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A Supergene-Linked Estrogen Receptor Drives Alternative Phenotypes in a Polymorphic Songbird
A supergene-linked estrogen receptor drives alternative phenotypes in a polymorphic songbird Jennifer R. Merritta,1, Kathleen E. Grogana, Wendy M. Zinzow-Kramera, Dan Sunb, Eric A. Ortlundc, Soojin V. Yib, and Donna L. Maneya aDepartment of Psychology, Emory University, Atlanta, GA 30322; bSchool of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332; and cDepartment of Biochemistry, Emory University, Atlanta, GA 30322 Edited by Gene E. Robinson, University of Illinois at Urbana–Champaign, Urbana, IL, and approved July 8, 2020 (received for review June 3, 2020) Behavioral evolution relies on genetic changes, yet few behaviors tan-striped (TS) morph are homozygous for the standard ar- can be traced to specific genetic sequences in vertebrates. Here we rangement, ZAL2 (13, 14) (Fig. 1A). The rearrangement is provide experimental evidence showing that differentiation of a maintained in the population because of the species’ unique dis- single gene has contributed to the evolution of divergent behav- assortative mating system; nearly every breeding pair consists of ioral phenotypes in the white-throated sparrow, a common back- one individual of each morph (15). Because almost all WS birds yard songbird. In this species, a series of chromosomal inversions are heterozygous for ZAL2m (15, 16), this mating system keeps has formed a supergene that segregates with an aggressive phe- ZAL2m in a near-constant state of heterozygosity (Fig. 1B), pro- notype. The supergene has captured ESR1, the gene that encodes foundly suppressing recombination and causing it to differentiate estrogen receptor α (ERα); as a result, this gene is accumulating from ZAL2 (15, 17). changes that now distinguish the supergene allele from the stan- The rearranged region of ZAL2m in white-throated sparrows dard allele. -
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. -
WO 2019/079361 Al 25 April 2019 (25.04.2019) W 1P O PCT
(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization I International Bureau (10) International Publication Number (43) International Publication Date WO 2019/079361 Al 25 April 2019 (25.04.2019) W 1P O PCT (51) International Patent Classification: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, C12Q 1/68 (2018.01) A61P 31/18 (2006.01) DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, HN, C12Q 1/70 (2006.01) HR, HU, ID, IL, IN, IR, IS, JO, JP, KE, KG, KH, KN, KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, (21) International Application Number: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, PCT/US2018/056167 OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (22) International Filing Date: SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 16 October 2018 (16. 10.2018) TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (26) Publication Language: English GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, TZ, (30) Priority Data: UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 62/573,025 16 October 2017 (16. 10.2017) US TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, ΓΕ , IS, IT, LT, LU, LV, (71) Applicant: MASSACHUSETTS INSTITUTE OF MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, SM, TECHNOLOGY [US/US]; 77 Massachusetts Avenue, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, Cambridge, Massachusetts 02139 (US). -
Modulating Antiviral Response Via CRISPR–Cas Systems
viruses Review Immunity and Viral Infections: Modulating Antiviral Response via CRISPR–Cas Systems Sergey Brezgin 1,2,3,† , Anastasiya Kostyusheva 1,†, Ekaterina Bayurova 4 , Elena Volchkova 5, Vladimir Gegechkori 6 , Ilya Gordeychuk 4,7, Dieter Glebe 8 , Dmitry Kostyushev 1,3,*,‡ and Vladimir Chulanov 1,3,5,‡ 1 National Medical Research Center of Tuberculosis and Infectious Diseases, Ministry of Health, 127994 Moscow, Russia; [email protected] (S.B.); [email protected] (A.K.); [email protected] (V.C.) 2 Institute of Immunology, Federal Medical Biological Agency, 115522 Moscow, Russia 3 Scientific Center for Genetics and Life Sciences, Division of Biotechnology, Sirius University of Science and Technology, 354340 Sochi, Russia 4 Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products of Russian Academy of Sciences, 108819 Moscow, Russia; [email protected] (E.B.); [email protected] (I.G.) 5 Department of Infectious Diseases, Sechenov University, 