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Article: Activation of brain protein phosphatase-1I following cardiac arrest and resuscitation involving an interaction with 14-3-3γ

Platholi, Jimcy / Heerdt, Paul M / Lim Tung, H.Y / Hemmings, Hugh C. Jr

Journal of neurochemistry. 2008 June, v. 105, no. 5

2008

Abstract: ... and C-TAK1 kinase. PP-1I purified from ischemic brain contained significantly less 14-3-3γ than PP-1I ...

Abstract	The intracellular signaling mechanisms that couple transient cerebral ischemia to cell death and neuroprotective mechanisms provide potential therapeutic targets for cardiac arrest. Protein phosphatase (PP)-1 is a major serine/threonine phosphatase that interacts with and dephosphorylates critical regulators of energy metabolism, ionic balance, and apoptosis. We report here that PP-1I, a major regulated form of PP-1, is activated in brain by approximately twofold in vivo following cardiac arrest and resuscitation in a clinically relevant pig model of transient global cerebral ischemia and reperfusion. PP-1I purified to near homogeneity from either control or ischemic pig brain consisted of the PP-1 catalytic subunit, the inhibitor-2 regulatory subunit, as well as the novel constituents 14-3-3γ, Rab GDP dissociation protein β, PFTAIRE kinase, and C-TAK1 kinase. PP-1I purified from ischemic brain contained significantly less 14-3-3γ than PP-1I purified from control brain, and purified 14-3-3γ directly inhibited the catalytic subunit of PP-1 and reconstituted PP-1I. These findings suggest that activation of brain PP-1I following global cerebral ischemia in vivo involves dissociation of 14-3-3γ, a novel inhibitory modulator of PP-1I. This identifies modulation of PP-1I by 14-3-3 in global cerebral ischemia as a potential signaling mechanism-based approach to neuroprotection.
Keywords	apoptosis ; protein phosphorylation
Language	English
Dates of publication	2008-06
Size	p. 2029-2038.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/j.1471-4159.2008.05300.x
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Localization of dopamine- and cAMP-regulated phosphoprotein-32 and inhibitor-1 in area 9 of Macaca mulatta prefrontal cortex.

Glausier, J R / Maddox, M / Hemmings, H C / Nairn, A C / Greengard, P / Muly, E C

Neuroscience

2010 Volume 167, Issue 2, Page(s) 428–438

Abstract: The actions of dopamine D1 family receptors (D1R) depend upon a signal transduction cascade that modulates the phosphorylation state of important effector proteins, such as glutamate receptors and ion channels. This is accomplished both through ... ...

Abstract	The actions of dopamine D1 family receptors (D1R) depend upon a signal transduction cascade that modulates the phosphorylation state of important effector proteins, such as glutamate receptors and ion channels. This is accomplished both through activation of protein kinase A (PKA) and the inhibition of protein phosphatase-1 (PP1). Inhibition of PP1 occurs through PKA-mediated phosphorylation of dopamine- and cAMP-regulated phosphoprotein 32 kDa (DARPP-32) or the related protein inhibitor-1 (I-1), and the availability of DARPP-32 is essential to the functional outcome of D1R activation in the basal ganglia. While D1R activation is critical for prefrontal cortex (PFC) function, especially working memory, the functional role played by DARPP-32 or I-1 is less clear. In order to examine this more thoroughly, we have utilized immunoelectron microscopy to quantitatively determine the localization of DARPP-32 and I-1 in the neuropil of the rhesus monkey PFC. Both were distributed widely in the different components of the neuropil, but were enriched in dendritic shafts. I-1 label was more frequently identified in axon terminals than was DARPP-32, and DARPP-32 label was more frequently identified in glia than was I-1. We also quantified the extent to which these proteins were found in dendritic spines. DARPP-32 and I-1 were present in small subpopulations of dendritic spines, (4.4% and 7.7% and respectively), which were substantially smaller than observed for D1R in our previous studies (20%). Double-label experiments did not find evidence for colocalization of D1R and DARPP-32 or I-1 in spines or terminals. Thus, at the least, not all prefrontal spines which contain D1R also contain I-1 or DARPP-32, suggesting important differences in D1R signaling in the PFC compared to the striatum.
MeSH term(s)	Animals ; Dendritic Spines/metabolism ; Dopamine and cAMP-Regulated Phosphoprotein 32/metabolism ; Macaca mulatta ; Microscopy, Immunoelectron ; Neuropil/metabolism ; Prefrontal Cortex/metabolism ; Prefrontal Cortex/ultrastructure ; Presynaptic Terminals/metabolism ; Protein Phosphatase 1/metabolism ; Proteins/metabolism ; Receptors, Dopamine D1/metabolism
Chemical Substances	Dopamine and cAMP-Regulated Phosphoprotein 32 ; Proteins ; Receptors, Dopamine D1 ; phosphoprotein phosphatase inhibitor 1 ; Protein Phosphatase 1 (EC 3.1.3.16)
Language	English
Publishing date	2010-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
DOI	10.1016/j.neuroscience.2010.02.014
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Article ; Online: Dung removal increases under higher dung beetle functional diversity regardless of grazing intensification.

