DOCSLIB.ORG

(12) United States Patent (10) Patent No.: US 7,970,552 B1

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) United States Patent (10) Patent No.: US 7,970,552 B1 US007970552B1 (12) United States Patent (10) Patent No.: US 7,970,552 B1 Stefanon et al. 45) Date of Patent: Jun. 28,9 2011 (54) DIAGNOSTIC SYSTEM FOR SELECTING 3. R 238, E. 1 NUTRITION AND PHARMACOLOGICAL 6,493,641- - w B1 12/2002 Singheblak et et al. al. PRODUCTS FOR ANIMALS 6,537,213 B2 3/2003 Dodds 6,730,023 B1 5, 2004 Dodds (76) Inventors: Bruno Stefanon, Martignacco (IT): W. 7,029.441 B2 4/2006 Dodds Jean Dodds, Santa Monica, CA (US) 7,296,5377,134,995 B2 12/200611/2006 BurghardiDodds et al. (*) Notice: Subject to any disclaimer, the term of this (Continued) patent is extended or adjusted under 35 U.S.C. 154(b) by 0 days. FOREIGN PATENT DOCUMENTS WO WO99-67642 A2 12/1999 (21) Appl. No.: 12/927,769 (Continued) (22) Filed: Nov. 19, 2010 OTHER PUBLICATIONS Related U.S. Application Data Swanson et al., “Nutritional Genomics: Implication for Companion Animals'. The American Society for Nutritional Sciences, (2003).J. (63) Continuation of application No. 12/316,824, filed on Nutr. 133:3033-3040 (18 pages). Dec. 16, 2008, now Pat. No. 7,873,482. (Continued) (51) Int. Cl. G06F 9/00 (2006.01) Primary Examiner — Edward Raymond (52) U.S. Cl. ......................................................... 702/19 (74) Attorney, Agent, or Firm — Greenberg Traurig, LLP 58) Field of Classification Search .................... 702/19, (58) 702/182 185 (57) ABSTRACT See application file for complete search history. An analysis of the profile of a non-human animal comprises: a) providing a genotypic database to the species of the non (56) References Cited human animal Subject or a selected group of the species; b) obtaining animal data; c) correlating the database of a) with U.S. PATENT DOCUMENTS the data ofb) to determine a relationship between the database 3,995,019 A 11, 1976 Jerome of a) and the data of b); c) determining the profile of the 5,691,157 A 1 1/1997 Gong et al. animal based on the correlating step; and d) determining a 5,817,025 A 10, 1998 Alekseev et al. genetic profile based on the molecular dietary signature, the 5,830,709 A 11/1998 Benson et al. 5,911,687 A 6, 1999 Sato et al. molecular dietary signature being a variation of expression of 5,954,640 A 9, 1999 Szabo a set of genes which may differ for the genotype of each 6,018,786 A 1/2000 Kricket al. animal or a group of animals Nutrition and pharmalogical 6,063,028 A 5, 2000 Luciano assessments are made. Reporting the determination is by the 6,081,786 A 6/2000 Barry et al. 6,135,055 A 10, 2000 Pratt Internet, and payment for the report is obtained through the 6,136,055 A 10, 2000 Stanek Internet. 