DOCSLIB.ORG

ABSTRACT RAJAB, SARAH, A. S.. an Integrated Metabolomic And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

ABSTRACT RAJAB, SARAH, A. S.. An Integrated Metabolomic and Transcriptomic Approach for Understanding White Muscle Growth Regulation in Hybrid Striped Bass Aquaculture. (Under the direction of Dr. Harry V. Daniels and Dr. Benjamin J. Reading). Farming of hybrid striped bass (HSB) (striped bass x white bass) is the fourth largest finfish aquaculture industry in the U.S., behind catfish, salmon and tilapia, however several knowledge gaps remain, particularly in regards to the cellular processes that underlie growth performance of these fish. Insight into these processes is critical for improvement of breeding and rearing methodologies geared towards foodfish production. Here, we describe a novel combinatorial machine learning analysis of transcriptomic and metabolomic data generated from white muscle and liver tissues to identify discrete molecular processes that underlie the regulation of enhanced growth and muscle accretion of HSB. HSB were reared in tanks and ponds according to standard two-phase culture procedures until harvest at market size. Individuals of the top and bottom 10% body size in weight and total length relative to the cohort were sampled (N = 10 fish per group) as representatives of fish that grow good and poorly, respectively. These cutoffs were chosen as they represent a body size that is typically larger and smaller than that desired at market and therefore represent extremes of the distribution. The data were linked to corresponding changes in metrics of growth including body weight, total length, hepatosomatic index, and gonadosomatic index. Transverse sections of white muscle tissue were taken to evaluate differences in muscle growth patterns and revealed that good- growth group fish trended towards hyperplastic growth and that poor-growth group fish had switched to hypertrophic growth. Additionally, muscle and liver samples were subjected to metabolomics analysis and a total of 469 and 464 metabolites, in muscle and liver, respectively were identified and analyzed by decision tree, where 30 metabolites were classified as the top most important growth predictors. As metabolites are the end products of gene and protein activities within the cell, they therefore underlie the physiological response of the animal. A determination of differential gene expression between groups was completed with Illumina-based RNA-Seq data generated from muscle tissue and a total of 72,893 genes were identified and ranked by importance using statistical inference, based on adjusted p-value, and machine learning (Support Vector Machines). Two reduced gene lists, 143 from inferential statistics and 150 from Class SVMAttributeEval machine learning model, were selected as a cutoff for pathway analysis and only eleven genes were found to be shared between the two lists. To ascertain the biological processes that determine size differences in the two groups of fish, Ingenuity Pathway Analysis (IPA) was conducted on the two differentially expressed gene lists and the top 30 metabolites. The IPA results, identified potential candidates and pathways that influence growth performance for guiding future experimental testing and feed design. In particular, pathways such as cell proliferation and cell differentiation, apoptosis, and inflammation may possibly underly the growth performance of the fish. Furthermore, combined with application of genetic improvement technology, manipulation of these pathways may enhance animal growth and body size. These studies combined, for the first time, two powerful approaches (metabolomics and transcriptomics), along with a novel machine learning-based model analysis tool using Support Vector Machines (SVMAttributeEval), to generate an informative list of the most important metabolite and gene biomarkers and their likely integrated pathways associated with HSB growth performance. These approaches, which ten years ago were neither available nor accessible, provide the most practical predictors of growth performance in fish and identify key metabolites and gene transcripts that may be indicators of growth performance. The integrated pathways of these components provide a great insight into the mechanisms of muscle development, which will inform future breeding and nutrition studies to help improve HSB aquaculture production and assure the successful continuation of the industry. © Copyright 2020 Sarah A. S. Rajab All Rights Reserved An Integrated Metabolomic and Transcriptomic Approach for Understanding White Muscle Growth Regulation in Hybrid Striped Bass Aquaculture By Sarah A. S. Rajab A dissertation submitted to the Graduate Faculty of North Carolina State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy Zoology Raleigh, North Carolina 2020 