Schulz H

References (5)

Title : Soluble epoxide hydrolase is a susceptibility factor for heart failure in a rat model of human disease - Monti_2008_Nat.Genet_40_529
Author(s) : Monti J , Fischer J , Paskas S , Heinig M , Schulz H , Gosele C , Heuser A , Fischer R , Schmidt C , Schirdewan A , Gross V , Hummel O , Maatz H , Patone G , Saar K , Vingron M , Weldon SM , Lindpaintner K , Hammock BD , Rohde K , Dietz R , Cook SA , Schunck WH , Luft FC , Hubner N
Ref : Nat Genet , 40 :529 , 2008
Abstract : We aimed to identify genetic variants associated with heart failure by using a rat model of the human disease. We performed invasive cardiac hemodynamic measurements in F2 crosses between spontaneously hypertensive heart failure (SHHF) rats and reference strains. We combined linkage analyses with genome-wide expression profiling and identified Ephx2 as a heart failure susceptibility gene in SHHF rats. Specifically, we found that cis variation at Ephx2 segregated with heart failure and with increased transcript expression, protein expression and enzyme activity, leading to a more rapid hydrolysis of cardioprotective epoxyeicosatrienoic acids. To confirm our results, we tested the role of Ephx2 in heart failure using knockout mice. Ephx2 gene ablation protected from pressure overload-induced heart failure and cardiac arrhythmias. We further demonstrated differential regulation of EPHX2 in human heart failure, suggesting a cross-species role for Ephx2 in this complex disease.
ESTHER : Monti_2008_Nat.Genet_40_529
PubMedSearch : Monti_2008_Nat.Genet_40_529
PubMedID: 18443590

Title : Structural studies of a bifunctional inhibitor of neprilysin and DPP-IV - Oefner_2007_Acta.Crystallogr.D.Biol.Crystallogr_63_975
Author(s) : Oefner C , Pierau S , Schulz H , Dale GE
Ref : Acta Crystallographica D Biol Crystallogr , 63 :975 , 2007
Abstract : Neutral endopeptidase (NEP) is the major enzyme involved in the metabolic inactivation of a number of bioactive peptides including the enkephalins, substance P, endothelin, bradykinin and atrial natriuretic factor, as well as the incretin hormone glucagon-like peptide 1 (GLP-1), which is a potent stimulator of insulin secretion. The activity of GLP-1 is also rapidly abolished by the serine protease dipeptidyl peptidase IV (DPP-IV), which led to an elevated interest in inhibitors of this enzyme for the treatment of type II diabetes. A dual NEP/DPP-IV inhibitor concept is proposed, offering an alternative strategy for the treatment of type 2 diabetes. Here, the synthesis and crystal structures of the soluble extracellular domain of human NEP (residues 52-749) complexed with the NEP, competitive and potent dual NEP/DPP-IV inhibitor MCB3937 are described.
ESTHER : Oefner_2007_Acta.Crystallogr.D.Biol.Crystallogr_63_975
PubMedSearch : Oefner_2007_Acta.Crystallogr.D.Biol.Crystallogr_63_975
PubMedID: 17704566

