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Author Report for: Zimmer A

Title: Regulation of adult neurogenesis by the endocannabinoid-producing enzyme diacylglycerol lipase alpha (DAGLa)
Schuele LL, Schuermann B, Bilkei-Gorzo A, Gorgzadeh S, Zimmer A, Leidmaa E
Ref: Sci Rep, 12:633, 2022 : PubMed
Abstract


ESTHER: Schuele_2022_Sci.Rep_12_633
PubMedSearch: Schuele 2022 Sci.Rep 12 633
PubMedID: 35022487
Gene_locus related to this paper: human-DAGLA, mouse-q6wqj1

Abstract

The endocannabinoid system modulates adult hippocampal neurogenesis by promoting the proliferation and survival of neural stem and progenitor cells (NSPCs). This is demonstrated by the disruption of adult neurogenesis under two experimental conditions: (1) NSPC-specific deletion of cannabinoid receptors and (2) constitutive deletion of the enzyme diacylglycerol lipase alpha (DAGLa) which produces the endocannabinoid 2-arachidonoylglycerol (2-AG). However, the specific cell types producing 2-AG relevant to neurogenesis remain unknown. Here we sought to identify the cellular source of endocannabinoids in the subgranular zone of the dentate gyrus (DG) in hippocampus, an important neurogenic niche. For this purpose, we used two complementary Cre-deleter mouse strains to delete Dagla either in neurons, or in astroglia and NSPCs. Surprisingly, neurogenesis was not altered in mice bearing a deletion of Dagla in neurons (Syn-Dagla KO), although neurons are the main source for the endocannabinoids in the brain. In contrast, a specific inducible deletion of Dagla in NPSCs and astrocytes (GLAST-CreERT2-Dagla KO) resulted in a strongly impaired neurogenesis with a 50% decrease in proliferation of newborn cells. These results identify Dagla in NSPCs in the DG or in astrocytes as a prominent regulator of adult hippocampal neurogenesis. We also show a reduction of Daglb expression in GLAST-CreERT2-Dagla KO mice, which may have contributed to the neurogenesis phenotype.



        

Title: Elevated levels of 2-arachidonoylglycerol promote atherogenesis in ApoE-/- mice
Jehle J, Schone B, Bagheri S, Avraamidou E, Danisch M, Frank I, Pfeifer P, Bindila L, Lutz B and Nickenig G <2 more author(s)> Jehle J, Schone B, Bagheri S, Avraamidou E, Danisch M, Frank I, Pfeifer P, Bindila L, Lutz B, Lutjohann D, Zimmer A, Nickenig G (- 2)
Ref: PLoS ONE, 13:e0197751, 2018 : PubMed
Abstract


ESTHER: Jehle_2018_PLoS.One_13_e0197751
PubMedSearch: Jehle 2018 PLoS.One 13 e0197751
PubMedID: 29813086

Abstract

BACKGROUND: The endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is a known modulator of inflammation and ligand to both, pro-inflammatory cannabinoid receptor 1 (CB1) and anti-inflammatory CB2. While the role of both receptors in atherogenesis has been studied extensively, the significance of 2-AG for atherogenesis is less well characterized. METHODS: The impact of 2-AG on atherogenesis was studied in two treatment groups of ApoE-/- mice. One group received the monoacylglycerol lipase (MAGL)-inhibitor JZL184 [5 mg/kg i.p.], which impairs 2-AG degradation and thus causes elevated 2-AG levels, the other group received vehicle for four weeks. Simultaneously, both groups were fed a high-cholesterol diet. The atherosclerotic plaque burden was assessed in frozen sections through the aortic sinus following oil red O staining and infiltrating macrophages were detected by immunofluorescence targeting CD68. In vitro, the effect of 2-AG on B6MCL macrophage migration was assessed by Boyden chamber experiments. Transcription of adhesion molecules and chemokine receptors in macrophages was assessed by qPCR. RESULTS: As expected, application of the MAGL-inhibitor JZL184 resulted in a significant increase in 2-AG levels in vascular tissue (98.2 +/- 16.1 nmol/g vs. 27.3 +/- 4.5 nmol/g; n = 14-16; p < 0.001). ApoE-/- mice with elevated 2-AG levels displayed a significantly increased plaque burden compared to vehicle treated controls (0.44 +/- 0.03 vs. 0.31 +/- 0.04; n = 14; p = 0.0117). This was accompanied by a significant increase in infiltrating macrophages within the atherosclerotic vessel wall (0.33 +/- 0.02 vs. 0.27 +/- 0.01; n = 13-14; p = 0.0076). While there was no alteration to the white blood counts of JZL184-treated animals, 2-AG enhanced macrophage migration in vitro by 1.8 +/- 0.2 -fold (n = 4-6; p = 0.0393) compared to vehicle, which was completely abolished by co-administration of either CB1- or CB2-receptor-antagonists. qPCR analyses of 2-AG-stimulated macrophages showed an enhanced transcription of the chemokine CCL5 (1.59 +/- 0.23 -fold; n = 5-6; p = 0.0589) and its corresponding receptors CCR1 (2.04 +/- 0.46 -fold; n = 10-11; p = 0.0472) and CCR5 (2.45 +/- 0.62 -fold; n = 5-6; p = 0.0554). CONCLUSION: Taken together, elevated 2-AG levels appear to promote atherogenesis in vivo. Our data suggest that 2-AG promotes macrophage migration, possibly by the CCL5-CCR5/CCR1 axis, and thereby contributes to vascular inflammation. Thus, decreasing vascular 2-AG levels might represent a promising therapeutic strategy in patients suffering from atherosclerosis and coronary heart disease.



        

Title: Monoglyceride lipase deficiency affects hepatic cholesterol metabolism and lipid-dependent gut transit in ApoE-/- mice
Vujic N, Korbelius M, Leopold C, Duta-Mare M, Rainer S, Schlager S, Goeritzer M, Kolb D, Eichmann TO and Kratky D <5 more author(s)> Vujic N, Korbelius M, Leopold C, Duta-Mare M, Rainer S, Schlager S, Goeritzer M, Kolb D, Eichmann TO, Diwoky C, Zimmer A, Zimmermann R, Lass A, Radovic B, Kratky D (- 5)
Ref: Oncotarget, 8:33122, 2017 : PubMed
Abstract


ESTHER: Vujic_2017_Oncotarget_8_33122
PubMedSearch: Vujic 2017 Oncotarget 8 33122
PubMedID: 28380440

Abstract

Monoglyceride lipase (MGL) hydrolyzes monoglycerides (MGs) to glycerol and fatty acids. Among various MG species MGL also degrades 2-arachidonoylglycerol (2-AG), the most abundant endocannabinoid and potent activator of cannabinoid receptors (CBR) 1 and 2. MGL-knockout (-/-) mice exhibit pronounced 2-AG accumulation, but lack central cannabimimetic effects due to CB1R desensitization. We have previously shown that MGL affects plaque stability in apolipoprotein E (ApoE)-/- mice, an established animal model for dyslipidemia and atherosclerosis. In the current study, we investigated functional consequences of MGL deficiency on lipid and energy metabolism in ApoE/MGL double knockout (DKO) mice. MGL deficiency affected hepatic cholesterol metabolism by causing increased cholesterol elimination via the biliary pathway. Moreover, DKO mice exhibit lipid-triggered delay in gastric emptying without major effects on overall triglyceride and cholesterol absorption. The observed phenotype of DKO mice is likely not a consequence of potentiated CB1R signaling but rather dependent on the activation of alternative signaling pathways. We conclude that MGL deficiency causes complex metabolic changes including cholesterol metabolism and regulation of gut transit independent of the endocannabinoid system.