APPROVED BY: _____________________________________ _____________________________________ Dr. Harry V. Daniels Dr. Benjamin J. Reading Co-Chair of Advisory Committee Co-Chair of Advisory Committee _______________________________________ _____________________________________ Dr. Peter Ferket Dr. Christopher Ashwell DEDICATION This thesis work is wholeheartedly dedicated to my beloved parents, Ahmad and Batoul, for encouraging my pursuit in sciences from a young age. For loving me unconditionally and whose good examples have taught me to work hard for the things that I aspire to achieve. They have been my source of inspiration and gave me strength when I thought of giving up, and have continuously provided their moral, spiritual, emotional, and finical support. This work is also dedicated to my beloved husband, Yousef. Yousef is also my best friend for being my constant source of support and encouragement during the challenges of graduate school and life. I am thankful that you have always believed in me and I am genuinely grateful for having you in my life. ii BIOGRAPHY Sarah Ahmad Sayed Rajab was born during the year 1984 to Ahmad Rajab and Batoul Haji. She has been passionate for science from a very young age and was mostly fascinated in nature and explicitly in animals. This led her to obtain a zoology degree with a minor in marine sciences from Kuwait University. She was awarded an honor student certificate for two consecutive years 2005-2006 during her undergraduate studies. Throughout her undergraduate career she had the opportunity to be involved in variety of different research projects all which were integrated with Kuwait marine environment. From that point onward, Sarah’s passion for the marine environment grow more and she contained to peruse her love for the sea by working during the summer at Lothan Youth Achievement Centre (LOYAC). Shortly after her graduation in 2006, she joined Kuwait Institute for Scientific Research (KISR) as a Research Assistant specializing in fish age determination and stock assessment. During that time, she participated in collaborated projects with The Gulf Cooperation Council (GCC). While there, she mastered several laboratorial techniques such a tissue and bone histology for fish age determination, Principles of Polymerase Chain Reaction (PCR), fish anatomy and classification , image analysis using highly advanced motorized compound, stereo, and scanning electron microscopy. Additionally, she was given the opportunity to attend a stock assessment modeling training course arranged by the International Council for the Exploration of the Sea (ICES) in Copenhagen, Denmark. Also she participated in the world 5th fisheries congress in Yokohama, Japan. iii In KISR, Sarah was granted a scholarship to continue her path in the field. She was awarded a Master Degree in “Applied Marine and Fishers Ecology an Implementation to Marine Protected Areas” at Aberdeen University in Scotland, the United Kingdom. Throughout her time in Scotland, Sarah also worked in Marine Scotland Science (MSS) where she refined her skills in the fish age determination laboratory, until her graduation in 2010. After graduation, Sarah continued working for KISR until August 2014 where she was matriculated to Kuwait University and granted a scholarship to pursue a doctorate degree at the North Carolina State University (NCSU). During her time in NSCU, she was able to work with a number of undergraduate and graduate students and present her research at several national scientific symposia. As of the writing of this dissertation, Sarah currently lives in Raleigh, NC with her Husband Yousef, her Mother Batoul, and her newly born son Mohammed. She has five siblings, two older brothers, Hashem and Mohammed, two older sisters, Saja and Sakeena, and one younger brother, Ibraheem. Sarah’s hobbies include watercolor painting, photography, reading National Geographic, and exploring the world. iv ACKNOWLEDGMENTS First and foremost, praises and thanks to God, the Almighty, for His showers of blessings throughout my research work to complete the research successfully. I offer my sincerest gratitude to my committee advisors, Dr. Benjamin Reading and Dr. Harry Daniels, my mentors, and trusted guides for their unending support and encouragement throughout my Northern Carolina State University experience. Dr. Benjamin Reading nurtured and refined my scientific research talents by encouraging me to be bold and creative, not afraid to “think outside the box.” I will forever be indebted to him for how he enriched my understanding of science, the scientific research process, and the ability to approach problem-solving with precision and clarity. It was a great privilege and honor to work and study under his guidance. I am incredibly
Recommended publications
  • 35 Disorders of Purine and Pyrimidine Metabolism