6,156,355 A 12/2000 Shields, Jr. et al. 6,218,122 B1 4/2001 Friend et al. 24 Claims, 23 Drawing Sheets 6,232,522 B1 5/2001 Harley et al. (6 of 23 Drawing Sheet(s) Filed in Color) A-38 US 7,970,552 B1 Page 2 U.S. PATENT DOCUMENTS Swanson et al., “Canine Nutritional Model: Influence of Age, Diet, 2002/0022772 A1 2/2002 Dodds and Genetics on Health and Well-Being'. Current Nutrition & Food 2003. O135096 A1 7, 2003 Dodds Science, vol. 2, No. 2, May 2006, pp. 115-126(12) (1 page). 2003/0233984 A1 12/2003 van de Ligt et al. M.F. Böttcher et al., “Total and allergen-specific immunoglobulin A 2005/00907 18 A1* 4/2005 Dodds ........................... 600/300 levels in Saliva in relation to the development of allergy in infants up 2006, OO45909 A1 3, 2006 Friesen et al. to 2 years of age” Clin. Exp. Allergy Sep. 2002, vol. 32, No. 9, pp. 2006, OO64250 A1 3, 2006 Goldstein 1293-1298. 2006/0200320 A1 9, 2006 Al-Murrani 2006/0283393 Al 12/2006 Burghardi et al. A.P. Foster et al., "Serum IgE and IgG responses to food antigens in 2007/0118295 A1 5, 2007 Al-Murrani normal and atopic dogs, and dogs with gastrointestinal disease' Vet. Immunol. Immunopathol. May 2003, vol. 92, pp. 113-124. FOREIGN PATENT DOCUMENTS Michael J. Day, “The Canine Model of Dietary Hypersensitivity” WO WOO1,28415 A1 4/2001 Proc. Nutr. Soc. Nov. 2005, vol. 64, No. 4, pp. 458-464. WO WOO1,69487 A1 9, 2001 Dodds (Veterinary Practice, 1992, vol. 4. No. 2, p. 25-31). WO WO 2004f1 1357O A2 12/2004 Hetzel et al., (The Journal of Nutrition, 1989, vol. 119, p. 145-151). WO WO 2010/075.007 A3 T 2010 Williams et al., (Nucleic Acids Research, 1990, vol. 18, No. 22, p. WO WO 2010/075,009 A3 T 2010 6531-6535). OTHER PUBLICATIONS Dodds (Advances in Veterinary Science and Comparative Medicine, Swanson et al., “Diet Affects Nutrient Digestibility, Hematology, and 1995, vol.39, p. 29-95). Serum Chemistry of Senior and Weanling Dogs”, Journal of Ameri R. Wolter, “La nutrition de l'animal de sport” Laboratoire de Nutri can Science, (2004) J. Anim. Sci. 2004. 82:1713-1724 (19 pages). tion sportive (INRA) Ecole Nationale Veterinaired Alfort, Science & Kato et al., “A Perspective on DNA Microarray Technology in Food Sports 2, (1987) p. 63-93. and Nutritional Science'. Current Opinion in Clinical Nutrition and Harrison et al., The Journal of Nutrition, 1987, vol. 117, p. 376-382. Metabolic Care, (2005) 8:516-522 (7 pages). K. McNutt, Phd., J.D., “The Individualized Prescriptive Foods Era Spielbauer et al., “Impact of Microarray Technology in Nutrition and Has Dawned'. Nutrition Today, May/Jun. 1993, p. 43-47, USA. Food Research”. (2005) Mol. Nutr. Food Res., 49, 908-917 (10 pages). * cited by examiner U.S. Patent Jun. 28, 2011 Sheet 1 of 23 US 7,970,552 B1 38. • gene registists, SN's * ixitxeities: * sistice ixitxxix. * xxxxiigists&state: * g ex38xisg, sixxiiity Nutriest sex-axwww.www.wawawawawawao