Limited Survival and Impaired Hepatic Fasting Metabolism in Mice with Constitutive Rag Gtpase Signaling
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Common Variants in SOX-2 and Congenital Cataract Genes Contribute to Age-Related Nuclear Cataract
ARTICLE https://doi.org/10.1038/s42003-020-01421-2 OPEN Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract Ekaterina Yonova-Doing et al.# 1234567890():,; Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10−16) with nuclear cataract and identified five new loci associated with this dis- ease: SOX2-OT (rs9842371, P = 1.7 × 10−19), TMPRSS5 (rs4936279, P = 2.5 × 10−10), LINC01412 (rs16823886, P = 1.3 × 10−9), GLTSCR1 (rs1005911, P = 9.8 × 10−9), and COMMD1 (rs62149908, P = 1.2 × 10−8). The results suggest a strong link of age-related nuclear cat- aract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye. #A list of authors and their affiliations appears at the end of the paper. COMMUNICATIONS BIOLOGY | (2020) 3:755 | https://doi.org/10.1038/s42003-020-01421-2 | www.nature.com/commsbio 1 ARTICLE COMMUNICATIONS BIOLOGY | https://doi.org/10.1038/s42003-020-01421-2 ge-related cataract is the leading cause of blindness, structure (meta-analysis genomic inflation factor λ = 1.009, accounting for more than one-third of blindness Supplementary Table 4 and Supplementary Fig. -
Supplementary Table S4. FGA Co-Expressed Gene List in LUAD
Supplementary Table S4. FGA co-expressed gene list in LUAD tumors Symbol R Locus Description FGG 0.919 4q28 fibrinogen gamma chain FGL1 0.635 8p22 fibrinogen-like 1 SLC7A2 0.536 8p22 solute carrier family 7 (cationic amino acid transporter, y+ system), member 2 DUSP4 0.521 8p12-p11 dual specificity phosphatase 4 HAL 0.51 12q22-q24.1histidine ammonia-lyase PDE4D 0.499 5q12 phosphodiesterase 4D, cAMP-specific FURIN 0.497 15q26.1 furin (paired basic amino acid cleaving enzyme) CPS1 0.49 2q35 carbamoyl-phosphate synthase 1, mitochondrial TESC 0.478 12q24.22 tescalcin INHA 0.465 2q35 inhibin, alpha S100P 0.461 4p16 S100 calcium binding protein P VPS37A 0.447 8p22 vacuolar protein sorting 37 homolog A (S. cerevisiae) SLC16A14 0.447 2q36.3 solute carrier family 16, member 14 PPARGC1A 0.443 4p15.1 peroxisome proliferator-activated receptor gamma, coactivator 1 alpha SIK1 0.435 21q22.3 salt-inducible kinase 1 IRS2 0.434 13q34 insulin receptor substrate 2 RND1 0.433 12q12 Rho family GTPase 1 HGD 0.433 3q13.33 homogentisate 1,2-dioxygenase PTP4A1 0.432 6q12 protein tyrosine phosphatase type IVA, member 1 C8orf4 0.428 8p11.2 chromosome 8 open reading frame 4 DDC 0.427 7p12.2 dopa decarboxylase (aromatic L-amino acid decarboxylase) TACC2 0.427 10q26 transforming, acidic coiled-coil containing protein 2 MUC13 0.422 3q21.2 mucin 13, cell surface associated C5 0.412 9q33-q34 complement component 5 NR4A2 0.412 2q22-q23 nuclear receptor subfamily 4, group A, member 2 EYS 0.411 6q12 eyes shut homolog (Drosophila) GPX2 0.406 14q24.1 glutathione peroxidase -
Aneuploidy: Using Genetic Instability to Preserve a Haploid Genome?