    35 Disorders of Purine and Pyrimidine Metabolism

    35 Disorders of Purine and Pyrimidine Metabolism Georges van den Berghe, M.- Françoise Vincent, Sandrine Marie 35.1 Inborn Errors of Purine Metabolism – 435 35.1.1 Phosphoribosyl Pyrophosphate Synthetase Superactivity – 435 35.1.2 Adenylosuccinase Deficiency – 436 35.1.3 AICA-Ribosiduria – 437 35.1.4 Muscle AMP Deaminase Deficiency – 437 35.1.5 Adenosine Deaminase Deficiency – 438 35.1.6 Adenosine Deaminase Superactivity – 439 35.1.7 Purine Nucleoside Phosphorylase Deficiency – 440 35.1.8 Xanthine Oxidase Deficiency – 440 35.1.9 Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency – 441 35.1.10 Adenine Phosphoribosyltransferase Deficiency – 442 35.1.11 Deoxyguanosine Kinase Deficiency – 442 35.2 Inborn Errors of Pyrimidine Metabolism – 445 35.2.1 UMP Synthase Deficiency (Hereditary Orotic Aciduria) – 445 35.2.2 Dihydropyrimidine Dehydrogenase Deficiency – 445 35.2.3 Dihydropyrimidinase Deficiency – 446 35.2.4 Ureidopropionase Deficiency – 446 35.2.5 Pyrimidine 5’-Nucleotidase Deficiency – 446 35.2.6 Cytosolic 5’-Nucleotidase Superactivity – 447 35.2.7 Thymidine Phosphorylase Deficiency – 447 35.2.8 Thymidine Kinase Deficiency – 447 References – 447 434 Chapter 35 · Disorders of Purine and Pyrimidine Metabolism Purine Metabolism Purine nucleotides are essential cellular constituents 4 The catabolic pathway starts from GMP, IMP and which intervene in energy transfer, metabolic regula- AMP, and produces uric acid, a poorly soluble tion, and synthesis of DNA and RNA. Purine metabo- compound, which tends to crystallize once its lism can be divided into three pathways: plasma concentration surpasses 6.5–7 mg/dl (0.38– 4 The biosynthetic pathway, often termed de novo, 0.47 mmol/l). starts with the formation of phosphoribosyl pyro- 4 The salvage pathway utilizes the purine bases, gua- phosphate (PRPP) and leads to the synthesis of nine, hypoxanthine and adenine, which are pro- inosine monophosphate (IMP).
  • Forms of Hypoxanthine Or, Through Interconversions, Guanine Or Adenine

