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51.
52.
Alexander Barth Andras Bilkei‐Gorzo Eva Drews David M. Otte Amalia Diaz‐Lacava Jeeva Varadarajulu Christoph W. Turck Thomas F. Wienker Andreas Zimmer 《Journal of neurochemistry》2014,128(6):807-817
Significant progress in elucidating the genetic etiology of anxiety and depression has been made during the last decade through a combination of human and animal studies. In this study, we aimed to discover genetic loci linked with anxiety as well as depression in order to reveal new candidate genes. Therefore, we initially tested the behavioral sensitivity of 543 F2 animals derived from an intercross of C57BL/6J and C3H/HeJ mice in paradigms for anxiety and depression. Next, all animals were genotyped with 269 microsatellite markers with a mean distance of 5.56 cM. Finally, a Quantitative Trait Loci (QTL) analysis was carried out, followed by selection of candidate genes. The QTL analysis revealed several new QTL on chromosome 5 with a common core interval of 19 Mb. We further narrowed this interval by comparative genomics to a region of 15 Mb. A database search and gene prioritization revealed Enoph1 as the most significant candidate gene on the prioritization list for anxiety and also for depression fulfilling our selection criteria. The Enoph1 gene, which is involved in polyamine biosynthesis, is differently expressed in parental strains, which have different brain spermidine levels and show distinct anxiety and depression‐related phenotype. Our result suggests a significant role in polyamines in anxiety and depression‐related behaviors.
53.
Camille Jung Jean-Frédéric Colombel Marc Lemann Laurent Beaugerie Matthieu Allez Jacques Cosnes Gwenola Vernier-Massouille Jean-Marc Gornet Jean-Pierre Gendre Jean-Pierre Cezard Frank M. Ruemmele Dominique Turck Fran?oise Merlin Habib Zouali Christian Libersa Philippe Dieudé Nadem Soufir Gilles Thomas Jean-Pierre Hugot 《PloS one》2012,7(12)
54.
Natacha Turck Xavier Robin Nadia Walter Catherine Fouda Alexandre Hainard Roman Sztajzel Ghislaine Wagner Denis F. Hochstrasser Joan Montaner Pierre R. Burkhard Jean-Charles Sanchez 《PloS one》2012,7(9)
Background
Ability to accurately determine time of stroke onset remains challenging. We hypothesized that an early biomarker characterized by a rapid increase in blood after stroke onset may help defining better the time window during which an acute stroke patient may be candidate for intravenous thrombolysis or other intravascular procedures.Methods
The blood level of 29 proteins was measured by immunoassays on a prospective cohort of stroke patients (N = 103) and controls (N = 132). Mann-Whitney U tests, ROC curves and diagnostic odds ratios were applied to evaluate their clinical performances.Results
Among the 29 molecules tested, GST-π concentration was the most significantly elevated marker in the blood of stroke patients (p<0.001). More importantly, GST-π displayed the best area under the curve (AUC, 0.79) and the best diagnostic odds ratios (10.0) for discriminating early (N = 22, <3 h of stroke onset) vs. late stroke patients (N = 81, >3 h after onset). According to goal-oriented distinct cut-offs (sensitivity(Se)-oriented: 17.7 or specificity(Sp)-oriented: 65.2 ug/L), the GST-π test obtained 91%Se/50%Sp and 50%Se/91%Sp, respectively. Moreover, GST-π showed also the highest AUC (0.83) and performances for detecting patients treated with tPA (N = 12) compared to ineligible patients (N = 103).Conclusions
This study demonstrates that GST-π can accurately predict the time of stroke onset in over 50% of early stroke patients. The GST-π test could therefore complement current guidelines for tPA administration and potentially increase the number of patients accessing thrombolysis. 相似文献55.
The impact of chromatin regulation on the floral transition 总被引:2,自引:0,他引:2
56.
Giuseppina Maccarrone Christiane Rewerts Maria Lebar Christoph W. Turck Daniel Martins‐de‐Souza 《Proteomics》2013,13(5):893-897
Peripheral blood mononuclear cells (MNCs) are accessible through blood collection and represent a useful source for investigations on disease mechanisms and treatment response. Aiming to build a reference proteome database, we generated three proteome data sets from MNCs using a combination of SDS‐PAGE and nanoflow LC‐MS. Experiments were performed in triplicates and 514 unique proteins were identified by at least two non‐redundant peptides with 95% confidence for all replicates. Identified proteins are associated with a range of dermatologic, inflammatory and neurological conditions as well as molecular processes, such as free radical scavenging and cellular growth and proliferation. Mapping the MNC proteome provides a valuable resource for studies on disease pathogenesis and the identification of therapeutic targets. 相似文献
57.