Title : Genome sequence of the Brown Norway rat yields insights into mammalian evolution - Gibbs_2004_Nature_428_493
Author(s) : Gibbs RA , Weinstock GM , Metzker ML , Muzny DM , Sodergren EJ , Scherer S , Scott G , Steffen D , Worley KC , Burch PE , Okwuonu G , Hines S , Lewis L , DeRamo C , Delgado O , Dugan-Rocha S , Miner G , Morgan M , Hawes A , Gill R , Celera , Holt RA , Adams MD , Amanatides PG , Baden-Tillson H , Barnstead M , Chin S , Evans CA , Ferriera S , Fosler C , Glodek A , Gu Z , Jennings D , Kraft CL , Nguyen T , Pfannkoch CM , Sitter C , Sutton GG , Venter JC , Woodage T , Smith D , Lee HM , Gustafson E , Cahill P , Kana A , Doucette-Stamm L , Weinstock K , Fechtel K , Weiss RB , Dunn DM , Green ED , Blakesley RW , Bouffard GG , de Jong PJ , Osoegawa K , Zhu B , Marra M , Schein J , Bosdet I , Fjell C , Jones S , Krzywinski M , Mathewson C , Siddiqui A , Wye N , McPherson J , Zhao S , Fraser CM , Shetty J , Shatsman S , Geer K , Chen Y , Abramzon S , Nierman WC , Havlak PH , Chen R , Durbin KJ , Egan A , Ren Y , Song XZ , Li B , Liu Y , Qin X , Cawley S , Cooney AJ , D'Souza LM , Martin K , Wu JQ , Gonzalez-Garay ML , Jackson AR , Kalafus KJ , McLeod MP , Milosavljevic A , Virk D , Volkov A , Wheeler DA , Zhang Z , Bailey JA , Eichler EE , Tuzun E , Birney E , Mongin E , Ureta-Vidal A , Woodwark C , Zdobnov E , Bork P , Suyama M , Torrents D , Alexandersson M , Trask BJ , Young JM , Huang H , Wang H , Xing H , Daniels S , Gietzen D , Schmidt J , Stevens K , Vitt U , Wingrove J , Camara F , Mar Alba M , Abril JF , Guigo R , Smit A , Dubchak I , Rubin EM , Couronne O , Poliakov A , Hubner N , Ganten D , Goesele C , Hummel O , Kreitler T , Lee YA , Monti J , Schulz H , Zimdahl H , Himmelbauer H , Lehrach H , Jacob HJ , Bromberg S , Gullings-Handley J , Jensen-Seaman MI , Kwitek AE , Lazar J , Pasko D , Tonellato PJ , Twigger S , Ponting CP , Duarte JM , Rice S , Goodstadt L , Beatson SA , Emes RD , Winter EE , Webber C , Brandt P , Nyakatura G , Adetobi M , Chiaromonte F , Elnitski L , Eswara P , Hardison RC , Hou M , Kolbe D , Makova K , Miller W , Nekrutenko A , Riemer C , Schwartz S , Taylor J , Yang S , Zhang Y , Lindpaintner K , Andrews TD , Caccamo M , Clamp M , Clarke L , Curwen V , Durbin R , Eyras E , Searle SM , Cooper GM , Batzoglou S , Brudno M , Sidow A , Stone EA , Payseur BA , Bourque G , Lopez-Otin C , Puente XS , Chakrabarti K , Chatterji S , Dewey C , Pachter L , Bray N , Yap VB , Caspi A , Tesler G , Pevzner PA , Haussler D , Roskin KM , Baertsch R , Clawson H , Furey TS , Hinrichs AS , Karolchik D , Kent WJ , Rosenbloom KR , Trumbower H , Weirauch M , Cooper DN , Stenson PD , Ma B , Brent M , Arumugam M , Shteynberg D , Copley RR , Taylor MS , Riethman H , Mudunuri U , Peterson J , Guyer M , Felsenfeld A , Old S , Mockrin S , Collins F
Ref : Nature , 428 :493 , 2004
Abstract : The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.
ESTHER : Gibbs_2004_Nature_428_493
PubMedSearch : Gibbs_2004_Nature_428_493
PubMedID: 15057822
Gene_locus related to this paper: rat-abhea , rat-abheb , rat-cd029 , rat-d3zaw4 , rat-dpp9 , rat-d3zhq1 , rat-d3zkp8 , rat-d3zuq1 , rat-d3zxw8 , rat-d4a4w4 , rat-d4a7w1 , rat-d4a9l7 , rat-d4a071 , rat-d4aa31 , rat-d4aa33 , rat-d4aa61 , rat-dglb , rat-f1lz91 , rat-Kansl3 , rat-nceh1 , rat-Tex30 , ratno-1hlip , ratno-1neur , ratno-1plip , ratno-2neur , ratno-3neur , ratno-3plip , ratno-ABH15 , ratno-ACHE , ratno-balip , ratno-BCHE , ratno-cauxin , ratno-Ces1d , ratno-Ces1e , ratno-Ces2f , ratno-d3ze31 , ratno-d3zp14 , ratno-d3zxi3 , ratno-d3zxq0 , ratno-d3zxq1 , ratno-d4a3d4 , ratno-d4aa05 , ratno-dpp4 , ratno-dpp6 , ratno-est8 , ratno-FAP , ratno-hyep , ratno-hyes , ratno-kmcxe , ratno-lmcxe , ratno-LOC246252 , ratno-MGLL , ratno-pbcxe , ratno-phebest , ratno-Ppgb , ratno-q4qr68 , ratno-q6ayr2 , ratno-q6q629 , ratno-SPG21 , ratno-thyro , rat-m0rc77 , rat-a0a0g2k9y7 , rat-a0a0g2kb83 , rat-d3zba8 , rat-d3zbj1 , rat-d3zcr8 , rat-d3zxw5 , rat-d4a340 , rat-f1lvg7 , rat-m0r509 , rat-m0r5d4 , rat-b5den3 , rat-d3zxk4 , rat-d4a1b6 , rat-d3zmg4 , rat-ab17c

