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Polyphosphate-Dependent Synthesis of ATP and ADP by the Family-2 Polyphosphate Kinases in Bacteria
Polyphosphate-dependent synthesis of ATP and ADP by the family-2 polyphosphate kinases in bacteria Boguslaw Noceka, Samvel Kochinyanb, Michael Proudfootb, Greg Brownb, Elena Evdokimovaa,b, Jerzy Osipiuka, Aled M. Edwardsa,b, Alexei Savchenkoa,b, Andrzej Joachimiaka,c,1, and Alexander F. Yakuninb,1 aMidwest Center for Structural Genomics and Structural Biology Center, Department of Biosciences, Argonne National Laboratory, 9700 South Cass Avenue, Building 202, Argonne, IL 60439; bBanting and Best Department of Medical Research, University of Toronto, Toronto, ON, Canada M5G 1L6; and cDepartment of Biochemistry and Molecular Biology, University of Chicago, 920 East 58th Street, Chicago, IL 60637 Edited by Robert Haselkorn, University of Chicago, Chicago, IL, and approved September 30, 2008 (received for review August 1, 2008) Inorganic polyphosphate (polyP) is a linear polymer of tens or hun- exopolysaccharide essential for the virulence of P. aeruginosa (12). dreds of phosphate residues linked by high-energy bonds. It is found In the social slime mold Dictyostelium discoideum, a different PPK in all organisms and has been proposed to serve as an energy source was found (DdPPK2) with sequence and properties similar to that in a pre-ATP world. This ubiquitous and abundant biopolymer plays of actin-related proteins (Arps) (14). DdPPK2 is a complex of 3 numerous and vital roles in metabolism and regulation in prokaryotes Arps (Arp1, Arp2, and Arpx) and resembles the actin family in and eukaryotes, but the underlying molecular mechanisms for most molecular weight, sequence, and filamentous structure. Remark- activities of polyP remain unknown. In prokaryotes, the synthesis and ably, DdPPK2 can polymerize into an actin-like filament concurrent utilization of polyP are catalyzed by 2 families of polyP kinases, PPK1 with the synthesis of polyP (14). -
ERK Phosphorylation of MED14 in Promoter Complexes During Mitogen-Induced Gene Activation by Elk-1 Matthew D
Published online 17 September 2013 Nucleic Acids Research, 2013, Vol. 41, No. 22 10241–10253 doi:10.1093/nar/gkt837 ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1 Matthew D. Galbraith1,2, Janice Saxton1,LiLi1, Samuel J. Shelton1,3, Hongmei Zhang1,4, Joaquin M. Espinosa2 and Peter E. Shaw1,* 1School of Biomedical Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, NG7 2UH, UK, 2Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, University of Colorado at Boulder, Boulder, CO 80309, USA, 3Department of Neurology, Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 90089, USA and 4Department of Pharmacology, Ningxia Medical University, Yinchuan 750004, China Received March 22, 2013; Revised August 21, 2013; Accepted August 28, 2013 ABSTRACT INTRODUCTION The ETS domain transcription factor Elk-1 stimu- The specific and temporal co-ordination of gene expres- lates expression of immediate early genes (IEGs) in sion is a fundamental process of cell-based life with response to mitogens. These events require phos- patterns of gene expression controlling proliferation, dif- phorylation of Elk-1 by extracellular signal-regulated ferentiation and cell death. Immediate early gene (IEG) expression has revealed how crucial regulatory events kinase (ERK) and phosphorylation-dependent inter- revolve around the interface between pathway-specific action of Elk-1 with co-activators, including histone transcription factors and components of the transcription acetyltransferases and the Mediator complex. Elk-1 machinery, involving a plethora of protein interactions also recruits ERK to the promoters of its target and modifications (1,2). -
Nitrate Prodrugs Able to Release Nitric Oxide in a Controlled and Selective