58.
Distinct phosphotyrosines on a growth factor receptor bind to specific molecules that mediate different signaling pathways. 总被引:105,自引:0,他引:105
W J Fantl J A Escobedo G A Martin C W Turck M del Rosario F McCormick L T Williams 《Cell》1992,69(3):413-423
The receptor for platelet-derived growth factor (PDGF) binds two proteins containing SH2 domains, GTPase activating protein (GAP) and phosphatidylinositol 3-kinase (PI3-kinase). The sites on the receptor that mediate this interaction were identified by using phosphotyrosine-containing peptides representing receptor sequences to block specifically binding of either PI3-kinase or GAP. These results suggested that PI3-kinase binds two phosphotyrosine residues, each located in a 5 aa motif with an essential methionine at the fourth position C-terminal to the tyrosine. Point mutations at these sites caused a selective elimination of PI3-kinase binding and loss of PDGF-stimulated DNA synthesis. Mutation of the binding site for GAP prevented the receptor from associating with or phosphorylating GAP, but had no effect on PI3-kinase binding and little effect on DNA synthesis. Therefore, GAP and PI3-kinase interact with the receptor by binding to different phosphotyrosine-containing sequence motifs. 相似文献
59.
M R Gold V W Chan C W Turck A L DeFranco 《Journal of immunology (Baltimore, Md. : 1950)》1992,148(7):2012-2022
Cross-linking of the B cell AgR results in activation of mature B cells and tolerization of immature B cells. The initial signaling events stimulated by membrane immunoglobulin (mIg) cross-linking are tyrosine phosphorylation of a number of proteins. Among the targets of mIg-induced tyrosine phosphorylation are the tyrosine kinases encoded by the lyn, blk, fyn, and syk genes, the mIg-associated proteins MB-1 and Ig-beta, phospholipase C-gamma 1 and -gamma 2, as well as many unidentified proteins. In this report we show that mIg cross-linking also regulates phosphatidylinositol 3-kinase (PtdIns 3-kinase), an enzyme that phosphorylates inositol phospholipids and plays a key role in mediating the effects of tyrosine kinases on growth control in fibroblasts. Cross-linking mIg on B lymphocytes greatly increased the amount of PtdIns 3-kinase activity which could be immunoprecipitated with anti-phosphotyrosine (anti-tyr(P) antibodies. This response was observed after mIg cross-linking in mIgM- and mIgG-bearing B cell lines and after cross-linking either mIgM or mIgD in murine splenic B cells. Thus, regulation of PtdIns 3-kinase is a common feature of signaling by several different isotypes of mIg. This response was rapid and peaked 2 to 3 min after the addition of anti-Ig antibodies. The anti-Ig-stimulated increase in PtdIns 3-kinase activity associated with anti-Tyr(P) immunoprecipitates could reflect increased tyrosine phosphorylation of PtdIns 3-kinase, increased activity of the enzyme, or both. In favor of the first possibility, the tyrosine kinase inhibitor herbimycin A blocked the increase in ant-Tyr(P)-immunoprecipitated PtdIns 3-kinase activity as well as the anti-Ig-induced tyrosine phosphorylation. Moreover, this response was not secondary to phospholipase C activation but rather seemed to be a direct consequence of mIg-induced tyrosine phosphorylation. Activation of the phosphoinositide pathway by a transfected M1 muscarinic acetylcholine receptor expressed in WEHI-231 B lymphoma cells did not increase the amount of PtdIns 3-kinase activity which could be precipitated with anti-Tyr(P) antibodies. Similarly, inhibition of the phosphoinositide pathway did not abrogate the ability of mIg cross-linking to stimulate this response. Thus, mIg-induced tyrosine phosphorylation regulates PtdIns 3-kinase, an important mediator of growth control in fibroblasts and potentially an important regulatory component in B cells as well. 相似文献
60.
Maja Bulatovi? ?alasan Oscar FC van den Bosch Marjonne CW Creemers Martijn Custers Antonius HM Heurkens Jan Maarten van Woerkom Nico M Wulffraat 《Arthritis research & therapy》2013,15(6):R217