        

Title: Myeloid-Specific Deletion of Diacylglycerol Lipase alpha Inhibits Atherogenesis in ApoE-Deficient Mice
Jehle J, Hoyer FF, Schone B, Pfeifer P, Schild K, Jenniches I, Bindila L, Lutz B, Lutjohann D and Nickenig G <1 more author(s)> Jehle J, Hoyer FF, Schone B, Pfeifer P, Schild K, Jenniches I, Bindila L, Lutz B, Lutjohann D, Zimmer A, Nickenig G (- 1)
Ref: PLoS ONE, 11:e0146267, 2016 : PubMed
Abstract


ESTHER: Jehle_2016_PLoS.One_11_e0146267
PubMedSearch: Jehle 2016 PLoS.One 11 e0146267
PubMedID: 26731274

Abstract

BACKGROUND: The endocannabinoid 2-arachidonoylglycerol (2-AG) is a known modulator of inflammation. Despite its high concentration in vascular tissue, the role of 2-AG in atherogenesis has not yet been examined.
METHODS: ApoE-deficient mice were sublethally irradiated and reconstituted with bone marrow from mice with a myeloid-specific knockout of the 2-AG synthesising enzyme diacylglycerol lipase alpha (Dagla) or control bone marrow with an intact 2-AG biosynthesis. After a cholesterol-rich diet for 8 weeks, plaque size and plaque morphology were examined in chimeric mice. Circulating inflammatory cells were assessed by flow cytometry. Aortic tissue and plasma levels of endocannabinoids were measured using liquid chromatography-multiple reaction monitoring.
RESULTS: Mice with Dagla-deficient bone marrow and circulating myeloid cells showed a significantly reduced plaque burden compared to controls. The reduction in plaque size was accompanied by a significantly diminished accumulation of both neutrophil granulocytes and macrophages in atherosclerotic lesions of Dagla-deficient mice. Moreover, CB2 expression and the amount of oxidised LDL within atherosclerotic lesions was significantly reduced. FACS analyses revealed that levels of circulating inflammatory cells were unaltered in Dagla-deficient mice.
CONCLUSIONS: Myeloid synthesis of the endocannabinoid 2-AG appears to promote vascular inflammation and atherogenesis. Thus, myeloid-specific disruption of 2-AG synthesis may represent a potential novel therapeutic strategy against atherosclerosis.



        

Title: Age-related changes in the endocannabinoid system in the mouse hippocampus
Piyanova A, Lomazzo E, Bindila L, Lerner R, Albayram O, Ruhl T, Lutz B, Zimmer A, Bilkei-Gorzo A
Ref: Mech Ageing Dev, 150:55, 2015 : PubMed
Abstract


ESTHER: Piyanova_2015_Mech.Ageing.Dev_150_55
PubMedSearch: Piyanova 2015 Mech.Ageing.Dev 150 55
PubMedID: 26278494

Abstract

Previous studies have demonstrated that the endocannabinoid system significantly influences the progression of brain ageing, and the hippocampus is one of the brain regions most vulnerable to ageing and neurodegeneration. We have further examined age-related changes in the hippocampal endocannabinoid system by measuring the levels of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) in young and old mice from two different mouse strains. We found a decrease in 2-AG but not AEA levels in aged mice. In order to identify the cause for 2-AG level changes, we investigated the levels of several enzymes that contribute to synthesis and degradation of 2-AG in the hippocampus. We found a selective decrease in DAGLalpha mRNA and protein levels as well as an elevated MAGL activity during ageing. We hypothesize that the observed decrease of 2-AG levels is probably caused by changes in DAGLalpha expression and MAGL activity. This finding can contribute to the existing knowledge about the processes underlying selective vulnerability of the hippocampus to ageing and age-related neurodegeneration.



        

Title: Genetic Manipulation of the Endocannabinoid System
Zimmer A
Ref: Handb Exp Pharmacol, 231:129, 2015 : PubMed
Abstract


ESTHER: Zimmer_2015_Handb.Exp.Pharmacol_231_129
PubMedSearch: Zimmer 2015 Handb.Exp.Pharmacol 231 129
PubMedID: 26408160

Abstract

The physiological and pathophysiological functions of the endocannabinoid system have been studied extensively using transgenic and targeted knockout mouse models. The first gene deletions of the cannabinoid CB(1) receptor were described in the late 1990s, soon followed by CB(2) and FAAH mutations in early 2000. These mouse models helped to elucidate the fundamental role of endocannabinoids as retrograde transmitters in the CNS and in the discovery of many unexpected endocannabinoid functions, for example, in the skin, bone and liver. We now have knockout mouse models for almost every receptor and enzyme of the endocannabinoid system. Conditional mutant mice were mostly developed for the CB(1) receptor, which is widely expressed on many different neurons, astrocytes and microglia, as well as on many cells outside the CNS. These mouse strains include "floxed" CB(1) alleles and mice with a conditional re-expression of CB(1). The availability of these mice made it possible to decipher the function of CB(1) in specific neuronal circuits and cell populations or to discriminate between central and peripheral effects. Many of the genetic mouse models were also used in combination with viral expression systems. The purpose of this review is to provide a comprehensive overview of the existing genetic models and to summarize some of the most important discoveries that were made with these animals.



        

Title: Activation of type 5 metabotropic glutamate receptors and diacylglycerol lipase-alpha initiates 2-arachidonoylglycerol formation and endocannabinoid-mediated analgesia
Gregg LC, Jung KM, Spradley JM, Nyilas R, Suplita RL, 2nd, Zimmer A, Watanabe M, Mackie K, Katona I and Hohmann AG <1 more author(s)> Gregg LC, Jung KM, Spradley JM, Nyilas R, Suplita RL, 2nd, Zimmer A, Watanabe M, Mackie K, Katona I, Piomelli D, Hohmann AG (- 1)
Ref: Journal of Neuroscience, 32:9457, 2012 : PubMed
Abstract


ESTHER: Gregg_2012_J.Neurosci_32_9457
PubMedSearch: Gregg 2012 J.Neurosci 32 9457
PubMedID: 22787031
Gene_locus related to this paper: human-DAGLA
Inhibitor(s) related to this paper: L-Isoleucine-Orlistat

Abstract

Acute stress reduces pain sensitivity by engaging an endocannabinoid signaling circuit in the midbrain. The neural mechanisms governing this process and molecular identity of the endocannabinoid substance(s) involved are unknown. We combined behavior, pharmacology, immunohistochemistry, RNA interference, quantitative RT-PCR, enzyme assays, and lipidomic analyses of endocannabinoid content to uncover the role of the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG) in controlling pain sensitivity in vivo. Here, we show that footshock stress produces antinociception in rats by activating type 5 metabotropic glutamate receptors (mGlu(5)) in the dorsolateral periaqueductal gray (dlPAG) and mobilizing 2-AG. Stimulation of mGlu(5) in the dlPAG with DHPG [(S)-3,5-dihydroxyphenylglycine] triggered 2-AG formation and enhanced stress-dependent antinociception through a mechanism dependent upon both postsynaptic diacylglycerol lipase (DGL) activity, which releases 2-AG, and presynaptic CB(1) cannabinoid receptors. Pharmacological blockade of DGL activity in the dlPAG with RHC80267 [1,6-bis(cyclohexyloximinocarbonylamino)hexane] and (-)-tetrahydrolipstatin (THL), which inhibit activity of DGL-alpha and DGL-beta isoforms, suppressed stress-induced antinociception. Inhibition of DGL activity in the dlPAG with THL selectively decreased accumulation of 2-AG without altering levels of anandamide. The putative 2-AG-synthesizing enzyme DGL-alpha colocalized with mGlu(5) at postsynaptic sites of the dlPAG, whereas CB(1) was confined to presynaptic terminals, consistent with a role for 2-AG as a retrograde signaling messenger. Finally, virally mediated silencing of DGL-alpha, but not DGL-beta, transcription in the dlPAG mimicked effects of DGL inhibition in suppressing both endocannabinoid-mediated stress antinociception and 2-AG formation. The results indicate that activation of the postsynaptic mGlu(5)-DGL-alpha cascade triggers retrograde 2-AG signaling in vivo. This pathway is required for endocannabinoid-mediated stress-induced analgesia.