Europäisches Patentamt *EP001336602A1* (19) European Patent Office Office européen des brevets (11) EP 1 336 602 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.7: C07C 205/00, A61K 31/00 20.08.2003 Bulletin 2003/34 (21) Application number: 02425075.5 (22) Date of filing: 13.02.2002 (84) Designated Contracting States: (71) Applicant: Scaramuzzino, Giovanni AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU 20052 Monza (Milano) (IT) MC NL PT SE TR Designated Extension States: (72) Inventor: Scaramuzzino, Giovanni AL LT LV MK RO SI 20052 Monza (Milano) (IT) (54) Nitrate prodrugs able to release nitric oxide in a controlled and selective way and their use for prevention and treatment of inflammatory, ischemic and proliferative diseases (57) New pharmaceutical compounds of general effects and for this reason they are useful for the prep- formula (I): F-(X)q where q is an integer from 1 to 5, pref- aration of medicines for prevention and treatment of in- erably 1; -F is chosen among drugs described in the text, flammatory, ischemic, degenerative and proliferative -X is chosen among 4 groups -M, -T, -V and -Y as de- diseases of musculoskeletal, tegumental, respiratory, scribed in the text. gastrointestinal, genito-urinary and central nervous sys- The compounds of general formula (I) are nitrate tems. prodrugs which can release nitric oxide in vivo in a con- trolled and selective way and without hypotensive side EP 1 336 602 A1 Printed by Jouve, 75001 PARIS (FR) EP 1 336 602 A1 Description [0001] The present invention relates to new nitrate prodrugs which can release nitric oxide in vivo in a controlled and selective way and without the side effects typical of nitrate vasodilators drugs. -
1 Long-Read Genome Sequencing for the Diagnosis Of
bioRxiv preprint doi: https://doi.org/10.1101/2020.07.02.185447; this version posted September 14, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Long-read genome sequencing for the diagnosis of neurodevelopmental disorders Susan M. Hiatt1, James M.J. Lawlor1, Lori H. Handley1, Ryne C. Ramaker1, Brianne B. Rogers1,2, E. Christopher Partridge1, Lori Beth Boston1, Melissa Williams1, Christopher B. Plott1, Jerry Jenkins1, David E. Gray1, James M. Holt1, Kevin M. Bowling1, E. Martina Bebin3, Jane Grimwood1, Jeremy Schmutz1, Gregory M. Cooper1* 1HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA, 35806 2Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA, 35924 3Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA, 35924 *[email protected], 256-327-9490 Conflicts of Interest The authors all declare no conflicts of interest. 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.07.02.185447; this version posted September 14, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. Abstract Purpose Exome and genome sequencing have proven to be effective tools for the diagnosis of neurodevelopmental disorders (NDDs), but large fractions of NDDs cannot be attributed to currently detectable genetic variation. This is likely, at least in part, a result of the fact that many genetic variants are difficult or impossible to detect through typical short-read sequencing approaches. -
Whole-Genome Microarray Detects Deletions and Loss of Heterozygosity of Chromosome 3 Occurring Exclusively in Metastasizing Uveal Melanoma
Anatomy and Pathology Whole-Genome Microarray Detects Deletions and Loss of Heterozygosity of Chromosome 3 Occurring Exclusively in Metastasizing Uveal Melanoma Sarah L. Lake,1 Sarah E. Coupland,1 Azzam F. G. Taktak,2 and Bertil E. Damato3 PURPOSE. To detect deletions and loss of heterozygosity of disease is fatal in 92% of patients within 2 years of diagnosis. chromosome 3 in a rare subset of fatal, disomy 3 uveal mela- Clinical and histopathologic risk factors for UM metastasis noma (UM), undetectable by fluorescence in situ hybridization include large basal tumor diameter (LBD), ciliary body involve- (FISH). ment, epithelioid cytomorphology, extracellular matrix peri- ϩ ETHODS odic acid-Schiff-positive (PAS ) loops, and high mitotic M . Multiplex ligation-dependent probe amplification 3,4 5 (MLPA) with the P027 UM assay was performed on formalin- count. Prescher et al. showed that a nonrandom genetic fixed, paraffin-embedded (FFPE) whole tumor sections from 19 change, monosomy 3, correlates strongly with metastatic death, and the correlation has since been confirmed by several disomy 3 metastasizing UMs. Whole-genome microarray analy- 3,6–10 ses