    Forms of Hypoxanthine Or, Through Interconversions, Guanine Or Adenine

    826 GENETICS: GOTS AND GOLLUB PROC. N. A. S. Summary.-The ribonucleic acids of isolated thymus nuclei can be separated into two distinct fractions, one of which probably represents ribonucleic acid of the nu- cleolus. Studies of the incorporation of orotic acid-6-C"4 and adenosine-8-C'4 into these RNA fractions in vitro show great differences in their metabolic activity and different susceptibilities to an inhibitor of RNA synthesis, the "nucleolar" RNA being by far the more active. It is a pleasure to acknowledge our indebtedness to Mr. Rudolf Meudt for his careful and expert technical assistance. * This research was supported in part by a grant (RG-4919 M&G) from the United States Public Health Service. I V. G. Allfrey, A. E. Mirsky, and S. Osawa, Nature, 176, 1042, 1955. 2 V. G. Allfrey, A. E. Mirsky, and S. Osawa, J. Gen. Physiol., 40, 451, 1957. 3 R. Logan and J. N. Davidson, Biochim. et Biophys. Acta, 24, 196, 1957. 4 S. Osawa, K. Takata, and Y. Hotta (in press). 6 J. M. Webb, J. Biol. Chem., 221, 635, 1956. 6 M. Bessis, in Traite de cytologie sanguine (Paris: Masson & Cie, 1954), p. 83. J. N. Davidson and R. M. S. Smellie. Biochem. J.. 52, 594, 1952. SEQUENTIAL BLOCKADE IN ADENINE BIOSYNTHESIS BY GENETIC LOSS OF AN APPARENT BIFUNCTIONAL DEACYLASE* By JOSEPH S. GOTS AND EDITH G. GOLLUB DEPARTMENT OF MICROBIOLOGY, SCHOOL OF MEDICINE, UNIVERSITY OF PENNSYLVANIA, PHILADELPHIA, PENNSYLVANIA Communicated by D. Wright Wilson, July 3, 1957 Along the biosynthetic pathway to the purines of nucleic acids, inosinic acid occurs as a pivotal point in a bifurcation which leads to adenylic acid along one branch and to guanylic acid along the other: (B) r- Adenylic acid (AMP) (A) Inosinic acid (IMP) (C) L|_ * Guanylic acid (GMP) Bacterial mutations may result in genetic impairments at three locations with respect to the pivotal inosinic acid, thus yielding auxotrophs with three broad classes of nutritional response.
  • Molecular Basis for SPIN·DOC-Spindlin1 Engagement and Its Role in Transcriptional Inhibition

    Molecular Basis for SPIN·DOC-Spindlin1 Engagement and Its Role in Transcriptional Inhibition

    bioRxiv preprint doi: https://doi.org/10.1101/2021.03.07.432812; this version posted March 7, 2021. 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-NC-ND 4.0 International license. Molecular basis for SPIN·DOC-Spindlin1 engagement and its role in transcriptional inhibition Fan Zhao1†, Fen Yang2,3†, Fan Feng1, Bo Peng1, Mark T. Bedford2*, and Haitao Li1,4* 1 MOE Key Laboratory of Protein Sciences, Beijing Frontier Research Center for Biological Structure, Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China, 2 Department of Epigenetics and Molecular Carcinogenesis, University of Texas MD Anderson Cancer Center, Smithville, Texas 78957, USA, 3Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, China, 4 Tsinghua-Peking Center for Life Sciences, Beijing 100084, China *To whom correspondence should be addressed. Tel: 86-10-62771392; Email: [email protected]; Correspondence may also be addressed to Mark T. Bedford. Tel: 512-237-9539; Email: [email protected]. ABSTRACT Spindlin1 is a transcriptional coactivator with three Tudor-like domains, of which the first and second Tudors are engaged in histone methylation readout, while the function of the third Tudor is largely unknown. Recent studies revealed that the transcriptional co-activator activity of Spindlin1 could be attenuated by SPIN•DOC. Here we solved the crystal structure of SPIN•DOC-Spindlin1 complex, revealing that a hydrophobic motif, DOCpep3 (256-281), of SPIN•DOC interacts with Tudor 3 of Spindlin1 and completes its β-barrel fold.
  • Supplementary Materials