Noriega, Jorge Ari / Hortal, Joaquín / deCastro-Arrazola, Indradatta / Alves-Martins, Fernanda / Ortega, Jean C G / Bini, Luis Mauricio / Andrew, Nigel R / Arellano, Lucrecia / Beynon, Sarah / Davis, Adrian L V / Favila, Mario E / Floate, Kevin D / Horgan, Finbarr G / Menéndez, Rosa / Milotic, Tanja / Nervo, Beatrice / Palestrini, Claudia / Rolando, Antonio / Scholtz, Clarke H /

Senyüz, Yakup / Wassmer, Thomas / Ádam, Réka / Araújo, Cristina de O / Barragan-Ramírez, José Luis / Boros, Gergely / Camero-Rubio, Edgar / Cruz, Melvin / Cuesta, Eva / Damborsky, Miryam Pieri / Deschodt, Christian M / Rajan, Priyadarsanan Dharma / D'hondt, Bram / Díaz Rojas, Alfonso / Dindar, Kemal / Escobar, Federico / Espinoza, Verónica R / Ferrer-Paris, José Rafael / Gutiérrez Rojas, Pablo Enrique / Hemmings, Zac / Hernández, Benjamín / Hill, Sarah J / Hoffmann, Maurice / Jay-Robert, Pierre / Lewis, Kyle / Lewis, Megan / Lozano, Cecilia / Marín-Armijos, Diego / de Farias, Patrícia Menegaz / Murcia-Ordoñez, Betselene / Karimbumkara, Seena Narayanan / Navarrete-Heredia, José Luis / Ortega-Echeverría, Candelaria / Pablo-Cea, José D / Perrin, William / Pessoa, Marcelo Bruno / Radhakrishnan, Anu / Rahimi, Iraj / Raimundo, Amalia Teresa / Ramos, Diana Catalina / Rebolledo, Ramón E / Roggero, Angela / Sánchez-Mercado, Ada / Somay, László / Stadler, Jutta / Tahmasebi, Pejman / Triana Céspedes, José Darwin / Santos, Ana M C

Nature communications

2023 Volume 14, Issue 1, Page(s) 8070

Abstract: Dung removal by macrofauna such as dung beetles is an important process for nutrient cycling in pasturelands. Intensification of farming practices generally reduces species and functional diversity of terrestrial invertebrates, which may negatively ... ...

Abstract	Dung removal by macrofauna such as dung beetles is an important process for nutrient cycling in pasturelands. Intensification of farming practices generally reduces species and functional diversity of terrestrial invertebrates, which may negatively affect ecosystem services. Here, we investigate the effects of cattle-grazing intensification on dung removal by dung beetles in field experiments replicated in 38 pastures around the world. Within each study site, we measured dung removal in pastures managed with low- and high-intensity regimes to assess between-regime differences in dung beetle diversity and dung removal, whilst also considering climate and regional variations. The impacts of intensification were heterogeneous, either diminishing or increasing dung beetle species richness, functional diversity, and dung removal rates. The effects of beetle diversity on dung removal were more variable across sites than within sites. Dung removal increased with species richness across sites, while functional diversity consistently enhanced dung removal within sites, independently of cattle grazing intensity or climate. Our findings indicate that, despite intensified cattle stocking rates, ecosystem services related to decomposition and nutrient cycling can be maintained when a functionally diverse dung beetle community inhabits the human-modified landscape.
MeSH term(s)	Animals ; Cattle ; Biodiversity ; Climate ; Coleoptera ; Ecosystem ; Farms ; Feces
Language	English
Publishing date	2023-12-06
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-43760-8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The dopaminergic innervation of the pigeon telencephalon

Durstewitz, D. / Kröner, S. / Hemmings, H. C. Jr. / Güntürkün, O.

Neuroscience

Distribution of DARPP-32 and co-occurrence with glutamate decarboxylase and tyrosine hydroxylase

1998 Volume 83, Issue 3, Page(s) 763–779

Abstract: Investigated the distribution of DARPP-32 (a phosphoprotein related to the dopamine D1 receptor) throughout the pigeon telencephalon using immunocytochemical techniques on the brains of a total of 14 adult pigeons (Columba livia). Using peroxidase- ... ...