using a single-nucleotide polymorphism microarray (aSNP) groups. Consequently, fluorescence in situ hybridization were performed on frozen tissue samples from four fatal dis- (FISH) detection of chromosome 3 using a centromeric probe omy 3 metastasizing UMs and three disomy 3 tumors with Ͼ5 became routine practice for UM prognostication; however, 5% years’ metastasis-free survival. to 20% of disomy 3 UM patients unexpectedly develop metas- tases.11 Attempts have therefore been made to identify the RESULTS. Two metastasizing UMs that had been classified as minimal region(s) of deletion on chromosome 3.12–15 Despite disomy 3 by FISH analysis of a small tumor sample were found these studies, little progress has been made in defining the key on MLPA analysis to show monosomy 3. -
Small Molecule–Mediated Reprogramming of the Epithelial–Mesenchymal Transition
bioRxiv preprint doi: https://doi.org/10.1101/106591; this version posted February 16, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Small molecule–mediated reprogramming of the epithelial–mesenchymal transition prevents fibrosis Running title: Reversion of fibrosis by chromones Han-Soo Kim,1,2* Jun-Hwan Kim,1,3* Ji Yong Lee,2 Young-Min Yoon,3 Ik-Hwan Kim,4 Ho- Sup Yoon5 and Byung-Soo Youn3# 1Institute for BioMedical Convergence, Catholic Kwandong University-International St. Mary’s Hospital, Incheon 22711, Republic of Korea , 2Department of Biomedical Sciences, Catholic Kwandong University College of Medicine, Gangneung-si, Gangwon-do 25601, Republic of Korea. 3#705 Ace High-end Tower 9th 233,Gasandigital-1-ro, Geumcheon- gu, Seoul, 08501, Republic of Korea, 4Department of Biotechnology, Korea University. Seoul 02841and 5Department of Genetic Engineering, College of Life Sciences, Kyung Hee University, Yongin-si, Gyeonggi-do 446-701, Republic of Korea and 5School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, 637551, Singapore *These contributes equally to this work. #Corresponding author: Byung-Soo Youn, PhD, OsteoNeuroGen, Inc. Ace High-end Tower 9th 233, Gasandigital-1-ro, Geumcheon-gu, Seoul, 08501, Republic of Korea Email: [email protected], Tel) 822- 6267 2737 Fax) 822-6267-2740 1 bioRxiv preprint doi: https://doi.org/10.1101/106591; this version posted February 16, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. -
Methods Mouse Strains and Housing Male Wild-Type Mice
Methods Mouse strains and housing Male wild-type mice (C57BL/6J background) and B6.Cg-Tg (APPSwFlLon, PSEN1*M146L*L286V) 6799Vas/Mmjax (5xFAD, JAX 008730) were purchased from the Jackson Laboratory. μMT-/- mice which are deficient in B cells were purchased from Shanghai Model Organisms Center, Inc. Both B6.Cg-Tg and μMT-/- mice were bred on a C57BL/6J background. 5xFAD mice and μMT-/- mice were crossed to generate μMT-/-/5xFAD mice. The mice were used at different ages that are indicated throughout the manuscript. Mice of all strains were specific pathogen free environment with controlled temperature and humidity, on 12 h light: dark cycles (lights on at 7:00), and fed with regular rodent’s chow and sterilized tap water ad libitum. All experiments were approved by the Institutional Animal Care and Use Committee of the Nanjing Medical University. Human samples Frontal cortex tissues were obtained from 4 cases within 4-6 h of death, via informed donation for the Medical Education and Research of Nanjing Medical University, with corresponding written consents prepared by the donors and their families. Cases that were died from brain associated diseases were excluded from this study. The utilization of human tissues was approved by the Ethics Committee of Nanjing Medical University. All obtained samples were fixed in a 4% formalin solution and kept in paraffin blocks until further sectioning. Animal surgery DcLN ligation: The procedure of surgical ligation of the lymphatics afferent to the dcLNs was according to published literature (3, 30). In brief, mice were anaesthetized by i.p. injection with ketamine and xylazine in saline, and fixed on a stereotaxic apparatus in a supine position. -
Environmental Influences on Endothelial Gene Expression