    Supplementary Materials

    Supplementary materials Supplementary Table S1: MGNC compound library Ingredien Molecule Caco- Mol ID MW AlogP OB (%) BBB DL FASA- HL t Name Name 2 shengdi MOL012254 campesterol 400.8 7.63 37.58 1.34 0.98 0.7 0.21 20.2 shengdi MOL000519 coniferin 314.4 3.16 31.11 0.42 -0.2 0.3 0.27 74.6 beta- shengdi MOL000359 414.8 8.08 36.91 1.32 0.99 0.8 0.23 20.2 sitosterol pachymic shengdi MOL000289 528.9 6.54 33.63 0.1 -0.6 0.8 0 9.27 acid Poricoic acid shengdi MOL000291 484.7 5.64 30.52 -0.08 -0.9 0.8 0 8.67 B Chrysanthem shengdi MOL004492 585 8.24 38.72 0.51 -1 0.6 0.3 17.5 axanthin 20- shengdi MOL011455 Hexadecano 418.6 1.91 32.7 -0.24 -0.4 0.7 0.29 104 ylingenol huanglian MOL001454 berberine 336.4 3.45 36.86 1.24 0.57 0.8 0.19 6.57 huanglian MOL013352 Obacunone 454.6 2.68 43.29 0.01 -0.4 0.8 0.31 -13 huanglian MOL002894 berberrubine 322.4 3.2 35.74 1.07 0.17 0.7 0.24 6.46 huanglian MOL002897 epiberberine 336.4 3.45 43.09 1.17 0.4 0.8 0.19 6.1 huanglian MOL002903 (R)-Canadine 339.4 3.4 55.37 1.04 0.57 0.8 0.2 6.41 huanglian MOL002904 Berlambine 351.4 2.49 36.68 0.97 0.17 0.8 0.28 7.33 Corchorosid huanglian MOL002907 404.6 1.34 105 -0.91 -1.3 0.8 0.29 6.68 e A_qt Magnogrand huanglian MOL000622 266.4 1.18 63.71 0.02 -0.2 0.2 0.3 3.17 iolide huanglian MOL000762 Palmidin A 510.5 4.52 35.36 -0.38 -1.5 0.7 0.39 33.2 huanglian MOL000785 palmatine 352.4 3.65 64.6 1.33 0.37 0.7 0.13 2.25 huanglian MOL000098 quercetin 302.3 1.5 46.43 0.05 -0.8 0.3 0.38 14.4 huanglian MOL001458 coptisine 320.3 3.25 30.67 1.21 0.32 0.9 0.26 9.33 huanglian MOL002668 Worenine
  • Structure-Based Design, Docking and Binding Free Energy Calculations of A366 Derivatives As Spindlin1 Inhibitors

    Structure-Based Design, Docking and Binding Free Energy Calculations of A366 Derivatives As Spindlin1 Inhibitors

    International Journal of Molecular Sciences Article Structure-Based Design, Docking and Binding Free Energy Calculations of A366 Derivatives as Spindlin1 Inhibitors Chiara Luise 1, Dina Robaa 1, Pierre Regenass 2, David Maurer 2 , Dmytro Ostrovskyi 2, Ludwig Seifert 3, Johannes Bacher 3, Teresa Burgahn 3, Tobias Wagner 3, Johannes Seitz 3, Holger Greschik 4, Kwang-Su Park 5 , Yan Xiong 5, Jian Jin 5 , Roland Schüle 4, Bernhard Breit 2, Manfred Jung 3,6 and Wolfgang Sippl 1,* 1 Institute of Pharmacy, Martin Luther University of Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120 Halle (Saale), Germany; [email protected] (C.L.); [email protected] (D.R.) 2 Institute for Organic Chemistry, University of Freiburg, Albertstr. 21, 79104 Freiburg, Germany; [email protected] (P.R.); [email protected] (D.M.); [email protected] (D.O.); [email protected] (B.B.) 3 Institute of Pharmaceutical Sciences, University of Freiburg, Albertstr. 25, 79104 Freiburg, Germany; [email protected] (L.S.); [email protected] (J.B.); [email protected] (T.B.); [email protected] (T.W.); [email protected] (J.S.); [email protected] (M.J.) 4 Department of Urology and Center for Clinical Research, University Freiburg Medical Center, Breisacherstr. 66, 79106 Freiburg, Germany; [email protected] (H.G.); [email protected] (R.S.) 5 Mount Sinai Center for Therapeutics Discovery, Departments
  • Module Analysis Using Single-Patient Differential Expression Signatures