tis 888& health and receix iggeraxtix: production sexes kxxxixi, sigs: taxsixties: * 88xyge regixties: *ish::is raisixties: * taxesgxi regisixties * gags: 8 gigs intexxsetix8. MRTAssoirrg" ssex sistics F.G. 1 U.S. Patent Jun. 28, 2011 Sheet 3 of 23 US 7,970,552 B1 EEE CE AAS: A3, AASE SE CY8. GENOTYPE AND FUNCTIONAL {x^i} ^{{^A. (Ex: { ECC 30: - 3.x: - 3\{Xiaxi NORMAL (HEALTHY) ANIMALS (JN-EA... Y. ANiviAS -arror x 3Ex AASE U.S. Patent Jun. 28, 2011 Sheet 4 of 23 US 7,970,552 B1 £Nia 3-8 fri: 888 NESS 8: 88,3-33 – EEE-388: 83C: Rikas. 3888 -80. 8Y 83&. 8NA ANAYS$8 e.g., 88:8AR8AY C:\;x&S R388 C38A-33. 388. A 3888 & ES fro- Ex; 28:88 ER N. & ASE EC38:38.8 WAKA8. CSS is 83- 3 {Chi8:ENS is SEN: YE GENOvic PROFES OF ANMAI.S wir-i : FERENT 3ENory:RES, IE&Y }}E N:3 A. 8 PATHOLOGY OF THE AN-MA. SENSYE ker---------------T- EFFECT ON THE FunCEONA. GENOMiC C. C. E. N TRENT A-A. AA3 from s----------------- Exi Y SER ---------------aa--- a--- h;$8. ESR; Nixi:NS U.S. Patent Jun. 28, 2011 Sheet 7 of 23 US 7,970,552 B1 01| 01+vo|| 1+o-go|1 V7|1 w c: -: Y: re U.S. Patent Jun. 28, 2011 Sheet 8 of 23 US 7,970,552 B1 KEEE CE SA38 xxi.A. fxxix.3 TESTx £xSAMPLE {{- OF{* AN{x^{S ANIMAL xasy-awa'assassaxxasaaxa-swaxxYaxxas: { i Niš (E^{i 38: NORRA -EA-Y. ABKOREA. N-EATY :^COxi.A. (Ex.: FuNCTIONAL GENOMC 88: 3. wwaawaawaawwaawa. EN AAS: a 3& FG. 6A U.S. Patent Jun. 28, 2011 Sheet 9 of 23 US 7,970,552 B1 NDvDJALTARGET SAMPLE O. As Akitiki. (8 Ki-C3, fx {-Yo ES pro A&Y C. Ng's SCC Sf Foops ES S :- $8 38-3 SEC his S$8 FiG, 63 U.S. Patent Jun. 28, 2011 Sheet 10 of 23 US 7,970,552 B1 ki. 8888: 88 88.88: 880 friC. 7 U.S. Patent Jun. 28, 2011 Sheet 11 of 23 US 7,970,552 B1 ********* 8(8)*** U.S. Patent Jun. 28, 2011 Sheet 12 of 23 US 7,970,552 B1 dieckia sigraise of 83rograxxxiiie sciectar signatire of circuit : w: 3& 88 s & 8 'ss : ** s & xx 8'* 8 8as x x& * 8c s s x &^ && &8° && &8 U.S. Patent Jun. 28, 2011 Sheet 13 of 23 US 7,970,552 B1 :ww. 8. : s: a; 8. i. : i g Sf s ar, : U.S. Patent Jun. 28, 2011 Sheet 14 of 23 US 7,970,552 B1 U.S. Patent Jun. 28, 2011 Sheet 15 of 23 US 7,970,552 B1 TNFAIP6 TNFRSF13C NRSA NBS 8. U.S. Patent Jun. 28, 2011 Sheet 17 Of 23 US 7,970,552 B1 §§ sae & : s: -eodz/so»na sanae %%%&&&&&&&&&&&&&&********** saman? ********! } ***************** U.S. Patent Jun. 28, 2011 Sheet 18 of 23 US 7,970,552 B1 FIG 15 - f x: 88: U.S. Patent Jun. 28, 2011 Sheet 19 Of 23 US 7,970,552 B1 §? xx | t U.S. Patent Jun. 28, 2011 Sheet 20 of 23 US 7,970,552 B1 60 www-was xas--------- &;3. ~i 8-i 8 8. M ---------------- Maxw Assi8.333 s process recistration ;: ww - 's-----awasepowawa wax-axaawaamamamasa-Ya-Yama'awa'a-o-ra, P--- U.S. Patent Jun. 28, 2011 Sheet 21 of 23 US 7,970.552 B1 Xe *********** U.S. Patent Jun. 28, 2011 Sheet 22 of 23 US 7,970,552 B1 (x3,..??********** US 7,970,552 B1 1.
