Acute responsivity of the serotonergic system to S-citalopram and positive emotionality : the moderating role of the 5-HTTLPR

According to the idea that the central serotonergic system has a modulatory function on behavior and personality in general, we aimed to highlight its association to habitual positive emotionality. In a placebo-controlled double-blind and randomized cross-over neuroendocrine challenge design (n = 72 healthy males) we investigated the association of the central serotonergic responsivity, 5-HTTLPR-genotype as well as their combined effects on positive emotionality. Regression analyses revealed an involvement of the serotonergic system in positive emotionality. There was, however, no direct association between positive emotionality and cortisol responses to S-citalopram; rather 5-HTTLPR-genotype showed an association (p < 0.05). That is, positive emotionality scores increased with the number of s-alleles carried by the individuals. Most notable was the moderating role of 5-HTTLPR-genotype (p < 0.05) on the association between acute serotonergic responsivity and positive emotionality. Indeed, this association was only found in ss-homozygotes, in which the acute responsivity of the serotonergic system additionally seems to contribute to the level of positive emotionality (r = 0.70, p < 0.05). The findings correspond to previous research demonstrating that the 5-HTTLPR is not only involved in the negative-emotional aspects of behavior and temperament, but is associated, moreover, with positive affectivity—supporting the assumption of its valence-neutrality. In addition, our data are in line with the idea of possible influences of the 5-HTTLPR-genotype on early neuronal development. They also indicate the need for further studies in order to clearly elucidate the role of the serotonergic system and its subcomponents in the regulation of positive emotionality

Non-Invasive Follow-up Evaluation of Post-Embolized AVM with Time-Resolved MRA: A Case Report

We report the hemodynamic assessment in a patient with cerebral arteriovenous malformation using time-resolved magnetic resonance angiography (TR-MRA), a non-invasive modality, and catheter-based digital subtraction angiography (DSA), before and after embolization. Comparison of the results showed that TR-MRA produced very fast dynamic images and the findings closely matched those obtained at DSA. For initial work-up and follow-up studies in patients with vascular lesions, TR-MRA and DSA are therefore comparable

Relationship of 5-HTTLPR Polymorphism with Various Factors of Pain Processing:Subjective Experience, Motor Responsiveness and Catastrophizing

Although serotonin is known to play an important role in pain processing, the relationship between the polymorphism in 5-HTTLPR and pain processing is not well understood. To examine the relationship more comprehensively, various factors of pain processing having putative associations with 5-HT functioning were studied, namely the subjective pain experience (pain threshold, rating of experimental pain), catastrophizing about pain (Pain Catastrophizing Scale = PCS) and motor responsiveness (facial expression of pain). In 60 female and 67 male participants, heat pain stimuli were applied by a contact thermode to assess pain thresholds, supra-threshold ratings and a composite score of pain-relevant facial responses. Participants also completed the PCS and were grouped based on their 5-HTTLPR genotype (bi-allelic evaluation) into a group with s-allele carriers (ss, sl) and a second group without (ll). S-allele carriers proved to have lower pain thresholds and higher PCS scores. These two positive findings were unrelated to each other. No other difference between genotype groups became significant. In all analyses, "age" and "gender" were controlled for. In s-allele carriers the subjective pain experience and the tendency to catastrophize about pain was enhanced, suggesting that the s-allele might be a risk factor for the development and maintenance of pain. This risk factor seems to act via two independent routes, namely via the sensory processes of subjective pain experiences and via the booster effects of pain catastrophizing

β-(1→3)-D-glucan modulates DNA binding of nuclear factors κB, AT and IL-6 leading to an anti-inflammatory shift of the IL-1β/IL-1 receptor antagonist ratio