    Module Analysis Using Single-Patient Differential Expression Signatures

    bioRxiv preprint doi: https://doi.org/10.1101/2020.01.05.894931; this version posted January 6, 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-NC-ND 4.0 International license. Module analysis using single-patient differential expression signatures improve the power of association study for Alzheimer's disease Jialan Huang1, Dong Lu1, and Guofeng Meng1,∗ 1Institute of interdisciplinary integrative Medicine Research, shanghai University of Traditional Chinese Medicine, shanghai, China Abstract The causal mechanism of Alzheimer's disease is extremely complex. It usually requires a huge number of samples to achieve a good statistical power in association studies. In this work, we illustrated a different strategy to identify AD risk genes by clustering AD patients into modules based on their single-patient differential expression signatures. Evaluation suggested that our method could enrich AD patients with common clinical manifestations. Applying it to a cohort of only 310 AD patients, we identified 175 AD risk loci at a strict threshold of empirical p < 0:05 while only two loci were identified using all the AD patients. As an evaluation, we collected 23 AD risk genes reported in a recent large-scale meta-analysis and found that 18 of them were re-discovered by association studies using clustered AD patients, while only three of them were re-discovered using all AD patients. Functional annotation suggested that AD associated genetic variants mainly disturbed neuronal/synaptic function.
  • Patterns and Mechanisms of Sex Ratio Distortion in the Collaborative

    Patterns and Mechanisms of Sex Ratio Distortion in the Collaborative

    bioRxiv preprint doi: https://doi.org/10.1101/2021.06.23.449644; this version posted June 23, 2021. 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 4.0 International license. 1 Patterns and Mechanisms of Sex Ratio Distortion in the 2 Collaborative Cross Mouse Mapping Population 3 4 5 Brett A. Haines*, Francesca Barradale†, Beth L. Dumont*,‡ 6 7 8 * The Jackson Laboratory, 600 Main Street, Bar Harbor ME 04609 9 † Department of Biology, Williams College, 59 Lab Campus Drive, Williamstown, MA 01267 10 11 ‡ Tufts University, Graduate School of Biomedical Sciences, 136 Harrison Ave, Boston MA 12 02111 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.06.23.449644; this version posted June 23, 2021. 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 4.0 International license. 13 Running Title: Sex Ratio Distortion in House Mice 14 15 Key words: sex ratio distortion, Collaborative Cross, intergenomic conflict, sex chromosomes, 16 ampliconic genes, Slx, Slxl1, Sly, Diversity Outbred, house mouse 17 18 Address for Correspondence: 19 20 Beth Dumont 21 The Jackson Laboratory 22 600 Main Street 23 Bar Harbor, ME 04609 24 25 P: 207-288-6647 26 E: [email protected] 2 bioRxiv preprint doi: https://doi.org/10.1101/2021.06.23.449644; this version posted June 23, 2021.
  • Supplementary Material Table of Contents

    Supplementary Material Table of Contents

    Supplementary M aterial Table of Contents 1 - Online S u pplementary Methods ………………………………………………...… . …2 1.1 Study population……………………………………………………………..2 1.2 Quality control and principal component analysis …………………………..2 1.3 Statistical analyses………………………………………… ………………...3 1.3.1 Disease - specific association testing ……………………………… ..3 1.3.2 Cross - phenotype meta - analysis …………………………………… .3 1.3.3 Model search ……………………………………………………… .4 1.3.4 Novelty of the variants …………………………………………… ..4 1.3.5 Functional Enrichment Analy sis ………………………………… ...4 1.3.6 Drug Target Enrichment Analysis ………………………………… 5 2 - Supplementary Figures………………………………………...………………… . …. 7 3 - Members of the Myositis Genetics Consortium (MYOGEN) ……………………. ..16 4 - Members of the Scleroderma Genetics Consortium ………………… ……………...17 5 - Supplementary References………………………………………………………… . .18 6 - Supplementary Tables………………………………………………………… . ……22 1 Online supplementary m ethods Study population This study was conducted using 12,132 affected subjects and 23 ,260 controls of European des cent population and all of them have been included in previously published GWAS as summarized in Table S1. [1 - 6] Briefly, a total of 3,255 SLE cases and 9,562 ancestry matched controls were included from six countrie s across Europe and North America (Spain, Germany, Netherlands, Italy, UK, and USA). All of the included patients were diagnosed based on the standard American College of Rheumatology (ACR) classification criteria. [7] Previously described GWAS data from 2,363 SSc cases and 5,181 ancestry
  • Histone H3Q5 Serotonylation Stabilizes H3K4 Methylation and Potentiates Its Readout