        

Title: Evolution of genes and genomes on the Drosophila phylogeny
Clark AG, Eisen MB, Smith DR, Bergman CM, Oliver B, Markow TA, Kaufman TC, Kellis M, Gelbart W and MacCallum I <405 more author(s)> Clark AG, Eisen MB, Smith DR, Bergman CM, Oliver B, Markow TA, Kaufman TC, Kellis M, Gelbart W, Iyer VN, Pollard DA, Sackton TB, Larracuente AM, Singh ND, Abad JP, Abt DN, Adryan B, Aguade M, Akashi H, Anderson WW, Aquadro CF, Ardell DH, Arguello R, Artieri CG, Barbash DA, Barker D, Barsanti P, Batterham P, Batzoglou S, Begun D, Bhutkar A, Blanco E, Bosak SA, Bradley RK, Brand AD, Brent MR, Brooks AN, Brown RH, Butlin RK, Caggese C, Calvi BR, Bernardo de Carvalho A, Caspi A, Castrezana S, Celniker SE, Chang JL, Chapple C, Chatterji S, Chinwalla A, Civetta A, Clifton SW, Comeron JM, Costello JC, Coyne JA, Daub J, David RG, Delcher AL, Delehaunty K, Do CB, Ebling H, Edwards K, Eickbush T, Evans JD, Filipski A, Findeiss S, Freyhult E, Fulton L, Fulton R, Garcia AC, Gardiner A, Garfield DA, Garvin BE, Gibson G, Gilbert D, Gnerre S, Godfrey J, Good R, Gotea V, Gravely B, Greenberg AJ, Griffiths-Jones S, Gross S, Guigo R, Gustafson EA, Haerty W, Hahn MW, Halligan DL, Halpern AL, Halter GM, Han MV, Heger A, Hillier L, Hinrichs AS, Holmes I, Hoskins RA, Hubisz MJ, Hultmark D, Huntley MA, Jaffe DB, Jagadeeshan S, Jeck WR, Johnson J, Jones CD, Jordan WC, Karpen GH, Kataoka E, Keightley PD, Kheradpour P, Kirkness EF, Koerich LB, Kristiansen K, Kudrna D, Kulathinal RJ, Kumar S, Kwok R, Lander E, Langley CH, Lapoint R, Lazzaro BP, Lee SJ, Levesque L, Li R, Lin CF, Lin MF, Lindblad-Toh K, Llopart A, Long M, Low L, Lozovsky E, Lu J, Luo M, Machado CA, Makalowski W, Marzo M, Matsuda M, Matzkin L, McAllister B, McBride CS, McKernan B, McKernan K, Mendez-Lago M, Minx P, Mollenhauer MU, Montooth K, Mount SM, Mu X, Myers E, Negre B, Newfeld S, Nielsen R, Noor MA, O'Grady P, Pachter L, Papaceit M, Parisi MJ, Parisi M, Parts L, Pedersen JS, Pesole G, Phillippy AM, Ponting CP, Pop M, Porcelli D, Powell JR, Prohaska S, Pruitt K, Puig M, Quesneville H, Ram KR, Rand D, Rasmussen MD, Reed LK, Reenan R, Reily A, Remington KA, Rieger TT, Ritchie MG, Robin C, Rogers YH, Rohde C, Rozas J, Rubenfield MJ, Ruiz A, Russo S, Salzberg SL, Sanchez-Gracia A, Saranga DJ, Sato H, Schaeffer SW, Schatz MC, Schlenke T, Schwartz R, Segarra C, Singh RS, Sirot L, Sirota M, Sisneros NB, Smith CD, Smith TF, Spieth J, Stage DE, Stark A, Stephan W, Strausberg RL, Strempel S, Sturgill D, Sutton G, Sutton GG, Tao W, Teichmann S, Tobari YN, Tomimura Y, Tsolas JM, Valente VL, Venter E, Venter JC, Vicario S, Vieira FG, Vilella AJ, Villasante A, Walenz B, Wang J, Wasserman M, Watts T, Wilson D, Wilson RK, Wing RA, Wolfner MF, Wong A, Wong GK, Wu CI, Wu G, Yamamoto D, Yang HP, Yang SP, Yorke JA, Yoshida K, Zdobnov E, Zhang P, Zhang Y, Zimin AV, Baldwin J, Abdouelleil A, Abdulkadir J, Abebe A, Abera B, Abreu J, Acer SC, Aftuck L, Alexander A, An P, Anderson E, Anderson S, Arachi H, Azer M, Bachantsang P, Barry A, Bayul T, Berlin A, Bessette D, Bloom T, Blye J, Boguslavskiy L, Bonnet C, Boukhgalter B, Bourzgui I, Brown A, Cahill P, Channer S, Cheshatsang Y, Chuda L, Citroen M, Collymore A, Cooke P, Costello M, D'Aco K, Daza R, De Haan G, DeGray S, DeMaso C, Dhargay N, Dooley K, Dooley E, Doricent M, Dorje P, Dorjee K, Dupes A, Elong R, Falk J, Farina A, Faro S, Ferguson D, Fisher S, Foley CD, Franke A, Friedrich D, Gadbois L, Gearin G, Gearin CR, Giannoukos G, Goode T, Graham J, Grandbois E, Grewal S, Gyaltsen K, Hafez N, Hagos B, Hall J, Henson C, Hollinger A, Honan T, Huard MD, Hughes L, Hurhula B, Husby ME, Kamat A, Kanga B, Kashin S, Khazanovich D, Kisner P, Lance K, Lara M, Lee W, Lennon N, Letendre F, LeVine R, Lipovsky A, Liu X, Liu J, Liu S, Lokyitsang T, Lokyitsang Y, Lubonja R, Lui A, Macdonald P, Magnisalis V, Maru K, Matthews C, McCusker W, McDonough S, Mehta T, Meldrim J, Meneus L, Mihai O, Mihalev A, Mihova T, Mittelman R, Mlenga V, Montmayeur A, Mulrain L, Navidi A, Naylor J, Negash T, Nguyen T, Nguyen N, Nicol R, Norbu C, Norbu N, Novod N, O'Neill B, Osman S, Markiewicz E, Oyono OL, Patti C, Phunkhang P, Pierre F, Priest M, Raghuraman S, Rege F, Reyes R, Rise C, Rogov P, Ross K, Ryan E, Settipalli S, Shea T, Sherpa N, Shi L, Shih D, Sparrow T, Spaulding J, Stalker J, Stange-Thomann N, Stavropoulos S, Stone C, Strader C, Tesfaye S, Thomson T, Thoulutsang Y, Thoulutsang D, Topham K, Topping I, Tsamla T, Vassiliev H, Vo A, Wangchuk T, Wangdi T, Weiand M, Wilkinson J, Wilson A, Yadav S, Young G, Yu Q, Zembek L, Zhong D, Zimmer A, Zwirko Z, Alvarez P, Brockman W, Butler J, Chin C, Grabherr M, Kleber M, Mauceli E, MacCallum I (- 405)
Ref: Nature, 450:203, 2007 : PubMed
Abstract