ENDOTHELIAL CELL GENE EXPRESSION John Matthew Jeff Herbert Supervisors: Prof. Roy Bicknell and Dr. Victoria Heath PhD thesis University of Birmingham August 2012 University of Birmingham Research Archive e-theses repository This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder. ABSTRACT Tumour angiogenesis is a vital process in the pathology of tumour development and metastasis. Targeting markers of tumour endothelium provide a means of targeted destruction of a tumours oxygen and nutrient supply via destruction of tumour vasculature, which in turn ultimately leads to beneficial consequences to patients. Although current anti -angiogenic and vascular targeting strategies help patients, more potently in combination with chemo therapy, there is still a need for more tumour endothelial marker discoveries as current treatments have cardiovascular and other side effects. For the first time, the analyses of in-vivo biotinylation of an embryonic system is performed to obtain putative vascular targets. Also for the first time, deep sequencing is applied to freshly isolated tumour and normal endothelial cells from lung, colon and bladder tissues for the identification of pan-vascular-targets. Integration of the proteomic, deep sequencing, public cDNA libraries and microarrays, delivers 5,892 putative vascular targets to the science community. -
Mouse Ppef1 Knockout Project (CRISPR/Cas9)
https://www.alphaknockout.com Mouse Ppef1 Knockout Project (CRISPR/Cas9) Objective: To create a Ppef1 knockout Mouse model (C57BL/6J) by CRISPR/Cas-mediated genome engineering. Strategy summary: The Ppef1 gene (NCBI Reference Sequence: NM_011147 ; Ensembl: ENSMUSG00000062168 ) is located on Mouse chromosome X. 16 exons are identified, with the ATG start codon in exon 1 and the TAA stop codon in exon 16 (Transcript: ENSMUST00000071204). Exon 2~4 will be selected as target site. Cas9 and gRNA will be co-injected into fertilized eggs for KO Mouse production. The pups will be genotyped by PCR followed by sequencing analysis. Note: Homozygous null female and hemizygous null male mice are viable, fertile and display no overt abnormalities. Exon 2 starts from about 2.41% of the coding region. Exon 2~4 covers 18.41% of the coding region. The size of effective KO region: ~10105 bp. The KO region does not have any other known gene. Page 1 of 8 https://www.alphaknockout.com Overview of the Targeting Strategy Wildtype allele 5' gRNA region gRNA region 3' 1 2 3 4 16 Legends Exon of mouse Ppef1 Knockout region Page 2 of 8 https://www.alphaknockout.com Overview of the Dot Plot (up) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 2000 bp section upstream of Exon 2 is aligned with itself to determine if there are tandem repeats. No significant tandem repeat is found in the dot plot matrix. So this region is suitable for PCR screening or sequencing analysis. Overview of the Dot Plot (down) Window size: 15 bp Forward Reverse Complement Sequence 12 Note: The 2000 bp section downstream of Exon 4 is aligned with itself to determine if there are tandem repeats. -
Ageing-Associated Changes in DNA Methylation in X and Y Chromosomes
Kananen and Marttila Epigenetics & Chromatin (2021) 14:33 Epigenetics & Chromatin https://doi.org/10.1186/s13072-021-00407-6 RESEARCH Open Access Ageing-associated changes in DNA methylation in X and Y chromosomes Laura Kananen1,2,3,4* and Saara Marttila4,5* Abstract Background: Ageing displays clear sexual dimorphism, evident in both morbidity and mortality. Ageing is also asso- ciated with changes in DNA methylation, but very little focus has been on the sex chromosomes, potential biological contributors to the observed sexual dimorphism. Here, we sought to identify DNA methylation changes associated with ageing in the Y and X chromosomes, by utilizing datasets available in data repositories, comprising in total of 1240 males and 1191 females, aged 14–92 years. Results: In total, we identifed 46 age-associated CpG sites in the male Y, 1327 age-associated CpG sites in the male X, and 325 age-associated CpG sites in the female X. The X chromosomal age-associated CpGs showed signifcant overlap between females and males, with 122 CpGs