    Histone H3Q5 Serotonylation Stabilizes H3K4 Methylation and Potentiates Its Readout

    Histone H3Q5 serotonylation stabilizes H3K4 methylation and potentiates its readout Shuai Zhaoa,1, Kelly N. Chuhb,1, Baichao Zhanga,1, Barbara E. Dulb, Robert E. Thompsonb, Lorna A. Farrellyc,d, Xiaohui Liue, Ning Xue, Yi Xuee, Robert G. Roederf, Ian Mazec,d,2, Tom W. Muirb,2, and Haitao Lia,g,2 aMinistry of Education Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China; bDepartment of Chemistry, Princeton University, Princeton, NJ 08540; cNash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029; dDepartment of Pharmacological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029; eNational Protein Science Technology Center, School of Life Sciences, Tsinghua University, Beijing 100084, China; fLaboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY 10065; and gTsinghua-Peking Center for Life Sciences, Tsinghua University, Beijing 100084, China Edited by Peter Cheung, York University, Toronto, ON, Canada, and accepted by Editorial Board Member Karolin Luger November 12, 2020 (received for review August 7, 2020) Serotonylation of glutamine 5 on histone H3 (H3Q5ser) was recently established that H3K4me3 regulates gene expression through re- identified as a permissive posttranslational modification that coexists cruitment of nuclear factors that contain reader domains specific with adjacent lysine 4 trimethylation (H3K4me3). While the resulting for the mark. These include ATP-dependent chromatin remod- dual modification, H3K4me3Q5ser, is enriched at regions of active eling enzymes, as well as several transcription factors (13).
  • Downloaded from Ftp://Ftp.Uniprot.Org/ on July 3, 2019) Using Maxquant (V1.6.10.43) Search Algorithm

    Downloaded from Ftp://Ftp.Uniprot.Org/ on July 3, 2019) Using Maxquant (V1.6.10.43) Search Algorithm

    bioRxiv preprint doi: https://doi.org/10.1101/2020.11.17.385096; this version posted November 17, 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. The proteomic landscape of resting and activated CD4+ T cells reveal insights into cell differentiation and function Yashwanth Subbannayya1, Markus Haug1, Sneha M. Pinto1, Varshasnata Mohanty2, Hany Zakaria Meås1, Trude Helen Flo1, T.S. Keshava Prasad2 and Richard K. Kandasamy1,* 1Centre of Molecular Inflammation Research (CEMIR), and Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, N-7491 Trondheim, Norway 2Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India *Correspondence to: Professor Richard Kumaran Kandasamy Norwegian University of Science and Technology (NTNU) Centre of Molecular Inflammation Research (CEMIR) PO Box 8905 MTFS Trondheim 7491 Norway E-mail: [email protected] (Kandasamy R K) Tel.: +47-7282-4511 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.11.17.385096; this version posted November 17, 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 CD4+ T cells (T helper cells) are cytokine-producing adaptive immune cells that activate or regulate the responses of various immune cells.
  • A Fairy Chemical, Imidazole-4-Carboxamide, Is