BACKGROUND: β-1→3-D-glucans represent a pathogen-associated molecular pattern and are able to modify biological responses. Employing a comprehensive methodological approach, the aim of our in vitro study was to elucidate novel molecular and cellular mechanisms of human peripheral blood immune cells mediated by a fungal β-1→3-D-glucan, i.e. glucan phosphate, in the presence of lipopolysaccharide (LPS) or toxic shock syndrome toxin 1 (TSST-1). RESULTS: Despite an activation of nuclear factor (NF)κB, NFinterleukin(IL)-6 and NFAT similar to LPS or TSST-1, we observed no significant production of IL-1β, IL-6, tumor necrosis factor α or interferon γ induced by glucan phosphate. Glucan phosphate-treated leukocytes induced a substantial amount of IL-8 (peak at 18 h: 5000 pg/ml), likely due to binding of NFκB to a consensus site in the IL-8 promoter. An increase in IL-1receptor antagonist(RA) production (peak at 24 h: 12000 pg/ml) by glucan phosphate-treated cells positively correlated with IL-8 levels. Glucan phosphate induced significant binding to a known NFIL-6 site and a new NFAT site within the IL-1RA promoter, which was confirmed by inhibition experiments. When applied in combination with either LPS or TSST-1 at the same time points, we detected that glucan phosphate elevated the LPS- and the TSST-1-induced DNA binding of NFκB, NFIL-6 and NFAT, leading to a synergistic increase of IL-1RA. Further, glucan phosphate modulated the TSST-1-induced inflammatory response via reduction of IL-1β and IL-6. As a consequence, glucan phosphate shifted the TSST-1-induced IL-1β/IL-1RA ratio towards an anti-inflammatory phenotype. Subsequently, glucan phosphate decreased the TSST-1-induced, IL-1-dependent production of IL-2. CONCLUSION: Thus, β-1→3-D-glucans may induce beneficial effects in the presence of pro-inflammatory responses, downstream of receptor binding and signaling by switching a pro- to an anti-inflammatory IL-1RA-mediated reaction. Our results also offer new insights into the complex regulation of the IL-1RA gene, which can be modulated by a β-1→3-D-glucan

Β-(I→3)-D-Glucan Modulates Dna Binding of Nuclear Factors κB, at and IL-6 Leading to an Anti-Inflammatory Shift of the IL-I β/IL-I Receptor Antagonist Ratio

Background: β-1→3-D-glucans represent a pathogen-associated molecular pattern and are able to modify biological responses. Employing a comprehensive methodological approach, the aim of our in vitro study was to elucidate novel molecular and cellular mechanisms of human peripheral blood immune cells mediated by a fungal β-1→3-D-glucan, i.e. glucan phosphate, in the presence of lipopolysaccharide (LPS) or toxic shock syndrome toxin 1 (TSST-1). Results: Despite an activation of nuclear factor (NF)κB, NFinterleukin(IL)-6 and NFAT similar to LPS or TSST-1, we observed no significant production of IL-1β, IL-6, tumor necrosis factor α or interferon γ induced by glucan phosphate. Glucan phosphate-treated leukocytes induced a substantial amount of IL-8 (peak at 18 h: 5000 pg/ ml), likely due to binding of NFκB to a consensus site in the IL-8 promoter. An increase in IL-1 receptor antagonist(RA) production (peak at 24 h: 12000 pg/ml) by glucan phosphate-treated cells positively correlated with IL-8 levels. Glucan phosphate induced significant binding to a known NFIL-6 site and a new NFAT site within the IL-1RA promoter, which was confirmed by inhibition experiments. When applied in combination with either LPS or TSST-1 at the same time points, we detected that glucan phosphate elevated the LPS- and the TSST-1-induced DNA binding of NFκB, NFIL-6 and NFAT, leading to a synergistic increase of IL-1RA. Further, glucan phosphate modulated the TSST-1-induced inflammatory response via reduction of IL-Iβ and IL-6. As a consequence, glucan phosphate shifted the TSST-1-induced IL-1β/IL-1RA ratio towards an anti-inflammatory phenotype. Subsequently, glucan phosphate decreased the TSST-1-induced, IL-1-dependent production of IL-2. Conclusion: Thus, β-1→3-D-glucans may induce beneficial effects in the presence of pro-inflammatory responses, downstream of receptor binding and signaling by switching a pro- to an anti-inflammatory IL-1RA-mediated reaction. Our results also offer new insights into the complex regulation of the IL-1RA gene, which can be modulated by a β-1→3-D-glucan