119991 Moscow, Russia; [email protected] 6 Department of Pharmaceutical and Toxicological Chemistry, Sechenov University, 119991 Moscow, Russia; [email protected] 7 Department of Organization and Technology of Immunobiological Drugs, Sechenov University, 119991 Moscow, Russia 8 National Reference Center for Hepatitis B Viruses and Hepatitis D Viruses, Institute of Medical Virology, Justus Liebig University of Giessen, 35392 Giessen, Germany; [email protected] * Correspondence: [email protected] † Co-first authors. Citation: Brezgin, S.; Kostyusheva, ‡ Co-senior authors. A.; Bayurova, E.; Volchkova, E.; Gegechkori, V.; Gordeychuk, I.; Glebe, Abstract: Viral infections cause a variety of acute and chronic human diseases, sometimes resulting D.; Kostyushev, D.; Chulanov, V. Immunity and Viral Infections: in small local outbreaks, or in some cases spreading across the globe and leading to global pandemics. -
Identification of Potential Key Genes and Pathway Linked with Sporadic Creutzfeldt-Jakob Disease Based on Integrated Bioinformatics Analyses
medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened. -
"Description"" ""Generatio"
TABLE S4 "ID ""Description"" ""GeneRatio"" ""BgRatio"" ""pvalue"" ""p.adjust"" ""qvalue"" ""geneID"" ""Count""" "GO:0003712 ""GO:0003712"" ""transcription coregulator activity"" ""84/1859"" ""454/22744"" 9.49597175224444e-13 9.80933882006851e-10 8.20651874588704e-10 ""Ncoa2/Zfp451/Dhx9/Hnrnpu/Cited2/Ncoa7/Ccar1/ Sirt1/Arid5b/Sirt6/Med1/Rara/Atxn7l3/Ddx5/Wbp2/Hdac9/Zmynd11/Cdyl/ Mier3/Sfmbt1/Gata4/Med4/Basp1/Zfpm2/Zhx2/Ddx17/Mkl2/Hes1/Nrip1/Usp16/ Elob/Rrp1b/Rxrb/Kat2b/Mta3/Hsbp1l1/Tle4/Sfr1/Eid1/Cops2/Sox12/Raly/ Ncoa6/Rbm39/Lpin3/Skil/Jade1/Maml3/Supt20/Med12l/Hdgf/Glmp/Nfib/Jun/ Pex14/Rere/Psmd9/Ncor2/Trim24/Ruvbl1/Rybp/Bhlhe40/Atf7ip/Ube3a/Mef2a/ Nrg1/Rbpms/Cnot7/Sin3b/Pou4f2/Pkn1/Cdyl2/Taf5l/Irf2bp2/Birc2/Yap1/ Skor1/Tfdp2/Rad54l2/Ctnnb1/Limd1/Med14/Rap2c/Tbl1x"" 84" "GO:0003779 ""GO:0003779"" ""actin binding"" ""65/1859"" ""414/22744"" 2.57546466939442e-07 8.86818334494813e-05 7.41914559148359e-05 ""Actr3/Cxcr4/Hnrnpu/Enah/Utrn/Epb41l2/Marcks/Ctnna3/Eef2/Pawr/ Ccdc88a/Anxa6/Gas7/Lasp1/Tns4/Syne2/Sipa1l1/Syne3/Phactr1/Enc1/Pxk/ Vcl/Ang/Myo10/Mtss1/Triobp/Mkl2/Afdn/Daam2/Svil/Ctnna1/Synpo/Myo5b/ Nrap/Ablim1/Shtn1/Fmnl2/Itprid2/Ino80/Pfn2/Myoz2/Pdlim5/Cap1/Macf1/ Epb41/Wasf2/Myom3/Ywhah/Coro1c/Ssh1/Hip1/Ppp1r9a/Wasl/Ctnna2/Mical3/ Eps8/Tlnrd1/Myom2/Klhl2/Sntb2/Spire2/Coro2b/Clasp2/Hdac6/Diaph2"" 65" "GO:0046332 ""GO:0046332"" ""SMAD binding"" ""22/1859"" ""84/22744"" 6.87941766027971e-07 0.000177660961076723 0.000148631628923412 ""Bmpr2/Cited2/Usp15/Ddx5/Axin2/Ppm1a/Yy1/Gata4/Tgif1/Ldlrad4/Smad7/ Acvr2a/Pmepa1/Skil/Trim33/Jun/Mef2a/Ipo7/Skor1/Rnf111/Tcf12/Ctnnb1"" -
Corepressive Function of Nuclear Receptor Coactivator 2 in Androgen
Takeda et al. BMC Cancer (2016) 16:332 DOI 10.1186/s12885-016-2378-y RESEARCH ARTICLE Open Access Corepressive function of nuclear receptor coactivator 2 in androgen receptor of prostate cancer cells treated with antiandrogen Keisuke Takeda1, Noboru Hara1,2,3*, Tsutomu Nishiyama1, Masayuki Tasaki1, Fumio Ishizaki1 and Yoshihiko Tomita1 Abstract Background: Recruitment of cofactors in the interaction of the androgen receptor (AR) and AR ligands plays a critical role in determining androgenic/antiandrogenic effects of the AR ligand on signaling, but the functions of key cofactors, including nuclear receptor coactivator (NCOA), remain poorly understood in prostate cancer cells treated with AR ligands. Methods: We examined prostate cancer cell lines LNCaP and VCaP expressing mutated and wild-type ARs, respectively, to clarify the significance of NCOAs in the effect of antiandrogens. Hydroxyflutamide showed antagonistic activity against VCaP and an agonistic effect on LNCaP. Bicalutamide served as an antagonist for both. We analyzed mRNA transcription and protein expression of NCOAs in these cells pretreated with dihydrotestosterone and thereafter treated with the mentioned antiandrogens. Transcriptional silencing of candidate NCOAs and AR was performed using small interfering RNA (siRNA). Cell proliferation was evaluated with MTT assay. Results: LNCaP treated with bicalutamide showed an about four-fold increase in the expression of NCOA2 mRNA compared to those pretreated with dihydrotestosterone alone (P <0.01). In VCaP pretreated with dihydrotestosterone, transcriptions of NCOA2 and NCOA7 were slightly increased with bicalutamide (1.96- and 2. 42-fold, respectively) and hydroxyflutamide (1.33-fold in both). With Western blotting, the expression of NCOA2 protein also increased in LNCaP cells treated with bicalutamide compared with that in control cells pretreated with dihydrotestosterone alone. -