Title translation	Die dopaminerge Innervation des Telenzephalons der Taube
Abstract	Investigated the distribution of DARPP-32 (a phosphoprotein related to the dopamine D1 receptor) throughout the pigeon telencephalon using immunocytochemical techniques on the brains of a total of 14 adult pigeons (Columba livia). Using peroxidase-antiperoxidase procedures, the indirect immunofluorescence technique, and immunoblotting, it was found that the distribution of DARPP-32 shared important features with that of D1 receptors and dopaminergic fibers, being highly abundant in the avian basal ganglia while present in medium to high concentrations in secondary sensory, associative, limbic, and motor regions, but in much lower concentrations in most primary sensory areas. Up to one third of DARPP-32-positive neurons were shown to receive basket-type innervation from tyrosine hydroxylase-positive fibers in the lateral and caudal neostriatum, half as many in the medial and frontal neostriatum, and fewer in the hyperstriatum. Glutamate decarboxylase-positive neurons were found not to be colocalized with DARPP-32 and not to receive tyrosine hydroxylase basket input. It is concluded that the pigeon dopaminergic system is organized similarly to that of mammals, dopamine having its primary function in the higher-level sensory, associative, and motor processes.
Keywords	Cerebrum ; Dopamin ; Dopamine ; Neural Receptors ; Pigeons ; Rezeptoren (Nervensystem) ; Tauben
Language	English
Document type	Article
ZDB-ID	196739-3
ISSN	1873-7544 ; 0306-4522
ISSN (online)	1873-7544
ISSN	0306-4522
Database	PSYNDEX

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Article ; Online: Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.

Nievergelt, Caroline M / Maihofer, Adam X / Atkinson, Elizabeth G / Chen, Chia-Yen / Choi, Karmel W / Coleman, Jonathan R I / Daskalakis, Nikolaos P / Duncan, Laramie E / Polimanti, Renato / Aaronson, Cindy / Amstadter, Ananda B / Andersen, Soren B / Andreassen, Ole A / Arbisi, Paul A / Ashley-Koch, Allison E / Austin, S Bryn / Avdibegoviç, Esmina / Babić, Dragan / Bacanu, Silviu-Alin /