Health Science Campus FINAL APPROVAL OF DISSERTATION Doctor of Philosophy in Biomedical Science (Cancer Biology) Aneuploidy: Using genetic instability to preserve a haploid genome? Submitted by: Ramona Ramdath In partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical Science Examination Committee Signature/Date Major Advisor: David Allison, M.D., Ph.D. Academic James Trempe, Ph.D. Advisory Committee: David Giovanucci, Ph.D. Randall Ruch, Ph.D. Ronald Mellgren, Ph.D. Senior Associate Dean College of Graduate Studies Michael S. Bisesi, Ph.D. Date of Defense: April 10, 2009 Aneuploidy: Using genetic instability to preserve a haploid genome? Ramona Ramdath University of Toledo, Health Science Campus 2009 Dedication I dedicate this dissertation to my grandfather who died of lung cancer two years ago, but who always instilled in us the value and importance of education. And to my mom and sister, both of whom have been pillars of support and stimulating conversations. To my sister, Rehanna, especially- I hope this inspires you to achieve all that you want to in life, academically and otherwise. ii Acknowledgements As we go through these academic journeys, there are so many along the way that make an impact not only on our work, but on our lives as well, and I would like to say a heartfelt thank you to all of those people: My Committee members- Dr. James Trempe, Dr. David Giovanucchi, Dr. Ronald Mellgren and Dr. Randall Ruch for their guidance, suggestions, support and confidence in me. My major advisor- Dr. David Allison, for his constructive criticism and positive reinforcement. -
Supplementary Material
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) J Neurol Neurosurg Psychiatry Page 1 / 45 SUPPLEMENTARY MATERIAL Appendix A1: Neuropsychological protocol. Appendix A2: Description of the four cases at the transitional stage. Table A1: Clinical status and center proportion in each batch. Table A2: Complete output from EdgeR. Table A3: List of the putative target genes. Table A4: Complete output from DIANA-miRPath v.3. Table A5: Comparison of studies investigating miRNAs from brain samples. Figure A1: Stratified nested cross-validation. Figure A2: Expression heatmap of miRNA signature. Figure A3: Bootstrapped ROC AUC scores. Figure A4: ROC AUC scores with 100 different fold splits. Figure A5: Presymptomatic subjects probability scores. Figure A6: Heatmap of the level of enrichment in KEGG pathways. Kmetzsch V, et al. J Neurol Neurosurg Psychiatry 2021; 92:485–493. doi: 10.1136/jnnp-2020-324647 BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) J Neurol Neurosurg Psychiatry Appendix A1. Neuropsychological protocol The PREV-DEMALS cognitive evaluation included standardized neuropsychological tests to investigate all cognitive domains, and in particular frontal lobe functions. The scores were provided previously (Bertrand et al., 2018). Briefly, global cognitive efficiency was evaluated by means of Mini-Mental State Examination (MMSE) and Mattis Dementia Rating Scale (MDRS). Frontal executive functions were assessed with Frontal Assessment Battery (FAB), forward and backward digit spans, Trail Making Test part A and B (TMT-A and TMT-B), Wisconsin Card Sorting Test (WCST), and Symbol-Digit Modalities test. -
Sec16b Is Involved in the Endoplasmic Reticulum Export of the Peroxisomal Membrane Biogenesis Factor Peroxin 16 (Pex16) in Mammalian Cells
Sec16B is involved in the endoplasmic reticulum export of the peroxisomal membrane biogenesis factor peroxin 16 (Pex16) in mammalian cells Shusuke Yonekawaa, Akiko Furunoa, Takashi Babaa, Yukio Fujikib,c, Yuta Ogasawarad, Akitsugu Yamamotod, Mitsuo Tagayaa, and Katsuko Tania,1 aSchool of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan; bDepartment of Biology, Faculty of Sciences, Kyushu University Graduate School, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan; cCore Research of Evolutional Science and Technology, Japan Science and Technology Agency, Chiyoda-ku, Tokyo 102-0075, Japan; and dFaculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan Edited by Randy Schekman, University of California, Berkeley, CA, and approved June 20, 2011 (received for review March 1, 2011) Sec16 plays a key role in the formation of coat protein II vesicles, from the endoplasmic reticulum (ER) en route to peroxisomes which mediate protein transport from the endoplasmic reticulum (13). In