Targeted Shrna Screening Identified Critical Roles of Pleckstrin-2 in Erythropoiesis
Hematopoiesis SUPPLEMENTARY APPENDIX Targeted shRNA screening identified critical roles of pleckstrin-2 in erythropoiesis Baobing Zhao,1* Ganesan Keerthivasan,1* Yang Mei,1 Jing Yang,1 James McElherne,1 Piu Wong,2 John G. Doench,3 Gang Feng,4 David E. Root,3 and Peng Ji1 1Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, IL; 2Whitehead Institute for Biomedical Research, Cambridge, MA; 3Broad Institute of Harvard University and the Massachusetts Institute of Technology, Cambridge, MA; and 4Biomedical Informatics Center, Northwestern University, Chicago, IL, USA *BZ and GK contributed equally to this work. ©2014 Ferrata Storti Foundation. This is an open-access paper. doi:10.3324/haematol.2014.105809 Manuscript received on February 12, 2014. Manuscript accepted on April 14, 2014. Correspondence: [email protected] Supplemental Methods Purification and culture of fetal liver cells for targeted screening Fetal liver cells were isolated from E13.5 C57BL/6 embryos and mechanically dissociated by pipetting in PBS containing 10% fetal bovine serum (GIBCO). Single-cell suspensions were prepared by passing the dissociated cells through 40 µm cell strainers (BD Biosciences). Total fetal liver cells were labeled with biotin-conjugated anti-TER119 antibody (1:100) (eBioscience), and TER119 negative cells were purified using EasySep column free cell isolation system according to the manufacturer’s instructions (Stem Cell Technologies). Purified cells were seeded in round bottom 96 well plates at a cell density of 1x103 cells/200µl media/well. The purified cells were infected by distinct lentiviruses encoding shRNAs against selected genes in each well of the 96-well plate. The infection strategies were schematically illustrated in Figure 1A. -
And Nfkb1-Mediated Gene Expression in Inflammation and Carcinogenesis
British Journal of Cancer (2008) 99, 2070 – 2082 & 2008 Cancer Research UK All rights reserved 0007 – 0920/08 $32.00 www.bjcancer.com Regulatory potential for concerted modulation of Nrf2- and Nfkb1-mediated gene expression in inflammation and carcinogenesis 1,4 2 3 1 *,2 S Nair ,STDoh, JY Chan , A-N Kong and L Cai 1 2 Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Biomedical Engineering, 3 Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA; Department of Pathology, University of California, Irvine, CA 92697, USA Many studies have implicated nuclear factor E2-related factor 2 (Nrf2) and nuclear factor-kB1 (Nfkb1) in inflammation and cancer. However, the regulatory potential for crosstalk between these two important transcription factors in inflammation and carcinogenesis has not been explored. To delineate conserved transcription factor-binding site signatures, we performed bioinformatic analyses on the promoter regions of human and murine Nrf2 and Nfkb1. We performed multiple sequence alignment of Nrf2 and Nfkb1 genes in five mammalian species – human, chimpanzee, dog, mouse and rat – to explore conserved biological features. We constructed a canonical regulatory network for concerted modulation of Nrf2 and Nfkb1 involving several members of the mitogen-activated protein kinase (MAPK) family and present a putative model for concerted modulation of Nrf2 and Nfkb1 in inflammation/ carcinogenesis. Our results reflect potential for putative crosstalk between Nrf2 and Nfkb1 modulated through the MAPK cascade that may influence inflammation-associated etiopathogenesis of cancer. Taken together, the elucidation of potential relationships between Nrf2 and Nfkb1 may help to better understand transcriptional regulation, as well as transcription factor networks, associated with the etiopathogenesis of inflammation and cancer. -
The Landscape of Ahr Regulators and Coregulators to Fine-Tune Ahr Functions