Switching the Post-translational Modification of Translation Elongation Factor EF-P

Tripeptides with two consecutive prolines are the shortest and most frequent sequences causing ribosome stalling. The bacterial translation elongation factor P (EF-P) relieves this arrest, allowing protein biosynthesis to continue. A seven amino acids long loop between beta-strands β3/β4 is crucial for EF-P function and modified at its tip by lysylation of lysine or rhamnosylation of arginine. Phylogenetic analyses unveiled an invariant proline in the -2 position of the modification site in EF-Ps that utilize lysine modifications such as Escherichia coli. Bacteria with the arginine modification like Pseudomonas putida on the contrary have selected against it. Focusing on the EF- Ps from these two model organisms we demonstrate the importance of the β3/β4 loop composition for functionalization by chemically distinct modifications. Ultimately, we show that only two amino acid changes in E. coli EF-P are needed for switching the modification strategy from lysylation to rhamnosylation

Quantitative diffusion tensor MR imaging of the brain: field strength related variance of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) scalars

The objectives were to study the "impact” of the magnetic field strength on diffusion tensor imaging (DTI) metrics and also to determine whether magnetic-field-related differences in T2-relaxation times of brain tissue influence DTI measurements. DTI was performed on 12 healthy volunteers at 1.5 and 3.0 Tesla (within 2 h) using identical DTI scan parameters. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured at multiple gray and white matter locations. ADC and FA values were compared and analyzed for statistically significant differences. In addition, DTI measurements were performed at different echo times (TE) for both field strengths. ADC values for gray and white matter were statistically significantly lower at 3.0 Tesla compared with 1.5 Tesla (% change between −1.94% and −9.79%). FA values were statistically significantly higher at 3.0 Tesla compared with 1.5 Tesla (% change between +4.04 and 11.15%). ADC and FA values are not significantly different for TE=91ms and TE=125ms. Thus, ADC and FA values vary with the used field strength. Comparative clinical studies using ADC or FA values should consequently compare ADC or FA results with normative ADC or FA values that have been determined for the field strength use

Beamline-Instrumentierung und Experimentautomatisierung fuer ROBL an der ESRF/Grenoble (F)

Durch das Forschungszentrum Rossendorf wurde in den Jahren 1996-1998 ein eigenes Strahlrohr fuer Experimente mit Synchrotronstrahlung an der ESRF (European Synchrotron Radioation Facility) in Grenoble/Frankreich aufgebaut. Das Strahlrohr verfuegt ueber zwei alternativ nutzbare Messplaetze fuer die Untersuchung von radioaktiven Proben mittels Roentgenabsorptionsspektroskopie und fuer Materialstrukturuntersuchungen mit Roentgendiffraktion. Der Bericht konzentriert sich auf die Arbeiten, die fuer die Steuerung der Optik und die Nutzung der Messplaetze hinsichtlich der Elektronik, Rechentechnik und Software erforderlich waren. Nach einer Beschreibung der Randbedingungen und einer Kurzcharakteristik der geraetetechnischen Basis werden wichtige Hardwarekomponenten fuer die Instrumentierung der Systeme vorgestellt. Die rechentechnische Basis wird anschliessend beschrieben. Die angewendeten Software-Grundprinzipien werden erlaeutert und diskutiert sowie an einigen Applikationen beispielhaft verdeutlicht. Abschliessend werden spezifische Probleme bei der Programmierung von Applikationen mit grafischer Bedienoberflaeche in Verbindung mit Geraetezugriffen behandelt. Tabellen, in denen die benutzten Hardware-Module und die Softwarekomponenten zusammengestellt sind, ermoeglichen einen Ueberblick ueber das Gesamtsystem. Das Literaturverzeichnis dient als Leitfaden fuer die Detaildokumentationen