRANGEMENT COMMON IN INFANT LEUKEMIA by Bhawana Bariar A dissertation submitted to the faculty of The University of North Carolina at Charlotte in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biology Charlotte 2013 Approved by: ______________________________ Dr. Christine Richardson ______________________________ Dr. Mark Clemens ______________________________ Dr. Laura Schrum ______________________________ Dr. Pinku Mukherjee ______________________________ Dr. Anthony Fodor ii ©2013 Bhawana Bariar ALL RIGHTS RESERVED iii ABSTRACT BHAWANA BARIAR. Topoisomerase II inhibitors induce an illegitimate genome rearrangement common in infant leukemia. (Under the direction of DR. CHRISTINE RICHARDSON) Infant acute leukemias account for ~30% of all malignancy seen in childhood across the Western world. They are aggressive and characterized by rapid onset shortly after birth. The majority of these have rearrangements involving the MLL (mixed lineage leukemia) gene. Although MLL fusion to more than 75 genes have been identified, AF9 is one of its most common translocation partners. Since MLL breakpoint sequences associated with infant acute leukemia are similar to those in secondary AML following exposure to the topoisomerase II (topo II) poison etoposide, it has been hypothesized that exposure during pregnancy to biochemically similar compounds may promote infant acute leukemia. Some studies have shown an epidemiological link between bioflavonoid intake -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
Liarozole Hydrochloride (BANM, USAN, Rinnm) Kinetin Hidrocloruro De Liarozol; Liarozole, Chlorhydrate De; Liarozoli 1
Isotretinoin/Liarozole 1603 Malignant neoplasms. Retinoids such as isotretinoin have 9. Matthay KK, et al. Treatment of high-risk neuroblastoma with Profile been studied in the treatment of various neoplastic or preneoplas- intensive chemotherapy, radiotherapy, autologous bone marrow Kinetin is a plant growth hormone that has been promoted in transplantation, and 13-cis-retinoic acid. N Engl J Med 1999; tic disorders. Although oral tretinoin is used for remission induc- 341: 1165–73. products for the management of photodamaged skin and hyper- tion in acute promyelocytic leukaemia (see p.1619), other retin- 10. Kohler JA, et al. A randomized trial of 13-cis retinoic acid in pigmentation but good evidence of efficacy appears to be lack- oids do not have an established role in the treatment of cancer. children with advanced neuroblastoma after high-dose therapy. ing. There may, however, be a place for the use of retinoids in the Br J Cancer 2000; 83: 1124–7. Preparations chemoprevention of some malignancies. Skin disorders. Apart from its established role in the treatment Proprietary Preparations (details are given in Part 3) There has been particular interest in the potential for retinoids to of acne (above), isotretinoin has been tried in many other skin Arg.: Kinerase†; Braz.: Kinerase; Hong Kong: Kinerase; Malaysia: Kin- prevent the formation of skin cancers (p.672) in patients at in- disorders not responding to usual therapy.1,2 Clinical responses to erase†; Mex.: Kinerase; Singapore: Kinerase; USA: Kinerase. creased risk. Maintenance immunosuppression may increase the oral isotretinoin have been reported1 in small numbers of patients incidence of pre-malignant and malignant skin lesions in solid with anogenital warts (p.1584), rosacea (p.1583), and lichen pla- organ transplant recipients; large numbers of lesions can develop nus (p.1580). -
Prox1regulates the Subtype-Specific Development of Caudal Ganglionic
The Journal of Neuroscience, September 16, 2015 • 35(37):12869–12889 • 12869 Development/Plasticity/Repair Prox1 Regulates the Subtype-Specific Development of Caudal Ganglionic Eminence-Derived GABAergic Cortical Interneurons X Goichi Miyoshi,1 Allison Young,1 Timothy Petros,1 Theofanis Karayannis,1 Melissa McKenzie Chang,1 Alfonso Lavado,2 Tomohiko Iwano,3 Miho Nakajima,4 Hiroki Taniguchi,5 Z. Josh Huang,5 XNathaniel Heintz,4 Guillermo Oliver,2 Fumio Matsuzaki,3 Robert P. Machold,1 and Gord Fishell1 1Department of Neuroscience and Physiology, NYU Neuroscience Institute, Smilow Research Center, New York University School of Medicine, New York, New York 10016, 2Department of Genetics & Tumor Cell Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee 38105, 3Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe 650-0047, Japan, 4Laboratory of Molecular Biology, Howard Hughes Medical Institute, GENSAT Project, The Rockefeller University, New York, New York 10065, and 5Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 Neurogliaform (RELNϩ) and bipolar (VIPϩ) GABAergic interneurons of the mammalian cerebral cortex provide critical inhibition locally within the superficial layers. While these subtypes are known to originate from the embryonic caudal ganglionic eminence (CGE), the specific genetic programs that direct their positioning, maturation, and integration into the cortical network have not been eluci- dated. Here, we report that in mice expression of the transcription factor Prox1 is selectively maintained in postmitotic CGE-derived cortical interneuron precursors and that loss of Prox1 impairs the integration of these cells into superficial layers. Moreover, Prox1 differentially regulates the postnatal maturation of each specific subtype originating from the CGE (RELN, Calb2/VIP, and VIP).