addition, several lines of evidence suggest that the ER (ER) to the Golgi apparatus. Mammals have two Sec16 isoforms: participates in the de novo formation of peroxisomes (13–20). A Sec16A, which is a longer primary ortholog of yeast Sec16, and very recent study involving a yeast cell-free system revealed Sec16B, which is a shorter distant ortholog. Previous studies have that ER-peroxisome carriers are formed in a Pex19-dependent shown that Sec16B, as well as Sec16A, defines ER exit sites, where manner (21). coat protein II vesicles are formed in mammalian cells. Here, we In this report, we show that Sec16B plays an important role in reveal an unexpected role of Sec16B in the biogenesis of mamma- the transport of Pex16 from the ER to peroxisomes in mam- lian peroxisomes. -
Construction of a Natural Panel of 11P11.2 Deletions and Further Delineation of the Critical Region Involved in Potocki–Shaffer Syndrome
European Journal of Human Genetics (2005) 13, 528–540 & 2005 Nature Publishing Group All rights reserved 1018-4813/05 $30.00 www.nature.com/ejhg ARTICLE Construction of a natural panel of 11p11.2 deletions and further delineation of the critical region involved in Potocki–Shaffer syndrome Keiko Wakui1,12, Giuliana Gregato2,3,12, Blake C Ballif2, Caron D Glotzbach2,4, Kristen A Bailey2,4, Pao-Lin Kuo5, Whui-Chen Sue6, Leslie J Sheffield7, Mira Irons8, Enrique G Gomez9, Jacqueline T Hecht10, Lorraine Potocki1,11 and Lisa G Shaffer*,2,4 1Department of Molecular & Human Genetics, Baylor College of Medicine, Houston, TX, USA; 2Health Research and Education Center, Washington State University, Spokane, WA, USA; 3Dip. Patologia Umana ed Ereditaria, Sez. Biologia Generale e Genetica Medica, Universita` degli Studi di Pavia, Italy; 4Sacred Heart Medical Center, Spokane, WA, USA; 5Department of Obstetrics and Gynecology, National Cheng-Kung University Medical College, Taiwan; 6Department of Pediatrics, Taipei Municipal Women and Children’s Hospital, Taiwan; 7Genetic Health Services Victoria, Murdoch Children’s Research Institute, Department of Paediatrics, University of Melbourne, Victoria, Australia; 8Division of Genetics, Department of Medicine, Children’s Hospital, Harvard Medical School, Boston, MA, USA; 9Area de Gene´tica, Centro de Desarrollo Infantil y Departamento de Pediatrı´a Hospital Materno Infantil-Hospital Regional Universitario ‘Infanta Cristina’, Badajoz, Spain; 10Department of Pediatrics, University of Texas Medical School at Houston, TX, USA; 11Texas Children’s Hospital, Houston, TX, USA Potocki–Shaffer syndrome (PSS) is a contiguous gene deletion syndrome that results from haploinsufficiency of at least two genes within the short arm of chromosome 11[del(11)(p11.2p12)]. -
Inheritest 500 PLUS
Inheritest® 500 PLUS 525 genes Specimen ID: 00000000010 Container ID: H0651 Control ID: Acct #: LCA-BN Phone: SAMPLE REPORT, F-630049 Patient Details Specimen Details Physician Details DOB: 01/01/1991 Date Collected: 08/05/2019 12:00 (Local) Ordering: Age (yyy/mm/dd): 028/07/04 Date Received: 08/06/2019 Referring: Gender: Female Date Entered: 08/06/2019 ID: Patient ID: 00000000010 Date Reported: 08/21/2019 15:29 (Local) NPI: Ethnicity: Unknown Specimen Type: Blood Lab ID: MNEGA Indication: Carrier screening Genetic Counselor: None SUMMARY: POSITIVE POSITIVE RESULTS DISORDER (GENE) RESULTS INTERPRETATION Spinal muscular atrophy AT RISK AT RISK to be a silent carrier (2+0). For ethnic-specific risk (SMN1) 2 copies of SMN1; positive for revisions see Methods/Limitations. Genetic counseling is NMID: NM_000344 c.*3+80T>G SNP recommended. Risk: AT INCREASED RISK FOR AFFECTED PREGNANCY. See Additional Clinical Information. NEGATIVE RESULTS DISORDER (GENE) RESULTS INTERPRETATION Cystic fibrosis NEGATIVE This result reduces, but does not eliminate the risk to be a (CFTR) carrier. NMID: NM_000492 Risk: NOT at an increased risk for an affected pregnancy. Fragile X syndrome NEGATIVE: Not a carrier of a fragile X expansion. (FMR1) 29 and 36 repeats NMID: NM_002024 Risk: NOT at an increased risk for an affected pregnancy. ALL OTHER DISORDERS NEGATIVE This result reduces, but does not eliminate the risk to be a carrier. Risk: The individual is NOT at an increased risk for having a pregnancy that is affected with one of the disorders covered by this test. For partner's gene-specific risks, visit www.integratedgenetics.com. -
Hamdan Medical Journal 2012; 5:313–326 (