Baker, Dewleen G / Batzler, Anthony / Beckham, Jean C / Belangero, Sintia / Benjet, Corina / Bergner, Carisa / Bierer, Linda M / Biernacka, Joanna M / Bierut, Laura J / Bisson, Jonathan I / Boks, Marco P / Bolger, Elizabeth A / Brandolino, Amber / Breen, Gerome / Bressan, Rodrigo Affonseca / Bryant, Richard A / Bustamante, Angela C / Bybjerg-Grauholm, Jonas / Bækvad-Hansen, Marie / Børglum, Anders D / Børte, Sigrid / Cahn, Leah / Calabrese, Joseph R / Caldas-de-Almeida, Jose Miguel / Chatzinakos, Chris / Cheema, Sheraz / Clouston, Sean A P / Colodro-Conde, Lucía / Coombes, Brandon J / Cruz-Fuentes, Carlos S / Dale, Anders M / Dalvie, Shareefa / Davis, Lea K / Deckert, Jürgen / Delahanty, Douglas L / Dennis, Michelle F / Desarnaud, Frank / DiPietro, Christopher P / Disner, Seth G / Docherty, Anna R / Domschke, Katharina / Dyb, Grete / Kulenović, Alma Džubur / Edenberg, Howard J / Evans, Alexandra / Fabbri, Chiara / Fani, Negar / Farrer, Lindsay A / Feder, Adriana / Feeny, Norah C / Flory, Janine D / Forbes, David / Franz, Carol E / Galea, Sandro / Garrett, Melanie E / Gelaye, Bizu / Gelernter, Joel / Geuze, Elbert / Gillespie, Charles F / Goleva, Slavina B / Gordon, Scott D / Goçi, Aferdita / Grasser, Lana Ruvolo / Guindalini, Camila / Haas, Magali / Hagenaars, Saskia / Hauser, Michael A / Heath, Andrew C / Hemmings, Sian M J / Hesselbrock, Victor / Hickie, Ian B / Hogan, Kelleigh / Hougaard, David Michael / Huang, Hailiang / Huckins, Laura M / Hveem, Kristian / Jakovljević, Miro / Javanbakht, Arash / Jenkins, Gregory D / Johnson, Jessica / Jones, Ian / Jovanovic, Tanja / Karstoft, Karen-Inge / Kaufman, Milissa L / Kennedy, James L / Kessler, Ronald C / Khan, Alaptagin / Kimbrel, Nathan A / King, Anthony P / Koen, Nastassja / Kotov, Roman / Kranzler, Henry R / Krebs, Kristi / Kremen, William S / Kuan, Pei-Fen / Lawford, Bruce R / Lebois, Lauren A M / Lehto, Kelli / Levey, Daniel F / Lewis, Catrin / Liberzon, Israel / Linnstaedt, Sarah D / Logue, Mark W / Lori, Adriana / Lu, Yi / Luft, Benjamin J / Lupton, Michelle K / Luykx, Jurjen J / Makotkine, Iouri / Maples-Keller, Jessica L / Marchese, Shelby / Marmar, Charles / Martin, Nicholas G / Martínez-Levy, Gabriela A / McAloney, Kerrie / McFarlane, Alexander / McLaughlin, Katie A / McLean, Samuel A / Medland, Sarah E / Mehta, Divya / Meyers, Jacquelyn / Michopoulos, Vasiliki / Mikita, Elizabeth A / Milani, Lili / Milberg, William / Miller, Mark W / Morey, Rajendra A / Morris, Charles Phillip / Mors, Ole / Mortensen, Preben Bo / Mufford, Mary S / Nelson, Elliot C / Nordentoft, Merete / Norman, Sonya B / Nugent, Nicole R / O'Donnell, Meaghan / Orcutt, Holly K / Pan, Pedro M / Panizzon, Matthew S / Pathak, Gita A / Peters, Edward S / Peterson, Alan L / Peverill, Matthew / Pietrzak, Robert H / Polusny, Melissa A / Porjesz, Bernice / Powers, Abigail / Qin, Xue-Jun / Ratanatharathorn, Andrew / Risbrough, Victoria B / Roberts, Andrea L / Rothbaum, Alex O / Rothbaum, Barbara O / Roy-Byrne, Peter / Ruggiero, Kenneth J / Rung, Ariane / Runz, Heiko / Rutten, Bart P F / de Viteri, Stacey Saenz / Salum, Giovanni Abrahão / Sampson, Laura / Sanchez, Sixto E / Santoro, Marcos / Seah, Carina / Seedat, Soraya / Seng, Julia S / Shabalin, Andrey / Sheerin, Christina M / Silove, Derrick / Smith, Alicia K / Smoller, Jordan W / Sponheim, Scott R / Stein, Dan J / Stensland, Synne / Stevens, Jennifer S / Sumner, Jennifer A / Teicher, Martin H / Thompson, Wesley K / Tiwari, Arun K / Trapido, Edward / Uddin, Monica / Ursano, Robert J / Valdimarsdóttir, Unnur / Van Hooff, Miranda / Vermetten, Eric / Vinkers, Christiaan H / Voisey, Joanne / Wang, Yunpeng / Wang, Zhewu / Waszczuk, Monika / Weber, Heike / Wendt, Frank R / Werge, Thomas / Williams, Michelle A / Williamson, Douglas E / Winsvold, Bendik S / Winternitz, Sherry / Wolf, Christiane / Wolf, Erika J / Xia, Yan / Xiong, Ying / Yehuda, Rachel / Young, Keith A / Young, Ross McD / Zai, Clement C / Zai, Gwyneth C / Zervas, Mark / Zhao, Hongyu / Zoellner, Lori A / Zwart, John-Anker / deRoon-Cassini, Terri / van Rooij, Sanne J H / van den Heuvel, Leigh L / Stein, Murray B / Ressler, Kerry J / Koenen, Karestan C

Nature genetics

2024

Abstract: Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi- ... ...

Abstract	Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	1108734-1
ISSN	1546-1718 ; 1061-4036
ISSN (online)	1546-1718
ISSN	1061-4036
DOI	10.1038/s41588-024-01707-9
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Zs.A 3613: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 46: Show issues

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Article: Emerging molecular mechanisms of general anesthetic action.

Hemmings, Hugh C / Akabas, Myles H / Goldstein, Peter A / Trudell, James R / Orser, Beverley A / Harrison, Neil L

Trends in pharmacological sciences

2005 Volume 26, Issue 10, Page(s) 503–510

Abstract: General anesthetics are essential to modern medicine, and yet a detailed understanding of their mechanisms of action is lacking. General anesthetics were once believed to be "drugs without receptors" but this view has been largely abandoned. During the ... ...