Load more

Recommended publications
  • RSF1 Regulates the Proliferation and Paclitaxel Resistance Via Modulating
    Journal of Cancer 2017, Vol. 8 354 Ivyspring International Publisher Journal of Cancer 2017; 8(3): 354-362. doi: 10.7150/jca.16720 Research Paper RSF1 regulates the proliferation and paclitaxel resistance via modulating NF-κB signaling pathway in nasopharyngeal carcinoma Yong Liu1,2, Guo Li1,2, Chao Liu1,2, Yaoyun Tang1,2, Shuai Zhang1,2 1. Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, China. 2. Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Changsha, 410008, Hunan, China. Corresponding author: Shuai Zhang, Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan, China. Tel.: +86073184327469; Fax: +86073184327469; E-mail: [email protected] (Zhang Shuai). © Ivyspring International Publisher. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions. Received: 2016.07.04; Accepted: 2016.10.15; Published: 2017.02.09 Abstract Purpose: Aberrant expression and dysfunction of RSF1 has been reported in diverse human malignancies. However, its exact role in nasopharyngeal carcinoma (NPC) remains unclear. Methods: The expression of RSF1 mRNA and protein were assayed by qRT-PCR and western blotting, and their correlations with clinicopathological parameters of patients with NPC were further analysed. Lentivirus mediated RSF1 shRNA and RSF1 cDNA were used to knockdown and upregulate the expression of RSF1. CCK8 assays and flow cytometry were applied to monitor the changes of proliferation and paclitaxel sensitivity caused by RSF1 modulation, inhibition of NF-κB pathway by inhibitor Bay 11-7082 and Survivin knockdown.
    [Show full text]
  • Wo 2010/075007 A2
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 1 July 2010 (01.07.2010) WO 2010/075007 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C12Q 1/68 (2006.01) G06F 19/00 (2006.01) kind of national protection available): AE, AG, AL, AM, C12N 15/12 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) International Application Number: DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/US2009/067757 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 11 December 2009 ( 11.12.2009) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, (26) Publication Language: English TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 12/3 16,877 16 December 2008 (16.12.2008) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, (71) Applicant (for all designated States except US): DODDS, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, W., Jean [US/US]; 938 Stanford Street, Santa Monica, TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, CA 90403 (US).
    [Show full text]
  • Upregulation of Peroxisome Proliferator-Activated Receptor-Α And
    Upregulation of peroxisome proliferator-activated receptor-α and the lipid metabolism pathway promotes carcinogenesis of ampullary cancer Chih-Yang Wang, Ying-Jui Chao, Yi-Ling Chen, Tzu-Wen Wang, Nam Nhut Phan, Hui-Ping Hsu, Yan-Shen Shan, Ming-Derg Lai 1 Supplementary Table 1. Demographics and clinical outcomes of five patients with ampullary cancer Time of Tumor Time to Age Differentia survival/ Sex Staging size Morphology Recurrence recurrence Condition (years) tion expired (cm) (months) (months) T2N0, 51 F 211 Polypoid Unknown No -- Survived 193 stage Ib T2N0, 2.41.5 58 F Mixed Good Yes 14 Expired 17 stage Ib 0.6 T3N0, 4.53.5 68 M Polypoid Good No -- Survived 162 stage IIA 1.2 T3N0, 66 M 110.8 Ulcerative Good Yes 64 Expired 227 stage IIA T3N0, 60 M 21.81 Mixed Moderate Yes 5.6 Expired 16.7 stage IIA 2 Supplementary Table 2. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of an ampullary cancer microarray using the Database for Annotation, Visualization and Integrated Discovery (DAVID). This table contains only pathways with p values that ranged 0.0001~0.05. KEGG Pathway p value Genes Pentose and 1.50E-04 UGT1A6, CRYL1, UGT1A8, AKR1B1, UGT2B11, UGT2A3, glucuronate UGT2B10, UGT2B7, XYLB interconversions Drug metabolism 1.63E-04 CYP3A4, XDH, UGT1A6, CYP3A5, CES2, CYP3A7, UGT1A8, NAT2, UGT2B11, DPYD, UGT2A3, UGT2B10, UGT2B7 Maturity-onset 2.43E-04 HNF1A, HNF4A, SLC2A2, PKLR, NEUROD1, HNF4G, diabetes of the PDX1, NR5A2, NKX2-2 young Starch and sucrose 6.03E-04 GBA3, UGT1A6, G6PC, UGT1A8, ENPP3, MGAM, SI, metabolism