Hamdan Medical Journal 2012; 5:313–326 (http://dx.doi.org/10.7707/hmj.v5i3.212) REVIEW FOR THE SHEIKH HAMDAN BIN RASHID AL MAKTOUM AWARD FOR MEDICAL SCIENCES Clinical, biochemical and genetic aspects of peroxisomal disorders – an expanding group of genetic diseases in humans Ronald JA Wanders University of Amsterdam, Academic Medical Centre, Department of Clinical Chemistry and Paediatrics, Emma Children’s Hospital, Laboratory Genetic Metabolic Diseases, Amsterdam, the Netherlands Abstract clitoris hypertrophy, camptodactyly and simian creases. Unaware of this publication Smith, Opitz and Zellweger syndrome (ZS) in its classic form is an autosomal recessive lethal 2 disease characterized by the absence of morphologically recognizable Inhorn in 1965 described ‘a syndrome of multiple peroxisomes. Detailed studies on ZS in the early 1980s have led to developmental defects including polycystic kidneys the discovery of a set of peroxisomal biomarkers in blood which has and intrahepatic biliary dysgenesis in two sibs’, revolutionized our knowledge about peroxisomes and peroxisomal disorders, who presented with a large number of comparable and formed the basis for the discovery of the group of peroxisomal diseases defects including severe hypotonia, high forehead, known at present. Peroxisomal disorders are classi!ed into two distinct shallow supraorbital ridges, camptodactyly, minor groups including the disorders of peroxisome biogenesis (group 1) and anomalies of the eyes, ears, palate and hands, peroxisome function (group 2). The enzymatic and molecular basis of most and failure to thrive. Two years later, Passarge and peroxisomal disorders has been identi!ed through the years and pre- and McAdams3 described #ve sisters with similar clinical post-natal diagnostic methods have been established. -
The Neuroprotective Role of the GM1 Oligosaccharide, Ii3neu5ac-Gg4, In
Molecular Neurobiology (2019) 56:6673–6702 https://doi.org/10.1007/s12035-019-1556-8 The Neuroprotective Role of the GM1 Oligosaccharide, 3 II Neu5Ac-Gg4, in Neuroblastoma Cells Elena Chiricozzi1 & Margherita Maggioni1 & Erika di Biase1 & Giulia Lunghi1 & Maria Fazzari1 & Nicoletta Loberto 1 & Maffioli Elisa2 & Francesca Grassi Scalvini2 & Gabriella Tedeschi 2,3 & Sandro Sonnino1 Received: 10 January 2019 /Accepted: 13 March 2019 /Published online: 26 March 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract 3 Recently, we demonstrated that the GM1 oligosaccharide, II Neu5Ac-Gg4 (OligoGM1), administered to cultured murine Neuro2a neuroblastoma cells interacts with the NGF receptor TrkA, leading to the activation of the ERK1/2 downstream pathway and to cell differentiation. To understand how the activation of the TrkA pathway is able to trigger key biochemical signaling, we performed a proteomic analysis on Neuro2a cells treated with 50 μM OligoGM1 for 24 h. Over 3000 proteins were identified. Among these, 324 proteins were exclusively expressed in OligoGM1-treated cells. Interestingly, several proteins expressed only in OligoGM1-treated cells are involved in biochemical mechanisms with a neuroprotective potential, reflecting the GM1 neuroprotective effect. In addition, we found that the exogenous administration of OligoGM1 reduced the cellular oxidative stress in Neuro2a cells and conferred protection against MPTP neurotoxicity. These results confirm and reinforce the idea that the molecular mechanisms underlying the GM1 neurotrophic and neuroprotective effects depend on its oligosaccharide chain, suggesting the activation of a positive signaling starting at plasma membrane level. Keywords GM1 ganglioside . GM1 oligosaccharide chain . TrkA neurotrophin receptor . Plasma membrane signaling . Neuroprotection . -
Renoprotective Effect of Combined Inhibition of Angiotensin-Converting Enzyme and Histone Deacetylase