identifed as age-associated in both sexes. Age-associated X chro- mosomal CpGs in both sexes were enriched in CpG islands and depleted from gene bodies and showed no strong trend towards hypermethylation nor hypomethylation. In contrast, the Y chromosomal age-associated CpGs were enriched in gene bodies, and showed a clear trend towards hypermethylation with age. Conclusions: Signifcant overlap in X chromosomal age-associated CpGs identifed in males and females and their shared features suggest that despite the uneven chromosomal dosage, diferences in ageing-associated DNA methylation changes in the X chromosome are unlikely to be a major contributor of sex dimorphism in ageing. -
UC Riverside UC Riverside Previously Published Works
UC Riverside UC Riverside Previously Published Works Title Analysis of the Candida albicans Phosphoproteome. Permalink https://escholarship.org/uc/item/0663w2hr Journal Eukaryotic cell, 14(5) ISSN 1535-9778 Authors Willger, SD Liu, Z Olarte, RA et al. Publication Date 2015-05-01 DOI 10.1128/ec.00011-15 License https://creativecommons.org/licenses/by-nc-sa/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Analysis of the Candida albicans Phosphoproteome S. D. Willger,a Z. Liu,b R. A. Olarte,c M. E. Adamo,d J. E. Stajich,c L. C. Myers,b A. N. Kettenbach,b,d D. A. Hogana Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USAa; Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire, USAb; Department of Plant Pathology and Microbiology, University of California, Riverside, California, USAc; Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire, USAd Candida albicans is an important human fungal pathogen in both immunocompetent and immunocompromised individuals. C. albicans regulation has been studied in many contexts, including morphological transitions, mating competence, biofilm forma- tion, stress resistance, and cell wall synthesis. Analysis of kinase- and phosphatase-deficient mutants has made it clear that pro- tein phosphorylation plays an important role in the regulation of these pathways. In this study, to further our understanding of phosphorylation in C. albicans regulation, we performed a deep analysis of the phosphoproteome in C. albicans. We identified 19,590 unique peptides that corresponded to 15,906 unique phosphosites on 2,896 proteins. -
Pharmacology and Toxicology of Amphetamine and Related Designer Drugs
Pharmacology and Toxicology of Amphetamine and Related Designer Drugs U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES • Public Health Service • Alcohol Drug Abuse and Mental Health Administration Pharmacology and Toxicology of Amphetamine and Related Designer Drugs Editors: Khursheed Asghar, Ph.D. Division of Preclinical Research National Institute on Drug Abuse Errol De Souza, Ph.D. Addiction Research Center National Institute on Drug Abuse NIDA Research Monograph 94 1989 U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Alcohol, Drug Abuse, and Mental Health Administration National Institute on Drug Abuse 5600 Fishers Lane Rockville, MD 20857 For sale by the Superintendent of Documents, U.S. Government Printing Office Washington, DC 20402 Pharmacology and Toxicology of Amphetamine and Related Designer Drugs ACKNOWLEDGMENT This monograph is based upon papers and discussion from a technical review on pharmacology and toxicology of amphetamine and related designer drugs that took place on August 2 through 4, 1988, in Bethesda, MD. The review meeting was sponsored by the Biomedical Branch, Division of Preclinical Research, and the Addiction Research Center, National Institute on Drug Abuse. COPYRIGHT STATUS The National Institute on Drug Abuse has obtained permission from the copyright holders to reproduce certain previously published material as noted in the text. Further reproduction of this copyrighted material is permitted only as part of a reprinting of the entire publication or chapter. For any other use, the copyright holder’s permission is required. All other matieral in this volume except quoted passages from copyrighted sources is in the public domain and may be used or reproduced without permission from the Institute or the authors.