Abstract	General anesthetics are essential to modern medicine, and yet a detailed understanding of their mechanisms of action is lacking. General anesthetics were once believed to be "drugs without receptors" but this view has been largely abandoned. During the past decade significant progress in our understanding of the mechanisms of general anesthetic action at the molecular, cellular and neural systems levels has been made. Different molecular targets in various regions of the nervous system are involved in the multiple components of anesthetic action, and these targets can vary between specific anesthetics. Neurotransmitter-gated ion channels, particularly receptors for GABA and glutamate, are modulated by most anesthetics, at both synaptic and extrasynaptic sites, and additional ion channels and receptors are also being recognized as important targets for general anesthetics. In this article, these developments, which have important implications for the development of more-selective anesthetics, are reviewed in the context of recent advances in ion channel structure and function.
MeSH term(s)	Anesthesia, General ; Anesthetics/metabolism ; Anesthetics/pharmacology ; Animals ; Humans ; Ion Channels/metabolism ; Ligands ; Receptors, GABA/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism
Chemical Substances	Anesthetics ; Ion Channels ; Ligands ; Receptors, GABA ; Receptors, N-Methyl-D-Aspartate
Language	English
Publishing date	2005-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	282846-7
ISSN	1873-3735 ; 0165-6147
ISSN (online)	1873-3735
ISSN	0165-6147
DOI	10.1016/j.tips.2005.08.006
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Article: Regional differences in nerve terminal Na⁺ channel subtype expression and Na⁺ channel-dependent glutamate and GABA release in rat CNS

Westphalen, Robert I / Yu, Jieying / Krivitski, Margarita / Jih, Ting-Yu / Hemmings Jr, Hugh C

Journal of neurochemistry. 2010 June, v. 113, no. 6

2010

Abstract: ... by measuring the sensitivity of 4-aminopyridine (4AP)-evoked [³H]glutamate and [¹⁴C]GABA release ...

Abstract	J. Neurochem. (2010) 113, 1611-1620. We tested the hypothesis that expression of pre-synaptic voltage-gated sodium channel (Nav) subtypes coupled to neurotransmitter release differs between transmitter types and CNS regions in a nerve terminal-specific manner. Nav coupling to transmitter release was determined by measuring the sensitivity of 4-aminopyridine (4AP)-evoked [³H]glutamate and [¹⁴C]GABA release to the specific Nav blocker tetrodotoxin (TTX) for nerve terminals isolated from rat cerebral cortex, hippocampus, striatum and spinal cord. Expression of various Nav subtypes was measured by immunoblotting using subtype-specific antibodies. Potencies of TTX for inhibition of glutamate and GABA release varied between CNS regions. However, the efficacies of TTX for inhibition of 4AP-evoked glutamate release were greater than for inhibition of GABA release in all regions except spinal cord. The relative nerve terminal expression of total Nav subtypes as well as of specific subtypes varied considerably between CNS regions. The region-specific potencies of TTX for inhibition of 4AP-evoked glutamate release correlated with greater relative expression of total nerve terminal Nav and Nav1.2. Nerve terminal-specific differences in the expression of specific Nav subtypes contribute to transmitter-specific and regional differences in pharmacological sensitivities of transmitter release.
Keywords	sodium channels ; tetrodotoxin
Language	English
Dates of publication	2010-06
Size	p. 1611-1620.
Publisher	Blackwell Publishing Ltd
Publishing place	Oxford, UK
Document type	Article
ZDB-ID	80158-6
ISSN	1471-4159 ; 0022-3042 ; 1474-1644
ISSN (online)	1471-4159
ISSN	0022-3042 ; 1474-1644
DOI	10.1111/j.1471-4159.2010.06722.x
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Article: Immunohistochemical evidence for the existence of a dopamine- and cyclic AMP-regulated phosphoprotein (DARPP-32) in brown adipose tissue of pigs

Meister, B / Fried, G / Hokfelt, T / Hemmings, H.C. Jr / Greengard, P

Proceedings of the National Academy of Sciences of the United States of America. Nov 1988. v. 85 (22)

1988

Keywords	piglets ; adipose tissue ; histochemistry ; immunochemistry ; thermoregulation ; fluorescent antibody technique ; phosphoproteins
Language	English
Dates of publication	1988-11
Size	p. 8713-8716., ill.
Document type	Article
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
Database	NAL-Catalogue (AGRICOLA)

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Article: Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders.

