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Selected AbstractsZebrafish smad7 is regulated by Smad3 and BMP signalsDEVELOPMENTAL DYNAMICS, Issue 3 2002Hans-Martin Pogoda Abstract Growth factors of the TGF-, superfamily such as BMPs and Nodals are important signaling factors during all stages of animal development. Smad proteins, the cytoplasmic mediators of most TGF-, signals in vertebrates, play central roles not only for transmission but also in controlling inductive TGF-, signals by feedback regulation. Here, we describe cloning, expression pattern, transcriptional regulation, and functional properties of two novel zebrafish Smad proteins: the TGF-, agonist Smad3b, and the anti-Smad Smad7. We show that zebrafish Smad3b, in contrast to the related zebrafish Smad2, can induce mesoderm independently of TGF-, signaling. Although mammalian Smad3 was shown to inhibit expression of the organizer-specific genes goosecoid, zebrafish smad3b activates organizer genes such as goosecoid. Furthermore, we show that Smad3 and BMP signals activate smad7. Because Smad7 blocks distinct TGF-, signals in early zebrafish development, our data provide hints for new roles of smad3 genes in the regulation and modulation of TGF-, signals. In summary, our analyses point out differences of Smad3b and Smad2 functions in zebrafish and provide the first link of smad3 and smad7 function in context of vertebrate development. © 2002 Wiley-Liss, Inc. [source] Covariations among fMRI, skin conductance, and behavioral data during processing of concealed informationHUMAN BRAIN MAPPING, Issue 12 2007Matthias Gamer Abstract Imaging techniques have been used to elucidate the neural correlates that underlie deception. The scientifically best understood paradigm for the detection of deception, however, the guilty knowledge test (GKT), was rarely used in imaging studies. By transferring a GKT-paradigm to a functional magnetic resonance imaging (fMRI) study, while additionally quantifying reaction times and skin conductance responses (SCRs), this study aimed at identifying the neural correlates of the behavioral and electrodermal response pattern typically found in GKT examinations. Prior to MR scanning, subjects viewed two specific items (probes) and were instructed to hide their knowledge of these. Two other specific items were designated as targets and required a different behavioral response during the experiment and eight items served as irrelevant stimuli. Reaction times and SCR amplitudes differed significantly between all three item types. The neuroimaging data revealed that right inferior frontal and mid-cingulate regions were more active for probe and target trials compared to irrelevants. Moreover, the differential activation in the right inferior frontal region was modulated by stimulus conflicts. These results were interpreted as an increased top-down influence on the stimulus-response-mapping for concealed and task-relevant items. Additionally, the influence of working memory and retrieval processes on this activation pattern is discussed. Using parametric analyses, reaction times and SCR amplitudes were found to be linearly related to activity in the cerebellum, the right inferior frontal cortex, and the supplementary motor area. This result provides a first link between behavioral measures, sympathetic arousal, and neural activation patterns during a GKT examination. Hum Brain Mapp 2007. © 2007 Wiley-Liss, Inc. [source] Microbial induction of CARD15 expression in intestinal epithelial cells via toll-like receptor 5 triggers an antibacterial response loop,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2006B. Begue With the discovery of CARD15 as susceptibility gene for Crohn's disease (CD) a first link to a potential defect in the innate immune system was made. In this work we aimed to analyze enterocyte NOD2/CARD15 expression and regulation in response to bacterial motifs and the consequences of the most common CD-specific CARD15 mutation on antibacterial responses of normal intestinal epithelial cells (IEC). Under normal conditions, IEC lines and ileal enterocytes did not express NOD2/CARD15 mRNA or protein, contrary to IEC derived from inflammatory CD sections. In vitro analyses revealed that the simple contact with non-pathogenic commensal E. Coli K12 was sufficient to induced NOD2/CARD15 mRNA and protein in human IEC (HIEC). We identified bacterial flagellin interacting with TLR5 as major motif in this regulation of NOD2/CARD15. E. Coli mutants not expressing flagellin (,FliC) failed to induce CARD15. Similarly, in HIEC transfected with a plasmid encoding dominant negative TLR5, no CARD15 induction was observed after K12 contact. Isolated TLR2 or TLR4 stimulation had no or only a marginal effect on NOD2/CARD15 expression. NOD2/CARD15 negative HIEC were unresponsive to muramyl dipeptide (MDP), but once NOD2/CARD15 was induced, HIEC and Caco2 cells responded to intra or extracellular MDP presentation with the activation of the NFkB pathway. IEC transfected with the Crohn-specific CARD15 mutant (F3020insC, FS) failed to activate NFkB after MDP-challenge, in contrast to CARD15WT IEC. In response to MDP, IEC induced a massive antibacterial peptide (ABP) response, seen in the apical release of CCL20. This was completely abolished in IEC carrying CARD15FS. These data suggest a critical role of NOD2/CARD15 in the bacterial clearance of the intestinal epithelium while CD-specific mutated NOD2/CARD15 causes an impaired epithelial barrier. J. Cell. Physiol. 