ESTHER: Clark_2007_Nature_450_203
PubMedSearch: Clark 2007 Nature 450 203
PubMedID: 17994087
Gene_locus related to this paper: droan-ACHE, droan-b3lx10, droan-b3lx75, droan-b3lxv7, droan-b3ly87, droan-b3lyh4, droan-b3lyh5, droan-b3lyh7, droan-b3lyh9, droan-b3lyi0, droan-b3lyi2, droan-b3lyi3, droan-b3lyi4, droan-b3lyj8, droan-b3lyj9, droan-b3lyx4, droan-b3lyx5, droan-b3lyx6, droan-b3lyx7, droan-b3lyx9, droan-b3lz72, droan-b3m1x3, droan-b3m2d4, droan-b3m3d9, droan-b3m4e3, droan-b3m5w1, droan-b3m6i7, droan-b3m7v2, droan-b3m9a5, droan-b3m9f4, droan-b3m9p3, droan-b3m254, droan-b3m259, droan-b3m260, droan-b3m262, droan-b3m524, droan-b3m635, droan-b3m845, droan-b3m846, droan-b3md01, droan-b3mdh7, droan-b3mdm6, droan-b3mdw8, droan-b3mee1, droan-b3mf47, droan-b3mf48, droan-b3mg94, droan-b3mgk2, droan-b3mgn6, droan-b3mii3, droan-b3mjk2, droan-b3mjk3, droan-b3mjk4, droan-b3mjk5, droan-b3mjl2, droan-b3mjl4, droan-b3mjl7, droan-b3mjl9, droan-b3mjm8, droan-b3mjm9, droan-b3mjs6, droan-b3mkr0, droan-b3ml20, droan-b3mly4, droan-b3mly5, droan-b3mly6, droan-b3mmm8, droan-b3mnb5, droan-b3mny9, droan-b3mtj5, droan-b3muw4, droan-b3muw8, droan-b3n0e7, droan-b3n2j7, droan-b3n247, droan-c5idb2, droer-ACHE, droer-b3n5c7, droer-b3n5d0, droer-b3n5d8, droer-b3n5d9, droer-b3n5t7, droer-b3n5y4, droer-b3n7d2, droer-b3n7d3, droer-b3n7d4, droer-b3n7k8, droer-b3n8e4, droer-b3n8f7, droer-b3n8f8, droer-b3n9e1, droer-b3n319, droer-b3n547, droer-b3n549, droer-b3n558, droer-b3n560, droer-b3n577, droer-b3n612, droer-b3nar5, droer-b3nb91, droer-b3nct9, droer-b3nd53, droer-b3ndh9, droer-b3ndq8, droer-b3ne66, droer-b3ne67, droer-b3ne97, droer-b3nfk3, droer-b3nfq9, droer-b3nim7, droer-b3nkn2, droer-b3nm11, droer-b3nmh4, droer-b3nmy2, droer-b3npx2, droer-b3npx3, droer-b3nq76, droer-b3nqg9, droer-b3nqm8, droer-b3nr28, droer-b3nrd3, droer-b3nst4, droer-b3nwa7, droer-b3nyp5.1, droer-b3nyp5.2, droer-b3nyp6, droer-b3nyp7, droer-b3nyp8, droer-b3nyp9, droer-b3nyq3, droer-b3nz06, droer-b3nz14, droer-b3nzj0, droer-b3p0c0, droer-b3p0c1, droer-b3p0c2, droer-b3p2x6, droer-b3p2x7, droer-b3p2x9, droer-b3p2y1, droer-b3p2y2, droer-b3p6d4, droer-b3p6d5, droer-b3p6w3, droer-b3p7b4, droer-b3p7h9, droer-b3p152, droer-b3p486, droer-b3p487, droer-b3p488, droer-b3p489, droer-EST6, droer-q670j5, drogr-ACHE, drogr-b4iwp3, drogr-b4iww3, drogr-b4iwy3, drogr-b4ixf7, drogr-b4ixh4, drogr-b4iyz5, drogr-b4j2s2, drogr-b4j2u8, drogr-b4j3u1, drogr-b4j3v3, drogr-b4j4g7, drogr-b4j4x9, drogr-b4j6e6, drogr-b4j9c9, drogr-b4j9y4, drogr-b4j156, drogr-b4j384, drogr-b4j605, drogr-b4j685, drogr-b4ja76, drogr-b4jay5, drogr-b4jcf0, drogr-b4jcf1, drogr-b4jdg6, drogr-b4jdg7, drogr-b4jdh6, drogr-b4jdz1, drogr-b4jdz2, drogr-b4jdz4, drogr-b4je66, drogr-b4je79, drogr-b4je82, drogr-b4je88, drogr-b4je89, drogr-b4je90, drogr-b4je91, drogr-b4jf76, drogr-b4jf79, drogr-b4jf80, drogr-b4jf81, drogr-b4jf82, drogr-b4jf83, drogr-b4jf84, drogr-b4jf85, drogr-b4jf87, drogr-b4jf91, drogr-b4jf92, drogr-b4jg66, drogr-b4jgh0, drogr-b4jgh1, drogr-b4jgr9, drogr-b4ji67, drogr-b4jls2, drogr-b4jnh9, drogr-b4jpc6, drogr-b4jpq3, drogr-b4jpx9, drogr-b4jql2, drogr-b4jrh5, drogr-b4jsb2, drogr-b4jth3, drogr-b4jti1, drogr-b4jul5, drogr-b4jur4, drogr-b4jvh3, drogr-b4jz00, drogr-b4jz03, drogr-b4jz04, drogr-b4jz05, drogr-b4jzh2, drogr-b4k0u2, drogr-b4k2r1, drogr-b4k234, drogr-b4k235, drome-BEM46, drome-CG3734, drome-CG9953, drome-CG11626, drome-GH02439, dromo-ACHE, dromo-b4k6a7, dromo-b4k6a8, dromo-b4k6q8, dromo-b4k6q9, dromo-b4k6r1, dromo-b4k6r3, dromo-b4k6r4, dromo-b4k6r5, dromo-b4k6r6, dromo-b4k6r7, dromo-b4k6r8, dromo-b4k6r9, dromo-b4k6s0, dromo-b4k6s1, dromo-b4k6s2, dromo-b4k9c7, dromo-b4k9d3, dromo-b4k571, dromo-b4k721, dromo-b4ka74, dromo-b4ka89, dromo-b4kaj4, dromo-b4kc20, dromo-b4kcl2, dromo-b4kcl3, dromo-b4kd55.1, dromo-b4kd55.2, dromo-b4kd56, dromo-b4kd57, dromo-b4kde1, dromo-b4kdg2, dromo-b4kdh4, dromo-b4kdh5, dromo-b4kdh6, dromo-A0A0Q9XDF2, dromo-b4kdh8.1, dromo-b4kdh8.2, dromo-b4kg04, dromo-b4kg05, dromo-b4kg06, dromo-b4kg16, dromo-b4kg44, dromo-b4kg90, dromo-b4kh20, dromo-b4kh21, dromo-b4kht7, dromo-b4kid3, dromo-b4kik0, dromo-b4kjx0, dromo-b4kki1, dromo-b4kkp6, dromo-b4kkp8, dromo-b4kkq8, dromo-b4kkr0, dromo-b4kkr3, dromo-b4kkr4, dromo-b4kks0, dromo-b4kks1, dromo-b4kks2, dromo-b4kla1, dromo-b4klv8, dromo-b4knt4, dromo-b4kp08, dromo-b4kp16, dromo-b4kqa6, dromo-b4kqa7, dromo-b4kqa8, dromo-b4kqh1, dromo-b4kst4, dromo-b4ksy6, dromo-b4kt84, dromo-b4ktf5, dromo-b4ktf6, dromo-b4kvl3, dromo-b4kvw2, dromo-b4kwv4, dromo-b4kwv5, dromo-b4kxz6, dromo-b4ky12, dromo-b4ky36, dromo-b4ky44, dromo-b4kzu7, dromo-b4l0n8, dromo-b4l4u5, dromo-b4l6l9, dromo-b4l084, drope-ACHE, drope-b4g3s6, drope-b4g4p7, drope-b4g6v4, drope-b4g8m0, drope-b4g8n6, drope-b4g8n7, drope-b4g9p2, drope-b4g815, drope-b4g816, drope-b4gat7, drope-b4gav5, drope-b4gb05, drope-b4gc08, drope-b4gcr3, drope-b4gdk2, drope-b4gdl9, drope-b4gdv9, drope-b4gei8, drope-b4gei9, drope-b4gej0, drope-b4ghz9, drope-b4gj62, drope-b4gj64, drope-b4gj74, drope-b4gkf4, drope-b4gkv2, drope-b4gky9, drope-b4gl76, drope-b4glf3, drope-b4gmt3, drope-b4gmt7, drope-b4gmt9, drope-b4gmu2, drope-b4gmu3, drope-b4gmu4, drope-b4gmu5, drope-b4gmu6, drope-b4gmu7, drope-b4gmv1, drope-b4gn08, drope-b4gpa7, drope-b4gq13, drope-b4grh7, drope-b4gsf9, drope-b4gsw4, drope-b4gsw5, drope-b4gsx2, drope-b4gsx7, drope-b4gsy6, drope-b4gsy7, drope-b4guj8, drope-b4gw36, drope-b4gzc2, drope-b4gzc6, drope-b4gzc7, drope-b4h4p9, drope-b4h5l3, drope-b4h6a0, drope-b4h6a8, drope-b4h6a9, drope-b4h6b0, drope-b4h7m7, drope-b4h462, drope-b4h601, drope-b4h602, drope-b4hay1, drope-b4hb18, drope-est5a, drope-est5b, drope-est5c, drops-ACHE, drops-b5dhd2, drops-b5dk96, drops-b5dpe3, drops-b5drp9, drops-b5dwa7, drops-b5dwa8, drops-b5dz85, drops-b5dz86, drops-est5a, drops-est5b, drops-q29bq2, drops-q29dd7, drops-q29ew0, drops-q291d5, drops-q291e8, drops-q293n1, drops-q293n4, drops-q293n5, drops-q293n6, drops-q294n6, drops-q294n7, drops-q294n9, drops-q294p4, drose-b4he97, drose-b4hfu2, drose-b4hg54, drose-b4hga0, drose-b4hgu9, drose-b4hgv0, drose-b4hgv3, drose-b4hgv4, drose-b4hhm8, drose-b4hhs6, drose-b4hie4, drose-b4him9, drose-b4hk63, drose-b4hkj5, drose-b4hr07, drose-b4hr81, drose-b4hre7, drose-b4hs13, drose-b4hsj9, drose-b4hsk0, drose-b4hsm8, drose-b4hvr5, drose-b4hwr7, drose-b4hwr8, drose-b4hwr9, drose-b4hws6, drose-b4hws7, drose-b4hwt0, drose-b4hwt2, drose-b4hwu1, drose-b4hwu2, drose-b4hxs9, drose-b4hxu4, drose-b4hxz1, drose-b4hyp8, drose-b4hyp9, drose-b4hyq0, drose-b4hyz4, drose-b4hyz5, drose-b4i1k8, drose-b4i2f3, drose-b4i2w5, drose-b4i4u3, drose-b4i4u7, drose-b4i4u9, drose-b4i4v0, drose-b4i4v1, drose-b4i4v4, drose-b4i4v5, drose-b4i4v6, drose-b4i4v7, drose-b4i4v8, drose-b4i4w0, drose-b4i7s6, drose-b4i133, drose-b4i857, drose-b4iam7, drose-b4iam9, drose-b4iaq6, drose-b4icf6, drose-b4icf7, drose-b4id80, drose-b4ifc5, drose-b4ihv9, drose-b4iie9, drose-b4ilj8, drose-b4in13, drose-b4inj9, drosi-ACHE, drosi-aes04a, drosi-b4nsh8, drosi-b4q3d7, drosi-b4q4w5, drosi-b4q4y7, drosi-b4q6h6, drosi-b4q7u2, drosi-b4q7u3, drosi-b4q9c6, drosi-b4q9c7, drosi-b4q9d3, drosi-b4q9d4, drosi-b4q9r0, drosi-b4q9r1, drosi-b4q9r3, drosi-b4q9s2, drosi-b4q9s3, drosi-b4q429, drosi-b4q530, drosi-b4q734, drosi-b4q782, drosi-b4q783, drosi-b4q942, drosi-b4qet1, drosi-b4qfv6, drosi-b4qge5, drosi-b4qgh5, drosi-b4qgs5, drosi-b4qhf3, drosi-b4qhf4, drosi-b4qhi5, drosi-b4qjr2, drosi-b4qjr3, drosi-b4qjv6, drosi-b4qk23, drosi-b4qk51, drosi-b4qlt1, drosi-b4qlz9, drosi-b4qmn9, drosi-b4qrq7, drosi-b4qs01, drosi-b4qs57, drosi-b4qs82, drosi-b4qs83, drosi-b4qs84, drosi-b4qs85, drosi-b4qs86, drosi-b4qsq1, drosi-b4quk6, drosi-b4qvg5, drosi-b4qvg6, drosi-b4qzn2, drosi-b4qzn3, drosi-b4qzn5, drosi-b4qzn7, drosi-b4qzn8, drosi-b4qzp2, drosi-b4qzp3, drosi-b4qzp4, drosi-b4qzp5, drosi-b4qzp6, drosi-b4qzp7, drosi-b4r1a4, drosi-b4r025, drosi-b4r207, drosi-b4r662, drosi-este6, drosi-q670k8, drovi-ACHE, drovi-b4lev2, drovi-b4lf33, drovi-b4lf51, drovi-b4lg54, drovi-b4lg72, drovi-b4lgc6, drovi-b4lgd5, drovi-b4lgg0, drovi-b4lgk5, drovi-b4lgn2, drovi-b4lh17, drovi-b4lh18, drovi-b4lk43, drovi-b4ll59, drovi-b4ll60, drovi-b4llm5, drovi-b4lln3, drovi-b4lmk4, drovi-b4lmp0, drovi-b4lnr4, drovi-b4lp47, drovi-b4lpd0, drovi-b4lps0, drovi-b4lqc6, drovi-b4lr00, drovi-b4lrp6, drovi-b4lrw2, drovi-b4lse7, drovi-b4lse9, drovi-b4lsf0, drovi-b4lsn0, drovi-b4lsq5, drovi-b4lt32, drovi-b4ltr1, drovi-b4lui7, drovi-b4lui9, drovi-b4luj8, drovi-b4luk0, drovi-b4luk3, drovi-b4luk8, drovi-b4luk9, drovi-b4lul0, drovi-b4lve2, drovi-b4lxi9, drovi-b4lxj8, drovi-b4lyf3, drovi-b4lyq2, drovi-b4lyq3, drovi-b4lz07, drovi-b4lz13, drovi-b4lz14, drovi-b4lz15, drovi-b4m0j7, drovi-b4m0s0, drovi-b4m2b6, drovi-b4m4h7, drovi-b4m4h8, drovi-b4m4i0, drovi-b4m4i2, drovi-b4m4i3.A, drovi-b4m4i3.B, drovi-b4m4i4, drovi-b4m4i5, drovi-b4m4i6, drovi-b4m4i7, drovi-b4m4i8, drovi-b4m4i9, drovi-b4m4j2, drovi-b4m5a0, drovi-b4m5a1, drovi-b4m5a2, drovi-b4m6b9, drovi-b4m7k9, drovi-b4m9g9, drovi-b4m9h0, drovi-b4m564, drovi-b4m599, drovi-b4m918, drovi-b4mb87, drovi-b4mc71, drovi-b4mfa4, drowi-ACHE, drowi-b4mjb9, drowi-b4mkt7, drowi-b4mlc1, drowi-b4mp68, drowi-b4mqe9, drowi-b4mqf0.2, drowi-b4mqf1, drowi-b4mqf3, drowi-b4mqf4, drowi-b4mqf5, drowi-b4mqq6, drowi-b4mrd1, drowi-b4mrk3, drowi-b4mtl5, drowi-b4mug2, drowi-b4muj8, drowi-b4mv18, drowi-b4mw32, drowi-b4mw85, drowi-b4mwp2, drowi-b4mwp6, drowi-b4mwq5, drowi-b4mwr0, drowi-b4mwr8, drowi-b4mwr9, drowi-b4mwt1, drowi-b4mwz7, drowi-b4mxn5, drowi-b4my54, drowi-b4myg1, drowi-b4myh5, drowi-b4n0d4, drowi-b4n1a7, drowi-b4n1c8, drowi-b4n3s9, drowi-b4n3x7, drowi-b4n4x9, drowi-b4n4y0, drowi-b4n6m1, drowi-b4n6n0, drowi-b4n6n7, drowi-b4n6u6, drowi-b4n7s6, drowi-b4n7s7, drowi-b4n7s8, drowi-b4n899.1, drowi-b4n8a1, drowi-b4n8a2, drowi-b4n8a3, drowi-b4n8a4, drowi-b4n8a9, drowi-b4n023, drowi-b4n075, drowi-b4n543, drowi-b4n888, drowi-b4n889, drowi-b4n891, drowi-b4n893, drowi-b4n895, drowi-b4n897, drowi-b4n898, drowi-b4n899.2, drowi-b4nae3, drowi-b4ner8, drowi-b4ng76, drowi-b4nga7, drowi-b4ngb5, drowi-b4nhz9, drowi-b4nj18, drowi-b4nj19, drowi-b4nja7, drowi-b4nja8, drowi-b4nja9, drowi-b4njk8, drowi-b4nkc8, drowi-b4nky0, drowi-b4nl36, drowi-b4nm27, drowi-b4nn59, drowi-b4nnc1, drowi-b4nng1, drowi-b4nng2, droya-ACHE, droya-aes04, droya-b4itg2, droya-b4itg6, droya-b4itu9, droya-b4iuv4, droya-b4iuv5, droya-b4nxe6, droya-b4nxg5, droya-b4nxg6, droya-b4nxg8, droya-b4nxw4, droya-b4ny57, droya-b4ny58, droya-b4ny86, droya-b4nzz8, droya-b4p0b5, droya-b4p0q9, droya-b4p0r0, droya-b4p0r7, droya-b4p0r8, droya-b4p0r9, droya-b4p0s0, droya-b4p0s2, droya-b4p0t0, droya-b4p0t1, droya-b4p3h4, droya-b4p3x8, droya-b4p5g8, droya-b4p6c9, droya-b4p6l9, droya-b4p6r1, droya-b4p6r2, droya-b4p7u4, droya-b4p8w7, droya-b4p023, droya-b4p241, droya-b4p774, droya-b4pat9, droya-b4pbl1, droya-b4pd22, droya-b4pd70, droya-b4pdm8, droya-b4pet9, droya-b4pff9, droya-b4pga7, droya-b4pgu0, droya-b4pig3, droya-b4pjt8, droya-b4pka2, droya-b4plh2, droya-b4pma3, droya-b4pmv3, droya-b4pmv4, droya-b4pmv5, droya-b4pn92, droya-b4pp65, droya-b4ppc5, droya-b4ppc6, droya-b4ppc7, droya-b4ppc8, droya-b4pq03, droya-b4prg6B, droya-b4prg9, droya-b4prh3, droya-b4prh4, droya-b4prh6, droya-b4prh7, droya-b4psz8, droya-b4psz9, droya-b4pv22, droya-b4q0g5, droya-b4q246, droya-EST6, droya-q71d76, drowi-b4n7m9, drope-b4gkk1, droer-b3n5s3, drose-b4i1w5, drowi-a0a0q9x0t3, drogr-b4jvm7, dromo-b4ku70, drovi-b4mcn9, drovi-b4lty2, drogr-b4jdu1, drovi-a0a0q9wiq8, dromo-b4kf70, drosi-b2zi86, droya-b4p2y4, drose-b2zic5, droer-b3n895