Nievergelt, Caroline M / Maihofer, Adam X / Atkinson, Elizabeth G / Chen, Chia-Yen / Choi, Karmel W / Coleman, Jonathan Ri / Daskalakis, Nikolaos P / Duncan, Laramie E / Polimanti, Renato / Aaronson, Cindy / Amstadter, Ananda B / Andersen, Soren B / Andreassen, Ole A / Arbisi, Paul A / Ashley-Koch, Allison E / Austin, S Bryn / Avdibegoviç, Esmina / Babic, Dragan / Bacanu, Silviu-Alin /

Baker, Dewleen G / Batzler, Anthony / Beckham, Jean C / Belangero, Sintia / Benjet, Corina / Bergner, Carisa / Bierer, Linda M / Biernacka, Joanna M / Bierut, Laura J / Bisson, Jonathan I / Boks, Marco P / Bolger, Elizabeth A / Brandolino, Amber / Breen, Gerome / Bressan, Rodrigo Affonseca / Bryant, Richard A / Bustamante, Angela C / Bybjerg-Grauholm, Jonas / Bækvad-Hansen, Marie / Børglum, Anders D / Børte, Sigrid / Cahn, Leah / Calabrese, Joseph R / Caldas-de-Almeida, Jose Miguel / Chatzinakos, Chris / Cheema, Sheraz / Clouston, Sean A P / Colodro-Conde, LucÍa / Coombes, Brandon J / Cruz-Fuentes, Carlos S / Dale, Anders M / Dalvie, Shareefa / Davis, Lea K / Deckert, Jürgen / Delahanty, Douglas L / Dennis, Michelle F / deRoon-Cassini, Terri / Desarnaud, Frank / DiPietro, Christopher P / Disner, Seth G / Docherty, Anna R / Domschke, Katharina / Dyb, Grete / Kulenovic, Alma Dzubur / Edenberg, Howard J / Evans, Alexandra / Fabbri, Chiara / Fani, Negar / Farrer, Lindsay A / Feder, Adriana / Feeny, Norah C / Flory, Janine D / Forbes, David / Franz, Carol E / Galea, Sandro / Garrett, Melanie E / Gelaye, Bizu / Gelernter, Joel / Geuze, Elbert / Gillespie, Charles F / Goci, Aferdita / Goleva, Slavina B / Gordon, Scott D / Grasser, Lana Ruvolo / Guindalini, Camila / Haas, Magali / Hagenaars, Saskia / Hauser, Michael A / Heath, Andrew C / Hemmings, Sian Mj / Hesselbrock, Victor / Hickie, Ian B / Hogan, Kelleigh / Hougaard, David Michael / Huang, Hailiang / Huckins, Laura M / Hveem, Kristian / Jakovljevic, Miro / Javanbakht, Arash / Jenkins, Gregory D / Johnson, Jessica / Jones, Ian / Jovanovic, Tanja / Karstoft, Karen-Inge / Kaufman, Milissa L / Kennedy, James L / Kessler, Ronald C / Khan, Alaptagin / Kimbrel, Nathan A / King, Anthony P / Koen, Nastassja / Kotov, Roman / Kranzler, Henry R / Krebs, Kristi / Kremen, William S / Kuan, Pei-Fen / Lawford, Bruce R / Lebois, Lauren A M / Lehto, Kelli / Levey, Daniel F / Lewis, Catrin / Liberzon, Israel / Linnstaedt, Sarah D / Logue, Mark W / Lori, Adriana / Lu, Yi / Luft, Benjamin J / Lupton, Michelle K / Luykx, Jurjen J / Makotkine, Iouri / Maples-Keller, Jessica L / Marchese, Shelby / Marmar, Charles / Martin, Nicholas G / MartÍnez-Levy, Gabriela A / McAloney, Kerrie / McFarlane, Alexander / McLaughlin, Katie A / McLean, Samuel A / Medland, Sarah E / Mehta, Divya / Meyers, Jacquelyn / Michopoulos, Vasiliki / Mikita, Elizabeth A / Milani, Lili / Milberg, William / Miller, Mark W / Morey, Rajendra A / Morris, Charles Phillip / Mors, Ole / Mortensen, Preben Bo / Mufford, Mary S / Nelson, Elliot C / Nordentoft, Merete / Norman, Sonya B / Nugent, Nicole R / O'Donnell, Meaghan / Orcutt, Holly K / Pan, Pedro M / Panizzon, Matthew S / Pathak, Gita A / Peters, Edward S / Peterson, Alan L / Peverill, Matthew / Pietrzak, Robert H / Polusny, Melissa A / Porjesz, Bernice / Powers, Abigail / Qin, Xue-Jun / Ratanatharathorn, Andrew / Risbrough, Victoria B / Roberts, Andrea L / Rothbaum, Barbara O / Rothbaum, Alex O / Roy-Byrne, Peter / Ruggiero, Kenneth J / Rung, Ariane / Runz, Heiko / Rutten, Bart P F / de Viteri, Stacey Saenz / Salum, Giovanni Abrahão / Sampson, Laura / Sanchez, Sixto E / Santoro, Marcos / Seah, Carina / Seedat, Soraya / Seng, Julia S / Shabalin, Andrey / Sheerin, Christina M / Silove, Derrick / Smith, Alicia K / Smoller, Jordan W / Sponheim, Scott R / Stein, Dan J / Stensland, Synne / Stevens, Jennifer S / Sumner, Jennifer A / Teicher, Martin H / Thompson, Wesley K / Tiwari, Arun K / Trapido, Edward / Uddin, Monica / Ursano, Robert J / Valdimarsdóttir, Unnur / van den Heuvel, Leigh Luella / Van Hooff, Miranda / van Rooij, Sanne Jh / Vermetten, Eric / Vinkers, Christiaan H / Voisey, Joanne / Wang, Zhewu / Wang, Yunpeng / Waszczuk, Monika / Weber, Heike / Wendt, Frank R / Werge, Thomas / Williams, Michelle A / Williamson, Douglas E / Winsvold, Bendik S / Winternitz, Sherry / Wolf, Erika J / Wolf, Christiane / Xia, Yan / Xiong, Ying / Yehuda, Rachel / Young, Ross McD / Young, Keith A / Zai, Clement C / Zai, Gwyneth C / Zervas, Mark / Zhao, Hongyu / Zoellner, Lori A / Zwart, John-Anker / Stein, Murray B / Ressler, Kerry J / Koenen, Karestan C