209: 241,252, 2006. © 2006 Wiley-Liss, Inc. [source] Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trialACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 7 2009A. KÄMÄRÄINEN Background: Intravenous infusion of ice-cold fluid is considered a feasible method to induce mild therapeutic hypothermia in cardiac arrest survivors. However, only one randomized controlled trial evaluating this treatment exists. Furthermore, the implementation rate of prehospital cooling is low. The aim of this study was to evaluate the efficacy and safety of this method in comparison with conventional therapy with spontaneous cooling often observed in prehospital patients. Methods: A randomized controlled trial was conducted in a physician-staffed helicopter emergency medical service. After successful initial resuscitation, patients were randomized to receive either +4 °C Ringer's solution with a target temperature of 33 °C or conventional fluid therapy. As an endpoint, nasopharyngeal temperature was recorded at the time of hospital admission. Results: Out of 44 screened patients, 19 were analysed in the treatment group and 18 in the control group. The two groups were comparable in terms of baseline characteristics. The core temperature was markedly lower in the hypothermia group at the time of hospital admission (34.1±0.9 °C vs. 35.2±0.8 °C, P<0.001) after a comparable duration of transportation. Otherwise, there were no significant differences between the groups regarding safety or secondary outcome measures such as neurological outcome and mortality. Conclusion: Spontaneous cooling alone is insufficient to induce therapeutic hypothermia before hospital admission. Infusion of ice-cold fluid after return of spontaneous circulation was found to be well tolerated and effective. This method of cooling should be considered as an important first link in the ,cold chain' of prehospital comatose cardiac arrest survivors. [source] RivR and the small RNA RivX: the missing links between the CovR regulatory cascade and the Mga regulonMOLECULAR MICROBIOLOGY, Issue 6 2007Samantha A. Roberts Summary The CovR/S two-component system regulates the transcription of many genes that are crucial for the virulence of Streptococcus pyogenes (group A Streptococcus, GAS). Previously, we demonstrated that one gene repressed directly by CovR is rivR, which encodes a member of the RofA-like family of transcriptional regulators. In this study, we deleted rivR and its downstream gene rivX in a ,covR background. Microarray analysis revealed that the products of the rivRX locus exert positive control over the transcription of members of the Mga regulon. Using mutational analysis, we established that rivX encodes a small regulatory RNA. We found that RivR enhances transcriptional activation by Mga in vivo and in vitro. An M1 ,covR,rivRX strain is attenuated for virulence in a murine model of invasive soft tissue infection and this attenuation is complemented by rivRX expressed from a plasmid, demonstrating the importance of the rivRX locus in pathogenesis. This study provides the first link between the CovR and Mga regulatory networks. By integrating the signals received through these two global regulators, GAS is able to select from its repertoire different combinations of specific virulence factors to express in response to a broad spectrum of environmental conditions. [source] The vitamin D slant on allergyPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 7 2006Matthias Wjst Oral vitamin D supplementation has been introduced into modern medicine to prevent rickets without the knowledge that this may have profound immunological consequences. The main vitamin D metabolite calcitriol suppresses dendritic cell maturation and consecutive Th1 cell development, which has independently described as a key mechanism of allergy development. Animal studies and epidemiological surveys now provide a first link of early vitamin D supplementation and later allergy where several vitamin D regulated genes seem to be involved. A randomized clinical trial of vitamin D supplementation could be a further step to follow up the vitamin hypothesis. [source] | |||||||||||||