    [Show full text]
  • Table 2. Significant
    Table 2. Significant (Q < 0.05 and |d | > 0.5) transcripts from the meta-analysis Gene Chr Mb Gene Name Affy ProbeSet cDNA_IDs d HAP/LAP d HAP/LAP d d IS Average d Ztest P values Q-value Symbol ID (study #5) 1 2 STS B2m 2 122 beta-2 microglobulin 1452428_a_at AI848245 1.75334941 4 3.2 4 3.2316485 1.07398E-09 5.69E-08 Man2b1 8 84.4 mannosidase 2, alpha B1 1416340_a_at H4049B01 3.75722111 3.87309653 2.1 1.6 2.84852656 5.32443E-07 1.58E-05 1110032A03Rik 9 50.9 RIKEN cDNA 1110032A03 gene 1417211_a_at H4035E05 4 1.66015788 4 1.7 2.82772795 2.94266E-05 0.000527 NA 9 48.5 --- 1456111_at 3.43701477 1.85785922 4 2 2.8237185 9.97969E-08 3.48E-06 Scn4b 9 45.3 Sodium channel, type IV, beta 1434008_at AI844796 3.79536664 1.63774235 3.3 2.3 2.75319499 1.48057E-08 6.21E-07 polypeptide Gadd45gip1 8 84.1 RIKEN cDNA 2310040G17 gene 1417619_at 4 3.38875643 1.4 2 2.69163229 8.84279E-06 0.0001904 BC056474 15 12.1 Mus musculus cDNA clone 1424117_at H3030A06 3.95752801 2.42838452 1.9 2.2 2.62132809 1.3344E-08 5.66E-07 MGC:67360 IMAGE:6823629, complete cds NA 4 153 guanine nucleotide binding protein, 1454696_at -3.46081884 -4 -1.3 -1.6 -2.6026947 8.58458E-05 0.0012617 beta 1 Gnb1 4 153 guanine nucleotide binding protein, 1417432_a_at H3094D02 -3.13334396 -4 -1.6 -1.7 -2.5946297 1.04542E-05 0.0002202 beta 1 Gadd45gip1 8 84.1 RAD23a homolog (S.
    [Show full text]
  • Transcriptomic Analysis of the Aquaporin (AQP) Gene Family
    Pancreatology 19 (2019) 436e442 Contents lists available at ScienceDirect Pancreatology journal homepage: www.elsevier.com/locate/pan Transcriptomic analysis of the Aquaporin (AQP) gene family interactome identifies a molecular panel of four prognostic markers in patients with pancreatic ductal adenocarcinoma Dimitrios E. Magouliotis a, b, Vasiliki S. Tasiopoulou c, Konstantinos Dimas d, * Nikos Sakellaridis d, Konstantina A. Svokos e, Alexis A. Svokos f, Dimitris Zacharoulis b, a Division of Surgery and Interventional Science, Faculty of Medical Sciences, UCL, London, UK b Department of Surgery, University of Thessaly, Biopolis, Larissa, Greece c Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece d Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Biopolis, Larissa, Greece e The Warren Alpert Medical School of Brown University, Providence, RI, USA f Riverside Regional Medical Center, Newport News, VA, USA article info abstract Article history: Background: This study aimed to assess the differential gene expression of aquaporin (AQP) gene family Received 14 October 2018 interactome in pancreatic ductal adenocarcinoma (PDAC) using data mining techniques to identify novel Received in revised form candidate genes intervening in the pathogenicity of PDAC. 29 January 2019 Method: Transcriptome data mining techniques were used in order to construct the interactome of the Accepted 9 February 2019 AQP gene family and to determine which genes members are differentially expressed in PDAC as Available online 11 February 2019 compared to controls. The same techniques were used in order to evaluate the potential prognostic role of the differentially expressed genes. Keywords: PDAC Results: Transcriptome microarray data of four GEO datasets were incorporated, including 142 primary Aquaporin tumor samples and 104 normal pancreatic tissue samples.