Title : Epidemiological investigations and experimental model studies on exposure of pesticides - Desi_1998_Toxicol.Lett_97_351
Author(s) : Desi I , Nagymajtenyi L , Schulz H , Nehez M
Ref : Toxicol Lett , 97 :351 , 1998
Abstract : Authors carried on epidemiological examinations on plant protection workers to find early symptoms (biomarkers) of moderate contamination by pesticides. Measurement of changes in cholinesterase and gamma glutamyltransferase enzyme activity did not reveal that people were affected. Determination of chromosome abnormalities from peripheral lymphocytes disclosed numerical aberrations at an early stage and lasted after cessation of work for several months. There were differences in the results among different groups of plant protection workers, as well as among those working in open field or in glasshouses. Women, who carried out horticultural work in glasshouses after spraying showed some chromosome abnormalities too. Experimental rats treated chronically with organophosphates exhibited changes in spontaneous and evoked brain electrical activity (ECoG). Concerning the peripheral nervous activity, conduction velocity became slower, absolute and relative refractory periods became longer. These proved sensitive biomarkers too, which could be used in early detection of contamination.
ESTHER : Desi_1998_Toxicol.Lett_97_351
PubMedSearch : Desi_1998_Toxicol.Lett_97_351
PubMedID: 9820688

Title : Life-time exposure to dichlorvos affects behaviour of mature rats - Schulz_1995_Human.Exp.Toxicol_14_721
Author(s) : Schulz H , Nagymajtenyi L , Desi I
Ref : Hum Exp Toxicol , 14 :721 , 1995
Abstract : Wistar rats were exposed to dichlorvos [CAS number 62737]. Doses were 1/25; 1/50; and 1/100 LD50, that is 3.88; 1.94; 1.46; and 0.97 mg kg-1 DDVP, respectively, throughout gestation (GD1-birth) and during suckling via oral dosing to the dams, and then via the same doses by gavage for the rest of their lives. The offspring were tested in an open field (OF), a multiple T-maze, and in a 'novelty-induced-grooming' test to assess behavioural competence as adults. Dose-related increases in running time and incorrect choices in the maze were observed during the first 2 weeks of a 3-week study at 9-11 weeks of age. Horizontal activity was increased, vertical activity decreased, and defecation decreased in the OF at 9-12 weeks of age; these changes were again dose-related. Sleep was also affected at 12 weeks of age. AChE activity in the brain and in blood at sacrifice was roughly 40% to 65% of control, again reflecting the doses administered. The significantly changed behavioural profile of DDVP treated rats may serve as a useful biomarker to judge functional damage of CNS properties.
ESTHER : Schulz_1995_Human.Exp.Toxicol_14_721
PubMedSearch : Schulz_1995_Human.Exp.Toxicol_14_721
PubMedID: 8579882