BASIC RESEARCH www.jasn.org Renoprotective Effect of Combined Inhibition of Angiotensin-Converting Enzyme and Histone Deacetylase † ‡ Yifei Zhong,* Edward Y. Chen, § Ruijie Liu,*¶ Peter Y. Chuang,* Sandeep K. Mallipattu,* ‡ ‡ † | ‡ Christopher M. Tan, § Neil R. Clark, § Yueyi Deng, Paul E. Klotman, Avi Ma’ayan, § and ‡ John Cijiang He* ¶ *Department of Medicine, Mount Sinai School of Medicine, New York, New York; †Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; ‡Department of Pharmacology and Systems Therapeutics and §Systems Biology Center New York, Mount Sinai School of Medicine, New York, New York; |Baylor College of Medicine, Houston, Texas; and ¶Renal Section, James J. Peters Veterans Affairs Medical Center, New York, New York ABSTRACT The Connectivity Map database contains microarray signatures of gene expression derived from approximately 6000 experiments that examined the effects of approximately 1300 single drugs on several human cancer cell lines. We used these data to prioritize pairs of drugs expected to reverse the changes in gene expression observed in the kidneys of a mouse model of HIV-associated nephropathy (Tg26 mice). We predicted that the combination of an angiotensin-converting enzyme (ACE) inhibitor and a histone deacetylase inhibitor would maximally reverse the disease-associated expression of genes in the kidneys of these mice. Testing the combination of these inhibitors in Tg26 mice revealed an additive renoprotective effect, as suggested by reduction of proteinuria, improvement of renal function, and attenuation of kidney injury. Furthermore, we observed the predicted treatment-associated changes in the expression of selected genes and pathway components. In summary, these data suggest that the combination of an ACE inhibitor and a histone deacetylase inhibitor could have therapeutic potential for various kidney diseases. -
Perkinelmer Genomics to Request the Saliva Swab Collection Kit for Patients That Cannot Provide a Blood Sample As Whole Blood Is the Preferred Sample
Autism and Intellectual Disability TRIO Panel Test Code TR002 Test Summary This test analyzes 2429 genes that have been associated with Autism and Intellectual Disability and/or disorders associated with Autism and Intellectual Disability with the analysis being performed as a TRIO Turn-Around-Time (TAT)* 3 - 5 weeks Acceptable Sample Types Whole Blood (EDTA) (Preferred sample type) DNA, Isolated Dried Blood Spots Saliva Acceptable Billing Types Self (patient) Payment Institutional Billing Commercial Insurance Indications for Testing Comprehensive test for patients with intellectual disability or global developmental delays (Moeschler et al 2014 PMID: 25157020). Comprehensive test for individuals with multiple congenital anomalies (Miller et al. 2010 PMID 20466091). Patients with autism/autism spectrum disorders (ASDs). Suspected autosomal recessive condition due to close familial relations Previously negative karyotyping and/or chromosomal microarray results. Test Description This panel analyzes 2429 genes that have been associated with Autism and ID and/or disorders associated with Autism and ID. Both sequencing and deletion/duplication (CNV) analysis will be performed on the coding regions of all genes included (unless otherwise marked). All analysis is performed utilizing Next Generation Sequencing (NGS) technology. CNV analysis is designed to detect the majority of deletions and duplications of three exons or greater in size. Smaller CNV events may also be detected and reported, but additional follow-up testing is recommended if a smaller CNV is suspected. All variants are classified according to ACMG guidelines. Condition Description Autism Spectrum Disorder (ASD) refers to a group of developmental disabilities that are typically associated with challenges of varying severity in the areas of social interaction, communication, and repetitive/restricted behaviors. -
Genetic Classification and Mutational Spectrum of More Than 600 Patients
Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder Merel Sanne Ebberink, Petra Mooyer, Jeannette Gootjes, Janet Koster, Ronald J.A. Wanders, Hans Waterham To cite this version: Merel Sanne Ebberink, Petra Mooyer, Jeannette Gootjes, Janet Koster, Ronald J.A. Wanders, et al.. Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syn- drome spectrum disorder. Human Mutation, Wiley, 2010, 32 (1), pp.59. 10.1002/humu.21388. hal-00599469 HAL Id: hal-00599469 https://hal.archives-ouvertes.fr/hal-00599469 Submitted on 10 Jun 2011 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Human Mutation Genetic classification and mutational spectrum of more than 600 patients with a Zellweger syndrome spectrum disorder For Peer Review Journal: Human Mutation Manuscript ID: humu-2010-0170.R1 Wiley - Manuscript type: Research Article Date Submitted by the 30-Aug-2010 Author: Complete List of Authors: Ebberink, Merel; Academic Medical Centre, University of Amsterdam, Laboratoy