    [Show full text]
  • 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.
    [Show full text]
  • Reinforcement of STAT3 Activity Reprogrammes Human Embryonic Stem Cells to Naive-Like Pluripotency
    ARTICLE Received 17 Apr 2014 | Accepted 2 Apr 2015 | Published 13 May 2015 DOI: 10.1038/ncomms8095 OPEN Reinforcement of STAT3 activity reprogrammes human embryonic stem cells to naive-like pluripotency Hongwei Chen1,2, Ire`ne Aksoy1,2,3, Fabrice Gonnot1,2, Pierre Osteil1,2, Maxime Aubry1,2, Claire Hamela1,2, Cloe´ Rognard1,2, Arnaud Hochard1,2, Sophie Voisin1,2,4, Emeline Fontaine1,2, Magali Mure1,2, Marielle Afanassieff1,2,4, Elouan Cleroux5, Sylvain Guibert5, Jiaxuan Chen3,Ce´line Vallot6, Herve´ Acloque7, Cle´mence Genthon7,Ce´cile Donnadieu7, John De Vos8,9, Damien Sanlaville10, Jean- Franc¸ois Gue´rin1,2, Michael Weber5, Lawrence W. Stanton3, Claire Rougeulle6, Bertrand Pain1,2,4, Pierre-Yves Bourillot1,2 & Pierre Savatier1,2 Leukemia inhibitory factor (LIF)/STAT3 signalling is a hallmark of naive pluripotency in rodent pluripotent stem cells (PSCs), whereas fibroblast growth factor (FGF)-2 and activin/nodal signalling is required to sustain self-renewal of human PSCs in a condition referred to as the primed state. It is unknown why LIF/STAT3 signalling alone fails to sustain pluripotency in human PSCs. Here we show that the forced expression of the hormone-dependent STAT3-ER (ER, ligand-binding domain of the human oestrogen receptor) in combination with 2i/LIF and tamoxifen allows human PSCs to escape from the primed state and enter a state char- acterized by the activation of STAT3 target genes and long-term self-renewal in FGF2- and feeder-free conditions. These cells acquire growth properties, a gene expression profile and an epigenetic landscape closer to those described in mouse naive PSCs.
    [Show full text]
  • 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.
    [Show full text]
  • 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.
    [Show full text]
  • Discovery of Candidate Genes for Stallion Fertility from the Horse Y Chromosome
    DISCOVERY OF CANDIDATE GENES FOR STALLION FERTILITY FROM THE HORSE Y CHROMOSOME A Dissertation by NANDINA PARIA Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY August 2009 Major Subject: Biomedical Sciences DISCOVERY OF CANDIDATE GENES FOR STALLION FERTILITY FROM THE HORSE Y CHROMOSOME A Dissertation by NANDINA PARIA Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Approved by: Chair of Committee, Terje Raudsepp Committee Members, Bhanu P. Chowdhary William J. Murphy Paul B. Samollow Dickson D. Varner Head of Department, Evelyn Tiffany-Castiglioni August 2009 Major Subject: Biomedical Sciences iii ABSTRACT Discovery of Candidate Genes for Stallion Fertility from the Horse Y Chromosome. (August 2009) Nandina Paria, B.S., University of Calcutta; M.S., University of Calcutta Chair of Advisory Committee: Dr. Terje Raudsepp The genetic component of mammalian male fertility is complex and involves thousands of genes. The majority of these genes are distributed on autosomes and the X chromosome, while a small number are located on the Y chromosome. Human and mouse studies demonstrate that the most critical Y-linked male fertility genes are present in multiple copies, show testis-specific expression and are different between species. In the equine industry, where stallions are selected according to pedigrees and athletic abilities but not for reproductive performance, reduced fertility of many breeding stallions is a recognized problem. Therefore, the aim of the present research was to acquire comprehensive information about the organization of the horse Y chromosome (ECAY), identify Y-linked genes and investigate potential candidate genes regulating stallion fertility.