Abstract

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.



        

Title: Locus ceruleus degeneration promotes Alzheimer pathogenesis in amyloid precursor protein 23 transgenic mice
Heneka MT, Ramanathan M, Jacobs AH, Dumitrescu-Ozimek L, Bilkei-Gorzo A, Debeir T, Sastre M, Galldiks N, Zimmer A and Staufenbiel M <3 more author(s)> Heneka MT, Ramanathan M, Jacobs AH, Dumitrescu-Ozimek L, Bilkei-Gorzo A, Debeir T, Sastre M, Galldiks N, Zimmer A, Hoehn M, Heiss WD, Klockgether T, Staufenbiel M (- 3)
Ref: Journal of Neuroscience, 26:1343, 2006 : PubMed
Abstract


ESTHER: Heneka_2006_J.Neurosci_26_1343
PubMedSearch: Heneka 2006 J.Neurosci 26 1343
PubMedID: 16452658

Abstract

Locus ceruleus (LC) degeneration and loss of cortical noradrenergic innervation occur early in Alzheimer's disease (AD). Although this has been known for several decades, the contribution of LC degeneration to AD pathogenesis remains unclear. We induced LC degeneration with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (dsp4) in amyloid precursor protein 23 (APP23) transgenic mice with a low amyloid load. Then 6 months later the LC projection areas showed a robust elevation of glial inflammation along with augmented amyloid plaque deposits. Moreover, neurodegeneration and neuronal loss significantly increased. Importantly, the paraventricular thalamus, a nonprojection area, remained unaffected. Radial arm maze and social partner recognition tests revealed increased memory deficits while high-resolution magnetic resonance imaging-guided micro-positron emission tomography demonstrated reduced cerebral glucose metabolism, disturbed neuronal integrity, and attenuated acetylcholinesterase activity. Nontransgenic mice with LC degeneration were devoid of these alterations. Our data demonstrate that the degeneration of LC affects morphology, metabolism, and function of amyloid plaque-containing higher brain regions in APP23 mice. We postulate that LC degeneration substantially contributes to AD development.



        

Title: The transcriptional landscape of the mammalian genome
Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B and Hayashizaki Y <184 more author(s)> Carninci P, Kasukawa T, Katayama S, Gough J, Frith MC, Maeda N, Oyama R, Ravasi T, Lenhard B, Wells C, Kodzius R, Shimokawa K, Bajic VB, Brenner SE, Batalov S, Forrest AR, Zavolan M, Davis MJ, Wilming LG, Aidinis V, Allen JE, Ambesi-Impiombato A, Apweiler R, Aturaliya RN, Bailey TL, Bansal M, Baxter L, Beisel KW, Bersano T, Bono H, Chalk AM, Chiu KP, Choudhary V, Christoffels A, Clutterbuck DR, Crowe ML, Dalla E, Dalrymple BP, de Bono B, Della Gatta G, di Bernardo D, Down T, Engstrom P, Fagiolini M, Faulkner G, Fletcher CF, Fukushima T, Furuno M, Futaki S, Gariboldi M, Georgii-Hemming P, Gingeras TR, Gojobori T, Green RE, Gustincich S, Harbers M, Hayashi Y, Hensch TK, Hirokawa N, Hill D, Huminiecki L, Iacono M, Ikeo K, Iwama A, Ishikawa T, Jakt M, Kanapin A, Katoh M, Kawasawa Y, Kelso J, Kitamura H, Kitano H, Kollias G, Krishnan SP, Kruger A, Kummerfeld SK, Kurochkin IV, Lareau LF, Lazarevic D, Lipovich L, Liu J, Liuni S, McWilliam S, Madan Babu M, Madera M, Marchionni L, Matsuda H, Matsuzawa S, Miki H, Mignone F, Miyake S, Morris K, Mottagui-Tabar S, Mulder N, Nakano N, Nakauchi H, Ng P, Nilsson R, Nishiguchi S, Nishikawa S, Nori F, Ohara O, Okazaki Y, Orlando V, Pang KC, Pavan WJ, Pavesi G, Pesole G, Petrovsky N, Piazza S, Reed J, Reid JF, Ring BZ, Ringwald M, Rost B, Ruan Y, Salzberg SL, Sandelin A, Schneider C, Schonbach C, Sekiguchi K, Semple CA, Seno S, Sessa L, Sheng Y, Shibata Y, Shimada H, Shimada K, Silva D, Sinclair B, Sperling S, Stupka E, Sugiura K, Sultana R, Takenaka Y, Taki K, Tammoja K, Tan SL, Tang S, Taylor MS, Tegner J, Teichmann SA, Ueda HR, van Nimwegen E, Verardo R, Wei CL, Yagi K, Yamanishi H, Zabarovsky E, Zhu S, Zimmer A, Hide W, Bult C, Grimmond SM, Teasdale RD, Liu ET, Brusic V, Quackenbush J, Wahlestedt C, Mattick JS, Hume DA, Kai C, Sasaki D, Tomaru Y, Fukuda S, Kanamori-Katayama M, Suzuki M, Aoki J, Arakawa T, Iida J, Imamura K, Itoh M, Kato T, Kawaji H, Kawagashira N, Kawashima T, Kojima M, Kondo S, Konno H, Nakano K, Ninomiya N, Nishio T, Okada M, Plessy C, Shibata K, Shiraki T, Suzuki S, Tagami M, Waki K, Watahiki A, Okamura-Oho Y, Suzuki H, Kawai J, Hayashizaki Y (- 184)
Ref: Science, 309:1559, 2005 : PubMed
Abstract


ESTHER: Carninci_2005_Science_309_1559
PubMedSearch: Carninci 2005 Science 309 1559
PubMedID: 16141072
Gene_locus related to this paper: mouse-abhd1, mouse-abhd3, mouse-abhd4, mouse-acot4, mouse-adcl4, mouse-DGLB, mouse-ephx3, mouse-Kansl3, mouse-lipli, mouse-LIPN, mouse-Ppgb, mouse-q3uuq7, mouse-srac1, mouse-Tex30, mouse-tmco4, mouse-tmm53, mouse-f172a

Abstract

This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.