International Journal of Molecular Sciences Review The Landscape of AhR Regulators and Coregulators to Fine-Tune AhR Functions Marco Gargaro †, Giulia Scalisi † , Giorgia Manni, Giada Mondanelli , Ursula Grohmann *,‡ and Francesca Fallarino *,‡ Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy; [email protected] (M.G.); [email protected] (G.S.); [email protected] (G.M.); [email protected] (G.M.) * Correspondence: [email protected] (U.G.); [email protected] (F.F.) † These authors contributed equally to this work. ‡ These authors share senior authorship. Abstract: The aryl-hydrocarbon receptor (AhR) is a ligand-activated transcription factor that me- diates numerous cellular responses. Originally investigated in toxicology because of its ability to bind environmental contaminants, AhR has attracted enormous attention in the field of immunology in the last 20 years. In addition, the discovery of endogenous and plant-derived ligands points to AhR also having a crucial role in normal cell physiology. Thus, AhR is emerging as a promiscuous receptor that can mediate either toxic or physiologic effects upon sensing multiple exogenous and endogenous molecules. Within this scenario, several factors appear to contribute to the outcome of gene transcriptional regulation by AhR, including the nature of the ligand as such and its further metabolism by AhR-induced enzymes, the local tissue microenvironment, and the presence of coregu- lators or specific transcription factors in the cell. Here, we review the current knowledge on the array of transcription factors and coregulators that, by interacting with AhR, tune its transcriptional activity in response to endogenous and exogenous ligands. -
Changes in Gene Expression of Histone Modification Enzymes in Rat
Maekawa et al. Journal of Ovarian Research (2016) 9:15 DOI 10.1186/s13048-016-0225-z RESEARCH Open Access Changes in gene expression of histone modification enzymes in rat granulosa cells undergoing luteinization during ovulation Ryo Maekawa, Lifa Lee, Maki Okada, Hiromi Asada, Masahiro Shinagawa, Isao Tamura, Shun Sato, Hiroshi Tamura and Norihiro Sugino* Abstract Background: The ovulatory LH surge rapidly alters the expression of steroidogenesis-related genes such as steroidogenic acute regulatory protein (StAR) in granulosa cells (GCs) undergoing luteinization. We recently reported that histone modifications contribute to these changes. Histone modifications are regulated by a variety of histone modification enzymes. This study investigated the changes in gene expression of histone modification enzymes in rat GCs undergoing luteinization after the induction of ovulation. The extracellular regulated kinase (ERK)-1/2 is a mediator in the intracellular signaling pathway stimulated by the ovulatory LH surge and regulates the expression of a number of genes in GCs. We further investigated whether ERK-1/2 is involved in the regulation of the histone modification at the StAR promoter region in GCs undergoing luteinization. Results: GCs were obtained from rats treated with equine chorionic gonadotropin (CG) before (0 h) and after human (h) CG injection. The expressions of 84 genes regulating histone modifications or DNA methylation were measured using a PCR array. Five genes (HDAC4, HDAC10, EZH2, SETDB2, and CIITA) were identified as histone acetylation- or histone methylation-related genes, and were significantly altered after hCG injection. None of the genes were related to DNA methylation. mRNA levels of EZH2, SETDB2, HDAC4,andHDAC10 decreased and CIITA mRNA levels increased 4 or 12 h after hCG injection. -
WO 2014/089124 Al 12 June 20 14 ( 12.06.20 14) W P O P C T
(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 WO 2014/089124 Al 12 June 20 14 ( 12.06.20 14) W P O P C T (51) International Patent Classification: BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, A61K 48/00 (2006.01) A61P 37/00 (2006.01) DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, A61K 39/395 (2006.01) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, (21) International Application Number: MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, PCT/US2013/072938 OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, (22) International Filing Date: SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, 3 December 2013 (03.12.2013) TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (25) Filing Language: English (84) Designated States (unless otherwise indicated, for every (26) Publication Language: English kind of regional protection available): ARIPO (BW, GH, (30) Priority Data: GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, SZ, TZ, 61/732,746 3 December 2012 (03. 12.2012) US UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, TJ, 61/747,653 31 December 2012 (3 1. 12.2012) US TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, ΓΓ, LT, LU, LV, (71) Applicants: CENEXYS, INC.