    A Fairy Chemical, Imidazole-4-Carboxamide, Is

    www.nature.com/scientificreports OPEN A Fairy Chemical, Imidazole-4- carboxamide, is Produced on a Novel Purine Metabolic Pathway in Received: 25 September 2018 Accepted: 14 May 2019 Rice Published: xx xx xxxx Hirohide Takemura1, Jae-Hoon Choi 2,3, Nobuo Matsuzaki1, Yuki Taniguchi2, Jing Wu3, Hirofumi Hirai2,3, Reiko Motohashi2,3, Tomohiro Asakawa4, Kazutada Ikeuchi5, Makoto Inai6, Toshiyuki Kan6 & Hirokazu Kawagishi1,2,3 Rings or arcs of fungus-regulated plant growth occurring on the foor of woodlands and grasslands are commonly called “fairy rings”. Fairy chemicals, 2-azahypoxanthine (AHX), imidazole-4-carboxamide (ICA), and 2-aza-8-oxohypoxanthine (AOH), are plant growth regulators involved in the phenomenon. The endogeny and biosynthetic pathways of AHX and AOH in plants have already been proven, however, those of ICA have remained unclear. We developed a high-sensitivity detection method for FCs including ICA and the endogenous ICA was detected in some plants for the frst time. The quantitative analysis of the endogenous level of ICA in rice and Arabidopsis were performed using 13C-double labeled ICA. In addition, the incorporation experiment and enzyme assay using the labeled compound into rice and partially purifed fraction of rice indicated that ICA is biosynthesized from 5-aminoimidazole-4- carboxamide (AICA), a metabolite on the purine metabolic pathway. The relationship between ICA and AHX was also discussed based on quantitative analysis and gene expression analysis. “Fairy rings” is a phenomenon in which fruiting bodies of higher fungi occur afer turfgrass grows and/or dies in the form of rings1. Tese diameters vary from a few centimeters to more than 15 meters and it is also known as a disease of turfgrass all over the world2,3.
  • The Therapeutic Targeting of Folate Receptor Alpha Positive Tumors

    The Therapeutic Targeting of Folate Receptor Alpha Positive Tumors

    Wayne State University Wayne State University Dissertations 1-1-2015 The Therapeutic Targeting Of Folate Receptor Alpha Positive Tumors Via Folate Receptor Selective Novel 5- And 6- Substituted Pyrrolo [2,3-D]pyrimidine Antifolates" Shermaine Kimberly Mitchell-Ryan Wayne State University, Follow this and additional works at: http://digitalcommons.wayne.edu/oa_dissertations Part of the Molecular Biology Commons, Oncology Commons, and the Pharmacology Commons Recommended Citation Mitchell-Ryan, Shermaine Kimberly, "The Therapeutic Targeting Of Folate Receptor Alpha Positive Tumors Via Folate Receptor Selective Novel 5- And 6- Substituted Pyrrolo [2,3-D]pyrimidine Antifolates"" (2015). Wayne State University Dissertations. Paper 1155. This Open Access Dissertation is brought to you for free and open access by DigitalCommons@WayneState. It has been accepted for inclusion in Wayne State University Dissertations by an authorized administrator of DigitalCommons@WayneState. THE THERAPEUTIC TARGETING OF FOLATE RECPTOR ALPHA POSITIVE TUMORS VIA FOLATE RECEPTOR-SELECTIVE NOVEL 5-AND 6- SUBSTITUTED PYRROLO [2,3-D] PYRIMIDINE ANTIFOLATES by SHERMAINE KIMBERLY MITCHELL-RYAN DISSERTATION Submitted to the Graduate School of Wayne State University, Detroit, Michigan In partial fulfilment of the requirements for the degree of DOCTOR OF PHILOSOPHY 2015 Major: CANCER BIOLOGY Approved By: ________________________________________ Advisor Date ________________________________________ ________________________________________ ________________________________________ ________________________________________ DEDICATION This dissertation is dedicated to Seamus Isaiah Ryan, my sun (son), my world and my very reason to press forward and claim every reward life has to offer. My sojourn through this process would not have been possible without the love, support and encouragement of my husband, Paul Seamus Ryan. Thank you for your steadfast devotion, patience and understanding.