medRxiv : the preprint server for health sciences

2023

Abstract: Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi- ... ...

Abstract	Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g.,
Language	English
Publishing date	2023-09-02
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.31.23294915
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Enhancing Discovery of Genetic Variants for Posttraumatic Stress Disorder Through Integration of Quantitative Phenotypes and Trauma Exposure Information.

Maihofer, Adam X / Choi, Karmel W / Coleman, Jonathan R I / Daskalakis, Nikolaos P / Denckla, Christy A / Ketema, Elizabeth / Morey, Rajendra A / Polimanti, Renato / Ratanatharathorn, Andrew / Torres, Katy / Wingo, Aliza P / Zai, Clement C / Aiello, Allison E / Almli, Lynn M / Amstadter, Ananda B / Andersen, Soren B / Andreassen, Ole A / Arbisi, Paul A / Ashley-Koch, Allison E /

Austin, S Bryn / Avdibegović, Esmina / Borglum, Anders D / Babić, Dragan / Bækvad-Hansen, Marie / Baker, Dewleen G / Beckham, Jean C / Bierut, Laura J / Bisson, Jonathan I / Boks, Marco P / Bolger, Elizabeth A / Bradley, Bekh / Brashear, Meghan / Breen, Gerome / Bryant, Richard A / Bustamante, Angela C / Bybjerg-Grauholm, Jonas / Calabrese, Joseph R / Caldas-de-Almeida, José M / Chen, Chia-Yen / Dale, Anders M / Dalvie, Shareefa / Deckert, Jürgen / Delahanty, Douglas L / Dennis, Michelle F / Disner, Seth G / Domschke, Katharina / Duncan, Laramie E / Džubur Kulenović, Alma / Erbes, Christopher R / Evans, Alexandra / Farrer, Lindsay A / Feeny, Norah C / Flory, Janine D / Forbes, David / Franz, Carol E / Galea, Sandro / Garrett, Melanie E / Gautam, Aarti / Gelaye, Bizu / Gelernter, Joel / Geuze, Elbert / Gillespie, Charles F / Goçi, Aferdita / Gordon, Scott D / Guffanti, Guia / Hammamieh, Rasha / Hauser, Michael A / Heath, Andrew C / Hemmings, Sian M J / Hougaard, David Michael / Jakovljević, Miro / Jett, Marti / Johnson, Eric Otto / Jones, Ian / Jovanovic, Tanja / Qin, Xue-Jun / Karstoft, Karen-Inge / Kaufman, Milissa L / Kessler, Ronald C / Khan, Alaptagin / Kimbrel, Nathan A / King, Anthony P / Koen, Nastassja / Kranzler, Henry R / Kremen, William S / Lawford, Bruce R / Lebois, Lauren A M / Lewis, Catrin / Liberzon, Israel / Linnstaedt, Sarah D / Logue, Mark W / Lori, Adriana / Lugonja, Božo / Luykx, Jurjen J / Lyons, Michael J / Maples-Keller, Jessica L / Marmar, Charles / Martin, Nicholas G / Maurer, Douglas / Mavissakalian, Matig R / McFarlane, Alexander / McGlinchey, Regina E / McLaughlin, Katie A / McLean, Samuel A / Mehta, Divya / Mellor, Rebecca / Michopoulos, Vasiliki / Milberg, William / Miller, Mark W / Morris, Charles Phillip / Mors, Ole / Mortensen, Preben B / Nelson, Elliot C / Nordentoft, Merete / Norman, Sonya B / O'Donnell, Meaghan / Orcutt, Holly K / Panizzon, Matthew S / Peters, Edward S / Peterson, Alan L / Peverill, Matthew / Pietrzak, Robert H / Polusny, Melissa A / Rice, John P / Risbrough, Victoria B / Roberts, Andrea L / Rothbaum, Alex O / Rothbaum, Barbara O / Roy-Byrne, Peter / Ruggiero, Kenneth J / Rung, Ariane / Rutten, Bart P F / Saccone, Nancy L / Sanchez, Sixto E / Schijven, Dick / Seedat, Soraya / Seligowski, Antonia V / Seng, Julia S / Sheerin, Christina M / Silove, Derrick / Smith, Alicia