        

Title: Genome sequence, comparative analysis and haplotype structure of the domestic dog
Lindblad-Toh K, Wade CM, Mikkelsen TS, Karlsson EK, Jaffe DB, Kamal M, Clamp M, Chang JL, Kulbokas EJ, 3rd and Lander ES <224 more author(s)> Lindblad-Toh K, Wade CM, Mikkelsen TS, Karlsson EK, Jaffe DB, Kamal M, Clamp M, Chang JL, Kulbokas EJ, 3rd, Zody MC, Mauceli E, Xie X, Breen M, Wayne RK, Ostrander EA, Ponting CP, Galibert F, Smith DR, deJong PJ, Kirkness E, Alvarez P, Biagi T, Brockman W, Butler J, Chin CW, Cook A, Cuff J, Daly MJ, Decaprio D, Gnerre S, Grabherr M, Kellis M, Kleber M, Bardeleben C, Goodstadt L, Heger A, Hitte C, Kim L, Koepfli KP, Parker HG, Pollinger JP, Searle SM, Sutter NB, Thomas R, Webber C, Baldwin J, Abebe A, Abouelleil A, Aftuck L, Ait-Zahra M, Aldredge T, Allen N, An P, Anderson S, Antoine C, Arachchi H, Aslam A, Ayotte L, Bachantsang P, Barry A, Bayul T, Benamara M, Berlin A, Bessette D, Blitshteyn B, Bloom T, Blye J, Boguslavskiy L, Bonnet C, Boukhgalter B, Brown A, Cahill P, Calixte N, Camarata J, Cheshatsang Y, Chu J, Citroen M, Collymore A, Cooke P, Dawoe T, Daza R, Decktor K, DeGray S, Dhargay N, Dooley K, Dorje P, Dorjee K, Dorris L, Duffey N, Dupes A, Egbiremolen O, Elong R, Falk J, Farina A, Faro S, Ferguson D, Ferreira P, Fisher S, FitzGerald M, Foley K, Foley C, Franke A, Friedrich D, Gage D, Garber M, Gearin G, Giannoukos G, Goode T, Goyette A, Graham J, Grandbois E, Gyaltsen K, Hafez N, Hagopian D, Hagos B, Hall J, Healy C, Hegarty R, Honan T, Horn A, Houde N, Hughes L, Hunnicutt L, Husby M, Jester B, Jones C, Kamat A, Kanga B, Kells C, Khazanovich D, Kieu AC, Kisner P, Kumar M, Lance K, Landers T, Lara M, Lee W, Leger JP, Lennon N, Leuper L, LeVine S, Liu J, Liu X, Lokyitsang Y, Lokyitsang T, Lui A, MacDonald J, Major J, Marabella R, Maru K, Matthews C, McDonough S, Mehta T, Meldrim J, Melnikov A, Meneus L, Mihalev A, Mihova T, Miller K, Mittelman R, Mlenga V, Mulrain L, Munson G, Navidi A, Naylor J, Nguyen T, Nguyen N, Nguyen C, Nicol R, Norbu N, Norbu C, Novod N, Nyima T, Olandt P, O'Neill B, O'Neill K, Osman S, Oyono L, Patti C, Perrin D, Phunkhang P, Pierre F, Priest M, Rachupka A, Raghuraman S, Rameau R, Ray V, Raymond C, Rege F, Rise C, Rogers J, Rogov P, Sahalie J, Settipalli S, Sharpe T, Shea T, Sheehan M, Sherpa N, Shi J, Shih D, Sloan J, Smith C, Sparrow T, Stalker J, Stange-Thomann N, Stavropoulos S, Stone C, Stone S, Sykes S, Tchuinga P, Tenzing P, Tesfaye S, Thoulutsang D, Thoulutsang Y, Topham K, Topping I, Tsamla T, Vassiliev H, Venkataraman V, Vo A, Wangchuk T, Wangdi T, Weiand M, Wilkinson J, Wilson A, Yadav S, Yang S, Yang X, Young G, Yu Q, Zainoun J, Zembek L, Zimmer A, Lander ES (- 224)
Ref: Nature, 438:803, 2005 : PubMed
Abstract


ESTHER: Lindblad-Toh_2005_Nature_438_803
PubMedSearch: Lindblad-Toh 2005 Nature 438 803
PubMedID: 16341006
Gene_locus related to this paper: canfa-1lipg, canfa-2neur, canfa-3neur, canfa-ACHE, canfa-BCHE, canfa-cauxin, canfa-CESDD1, canfa-e2qsb1, canfa-e2qsl3, canfa-e2qsz2, canfa-e2qvk3, canfa-e2qw15, canfa-e2qxs8, canfa-e2qzs6, canfa-e2r5t3, canfa-e2r6f6, canfa-e2r7e8, canfa-e2r8v9, canfa-e2r8z1, canfa-e2r9h4, canfa-e2r455, canfa-e2rb70, canfa-e2rcq9, canfa-e2rd94, canfa-e2rgi0, canfa-e2rkq0, canfa-e2rlz9, canfa-e2rm00, canfa-e2rqf1, canfa-e2rss9, canfa-f1p6w8, canfa-f1p8b6, canfa-f1p9d8, canfa-f1p683, canfa-f1pb79, canfa-f1pgw0, canfa-f1phd0, canfa-f1phx2, canfa-f1pke8, canfa-f1pp08, canfa-f1ppp9, canfa-f1ps07, canfa-f1ptf1, canfa-f1pvp4, canfa-f1pw93, canfa-f1pwk3, canfa-pafa, canfa-q1ert3, canfa-q5jzr0, canfa-e2rmb9, canlf-f6v865, canlf-e2rjg6, canlf-e2r2h2, canlf-f1p648, canlf-f1pw90, canlf-j9p8v6, canlf-f1pcc4, canlf-e2qxh0, canlf-e2r774, canlf-f1pf96, canlf-e2rq56, canlf-j9nwb1, canlf-f1ptw2, canlf-j9p8h1, canlf-e2ree2, canlf-f1prs1, canlf-j9nus1, canlf-e2rf91, canlf-f1pg57, canlf-f1q111

Abstract

Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.