    [Show full text]
  • Boosting the Cellular Potency of Embryonic Stem Cells by Spliceosome Targeting ✉ Wilfried A
    Signal Transduction and Targeted Therapy www.nature.com/sigtrans RESEARCH HIGHLIGHT OPEN Boosting the cellular potency of embryonic stem cells by spliceosome targeting ✉ Wilfried A. Kues1 Signal Transduction and Targeted Therapy (2021) 6:324; https://doi.org/10.1038/s41392-021-00743-9 In recent work published in Cell, Shen et al.1 identified transfected ES cells with short interfering RNAs against different spliceosome inhibition in embryonic stem (ES) cells as a key spliceosome transcripts (the spliceosome consisted of 5 core and mechanism for the transition from pluri- to totipotency. Spliceo- several cofactor subunits, here 14 transcripts were targeted), some inhibition, achieved by RNA interference or the chemical respectively. Transient repression of 10 of the 14 splicing factors inhibitor pladienolide B, may gain widespread relevance to the resulted in ES cells, which maintained the typical colony culture of totipotent ES cells, in vitro differentiation of extra- morphology, however, pluripotent marker genes—Oct4 (Pou5f1), embryonal tissue and organoids, translation to the maintenance of Nanog, Sox2, Zfp42 and others—became down-regulated, at the pluripotent cells of other mammal species, including humans, and same time marker genes of totipotency—particularly Zscan4s and a better molecular understanding of cellular potency in stem cells MERVL—were up-regulated. Zscan4s (Zink finger and SCAN and cancer. domain containing 4) is a transcription factor and MERVL (murine The first successful isolation and maintenance of ES derived endogenous retrovirus L) an endogenous retrovirus with a usually fi 1234567890();,: from the inner cell mass (ICM) of murine blastocyst stages was restricted expression to 2-cell embryos. These results were veri ed described in 1981,2 and since then acted as game changer for by supplementing the culture medium with pladienolide B, a genetic studies in this mammalian model organism.
    [Show full text]
  • Genetic and Genomic Analysis of Hyperlipidemia, Obesity and Diabetes Using (C57BL/6J × TALLYHO/Jngj) F2 Mice
    University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Nutrition Publications and Other Works Nutrition 12-19-2010 Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice Taryn P. Stewart Marshall University Hyoung Y. Kim University of Tennessee - Knoxville, [email protected] Arnold M. Saxton University of Tennessee - Knoxville, [email protected] Jung H. Kim Marshall University Follow this and additional works at: https://trace.tennessee.edu/utk_nutrpubs Part of the Animal Sciences Commons, and the Nutrition Commons Recommended Citation BMC Genomics 2010, 11:713 doi:10.1186/1471-2164-11-713 This Article is brought to you for free and open access by the Nutrition at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Nutrition Publications and Other Works by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. Stewart et al. BMC Genomics 2010, 11:713 http://www.biomedcentral.com/1471-2164/11/713 RESEARCH ARTICLE Open Access Genetic and genomic analysis of hyperlipidemia, obesity and diabetes using (C57BL/6J × TALLYHO/JngJ) F2 mice Taryn P Stewart1, Hyoung Yon Kim2, Arnold M Saxton3, Jung Han Kim1* Abstract Background: Type 2 diabetes (T2D) is the most common form of diabetes in humans and is closely associated with dyslipidemia and obesity that magnifies the mortality and morbidity related to T2D. The genetic contribution to human T2D and related metabolic disorders is evident, and mostly follows polygenic inheritance. The TALLYHO/ JngJ (TH) mice are a polygenic model for T2D characterized by obesity, hyperinsulinemia, impaired glucose uptake and tolerance, hyperlipidemia, and hyperglycemia.
    [Show full text]