K / Smoller, Jordan W / Sponheim, Scott R / Stein, Dan J / Stevens, Jennifer S / Teicher, Martin H / Thompson, Wesley K / Trapido, Edward / Uddin, Monica / Ursano, Robert J / van den Heuvel, Leigh Luella / Van Hooff, Miranda / Vermetten, Eric / Vinkers, Christiaan H / Voisey, Joanne / Wang, Yunpeng / Wang, Zhewu / Werge, Thomas / Williams, Michelle A / Williamson, Douglas E / Winternitz, Sherry / Wolf, Christiane / Wolf, Erika J / Yehuda, Rachel / Young, Keith A / Young, Ross McD / Zhao, Hongyu / Zoellner, Lori A / Haas, Magali / Lasseter, Heather / Provost, Allison C / Salem, Rany M / Sebat, Jonathan / Shaffer, Richard A / Wu, Tianying / Ripke, Stephan / Daly, Mark J / Ressler, Kerry J / Koenen, Karestan C / Stein, Murray B / Nievergelt, Caroline M

Biological psychiatry

2021 Volume 91, Issue 7, Page(s) 626–636

Abstract: Background: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) ... ...

Abstract	Background: Posttraumatic stress disorder (PTSD) is heritable and a potential consequence of exposure to traumatic stress. Evidence suggests that a quantitative approach to PTSD phenotype measurement and incorporation of lifetime trauma exposure (LTE) information could enhance the discovery power of PTSD genome-wide association studies (GWASs). Methods: A GWAS on PTSD symptoms was performed in 51 cohorts followed by a fixed-effects meta-analysis (N = 182,199 European ancestry participants). A GWAS of LTE burden was performed in the UK Biobank cohort (N = 132,988). Genetic correlations were evaluated with linkage disequilibrium score regression. Multivariate analysis was performed using Multi-Trait Analysis of GWAS. Functional mapping and annotation of leading loci was performed with FUMA. Replication was evaluated using the Million Veteran Program GWAS of PTSD total symptoms. Results: GWASs of PTSD symptoms and LTE burden identified 5 and 6 independent genome-wide significant loci, respectively. There was a 72% genetic correlation between PTSD and LTE. PTSD and LTE showed largely similar patterns of genetic correlation with other traits, albeit with some distinctions. Adjusting PTSD for LTE reduced PTSD heritability by 31%. Multivariate analysis of PTSD and LTE increased the effective sample size of the PTSD GWAS by 20% and identified 4 additional loci. Four of these 9 PTSD loci were independently replicated in the Million Veteran Program. Conclusions: Through using a quantitative trait measure of PTSD, we identified novel risk loci not previously identified using prior case-control analyses. PTSD and LTE have a high genetic overlap that can be leveraged to increase discovery power through multivariate methods.
MeSH term(s)	Genetic Predisposition to Disease ; Genome-Wide Association Study/methods ; Humans ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Stress Disorders, Post-Traumatic/genetics
Language	English
Publishing date	2021-09-28
Publishing country	United States
Document type	Journal Article ; Meta-Analysis ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209434-4
ISSN	1873-2402 ; 0006-3223
ISSN (online)	1873-2402
ISSN	0006-3223
DOI	10.1016/j.biopsych.2021.09.020
Database	MEDical Literature Analysis and Retrieval System OnLINE

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