        

Title: The genome of M. acetivorans reveals extensive metabolic and physiological diversity
Galagan JE, Nusbaum C, Roy A, Endrizzi MG, Macdonald P, FitzHugh W, Calvo S, Engels R, Smirnov S and Birren B <45 more author(s)> Galagan JE, Nusbaum C, Roy A, Endrizzi MG, Macdonald P, FitzHugh W, Calvo S, Engels R, Smirnov S, Atnoor D, Brown A, Allen N, Naylor J, Stange-Thomann N, DeArellano K, Johnson R, Linton L, McEwan P, McKernan K, Talamas J, Tirrell A, Ye W, Zimmer A, Barber RD, Cann I, Graham DE, Grahame DA, Guss AM, Hedderich R, Ingram-Smith C, Kuettner HC, Krzycki JA, Leigh JA, Li W, Liu J, Mukhopadhyay B, Reeve JN, Smith K, Springer TA, Umayam LA, White O, White RH, Conway de Macario E, Ferry JG, Jarrell KF, Jing H, Macario AJ, Paulsen I, Pritchett M, Sowers KR, Swanson RV, Zinder SH, Lander E, Metcalf WW, Birren B (- 45)
Ref: Genome Res, 12:532, 2002 : PubMed
Abstract


ESTHER: Galagan_2002_Genome.Res_12_532
PubMedSearch: Galagan 2002 Genome.Res 12 532
PubMedID: 11932238
Gene_locus related to this paper: metac-MA0077, metac-MA0362, metac-MA0419, metac-MA0736, metac-MA0993, metac-MA1571, metac-MA1856, metac-MA1857, metac-MA2002, metac-MA2343, metac-MA2629, metac-MA2691, metac-MA2743, metac-MA2933, metac-MA3611, metac-MA3635, metac-MA3920, metac-META

Abstract

Methanogenesis, the biological production of methane, plays a pivotal role in the global carbon cycle and contributes significantly to global warming. The majority of methane in nature is derived from acetate. Here we report the complete genome sequence of an acetate-utilizing methanogen, Methanosarcina acetivorans C2A. Methanosarcineae are the most metabolically diverse methanogens, thrive in a broad range of environments, and are unique among the Archaea in forming complex multicellular structures. This diversity is reflected in the genome of M. acetivorans. At 5,751,492 base pairs it is by far the largest known archaeal genome. The 4524 open reading frames code for a strikingly wide and unanticipated variety of metabolic and cellular capabilities. The presence of novel methyltransferases indicates the likelihood of undiscovered natural energy sources for methanogenesis, whereas the presence of single-subunit carbon monoxide dehydrogenases raises the possibility of nonmethanogenic growth. Although motility has not been observed in any Methanosarcineae, a flagellin gene cluster and two complete chemotaxis gene clusters were identified. The availability of genetic methods, coupled with its physiological and metabolic diversity, makes M. acetivorans a powerful model organism for the study of archaeal biology. [Sequence, data, annotations and analyses are available at http://www-genome.wi.mit.edu/.]



        

Title: Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs
Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S, Nikaido I, Osato N, Saito R and Hayashizaki Y <127 more author(s)> Okazaki Y, Furuno M, Kasukawa T, Adachi J, Bono H, Kondo S, Nikaido I, Osato N, Saito R, Suzuki H, Yamanaka I, Kiyosawa H, Yagi K, Tomaru Y, Hasegawa Y, Nogami A, Schonbach C, Gojobori T, Baldarelli R, Hill DP, Bult C, Hume DA, Quackenbush J, Schriml LM, Kanapin A, Matsuda H, Batalov S, Beisel KW, Blake JA, Bradt D, Brusic V, Chothia C, Corbani LE, Cousins S, Dalla E, Dragani TA, Fletcher CF, Forrest A, Frazer KS, Gaasterland T, Gariboldi M, Gissi C, Godzik A, Gough J, Grimmond S, Gustincich S, Hirokawa N, Jackson IJ, Jarvis ED, Kanai A, Kawaji H, Kawasawa Y, Kedzierski RM, King BL, Konagaya A, Kurochkin IV, Lee Y, Lenhard B, Lyons PA, Maglott DR, Maltais L, Marchionni L, McKenzie L, Miki H, Nagashima T, Numata K, Okido T, Pavan WJ, Pertea G, Pesole G, Petrovsky N, Pillai R, Pontius JU, Qi D, Ramachandran S, Ravasi T, Reed JC, Reed DJ, Reid J, Ring BZ, Ringwald M, Sandelin A, Schneider C, Semple CA, Setou M, Shimada K, Sultana R, Takenaka Y, Taylor MS, Teasdale RD, Tomita M, Verardo R, Wagner L, Wahlestedt C, Wang Y, Watanabe Y, Wells C, Wilming LG, Wynshaw-Boris A, Yanagisawa M, Yang I, Yang L, Yuan Z, Zavolan M, Zhu Y, Zimmer A, Carninci P, Hayatsu N, Hirozane-Kishikawa T, Konno H, Nakamura M, Sakazume N, Sato K, Shiraki T, Waki K, Kawai J, Aizawa K, Arakawa T, Fukuda S, Hara A, Hashizume W, Imotani K, Ishii Y, Itoh M, Kagawa I, Miyazaki A, Sakai K, Sasaki D, Shibata K, Shinagawa A, Yasunishi A, Yoshino M, Waterston R, Lander ES, Rogers J, Birney E, Hayashizaki Y (- 127)
Ref: Nature, 420:563, 2002 : PubMed
Abstract


ESTHER: Okazaki_2002_Nature_420_563
PubMedSearch: Okazaki 2002 Nature 420 563
PubMedID: 12466851
Gene_locus related to this paper: mouse-1lipg, mouse-1llip, mouse-1plrp, mouse-3neur, mouse-ABH15, mouse-abhd4, mouse-abhd5, mouse-Abhd8, mouse-Abhd11, mouse-abhda, mouse-acot4, mouse-adcl4, mouse-AI607300, mouse-BAAT, mouse-bphl, mouse-C87498, mouse-Ldah, mouse-Ces1d, mouse-Ces2e, mouse-CMBL, mouse-DGLB, mouse-dpp9, mouse-ES10, mouse-F135A, mouse-FASN, mouse-hslip, mouse-hyes, mouse-Kansl3, mouse-LIPH, mouse-LIPK, mouse-lipli, mouse-LIPM, mouse-lypla1, mouse-lypla2, mouse-MEST, mouse-MGLL, mouse-ndr4, mouse-OVCA2, mouse-pafa, mouse-pcp, mouse-ppce, mouse-Ppgb, mouse-PPME1, mouse-q3uuq7, mouse-Q8BLF1, mouse-ACOT6, mouse-Q8C1A9, mouse-Q9DAI6, mouse-Q80UX8, mouse-Q8BGG9, mouse-Q8C167, mouse-rbbp9, mouse-SERHL, mouse-tssp

Abstract

Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.



        

Title: Pharmacokinetic and pharmacodynamic aspects of an ophthalmic pilocarpine nanoparticle-delivery-system
Zimmer A, Mutschler E, Lambrecht G, Mayer D, Kreuter J
Ref: Pharm Res, 11:1435, 1994 : PubMed
Abstract


ESTHER: Zimmer_1994_Pharm.Res_11_1435
PubMedSearch: Zimmer 1994 Pharm.Res 11 1435
PubMedID: 7855048

Abstract

The regional pharmacokinetics as well as the pharmacodynamics of pilocarpine-loaded nanoparticles for the treatment of glaucoma were investigated and compared to a solution of this drug. Polybutylcyanoacrylate nanoparticles were prepared by an emulsion polymerization process. Formulations with different drug concentrations (2-6%) as well as different particle concentrations were investigated and analyzed for size and drug loading. Drug binding to the particles was achieved at a level of 10-18% of the total drug content. The colloidal nanoparticles were sufficiently small (diameter: 100-300 nm) for a non-irritating application to the eye. All preparations were applied to the eyes of New Zealand white rabbits which were treated with betamethasone before to create an elevated intraocular pressure (IOP). Pilocarpine concentrations, assayed from aqueous humor using gaschromatography, increased by 23% (AUC) for nanoparticle suspensions compared to aqueous reference solutions. Additionally, t1/2 was prolonged and the elimination coefficient was significantly decreased. Pharmacodynamic effects such as miosis and IOP reduction were investigated. tmax values of aqueous humor concentration were observed to be in a similar time range as miosis tmax readings. It was found that at lower drug contents a more pronounced prolongation of miosis was achieved with nanoparticles versus a standard solution. The IOP-reduction was significantly prolonged with nanoparticles preparations; whereas maximum reduction was obtained with a reference solution after 1-2 hours, it was reached with nanoparticles at about 2-3 hours. Differences between nanoparticles and aqueous solutions were most pronounced at lower drug concentrations.